Novel B cell subsets as potential biomarkers in Idiopathic Inflammatory Myopathies: insights into disease pathogenesis and disease activity.

Idiopathic inflammatory myopathies are a heterogeneous group of rare autoimmune disorders characterized by progressive muscle weakness and the histopathologic findings of inflammatory infiltrates in muscle tissue. Although their pathogenesis remains indefinite, the association of autoantibodies with clinical manifestations and the evidence of high effectiveness of depleting therapies suggest that B cells could be implicated. Therefore, we explored the landscape of peripheral B cells in this disease by multiparametric flow cytometry, finding significant numerical decreases in memory and double negative subsets, as well as an expansion of the naïve compartment relative to healthy controls, that contribute to defining disease-associated B cell subset signatures and correlating with different clinical features of patients. Additionally, we determined the potential value of these subsets as diagnostic biomarkers, thus positioning B cells as neglected key elements possibly participating in idiopathic inflammatory myopathies onset or development.

Acute Type A Aortic Dissection Diagnosed by POCUS in a 29-year-old Man.

Aortic dissection (AD) is a medical emergency with a poor prognosis if not recognized early and treated promptly. In this setting, clinical data may be equivocal, while electrocardiogram, laboratory tests, and chest radiography often show nonspecific findings. In contrast, cardiac point of care ultrasound (POCUS) has proven useful in the diagnosis and detection of complications of AD. We present the case of a 29-year-old man with marfanoid habitus presenting with chest pain and acute heart failure, in whom cardiac POCUS aided in the rapid diagnosis of type A AD and pulmonary edema. POCUS contributed to optimizing the medical treatment and allowed for early activation of the surgical team.

Another in need enhances prosociality and modulates frontal theta oscillations in young adults.

Introduction: Decision-making is a process that can be strongly affected by social factors. Evidence has shown how people deviate from traditional rational-choice predictions under different levels of social interactions. The emergence of prosocial decision-making, defined as any action that is addressed to benefit another individual even at the expense of personal benefits, has been reported as an example of such social influence. Furthermore, brain evidence has shown the involvement of structures such as the prefrontal cortex, anterior insula, and midcingulate cortex during decision settings in which a decision maker interacts with others under physical pain or distress or while being observed by others. Methods: Using a slightly modified version of the dictator game and EEG recordings, we tested the hypothesis that the inclusion of another person into the decision setting increases prosocial decisions in young adults and that this increase is higher when the other person is associated with others in need. At the brain level, we hypothesized that the increase in prosocial decisions correlates with frontal theta activity. Results and Discussion: The results showed that including another person in the decision, setting increased prosocial behavior only when this presence was associated with someone in need. This effect was associated with an increase in frontocentral theta-oscillatory activity. These results suggest that the presence of someone in need enhances empathy concerns and norm compliance, raising the participants' prosocial decision-making.

Allostatic-interoceptive anticipation of social rejection.

Anticipating social stress evokes strong reactions in the organism, including interoceptive modulations. However, evidence for this claim comes from behavioral studies, often with inconsistent results, and relates almost solely to the reactive and recovery phase of social stress exposure. Here, we adopted an allostatic-interoceptive predictive coding framework to study interoceptive and exteroceptive anticipatory brain responses using a social rejection task. We analyzed the heart-evoked potential (HEP) and task-related oscillatory activity of 58 adolescents via scalp EEG, and 385 human intracranial recordings of three patients with intractable epilepsy. We found that anticipatory interoceptive signals increased in the face of unexpected social outcomes, reflected in larger negative HEP modulations. Such signals emerged from key brain allostatic-interoceptive network hubs, as shown by intracranial recordings. Exteroceptive signals were characterized by early activity between 1-15 Hz across conditions, and modulated by the probabilistic anticipation of reward-related outcomes, observed over distributed brain regions. Our findings suggest that the anticipation of a social outcome is characterized by allostatic-interoceptive modulations that prepare the organism for possible rejection. These results inform our understanding of interoceptive processing and constrain neurobiological models of social stress.

Autonomous sensory meridian response is associated with a larger heartbeat-evoked potential amplitude without differences in interoceptive awareness.

