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Purpose Muscle invasive bladder cancer surgical management has been historically a radical cystoprostatectomy in males and an anterior exenteration in females. Uterine, ovarian, and vaginal preservation are utilized, but raise concerns regarding risk to oncologic control, especially in variant histopathology or advanced stage. Materials and Methods A retrospective single institutional analysis identified radical cystectomies performed in women, including those with variant histology, which were defined as reproductive organ sparing (uterine, vaginal, and ovary sparing) or non-organ sparing. The Kaplan-Meier method was used for recurrence-free (RFS) cancer specific survival (CSS) and overall (OS) survival in patients with advanced disease. Results From 2000 to 2020, 289 women were identified, 188 underwent reproductive organ-sparing cystectomy. No statistical differences were noted for clinical parameters or presence of variant histology for organ-sparing (ROS) and non-organ sparing (non-ROS). Positive margin rates did not differ for ROS and non-ROS; 4.3% vs 7.9%, p=0.19, respectively. Median RFS was not statistically significantly different for ROS vs non-ROS (26.1 vs 15.3 months) p=0.937 HR 1.024. CSS was not statistically different for ROS vs non-ROS (36.3 vs 28.6 months), p=0.755 HR 0.9. OS was not statistically different for ROS vs non-ROS (25.8 v 23.8 months), p=0.5 HR=1.178. Variant histology did not change survival (HR 1.1, p=0.643). Conclusions In this analysis, ROS in women with advanced disease did not increase positive margin rates or decrease RFS, CSS, or OS compared to non-ROS. Variant histology did not decrease survival odds. Based on preoperative assessment and intraoperative findings, ROS in patients with variant histology and advanced disease should be considered.

Klotho is an aging-suppressor gene. The purpose of this study was to determine whether deletion of the klotho gene in kidneys causes aortic aneurysm (AA) and investigate the underlying mechanisms. Klotho-floxed alleles and tamoxifen-inducible kidney-specific CreER T2 mice were crossed to generate KL flox/flox (floxed Klotho); KspCadCreER T2 mice. Tamoxifen injection induced kidney-specific deletion of klotho gene, which led to severe hyperphosphatemia and thoracic and abdominal AA formation in mice on a normal diet. The architectural destruction of the aortic wall in the first 7 days post-Klotho ablation was manifested by overwhelming aortic cell death and calcification, massive MMP (metalloproteinase) 2/9 secretion, elastin degradation, and limited collagen deposition, resulting in aortic wall thinning and AA formation. The adverse reparative remodeling of aortas in the following 7 days exhibited robust fibroblast proliferation and osteogenic differentiation and redundant collagen deposition, further promoting aortic wall thickening and AA progression. These changes were accompanied by aortic macrophage infiltration and osteoclast transition. Interestingly, low-phosphorus diet normalized serum phosphate levels, prevented vascular cell apoptosis and osteogenic differentiation, and consequently retained aortic structure in Klotho-deficient mice. Mechanistically, excessive inorganic phosphate and calcium promoted vascular cell death, osteogenic differentiation, and MMP2/9 secretion ex vivo and in vitro. We found that NF-κB (nuclear factor-kappa B) mediated phosphate-induced MMP2 generation in human aortic smooth muscle cells in vitro. These findings provide the first evidence for a causative role of Klotho deficiency–induced hyperphosphatemia in AA development. Interventional control of dietary phosphorus may be a new preventive and therapeutic strategy for AA.

This paper covers the impact and trend of COVID-19 on Chinese tourism industry, specifically about tourist attraction, tour company, and accommodation. The whole tourism industry is facing a huge loss, and expectedly it can fully recover at the end of the third quarter. Chinese governments set up the tourism support policies to help with those companies, and many of them have already taken actions to provide things online to save their loss of income.

A 74-year-old man with a penile mass was diagnosed with sarcomatoid urothelial carcinoma. Further workup did not show any other lesions or metastases. He was treated with a total penectomy, bilateral inguinal lymph node dissection, and pelvic lymphadenectomy. Following surgery, he received six cycles of cisplatin and gemcitabine. Sarcomatoid carcinoma and carcinosarcoma of the urethra are rare; six prior cases have been reported in the literature, with this being the first urothelial with sarcomatoid component. Survival in patients with sarcomatoid carcinoma or carcinosarcoma of the urinary tract is poor, with the limited data supporting a multimodal approach to improve survival.

