Correlatos del índice de masa corporal en los pacientes moderados y graves con el síndrome del intestino irritable

Irritable bowel syndrome (IBS) is a common and potentially disabling gastrointestinal (GI) disorder that is subject to strong psychological influences particularly among more severe IBS patients. Little is known about the role of actionable lifestyle factors (e.g., obesity) that influence the trajectory of other chronic diseases. This study examined the associations between obesity and different aspects of illness experience among more severe IBS patients. We hypothesized that Body Mass Index (BMI) would positively correlate with worse health outcomes including more severe IBS symptoms, extraintestinal complaints, and emotional distress. At pretreatment baseline in a National Institutes of Health (NIH)-funded behavioral trial, 448 Rome-diagnosed IBS patients (MAGE  = 41; MBMI = 26, Female = 8%) were administered a test battery that included a variety of clinical (IBS symptom severity, fear of GI symptoms, BMI, etc.), and sociodemographic (e.g. age, etc.) variables. BMI was positively and significantly correlated with somatization (unexplained somatic complaints) but not IBS symptom severity or emotional distress. A series of moderated multiple regression analyses showed that the associations between BMI and somatization were moderated by the interaction between BMI and age, and fear of GI symptoms. Older patients with higher BMI reported higher levels of somatization and patients who were more fearful of GI symptoms were more likely to experience somatization if they also had a high BMI. These data highlight the relationship between lifestyle factors and extraintestinal symptoms among more severe IBS patients and the impact of both sociodemographic (age) and psychosocial (fear of GI symptoms) factors on this relationship.SII es un trastorno gastrointestinal común y potencialmente incapacitante, susceptible a las influencias psicológicas fuertes, especialmente entre los pacientes más graves. Se sabe poco sobre el papel de los factores del estilo de vida (p.ej. obesidad) que influyen en la trayectoria de otras enfermedades crónicas. Este estudio ha examinado la correlación entre la obesidad y los diferentes aspectos de la experiencia de enfermedad en los pacientes más graves con el SII. Nuestra hipótesis fue que el SII se podría correlacionar positivamente con peores resultados de salud, incluyendo síntomas más graves del SII, molestias extraintestinales y angustia emocional. Durante el pretratamiento, en una prueba de comportamiento basada en NIH, 448 pacientes con el SII diagnosticados mediante los criterios de Roma (MEDAD = 41, MIMC = 26, F = 8%) fueron sometidos a una batería de prueba que incluía una variedad de variables clínicas (gravedad del SII, miedo de síntomas gastrointestinales, IMC etc.) y sociodemográficas (p. ej. edad etc.) El IMC fue positiva y significativamente correlacionado con la somatización (molestias somáticas inexplicadas), pero no con la gravedad de los síntomas del SII o angustia emocional. Una serie de múltiples análisis regresivos moderados demostró que la relación entre el IMC y la somatización fue moderada por la interacción entre el IMC, la edad y el miedo de los síntomas gastrointestinales. Los pacientes mayores con el IMC más alto mostraron niveles de somatización más altos, y los pacientes que tenían más miedo de los síntomas gastrointestinales tenían más posibilidad de sufrir la somatización si tenían también el IMC alto. Estos datos subrayan la relación entre los factores de estilo de vida y los síntomas extraintestinales entre los pacientes más graves con el SII, tanto como el impacto que tienen factores sociodemográficos (edad) y psicosociales (miedo de los síntomas gastrointestinales) en su relación

The sensory feedback mechanisms enabling couples to walk synchronously: An initial investigation

The inattentive eye often will not notice it, but synchronization among human walking partners is quite common. In this first investigation of this phenomenon, we studied its frequency and the mechanisms that contribute to this form of "entrainment." Specifically, by modifying the available communication links between two walking partners, we isolated the feedback mechanisms that enable couples to synchronize their stepping pattern when they walk side-by-side. Although subjects were unaware of the research aims and were not specifically asked to walk in synchrony, we observed synchronized walking in almost 50% of the walking trials, among couples who do not usually walk together. The strongest in-phase synchrony occurred in the presence of tactile feedback (i.e., handholding), perhaps because of lower and upper extremity coupling driven in part by arm swing. Interestingly, however, even in the absence of visual or auditory communication, couples also frequently walked in synchrony while 180 degrees out-of-phase, likely using different feedback mechanisms. These findings may partially explain how patients with certain gait disorders and disturbed rhythm enhance their gait when they walk with a partner and suggest alternative interventions that might improve the stepping pattern. Further, this preliminary investigation highlights the relatively ubiquitous nature of an interesting phenomenon that has not previously been studied and suggests that further work is needed to better understand the mechanisms that entrain the gait of two walking partners and allows couples to walk in synchrony with minimal or no conscious effort

A cellular trafficking signal in the SIV envelope protein cytoplasmic domain is strongly selected for in pathogenic infection

