Miracle-dz/UniFAR-FTUs huggingface dataset:
Increased Saturated Fatty Acids in Obesity Alter Resolution of Inflammation in Part by Stimulating Prostaglandin Production

Extensive evidence indicates that nutrient excess associated with obesity and type 2 diabetes activates innate immune responses that lead to chronic, sterile low-grade inflammation, and obese and diabetic humans also have deficits in wound healing and increased susceptibility to infections. Nevertheless, the mechanisms that sustain unresolved inflammation during obesity remain unclear. In this study, we report that saturated free fatty acids that are elevated in obesity alter resolution of acute sterile inflammation by promoting neutrophil survival and decreasing macrophage phagocytosis. Using a targeted mass spectrometry–based lipidomics approach, we found that in db/db mice, PGE2/D2 levels were elevated in inflammatory exudates during the development of acute peritonitis. Moreover, in isolated macrophages, palmitic acid stimulated cyclooxygenase-2 induction and prostanoid production. Defects in macrophage phagocytosis induced by palmitic acid were mimicked by PGE2 and PGD2 and were reversed by cyclooxygenase inhibition or prostanoid receptor antagonism. Macrophages isolated from obese-diabetic mice expressed prostanoid receptors, EP2 and DP1, and contained significantly higher levels of downstream effector, cAMP, compared with wild-type mice. Therapeutic administration of EP2/DP1 dual receptor antagonist, AH6809, decreased neutrophil accumulation in the peritoneum of db/db mice, as well as the accumulation of apoptotic cells in the thymus. Taken together, these studies provide new insights into the mechanisms underlying altered innate immune responses in obesity and suggest that targeting specific prostanoid receptors may represent a novel strategy for resolving inflammation and restoring phagocyte defects in obese and diabetic individuals.
Spatial factors in the perceived intensity of vibrotactile patterns.

A series of studies examined the relationship between sensation magnitude and number of pattern elements on a 64-contactor vibrotactile matrix placed on the thigh. Vibrotactile sensation magnitude, or "loudness," was found to increase linearly with the number of active vibrators in the pattern, with a doubling in the number resulting in a doubling of loudness. The slope of the function was independent of both the overall intensity and the spatial density of the elements in the patterns. Only the frequency of vibration, if less than 40 Hz, reduced the slope of the function. The slope of the power function relating growth of loudness to stimulus intensity was determined to be approximately 3. The relationships among number of active elements, their physical intensity, and the overall sensation magnitude of complex spatiotemporal patterns are discussed with reference to pattern perception on dense vibrotactile arrays.
Gender differences in the relationships between plasma plasminogen activator inhibitor-1 activity and factors linked to the insulin resistance syndrome in essential hypertension.

Impaired fibrinolysis due to elevated levels of plasma plasminogen activator inhibitor type 1 (PAI-1) is a risk factor for thromboembolic disease. Hypertension, obesity, derangements in lipid and glucose homeostasis, and elevated levels of PAI-1 are features of the insulin resistance syndrome. The interrelationships between PAI-1 and the metabolic disturbances seen in this condition are unsettled. We investigated the associations between PAI-1 activity and components of the insulin resistance syndrome in 53 men and 31 women with untreated hypertension. In men, PAI-1 activity correlated significantly with plasma glucose (r = .41, P = .002), insulin sensitivity (r = -.35, P = .01), and insulin-induced suppression of nonesterified fatty acid (NEFA) (r = -.43, P = .007). Plasma glucose and NEFA suppression were independently associated with PAI-1 activity in a multivariate analysis. In women, PAI-1 activity correlated with body mass index (r = .62, P = .0005), waist-to-hip ratio (r = .75, P = .0001), plasma glucose (r = .50, P = .007), insulin (r = .49, P = .009), proinsulin (r = .57, P = .002), C-peptide (r = .60, P = .0009), insulin sensitivity (r = -.74, P = .0001), NEFA suppression (r = -.64, P = .003), and triglycerides (r = .58, P = .001). In multivariate analyses, insulin sensitivity and NEFA suppression were independently associated with PAI-1 if waist-to-hip ratio was not included in the model. After introduction of waist-to-hip ratio into the model, waist-to-hip ratio was the only independent predictor of PAI-1 activity. We conclude that in women, waist-to-hip ratio, body mass index, and insulin-induced NEFA suppression are determinants for PAI-1 activity. In men, insulin-induced NEFA suppression and plasma glucose are independently associated with PAI-1 activity.
Surface morphology and topography of patello-femoral cartilage fibrillation in Liverpool necropsies.