INTRODUCTION AND OBJECTIVE:Muscle invasive bladder cancer (MIBC) surgical management has been historically a radical cystoprostatectomy in males and an anterior exenteration in females. Uterine and...

Rationale: Cardiac aging is an important contributing factor for heart failure, which affects a large population but remains poorly understood. Objective: The purpose of this study is to investigate whether Klotho plays a role in cardiac aging. Methods and Results: Heart function declined in old mice (24 months), as evidenced by decreases in fractional shortening, ejection fraction, and cardiac output. Heart size and weight, cardiomyocyte size, and cardiac fibrosis were increased in old mice, indicating that aging causes cardiac hypertrophy and remodeling. Circulating Klotho levels were dramatically decreased in old mice, which prompted us to investigate whether the Klotho decline may cause heart aging. We found that Klotho gene mutation (KL−/−) largely decreased serum klotho levels and impaired heart function. Interestingly, supplement of exogenous secreted Klotho prevented heart failure, hypertrophy, and remodeling in both old mice and KL (−/−) mice. Secreted Klotho treatment inhibited excessive cardiac oxidative stress, senescence and apoptosis in old mice and KL (−/−) mice. Serum phosphate levels in KL (−/−) mice were kept in the normal range, suggesting that Klotho deficiency-induced heart aging is independent of phosphate metabolism. Mechanistically, Klotho deficiency suppressed GR (glutathione reductase) expression and activity in the heart via inhibition of transcription factor Nrf2 (nuclear factor-erythroid 2 p45-related factor 2). Furthermore, cardiac-specific overexpression of GR prevented excessive oxidative stress, apoptosis, and heart failure in both old and KL (−/−) mice. Conclusions: Klotho deficiency causes cardiac aging via impairing the Nrf2-GR pathway. Supplement of exogenous secreted Klotho represents a promising therapeutic strategy for aging-associated cardiomyopathy and heart failure.

Senescence-accelerated mice P1 (SAMP1) is an aging model characterized by shortened lifespan and early signs of senescence. Klotho is an aging-suppressor gene. The purpose of this study is to investigate whether in vivo expression of secreted klotho ( Skl ) gene attenuates aortic valve fibrosis in SAMP1 mice. SAMP1 mice and age-matched (AKR/J) control mice were used. SAMP1 mice developed obvious fibrosis in aortic valves, namely fibrotic aortic valve disease. Serum level of Skl was decreased drastically in SAMP1 mice. Expression of MCP-1 (monocyte chemoattractant protein 1), ICAM-1 (intercellular adhesion molecule 1), F4/80, and CD68 was increased in aortic valves of SAMP1 mice, indicating inflammation. An increase in expression of α-smooth muscle actin (myofibroblast marker), transforming growth factorβ-1, and scleraxis (a transcription factor of collagen synthesis) was also found in aortic valves of SAMP1 mice, suggesting that accelerated aging is associated with myofibroblast transition and collagen gene activation. We constructed adeno-associated virus 2 carrying mouse Skl cDNA for in vivo expression of Skl. Skl gene delivery effectively increased serum Skl of SAMP1 mice to the control level. Skl gene delivery inhibited inflammation and myofibroblastic transition in aortic valves and attenuated fibrotic aortic valve disease in SAMP1 mice. It is concluded that senescence-related fibrotic aortic valve disease in SAMP1 mice is associated with a decrease in serum klotho leading to inflammation, including macrophage infiltration and transforming growth factorβ-1/scleraxis-driven myofibroblast differentiation in aortic valves. Restoration of serum Skl levels by adeno-associated virus 2 carrying mouse Skl cDNA effectively suppresses inflammation and myofibroblastic transition and attenuates aortic valve fibrosis. Skl may be a potential therapeutic target for fibrotic aortic valve disease.

