Ultra-Long-Term-EEG Monitoring (ULTEEM) Systems: Towards User-Friendly Out-of-Hospital Recordings of Electrical Brain Signals in Epilepsy.

Epilepsy is characterized by the occurrence of epileptic events, ranging from brief bursts of interictal epileptiform brain activity to their most dramatic manifestation as clinically overt bilateral tonic-clonic seizures. Epileptic events are often modulated in a patient-specific way, for example by sleep. But they also reveal temporal patterns not only on ultra- and circadian, but also on multidien scales. Thus, to accurately track the dynamics of epilepsy and to thereby enable and improve personalized diagnostics and therapies, user-friendly systems for long-term out-of-hospital recordings of electrical brain signals are needed. Here, we present two wearable devices, namely ULTEEM and ULTEEMNite, to address this unmet need. We demonstrate how the usability concerns of the patients and the signal quality requirements of the clinicians have been incorporated in the design. Upon testbench verification of the devices, ULTEEM was successfully benchmarked against a reference EEG device in a pilot clinical study. ULTEEMNite was shown to record typical macro- and micro-sleep EEG characteristics in a proof-of-concept study. We conclude by discussing how these devices can be further improved and become particularly useful for a better understanding of the relationships between sleep, epilepsy, and neurodegeneration.

Indirect evaluation of amyloid deposition by ultrasonography and its relationship with MEFV gene mutation in FMF patients.

OBJECTIVE: The most significant complication in familial mediterranean fever (FMF) patients is dysfunction and organ failure developing depending on amyloid deposition in organs. The golden standard for showing amyloid deposition is the biopsy; however, tissue stiffness was examined by shear wave elastography as a non-invasive method in a restricted number of studies conducted, and it is considered that amyloid deposition can be shown indirectly. In our study, we aimed to indirectly evaluate amyloid deposition in organs with Shear wave and Doppler ultrasonography and to reveal its relationship with MEFV gene mutation analysis. METHOD: 42 FMF patients with normal thyroid and renal function tests and 35 participants with no FMF symptoms were included in our study. FMF patients were grouped depending on their MEFV mutation analyses. Thyroid, salivary glands, and renal parenchymal tissue stiffness were evaluated by shear wave elastography. Thyroidal artery and both renal artery resistances were evaluated by Doppler ultrasonography. RESULTS: Both parotis gland, thyroid and renal parenchymal stiffness and arterial vascular resistances in the patient group were found higher than the control group. A significant difference was not found in any parameters in classification based on gender. Tissue stiffness and vascular resistance values in the patient group with M694V homozygote mutation were found statistically significantly higher than the other mutation groups (p < 0.001). CONCLUSION: Our study shows that identifying genetic mutation type in FMF patients will help determine possibly amyloidosis risk. Imaging of tissue stiffness by shear wave elastography and evaluation of vascular resistance by Doppler can be useful for routine screening of those patients.

Evaluation of a Wearable System for Fetal ECG Monitoring Using Cooperative Sensors.

Fetal electrocardiography (fECG) has gotten widespread interest in the last years as technology for fetal monitoring. Compared to cardiotocography (CTG), the current state of the art, it can be designed in smaller formfactor and is thus suited for long-term and unsupervised monitoring. In the present study we evaluated a wearable system which is based on CSEM's cooperative sensors, a versatile technology that allows for the measurement of multiple biosignals and an easy integration into a garment or patch. The system was tested on 25 patients with singleton pregnancies and an age of gestation ≥ 37 weeks. To reject unreliable fetal heart rate (fHR) estimations, the signal processing algorithm provides a signal quality index. In 12 out of 21 patients available for analysis, a good performance of fHR estimations was obtained with a mean absolute error < 5 bpm and an acceptance rate >70%. However, the remaining 9 patients showed low acceptance rates and high errors. Besides investigating the source of these high errors, future work includes the investigating improved signal processing algorithms, different body positions and the use of dry electrodes. Clinical Relevance - The aim of this work is to develop a wearable system that can be offered in hospitals as an alternative to cardiotocography, or as a home monitoring tool for at risk fetuses, in the era of evolving telemedicine.

