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Borderline Personality Disorder (BPD) symptoms include inappropriate control of anger and severe emotional dysregulation after rejection in daily life. Nevertheless, when using the Cyberball paradigm, a tossing game to simulate social exclusion, the seven basic emotions (happiness, sadness, anger, surprise, fear, disgust, and contempt) have not been exhaustively tracked out. It was hypothesized that these patients would show anger, contempt, and disgust during the condition of exclusion versus the condition of inclusion. When facial emotions are automatically detected by Artificial Intelligence, “blending”, -or a mixture of at least two emotions- and “masking”, -or showing happiness while expressing negative emotions- may be most easily traced expecting higher percentages during exclusion rather than inclusion. Therefore, face videos of fourteen patients diagnosed with BPD (26 ± 6 years old), recorded while playing the tossing game, were analyzed by the FaceReader software. The comparison of conditions highlighted an interaction for anger: it increased during inclusion and decreased during exclusion. During exclusion, the masking of surprise; i.e., displaying happiness while feeling surprised, was significantly more expressed. Furthermore, disgust and contempt were inversely correlated with greater difficulties in emotion regulation and symptomatology, respectively. Therefore, the automatic detection of emotional expressions during both conditions could be useful in rendering diagnostic guidelines in clinical scenarios.

Summary: Nerve growth factor receptor (NGFR) is expressed by follicular dendritic cells (FDCs). However, the role of NGFR in the humoral response is not well defined. Here, we study the effect of Ngfr loss on lymph node organization and function, demonstrating that Ngfr depletion leads to spontaneous germinal center (GC) formation and an expansion of the GC B cell compartment. In accordance with this effect, stromal cells are altered in Ngfr−/− mice with a higher frequency of FDCs, characterized by CD21/35, MAdCAM-1, and VCAM-1 overexpression. GCs are located ectopically in Ngfr−/− mice, with lost polarization together with impaired high-affinity antibody production and an increase in circulating autoantibodies. We observe higher levels of autoantibodies in Bcl2 Tg/Ngfr−/− mice, concomitant with a higher incidence of autoimmunity and lower overall survival. Our work shows that NGFR is involved in maintaining GC structure and function, participating in GC activation, antibody production, and immune tolerance.

Using new continuum and molecular line data from the Atacama Large Millimeter/submillimeter Array Three-millimeter Observations of Massive Star-forming Regions (ATOMS) survey and archival Very Large Array, 4.86 GHz data, we present direct observational evidence of hierarchical triggering relating three epochs of massive star formation in a ringlike H ii region, G24.47+0.49. We find from radio flux analysis that it is excited by a massive star(s) of spectral type O8.5V–O8V from the first epoch of star formation. The swept-up ionized ring structure shows evidence of secondary collapse, and within this ring, a burst of massive star formation is observed in different evolutionary phases, which constitutes the second epoch. ATOMS spectral line (e.g., HCO ^+ (1–0)) observations reveal an outer concentric molecular gas ring expanding at a velocity of ∼9 km s ^−1 , constituting the direct and unambiguous detection of an expanding molecular ring. It harbors twelve dense molecular cores with surface mass density greater than 0.05 g cm ^−2 , a threshold typical of massive star formation. Half of them are found to be subvirial and thus in gravitational collapse making them the third epoch of potential massive star-forming sites.

The pre-Bötzinger complex, situated in the ventrolateral medulla, serves as the central generator for the inspiratory phase of the respiratory rhythm. Evidence strongly supports its pivotal role in generating, and, in conjunction with the post-inspiratory complex and the lateral parafacial nucleus, in shaping the respiratory rhythm. While there remains an ongoing debate concerning the mechanisms underlying these nuclei’s ability to generate and modulate breathing, transgenic rodent models have significantly contributed to our understanding of these processes. However, there is a significant knowledge gap regarding the spectrum of transgenic rodent lines developed for studying respiratory rhythm, and the methodologies employed in these models. In this study, we conducted a scoping review to identify commonly used transgenic rodent lines and techniques for studying respiratory rhythm generation and modulation. Following PRISMA guidelines, we identified relevant papers in PubMed and EBSCO on 29 March 2023, and transgenic lines in Mouse Genome Informatics and the International Mouse Phenotyping Consortium. With strict inclusion and exclusion criteria, we identified 80 publications spanning 1997–2022 using 107 rodent lines. Our findings revealed 30 lines focusing on rhythm generation, 61 on modulation, and 16 on both. The primary in vivo method was whole-body plethysmography. The main in vitro method was hypoglossal/phrenic nerve recordings using the en bloc preparation. Additionally, we identified 119 transgenic lines with the potential for investigating the intricate mechanisms underlying respiratory rhythm. Through this review, we provide insights needed to design more effective experiments with transgenic animals to unravel the mechanisms governing respiratory rhythm. The identified transgenic rodent lines and methodological approaches compile current knowledge and guide future research towards filling knowledge gaps in respiratory rhythm generation and modulation.

ABSTRACTBacillus Calmette-Guérin (BCG), the nonpathogenic Mycobacterium bovis strain used as tuberculosis vaccine, has been successfully used as treatment for non-muscle invasive bladder cancer for decades, and suggested to potentiate cellular and humoral immune responses. However, the exact mechanism of action is not fully understood. We previously described that BCG mainly activated anti-tumor cytotoxic NK cells with upregulation of CD56 and a CD16+ phenotype. Now, we show that stimulation of human peripheral blood mononuclear cells with iBCG, a preparation based on BCG-Moreau, expands oligoclonal γδ T-cells, with a cytotoxic phenotype, together with anti-tumor CD56high CD16+ NK cells. We have used scRNA-seq, flow cytometry, and functional assays to characterize these BCG-activated γδ T-cells in detail. They had a high IFNγ secretion signature with expression of CD27+ and formed conjugates with bladder cancer cells. BCG-activated γδ T-cells proliferated strongly in response to minimal doses of cytokines and had anti-tumor functions, although not fully based on degranulation. BCG was sufficient to stimulate proliferation of γδ T-cells when cultured with other PBMC; however, BCG alone did not stimulate expansion of purified γδ T-cells. The characterization of these non-donor restricted lymphocyte populations, which can be expanded in vitro, could provide a new approach to prepare cell-based immunotherapy tools.