BackgroundVascular cognitive impairment (VCI) results from cerebrovascular disease, and worldwide, it is the second most common type of cognitive dysfunction. While targeted aerobic training is a promising approach to delay the progression of VCI by reducing cardiometabolic risk factors, few randomised controlled trials to date have specifically assessed the efficacy of aerobic training on cognitive and brain outcomes in this group at risk for functional decline.AimTo examine the effect of moderate-intensity aerobic training on executive functions and functional neural activity among older adults with mild subcortical ischaemic VCI (SIVCI).MethodsOlder adults with mild SIVCI were randomly assigned to: (1) 6-month, 3×/week aerobic training (n=10) or (2) usual care (control; n=11). Participants completed functional MRI (fMRI) at baseline and trial completion. During the fMRI sessions, behavioural performance on the Eriksen flanker task and task-evoked neural activity were assessed.ResultsAt trial completion, after adjusting for baseline general cognition, total white matter lesion volume and flanker performance, compared with the control group, the aerobic training group significantly improved flanker task reaction time. Moreover, compared with the controls, the aerobic training group demonstrated reduced activation in the left lateral occipital cortex and right superior temporal gyrus. Reduced activity in these brain regions was significantly associated with improved (ie, faster) flanker task performance at trial completion.SummaryAerobic training among older adults with mild SIVCI can improve executive functions and neural efficiency of associated brain areas. Future studies with greater sample size should be completed to replicate and extend these findings.

Background and Objective: Aging is associated with increased prevalence of arterial stiffness and hypertension. The senescence-accelerated mouse (SAMP1) demonstrates early and spontaneous aging phenotypes around 6-8 months of age. In contrast, microRNA-150 knockout (miR-150 KO) slows down the aging process and extends lifespan in mice by 20-30%. The object of this study is to investigate whether transplantation of bone marrow cells (BMCs) from miR-150 KO mice attenuates arterial stiffening and hypertension in SAMP1 mice. Method and Results: Pulse wave velocity (PWV) and blood pressure (BP) levels were increased significantly in the SAMP1 mice compared with the age-matched control (AKR/J) mice (10 months), indicating that SAMP1 mice developed arterial stiffening and hypertension. Interestingly, transplantation of bone marrow cells (BMCs) from miR-150-KO mice decreased PWV and BP in SAMP1 mice to nearly control levels within 3 months. BMC transplantation decreased expression of collagen1, TGFβ1, Scleraxis (collagen gene transcription factor), MMP-2 and MMP-9 but increased expression of elastin in aortas of SAMP1 mice, indicating improved arterial remodeling. BMC transplantation from miR-150-KO mice partially rescued the downregulation of B cells lymphocytes and increased the serum level of IgG and IgM, abolished infiltration of T cells and macrophages, and decreased inflammatory cytokine expression in aortas in SAMP1 mice. In the cell culture study, IgG deficiency increased inflammatory factor cytokine expression in endothelial cells, which can be abolished by addition of IgG protein. Conclusion: BMC transplantation from miR-150-KO mice reversed arterial stiffness and hypertension in SAMP1 mice likely via modulation of the immune function. This study demonstrates, for the first time, that BMC transplantation may be an effective therapeutic strategy for aging-related arterial stiffness and hypertension.

Re-excision due to inability to visualize positive margins following breast-conserving surgery is a significant clinical challenge. 5-aminolevulinic acid (5-ALA), a non-fluorescent prodrug, leads to intracellular accumulation of fluorescent porphyrins in tumor cells. This single-centre Phase II randomized controlled trial evaluated the clinical safety, feasibility and diagnostic performance of a new handheld fluorescence imaging device (PRODIGI) combined with 5-ALA hydrochloride (HCl) for intraoperative visualization of invasive breast carcinomas. Fifty-four patients were enrolled in the study and randomized to receive no 5-ALA HCl or orally administered 5-ALA HCl (15 mg/kg or 30 mg/kg BW). Forty-five patients (n = 15/group) were included in the analysis. Fluorescence imaging of the excised surgical specimen was performed and biopsies were collected from within and outside the clinically-demarcated tumor border for blinded histopathological analysis. In the absence of 5-ALA HCl, tissue autofluorescence imaging lacked tumor-specific fluorescent contrast. Administration of 5-ALA HCl resulted in tumors that fluoresced bright red with improved visualization of tumor contrasted against normal tissue autofluorescence. In the 15 mg/kg 5-ALA dose group the positive predictive value (PPV) for detecting tumor inside and outside the grossly demarcated tumor border was 100.0% and 55.6%, respectively and 100.0% and 50.0% respectively in the 30 mg/kg dose group. No drug or device-related adverse events were observed and technical feasibility and clinical integration of this intraoperative tumor visualization approach were confirmed. This is the first known clinical report of visualization of 5-ALA HCl-induced fluorescence in invasive lobular and ductal breast carcinoma using a real-time handheld intraoperative fluorescence imaging device.