Two main forms of non-inflammatory destructive change in articular cartilage are encountered in human synovial joints: 'age-related cartilage fibrillation', as seen in necropsy material, and 'osteoarthritic' cartilage lesions, as seen in surgical excision specimens from patients with clinical evidence of osteoarthrosis. The relationship between these two forms of destructive change is debatable; moreover, the matter may require separate consideration for the hip, knee and other joints. At the hip, for example, the two forms appear to differ in their topographical distribution and pathogenesis (Byers, Contepomi & Farkas, 1970), although both are basically similar in their histology (Meachim, 1972a). The present findings concern the destructive cartilage lesions seen in necropsy material. Studies based on qualitative assessment of the state of the articular surfaces in various joints have shown that the incidence and severity of such lesions increases with advancing age (Heine, 1926; Bennett, Waine & Bauer, 1942; Goodfellow & Bullough, 1967). Quantitative data recently obtained from the patellofemoral articulation in a random series of Liverpool necropsies have confirmed that the destructive process is age-related (Meachim, 1972b; Meachim & Emery, 1974). The quantitative data were obtained by point-counting the patellar and the opposing femoral surfaces to determine for each the percentage of the total surface area occupied by sites of various types of cartilage change. The findings indicated that destructive cartilage changes are extremely common at the patello-femoral articulation amongst Liverpool adults, and that such changes are often already apparent in teenagers. With advancing age, destructive change, subject to a variation from individual to individual in its rate of development, sooner or later involves virtually the whole of the patellar and, particularly in women, a considerable proportion of the opposing femoral surface. Although its average rate of development is relatively slow in terms of the expected total life span of an individual, the destructive process can give rise to areas of full-thickness cartilage loss and bone exposure amongst some subjects aged over 50 years. The point-counting technique referred to above provides quantitative data on the extent of spread of the destructive process across the articular surface within the tangential plane. A complementary approach is to observe and record the surface
Critical Role for CD8 in Binding of MHC Tetramers to TCR: CD8 Antibodies Block Specific Binding of Human Tumor- Specific MHC-Peptide Tetramers to TCR1

There are conflicting opinions about the role that the T cell coreceptors CD4 and CD8 play in TCR binding and activation. Recent evidence from transgenic mouse models suggests that CD8 plays a critical role in TCR binding and activation by peptide-MHC complex multimers (tetramers). Here we show with a human CTL clone specific for a tumor-associated MHC-peptide complex that the binding of tetramers to the TCR on these cells is completely blocked by anti-human CD8 Abs. Moreover, the staining of CTLs with specific MHC-peptide tetramers simultaneously with anti-CD8 Abs was completely blocked with three different anti-CD8 Abs. This blockage was mediated by anti-CD8 Abs but not anti-CD3 Abs and was dose dependent. The blocking effect of the anti-CD8 Abs was attributable to directly inhibiting tetramer binding and was not attributable to Ab-mediated TCR-CD8 internalization and down-regulation. Our results have important implications in TCR binding to MHC-peptide tetramers. MHC-peptide tetramers are widely used today in combination with anti-CD8 Abs for the phenotypic analysis of T cell populations and in the study of T cell responses under various pathological conditions such as infectious diseases and cancer. Our results indicate that also in the human system CD8 plays a critical role in the interaction of MHC-peptide multimers with TCR.
Epidermal growth factor chronically upregulates Ca2+‐dependent Cl− conductance and TMEM16A expression in intestinal epithelial cells

