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.
The reverse total shoulder arthroplasty is a popular surgical treatment for a degenerative shoulder with a nonfunctional rotator cuff. Currently, more than 36 different brands with small different features are available. This creates choice stress among many surgeons, who no longer know which parameters and surgical factors are important to optimize the placement of the implant. The first purpose of this pilot study was to compare the passive range of motion (ROM) of 6 different implant designs implanted following the manufacturer’s guidelines. The second goal was to identify the impingements after implantation which determines the maximal ROM. The last goal of the study was to link the different parameters of an implant with the ROM. Six implant systems were implanted on identical sawbones. The procedure was repeated 3 times on a different sawbone to objectify the surgical repeatability of the procedures. A Stäubli TX-90 robot was used to perform and control the humerus' kinematic movement. An optical tracking system was used to perform the system's calibrations, track the humerus and scapula in space, and compute the center of rotation. There was a wide ROM in the scapular plane (44.8°-105.5°) while the minimal elevation (adduction) varied between −4.8° and 35.6°. The rotational movements were limited by contact of the superior humeral polyethylene inlay and the inferior scapular neck. The adduction in the coronal and scapular plane was limited by inferior scapular impingement, whereas the maximal abduction was limited either by bony contact between the humerus and acromion or by contact between the humeral polyethylene inlay and the superior glenoid cavity. A bigger radius of the glenosphere resulted in a larger passive humeroscapular ROM (P < .001). A larger Neck-Shaft-Angle results in a better abduction (P < .001) but compromised adduction (P < .001). The localization of the center of rotation has a significant impact on the ROM. The medialized designs have larger abduction and rotational angles (P < .001). There is a wide variation in the measured glenohumeral ROM between the 6 frequently implanted prostheses. The most important factor to optimize the impingement-free ROM in all types of prostheses is the creation of the prosthetic overhang of the glenosphere to the bone. Too much lateralization of the center of the glenosphere with or without lateralization of the humeral stem can create a subacromial and/or subcoracoidal impingement.
Even in healthy populations, conditioned pain modulation (CPM) magnitude varies. This may be accounted for by (non-)modifiable factors, including physical activity (PA). Yet, little research has thoroughly examined PA and its relation with CPM magnitude in a representative sample. Therefore, the present study investigated the predictive effect of PA on CPM magnitude in 105 healthy adults. PA was assessed during 7 consecutive days by self-report using the International Physical Activity Questionnaire and by monitor-based accelerometry. CPM was examined using a heterotopic noxious-conditioning stimulation protocol during which the effect of a hot water-conditioning stimulus on pressure pain thresholds was evaluated. Comparative, correlation, and hierarchical linear regression analyses were performed. Report-based walking predicts 4.8% of variance in pain-modulatory capacity, moderate PA predicts 10.2% of variance in pain-modulatory capacity, and report-based time spent on total PA predicts 7.0% of variance in pain-modulatory capacity. More metabolic equivalent-minutes/week spent on total PA, including walking and moderate PA, is associated with greater pain-modulatory capacity. The findings of this study add to the limited evidence on the predictive effect of PA on CPM. It urges to consider PA a confounding factor when examining CPM. The current study provides evidence that a physically active lifestyle benefits endogenous pain modulation in healthy adults. Given its potential, walking and moderate-intensity PA might be achievable treatment strategies for pain patients known to have impaired CPM. PERSPECTIVE: The results of this article show that a physically active lifestyle, including larger amounts of walking and moderate activity, predicts greater pain-modulatory capacity. TRIAL REGISTRATION: This study has not been preregistered.