This article examines KidZania Kuala Lumpur – an ‘edutainment park’ in Malaysia – within the context of the literature on play and the literature on globalisation. Changes in young Malaysian’s experiences of play resulting from globalisation and global corporate interests point to broader changes in Malaysian society. While KidZania claims to provide edutainment through role-play, it seems that the children’s play is often highly structured. While the children may appear amazed by KidZania’s impressive facades, this realistic environment leaves little room for imaginative play. Furthermore, because the experience of KidZania is essentially based around the production and consumption of regional and global commodities, the label ‘advertainment’ seems justified. Many of the issues raised in this paper actually reflect and reinforce broader issues in Malaysian society – and appear to be exasperated by the recruitment of largely young and potentially inexperienced workers. KidZania’s apparent weakness...

Objective Fibromyalgia (FM) in rheumatoid arthritis (RA) can cause consternation because symptoms are seen to be out of proportion to physician and laboratory assessments, and composite RA activity scores such as the 28 joint Disease Activity Score, Clinical Disease Activity Index, and Routine Assessment of Patient Index Data 3 (RAPID-3) can yield apparently “wrong” results. We explored the effect of polysymptomatic distress (PSD), a measure of fibromyalgianess and a quantity derived from the American College of Rheumatology 2010 FM diagnostic criteria, to explain the relationship of patient to physician variables. Methods We obtained PSD scores on 300 RA patients prior to ordinary clinical care, and assessed the associations of PSD with tender and swollen joints, physician global estimate of RA activity, pain, Health Assessment Questionnaire score, and composite RA activity measures during routine clinic assessments. Results PSD scores greater than the sample mean (8.8) were associated with increased patient symptoms regardless of the presence or absence of FM, while scores below the mean were associated with better patient outcomes. PSD scores predicted all patient outcomes and less strongly predicted physician outcomes. The discrepancy between patient and physician measures was greatest at low levels of physician-estimated disease activity. Conclusion PSD rather than FM diagnosis more usefully identifies and predicts disproportionate responses. Just as there are patients who lean disproportionately toward greater severity, there are also patients who disproportionately report milder symptoms. Composite measures used to assess RA are flawed, as they confound RA inflammation and patient distress, and more consideration should be given to disaggregated assessments. PSD also appears to be influenced weakly by RA disease activity.

Vascular cognitive ischaemia (VCI) is the second most common type of cognitive dysfunction worldwide and is due to cerebrovascular disease. While targeted aerobic exercise is a promising approach to delay the progression of VCI by reducing cardiometabolic risk factors, few randomized controlled trials to date have specifically assessed the efficacy of aerobic exercise on cognitive and brain outcomes in this high-risk group. Thus, the goal of this secondary analysis study was to examine the effect of moderate-intensity aerobic exercise training on executive functions and functional neural plasticity among older adults with mild subcortical ischaemic vascular cognitive impairment (SIVCI). Seventy-one older adults with mild SIVCI were randomly assigned to: 1) a 6-month, 3x/week aerobic training (AT; n=36) or usual care (CON; n=35). This secondary analysis included 21 (mean age 71.5 years) participants; 10 from AT group and 11 from CON group. All 21 participants completed functional magnetic resonance imaging (fMRI) sessions at baseline and trial-completion. During the fMRI sessions, performance on the Eriksen flanker task and task-evoked neural activity were assessed. At trial completion, after adjusting for baseline MoCA, baseline total white matter lesion volume, and baseline performance, compared with the CON group, the AT group significantly improved flanker task performance. Moreover, compared with the CON, the AT group demonstrated reduced activation in the left lateral occipital cortex and right superior temporal gyrus. Reduced activity in these brain regions was significantly associated with improved (i.e., faster) flanker task performance at trial completion, suggesting aerobic training increased neural efficiency. Thus, aerobic training among older adults with mild SIVCI can improve executive functions and neural efficiency of associated brain areas.

