Overweight status is associated with extensive signs of microvascular dysfunction and cardiovascular risk

The aim of this present study was to investigate if overweight individuals exhibit signs of vascular dysfunction associated with a high risk for cardiovascular disease (CVD). One hundred lean and 100 overweight participants were recruited for the present study. Retinal microvascular function was assessed using the Dynamic Retinal Vessel Analyser (DVA), and systemic macrovascular function by means of flow-mediated dilation (FMD). Investigations also included body composition, carotid intimal-media thickness (c-IMT), ambulatory blood pressure monitoring (BP), fasting plasma glucose, triglycerides (TG), cholesterol levels (HDL-C and LDL-C), and plasma von Willebrand factor (vWF). Overweight individuals presented with higher right and left c-IMT (p = 0.005 and p = 0.002, respectively), average 24-h BP values (all p <0.001), plasma glucose (p = 0.008), TG (p = 0.003), TG: HDL-C ratio (p = 0.010), and vWF levels (p = 0.004). Moreover, overweight individuals showed lower retinal arterial microvascular dilation (p = 0.039) and baseline-corrected flicker (bFR) responses (p = 0.022), as well as, prolonged dilation reaction time (RT, p = 0.047). These observations emphasise the importance of vascular screening and consideration of preventive interventions to decrease vascular risk in all individuals with adiposity above normal range

Molecular study of the perforin gene in familial hematological malignancies

Perforin gene (PRF1) mutations have been identified in some patients diagnosed with the familial form of hemophagocytic lymphohistiocytosis (HLH) and in patients with lymphoma. The aim of the present study was to determine whether patients with a familial aggregation of hematological malignancies harbor germline perforin gene mutations. For this purpose, 81 unrelated families from Tunisia and France with aggregated hematological malignancies were investigated. The variants detected in the PRF1 coding region amounted to 3.7% (3/81). Two of the three variants identified were previously described: the p.Ala91Val pathogenic mutation and the p.Asn252Ser polymorphism. A new p.Ala 211Val missense substitution was identified in two related Tunisian patients. In order to assess the pathogenicity of this new variation, bioinformatic tools were used to predict its effects on the perforin protein structure and at the mRNA level. The segregation of the mutant allele was studied in the family of interest and a control population was screened. The fact that this variant was not found to occur in 200 control chromosomes suggests that it may be pathogenic. However, overexpression of mutated PRF1 in rat basophilic leukemia cells did not affect the lytic function of perforin differently from the wild type protein

Functional kinds: a skeptical look

The functionalist approach to kinds has suffered recently due to its association with law-based approaches to induction and explanation. Philosophers of science increasingly view nomological approaches as inappropriate for the special sciences like psychology and biology, which has led to a surge of interest in approaches to natural kinds that are more obviously compatible with mechanistic and model-based methods, especially homeostatic property cluster theory. But can the functionalist approach to kinds be weaned off its dependency on laws? Dan Weiskopf has recently offered a reboot of the functionalist program by replacing its nomological commitments with a model-based approach more closely derived from practice in psychology. Roughly, Weiskopf holds that the natural kinds of psychology will be the functional properties that feature in many empirically successful cognitive models, and that those properties need not be localized to parts of an underlying mechanism. I here skeptically examine the three modeling practices that Weiskopf thinks introduce such non-localizable properties: fictionalization, reification, and functional abstraction. In each case, I argue that recognizing functional properties introduced by these practices as autonomous kinds comes at clear cost to those explanations’ counterfactual explanatory power. At each step, a tempting functionalist response is parochialism: to hold that the false or omitted counterfactuals fall outside the modeler’s explanatory aims, and so should not be counted against functional kinds. I conclude by noting the dangers this attitude poses to scientific disagreement, inviting functionalists to better articulate how the individuation conditions for functional kinds might outstrip the perspective of a single modeler

Murine CD4+ T Cell Responses Are Inhibited by Cytotoxic T Cell-Mediated Killing of Dendritic Cells and Are Restored by Antigen Transfer

Cytotoxic T lymphocytes (CTL) provide protection against pathogens and tumors. In addition, experiments in mouse models have shown that CTL can also kill antigen-presenting dendritic cells (DC), reducing their ability to activate primary and secondary CD8+ T cell responses. In contrast, the effects of CTL-mediated killing on CD4+ T cell responses have not been fully investigated. Here we use adoptive transfer of TCR transgenic T cells and DC immunization to show that specific CTL significantly inhibited CD4+ T cell proliferation induced by DC loaded with peptide or low concentrations of protein antigen. In contrast, CTL had little effect on CD4+ T cell proliferation induced by DC loaded with high protein concentrations or expressing antigen endogenously, even if these DC were efficiently killed and failed to accumulate in the lymph node (LN). Residual CD4+ T cell proliferation was due to the transfer of antigen from carrier DC to host APC, and predominantly involved skin DC populations. Importantly, the proliferating CD4+ T cells also developed into IFN-γ producing memory cells, a property normally requiring direct presentation by activated DC. Thus, CTL-mediated DC killing can inhibit CD4+ T cell proliferation, with the extent of inhibition being determined by the form and amount of antigen used to load DC. In the presence of high antigen concentrations, antigen transfer to host DC enables the generation of CD4+ T cell responses regardless of DC killing, and suggests mechanisms whereby CD4+ T cell responses can be amplified

