Evaluation of hydraulic radial forces on the impeller by the volute in a centrifugal rotary blood pump

In many state-of-the-art rotary blood pumps for long-term ventricular assistance, the impeller is suspended within the casing by magnetic or hydrodynamic means. For the design of such suspension systems, profound knowledge of the acting forces on the impeller is crucial. Hydrodynamic bearings running at low clearance gaps can yield increased blood damage and magnetic bearings counteracting high forces consume excessive power. Most current rotary blood pump devices with contactless bearings are centrifugal pumps that incorporate a radial diffuser volute where hydraulic forces on the impeller develop. The yielding radial forces are highly dependent on impeller design, operating point and volute design. There are three basic types of volute design--singular, circular, and double volute. In this study, the hydraulic radial forces on the impeller created by the volute in an investigational centrifugal blood pump are evaluated and discussed with regard to the choice of contactless suspension systems. Each volute type was tested experimentally in a centrifugal pump test setup at various rotational speeds and flow rates. For the pump's design point at 5 L/min and 2500 rpm, the single volute had the lowest radial force (～0 N), the circular volute yielded the highest force (～2 N), and the double volute possessed a force of approx. 0.5 N. Results of radial force magnitude and direction were obtained and compared with a previously performed computational fluid dynamics (CFD) study.     

Novel Hedgehog pathway targets against basal cell carcinoma

The Hedgehog signaling pathway plays a key role in directing growth and patterning during embryonic development and is required in vertebrates for the normal development of many structures, including the neural tube, axial skeleton, skin, and hair. Aberrant activation of the Hedgehog (Hh) pathway in adult tissue is associated with the development of basal cell carcinoma (BCC), medulloblastoma, and a subset of pancreatic, gastrointestinal, and other cancers. This review will provide an overview of what is known about the mechanisms by which activation of Hedgehog signaling leads to the development of BCCs and will review two recent papers suggesting that agents that modulate sterol levels might influence the Hh pathway. Thus, sterols may be a new therapeutic target for the treatment of BCCs, and readily available agents such as statins (HMG-CoA reductase inhibitors) or vitamin D might be helpful in reducing BCC incidence.     

Pharmacologic retinoid signaling and physiologic retinoic acid receptor signaling inhibit basal cell carcinoma tumorigenesis

Basal cell carcinoma (BCC) is the most common human cancer. Patients with basal cell nevus syndrome (Gorlin syndrome) are highly susceptible to developing many BCCs as a result of a constitutive inactivating mutation in one allele of PATCHED 1, which encodes a tumor suppressor that is a major inhibitor of Hedgehog signaling. Dysregulated Hedgehog signaling is a common feature of both hereditary and sporadic BCCs. Recently, we showed remarkable anti-BCC chemopreventive efficacy of tazarotene, a retinoid with retinoic acid receptor (RAR) beta/gamma specificity, in Ptch1+/- mice when treatment was commenced before carcinogenic insults. In this study, we assessed whether the effect of tazarotene against BCC carcinogenesis is sustained after its withdrawal and whether tazarotene is effective against preexisting microscopic BCC lesions. We found that BCCs did not reappear for at least 5 months after topical drug treatment was stopped and that already developed, microscopic BCCs were susceptible to tazarotene inhibition. In vitro, tazarotene inhibited a murine BCC keratinocyte cell line, ASZ001, suggesting that its effect in vivo is by direct action on the actual tumor cells. Down-regulation of Gli1, a target gene of Hedgehog signaling and up-regulation of CRABPII, a target gene of retinoid signaling, were observed with tazarotene treatment. Finally, we investigated the effects of topical applications of other retinoid-related compounds on BCC tumorigenesis in vivo. Tazarotene was the most effective of the preparations studied, and its effect most likely was mediated by RARgamma activation. Furthermore, inhibition of basal RAR signaling in the skin promoted BCC carcinogenesis, suggesting that endogenous RAR signaling restrains BCC growth.     