Objective To describe use of the American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) rheumatoid arthritis (RA) remission criteria in clinical practice. Methods Remission was examined using data on 1,341 patients with RA (91% men) from the US Department of Veterans Affairs RA (VARA) registry (total of 9,700 visits) and 1,153 patients with RA (25.8% men) in a community rheumatology practice (Arthritis and Rheumatology Clinics of Kansas [ARCK]) (total of 6,362 visits). Cross-sectional and cumulative probabilities were studied, and agreement between the various remission criteria was assessed. Aspects of reliability of the criteria were determined using Boolean-based definitions, as well as the Clinical Disease Activity Index (CDAI) and Simplified Disease Activity Index (SDAI) scoring methods proposed by the ACR/EULAR joint committee. Results When the 3-variable ACR/EULAR definition of remission recommended for use in community practice (swollen and tender joint counts ≤1, and visual analog scale score for patient's global assessment of disease activity ≤1) was applied, cross-sectional remission was 7.5% (95% confidence interval [95% CI] 6.4, 8.7%) for ARCK and 8.9% (95% CI 7.9, 9.9%) for VARA, and cumulative remission (remission at any observation) was 18.0% (for ARCK) and 24.4% (for VARA), over a mean followup of ∼2.2 years. Addition of the erythrocyte sedimentation rate or C-reactive protein level to the criteria set reduced remission to 5.0–6.2%, and use of the CDAI/SDAI increased the proportions to 6.9–10.1%. Moreover, 1.8–4.6% of the patients met remission criteria at ≥2 visits. Agreement between criteria definitions was good, as assessed by kappa statistics and Jaccard coefficients. Among patients in remission, the probability of a remission lasting 2 years was 6.0–14.1%. Among all patients, the probability of a remission lasting 2 years was

Objective.To investigate whether fatigue is an inflammatory (rheumatoid arthritis; RA) variable, the contributions of RA variables to fatigue, and the levels of fatigue in RA compared with osteoarthritis (OA) and fibromyalgia (FM).Methods.We studied 2096 RA patients, 1440 with OA, and 1073 with FM in a clinical setting, and 14,607 RA, 3173 OA, and 2487 patients with FM in survey research. We partitioned variables into inflammatory and noninflammatory factors and examined variable contribution to fatigue (0–10 visual analog scale).Results.Factor analysis identified Disease Activity Score-28 (DAS28) and swollen (SJC) and tender joint count (TJC) as a physician-inflammation factor, and patient global assessment, pain, Health Assessment Questionnaire, and fatigue as patient components. Fatigue demonstrated weak correlations with erythrocyte sedimentation rate (ESR; r = 0.071) and SJC (r = 0.112), weak to fair correlations with TJC (r = 0.294), physician global assessment of RA activity (r = 0.384), and DAS28 (r = 0.399), but strong correlation with patient global assessment of severity (r = 0.567). In hierarchical regression analysis, patient global explained 43.1% of DAS28 fatigue variance; when SJC, TJC, and ESR were entered, the explained variance increased to 43.7%. In reverse order, SJC, TJC, and ESR explained 9.2% of the variance, but explained variance increased to 43.7% when patient global was added. The mean clinic fatigue scores were RA 4.9, OA 4.8, FM 7.6; mean survey scores were RA 4.5, OA 4.4, FM 6.3. Adjusted for age and sex, RA and OA fatigue scores were not significantly different.Conclusion.Inflammatory components of the DAS28 contribute minimally to fatigue. RA and OA fatigue levels do not differ. Fatigue is not an inflammatory variable and has no unique association with RA or RA therapy.

Pimecrolimus is an ascomycin macrolactam derivative that has been recently approved for the topical treatment of atopic dermatitis. In this study we report for the first time on a direct comparison of the inhibitory activity of pimecrolimus and the glucocorticosteroids betamethasone 17-valerate, dexamethasone and hydrocortisone at the level of T-cell proliferation and cytokine production. Stimulated human peripheral blood mononuclear cell (PBMC) systems were used that are either sensitive or resistant to calcineurin inhibitors or glucocorticosteroids. Pimecrolimus and the glucocorticosteroids inhibited dose-dependently T-cell proliferation and cytokine production in a sensitive system (anti-CD3 mAb-stimulated PBMC) with the following rank order of potency: pimecrolimus approximately betamethasone 17-valerate approximately dexamethasone > hydrocortisone. In resistant systems (anti-CD3 plus anti-CD28- or Staphylococcal enterotoxin B-stimulated PBMC), pimecrolimus or the glucocorticosteroids alone exerted either no effect, or only a partial inhibitory effect. However, combinations of pimecrolimus with a glucocorticosteroid synergistically and strongly inhibited T-cell proliferation. Taken together, the data indicate that medium potency glucocorticosteroids, such as betamethasone 17-valerate and dexamethasone, are as potent T-cell inhibitors as pimecrolimus. Furthermore, the experimental evidence suggests that combinations of glucocorticosteroids and pimecrolimus could be used clinically to achieve superior therapeutic efficacy, when monotherapy with the individual agents is unsatisfactory.