Autonomous sensory meridian response (ASMR) describes the experience of a pleasant body sensation accompanied by a feeling of well-being and relaxation in response to specific audiovisual stimuli, such as whispers and personal attention. Previous work suggests a relationship between this experience with the processing of affective and body states; however, no research has explored differences in interoception between people experiencing ASMR and those who do not. We hypothesized that the ASMR experience is based on interoception processing. To test this, we assessed group differences across different dimensions of interoception: Interoceptive sensibility (IS), measured using the multidimensional assessment of interoceptive awareness (MAIA); Interoceptive accuracy score (IAS), measured by calculating performance in a heartbeat counting task (HCT), and the electrophysiological index of interoception, the heartbeat evoked potential (HEP), which was calculated during the HCT and an ASMR tingle reporting task (ASMR-TRT). Our results showed that IS and IAS, dimensions requiring conscious awareness, showed no differences between groups. However, HEP amplitude was larger in the ASMR group in both tasks. We concluded that the ASMR experience is based on an unconscious interoceptive mechanism, reflected by HEP, where exteroceptive social-affective stimuli are integrated to represent a body state of positive affective feelings and relaxation, as has been described for affective touch. The relevance of this finding relies on that interoceptive function, body regulation, and emotional/affective experiences are fundamental for well-being, and the relationship between ASMR and interoception opens the way to future research exploring the causal relationship between them and their potential clinical applications.

Arousal dysregulation and executive dysfunction in attention deficit hyperactivity disorder (ADHD).

Attention deficit/hyperactivity disorder (ADHD) is a heterogeneous neurodevelopmental condition, that continues to have an elusive etiological background. A number of extant models and theories have historically intended to explain the many factors contributing to ADHD behaviors. One of the most accepted hypotheses has been the executive dysfunction theory associating reduction in executive control to abnormalities in structure and operational dysfunction of dopaminergic signaling networks. Nevertheless, executive functions are not always impaired in ADHD, and the literature describes other symptoms commonly reported suggesting individuals with ADHD would appear to suffer from a more general deficit. Another existing line of research, that has gained much attention recently, establishes that ADHD would have dysregulated states of brain arousal that would account for its commonly observed cognitive deficits and behavioral symptoms, described as the state regulation theory, which has now included measures of autonomic function. This article describes some important aspects that compose and challenge these two most influential theoretical constructs, executive dysfunction and state-regulation, based on their empirical evidence, implying the need to reevaluate the norms used to classify individuals and establish ADHD diagnosis. Large number of controversial results continue to exist within the study of ADHD biological and/or performance markers, possibly due to such heterogeneity and variability within the same diagnosis. The need to resolve these issues and establish newly revised diagnostic criteria for ADHD is critical, as therapeutic success depends on having accurately identified underlying neurophysiological factors in order to appropriately address them in treatment.

Epidemiology and factors associated with acute stress disorder in burned patients: a case-control study.

INTRODUCTION: A burn injury is a very painful experience, with subsequent emotional problems, which have been gaining relevance to the extent that survival from burns has improved. Among the alterations of the mental sphere in this population is Acute Stress Disorder (ASD) that has been described in up to one-third of patients with major burns. METHODOLOGY: A nested case-control study was carried out in a cohort of hospitalized patients in a burn referral unit, in patients over 16 years of age. A total of 135 patients, 41 cases, and 94 controls were included. All of them underwent a psychiatric interview, a standardized form was filled out on sociodemographic and clinical information, and the PID-5-BF scale was applied to evaluate associated personality elements. The diagnosis of acute stress was made with the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) criteria. RESULTS: The incidence of acute stress was 23.4%. When the clinical and sociodemographic characteristics of both the cases and the controls were compared, the risk factors were subsidized insurance, flame burn, burn in a special area, third-degree burn, high pain, stay in the Intensive Care Unit (ICU), peritraumatic amnesia and life threat. Patients also had a higher percentage of burned body surface, higher average pulse, longer hospital length of stay, higher average in the negative affect variable and in the psychoticism variable of the PID-5-BF scale. But for the multivariate analysis using logistic regression, the model that best explains the presence of acute stress only includes the variables life threat (Odds Ratio adjusted (ORa): 117.0; Confidence Interval (CI): 10.9-1258.5), severe pain (ORa: 9.9; CI: 1.8-52.8), electrical burn (ORa: 20.8; CI: 17.2-250), burn in a special area (ORa: 8.9; CI: 1, 0-76.8), third-degree burn (ORa: 10.4; CI: 0.7-166.7). CONCLUSION: Acute stress disorder is frequent in the hospitalised burn population, and is more frequent than in other types of trauma. Associated factors with the presentation of Acute Stress Disorder are the feeling of life threat at the time of the burn, having pain classified as strong (Visual Analog Scale (VAS) 5-10), electrical burn, and burns in special areas.