Split electrodes for electrical-conductivity-based tissue discrimination.

This work presents a method to minimize the inadvertent cutting of tissues in surgeries involving bone drilling. We present electrical impedance measurements as an assistive technology to image-guided surgery to achieve online guidance. Proposed concept is to identify and localize the landmarks via impedance measurements and then use this information to superimpose the estimated drilling trajectory on the offline maps obtained by pre-operative imaging. To this end., we propose an asymmetric electrode geometry., split electrodes., capable of distinguishing impedance variations as a function of rotation angle. The feasibility of the proposed approach is verified with numerical analysis. A probe with stainless steel electrodes has been fabricated and tested with a technical phantom. Although the results are impacted by a non-ideality in the phantom., we could show that the variation of impedance as a function of rotation angle can be used to localize the regions with different impedivities. Clinical Relevance- Presented approach may be used to minimize the inadvertent cutting of tissues in surgeries involving bone drilling.

Evaluation of the early cervical structural change in patients with non-radiographic axial spondyloarthropathy.

In this double-blind, controlled, cross-sectional study, we compared structural changes in the cervical vertebrae of patients with nonradiographic axial spondyloarthropathy (nr-axSpA), patients with ankylosing spondylitis (AS), and a control group. We used the modified Stoke Ankylosing Spondylitis Spinal Score (mSASSS) to determine whether the involvement of the cervical spine occurs earlier and is more severe than that of the lumbar spine in axial spondyloarthropathy (axSpA). A statistically significant difference was found in the total mSASSS between the AS and nr-axSpA groups (p = 0.038), but not in the cervical and lumbar mSASSS. Although the duration of the symptoms was shorter in the nr-axSpA group than in the AS group, no statistically significant difference was found in the cervical mSASSS between the AS and nr-axSpA groups. In both the AS and nr-axSpA groups, the cervical mSASSS values were found to be higher than the lumbar mSASSS values for the majority of the patients (82.8 and 89.5%, respectively). This may indicate that structural changes in the cervical spine occur during an early period of axSpA.

Deletion analysis of Pichia pastoris alcohol dehydrogenase 2 (ADH2) promoter and development of synthetic promoters.

Pichia pastoris (Komagataella phaffii) is a non-conventional Crabtree-negative yeast with the capability of reaching very high cell densities in a fed-batch fermentation process. The alcohol dehydrogenase (ADH) genes of P. pastoris involved in ethanol metabolism were identified and were previously characterized. This work aimed to extend current knowledge of the regulation of the ADH2 promoter. To this end, we first determined the upstream activator (UAS) and repressor (URS) sequences of the promoter by deletion assays. Two upstream activator sites have been identified, positioned between -900 and -801 bp, and -284 and -108 bp upstream of the ADH2 transcription start site. The sequences positioned between -361 and -262 bp had a negative effect on the promoter activity and designated a repressor sequence (URS). We then demonstrated that Mxr1 (methanol expression regulator 1) transcription factor activates the ADH2 promoter through the direct interaction with UAS regions in response to ethanol. Furthermore, five different synthetic promoters were constructed by adding or deleting the regulatory sites. These synthetic promoters were tested for extracellular xylanase production at shake flask level by inducing with ethanol. These promoter variants improved the xylanase production ranging between 165% and 200% of the native promoter. The synthetic promoter 5 (SNT5) that displayed the highest activity was further evaluated at the fermenter scale. The modification in the promoter features might have several implications for industrial processes where decoupling the cell growth and product formation is advantageous.

A Wearable Stethoscope for Long-Term Ambulatory Respiratory Health Monitoring.