Key points • Cl− secretion, the predominant driving force for fluid secretion in the intestine, can be dysregulated in conditions of disease, such as cystic fibrosis. • We have previously shown that acute exposure to epidermal growth factor (EGF) chronically upregulates the capacity of colonic epithelial cells to secrete Cl−. • Here, we show that the effects of EGF are mediated by upregulation of the Ca2+‐dependent Cl− channel, transmembrane protein 16A (TMEM16A), in the apical membrane of colonic epithelial cells. • EGF‐induced TMEM16A expression is mediated by sequential activation of phosphatidylinositol 3‐kinase and PKCδ. • These findings are among the first to elucidate molecular mechanisms that regulate TMEM16A expression in epithelial cells and suggest the channel represents a good target for development of new therapeutics for intestinal transport disorders.
Automatic mining of the literature to generate new hypotheses for the possible link between periodontitis and atherosclerosis: lipopolysaccharide as a case study.

AIM The aim of the current report was to generate and explore new hypotheses into how, in a pathophysiological sense, atherosclerosis and periodontitis could be linked. MATERIAL AND METHODS Two different biomedical informatics techniques were used: an association-based technique that generated a ranked list of genes associated with the diseases, and a natural language processing tool that extracted the relationships between the retrieved genes and lipopolysaccharide (LPS). RESULTS This combined approach of association-based and natural language processing-based literature mining identified a hit list of 16 candidate genes, with PON1 as the primary candidate. CONCLUSIONS Further study of the literature prompted the hypothesis that PON1 might connect periodontitis with atherosclerosis in both an LPS-dependent and a non-LPS-dependent manner. Furthermore, the resulting genes not only confirmed already known associations between the two diseases, but also provided genes or gene products that have only been investigated separately in the two disease states, and genes or gene products previously reported to be involved in atherosclerosis. These findings remain to be investigated through clinical studies. This example of multidisciplinary research illustrates how collaborative efforts of investigators from different fields of expertise can result in the discovery of new hypotheses.
Effect of patient counseling on quality of life in type-2 diabetes mellitus patients in two selected South Indian community pharmacies: A study

This study was carried out to assess the influence of pharmacist provided patient counseling on patients' perception about the disease management and quality of life in type 2 diabetes mellitus patients. The present study was a randomized, prospective controlled study conducted over a period of six months in two community pharmacies in Calicut, Kerala, India. A total of seventy (48 male and 22 female) type 2 diabetes mellitus patients were enrolled and randomized into test and control groups. Patients in the test group received patient counseling and patient information leaflets from the pharmacist, where as the control group patients received the counseling and patient information leaflets only at the end of the study. After the baseline, two follow-ups were made with sixty days interval between the follow-ups. During each visit patient's random capillary blood glucose was measured by using a standard Glucometer. Suitably designed and validated knowledge, attitude and practices questionnaire was administered at baseline and final follow up for both test and control group patients to assess the disease management awareness. Audit of diabetes-dependent quality of life questionnaire was administered to measure the quality of life in both control and test group patients at each follow up. At the end of the study, knowledge, attitude and practices scores found markedly improved in test group patients. Mean capillary blood glucose levels were decreased in test group ( P 0.05) was observed in the control group patients. The correlation between the capillary blood glucose levels and quality of life scores were also found to be highly significant in the test group (r= 0.955). The results of the study suggests that, pharmacist provided patient counseling has an impact in improving the perception about disease, diet and life style changes and in turn on glycemic control and overall quality of life in diabetic patients. Pharmacist provided patient counseling might be considered as an important element in implementing the disease management program.
Infliximab Does Not Affect Postoperative Complication Rates in Crohn's Patients Undergoing Abdominal Surgery