Retroaortic Anomalous Coronary Artery Visualization on Transthoracic Echocardiogram.

Incidental findings are not uncommon in echocardiography. A transthoracic echocardiogram (TTE) of an adult woman with arterial hypertension showed a tubular structure with hyperechoic walls in the atrial side of the atrioventricular groove in apical views. Coronary computed tomography angiography correlated this finding with a retroaortic course of the anomalous circumflex artery (retroaortic anomalous coronary artery [RAC], benign coronary artery variant). Recently described as the RAC sign on TTE, practitioners should be aware of this finding to avoid mistaken it as artifacts, catheters/leads, or calcified mitral annulus.

Dry Powder Mixing Is Feasible in Continuous Twin Screw Extruder: Towards Lean Extrusion Process for Oral Solid Dosage Manufacturing.

Using discrete element method (DEM) modeling and near-infrared (NIR) spectroscopy, the feasibility of powder mixing in the initial pre-melting zones of a twin screw extruder using two independent feeders was studied. Previous work in the pharmaceutical and food industry has focused on mixing when materials are melted or on material homogeneity at the extruder's output. Depending on the formulation, ensuring a fully blended formulation prior to melting may be desired. Experiments were conducted using a Coperion ZSK-18 extruder to evaluate if blend uniformity can be achieved by exploring screw configuration, screw speed, and powder feed rate. As powder exited the extruder and deposited on a conveyor belt, an in-line NIR spectrophotometer measured spectra of material. Chemometric-based models predicted unknown concentrations to evaluate if blend uniformity was achieved. Using the EDEM software, Hertz-Mindlin contact model, and dimensions of the extruder, DEM simulations complemented the experimental work. The DEM computational models provided understanding of mixing patterns inside the extruder at particle scale and helped select the screw configuration before doing experimentation. The simulations showed good axial mixing for all the screw configurations studied, while good cross (radial) mixing was only observed for the screw configuration with 90-degree kneading elements. Therefore, the screw configuration with two 90-degree kneading elements was chosen for the experimental study. The RTD profiles when using a screw configuration with only conveying screw elements are comparable to a plug flow reactor (PFR), while the profiles when using kneading elements are more comparable to an ideal continuous stirred tank reactor (CSTR). For the screw configuration with 90 degrees kneading elements, the mean residence time (MRT) decreases with an increase in the screw speed. Experimental NIR spectra showed that concentrations can be predicted with an error of 2%. It was demonstrated that the twin screw extruder can provide proper dry powder mixing of two powder feed streams based on a unit dose scale, enabling continuous powder mixing prior to the melting zone in the extruder for the formulation studied with a cohesive API. This setup may also work for other types of formulations. These studies can help in developing lean hot melt as well as wet extrusion/granulation processes using twin screw extruders for the continuous manufacturing of oral solid dosage products.

API Content and Blend Uniformity Using Quantum Cascade Laser Spectroscopy Coupled with Multivariate Analysis.

The process analytical technology (PAT) initiative proposed by the US Food and Drug Administration (FDA) suggests innovative methods to better understand pharmaceutical processes. The development of analytical methods that quantify active pharmaceutical ingredients (APIs) in powders and tablets is fundamental to monitoring and controlling a drug product's quality. Analytical methods based on vibrational spectroscopy do not require sample preparation and can be implemented during in-line manufacturing to maintain quality at each stage of operations. In this study, a mid-infrared (MIR) quantum cascade laser (QCL) spectroscopy-based protocol was performed to quantify ibuprofen in formulations of powder blends and tablets. Fourteen blends were prepared with varying concentrations from 0.0% to 21.0% (w/w) API. MIR laser spectra were collected in the spectral range of 990 to 1600 cm-1. Partial least squares (PLS) models were developed to correlate the intensities of vibrational signals with API concentrations in powder blends and tablets. PLS models were evaluated based on the following figures of merit: correlation coefficient (R2), root mean square error of calibration, root mean square error of prediction, root mean square error of cross-validation, and relative standard error of prediction. QCL assisted by multivariate analysis was demonstrated to be accurate and robust for analysis of the content and blend uniformity of pharmaceutical compounds.