La martucha (Potos flavus) es una especie amenazada en México y ha sido registrada previamente en el estado de Guerrero. Recopilamos y ampliamos su distribución en el estado de Guerrero. Se realizó una búsqueda de ocurrencias de la especie en los repositorios electrónicos EncicloVida, Naturalista y GBIF, así como en la literatura científica publicada para el estado, que incluyó observaciones directas e indirectas (piel, restos óseos, e individuos atropellados o cazados). Se recopilaron 41 registros de P. flavus, de los cuales el 34 % fueron ocurrencias de la literatura y los repositorios electrónicos, y el 66 % de muestreos de campo en los últimos 16 años. Se resalta la importancia de seguir realizando exploraciones científicas dirigidas a aquellas áreas poco exploradas, así como la necesidad de describir principales amenazas y el estado de conservación de las poblaciones de P. flavus. Se sugiere la realización de pláticas divulgativas que ayuden a entender la importancia y los servicios que brinda esta especie a los ecosistemas.

Abstract Here we explored the role of interleukin-1β (IL-1β) repressor cytokine, IL-1 receptor antagonist (IL-1rn), in both healthy and abnormal hematopoiesis. Low IL-1RN is frequent in acute myeloid leukemia (AML) patients and represents a prognostic marker of reduced survival. Treatments with IL-1RN and the IL-1β monoclonal antibody canakinumab reduce the expansion of leukemic cells, including CD34+ progenitors, in AML xenografts. In vivo deletion of IL-1rn induces hematopoietic stem cell (HSC) differentiation into the myeloid lineage and hampers B cell development via transcriptional activation of myeloid differentiation pathways dependent on NFκB. Low IL-1rn is present in an experimental model of pre-leukemic myelopoiesis, and IL-1rn deletion promotes myeloproliferation, which relies on the bone marrow hematopoietic and stromal compartments. Conversely, IL-1rn protects against pre-leukemic myelopoiesis. Our data reveal that HSC differentiation is controlled by balanced IL-1β/IL-1rn levels under steady-state, and that loss of repression of IL-1β signaling may underlie pre-leukemic lesion and AML progression.

Este trabajo documenta el primer registro de anomalías cromáticas en el pecarí de collar (Pecari tajacu) y el tercero en el mapache (Procyon lotor) para México. Los hallazgos se realizaron durante el monitoreo realizado entre el 2009 y el 2021, utilizando cámaras-trampa, principalmente en la ecorregión de la Sierra Madre del Sur del estado de Guerrero, México. Procyon lotor fue registrado entre el 5 de noviembre y el 1 de diciembre de 2019, en vegetación riparia de bosque tropical caducifolio (17°47’35”N, 98°39’59”W, 1134 m de altitud). Mientras que Pecari tajacu se registró el 7 de junio y el 22 de julio del 2021 en una brecha saca cosecha abandonada (17°38’12”N, 100°40’50”W; 1532 m de altitud).

ABSTRACT BACKGROUND: In Latin America, liver cancer is one of the top causes of cancer mortality. It is the fifth most common cause of death among malignant tumors in Mexico and is the leading cause in Hidalgo State (43.8% of the population living in poverty). OBJECTIVE: To conduct a correlational analysis on the main risk factors for liver cancer in Hidalgo State, Mexico, including municipal disaggregation and comparison with the national level. DESIGN AND SETTING: Cross-sectional, correlational, descriptive and comparative epidemiological study using Mexican governmental databases covering 1990-2019. METHODS: A comprehensive review of the databases of the General Directorate of Health Information (DGIS) was performed to analyze official death figures, hospital discharges and national and municipal population projections, using specific search criteria defined in the Global Burden of Disease classification, based on the risk factors for liver cancer. RESULTS: Liver cancer rates showed an evident rise in Hidalgo (183%), moving from 21st place in Mexico in 1990 to 9th place in 2019. This increase was correlated with alcoholism. An increasing trend for liver cancer deaths, of 133.89%, is projected for 2030. Females and the population over 60 years of age are more affected. There are some critical regions with liver cancer death rates twice the national rate or more. CONCLUSION: Targeted effective public health strategies should be structured by identifying, characterizing and regionalizing critical marginalized municipalities that are vulnerable to alcoholism and other risk factors for liver cancer. This approach may be helpful for other states in Mexico or similar countries.

The individual contribution of specific myeloid subsets such as CD1c+ conventional DC (cDC) to perpetuation of rheumatoid arthritis (RA) pathology remains unclear. In addition, the specific innate sensors driving pathogenic activation of CD1c+ cDC in patients with RA and their functional implications have not been characterized. Here, we assessed phenotypical, transcriptional, and functional characteristics of CD1c+ and CD141+ cDC and monocytes from the blood and synovial fluid of patients with RA. Increased levels of CCR2 and the IgG receptor CD64 on circulating CD1c+ cDC was associated with the presence of this DC subset in the synovial membrane in patients with RA. Moreover, synovial CD1c+ cDC are characterized by increased expression of proinflammatory cytokines and high abilities to induce pathogenic IFN-γ+IL-17+CD4+ T cells in vitro. Finally, we identified the crosstalk between Fcγ receptors and NLRC4 as a potential molecular mechanism mediating pathogenic activation, CD64 upregulation, and functional specialization of CD1c+ cDC in response to dsDNA-IgG in patients with RA.

