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In the pursuit of personalized diagnostics and tailored treatments, quantitative protein tests contribute to a more precise definition of health and disease. The development of new quantitative protein tests should be driven by an unmet clinical need and performed in a collaborative effort that involves all stakeholders. With regard to the analytical part, mass spectrometry (MS)-based platforms are an excellent tool for quantification of specific proteins in body fluids, for example focused on cancer. The obtained readouts have great potential in deter-mining tumor aggressiveness to facilitate treatment decisions, and can furthermore be used to monitor patient response. Internationally standardized TNM classifications of malignant tumors are beneficial for diagnosis, however treatment outcome and survival of cancer patients is poorly predicted. To this end, the importance of the tumor microenvironment has endorsed the introduction of the tumor-stroma ratio as a prognostic parameter in solid primary tumor types. Currently, the stromal content of tumor tissues is determined via routine diagnostic pathology slides. With the development of liquid chromatography (LC)-MS methods we aim at quantification of tumor-stroma specific proteins in body fluids. In this mini-review the analytical aspect of this developmental trajectory is further detailed.

Background The optimum method of defining cognitive impairment in virally suppressed people living with HIV is unknown. We evaluated the relationships between cognitive impairment, including using a novel multivariate method (NMM), patient– reported outcome measures (PROMs), and neuroimaging markers of brain structure across 3 cohorts. Methods Differences in the prevalence of cognitive impairment, PROMs, and neuroimaging data from the COBRA, CHARTER, and POPPY cohorts (total n = 908) were determined between HIV-positive participants with and without cognitive impairment defined using the HIV-associated neurocognitive disorders (HAND), global deficit score (GDS), and NMM criteria. Results The prevalence of cognitive impairment varied by up to 27% between methods used to define impairment (eg, 48% for HAND vs 21% for NMM in the CHARTER study). Associations between objective cognitive impairment and subjective cognitive complaints generally were weak. Physical and mental health summary scores (SF-36) were lowest for NMM-defined impairment (P < .05). There were no differences in brain volumes or cortical thickness between participants with and without cognitive impairment defined using the HAND and GDS measures. In contrast, those identified with cognitive impairment by the NMM had reduced mean cortical thickness in both hemispheres (P < .05), as well as smaller brain volumes (P < .01). The associations with measures of white matter microstructure and brain-predicted age generally were weaker. Conclusion Different methods of defining cognitive impairment identify different people with varying symptomatology and measures of brain injury. Overall, NMM-defined impairment was associated with most neuroimaging abnormalities and poorer self-reported health status. This may be due to the statistical advantage of using a multivariate approach., We have previously described a novel multivariate method (NMM) with theoretical statistical advantages over existing methods, which we assessed here in 3 cohorts of people living with HIV. Overall, NMM-defined impairment was associated with most neuroimaging abnormalities and poorer self-reported health status.

Alzheimer’s Disease is the most common neurodegenerative disorder. A hallmark of this disease is aggregation of the protein Tau into fibrillar tangles, which is ultimately linked to neuronal death 1,2. Oligomeric precursors of Tau fibrils are suspected to be the neurotoxic agent while fibrils themselves may be less harmful end products of the aggregation process 3,4. Evolutionary conserved families of molecular chaperones maintain protein homeostasis in healthy cells, preventing aggregation 5,6. Here, we investigate whether such chaperones could possibly reverse the aggregation reaction and dissolve Tau fibrils. Indeed we find that the human Hsp70 chaperone system disaggregates Tau fibrils. Both the bacterial and human Hsp70 chaperone systems disassemble fibril superstructures assembled of several fibril strands into single fibrils, indicating that this is an evolutionary conserved capacity of the Hsp70 system. However, further disaggregation of Tau fibrils into oligomers and even monomers is reserved to the human homologue. Thus, although bacteria possess an effective machinery to dissolve amorphous aggregates 7-9, we see that they do not have the means to disaggregate fibrils. Fibrillar aggregates, therefore, require different chaperone systems than amorphous aggregates, and this is a property acquired by Hsp70 during evolution. This makes the Hsp70 system an interesting target for novel drug strategies in Alzheimer.

The reliability and validity of the earlier developed Buruli ulcer functional limitation score (BUFLS) questionnaire was assessed. Of 638 former Buruli ulcer patients (of 678 individuals examined), sufficient items on daily activities (>= 13 of the 19) were applicable to calculate a score. To determine the validity, the functional limitation scores of the 638 individuals were compared with the global impression of the limitations, range of motion (ROM), and the social impact (change of occupation or education) of Buruli ulcer. To determine inter-observer reliability, the functional limitation score was reassessed in 107 participants within one and three weeks after the first interview by another interviewer and interpreter. Both global impression and ROM correlated well with the functional limitation scores (p 0.66 and p = 0.61). The inter-observer reliability of 107 participants as measured by an intra-class correlation coefficient of 0.86 was very good. The functional limitation scores measured in the second assessment were significantly higher than in the first assessment. This should be taken into account when the functional limitation score is used for the individual patient. The BUFLS can be used as for between group comparisons of endpoints in clinical trials and in the planning of resources.