The medial olivocochlear reflex strength is modulated during a visual working memory task.

Top-down modulation of sensory responses to distracting stimuli by selective attention has been proposed as an important mechanism by which our brain can maintain relevant information during working memory tasks. Previous works in visual working memory (VWM) have reported modulation of neural responses to distracting sounds at different levels of the central auditory pathways. Whether these modulations occur also at the level of the auditory receptor is unknown. Here, we hypothesize that cochlear responses to irrelevant auditory stimuli can be modulated by the medial olivocochlear system during VWM. Twenty-one subjects (13 males, mean age 25.3 yr) with normal hearing performed a visual change detection task with different VWM load conditions (high load = 4 visual objects; low load = 2 visual objects). Auditory stimuli were presented as distractors and allowed the measurement of distortion product otoacoustic emissions (DPOAEs) and scalp auditory evoked potentials. In addition, the medial olivocochlear reflex strength was evaluated by adding contralateral acoustic stimulation. We found larger contralateral acoustic suppression of DPOAEs during the visual working memory period (n = 21) compared with control experiments (n = 10), in which individuals were passively exposed to the same experimental conditions. These results show that during the visual working memory period there is a modulation of the medial olivocochlear reflex strength, suggesting a possible common mechanism for top-down filtering of auditory responses during cognitive processes.NEW & NOTEWORTHY The auditory efferent system has been proposed to function as a biological filter of cochlear responses during selective attention. Here, we recorded electroencephalographic activity and otoacoustic emissions in response to auditory distractors during a visual working memory task in humans. We found that the olivocochlear efferent activity is modulated during the visual working memory period suggesting a common mechanism for suppressing cochlear responses during selective attention and working memory.

Electrophysiological Dynamics of Visual Speech Processing and the Role of Orofacial Effectors for Cross-Modal Predictions.

The human brain generates predictions about future events. During face-to-face conversations, visemic information is used to predict upcoming auditory input. Recent studies suggest that the speech motor system plays a role in these cross-modal predictions, however, usually only audio-visual paradigms are employed. Here we tested whether speech sounds can be predicted on the basis of visemic information only, and to what extent interfering with orofacial articulatory effectors can affect these predictions. We registered EEG and employed N400 as an index of such predictions. Our results show that N400's amplitude was strongly modulated by visemic salience, coherent with cross-modal speech predictions. Additionally, N400 ceased to be evoked when syllables' visemes were presented backwards, suggesting that predictions occur only when the observed viseme matched an existing articuleme in the observer's speech motor system (i.e., the articulatory neural sequence required to produce a particular phoneme/viseme). Importantly, we found that interfering with the motor articulatory system strongly disrupted cross-modal predictions. We also observed a late P1000 that was evoked only for syllable-related visual stimuli, but whose amplitude was not modulated by interfering with the motor system. The present study provides further evidence of the importance of the speech production system for speech sounds predictions based on visemic information at the pre-lexical level. The implications of these results are discussed in the context of a hypothesized trimodal repertoire for speech, in which speech perception is conceived as a highly interactive process that involves not only your ears but also your eyes, lips and tongue.

Biocontrol of Alternaria alternata and Fusarium oxysporum by Trichoderma asperelloides and Bacillus paralicheniformis in tomato plants.

The objective of this work was to evaluate the effectiveness of the putative biocontrol agents (PBA) Bacillus paralicheniformis and Trichoderma asperelloides in vitro and in vivo to control two of the most important tomato plant diseases: vascular wilt (Fusarium oxysporum) and early blight (Alternaria alternata). The assessment of the in vitro interactions between the PBA and the phytopathogenic fungi was performed by dual confrontation assays. The biocontrol effectiveness of the individual and combined PBA treatments towards individual phytopathogen inoculations was evaluated in tomato plants. T. asperelloides was able to exert an outstanding mycoparasitic effect on both phytopathogenic fungi in the in vitro tests by hyphal strangulation and penetration. In addition, the individual PBA treatments were effective in the biocontrol of A. alternata and F. oxysporum in tomato plants reducing the plant disease severity in more than 53.8 and 66.7% for each of the pathogens, respectively. On the other hand, the combined use of the tested strains showed similar effectiveness in the biocontrol of A. alternata, but no synergism was observed. In addition, it was concluded that B. paralicheniformis protected the plants from the attack of A. alternata through the induction of the systemic resistance of the plant. This study demonstrated the effectiveness of the individual and combined use of the strains tested for the biocontrol of A. alternata and F. oxysporum in tomato plants.

