Bicycle helmet ventilation and comfort angle dependence

Five modern bicycle helmets were studied to elucidate some of the variations in ventilation performance, using both a heated manikin headform and human subjects (n=7). Wind speed and head angle were varied to test their influence on the measured steady-state heat exchange (cooling power) in the skull section of the headform. The cooling power transmitted by the helmets varied from about 60% to over 90% of that of the nude headform, illustrating the range of present manufacturer designs. Angling the head forward by 30° was found to provide better cooling power to the skull (up to 25%) for three of the helmets and almost equal cooling power in the remaining two cases. Comparisons of skull ventilation at these angles with human subjects strongly supported the headform results.     

Mixed epithelial and stromal tumors of the kidney. A report of 22 cases

Mixed epithelial and stromal tumor of the kidney (MESTK) is a recently described subset of renal neoplasm that tends to occur in middle-aged and older women and is characterized by a distinctive histological appearance. To further characterize this lesion, we report the clinicopathological and immunohistochemical features of 22 additional cases from our institutional files. Grossly, the tumors ranged in size from 1 cm to 14 cm (mean 6.7 cm), were well circumscribed but unencapsulated, and showed a cystic cut surface. The tumors were composed of a spindle cell proliferation that resembled ovarian stroma, as well as an epithelial component lining the cystic structures, which usually consisted of flat to hobnailed cells typical of collecting-duct epithelium. Areas displaying features of Müllerian differentiation were also documented in 6 cases, including epithelium of endometrioid, tubal, clear cell and squamous cell type as well as one case showing an architecture that closely resembled Müllerian adenofibroma and adenosarcoma. Follow-up in 14 patients (average 4.4 years) showed no evidence of recurrence or metastasis. We believe these tumors represent the renal counterpart of similar mixed epithelial and stromal neoplasms occurring in the biliary tract and pancreas, which is also characterized by cystic structures lined by epithelium, admixed with ovarian-type stroma. The differential diagnosis for these tumors includes cystic nephroma and cystic partially differentiated nephroblastoma, which we believe to represent clinically and morphologically distinct entities from MESTK. In particular, the distinction from cystic nephroma in adult male patients is emphasized, and two cases of this entity are included in the study for comparison.     

Kin KeeperSM: Design and baseline characteristics of a community-based randomized controlled trial promoting cancer screening in Black,Latina, and Arab women

BackgroundAlthough breast and cervical cancer deaths have declined due to early screening, detection, and more effective treatment, racial and ethnic disparities persist. This paper describes the study design and baseline characteristics of a randomized controlled trial (RCT) evaluating the effectiveness of the Kin Keeper^SM Cancer Prevention Intervention, a family-focused educational intervention for underserved women applied in a community-based setting to promote health literacy and screening adherence to address cancer disparities.MethodsFemale public health community health workers (CHWs) were trained to administer the intervention. They recruited female clients from their public health program caseload and asked each to assemble two to four adult female family members for the breast and cervical cancer home-based education sessions the CHWs would deliver in English, Spanish or Arabic. We randomized the clients into the kin keeper group (treatment) or the participant client group (control).ResultsComplete data were obtained on 514 Black, Latina, and Arab women. Close to half were unemployed and had yearly family income below $20,000. Thirty-four percent had no medical insurance, and 21% had diabetes. Almost 40% had no mammography in the last year. Treatment and control groups were similar on most sociodemographics but showed differences in breast and cervical screening history.ConclusionsThis innovative study demonstrates the implementation of an RCT using community-based participatory research, while delivering cancer prevention education across woman's life span with women not connected to the health care system.     

Cardiovascular Characteristics in Subjects With Increasing Levels of Abnormal Glucose Regulation: The Strong Heart Study

OBJECTIVE

To evaluate whether impaired fasting glucose (IFG) or the combination of IFG and impaired glucose tolerance (IGT) is associated with progressive abnormalities of cardiac geometry and function.

RESEARCH DESIGN AND METHODS

We studied 562 nondiabetic (311 women), nonhypertensive participants of the second Strong Heart Study exam, without prevalent cardiovascular (CV) disease and with estimated glomerular filtration rate ≥60 mL/min/1.73 m² (age 46–65 years, 198 with isolated IFG [35%], and 132 with combined IFG and IGT [23%]). Anthropometric parameters, insulin resistance, fibrinogen, C-reactive protein (CRP), lipid profile, blood pressure (BP), and echocardiographic parameters were compared with 232 participants with normal glucose tolerance (NGT).