Impaired mobility is a major concern for older adults and has significant consequences. While the widely accepted belief is that improved physical function underlies the effectiveness of targeted exercise training in improving mobility and reducing falls, recent evidence suggests cognitive and neural benefits gained through exercise may also play an important role in promoting mobility. However, the underlying neural mechanisms of this relationship are currently unclear. Thus, our main objective was to investigate whether six months of progressive aerobic exercise training alters frontoparietal network (FPN) connectivity during a motor task among older adults at risk for mobility disability – individuals with mild subcortical ischemic vascular cognitive impairment (SIVCI)—and whether exercise-induced changes in FPN connectivity correlate with concurrent changes in mobility. We focused on the FPN as it is involved in top-down attentional control as well as motor planning and motor execution. Participants were randomized either to usual-care (CON) or thrice-weekly aerobic training (AT). Functional magnetic resonance imaging was acquired at baseline and trial completion. At trial completion, compared with AT, CON showed significantly increased FPN connectivity strength during right finger tapping (p

Objective.To investigate what factors influence patient global health assessment (PtGlobal), and how those factors and the reliability of PtGlobal affect the rate, reliability, and validity of recently published American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) rheumatoid arthritis (RA) remission criteria when used in clinical practice.Methods.We examined consecutive patients with RA in clinical practice and identified 77 who met ACR/EULAR joint criteria for remission (≤ 1 swollen joint and ≤ 1 tender joint). We evaluated factors associated with a PtGlobal > 1, because a PtGlobal ≤ 1 defined ACR/EULAR remission in this group of patients who had already met ACR/EULAR joint criteria.Results.Of the 77 patients examined, only 17 (22.1%) had PtGlobal ≤ 1 and thus fully satisfied ACR/EULAR criteria. A large proportion of patients not in remission by ACR/EULAR criteria had high PtGlobal related to noninflammatory issues, including low back pain, fatigue, and functional limitations, and a number of patients clustered in the range of PtGlobal > 1 and ≤ 2. However, the minimal detectable difference for PtGlobal was 2.3. In addition, compared with a PtGlobal severity score, a PtGlobal activity score was 3.3% less likely to be abnormal (> 1).Conclusion.Noninflammatory factors contribute to the level of PtGlobal and result in the exclusion of many patients who would otherwise be in “true” remission according to the ACR/EULAR definition. Reliability problems associated with PtGlobal can also result in misclassification, and may explain the observation of low longterm remission rates in RA. As currently constituted, the use of the ACR/EULAR remission criteria in clinical practice appears to be problematic.

We address what happens before negotiators reach the table. We hypothesize that negotiators, particularly novice negotiators who may have little insight into the advantages of certain kinds of substantive information, will prefer relational over substantive information when given the choice to select it. We also hypothesize that Negotiators who are epistemically motivated will be more likely to choose heterogeneous information compared to those who are not epistemically motivated.

Background: Recent studies in murine models of allergic contact dermatitis have shown that systemic treatment with pimecrolimus in contrast to tacrolimus did not inhibit the sensitization phase, whereas both compounds equivalently suppressed the inflammatory response in sensitized animals. This finding indicated a differential sensitivity of antigen-naïve and primed T cells towards pimecrolimus and tacrolimus. Methods: T cells obtained from healthy and allergic donors were subjected to primary and secondary stimulation by allogeneic or staphylococcal superantigen-presenting dendritic cells (DC). Human skin-derived, allergen-specific T cell clones from an atopic dermatitis patient were activated by anti-CD3 antibodies or by specific allergen-presenting DC. The inhibition of T cell proliferation and cytokine release by graded doses of calcineurin inhibitors was evaluated. Results: Primary stimulation of T cells was inhibited by pimecrolimus with an approximately 8-fold lower potency as compared with tacrolimus. In contrast, the secondary response of ex vivo expanded T cells activated by allogeneic or staphylococcal superantigen-presenting DC was inhibited by both compounds with equivalent potency. Likewise, both drugs showed very similar potency to inhibit the proliferation and cytokine synthesis from antigen- stimulated T cell clones and the induction of cytokines in Jurkat T cells. Conclusion: These data indicate that pimecrolimus has a selectivity for antigen-primed memory T cells not seen with tacrolimus.