Lung sounds acquired by stethoscopes are extensively used in diagnosing and differentiating respiratory diseases. Although an extensive know-how has been built to interpret these sounds and identify diseases associated with certain patterns, its effective use is limited to individual experience of practitioners. This user-dependency manifests itself as a factor impeding the digital transformation of this valuable diagnostic tool, which can improve patient outcomes by continuous long-term respiratory monitoring under real-life conditions. Particularly patients suffering from respiratory diseases with progressive nature, such as chronic obstructive pulmonary diseases, are expected to benefit from long-term monitoring. Recently, the COVID-19 pandemic has also shown the lack of respiratory monitoring systems which are ready to deploy in operational conditions while requiring minimal patient education. To address particularly the latter subject, in this article, we present a sound acquisition module which can be integrated into a dedicated garment; thus, minimizing the role of the patient for positioning the stethoscope and applying the appropriate pressure. We have implemented a diaphragm-less acousto-electric transducer by stacking a silicone rubber and a piezoelectric film to capture thoracic sounds with minimum attenuation. Furthermore, we benchmarked our device with an electronic stethoscope widely used in clinical practice to quantify its performance.

Photo-acoustic dual-frequency comb spectroscopy.

Photo-acoustic spectroscopy (PAS) is one of the most sensitive non-destructive analysis techniques for gases, fluids and solids. It can operate background-free at any wavelength and is applicable to microscopic and even non-transparent samples. Extension of PAS to broadband wavelength coverage is a powerful tool, though challenging to implement without sacrifice of wavelength resolution and acquisition speed. Here we show that dual-frequency comb spectroscopy (DCS) and its potential for unmatched precision, speed and wavelength coverage can be combined with the advantages of photo-acoustic detection. Acoustic wave interferograms are generated in the sample by dual-comb absorption and detected by a microphone. As an example, weak gas absorption features are precisely and rapidly sampled; long-term coherent averaging further increases the sensitivity. This novel approach of dual-frequency comb photo-acoustic spectroscopy (DCPAS) generates unprecedented opportunities for rapid and sensitive multi-species molecular analysis across all wavelengths of light.

Ultrasonographic evaluation of Achilles tendon: Is there any difference between ankylosing spondylitis, non-radiographic axial spondyloarthropathy and controls?

PURPOSE: The aim is to evaluate Achilles tendon enthesopathy with ultrasound (US) in ankylosing spondylitis (AS) and non-radiographic axial SpA (nr-axSpA) patients and controls, and compare these groups in terms of associations between disease activity parameters and ultrasonographic Achilles enthesitis signs. METHODS: A total of 24 AS and 20 nr-axSpA patients fulfilling the Assessment in Spondyloarthritis International Working Group criteria for axSpA and 30 controls were enrolled. Demographic characteristics, erythrocyte sedimentation rate, C-reactive protein (CRP), human leukocyte antigen (HLA)-B27, Bath AS Disease Activity Index, Bath AS Functional Index, Bath AS Metrology Index, Maastricht AS Enthesitis Score (MASES), AS Disease Activity Score-CRP, modified Stoke AS Spine Score (m-SASSS) scores and ultrasonographic findings were noted. RESULTS: HLA-B27 positivity, extra-articular and peripheral involvement, disease activity, functional status, mean m-SASSS, ultrasonographic gray scale (GS) and total scores were similar between AS and nr-axSpA groups. In GS, tendon echotexture scores were significantly different across all groups (0.812 ± 0.384 in AS, 0.575 ± 0.466 in nr-axSpA, 0.017 ± 0.091 in controls; P < .001). Entheseal calcification scores were similar in AS and nr-axSpA patients, and higher than controls (P = .001). Bone profile scores were similar in patients with AS and nr-axSpA, and higher than controls (P = .010). When the correlations between US findings and disease activity and functional status were considered, power Doppler US (PDUS) and MASES total scores were positively correlated in the AS group (P = .045; r = .41). CONCLUSION: AS and nr-axSpA patients were found to be similar in various clinical, functional, and US findings indicating that these 2 entities are different phenotypic reflections of the same disease spectrum. The positive correlation between PDUS and MASES scores in AS patients substantiate the performance of MASES in evaluation of entheseal activity.