Background: In patients with Crohn's disease (CD), the effect of anti‐tumor necrosis factor alpha (TNF‐&agr;) antibody therapy on postoperative complications remains unclear. We aimed to determine the effects of infliximab on postoperative complication rates in patients undergoing abdominal surgery for CD. Methods: Infliximab‐treated CD patients undergoing abdominal surgery were identified in a prospective database. Gender‐ and age‐matched CD patients without infliximab treatment served as controls. General and complication‐related information was retrieved from patient records. Results: Forty‐eight patients underwent abdominal surgery within 3 months (median 60 days, range 1–90 days) after infliximab administration (56% female, median age 35 years, range 17–66 years). Forty‐eight patients without infliximab served as controls (50% female, 39 [17–68] years). Patient characteristics and number of minor complications were comparable between groups: wound infection (infliximab: 19% vs. controls: 15%), prolonged postoperative ileus (15% vs. 4%), and urinary tract infection (2% vs. 0%; all P > 0.05). No differences were found in major complications: anastomotic leakage (infliximab: 4% vs. controls: 13%), abscess formation (6% vs. 10%), bowel perforation (2% vs. 4%), stoma complication (6% vs. 2%), postoperative hemorrhage (8% vs. 2%), and enterocutaneous fistula (4% vs. 0%; all P > 0.05). One malnourished infliximab‐treated patient with a complicated course of disease died postoperatively after anastomotic leakage, sepsis, and cardiac arrhythmia. Eleven infliximab and 10 control patients required reoperation (P > 0.05). Hospital stay was comparable between groups (infliximab: 13 [5–41] vs. controls: 12 [5–54] days; P > 0.05). Conclusions: Infliximab does not affect postoperative complication rates, suggesting no need to alter surgical management in these patients. (Inflamm Bowel Dis 2011;)
Glyoxalase 2 drives tumorigenesis in human prostate cells in a mechanism involving androgen receptor and p53‐p21 axis

Glyoxalase 2 (Glo2), a metabolic enzyme, is overexpressed in some human cancers which suggests this enzyme may play a role in human tumorigenesis. In prostate cancer (PCa), the role of Glo2 has been scarcely investigated and there are no studies addressing a causative involvement of this protein in this neoplasia. Here, we examined the immunohistochemical profile of Glo2 in human PCa and benign adjacent tissues and investigated Glo2 involvement in PCa development in human prostate cell lines. PCa and matched adjacent normal tissues were obtained from paraffin sections of primary PCa from 20 patients who had undergone radical prostatectomy. Histopathological diagnosis was confirmed for each sample. Glo2 expression analysis was performed by immunohistochemistry in prostate tissues, and by qRT‐PCR and immunoblotting in prostate cell lines. The causative and mechanistic role of Glo2 in prostate tumorigenesis was demonstrated by Glo2 ectopic expression/silencing and employing specific activators/inhibitors. Our results showed that Glo2 was selectively expressed in PCa but not in the luminal compartment of the adjacent benign epithelium consistently in all the examined 20 cases. Glo2 expression in PCa was dependent on androgen receptor (AR) and was aimed at stimulating cell proliferation and eluding apoptosis through a mechanism involving the p53‐p21 axis. Glo2 was intensely expressed in the basal cells of benign glands but was not involved in PCa genesis. Our results demonstrate for the first time that Glo2 drives prostate tumorigenesis and suggest that it may represent a novel adjuvant marker in the pathological diagnosis of early PCa.
DEPRESSION DURING EARLY RECOVERY FROM HEART SURGERY AMONG EARLY MIDDLE-AGE, MIDLIFE, AND ELDERLY WOMEN

Theories and studies about the psychological processes of midlife propose a transition that may result in a more integrated personality structure throughout the second half of life. This more integrated structure includes concepts such as generativity, self-assertion, and independence. However, this structure, especially in early middle-age, can be affected by a life-threatening health disruption such as heart disease. One hundred and fifty-five women participated in a cross-sectional survey designed to investigate depression in early middle age, midlife, and elderly women who had undergone heart surgery. Women aged 40–55 years composed the early middle-age group, women aged 56–65 years composed the midlife age group, and women aged 66+ years were identified as the elderly age group. Affective components of depression were measured by asking participants to respond to three items regarding frequency of sadness, depression, and “the blues. ” Affective depression scores were summed and a mean score derived. Mean scores significantly differed by age group (F [2, 152] = 3.05, p =. 05). Older women in the study fared better than their younger counterparts in terms of depression scores after a major cardiac health disruption. Post hoc comparisons indicated that mean scores for the early middle-age participants were significantly higher than for the midlife and older participants. Depression in the context of a cardiac health disruption appears to be linked to the developmental stage of a woman’s life trajectory on which it is superimposed.
Ischemic preconditioning versus intermittent reperfusion to improve blood flow to a vascular isolated skeletal muscle flap of rats.

