Digestivamente: Mobile application for patients with irritable bowel syndrome / Digestivamente: Aplicación móvil para pacientes con Síndrome de Intestino Irritable.

Irritable Bowel Syndrome (IBS) is a chronic functional gastrointestinal disorder that represents a significant public health problem due to the impact it produces on quality of life. Recommended treatments include cognitive-behavioral therapy to address psychological factors that may exacerbate symptoms. The use of technology and particularly mobile applications has grown significantly in recent years. In Argentina, no applications have been developed for IBS. Digestivamente is a mobile application, based on cognitive-behavioral therapy developed in this country. It aims to register the psychological factors of patients with IBS, in the context of a psychotherapeutic treatment. This work describes the application and its functionalities. The use of the application is expected to allow greater adherence to treatment and an improvement in the symptoms of these patients.

El Síndrome de Intestino Irritable (SII) es un trastorno gastrointestinal funcional crónico que representa un problema en salud pública debido al impacto que produce en la calidad de vida. Los tratamientos recomendados incluyen a la terapia cognitivo-conductual para el abordaje de aquellos factores psicológicos que exacerban los síntomas. El uso de la tecnología y particularmente de aplicaciones móviles ha crecido de manera significativa durante los últimos años. En Argentina no se han desarrollado aplicaciones para SII. Digestivamente es una aplicación móvil, basada en la terapia cognitivo-conductual desarrollada en este país. Tiene por objetivo el registro de los factores psicológicos de los pacientes con SII en el contexto de un tratamiento psicoterapéutico. En el presente trabajo se describe la aplicación y sus funcionalidades. Se espera que la utilización de la aplicación permita mayor adherencia al tratamiento y una mejoría en la sintomatología de estos pacientes.

Low-field thoracic magnetic stimulation increases peripheral oxygen saturation levels in coronavirus disease (COVID-19) patients: A single-blind, sham-controlled, crossover study.

ABSTRACT: Severe acute respiratory syndrome coronavirus-2 may cause low oxygen saturation (SpO2) and respiratory failure in patients with coronavirus disease (COVID-19). Hence, increased SpO2 levels in COVID-19 patients could be crucial for their quality of life and recovery. This study aimed to demonstrate that a 30-minute single session of dorsal low-field thoracic magnetic stimulation (LF-ThMS) can be employed to increase SpO2 levels in COVID-19 patients significantly. Furthermore, we hypothesized that the variables associated with LF-ThMS, such as frequency, magnetic flux density, and temperature in the dorsal thorax, might be correlated to SpO2 levels in these patients.Here we employed an LF-ThMS device to noninvasively deliver a pulsed magnetic field from 100 to 118 Hz and 10.5 to 13.1 milliTesla (i.e., 105 to 131 Gauss) to the dorsal thorax. These values are within the intensity range of several pulsed electromagnetic field devices employed in physical therapy worldwide. We designed a single-blind, sham-controlled, crossover study on 5 COVID-19 patients who underwent 2 sessions of the study (real and sham LF-ThMS) and 12 patients who underwent only the real LF-ThMS.We found a statistically significant positive correlation between magnetic flux density, frequency, or temperature, associated with the real LF-ThMS and SpO2 levels in all COVID-19 patients. However, the 5 patients in the sham-controlled study did not exhibit a significant change in their SpO2 levels during sham stimulation. The employed frequencies and magnetic flux densities were safe for the patients. We did not observe adverse events after the LF-ThMS intervention.This study is a proof-of-concept that a single session of LF-ThMS applied for 30 minutes to the dorsal thorax of 17 COVID-19 patients significantly increased their SpO2 levels. However, future research will be needed to understand the physiological mechanisms behind this finding.The study was registered at ClinicalTrials.gov (Identifier: NCT04895267, registered on May 20, 2021) retrospectively registered. https://clinicaltrials.gov/ct2/show/NCT04895267.

Modeling Post-Scratching Locomotion with Two Rhythm Generators and a Shared Pattern Formation.