The HIV/SIV envelope glycoprotein (Env) cytoplasmic domain contains a highly conserved Tyr-based trafficking signal that mediates both clathrin-dependent endocytosis and polarized sorting. Despite extensive analysis, the role of these functions in viral infection and pathogenesis is unclear. An SIV molecular clone (SIVmac239) in which this signal is inactivated by deletion of Gly-720 and Tyr-721 (SIVmac239ΔGY), replicates acutely to high levels in pigtail macaques (PTM) but is rapidly controlled. However, we previously reported that rhesus macaques and PTM can progress to AIDS following SIVmac239ΔGY infection in association with novel amino acid changes in the Env cytoplasmic domain. These included an R722G flanking the ΔGY deletion and a nine nucleotide deletion encoding amino acids 734–736 (ΔQTH) that overlaps the rev and tat open reading frames. We show that molecular clones containing these mutations reconstitute signals for both endocytosis and polarized sorting. In one PTM, a novel genotype was selected that generated a new signal for polarized sorting but not endocytosis. This genotype, together with the ΔGY mutation, was conserved in association with high viral loads for several months when introduced into naïve PTMs. For the first time, our findings reveal strong selection pressure for Env endocytosis and particularly for polarized sorting during pathogenic SIV infection in vivo

Using Strategic Movement to Calibrate a Neural Compass: A Spiking Network for Tracking Head Direction in Rats and Robots

The head direction (HD) system in mammals contains neurons that fire to represent the direction the animal is facing in its environment. The ability of these cells to reliably track head direction even after the removal of external sensory cues implies that the HD system is calibrated to function effectively using just internal (proprioceptive and vestibular) inputs. Rat pups and other infant mammals display stereotypical warm-up movements prior to locomotion in novel environments, and similar warm-up movements are seen in adult mammals with certain brain lesion-induced motor impairments. In this study we propose that synaptic learning mechanisms, in conjunction with appropriate movement strategies based on warm-up movements, can calibrate the HD system so that it functions effectively even in darkness. To examine the link between physical embodiment and neural control, and to determine that the system is robust to real-world phenomena, we implemented the synaptic mechanisms in a spiking neural network and tested it on a mobile robot platform. Results show that the combination of the synaptic learning mechanisms and warm-up movements are able to reliably calibrate the HD system so that it accurately tracks real-world head direction, and that calibration breaks down in systematic ways if certain movements are omitted. This work confirms that targeted, embodied behaviour can be used to calibrate neural systems, demonstrates that ‘grounding’ of modelled biological processes in the real world can reveal underlying functional principles (supporting the importance of robotics to biology), and proposes a functional role for stereotypical behaviours seen in infant mammals and those animals with certain motor deficits. We conjecture that these calibration principles may extend to the calibration of other neural systems involved in motion tracking and the representation of space, such as grid cells in entorhinal cortex

Engineering HIV-Resistant Human CD4+ T Cells with CXCR4-Specific Zinc-Finger Nucleases

HIV-1 entry requires the cell surface expression of CD4 and either the CCR5 or CXCR4 coreceptors on host cells. Individuals homozygous for the ccr5Δ32 polymorphism do not express CCR5 and are protected from infection by CCR5-tropic (R5) virus strains. As an approach to inactivating CCR5, we introduced CCR5-specific zinc-finger nucleases into human CD4+ T cells prior to adoptive transfer, but the need to protect cells from virus strains that use CXCR4 (X4) in place of or in addition to CCR5 (R5X4) remains. Here we describe engineering a pair of zinc finger nucleases that, when introduced into human T cells, efficiently disrupt cxcr4 by cleavage and error-prone non-homologous DNA end-joining. The resulting cells proliferated normally and were resistant to infection by X4-tropic HIV-1 strains. CXCR4 could also be inactivated in ccr5Δ32 CD4+ T cells, and we show that such cells were resistant to all strains of HIV-1 tested. Loss of CXCR4 also provided protection from X4 HIV-1 in a humanized mouse model, though this protection was lost over time due to the emergence of R5-tropic viral mutants. These data suggest that CXCR4-specific ZFNs may prove useful in establishing resistance to CXCR4-tropic HIV for autologous transplant in HIV-infected individuals

RANTES/CCL5 and risk for coronary events: Results from the MONICA/KORA Augsburg case-cohort, Athero-express and CARDIoGRAM studies

Background: The chemokine RANTES (regulated on activation, normal T-cell expressed and secreted)/CCL5 is involved in the pathogenesis of cardiovascular disease in mice, whereas less is known in humans. We hypothesised that its relevance for atherosclerosis should be reflected by associations between CCL5 gene variants, RANTES serum concentrations and protein levels in atherosclerotic plaques and risk for coronary events. Methods and Findings: We conducted a case-cohort study within the population-based MONICA/KORA Augsburg studies. Baseline RANTES serum levels were measured in 363 individuals with incident coronary events and 1,908 non-cases (mean follow-up: 10.2±