OBJECTIVES We investigated whether intermittent restoration of blood flow just before reperfusion after ischemia could create beneficial effects similar to ischemic preconditioning, which involves intermittent stoppage of blood flow just before ischemia. METHODS Male Sprague-Dawley rats were prepared with vascular isolated cremaster muscles, then subjected to 4 hours of ischemia and 60 minutes of reperfusion. Arteriole diameters and capillary perfusion were measured by using intravital microscopy. Four groups were used: (1) untreated, (2) ischemic preconditioning (IP), (3) intermittent reperfusion (IR), and (4) ischemic preconditioning plus intermittent reperfusion (IP+IR). RESULTS Our results showed that IP significantly attenuated both ischemia/reperfusion-induced vasospasm and capillary noreflow. IR was effective in attenuating vasospasm in terminal arterioles. However, IR alone was unable to significantly attenuate capillary no-reflow. Combining both IP and IR achieved the best results. CONCLUSION Our results suggest both ischemic preconditioning and intermittent reperfusion are useful techniques for attenuating ischemia/reperfusion injury.
A New Resource-Constrained Multicommodity Flow Model for Conflict-Free Train Routing and Scheduling

This paper addresses the problem of generating conflict-free train schedules on a microscopic model of the railway infrastructure. Conflicts arise if two or more trains are scheduled to block the same track section at the same time. A standard model for this problem is the so-called conflict graph, where each considered train path corresponds to a vertex, and edges represent pairwise conflicts so that a conflict-free schedule corresponds to a maximum independent set. Because the linear programming relaxation of the conflict graph formulation is typically very weak, we develop an alternative model using the sequence of resources that each train path passes, encoded in a resource tree. For each resource, we can efficiently determine the maximal conflict cliques by scanning through the blocking times of all train paths and use these cliques as strong cutting planes in an integer linear programming formulation. We show that the number of maximal conflict cliques is linear in the number of train paths, so the ILP formulation uses much fewer but stronger constraints compared to the conflict graph model. In tests with real-world data from the Swiss Federal Railways, the new Resource Tree Conflict Graph model generates for major stations within seconds, even though the underlying model contains about half a million binary variables. This corresponds to a reduction of the computation time of roughly two orders of magnitude when compared to previous approaches and thus allows us to tackle considerable larger problem instances.
Aging fathers of adult children with schizophrenia: the toll of caregiving on their mental and physical health.

OBJECTIVE The primary purpose of this study was to compare the physical and psychological well-being of caregiving fathers of an adult son or daughter with schizophrenia with a comparison group of fathers who do not have children with schizophrenia. METHODS Data for the caregiving fathers (N=95) were drawn from a study of families of adults with schizophrenia; the comparison group of fathers (N=95) was drawn from the Wisconsin Longitudinal Study (WLS). Samples were matched on sociodemographic variables and analyzed with independent-samples t tests. RESULTS Fathers of adults with schizophrenia experienced higher levels of depression, poorer perceived health, lower levels of psychological well-being, and less marital satisfaction compared with their age-matched peers in the WLS. CONCLUSIONS This study found hidden personal costs of caregiving among fathers of adults with schizophrenia; strategies are needed for supporting these fathers.
Vascular grafts in the rat model: An anatomic study

Vascular grafts in animal models have been used extensively in the microsurgical laboratory, and the rat offers an excellent source of graft to meet these needs. In this study, we compiled a list of vessels that were previously identified in experimental literature for use as vascular grafts in the rat model. We then dissected and measured both arterial and venous grafts taken from these sites in 12 adult rats. The surgical procedure for approaching each vascular graft was recorded. The diameter and harvestable length, the start and end points, and the number of branches of the graft were tabulated. We believe that these data will provide valuable insight applicable to the use of the rat vascular graft in microsurgical research and training. © 2001 Wiley‐Liss, Inc. Microsurgery 21:80–83 2001