RESULTS

BMI, prevalence of central obesity, homeostatic model assessment index of insulin resistance, plasma triglycerides, fibrinogen, and CRP increased progressively across categories of glucose intolerance (P < 0.0001), with the IFG+IGT group having higher values than those with isolated IFG (0.05 < P < 0.0001). Compared with NGT, both IFG and IFG+IGT exhibited greater left ventricular (LV) mass (P < 0.0001) and lower Doppler early peak rapid filling velocity to peak atrial filling velocity ratio (P < 0.005), without differences in LV systolic function. The odds of LV hypertrophy (LV mass index >46.7 in women or >49.2 g/m^2.7 in men) was 3.5 in IFG participants (95% CI 0.68–17.76; P = NS) and 9.76 (2.03–46.79; P = 0.004) in IFG+IGT, compared with NGT, after adjustment for age, sex, heart rate, systolic BP, and waist circumference (WC). In the overall sample, LV mass index was associated with WC (P = 0.033), CRP (P = 0.027), and 2-h oral glucose tolerance test (P = 0.001) independently of confounders.

CONCLUSIONS

Cardiometabolic profile and markers of inflammation are more severely altered in men and women with both IFG and IGT compared with those with IFG alone. These individuals, in the absence of hypertension, have a 10-fold greater probability of preclinical CV disease (LV hypertrophy).Diabetes increases the risk of cardiovascular (CV) disease and mortality (1), an association that is independent of other CV risk factors (2). Evidence has also emerged of an increased CV risk in individuals with abnormal glucose regulation (3,4). Both states of abnormal glucose regulation (i.e., impaired fasting glucose [IFG] and impaired glucose tolerance [IGT]) are reported to be associated with excess body weight and increased levels of CV risk factors, morbidity, and mortality (5–7), although these associations are not universally recognized (8,9).Whether increased plasma glucose above the normal range but below that of clinical diabetes has an impact on cardiac geometry and function is little explored. Cohort studies in communities have shown increased left ventricular (LV) mass and remodeling in individuals with prediabetes (10–12), which appear to be mediated by insulin resistance and body fat distribution (11). However, there are limited clinical or population studies examining CV phenotype in individuals with IGT (13,14), and they included participants with hypertension and/or CV disease, making it difficult to evaluate the role of abnormal glucose levels.Glucose dysregulation is a continuum from elevation of either fasting or postprandial glucose concentration to impairment of both and, eventually, to type 2 diabetes. This progression is associated with worsening CV risk profile, and individuals with both IFG and IGT have more severe metabolic abnormalities and a greater risk of conversion to type 2 diabetes than those with isolated IFG or IGT (5). Thus, it is plausible that CV phenotype also may worsen in parallel with more severe glucose impairment. Accordingly, in the population of the Strong Heart Study (SHS), we compared the metabolic and echocardiographic features of nondiabetic participants who had either IFG or IFG and IGT combined from the second exam; we hypothesized that the combination of IFG and IGT is associated with more severe abnormalities of cardiac geometry and function than isolated IFG.     

Increased expression and release of functional tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) by T cells from lupus patients with active disease

Increased expression of TRAIL in membrane-bound and soluble form in patients with systemic lupus erythematosus (SLE) has been previously reported. In this study, we characterized the upregulation of T-cell-associated and soluble TRAIL (sTRAIL) in vivo and the modulation of TRAIL expression and soluble protein release in vitro following T cell activation and IFNalpha exposure. The expression of membrane-bound TRAIL as determined by flow cytometry was higher on CD4(+) and CD8(+) T cells from lupus patients compared to controls, particularly on activated CD69(+)CD8(+) T cells. Similarly, sTRAIL levels determined by ELISA were significantly elevated in serum from patients with active SLE and correlated with levels of IFNalpha. In vitro, both T-cell-associated and sTRAIL were maximally induced by T cell activation plus IFNalpha in patients and controls. By Western blot analysis, sTRAIL was detected in sera in both the monomeric and multimeric, functional form. Both forms of TRAIL were functional in vitro as determined by Annexin V staining and (51)Cr release assay but the apoptotic activity of membrane TRAIL was 2.5-fold higher compared to that of sTRAIL. These results indicate that IFNalpha-induced enhancement of TRAIL expression and of TRAIL-mediated apoptosis may amplify the abnormal apoptotic process in SLE.     