Recomendaciones para el uso de la hormona de crecimiento humana recombinante en pacientes pediátricos de talla baja en Colombia / Recommendations for treatment with recombinant human growth hormone in pediatric patients in Colombia

resumen está disponible en el texto completo

Abstract In Colombia there are no guidelines for diagnosis and management of patients with short stature and for the use of recombinant human growth hormone, mainly caused by the diversity of training centers in pediatric endocrinology. In response to this situation, the Asociación Colegio Colombiana de Endocrinología Pediátrica leds the first colombian short stature expert committee in order to standardize the use of human recombinant growth hormone. This work had the participation and endorsement of a consortium of clinical experts representing the Sociedad Colombiana de Pediatría, Secretaría Distrital de Salud de Bogotá- Subred Integrada de Servicios de Salud Suroccidente, Fundación Universitaria Sanitas, Universidad de los Andes and some public and private health institutions in the country, in addition to the participation of methodological experts from the Instituto Global de Excelencia Clínica Keralty. By reviewing the literature and with the best available evidence, we proposed to unify definitions, a diagnostic algorithm, biochemical and dynamic tests with their reference parameters, a description of the considerations about growth hormone use among the indications approved by regulatory agency for medications and food in Colombia and finally a proposal for an informed consent and a medication fact sheet available for parents and patients.

Influence of violent contexts on facial reactions elicited by angry and neutral faces.

This study focuses on determining whether violent contexts influence the perception of aggressiveness in faces analysing spontaneous corrugator supercilii activity. Participants viewed pictures of neutral and angry faces preceded by a contextual sentence describing either violent or neutral actions. They were instructed to judge each face according to whether it was aggressive or non-aggressive. Results show a higher level of perceived aggressiveness for neutral faces preceded by violent contexts, accompanied by longer reaction times, and a significant increase of corrugator activity. Angry faces preceded by neutral contexts were judged as less aggressive and elicited less corrugator activity. In conclusion, our results provide evidence that facial reactions and aggressiveness judgment for faces are context-dependent. With this work, we contribute to the view that contextual cues guide the face's emotional meaning, under top-down processing.

Neurocognitive mechanisms underlying working memory encoding and retrieval in Attention-Deficit/Hyperactivity Disorder.

Working memory (WM) impairments in ADHD have been consistently reported along with deficits in attentional control. Yet, it is not clear which specific WM processes are affected in this condition. A deficient coupling between attention and WM has been reported. Nevertheless, most studies focus on the capacity to retain information rather than on the attention-dependent stages of encoding and retrieval. The current study uses a visual short-term memory binding task, measuring both behavioral and electrophysiological responses to characterize WM encoding, binding and retrieval comparing ADHD and non-ADHD matched adolescents. ADHD exhibited poorer accuracy and larger reaction times than non-ADHD on all conditions but especially when a change across encoding and test displays occurred. Binding manipulation affected equally both groups. Encoding P3 was larger in the non-ADHD group. Retrieval P3 discriminated change only in the non-ADHD group. Binding-dependent ERP modulations did not reveal group differences. Encoding and retrieval P3 were significantly correlated only in non-ADHD. These results suggest that while binding processes seem to be intact in ADHD, attention-related encoding and retrieval processes are compromised, resulting in a failure in the prioritization of relevant information. This new evidence can also inform recent theories of binding in visual WM.

Data from brain activity during visual working memory replicates the correlation between contralateral delay activity and memory capacity.

This article provides data from statistical analysis of event-related brain potentials (ERPs) and behavioural performance from 23 participants during a working memory task. Specifically, we used the change detection task from Vogel 2004, using the same timing but a modified size and distance between stimuli. Contralateral delay activity (CDA) was calculated from posterior parieto-occipital electrodes and then it was compared between conditions with different memory load (one, two and four items). Working memory capacity (WMC) was calculated from behavioural data using the formula developed by Pashler (1988). Correlation was performed between WMC and the CDA amplitude difference (from two to four items). The correlation replicates the results from the original paper of Vogel 2004 [1], even though some parameters are different from the original design.