Impact of the nurse-led case management program with retention in care on mortality among people with HIV-1 infection: a prospective cohort study

BackgroundLong-term retention of patients in care is emerging as an important factor for the mortality among persons with human immunodeficiency virus (HIV) infection.ObjectivesThe study was to determine the impact of the case management with retention in care on mortality among HIV infected patients.Design and settingsA longitudinal prospective cohort study was conducted at a tertiary referral HIV-designated hospital in Taiwan.ParticipantsCharts from 1040 patients who had made at least one visit for HIV care at the HIV Clinic in the study hospital in 2009 were abstracted.MethodsA computerized data collection form was used to retrospectively retrieve the electronic demographic and clinical data generated during each clinic visit. Follow-up ended at death or at the last clinic visit as of December 31, 2009.ResultsLess than half (44.2%) of 961 HIV-infected patients were retained for follow-up from 2005 to 2009. Patients who received case management were 4.78 times more likely to remain consistently in care than those who did not receive case management, after controlling for other confounding variables. In the Cox proportional hazard analysis, higher hazards of death were independently associated with older age (hazard ratio [HR]: 1.04; 95% confidence interval [CI]: 1.026–1.055), entering care before 2005 (HR: 1.73; 95% CI: 1.035–2.885), low baseline CD4 cell count (HR: 0.997; 95% CI: 0.995–0.998), without antiretroviral therapy (HR: 0.55; 95% CI: 0.334–0.909), irregular attendance of HIV care or loss to follow-up (HR: 0.058; 95% CI: 0.023–0.148), acquisition of HIV infection through sexual contact (HR: 2.95; 95% CI: 1.517–5.746), and irregular attendance or lost to follow-up and did not enrolled in the case management program (HR: 3.76; 95% CI: 1.015–14.777).ConclusionRetention in care is independently predictive of survival, and case management is a mediator affecting retention on survival. Case managers need to identify high risk patients for irregular attendance and to retain them in HIV care in order to maximize their health outcomes.     

Prediction of community-onset bacteremia among febrile adults visiting an emergency department: rigor matters

Objectives

Bacteremia is a severe bacterial infection with significant mortality and morbidity. Clinical parameters that reliably predict the presence of community-onset bacteremia are less elucidated.

Methods

During 96 randomly selected days between August 2006 and July 2007, a prospective study was conducted to analyze the risk factors of community-onset bacteremia among febrile adults who visited the emergency department (ED) of a medical center. Patients hospitalized in the 30 days prior to the study, patients experiencing consciousness alteration, and nursing facility residents were excluded.

Results

The mean age of the 396 febrile adults enrolled in the study was 53.8 years (range, 18–95 years), and 60 (15.2%) patients had true bacteremia, with the predominance of monomicrobial Gram-negative pathogens (42 patients). In a multivariate analysis, several factors were independently associated with community-onset bacteremia, including an age of >65 years (odds ratio [OR], 2.81; 95% confidence interval [CI], 1.25–6.33), the presence of rigor (OR, 13.7; 95% CI, 4.47–42.0) or chills (OR, 6.04; 95% CI, 1.10–32.9), a body temperature >39.9 °C (OR, 2.68; 95% CI, 1.03–6.94), blood urea nitrogen >20 mg/dL (OR, 5.56; 95% CI, 2.03–15.7), a blood urea nitrogen/creatinine ratio >16 (OR, 2.29; 95% CI, 1.03–5.11), and thrombocytopenia (OR, 6.09; 95% CI, 1.84–20.0). After scoring each risk factor, a logistic regression model for the prediction of bacteremia was developed, and the area under the receiver operating characteristic curve was 0.91.

Conclusions

Some easily determined clinical parameters were independently associated with community-onset bacteremia among febrile adults, and the most significant predictor was the presence of rigor. Although the proposed predictive model needs further validation, it may be of use for the early identification of bacteremic episodes in ED practice.     