Summary: Autologous hematopoietic stem cell transplantation (autoHSCT) is a treatment option for hematological disorders and pediatric solid tumors. After an autoHSCT, natural killer (NK) cells are the first lymphocyte subset returning to normal levels. To uncover global changes during NK cell reconstitution after autoHSCT, we performed RNA-sequencing on NK cells before and after autoHSCT. Results showed profound changes in the gene expression profile of NK cells immediately after autoHSCT. Several biological processes including cell cycle, DNA replication and the mevalonate pathway were enriched. Significantly, we observed that following autoHSCT, NK cells acquired a decidual-like gene expression profile, including the expression of CD9. By using multiparametric flow cytometry, we confirmed the expansion of NK cells expressing CD9 immediately after autoHSCT, which exhibited higher granzyme B and perforin expression levels than CD9− NK cells. These results provide insights into the physiopathology of NK cells during their reconstitution after autoHSCT.

Education in the pandemic time often received an improvised and non-realistic treatment. This is a major reason for planning now the post-pandemic period. According to the literature and document analysis, social, international and intra-national fractures, detected by current theories, were largely exposed. Besides Covid-19, other crises developed, such as impoverishment and violence. In general, the population has had losses; however, the least privileged have been subject to a greater burden. Countries cannot repeat past mistakes or try to restore Education as it was before, since the circumstances are different. Furthermore, in addition to the learning deficit, it is urgent to recover Education in its multiple ends and goals. Therefore, it is important to support educators, students and families, with a specific focus on the underprivileged, counting on the participation of the social forces of community and society.

The Atacama Large Millimeter/submillimeter Array (ALMA) Survey of Star Formation and Evolution in Massive Protoclusters with Blue Profiles (ASSEMBLE) aims to investigate the process of mass assembly and its connection to high-mass star formation theories in protoclusters in a dynamic view. We observed 11 massive ( M _clump ≳ 10 ^3 M _⊙ ), luminous ( L _bol ≳ 10 ^4 L _⊙ ), and blue-profile (infall signature) clumps by ALMA with resolution of ∼2200–5500 au (median value of 3500 au) at 350 GHz (870 μ m). We identified 248 dense cores, including 106 cores showing protostellar signatures and 142 prestellar core candidates. Compared to early stage infrared dark clouds (IRDCs) by ASHES, the core mass and surface density within the ASSEMBLE clumps exhibited a significant increment, suggesting concurrent core accretion during the evolution of the clumps. The maximum mass of prestellar cores was found to be 2 times larger than that in IRDCs, indicating that evolved protoclusters have the potential to harbor massive prestellar cores. The mass relation between clumps and their most massive core (MMCs) is observed in ASSEMBLE but not in IRDCs, which is suggested to be regulated by multiscale mass accretion. The mass correlation between the core clusters and their MMCs has a steeper slope compared to that observed in stellar clusters, which can be due to fragmentation of the MMC and stellar multiplicity. We observe a decrease in core separation and an increase in central concentration as protoclusters evolve. We confirm primordial mass segregation in the ASSEMBLE protoclusters, possibly resulting from gravitational concentration and/or gas accretion.

There is growing evidence that high-mass star formation and hub-filament systems (HFS) are intricately linked. The gas kinematics along the filaments and the forming high-mass star(s) in the central hub are in excellent agreement with the new generation of global hierarchical high-mass star formation models. In this paper, we present an observational investigation of a typical HFS cloud, G310.142+0.758 (G310 hereafter), which reveals unambiguous evidence of mass inflow from the cloud scale via the filaments onto the forming protostar(s) at the hub conforming with the model predictions. Continuum and molecular line data from the ATOMS and MALT90 surveys that cover different spatial scales are used. Three filaments (with a total mass of 5.7 ± 1.1 × 10 ^3 M _⊙ ) are identified converging toward the central hub region where several signposts of high-mass star formation have been observed. The hub region contains a massive clump (1280 ± 260 M _⊙ ) harboring a central massive core. Additionally, five outflow lobes are associated with the central massive core implying a forming cluster. The observed large-scale, smooth, and coherent velocity gradients from the cloud down to the core scale, and the signatures of infall motion seen in the central massive clump and core, clearly unveil a nearly continuous, multi-scale mass accretion/transfer process at a similar mass infall rate of ∼10 ^−3 M _⊙ yr ^−1 over all scales, feeding the central forming high-mass protostar(s) in the G310 HFS cloud.

A direct comparison between hydrodynamical simulations and observations is needed to improve the physics included in the former and to test biases in the latter. Post-processing radiative transfer and synthetic observations are now the standard way to do this. We report on the first application of the SKIRT radiative-transfer code to simulations of a star-forming cloud. The synthetic observations are then analyzed following traditional observational workflows. We find that in the early stages of the simulation, stellar radiation is inefficient in heating dust to the temperatures that are observed in Galactic clouds, thus the addition of an interstellar radiation field is necessary. The spectral energy distribution of the cloud settles rather quickly after ∼3 Myr of evolution from the onset of star formation, but its morphology continues to evolve for ∼8 Myr due to the expansion of H ii regions and the respective creation of cavities, filaments, and ridges. Modeling synthetic Herschel fluxes with one- or two-component modified blackbodies underestimates total dust masses by a factor of ∼2. However, spatially resolved fitting recovers up to about 70% of the intrinsic value. This “missing mass” is located in a very cold dust component with temperatures below 10 K, which does not contribute appreciably to the far-infrared flux. This effect could bias real observations if this dust exists in large amounts. Finally, we tested observational calibrations of the SFR based on infrared fluxes and concluded that they are in agreement when compared to the intrinsic SFR of the simulation averaged over ∼100 Myr.

