Members of the low‐density lipoprotein receptor‐related proteins provide a differential molecular signature between parental and CD133(+) DAOY medulloblastoma cells

Members of the low‐density lipoprotein receptor‐related protein (LRP) family are involved in metabolic stress and resistance phenotypes of cancer cells. New breakthroughs in brain cancer therapy have exploited that molecular signature and proved that efficient delivery of therapeutic agents involve LRP‐mediated mechanisms. We performed gene expression profiling of CD133, a cell surface cancer stem cell marker, and of LRP in response to in vitro nutrient deprivation. We found that CD133 was selectively induced in serum‐starved DAOY medulloblastoma cells but not in U87MG glioblastoma cells. Such CD133 induction was correlated to increases in LRP‐1 and LRP‐1b gene and protein expression. When a specific CD133(+) DAOY cell population was sorted from parental DAOY, we found increases in LRP‐5 and LRP‐8. Uptake of α₂‐macroglobulin, a specific LRP‐1/1b ligand, was increased in serum‐starved parental DAOY cells but not in CD133(+) DAOY cells, and receptor‐associated protein (RAP), which binds to all cell surface LRPs, was able to compete for that uptake. Conversely, RAP binding was increased in serum‐starved parental DAOY but α₂‐macroglobulin was unable to compete for such uptake. Strategies aiming at targeting cancer stem cell metabolic adaptative responses, such as that through LRP differential expression within the brain tissue microenvironmental niche, can now be envisioned. © 2010 Wiley‐Liss, Inc.     

Physiotherapy for cystic fibrosis in Australia and New Zealand: A clinical practice guideline

Physiotherapy management is a key element of care for people with cystic fibrosis (CF) throughout the lifespan. Although considerable evidence exists to support physiotherapy management of CF, there is documented variation in practice. The aim of this guideline is to optimize the physiotherapy management of people with CF in Australia and New Zealand. A systematic review of the literature in key areas of physiotherapy practice for CF was undertaken. Recommendations were formulated based on National Health and Medical Research Council (Australia) guidelines and considered the quality, quantity and level of the evidence; the consistency of the body of evidence; the likely clinical impact; and applicability to physiotherapy practice in Australia and New Zealand. A total of 30 recommendations were made for airway clearance therapy, inhalation therapy, exercise assessment and training, musculoskeletal management, management of urinary incontinence, managing the newly diagnosed patient with CF, delivery of non‐invasive ventilation, and physiotherapy management before and after lung transplantation. These recommendations can be used to underpin the provision of evidence‐based physiotherapy care to people with CF in Australia and New Zealand.     

Substernal goiters

In a series of 363 patients operated for goiter, 60 were retrosternal (16.5%). The female incidence although less than in cervical goiters remains predominant (2,5:1). Most patients are in older age group, 68% being above 40 years. The majority of goiters are multinodular and of long duration. Bilateral (37%) and left sided location (43%) were common. The incidence of cancer was 7%, thyrotoxicosis was noted in 5 patients (8%). Most patients were symptomatic (97%). Diagnosis is easily done by physical examination, chest X-Ray and thyroid scintigraphy. Computed tomography might be helpful. Retrosternal goiter is an indication to surgery except in high risk patients. The cervical approach has been used in 98% of cases. There were no post-operative death and no major complications (compressive hematoma, laryngeal nerve paralysis, hypocalcemia).     

Establishing the Feasibility of Face Transplantation in Granulomatosis With Polyangiitis

Granulomatosis with polyangiitis (GPA; formerly Wegener's granulomatosis) is a rare vasculitis that commonly starts in the craniofacial region. We report a case that was masked by prior facial trauma and associated with pyoderma gangrenosum (PG). Disease progression and aggressive debridements led to severe facial tissue loss. The decision to perform a face transplant was controversial because of the risk of disease relapse on the facial allograft. We reviewed renal transplant outcomes in GPA for possible relevance. A PubMed search retrieved 29 studies. Patient and graft survival, relapse, morbidity, mortality, rejection and immunosuppression were assessed. Ten‐year patient survival and graft survival were 84.4% and 72.6%, respectively. GPA relapse occurred in 31.5%, and upper airway/ocular relapse occurred in 17.8% (resolved in 76.9%). Mortality was 12.3%. Acute and chronic rejection rates were 14.9% and 6.8%, respectively. Traditional posttransplant immunosuppression was effective. Our review suggests that GPA renal transplant outcomes are comparable to general renal transplant cohorts. Furthermore, transplanted GPA patients exhibit lower disease relapse secondary to lifelong immunosuppression. This supported our decision to perform a face transplant in this patient, which has been successful up to the present time (1‐year posttransplantation). Untreated GPA and PG are potential causes of worse surgical outcomes in the craniofacial region.     