This study aimed to present a model of post-scratching locomotion with two intermixed central pattern generator (CPG) networks, one for scratching and another for locomotion. We hypothesized that the rhythm generator layers for each CPG are different, with the condition that both CPGs share their supraspinal circuits and their motor outputs at the level of their pattern formation networks. We show that the model reproduces the post-scratching locomotion latency of 6.2 ± 3.5 s, and the mean cycle durations for scratching and post-scratching locomotion of 0.3 ± 0.09 s and 1.7 ± 0.6 s, respectively, which were observed in a previous experimental study. Our findings show how the transition of two rhythmic movements could be mediated by information exchanged between their CPG circuits through routes converging in a common pattern formation layer. This integrated organization may provide flexible and effective connectivity despite the rigidity of the anatomical connections in the spinal cord circuitry.

Tapirus bairdii-Associated Fecal Microbiome from a Critical Conservation Area: Calakmul, México.

Baird's tapir (Tapirus bairdii) is the largest native terrestrial mammal in the Neotropics, which is endangered primarily as a consequence of habitat loss and overhunting. Baird's tapir is predominantly nocturnal and exists at low densities which complicates field studies. Baird's tapir is a large-bodied herbivore that plays a key role in maintaining healthy tropical forests through seed dispersal in its feces. Studies of gut microbiome are essential and valuable to assess the health status of the host and the interaction with the environment. In this study, we collected fresh fecal samples of T. bairdii to analyze its gut microbiome during the rainy and dry seasons in the Calakmul region, which is a critical rainforest conservation area in Mexico. The results of a high-throughput 16S rDNA gene sequencing approach suggest that the fecal microbiome of Baird's tapir has no significant differences in composition among seasons. The most common phyla were Firmicutes, Bacteroidetes, Proteobacteria, Kiritimatiellaeota, and Spirochaetes. This study suggests that the stability of the fecal microbiome is related to similar feeding strategies throughout the year, and emphasizes the value of tapir in seed dispersal (and associated microbes) to the well-conserved forests of the Greater Calakmul region as biodiversity hotspots for conservation.

Low-field thoracic magnetic stimulation increases peripheral oxygen saturation levels in coronavirus disease (COVID-19) patients: a single-blind, sham-controlled, crossover study

The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) may cause low oxygen saturation (SpO2) and respiratory failure in coronavirus disease (COVID-19) patients. Hence the increase of SpO2 levels could be crucial for the quality of life and recovery of these patients. Here we introduce an electromagnetic device termed low-field thoracic magnetic stimulation (LF-ThMS) system. This device was designed to non-invasively deliver a pulsed magnetic field from 100 to 118 Hz and 10.5 to 13.1 mT (i.e., 105 to 131 Gauss) to the dorsal thorax. We show that these frequencies and magnetic flux densities are safe for the patients. We also present a proof-of-concept that a single session of LF-ThMS applied for 30 minutes to the dorsal thorax of 17 COVID-19 patients significantly increases their SpO2 levels. We designed a single-blind, sham-controlled, crossover study on 5 COVID-19 patients who underwent two sessions of the study (real and sham LF-ThMS) and 12 COVID-19 patients who underwent only the real LF-ThMS. We found a statistically significant correlation between magnetic flux density, frequency, or temperature associated with the real LF-ThMS and SpO2 levels in all COVID-19 patients. However, the five patients of the sham-controlled study did not exhibit a significant change in their SpO2 levels during sham stimulation. All the patients did not present adverse events after the LF-ThMS intervention. Trial registrationClinicalTrials.gov IdentifierNCT04895267

Adults with systemic lupus exhibit distinct molecular phenotypes in a cross-sectional study.

