Primary Progressive Aphasia (PPA) refers to a group of clinical syndromes characterized by the progressive loss of language functions with initial preservation of the other cognitive functions. Despite the availability of international guidelines for diagnosing PPA and its variants (Gorno-Tempini et al., 2011), the differential diagnosis and clinical distinction between variants in the early disease stage remains complex and challenging. Consequently, the aim of this systematic review was to establish language, speech and electrophysiological markers to identify PPA and its variants. To provide clinical markers, studies in which the initial symptoms were reported by the patients or their family and studies in which the quantitative and qualitative results of the speech and language assessments performed at initial specialty referral were described, were included. Furthermore, studies in which an electrophysiological measurement technique was used in patients with PPA were included in the systematic review. An overview of the initial symptoms, the initial speech and language assessments and electrophysiological techniques to improve an early-stage diagnosis of PPA is provided in this poster. However, research on the electrophysiological processes in PPA is still limited, only seven electrophysiological studies were included in this review. Further research is required to investigate the applicability of electrophysiological measurement techniques for diagnosing PPA.
variables in a controlled and systematic manner, is currently lacking. Therefore, we initiated the exRNA quality control (exRNAQC) study to systematically evaluate the effect of the type of blood collection tube (n=10), time between blood draw and plasma preparation (n=3), centrifugation speed during plasma preparation (n=5), input volume and RNA purification method (n=8). The impact of these factors is assessed by unbiased transcriptome exRNA profiling of all microRNAs and messenger RNAs from healthy donors’ plasma using established RNA -sequencing workflows. In the first phase of our study, we assessed the impact of each pre-analytical variable separately. We observed differences in RNA purification kit performance in terms of reproducibility, yield (up to 37-fold) and transcriptome complexity (2500 vs 15 000 genes detected). We are currently analyzing the blood collection tube exRNA profiles. Once all pre-analytical variables are evaluated separately, we will integrate our findings into a full factorial experiment and plan dedicated follow-up experiments to validate our results. Using this systematic approach, we aim to develop quality control metrics and guidelines for the study of exRNA in order to facilitate further progress in the field.
Purpose The purpose of this study was to compare the voice patient's opinion regarding three service delivery models for voice therapy: a short-term intensive voice therapy with individual sessions (IVT-I), a short-term intensive voice therapy with group sessions (IVT-G), or a long-term traditional voice therapy with individual sessions (TVT). Method Forty-six adult voice patients who followed either IVT-I, IVT-G, or TVT were contacted by e-mail with the request to fill in an online questionnaire reviewing their opinion about the received therapy. Several items concerning satisfaction, progress, time-related variables, transfer, and need for further therapy were scored by means of visual analog scales. Participants were also asked whether or not they continued voice therapy after the study. Results There were no significant differences between the three groups regarding the patients' perception of vocal quality improvement, degree of resolution of the voice disorder, duration of one session, total therapy duration, degree of transfer, need for further therapy, and actual continuation of therapy. A higher satisfaction rate was found for patients of the IVT-I and TVT groups than patients of the IVT-G group. The IVT-I group rated the therapy as too frequent compared with the TVT group who rated the frequency as optimal. Conclusion Results suggest that patients are equally satisfied and perceive a similar progress after individual short-term intensive voice therapy and individual long-term traditional voice therapy. This finding creates flexibility in selecting time-related variables depending on the specific case and situation. Patients who received individual therapy were more satisfied than patients who received group therapy. Future larger scale investigation is needed to confirm these results.
Uveal melanoma is the most common intraocular malignancy in adults. The lack of an effective treatment results in a median survival time less than one year for patients with metastatic disease. Recently, our lab identified the melanoma-specific long non-coding RNA (lncRNA) SAMMSON as a novel therapeutic target in skin melanoma. Analysis of a PAN cancer RNA-sequencing dataset revealed consistent expression of SAMMSON in uveal melanoma tumors. Although SAMMSON expression was lower in uveal compared to skin melanoma, over 90% of uveal melanoma tumors showed detectable SAMMSON expression. Further analysis also revealed SAMMSON expression in conjunctival melanoma, another form of ocular melanoma. To evaluate the therapeutic potential of SAMMSON inhibition in uveal and conjunctival melanoma, we treated 8 representative cell lines with SAMMSON-specific ASOs and observed a strong reduction in cell viability, accompanied by induction of apoptosis. In line with the role of SAMMSON in modulating mitochondrial metabolism, SAMMSON knock down resulted in decreased mitochondrial oxygen consumption. Uveal melanomas are characterized by activated MEK-signaling through mutations in GNA11/GNAQ. Combining SAMMSON-specific ASOs with the MEK-inhibitor Trametinib, induced strong synergistic effects, resulting in a nearly complete abrogation of tumor cells at nanomolar concentrations of Trametinib. The in vivo effects of SAMMSON inhibition, whether or not in combination with Trametinib, are currently being investigated in a uveal melanoma PDX model. Together, our results demonstrate the efficacy of SAMMSON inhibition as a novel treatment option for uveal melanoma and demonstrate its synergism with MEK inhibition making SAMMSON a promising anti-cancer target for uveal melanoma patients.