Management of Psoriatic Arthritis: Turkish League Against Rheumatism (TLAR) Expert Opinions.

OBJECTIVES: This study aims to establish the first national treatment recommendations by the Turkish League Against Rheumatism (TLAR) for psoriatic arthritis (PsA) based on the current evidence. PATIENTS AND METHODS: A systematic literature review was performed regarding the management of PsA. The TLAR expert committee consisted of 13 rheumatologists and 12 physical medicine and rehabilitation specialists experienced in the treatment and care of patients with PsA from 22 centers. The TLAR recommendations were built on those of European League Against Rheumatism (EULAR) 2015. Levels of evidence and agreement were determined. RESULTS: Recommendations included five overarching principles and 13 recommendations covering therapies for PsA, particularly focusing on musculoskeletal involvement. Level of agreement was greater than eight for each item. CONCLUSION: This is the first paper that summarizes the recommendations of TLAR as regards the treatment of PsA. We believe that this paper provides Turkish physicians dealing with PsA patients a practical guide in their routine clinical practice.

Turkish League Against Rheumatism Consensus Report: Recommendations For Management of Axial Spondyloarthritis.

OBJECTIVES: This study aims to update 2011 Turkish League Against Rheumatism SpondyloArthritis Recommendations, and to compose a national expert opinion on management of axial spondyloArthritis under guidance of current guidelines, and implantation and dissemination of these international guidelines into our clinical practice. PATIENTS AND METHODS: A scientific committee of 28 experts consisting of 14 rheumatologists and 14 physical medicine and rehabilitation specialists (one of them also has an immunology PhD) was formed. The recommendations, systematic reviews, and meta-analyses including pharmacologic and non-pharmacologic treatment were scrutinized paying special attention with convenient key words. The draft of Turkish League Against Rheumatism opinion whose roof consisted of international treatment recommendations, particularly the Assessment of SpondyloArthritis International Society/European League Against Rheumatism recommendations was composed. Assessment of level of agreement with opinions by task force members was established through the Delphi technique. Voting using a numerical rating scale assessed the strength of each recommendation. RESULTS: Panel compromised on five basic principles and 13 recommendations including pharmacological and nonpharmacological methods. All of the recommendations had adequate strength. CONCLUSION: Turkish League Against Rheumatism expert opinion for the management of axial spondyloArthritis was developed based on scientific evidence. These recommendations will be updated regularly in accordance with current developments.

Turkish League Against Rheumatism (TLAR) Recommendations for the Pharmacological Management of Rheumatoid Arthritis: 2018 Update Under Guidance of Current Recommendations.

OBJECTIVES: This study aims to report the assessment of the Turkish League Against Rheumatism (TLAR) expert panel on the compliance and adaptation of the European League Against Rheumatism (EULAR) 2016 recommendations for the management of rheumatoid arthritis (RA) in Turkey. PATIENTS AND METHODS: The EULAR 2016 recommendations for the treatment of RA were voted by 27 specialists experienced in this field with regard to participation rate for each recommendation and significance of items. Afterwards, each recommendation was brought forward for discussion and any alteration gaining ≥70% approval was accepted. Also, Turkish version of each item was rearranged. Last version of the recommendations was then revoted to determine the level of agreement. Levels of agreement of the two voting rounds were compared with Wilcoxon signed-rank test. In case of significant difference, the item with higher level of agreement was accepted. In case of no difference, the changed item was selected. RESULTS: Four overarching principles and 12 recommendations were assessed among which three overarching principles and one recommendation were changed. The changed overarching principles emphasized the importance of physical medicine and rehabilitation specialists as well as rheumatologists for the care of RA patients in Turkey. An alteration was made in the eighth recommendation on treatment of active RA patients with unfavorable prognostic indicators after failure of three conventional disease modifying anti-rheumatic drugs. Remaining principles were accepted as the same although some alterations were suggested but could not find adequate support to reach significance. CONCLUSION: Expert opinion of the TLAR for the treatment of RA was composed for practices in Turkish rheumatology and/or physical medicine and rehabilitation clinics.