BACKGROUND: The clinical and pathologic diversity of systemic lupus erythematosus (SLE) hinders diagnosis, management, and treatment development. This study addresses heterogeneity in SLE through comprehensive molecular phenotyping and machine learning clustering. METHODS: Adult SLE patients (n = 198) provided plasma, serum, and RNA. Disease activity was scored by modified SELENA-SLEDAI. Twenty-nine co-expression module scores were calculated from microarray gene-expression data. Plasma soluble mediators (n = 23) and autoantibodies (n = 13) were assessed by multiplex bead-based assays and ELISAs. Patient clusters were identified by machine learning combining K-means clustering and random forest analysis of co-expression module scores and soluble mediators. FINDINGS: SLEDAI scores correlated with interferon, plasma cell, and select cell cycle modules, and with circulating IFN-α, IP10, and IL-1α levels. Co-expression modules and soluble mediators differentiated seven clusters of SLE patients with unique molecular phenotypes. Inflammation and interferon modules were elevated in Clusters 1 (moderately) and 4 (strongly), with decreased T cell modules in Cluster 4. Monocyte, neutrophil, plasmablast, B cell, and T cell modules distinguished the remaining clusters. Active clinical features were similar across clusters. Clinical SLEDAI trended highest in Clusters 3 and 4, though Cluster 3 lacked strong interferon and inflammation signatures. Renal activity was more frequent in Cluster 4, and rare in Clusters 2, 5, and 7. Serology findings were lowest in Clusters 2 and 5. Musculoskeletal and mucocutaneous activity were common in all clusters. INTERPRETATION: Molecular profiles distinguish SLE subsets that are not apparent from clinical information. Prospective longitudinal studies of these profiles may help improve prognostic evaluation, clinical trial design, and precision medicine approaches. FUNDING: US National Institutes of Health.

B-Cell and Monocyte Contribution to Systemic Lupus Erythematosus Identified by Cell-Type-Specific Differential Expression Analysis in RNA-Seq Data.

Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by complex interplay among immune cell types. SLE activity is experimentally assessed by several blood tests, including gene expression profiling of heterogeneous populations of cells in peripheral blood. To better understand the contribution of different cell types in SLE pathogenesis, we applied the two methods in cell-type-specific differential expression analysis, csSAM and DSection, to identify cell-type-specific gene expression differences in heterogeneous gene expression measures obtained using RNA-seq technology. We identified B-cell-, monocyte-, and neutrophil-specific gene expression differences. Immunoglobulin-coding gene expression was altered in B-cells, while a ribosomal signature was prominent in monocytes. On the contrary, genes differentially expressed in the heterogeneous mixture of cells did not show any functional enrichment. Our results identify antigen binding and structural constituents of ribosomes as functions altered by B-cell- and monocyte-specific gene expression differences, respectively. Finally, these results position both csSAM and DSection methods as viable techniques for cell-type-specific differential expression analysis, which may help uncover pathogenic, cell-type-specific processes in SLE.

Improved detection of magnetic signals by a MEMS sensor using stochastic resonance.

We introduce the behavior of the electrical output response of a magnetic field sensor based on microelectromechanical systems (MEMS) technology under different levels of controlled magnetic noise. We explored whether a particular level of magnetic noise applied on the vicinity of the MEMS sensor can improve the detection of subthreshold magnetic fields. We examined the increase in the signal-to-noise ratio (SNR) of such detected magnetic fields as a function of the magnetic noise intensity. The data disclosed an inverted U-like graph between the SNR and the applied magnetic noise. This finding shows that the application of an intermediate level of noise in the environment of a MEMS magnetic field sensor improves its detection capability of subthreshold signals via the stochastic resonance phenomenon.

Two functional lupus-associated BLK promoter variants control cell-type- and developmental-stage-specific transcription.

Efforts to identify lupus-associated causal variants in the FAM167A/BLK locus on 8p21 are hampered by highly associated noncausal variants. In this report, we used a trans-population mapping and sequencing strategy to identify a common variant (rs922483) in the proximal BLK promoter and a tri-allelic variant (rs1382568) in the upstream alternative BLK promoter as putative causal variants for association with systemic lupus erythematosus. The risk allele (T) at rs922483 reduced proximal promoter activity and modulated alternative promoter usage. Allelic differences at rs1382568 resulted in altered promoter activity in B progenitor cell lines. Thus, our results demonstrated that both lupus-associated functional variants contribute to the autoimmune disease association by modulating transcription of BLK in B cells and thus potentially altering immune responses.