ABSTRACT Ebola virus (EBOV) VP24 protein is a nucleocapsid-associated protein that inhibits interferon (IFN) gene expression and counteracts the IFN-mediated antiviral response, preventing nuclear import of signal transducer and activator of transcription 1 (STAT1). Proteomic studies to identify additional EBOV VP24 partners have pointed to the nuclear membrane component emerin as a potential element of the VP24 cellular interactome. Here, we have further studied this interaction and its impact on cell biology. We demonstrate that VP24 interacts with emerin but also with other components of the inner nuclear membrane, such as lamin A/C and lamin B. We also show that VP24 diminishes the interaction between emerin and lamin A/C and compromises the integrity of the nuclear membrane. This disruption is associated with nuclear morphological abnormalities, activation of a DNA damage response, the phosphorylation of extracellular signal-regulated kinase (ERK), and the induction of interferon-stimulated gene 15 (ISG15). Interestingly, expression of VP24 also promoted the cytoplasmic translocation and downmodulation of barrier-to-autointegration factor (BAF), a common interactor of lamin A/C and emerin, leading to repression of the BAF-regulated CSF1 gene. Importantly, we found that EBOV infection results in the activation of pathways associated with nuclear envelope damage, consistent with our observations in cells expressing VP24. In summary, here we demonstrate that VP24 acts at the nuclear membrane, causing morphological and functional changes in cells that recapitulate several of the hallmarks of laminopathy diseases. IMPORTANCE The Ebola virus (EBOV) VP24 protein is a nucleocapsid-associated protein with multiple functions. Proteomic studies have identified the cellular nuclear membrane component emerin as a potential VP24 interactor. Here, we demonstrate that VP24 not only interacts with emerin but also with lamin A/C and lamin B, prompting nuclear membrane disruption. This disruption is associated with nuclear morphological abnormalities, activation of a DNA damage response, the phosphorylation of extracellular signal-regulated kinase (ERK), and the induction of interferon-stimulated gene 15 (ISG15). Interestingly, VP24 also promotes the cytoplasmic translocation and downmodulation of barrier-to-autointegration factor (BAF), leading to repression of the BAF-regulated CSF1 gene. Finally, we show that EBOV infection also results in the activation of pathways associated with nuclear envelope damage, consistent with our observations in cells expressing VP24. These results reveal novel activities of EBOV VP24 protein, resulting in a cell phenotype similar to that of most laminopathies, with potential impact on EBOV replication.

Para determinar el efecto del peso al nacimiento sobre los balances de nitrógeno (N) y energía (E) en cerdos en crecimiento se realizaron balances de N y E a cinco pares de hermanos. Cada par constó de un cerdo de peso bajo al nacimiento (PBN=912 ± 40 g) y un cerdo de peso normal al nacimiento (PNN=1,610 ± 223 g). Los cerdos se manejaron de manera normal hasta los 90 días de edad, cuando se trasladaron a la Unidad Metabólica para realizar los dos estudios de balance: a los 50 kg de peso y a la misma edad (cuando el cerdo PBN pesó 50 kg). Los PNN digirieron más (P

El trastorno por déficit de atención e hiperactividad (TDAH) ha sido comúnmente asociado a déficits en los subprocesos atencionales y en las funciones ejecutivas. El presente trabajo pretende estudiar el rendimiento cognitivo-ejecutivo de niños y niñas entre 8 y 15 años de edad con diagnóstico de TDAH, comparándolo con el rendimiento de un grupo normativo. La muestra total estaba compuesta por 47 participantes a los que se les administró una batería de pruebas neuropsicológicas. Las puntuaciones relativas al funcionamiento cognitivo-ejecutivo de la muestra clínica son indicativas de un rendimiento medio. Se obtienen diferencias estadísticamente significativas entre el grupo clínico y el control en velocidad de procesamiento psicomotor y lector, atención selectiva, inhibición cognitiva, capacidad de concentración y resistencia a la interferencia. El abordaje neuropsicológico del TDAH se demuestra como una herramienta capaz de identificar alteraciones en los procesos cognitivo-ejecutivos y de proporcionar a los sujetos estrategias metacognitivas de orden superior, que podrían mejorar su capacidad de aprendizaje y de autorregulación de la conducta.

Meis genes have been shown to control essential processes during development of the central and peripheral nervous system. Here we have explored the roles of the Meis2 gene during vertebrate inner ear induction and the formation of the cochlea. Meis2 is expressed in several tissues required for inner ear induction and in non-sensory tissue of the cochlear duct. Global inactivation of Meis2 in the mouse leads to a severely reduced size of the otic vesicle. Tissue-specific knock outs of Meis2 reveal that its expression in the hindbrain is essential for otic vesicle formation. Inactivation of Meis2 in the inner ear itself leads to an aberrant coiling of the cochlear duct. By analyzing transcriptomes obtained from Meis2 mutants and ChIPseq analysis of an otic cell line, we define candidate target genes for Meis2 which may be directly or indirectly involved in cochlear morphogenesis. Taken together, these data show that Meis2 is essential for inner ear formation and provide an entry point to unveil the network underlying proper coiling of the cochlear duct.

The pre-Bötzinger complex is a neural network located in the ventrolateral brainstem that generates the respiratory rhythm. Under normoxic conditions, this area shows two inspiratory burst patterns, sigh and non-sigh. Several studies have shown that in vitro application of peptides, such as bombesin, stimulates the respiratory rate and increases the appearance of sighs. However, it is difficult to distinguish between sighs and non-sighs waveforms, which makes it difficult to study their properties under experimental conditions. The fractal and multifractal analysis have proven to be valuable tools for studying physiological time series, thus in this study, we applied this methodology to characterize sighs and non-sighs. Our results regarding fractality, shown that the sighs and non-sighs have similar Hurst exponents and that the application of bombesin only decreased the Hurst exponent of non-sighs. On the other hand, our results on multifractality parameters scaling exponent (τ(q)) and generalized Hurst exponent (H(q)) shown that both sighs and non-sighs were multifractal and this remained even after the application of bombesin. Further analysis showed that sighs and non-sighs had different H(q) values, which changed after the bombesin application. To quantitatively analyzed the multifractal spectrum, we calculated the area of the spectrum (Iα), which was similar between sighs and non-sighs and the application of bombesin did not change this. Altogether, these results show that the analysis of fractal and multifractal parameters allows to characterize and find statistical differences of sighs and non-sighs within and between different experimental conditions. Statement of Significance: The characterization of the respiratory recordings is very difficult and time consuming when is done manually by a researcher. An automated software that can aid this can be very useful. Furthermore, this gives some parameters that can help to statistically differentiate between sighs and non sighs. One interesting finding was that multifractality show differences in the same condition between sighs and non sighs. Also, we found that the neuropeptide bombesin increases the number of sighs without changing the intrinsic structure of the respiration system. This is important to avoid the collapse of the lungs that can be incorporated in mechanical ventilators. We hope that you will find our paper suitable for publication in Brain Multiphysics and will look forward to receiving your response.