Efficient expression of codon-adapted affinity tagged super folder green fluorescent protein for synchronous protein localization and affinity purification studies in Tetrahymena thermophila.

BACKGROUND: A superior Green Fluorescent Protein (GFP) mutant, known as superfolder GFP (sfGFP), is more soluble, faster folding, and is the brightest of the known GFP mutants. This study aimed to create a codon-adapted sfGFP tag (TtsfGFP) for simultaneous protein localization and affinity purification in Tetrahymena thermophila. RESULTS: In vivo fluorescence spectroscopic analyses of clones carrying a codon-adapted and 6 × His tagged TtsfGFP cassette showed approximately 2-4-fold increased fluorescence emission compared with the control groups at 3 h. Fluorescence microscopy also revealed that TtsfGFP reached its emission maxima at 100 min, which was much earlier than controls expressing EGFP and sfGFP (240 min). A T. thermophila ATP-dependent DNA ligase domain containing hypothetical gene (H) was cloned into the 3' end of 6 × His-TtsfGFP to assess the affinity/localization dual tag feature. Fluorescence microscopy of the 6 × His-TtsfGFP-H clone confirmed its localization in the macro- and micronucleus of vegetative T. thermophila. Simultaneous affinity purification of TtsfGFP and TtsfGFP-H with Ni-NTA beads was feasible, as shown by Ni-NTA purified proteins analysis by SDS-PAGE and western blotting. CONCLUSIONS: We successfully codon adapted the N-terminal 6 × His-TtsfGFP tag and showed that it could be used for protein localization and affinity purification simultaneously in T. thermophila. We believe that this dual tag will advance T. thermophila studies by providing strong visual traceability of the target protein in vivo and in vitro during recombinant production of heterologous and homologous proteins.

Remote powering platform for implantable sensor systems at 2.45 GHz.

Far-field remotely powered sensor systems enable long distance operation for low-power sensor systems. In this work, we demonstrate a remote powering platform with a miniaturized antenna and remote powering base station operating at 2.45 GHz. The rectenna, which is the energy receiving and conversion element of the sensor system, is designed and measured. The measurements for the tag are performed within 15 cm distance from the remote powering base station. The realized gain of the tag antenna is measured as -3.3 dB, which is 0.5 dB close to the simulations, where simulated realized gain is -2.8 dB.

A MEMS-based spiral channel dielectrophoretic chromatography system for cytometry applications.

In this paper design, fabrication, and evaluation of an easy-to-use and low cost dielectrophoretic quantizer are introduced. The device works with standard tools in a biomedical laboratory: a stereo microscope with CCD camera and a voltage supply. A novel spiral microchannel geometry together with the coaxial electrode configuration is established. The device works with a droplet of sample, eliminating microfluidic connections, and external syringes. The proposed geometry decreases the footprint, therefore reduces the device cost, without compromizing the separation and quantization performances. Coaxial electrode geometry enables continuous electric-field application with simple voltage supplies. The devices are fabricated using a simple 3-mask process, and experiments are realized with 1 and 10 µm polystyrene beads. The results show that 1 µm particles have an average speed of 4.57 µm/s with 1.06 µm/s SD, and 10 µm particles have an average speed of 544 µm/s with 105 µm/s SD. The speed variation coefficient for 1 and 10 µm beads can be calculated as 23 and 19%, respectively. The size accuracy of the device is ± 10%, while the resolution is 20%, i.e., particles with radii different from each other by 20% can be separated. Hence, moderate separation performance with minimized cost and standard laboratory equipment is enabled.

An integrated process for partial oxidation of alkanes.

The partial oxidation of alkanes via bromination followed by the reaction with solid metal oxide mixtures (MO) is shown to give an array of products that can be tuned by varying the MO and the reaction conditions.