Electrophysiological evidence of the differential modulation of approach-related processes toward attractive foods by immersive or mindful viewing conditions.

Awareness of mental events as mere representations rather than as accurate depictions of reality, also known as dereification, is one of the key features of mindfulness meditation. Dereification is juxtaposed to subjective realism, the process of being lost or totally immersed in the contents of one's mind. Excessive subjective realism is a hallmark of several psychiatric disorders. Here, we investigated whether a "mindful" (dereified) compared with an "immersed" (highly subjectively real) attitude, induced by instructions, differentially modulates approach-avoidance tendencies when processing visual stimuli. We presented novices and experienced meditators with neutral and attractive food images under both mindful and immersed states. Then, participants performed an approach-avoidance Task (AAT) during which we obtained behavioral data, salivary volume, EEG recordings, and self-report measures. The approach bias toward attractive food was correlated with N2 amplitude, a marker of response inhibition, and the regulation of this bias by the mindful instruction compared to the immersed instruction was associated with a modulation of the visual N1 amplitude, a marker of early selective attention. Individuals with more expertise in mindfulness meditation engaged in less late affective reappraisal during mindfulness than during immersion, as measured by lower amplitude in the late positive potential (LPP). Additionally, the ERPs sensitive to the AAT manipulation was also associated to self-report measures of subjective realism, food bias, and mindfulness meditation expertise but not to salivation measures. These findings provide novel insights into the mechanisms by which mindfulness-based interventions could be effective in a range of psychiatric conditions.

Humor Improves Women's but Impairs Men's Iowa Gambling Task Performance.

The Iowa Gambling Task (IGT) is a popular method for examining real-life decision-making. Research has shown gender related differences in performance, in that men consistently outperform women. It has been suggested that these performance differences are related to decreased emotional control in women compared to men. Given the likely role of emotion in these gender differences, in the present study, we examine the effect of a humor induction on IGT performance and whether the effect of humor is moderated by gender. IGT performance and parameters from the Expectancy Valence Model (EVM) were measured in 68 university students (34 men; mean age 22.02, SD = 4.3 and 34 women; mean age 22.3, SD = 4.1) during a 100 trial-IGT task. Participants were exposed to a brief video before each of the IGT decisions available; one half of the samples (17 men and 17 women) was exposed to 100 humor videos, while the other half was exposed to 100 non-humor videos during the task. We observed a significant interaction between gender and humor, such that under humor, women's performance during the last block (trials 80-100) improved (compared to women under non-humor), whereas men's performance during the last block was worse (compared to men under non-humor). Consistent with previous work, under non-humor, men outperformed women in the last block. Lastly, our EVM results show that humor impacts the learning mechanisms of decision-making differently in men and women. Humor impaired men's ability to acquire knowledge about the payoff structure of the decks, and as a consequence, they were stuck in suboptimal performance. On the other hand, humor facilitated women's ability to explore and to learn from experience, improving performance. These findings deepen our understanding of the mechanisms underlying IGT decision-making and differential effects of humor in men and women.

Origin and evolution of human speech: Emergence from a trimodal auditory, visual and vocal network.

In recent years, there have been important additions to the classical model of speech processing as originally depicted by the Broca-Wernicke model consisting of an anterior, productive region and a posterior, perceptive region, both connected via the arcuate fasciculus. The modern view implies a separation into a dorsal and a ventral pathway conveying different kinds of linguistic information, which parallels the organization of the visual system. Furthermore, this organization is highly conserved in evolution and can be seen as the neural scaffolding from which the speech networks originated. In this chapter we emphasize that the speech networks are embedded in a multimodal system encompassing audio-vocal and visuo-vocal connections, which can be referred to an ancestral audio-visuo-motor pathway present in nonhuman primates. Likewise, we propose a trimodal repertoire for speech processing and acquisition involving auditory, visual and motor representations of the basic elements of speech: phoneme, observation of mouth movements, and articulatory processes. Finally, we discuss this proposal in the context of a scenario for early speech acquisition in infants and in human evolution.