Fiber type composition, organization, and distribution are key elements in muscle functioning. These properties can be modified by intrinsic and/or extrinsic factors, such as undernutrition and injuries. Currently, there is no methodology to quantitatively analyze such modifications. On one hand, we propose a fractal approach to determine fiber type organization, using the fractal correlation method in software Fractalyse. On the other hand, we applied the kernel methodology from machine learning to build radial-basis functions for the spatial distribution of fibers (distribution functions), by dividing into square cells a two-dimensional binary image for the spatial distribution of fibers from a muscle fascicle and mounting on each cell a radial-basis function in such a way that the sum of all cell functions creates a smooth version of the fiber histogram on the cell grid. The distribution functions thus created belong in a reproducing kernel Hilbert space which permits us to regard them as vectors and measure distances and angles between them. In the present study, we analyze fiber type organization and distribution in fascicles (F2, F3, F4, and F5) of the extensor digitorum longus muscle (EDLm) from control and undernourished male rats. Fibers were classified according to the ATPase activity in slow, intermediate, and fast. Then, (x, y) coordinates of fibers were used to build binary images and distribution functions for each fiber type and both conditions. The fractal organization analysis showed that fast and intermediate fibers, from both groups, had a fractal organization within the four fascicles, i.e., the fiber assembly is distributed in clusters. We also show that chronic undernutrition altered the organization of fast fibers in the F3, although it still is considered a fractal organization. Distribution function analysis showed that each fiber type (slow, intermediate, and fast) has a unique distribution within the fascicles, in both conditions. However, chronic undernutrition modified the intra-fascicular fiber type distributions, except in the F2. Altogether, these results showed that the methodology herein proposed allows for analyzing fiber type organization and distribution modifications. On the other side, we show that chronic undernutrition alters not only the fiber type composition but also the organization and distribution, which could affect the muscle functioning, and ultimately, its behavior (e.g., locomotion).

An early analysis of circulating monocytes may be critical for predicting COVID-19 course and its sequelae. In 131 untreated, acute COVID-19 patients at emergency room arrival, monocytes showed decreased surface molecule expression, including low HLA-DR, in association with an inflammatory cytokine status and limited anti-SARS-CoV-2-specific T cell response. Most of these alterations had normalized in post-COVID-19 patients 6 months after discharge. Acute COVID-19 monocytes transcriptome showed upregulation of anti-inflammatory tissue repair genes such as BCL6, AREG and IL-10 and increased accessibility of chromatin. Some of these transcriptomic and epigenetic features still remained in post-COVID-19 monocytes. Importantly, a poorer expression of surface molecules and low IRF1 gene transcription in circulating monocytes at admission defined a COVID-19 patient group with impaired SARS-CoV-2-specific T cell response and increased risk of requiring intensive care or dying. An early analysis of monocytes may be useful for COVID-19 patient stratification and for designing innate immunity-focused therapies.

The immunological markers help to know if there is a good recovery of the immunological system in patients infected with HIV. Among them, the lymphocyte T CD4 rate is the main indicator of the patient’s immunological state being used for staging HIV infection, evaluating the mortality or comorbidity risk and the vulnerability to certain oportunistic infections. However, its link with the presence of cognitive alterations is not clear. Therefore, the aim of this article is to study if lymphocyte T CD4 levels are connected with the neuropsychological performance of a group of people infected with HIV and with a previous history of substance use. The sample consisted of 80 seropositive males with a previous history of substance use. They were evaluated by means of a neuropsychological battery which assesses the most affected cognitive domains in HIV population. The results showed that the patients having a higher level of immunodeficiency have a poorer performance in terms of attention, visuomotor dexterity, visual memory, visual perception, auditory-verbal learning and inhibition. Therefore, our results show a realtion between the lymphocyte T CD4 rate and the neuropsychological performance in seropositive people with a previsous history of substance use.

Estudiamos la fijación del curso de acción que ha de seguirse en el desarrollo de una Auditoria Administrativa, determinando los principios que sirven para orientar y marcar la secuencia de las operaciones necesarias para efectuarla. En primer lugar, vamos a determinar las actividades indispensables de investigación para la planeación de la Auditoria Administrativa, presentándolas en el orden que a nuestro juicio es el más lógico. En primer lugar, la Investigación preliminar, posteriormente Entrevistas previas y como parte fundamental dos puntos que convergen en la parte medular de este apartado la Definición del área a investigar y Determinación de los detalles a estudiar.

Background: Up to 30% of patients with pediatric inflammatory bowel disease (IBD) do not respond to anti-Tumor Necrosis Factor (anti-TNF) therapy. The aim of this study was to identify pharmacogenomic markers that predict early response to anti-TNF drugs in pediatric patients with IBD. Methods: An observational, longitudinal, prospective cohort study was conducted. The study population comprised 38 patients with IBD aged < 18 years who started treatment with infliximab or adalimumab (29 responders and nine non-responders). Whole gene expression profiles from total RNA isolated from whole blood samples of six responders and six non-responders taken before administration of the biologic and after two weeks of therapy were analyzed using next-generation RNA sequencing. The expression of six selected genes was measured for purposes of validation in all of the 38 patients recruited using qPCR. Results: Genes were differentially expressed in non-responders and responders (32 before initiation of treatment and 44 after two weeks, Log2FC (Fold change) >0.6 or p value < 0.05). After validation, FCGR1A, FCGR1B, and GBP1 were overexpressed in non-responders two weeks after initiation of anti-TNF treatment (Log2FC 1.05, 1.21, and 1.08, respectively, p value < 0.05). Conclusion: Expression of the FCGR1A, FCGR1B, and GBP1 genes is a pharmacogenomic biomarker of early response to anti-TNF agents in pediatric IBD.