Changes in Corneal Basal Epithelial Phenotypes in an Altered Basement Membrane

To examine the corneal epithelial phenotype in an altered basement membrane.Corneas from 9 patients with symptoms of continuous unstable corneal curvature (CUCC) were harvested by penetrating keratoplasty and subjected to histology examination and immunohistochemical staining with transactivating and N-terminally truncated pP63 transcript (ΔNp63), cytokeratin 3 (Krt3), ATP-binding cassette sub-family G member 2 (ABCG2), connexin 43 (CX43), p38 mitogen-activated protein kinases (p38MAPK), activating protein 2 (TFAP2), and extracellular signal-regulated kinase (Erk1/2) monoclonal antibodies. Positive immunostaining with ABCG2, p38MAPK, and TFAP2 monoclonal antibodies was observed in the basal epithelial cells of CUCC patients, and CX43 and ΔNp63 were detected in the full-thickness epithelial cells of CUCC patients.Our results indicate that alteration of the corneal basement membrane induces a de-differentiation-like phenotype in corneal basal epithelial cells

Outcome of crisis intervention for borderline personality disorder and post traumatic stress disorder: a model for modification of the mechanism of disorder in complex post traumatic syndromes

<p>Abstract</p> <p>Background</p> <p>This study investigates the outcome of crisis intervention for chronic post traumatic disorders with a model based on the theory that such crises manifest trauma in the present. The sufferer's behavior is in response to the current perception of dependency and entrapment in a mistrusted relationship. The mechanism of disorder is the sufferer's activity, which aims to either prove or disprove the perception of entrapment, but, instead, elicits more semblances of it in a circular manner. Patients have reasons to keep such activity private from therapy and are barely aware of it as the source of their symptoms.</p> <p>Methods</p> <p>The hypothesis is that the experimental intervention will reduce symptoms broadly within 8 to 24 h from initiation of treatment, compared to treatment as usual. The experimental intervention sidesteps other symptoms to engage patients in testing the trustworthiness of the troubled relationship with closure, thus ending the circularity of their own ways. The study compares 32 experimental subjects with 26 controls at similar crisis stabilization units.</p> <p>Results</p> <p>The results of the Brief Psychiatric Rating Scale (BPRS) supported the hypothesis (both in total score and for four of five subscales), as did results with Client Observation, a pilot instrument designed specifically for the circular behavior targeted by the experimental intervention. Results were mostly non-significant from two instruments of patient self-observation, which provided retrospective pretreatment scores.</p> <p>Conclusions</p> <p>The discussion envisions further steps to ascertain that this broad reduction of symptoms ensues from the singular correction that distinguishes the experimental intervention.</p> <p>Trial registration</p> <p>Protocol Registration System NCT00269139. The PRS URL is <url>https://register.clinicaltrials.gov</url></p

Herbal remedy knowledge acquisition and transmission among the Yucatec Maya in Tabi, Mexico: a cross-sectional study

BACKGROUND: Ethnobotanical knowledge continues to be important for treating illness in many rural communities, despite access to health care clinics and pharmaceuticals. However, access to health care clinics and other modern services can have an impact on the distribution of medical ethnobotanical knowledge. Many factors have been shown to be associated with distributions in this type of knowledge. The goal of the sub-analyses reported in this paper was to better understand the relationship between herbal remedy knowledge, and two such factors, age and social network position, among the Yucatec Maya in Tabi, Yucatan. METHODS: The sample consisted of 116 Yucatec Maya adults. Cultural consensus analysis was used to measure variation in herbal remedy knowledge using competence scores, which is a measure of participant agreement within a domain. Social network analysis was used to measure individual position within a network using in-degree scores, based on the number of people who asked an individual about herbal remedies. Surveys were used to capture relevant personal attributes, including age. RESULTS: Analysis revealed a significant positive correlation between age and the herbal medicine competence score for individuals 45 and under, and no relationship for individuals over 45. There was an insignificant relationship between in-degree and competence scores for individuals 50 and under and a significant positive correlation for those over 50. CONCLUSIONS: There are two possible mechanisms that could account for the differences between cohorts: 1) knowledge accumulation over time; and/or 2) the stunting of knowledge acquisition through delayed acquisition, competing treatment options, and changes in values. Primary ethnographic evidence suggests that both mechanisms may be at play in Tabi. Future studies using longitudinal or cross-site comparisons are necessary to determine the whether and how the second mechanism is influencing the different cohorts.This item is part of the UA Faculty Publications collection. For more information this item or other items in the UA Campus Repository, contact the University of Arizona Libraries at [email protected]