The influence of simulated aging on the color stability of composite resin cements

Statement of problem

Data for the color stability of dual-polymerized and light-polymerized resin cements used in esthetic dentistry are lacking.

Cardiac gated equilibrium radionuclide angiography and multiharmonic Fourier phase analysis: Optimal acquisition parameters in arrhythmogenic right ventricular cardiomyopathy

BACKGROUND: Multiharmonic Fourier phase analysis of radionuclide angiography is a well-established method for the diagnosis of arrhythmogenic right ventricular cardiomyopathy. We sought to determine the optimal acquisition parameters: number of frames per cycle and number of counts per frame, with all other acquisition and processing parameters being fixed. METHODS AND RESULTS: Radionuclide angiography with list mode acquisition was performed in 10 normal subjects (pilot group) and 11 patients with arrhythmogenic right ventricular cardiomyopathy (validation group), allowing the reconstruction of electrocardiography-gated constant phase studies with different parameters: 16, 24, and 32 frames per cycle and 200, 400, 600, and 800 kcounts per frame. Three harmonics Fourier phase analysis was applied, and optimal acquisition parameters (defined as those providing best homogeneous phase distribution histogram in the pilot group) were defined as judged by the H3 right ventricular phase SD and delta 95%. These were 16 frames per cycle and 600 kcounts per frame. Then we verified in the validation group that these optimal acquisition parameters did not induce any significant relative loss of information compared with other acquisition parameters with more temporal resolution (24 and 32 frames per cycle) or more statistics (800 kcounts per frame). This result was realized by the calculation of normalized H3 right ventricular SD, right ventricular delta 95%, and (SD[left ventricle] - SD[right ventricle]). CONCLUSIONS: In practice, 16 frames per cycle and 600 kcounts per frame are optimal for multiharmonic Fourier phase analysis, with all other acquisition and processing variables being fixed as specified.     

Difference in susceptibility to malaria between two sympatric ethnic groups in Mali

We compared malaria indicators among sympatric groups to study human heterogeneities in the response to Plasmodium falciparum malaria infection. Four cross-sectional surveys and two longitudinal surveys in two sympatric ethnic groups (Dogon and Fulani) in Mali were carried out from 1998 to 2000. Spleen and parasite rates were evaluated during the cross-sectional surveys and disease incidence was assessed during longitudinal surveys. In spite of similar sociocultural factors and entomologic inoculation rates between ethnic groups, the Fulani had a significantly higher spleen enlargement rate, lower parasite rate, and were less affected by the disease than the Dogon group, whose frequency of hemoglobin C was higher than that recorded among the Fulani group. The Fulani group had significantly higher levels of IgG and IgE against crude malaria antigen than the Dogon group, suggesting a role of anti-malaria antibodies in the immune protection seen in this group.     

Réponse humorale anti-Plasmodium falciparum AMA1 et MSP1 dans deux groupes ethniques vivant en sympatrie au Mali

Fulani of Mali are known for their lower susceptibility to Plasmodium falciparum malaria than their neighbours, the Dogon, despite similar transmission conditions. However, the mechanisms underlying these differences are poorly understood, particularly those concerning antigenspecific immune responses. The Apical Membrane Antigen 1 (AMA1) and the Merozoite Surface Antigen 1 (MSP1) are two malaria vaccine candidates, which play a pivotal role during the invasion of parasites into erythrocytes, and in the case of AMA1, of hepatocytes. Therefore, we analyzed the level of anti-AMA1 and anti-MSP1 antibodies (FVO and 3D7 alleles), by using ELISA (Enzyme Linked Immuno Sorbent Assay) to investigate whether there are differences between the two ethnic groups. Our results show that the splenic rate, the level of anti-AMA1 and anti-MSP1 were significantly higher in Fulani compared to Dogon; while the parasite rate was lower in Fulani group compared to Dogon. Our results suggest that the lower susceptibility of Fulani to malaria could be due to the higher specific humoral responses against AMA1 and MSP 1 in Fulani??s ethnic group compared to Dogon.