Probiotic bacteria are widely used in functional foods or as dietary supplements. However, the signalling pathways by which they promote beneficial effects on the immune system are not fully understood. The effects of six different probiotics on monocyte-derived dendritic cells (MoDCs) were examined in this study. We found that Lactobacillus rhamnosus triggered full maturation of MoDCs, whereas L. fermentum induced a state of semi-maturation, and Bifidobacterium lactis strains barely modified MoDC basal state. Analysis of expression of genes associated with Toll-like receptor signalling revealed that B. lactis strains induced a weak pro-inflammatory response, and L. fermentum did not affect gene expression of downstream pathways, whereas it increased the expression of cytokines related with STAT3 pathway. Further insight into the pathways triggered by probiotics would facilitate a more appropriate use of probiotics to restore homeostasis in different immune disorders, like inflammatory bowel disease or allergies.

La variedad Maradol es la principal papa - ya cultivada en México y uno de los principales cultivos del estado de Yucatán. Presenta algunos inconvenientes, como la susceptibilidad a viro - sis, por lo que se buscan nuevos materiales que puedan superar en rendimiento a Maradol, pero es necesario que presenten características de cali - dad similares. El objetivo del presente trabajo fue evaluar las características de calidad de los fru - tos de nuevos genotipos producidos en Yucatán. Se usaron 6 materiales comerciales (Maradol, Sensation, Intenzza, Siluet, Lenia Plus y Jíbara) y 2 híbridos generados por INIFAP (Azteca y MSXJ). Se evaluó el tamaño de los frutos, color de cáscara y pulpa, firmeza de la pulpa y conte - nido de sólidos solubles totales. En el tamaño de frutos, excepto Jíbara que es muy grande (2,900 kg) y Siluet que es muy pequeño (1,200 kg), los 6 materiales restantes fueron similares a Maradol. En color de la cás - cara, Intenzza y Siluet presentaron tono similar a Maradol (65 a 67º) pero fueron más luminosos. Siluet y Sensation tuvieron mayor contenido de grados Brix que Maradol, pero también menor firmeza de la pulpa. Considerando el tamaño de los frutos, la firmeza de la pulpa, el contenido desólidos solubles totales y el color de la cáscara y pulpa, los genotipos Sensation, Lenia Plus y MSXJ presentan buenas características, por lo que pueden competir en calidad con la variedad Maradol.

Objective To explore the presence and magnitude of – and change in – socioeconomic and health inequalities between and within Brazil, the Russian Federation, India, China and South Africa – the countries known as BRICS – between 1990 and 2010. Methods Comparable data on socioeconomic and health indicators, at both country and primary subnational levels, were obtained from publicly available sources. Health inequalities between and within countries were identified and summarized by using standard gap and gradient metrics. Findings Four of the BRICS countries showed increases in both income level and income inequality between 1990 and 2010. The exception was Brazil, where income inequality decreased over the same period. Between-country inequalities in level of education and access to sanitation remained mostly unchanged but the largest between-country difference in mean life expectancy increased, from 9 years in 1990 to 20 years in 2010. Throughout the study period, there was disproportionality in the burden of disease between BRICS. However, the national infant mortality rate fell substantially over the study period in all five countries. In Brazil and China, the magnitude of subnational income-related inequalities in infant mortality, both absolute and relative, also decreased substantially. Conclusion Despite the economic prosperity and general improvements in health seen since 1990, profound inequalities in health persist both within and between BRICS. However, the substantial reductions observed – within Brazil and China – in the inequalities in income-related levels of infant mortality are encouraging.

Barrett's esophagus is an area of great interest in Gastroenterology, with an increasing number of research studies being published in recent years and decades. Due to the fast growing evidence regarding this disease, it has become extremely difficult to keep updated on this subject. The present review article aims to summarize and update what is known regarding diagnosis and therapy in Barrett's esophagus. A critical and detailed review is made and the role of surveillance for this condition, techniques available for diagnosis (standard white light endoscopy, virtual chromoendoscopy, magnification...) and treatment (mucosectomy, ablation...) are presented. New and emerging technologies are described in detail and existing evidence is presented.

Lung cancer is one of the most frequent neoplasms in our environment, and represents the first cause of cancer related death in western countries. Diagnostic and therapeutic approach to these patients may be complicated, with endoscopic ultrasound guided fine needle aspiration (EUS-FNA), classically performed by gastroenterologists, playing a very important role. As this disease is not closely related to the "digestive tract", gastroenterologists have been forced to update their knowledge on this field o adequately diagnose this significant group of patients. The recent advent of modern and promising techniques like endobronchial ultrasound guided fine needle aspiration (EBUS-FNA) have prompted new approaches for diagnosis and staging of this type of patients. In this clinical guideline, the "Sociedad Española de Endoscopia Digestiva" (SEED), "Sociedad Española de Patología Digestiva" (SEPD) and the "Asociación Española de Gastroenterología", have jointed efforts to update the existing knowledge on the field and provide their members with evidence based recommendations.