Pitfalls in using serum C-reactive protein to predict bacteremia in febrile adults in the ED

Objectives

The diagnostic performance of serum C-reactive protein (CRP) in prediction of bacteremia among febrile patients visiting an emergency department (ED) was analyzed.

Methods

During randomly selected 96 days between August 2006 and July 2007, a prospective study of febrile adults visiting the ED of a medical center was conducted to analyze the clinical characters associated with bacteremia.

Results

Of the total 454 febrile adults enrolled, their mean age was 54.1 years, and 232 (54.6%) were women. Major comorbidities included cardiovascular disease (137 patients, or 30.1%) and diabetes mellitus (105, or 23.1%). Seventy-four patients (16.2%) had true bloodstream infections with the predominance of monomicrobial gram-negative bacteremia in 49 patients (10.7%). Four risk factors, including low platelet count (<100 000/mm³; odds ratio [OR], 4.19; 95% confidence interval [CI], 1.85-9.47; P = .001), high blood urea nitrogen (>20 mg/dL; OR, 4.61; 95% CI, 2.56-8.31; P < .001), high fever (>39.0°C; OR, 3.67; 95% CI, 2.05-6.59; P < .001), and high Pittsburg bacteremia scores (≧4 points; OR, 2.95; 95% CI, 1.01-8.57; P = .04) were independently associated with bacteremic episodes. Of note, high CRP (>150 mg/dL; OR, 1.75; 95% CI, 0.73-3.99; P = .21) was not an independent risk factor. In further analysis, the difference of serum CRP levels between bacteremic and nonbacteremic adults was significant only when the period from fever onset to ED arrival was more than 12 hours.

Conclusions

The CRP level was not reliable to distinguish the bacteremia from nonbacteremic infection, whereas duration after fever onset was less than 12 hours. Clinicians must consider the history of fever onset to improve the accuracy of early prediction of serum CRP before the microbiological results of blood cultures is available.     

Lack of association between a functional genetic variant of connexin 37 and ischemic stroke in a Taiwanese population

Introduction

Connexin 37, encoded by the GJA4 gene, protects against atherosclerosis. A recent study reported an association between polymorphism rs1764391 at GJA4 and ischemic stroke in a Chinese population. We aimed to replicate this result.

Materials and Methods

A total of 958 ischemic stroke patients and 2196 controls were enrolled for the study. All participants were Chinese residing in Taiwan. Logistic regression analysis with adjustment for traditional risk factors was used to estimate the genetic effect. We also performed stratification analyses by sex and stroke subtypes. Literature reviews were conducted for available genetic association studies investigating rs1764391 and cardiovascular phenotypes.

Results

We did not find any significant association for overall stroke (p = 0.87) or from any subset analyses. Eight studies addressing the associations between rs1764391 and cardiovascular phenotypes had a sample size greater than 1000. Including the present study, five out of the eight large-scale studies found no association.

Conclusions

GJA4 polymorphism is not associated with stroke risk in the Taiwanese population.     

Isolated hand weakness in cortical infarctions.

Isolated hand weakness due to stroke is infrequently observed, and often misdiagnosed as peripheral lesions. This study investigated the clinical and radiologic profiles in such patients. Five men and one woman were studied. All patients underwent cranial magnetic resonance imaging (MRI) to confirm the diagnosis. Four patients had uniform weakness and the other two had either differential radial or ulnar weakness, respectively. MRI showed acute infarctions involving the hand knob area of the primary motor cortex (M1) in five patients and the postcentral gyrus sparing the precentral gyrus in one patient. Two patients with uniform digit weakness had additional involvement of the inferior parietal lobule. These findings suggest that isolated or predominant hand weakness in patients with cerebral infarctions is not necessarily caused by lesions in the M1 knob area, and that the control center of hand movement is not limited to the knob area alone.