Abstract Pancreatic cancer is considered one of the deadliest malignancies, with only an 8% 5-year survival. The diagnosis of pancreatic cancer is very challenging since early-stage pancreatic cancer is associated with nonspecific and rarely noticeable symptoms. Additionally, the current diagnostic tools (such as imaging and the measurement of serum tumor marker CA19-9 levels) have limitations. Liquid biopsies make it possible to detect tumor-specific molecular alterations by analysis of cell-free DNA (cfDNA) isolated from plasma, which contains circulating tumor DNA (ctDNA). Large genomic rearrangements have become evident as key mutagenic events in the progression of solid tumors. In this study we evaluated the prevalence of large-scale genomic rearrangements in pancreatic resections and cell-free DNA (cfDNA) of pancreatic cancer patients. Genome-wide copy number profiles were derived from shallow whole-genome sequencing (sWGS). We applied sWGS to cfDNA samples from all patients at different time points. Concordance of the profiles was evaluated between cfDNA and matched FFPE tumor tissue in samples of operable pancreatic cancer patients. Clear copy number variations (CNVs) were observed in 13 FFPE tumor samples of 16 resectable patients (81%). This indicates that chromosomal instability is a frequent mechanism in pancreatic cancer. We then evaluated if CNVs could be detected in cfDNA of operable patients. Unfortunately, in none of the 50 operable patients were CNVs established. In contrast, cfDNA analysis in metastatic patients revealed clear CNVs in 66.7% (10/15) of the patients at the time of diagnosis. Although cfDNA concentrations were not statistically significantly increased compared to operable patients, remarkably higher CA19-9 values were determined in nonoperable patients. Preliminary data indicate that this approach can predict recurrence. For instance, a copy number change in a follow-up sample (1-year post-surgery; 6-months post-chemotherapy) was observed in a borderline-operative patient diagnosed with a liver metastasis. The CNV profiles obtained in both FFPE resections as well as in cfDNA were patient unique, but some recurrent alterations on chromosome 9 (region with CDKN2A and CDKN2B) and on chromosome 12 (region with KRAS) were ascertained. These results demonstrate detection of tumor-derived CNVs in cfDNA of advanced pancreatic cancer cases. We also show that there is potential to use cfDNA-derived profiles to monitor treatment response. Based on the results of this proof-of-concept study, additional patients are currently being analyzed. Citation Format: Greet Wieme, Frederik Berrevoet, Aude Vanlander, Jo Van Dorpe, Anne Hoorens, Bram Parton, Jurgen Van Limmen, Ann De Bruyne, Marc De Man, Karen Geboes, Kathleen Claes. Detection of genome-wide copy number alterations in tumor tissue and cell-free DNA of pancreatic cancer patients [abstract]. In: Proceedings of the AACR Special Conference on Advances in Liquid Biopsies; Jan 13-16, 2020; Miami, FL. Philadelphia (PA): AACR; Clin Cancer Res 2020;26(11_Suppl):Abstract nr A15.
The hippocampus plays a crucial role in seizure generation in temporal lobe epilepsy (TLE). Chemogenetic inhibition of excitatory neurons in the epileptic hippocampus using hM4Di, a Designer Receptor Exclusively Activated by Designer Drugs (DREADD), could be a novel way to reduce hippocampal excitability and suppress spontaneous seizures. We evaluated the effect of activating hM4Di, selectively expressed in excitatory hippocampal neurons, on excitability of dentate gyrus in non-epileptic and epileptic rats.
The use of inexpensive microprocessors or commercial of the shelf (COTS) components is one of the most common cost-saving methods in the constructions of CubeSats. Design of electronics that can maintain full functionality over the duration of the mission requires careful determination of the space radiation environment and total ionizing dose (TID) delivered to the components. Larger, more expensive or longer mission satellites tend to use more expensive components than the ones used in CubeSat to assure reliability. Radiation survivability of a Raspberry Pi Zero was studied with the USU Space Survivability Test Chamber using 0.2 to 2.5 MeV beta radiation from a Sr90 source to determine the amount of ionizing radiation that the memory and processor units can be exposed to before they exhibit radiation-induced damage or stop working altogether. We also analyzed the type of error produced by radiation exposure to determine if it was a recoverable or a critical error and how much shielding the processor would need to work reliably over the mission lifetime. The results of these evaluations will be used in the USU-led OPAL CubeSat which plans to incorporate a Raspberry Pi as its basic processor unit and to determine if this inexpensive microcomputer will be able to survive the TID received during its mission in LEO lasting 1-2 years, up to a TID >200 krad.
State of the art. Theater actors are a high risk group for developing voice disorders. Aims. The first purpose of this study was to examine and compare the objective and subjective vocal quality between professional theater actors, non-professional theater actors and a control group of professional dancers. Secondly, the impact of one theater performance on the objective and subjective vocal quality was investigated within and between the groups. It is hypothesized that actors will experience vocal fatigue and a deteriorated vocal quality compared with dancers as a result of the vocal load during the performance. Dancers will face more general fatigue and smaller vocal changes due to the impact of a performance including stress, decompensation and physical fatigue. Methods. Recordings of 27 professional actors, 19 non-professional actors and 16 professional dancers were collected before and after a performance using the PRAAT software. Voice samples included sustained vowel phonation, continuous speech, aerodynamic measurements and voice range profile. Both Acoustic Voice Quality Index and Dysphonia Severity Index were computed. For auditory-perceptual evaluations the GRBASI scale was used. Several questionnaires were completed pre and post performance to capture vocal risk factors. Results. Vocal quality between groups showed lower fundamental frequency (f(o)) values (female), larger fundamental frequency (female) and intensity ranges and a longer maximum phonation time (female) in professional actors compared to non-professionals. Professional dancers showed higher Acoustic Voice Quality Index values compared to non-professional actors. Dysphonia Severity Index, Voice Handicap Index, Vocal Tract Discomfort Scale and GRBASI results did not differ between groups at the baseline. Both objective measurements and questionnaires did not show significantly different results post performance. Questionnaires revealed poor vocal habits in professional actors. Conclusion. Professional actors have better vocal capacities than non-professionals. Dancers' vocal quality is worse than actors. The results show no impact of one performance on the vocal quality in theater actors and dancers. The long-term impact of performing, however, is subject for further research.