Adverse gastrointestinal (GI) outcome after cardiac surgery is an infrequent event but is a clinically important health care problem because of associated increased morbidity and mortality. The ability to identify patients at greatest risk before surgery may be helpful in planning appropriate perioperative management strategies. We examined the pre- and intraoperative characteristics of 2417 patients from 24 diverse United States medical centers enrolled in the Multicenter Study of Perioperative Ischemia Study who were undergoing cardiac surgery using cardiopulmonary bypass as predictors for adverse GI outcome. Resource utilization was evaluated for patients with and without adverse GI outcomes. Adverse GI outcomes occurred in 5.5% of patients (133 of 2417), increased in-hospital mortality 6.5-fold, prolonged the mean intensive care unit length of stay by 1 wk, and more than doubled the mean postoperative hospital stay (P0.0001). Predictors of adverse GI outcome included decreased left ventricular function, hyperbilirubinemia, thrombocytopenia, prolonged partial thromboplastin time, prior cardiovascular surgery, combined coronary artery bypass graft surgery and intracardiac or proximal aortic surgery, pharmacological cardiovascular support, and intraoperative transfusion. The literature suggests that adverse GI outcome after cardiac surgery is secondary to poor splanchnic perfusion, which many of these risk factors may predict. Therefore, patients deemed to be at risk before surgery may benefit from tightly controlled hemodynamic management and other strategies that optimize perioperative organ perfusion.We identified the preoperative and intraoperative predictors associated with an increased incidence of postoperative gastrointestinal complications after cardiac surgery using cardiopulmonary bypass. Because these complications are associated with frequent morbidity and mortality, these predictors may be helpful in identifying patients at increased risk so that risk stratification can be modified and perioperative management can be appropriately adjusted.

Electrical resistivity of chicken breast meat and pork chop was investigated. Effects of various combinations of sinusoidal, square and saw-tooth wave electric signals, eight frequencies in the range of 10 and 10kHz, and three AC voltages, 10, 20 and 30 volts, on the resistivity property were evaluated. Increase in the input voltage and the frequency decreased the resistivity. Square wave produced the least resistivity irrespective of voltage and frequency followed by sinusoidal and saw-tooth waves. With the increase in frequency the differences in the resistivity values decreased among all three input voltages, irrespective of signals. Resistivity was higher across the myofiber direction than along the myofober direction.

The persistent variability in red blood cell transfusion practice in coronary artery bypass graft (CABG) patients, despite established guidelines, suggests inappropriate use. Our objective was to determine the impact of postoperative red blood cell (RBC) transfusion in entirely stable CABG patients. We investigated a cohort of 940 stable CABG patients from the 5,065 patients enrolled in the Multicenter Study of Perioperative Ischemia Epidemiology II (EPI II) Study with (1) low to moderate risk profile; (2) postoperative hemoglobin levels ≥ 10 g/dL; (3) minimal postoperative blood loss, and (4) no evidence of any morbid event on the day of surgery. RBC transfusion was assessed during the first 24 postoperative hours and multiorgan outcomes as well as markers of resource utilization from postoperative day one to hospital discharge. Transfused patients (N =190, 20.2 %) were more likely to suffer myocardial infarction (OR, 1.89; 95 % CI, 1.08 to 3.29; P = 0.02); renal dysfunction (OR, 3.35; 95 % CI, 1.01 to 11.1; P = 0.04); renal failure requiring dialysis (OR, 4.01; 95 % CI, 0.99 to 16.2; P = 0.05); and/or harvest site wound infection (OR, 5.45; 95 % CI, 1.87 to 15.9; P = 0.001). RBC transfusion was shown to be an independent predictor of composite morbidity outcome, cardiac morbidity, and harvest site wound infection in multivariate analysis. In transfused patients, the mean duration of hospitalization was increased by 2.5 days (14.4 days vs. 11.9 days; P < 0.001). In CABG patients with low to moderate mortality risk profiles, adequate hemoglobin values and low bleeding rates, postoperative RBC transfusion is associated with an increased risk for cardiac, renal and infectious morbidity, as well as increased health care expenses, without any detectable benefit.