Digital signal processing by virtual instrumentation of a MEMS magnetic field sensor for biomedical applications.

We present a signal processing system with virtual instrumentation of a MEMS sensor to detect magnetic flux density for biomedical applications. This system consists of a magnetic field sensor, electronic components implemented on a printed circuit board (PCB), a data acquisition (DAQ) card, and a virtual instrument. It allows the development of a semi-portable prototype with the capacity to filter small electromagnetic interference signals through digital signal processing. The virtual instrument includes an algorithm to implement different configurations of infinite impulse response (IIR) filters. The PCB contains a precision instrumentation amplifier, a demodulator, a low-pass filter (LPF) and a buffer with operational amplifier. The proposed prototype is used for real-time non-invasive monitoring of magnetic flux density in the thoracic cage of rats. The response of the rat respiratory magnetogram displays a similar behavior as the rat electromyogram (EMG).

Respiratory magnetogram detected with a MEMS device.

Magnetic fields generated by the brain or the heart are very useful in clinical diagnostics. Therefore, magnetic signals produced by other organs are also of considerable interest. Here we show first evidence that thoracic muscles can produce a strong magnetic flux density during respiratory activity, that we name respiratory magnetogram. We used a small magnetometer based on microelectromechanical systems (MEMS), which was positioned inside the open thoracic cage of anaesthetized and ventilated rats. With this new MEMS sensor of about 20 nT resolution, we recorded a strong and rhythmic respiratory magnetogram of about 600 nT.

Evidence of dynamically dysregulated gene expression pathways in hyperresponsive B cells from African American lupus patients.

Recent application of gene expression profiling to the immune system has shown a great potential for characterization of complex regulatory processes. It is becoming increasingly important to characterize functional systems through multigene interactions to provide valuable insights into differences between healthy controls and autoimmune patients. Here we apply an original systematic approach to the analysis of changes in regulatory gene interconnections between in Epstein-Barr virus transformed hyperresponsive B cells from SLE patients and normal control B cells. Both traditional analysis of differential gene expression and analysis of the dynamics of gene expression variations were performed in combination to establish model networks of functional gene expression. This Pathway Dysregulation Analysis identified known transcription factors and transcriptional regulators activated uniquely in stimulated B cells from SLE patients.

Effects of IRF5 lupus risk haplotype on pathways predicted to influence B cell functions.

Both genetic and environmental interactions affect systemic lupus erythematosus (SLE) development and pathogenesis. One known genetic factor associated with lupus is a haplotype of the interferon regulatory factor 5 (IRF5) gene. Analysis of global gene expression microarray data using gene set enrichment analysis identified multiple interferon- and inflammation-related gene sets significantly overrepresented in cells with the risk haplotype. Pathway analysis using expressed genes from the significant gene sets impacted by the IRF5 risk haplotype confirmed significant correlation with the interferon pathway, Toll-like receptor pathway, and the B-cell receptor pathway. SLE patients with the IRF5 risk haplotype have a heightened interferon signature, even in an unstimulated state (P = 0.011), while patients with the IRF5 protective haplotype have a B cell interferon signature similar to that of controls. These results identify multiple genes in functionally significant pathways which are affected by IRF5 genotype. They also establish the IRF5 risk haplotype as a key determinant of not only the interferon response, but also other B-cell pathways involved in SLE.

Genetic and physical interaction of the B-cell systemic lupus erythematosus-associated genes BANK1 and BLK.

