Our data suggest that differences in HER-2 expression between primary tumors and their lymph node metastases cannot explain the high fraction of nonresponders to trastuzamab therapy.

It is becoming increasingly clear that under natural conditions parasitic infections commonly consist of co-infections with multiple conspecific strains. Multiple-strain infections lead to intraspecific interactions and may have important ecological and evolutionary effects on both hosts and parasites. However, experimental evidence on intraspecific competition or facilitation in infections has been scarce because of the technical challenges of distinguishing and tracking individual co-infecting strains. To overcome this limitation, we engineered transgenic strains of the protozoan parasite Trypanosoma brucei, the causal agent of human African sleeping sickness. Different strains were transfected with fluorescence genes of different colors to make them visually distinguishable in order to investigate the effects of multiple-strain infections on parasite population dynamics and host fitness. We infected mice either with each strain alone or with mixes of two strains. Our results show a strong mutual competitive suppression of co-infecting T. brucei strains very early in infection. This mutual suppression changes within-host parasite dynamics and alleviates the effects of infection on the host. The strength of suppression depends on the density of the co-infecting strain, and differences in life-history traits between the strains determine the consequences of strain-strain competition for the host. Unexpectedly, co-infection with a less virulent strain significantly enhances host survival (+15%). Analysis of the strain dynamics reveals that this is due to the suppression of the density of the more virulent strain (-33%), whose degree of impact ultimately determines the physical condition of the host. The competitive suppression is likely caused by allelopathic interference or by apparent competition mediated by strain-specific immune responses. These findings highlight the importance of intraspecific variation for parasite-parasite and parasite-host interactions. To fully understand parasite and disease dynamics, the genetic diversity of infections must be taken into account. Through changes in parasite dynamics, intraspecific variation may further affect transmission dynamics and select for increased virulence of each strain. The precise mechanisms underlying mutual suppression are not yet understood but may be exploitable to fight this devastating parasite. Our results are therefore not only of basic ecological interest investigating an important form of intraspecific competition, but may also have applied relevance for public health.

It becomes evident from our combined metabolic-structural approach that a prediction model, to identify which individual is at risk of developing a photoreceptor degeneration of RCD type, can be proposed. It will take into account the peripapillary retinal oxygen saturation, the retinal vessel diameter and the RNFL thickness values.

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BackgroundThe aim of this epidemiological study was to investigate the relationship of thermal discomfort with cold extremities (TDCE) to age, gender, and body mass index (BMI) in a Swiss urban population.MethodsIn a random population sample of Basel city, 2,800 subjects aged 20-40 years were asked to complete a questionnaire evaluating the extent of cold extremities. Values of cold extremities were based on questionnaire-derived scores. The correlation of age, gender, and BMI to TDCE was analyzed using multiple regression analysis.ResultsA total of 1,001 women (72.3% response rate) and 809 men (60% response rate) returned a completed questionnaire. Statistical analyses revealed the following findings: Younger subjects suffered more intensely from cold extremities than the elderly, and women suffered more than men (particularly younger women). Slimmer subjects suffered significantly more often from cold extremities than subjects with higher BMIs.ConclusionsThermal discomfort with cold extremities (a relevant symptom of primary vascular dysregulation) occurs at highest intensity in younger, slimmer women and at lowest intensity in elderly, stouter men.

Previous research evaluating the use of adjuvant endocrine therapy among postmenopausal breast cancer patients showed with 15 -50% wide ranges of non-adherence rates. We evaluated this issue by analysing an unselected study group comprising of 325 postmenopausal women, diagnosed from 1997 to 2003 with hormonal receptor-positive invasive breast cancer. The different clinical situations that led to the discontinuation of adjuvant endocrine therapy were clearly defined and differentiated: non-adherence was not simply the act of stopping medication, but rather the manifestation of an intentional behaviour of the patient. Of the 287 patients who initiated endocrine therapy, 191 (66.6%) fully completed this treatment. Thirty-one patients (10.8%) showed non-adherence to therapy. Patients who had follow-up with a general practitioner, rather than in an oncologic unit, were more likely to be non-adherent (P ¼ 0.0088). Of 25 patients who changed medication due to therapy-related adverse effects, 20 (80%) patients fully completed the therapy after drug change. In adjuvant endocrine therapy, a lowering of the non-adherence rate to 10.8%, the lowest reported in the literature, is realistic when patients are cared for by a specialised oncologic unit focusing on the individual needs of the patients.

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ABSTRACT.Purpose: To determine a relationship between the retinal vessel saturation alterations and the residual retinal function measured by means of full-field electroretinography (full-field ERG), electrooculogram (EOG) and multifocal electroretinography (mfERG) in patients with retinitis pigmentosa (RP). Methods: Retinal vessel oximetry (RO), full-field ERG, EOG and mfERG were performed on 43 eyes of 22 patients suffering from RP and were compared to those of 26 eyes of 13 healthy controls. The oxygen saturation in the first and second branch retinal arterioles (A-SO 2 ) and venules (V-SO 2 ) was measured, and their difference (A-V SO 2 ) was calculated. Full-field ERG amplitudes, EOG parameters and averaged mfERG response amplitudes (within central 3°, between 3°and 8°, 8°and 15°, 15°and 24°) were evaluated in relation to the RO measurements. Results: V-SO 2 correlated negatively with the full-field ERG and EOG values, with increasing functional damage the V-SO 2 was higher. The RP group was well distinguished from the controls when the RO measurements were correlated to the averaged N1 (baseline to trough), but also to the N1P1 (trough-to-peak) mfERG response amplitudes. Receiver operating characteristic (ROC) curve of V-SO 2 , compared to those of N1 and N1P1 mfERG response averages (15-24°), presented a high differential margin between RP and controls (p < 0.001), shown by an area under the ROC curve of 0.912 (95% CI: 0.840-0.984). Conclusion: Retinal vessel saturation showed a significant relation to full-field ERG, EOG and mfERG. Thus, retinal vessel oximetry could potentially complement electrophysiological tests in monitoring disease progression in patients with RP.