In fission yeast, the ste11 gene encodes the master regulator initiating the switch from vegetative growth to gametogenesis. In a previous paper, we showed that the methylation of H3K4 and consequent promoter nucleosome deacetylation repress ste11 induction and cell differentiation (Materne et al., 2015) but the regulatory steps remain poorly understood. Here we report a genetic screen that highlighted H2B deubiquitylation and the RSC remodeling complex as activators of ste11 expression. Mechanistic analyses revealed more complex, opposite roles of H2Bubi at the promoter where it represses expression, and over the transcribed region where it sustains it. By promoting H3K4 methylation at the promoter, H2Bubi initiates the deacetylation process, which decreases chromatin remodeling by RSC. Upon induction, this process is reversed and efficient NDR (nucleosome depleted region) formation leads to high expression. Therefore, H2Bubi represses gametogenesis by opposing the recruitment of RSC at the promoter of the master regulator ste11 gene.

Background: endoscopic ultrasonography (EUS) and magnetic resonance cholangiography (MRC) are the elective tests in the diagnosis of choledocholithiasis. MRC is best accepted by patients, but its sensitivity might decrease in the evaluation of microlithiasis. Aim: to evaluate the diagnostic accuracy and therapeutic impact of EUS in a prospective cohort of patients with intermediate suspicion of choledocolithiasis and no findings in MRC (normal MRC). Material and methods: during a period of 24 months, all the patients with clinical intermediate suspicion of choledocholithiasis and normal MRC were included. Sensitivity, specificity, diagnostic accuracy, positive predictive value (PPV) and negative predictive value (NPV) of MRC and EUS were compared, and so their impact in the management of these patients. Results: seventy six patients were evaluated (lithiasis in 30% of them). Sensitivity and diagnostic accuracy of EUS (100%, 92%) were significantly higher than MRC values (0%, 70%) (p < 0.05). EUS findings (suspicion of choledocholithiasis) favored a significant change in therapeutic attitude (therapeutic ERCP was performed) in 38% of the patients (in which MRC had ruled out the presence of choledocholithiasis, and so, ERCP had not been performed) (p < 0.05). Conclusions: EUS allows the diagnosis of lithiasis in approximately 1/3 of patients with intermediate suspicion of choledocholithiasis and normal MRC. EUS findings involve a significant change in the management of these patients; this supports the use of EUS in clinical practice.Antecedentes: la ultrasonografía endoscópica (USE) y la colangiografía por resonancia magnética nuclear (CRM) son las técnicas de elección para el diagnóstico de litiasis en la vía biliar. Aunque la CRM es mejor aceptada por los pacientes, la sensibilidad de esta para detectar litiasis de pequeño tamaño podría ser insuficiente. Objetivo: estudiar de forma prospectiva la precisión diagnóstica y el impacto terapéutico de la USE en los pacientes con sospecha intermedia de coledocolitiasis y CRM normal. Material y métodos: se incluyeron prospectivamente durante 24 meses todos los pacientes con sospecha clínica intermedia de coledocolitiasis y CRM negativa. Se compar�� la sensibilidad, especificidad, precisión diagnóstica, valor predictivo positivo y negativo de CRM y USE, así como su impacto en el tratamiento. Resultados: se evaluaron 76 pacientes (litiasis en el 30%). La sensibilidad y precisión diagnóstica de USE (100%, 92%) eran significativamente superiores a las alcanzadas por la CRM (0%, 70%) (p < 0,05). Los hallazgos de la USE (sospecha de coledocolitiasis) propiciaron un cambio significativo en la actitud terapéutica (realización de CPRE terapéutica) en el 38% de los pacientes (CRM había descartado coledocolitiasis y contraindicado la CPRE) (p < 0,05). Conclusiones: en pacientes con sospecha intermedia de coledocolitiasis y CRM normal, la USE permite diagnosticar litiasis en aproximadamente una tercera parte de ellos. Los hallazgos endosonográficos permiten modificar significativamente la actitud terapéutica en estos pacientes, lo que apoya su utilización en la práctica clínica diaria.

Background and objective: the prevalence of gastric polyps in esophagogastroduodenoscopies (EGDs) ranges between 0.33 and 6.35%. The relative frequency of histological subspecies varies widely among published series. The objective is to describe the endoscopic and histological characteristics of the polypoid lesions, and to study possible associations. Material and methods: we retrospectively revised the EGDs done in our center in 2009. Demographic, endoscopic and histological data were gathered. We proceeded to a descriptive analysis and studied possible associations. Results: gastric polypoid lesions were found in 269 of the 6,307 (4.2%) reviewed EGDs, 61% were found in women. Mean age was 64.93 years (SD: ±15.23). A single polyp was found in 186 patients (69.1%), over 10 lesions appeared in 31 (11.5%). An estimated size of ≤ 3 mm was found in 108 lesions (37.2%) and greater than 10 mm in 52 cases (17.9%). Most lesions were sessile (90.8%). The location of 34.8% was the gastric antrum, 39.3% were found in the gastric body and 25.9% were in the fundus. Chronic gastritis was confirmed in 53.5% of the patients and 46.5% had received PPIs. Histopathological diagnosis was: hyperplastic polyps 50.9%, fundic gland polyps 7.4%, adenomas 3%, adenocarcinomas 1.9% and normal mucosa 29.7%. We found no significant association between the histopathological type of lesions and the use of proton pump inhibitor. Conclusions: we found polypoid lesions in 4.2% of the EGDs. The most frequent histopathological findings were hyperplastic polyps (50.9%), followed by fundic gland polyps (7.4%), adenomas (3%), and adenocarcinomas (1.9%).Antecedentes y objetivo: la prevalencia de pólipos gástricos en la endoscopia digestiva alta (EDA) oscila entre el 0,33 y el 6,35%. La frecuencia de los subtipos histológicos varía ampliamente entre las series publicadas. El objetivo de nuestro estudio es describir las características endoscópicas e histológicas de los pólipos hallados en las EDA y valorar posibles asociaciones. Material y métodos: revisamos retrospectivamente las EDA realizadas en nuestro centro en 2009. Se recogieron variables demográficas, endoscópicas e histológicas. Se realizó un análisis descriptivo y se estudiaron posibles asociaciones. Resultados: se analizaron 6.307 EDA identificándose lesiones polipoideas en 269 (4,2%), el 61% en mujeres. La edad media fue de 64,93 años (DE: ±15.23). En 186 pacientes (69,1%) se objetivó un solo pólipo y en 31 (11,5%), más de 10. Se estimó un tamaño ≤ 3 mm en 108 lesiones (37,2%), y mayor de 10 mm en 52 casos (17,9%). La mayoría de los pólipos eran sésiles (90,8%). El 34,8% se ubicaban en antro, el 39,3% en cuerpo y el 25,9% en fundus. El 53,5% de los pacientes presentaba gastritis crónica y el 46,5% había recibido inhibidores de la bomba de protones (IBP). Los hallazgos histológicos principales fueron: pólipos hiperplásicos 50,9%, pólipos de glándulas fúndicas 7,4%, adenomatosos 3% y adenocarcinomas 1,9%. En el 29,7% la biopsia mostró una mucosa normal. No se objetivó asociación entre el tipo histológico y el consumo de IBP. Conclusiones: encontramos lesiones polipoideas en el 4,2% de las EDA. La histología relevante más frecuente fueron pólipos hiperplásicos (50,9%), de glándulas fúndicas (7,4%), adenomas (3%) y adenocarcinomas (1,9%).