OBJECTIVES: Altered signalling in B cells is a predominant feature of systemic lupus erythematosus (SLE). The genes BANK1 and BLK were recently described as associated with SLE. BANK1 codes for a B-cell-specific cytoplasmic protein involved in B-cell receptor signalling and BLK codes for an Src tyrosine kinase with important roles in B-cell development. To characterise the role of BANK1 and BLK in SLE, a genetic interaction analysis was performed hypothesising that genetic interactions could reveal functional pathways relevant to disease pathogenesis. METHODS: The GPAT16 method was used to analyse the gene-gene interactions of BANK1 and BLK. Confocal microscopy was used to investigate co-localisation, and immunoprecipitation was used to verify the physical interaction of BANK1 and BLK. RESULTS: Epistatic interactions between BANK1 and BLK polymorphisms associated with SLE were observed in a discovery set of 279 patients and 515 controls from northern Europe. A meta-analysis with 4399 European individuals confirmed the genetic interactions between BANK1 and BLK. As BANK1 was identified as a binding partner of the Src tyrosine kinase LYN, the possibility that BANK1 and BLK could also show a protein-protein interaction was tested. The co-immunoprecipitation and co-localisation of BLK and BANK1 were demonstrated. In a Daudi cell line and primary naive B cells endogenous binding was enhanced upon B-cell receptor stimulation using anti-IgM antibodies. CONCLUSION: This study shows a genetic interaction between BANK1 and BLK, and demonstrates that these molecules interact physically. The results have important consequences for the understanding of SLE and other autoimmune diseases and identify a potential new signalling pathway.

Cognitive Factors in Fibromyalgia: The Role of Self-Concept and Identity Related Conflicts.

Fibromyalgia is a syndrome characterized by the presence of diffuse and chronic musculoskeletal pain of unknown etiology. Clinical diagnosis and the merely palliative treatments considerably affect the patient's experience and the chronic course of the disease. Therefore, several authors have emphasized the need to explore issues related to self in these patients. The repertory grid technique (RGT), derived from personal construct theory, is a method designed to assess the patient's construction of self and others. A group of women with fibromyalgia (n = 30) and a control group (n = 30) were assessed using RGT. Women with fibromyalgia also completed the Fibromyalgia Impact Questionnaire and a visualanalogue scale for pain, and painful tender points were explored. Results suggest that these women had a higher present self-ideal self discrepancy and a lower perceived adequacy of others, and it was more likely to find implicative dilemmas among them compared to controls. These dilemmas are a type of cognitive conflict in which the symptom is construed as "enmeshed" with positive characteristics of the self. Finally, implications of these results for the psychological treatment of fibromyalgia are suggested to give a more central role to self-identity issues and to the related cognitive conflicts.

Interaction of calcium and Ro60: increase of antigenicity.

The structural and functional integrity of the cell is largely maintained by protein-protein interactions. Recently, we demonstrated that multiple antigenic peptides (MAPs) constructed from 60 kDa Ro sequence could be used to show intramolecular and intermolecular protein-protein interaction within the 60 kDa Ro ribonucleoprotein particle. We were interested in understanding the mechanism of this binding and hypothesized that this interaction might be mediated through divalent metal ions. The 60 kDa Ro-MAPs failed to interact with purified 60 kDa Ro in the presence of EDTA or EGTA when analyzed by Ouchterlony or surface plasmon resonance (SPR) analysis. When purified 60 kDa Ro was incubated with various metal ions such as Cu2+, Mg2+, Zn2+ and Ca2+, and analyzed by Ouchterlony or SPR for binding to specific 60 kDa Ro-MAPs only Ca2+ ions significantly increased the binding. It was interesting to note that recombinant 60 kDa Ro formed precipitin lines with Ro-MAPs only in the presence of Ca2+ ions. Anti-Ro60 containing SLE sera bound to recombinant Ro60 strongly when incubated in the presence of Ca2+ ions but not in the absence of Ca2+ ions. Using SPR analysis we also found that native Ro60 binds to La only in the presence of Ca2+. These data imply that Ca2+ induces a more native tertiary structure to recombinant 60 kDa Ro and makes it more antigenic. Thus, the observed intramolecular and intermolecular interactions and antigen-antibody interactions could be Ca2+ ion mediated conformational interactions, and we propose that 60 kDa Ro is a calcium binding protein.