Outdated and incomplete: a review of thyroid cancer on the World Wide Web.

OBJECTIVE: To evaluate the most frequently searched thyroid cancer websites for completeness, accuracy, and consumer friendliness. DESIGN: The 50 most popular thyroid cancer websites were evaluated using a novel instrument developed by a Delphi panel of endocrine experts and based on practice guidelines. Each website received independent scores for disease-specific information and a final quality score. Quality was related to website demographics using the Student t test, chi-square, and ANOVA analyses. MAIN OUTCOMES: Interrater reliability was excellent (kappa = 0.81). Most websites were not specific to thyroid cancer alone (72%), contained advertisements (72%), lacked references (66%), and were privately sponsored (50%). Only 38% had been updated within 2 years. "Government" and "Non-Profit" websites were the most consumer friendly. Mean quality score of medical content was 38%, with websites receiving the highest score in "Anatomy/Physiology" (55%) and lowest in "Surgery" (29%). Low quality score was attributed to information deficiency rather than inaccuracy. On univariate analysis, no significant associations were found between quality score and country of origin, currency, sponsorship, authorship, administration, advertisements, or references. CONCLUSIONS: Thyroid cancer websites are out of date and incomplete, lacking important information sought by patients, particularly surgical information. An accurate, comprehensive, easily available, and patient-oriented thyroid cancer Internet resource is needed for patients.     

Inflammatory mediators are insufficient for full dendritic cell activation and promote expansion of CD4+ T cell populations lacking helper function

Dendritic cells (DCs) can be activated directly by triggering of receptors for pathogens or, indirectly, by exposure to inflammatory signals. It remains unclear, however, whether the two pathways result in qualitatively similar DCs or lead to equivalent adaptive immune responses. Here we report that indirect activation by inflammatory mediators generated DCs that supported CD4(+) T cell clonal expansion but failed to direct T helper cell differentiation. In contrast, exposure to pathogen components resulted in fully activated DCs that promoted T helper responses. These results indicate that inflammation cannot substitute for contact with pathogen components in DC activation and suggest that the function of pattern recognition by DCs is to couple the quality of the adaptive immune response to the nature of the pathogen.     

Inhibitors of cytochrome P450 4A suppress angiogenic responses

Cytochrome P450 enzymes of the 4A family (CYP4A) convert arachidonic acid to 20-hydroxyeicosatetraenoic acid (20-HETE) in blood vessels of several vascular beds. The present study examined the effects of inhibiting the formation of 20-HETE with N-hydroxy-N'-(4-butyl-2-methylphenol) formamidine (HET0016) on the mitogenic response of vascular endothelial growth factor (VEGF) in human umbilical vein endothelial cells (HUVECs) in vitro, and on growth factor-induced angiogenesis in the cornea of rats in vivo. HET0016 (10 micromol/L and 20 microg, respectively) abolished the mitogenic response to VEGF in HUVECs and the angiogenic response to VEGF, basic fibroblast growth factor, and epidermal growth factor in vivo by 80 to 90% (P < 0.001). Dibromododecenyl methylsulfonimide (DDMS), a structurally and mechanistically different inhibitor of 20-HETE synthesis, also abolished angiogenic responses when tested with VEGF. Additionally, administration of the stable 20-HETE agonist, 20-hydroxyeicosa-6(Z) 15(Z)-dienoic acid (WIT003) induced mitogenesis in HUVECs and angiogenesis in the rat cornea in vivo. We studied the ability of HET0016 to alter the angiogenic response in the rat cornea to human glioblastoma cancer cells (U251). When administered locally into the cornea, HET0016 (20 microg) reduced the angiogenic response to U251 cancer cells by 70%. These results suggest that a product of CYP4A product, possibly 20-HETE, plays a critical role in the regulation of angiogenesis and may provide a useful target for reduction of pathological angiogenesis.