Modeling emission lines from the millimeter to the UV and producing synthetic spectra is crucial for a good understanding of observations, yet it is an art filled with hazards. This is the proceedings of “Walking the Line”, a 3-day conference held in 2018 that brought together scientists working on different aspects of emission line simulations, in order to share knowledge and discuss the methodology. Emission lines across the spectrum from the millimeter to the UV were discussed, with most of the focus on the interstellar medium, but also some topics on the circumgalactic medium. The most important quality of a useful model is a good synergy with observations and experiments. Challenges in simulating line emission are identified, some of which are already being worked upon, and others that must be addressed in the future for models to agree with observations. Recent advances in several areas aiming at achieving that synergy are summarized here, from micro-physical to galactic and circum-galactic scale.

Internet of Things platforms for Smart Cities are technologically complex and deploying them at large scale involves high costs and risks. Therefore, pilot schemes that allow validating proof of concepts, experimenting with different technologies and services, and fine-tuning them before migrating them to actual scenarios, are especially important in this context. The IoT platform deployed across the engineering schools of the Universidad Politécnica de Madrid in the Moncloa Campus of International Excellence represents a good example of a test bench for experimentation with Smart City services. This paper presents the main features of this platform, putting special emphasis on the technological challenges faced and on the solutions adopted, as well as on the functionality, services and potential that the platform offers.

Maradol is the main papaya cultivated in Mexico and one of the main crops in Yucatan. It presents some inconveniences, such as susceptibility to viruses, so new cultivars that can surpass Maradol yield are looked for, but it is necessary that they show similar quality characteristics. The objective of this study was to evaluate the quality characteristics of the fruits of new genotypes produced in Yucatan. Six commercial materials (Maradol, Sensation, Intenzza, Siluet, Lenia Plus and Jibara) and 2 hybrids generated by INIFAP (Azteca and MSXJ) were evaluated. Size, color of peel and pulp, firmness of the pulp and total soluble solids content were assessed. In fruit size, except for Jibara which is very big (2.900 kg) and Siluet, which is very small (1.200 kg), the remaining 6 varieties were similar to Maradol. As for peel color, Intenzza and Siluet presented a similar hue than Maradol (65 a 67o), but more luminosity. Siluet and Sensation had more total soluble solids than Maradol, but less pulp firmness. Sensation, Lenia Plus and MSXJ show good characteristics considering fruit size, pulp firmness, total soluble solids content and peel and pulp color, thus can compete in quality with Maradol variety.

Nucleosomes are the basic structural units of chromatin. Most of the yeast genome is organized in a pattern of positioned nucleosomes that is stably maintained under a wide range of physiological conditions. In this work, we have searched for sequence determinants associated with positioned nucleosomes in four species of fission and budding yeasts. We show that mononucleosomal DNA follows a highly structured base composition pattern, which differs among species despite the high degree of histone conservation. These nucleosomal signatures are present in transcribed and non-transcribed regions across the genome. In the case of open reading frames, they correctly predict the relative distribution of codons on mononucleosomal DNA, and they also determine a periodicity in the average distribution of amino acids along the proteins. These results establish a direct and species-specific connection between the position of each codon around the histone octamer and protein composition.

BackgroundNon-hereditary colorectal cancer (CRC) is a complex disorder resulting from the combination of genetic and non-genetic factors. Genome-wide association studies (GWAS) are useful for identifying such genetic susceptibility factors. However, the single loci so far associated with CRC only represent a fraction of the genetic risk for CRC development in the general population. Therefore, many other genetic risk variants alone and in combination must still remain to be discovered. The aim of this work was to search for genetic risk factors for CRC, by performing single-locus and two-locus GWAS in the Spanish population.ResultsA total of 801 controls and 500 CRC cases were included in the discovery GWAS dataset. 77 single nucleotide polymorphisms (SNP)s from single-locus and 243 SNPs from two-locus association analyses were selected for replication in 423 additional CRC cases and 1382 controls. In the meta-analysis, one SNP, rs3987 at 4q26, reached GWAS significant p-value (p = 4.02×10(-8)), and one SNP pair, rs1100508 CG and rs8111948 AA, showed a trend for two-locus association (p = 4.35×10(-11)). Additionally, our GWAS confirmed the previously reported association with CRC of five SNPs located at 3q36.2 (rs10936599), 8q24 (rs10505477), 8q24.21(rs6983267), 11q13.4 (rs3824999) and 14q22.2 (rs4444235).ConclusionsOur GWAS for CRC patients from Spain confirmed some previously reported associations for CRC and yielded a novel candidate risk SNP, located at 4q26. Epistasis analyses also yielded several novel candidate susceptibility pairs that need to be validated in independent analyses.