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COVID-19’s long-term effects, known as Long-COVID, present psychiatric and physical challenges in recovered patients. Similarly, rare long-term post-vaccination side effects, resembling Long-COVID, are emerging (called Post-Vaccine). However, effective treatments for both conditions are scarce. Our clinical experience suggests that transcranial magnetic stimulation (TMS) often aids recovery in Long-COVID and Post-Vaccine patients. However, its effectiveness is reduced in patients with severe fatigue. Therefore, we retrospectively analysed Tokyo TMS Clinic’s outpatient records (60 in total; mean age, 38 years) to compare Long-COVID and post-vaccine patients’ characteristics and symptoms, assess the impact of TMS on their symptoms, and investigate the role of fatigue in depression recovery with TMS. The primary outcome was the regression coefficient of the initial fatigue score on depression score improvement using TMS. Secondary outcomes included psychiatric/physical scores before and after TMS and their improvement rates. We found no differences in the initial symptoms and background factors between Long-COVID and Post-Vaccine patients. After ten TMS sessions, all psychiatric and physical symptom scores improved significantly. TMS improves depression, insomnia, anxiety, and related neuropsychiatric symptoms, which were the primary complaints in this study. Thus, we conclude that TMS improves depression and anxiety. The effectiveness of TMS in treating depression in Long-COVID and Post-Vaccine patients decreased as fatigue severity increased. In conclusion, TMS relieved depressive symptoms following COVID-19 and vaccination; however, fatigue may hinder its effectiveness.

BackgroundPatients recovering from COVID-19 often suffer long-term Long-COVID (e.g., depression, poor concentration, anxiety, sleep disturbances, and fatigue). Similar symptoms also rarely seem to occur after COVID-19 vaccination. There is still no effective treatment for these symptoms. We have had a clinical experience that patients presenting with psychiatric/physical symptoms due to COVID-19 or COVID-19 vaccination (defined as Long-COVID and Post-Vaccine patients) often recover after transcranial magnetic stimulation (TMS) and that TMS poorly heals depression in strongly fatigued patients.Aims1. Determine whether there are differences in background characteristics and symptoms between Long-COVID and Post-Vaccine patients; 2. Examine whether TMS led to an improvement in their symptoms; 3. Test the involvement of fatigue in the recovery of depression of Long-COVID and Post-Vaccine patients with TMS.MethodsWe conducted a retrospective analysis using the medical records of the outpatient clinic of Tokyo TMS Clinic.Results1. We found no differences in initial symptoms and courses of treatment between Long-COVID and Post-Vaccine patients. 2. All psychiatric/physical symptom scores after 10 TMS treatments were significantly better than before. Though these results are of before-and-after studies, numerous reports have suggested that TMS effectively improves depression, insomnia, anxiety, and related neuropsychiatric symptoms, which were also primary complaints of patients in this study. We thus attributed the improvement in QIDS, PHQ9 (Both indices of depression), and GAD7 (anxiety indicator) to TMS. 3. The recovery rate of depression in Long-Covid and Post-Vaccine patients with TMS decreased with the severity of fatigue.ConclusionsThis is the first report to elucidate the efficacy of TMS and the factors affecting it for psychiatric symptoms after COVID-19 and COVID-19 vaccination. Our study may lead to further validation of the effectiveness and mechanisms of TMS in patients suffering from Long-COVID and COVID-19 vaccine long-term adverse reactions.

Screening of early-stage keratoconus using auto-keratometer parameters.Evaluation of a screening approach.At 5 major centers in Japan, we enrolled 123 eyes of 123 patients with Amsler-Krumeich classification stage 1 (50 years of age [average 26.36 ± 8.68 years]; 84/39 male/female) and 205 eyes of 205 healthy subjects (average age 26.20 ± 7.34 years, 139/66 male/female). Participants were divided 2:1 into a prediction group and an application group. In the prediction group, multivariate logistic regression analysis was performed with keratoconus diagnosis as the dependent variable, and auto-keratometer parameters including average K, steep K, flat K, astigmatism, and astigmatic axis (no, with-the-rule, against-the-rule, and oblique) as independent variables. The diagnostic probability determined by regression analysis was defined as the keratometer keratoconus index. The cutoff value was determined from the receiver operating characteristic curve. This prediction equation was evaluated in the application group. Our primary outcome measure was the accuracy of the prediction equation for discriminating keratoconus from normal eyes.The selected explanatory variables were steep K (partial regression coefficient [β] 1.284, odds ratio [OR] 3.610), flat K (β -0.618, OR 0.539), and with-the-rule astigmatism (β -3.163, OR 0.042). The area under the receiver operating characteristic curve of keratometer keratoconus index was 0.90, which was significantly better than individual parameters (P.001). The sensitivity and specificity values in the application group were 85.0% and 86.7%, respectively.Although the sensitivity/specificity was not high, the new prediction equation using auto-keratometer-derived parameters enabled better discrimination of early-stage keratoconus than the isolated parameters.

Background Although the association between dysregulated coagulation and atherosclerosis is well recognized, individual assays have been of minimal value in understanding disease susceptibility. Here we investigated the association of global coagulation profiles with coronary artery disease with consideration of sex differences. Methods and Results The study included patients from the BioHEART‐CT (The BioHEART Study: Assessing Patients With Suspected Cardiovascular Disease for New Disease Markers and Risk Factors) biobank who had computed tomography coronary angiograms scored for coronary artery calcium score (CACS) and Gensini score. The cohort included 206 adult patients who were referred for clinically indicated computed tomography coronary angiography and had a median of 2 major cardiac risk factors; 50% were women and the average age was 62.6 years (±9.9 years). The overall hemostatic potential (OHP) and calibrated automated thrombography generation assays were performed on platelet‐poor plasma. CACS and Gensini score in men were significantly correlated in bivariate analysis with measures from the OHP assay, and regression models predicting disease severity by CACS or Gensini score were improved by adding the OHP assay variables in men but not in women. The calibrated automated thrombography generation assay demonstrated a more hypercoagulable profile in women than in men. The OHP assay showed hypercoagulable profiles in women with hyperlipidemia and men with obesity. Conclusions The OHP assay identified hypercoagulable profiles associated with different risk factors for each sex and was associated with CACS and Gensini score severity in men, emphasizing the associations between increased fibrin generation and reduced fibrinolysis with cardiac risk factors and early atherosclerosis. Registration Information www.anzctr.org.au . Identifier: ACTRN12618001322224.

The vascular permeability of the endothelium is finely controlled by vascular endothelial (VE)-cadherin-mediated endothelial cell-cell junctions. In the majority of normal adult tissues, endothelial cells in blood vessels maintain vascular permeability at a relatively low level, while in response to inflammation, they limit vascular barrier function to induce plasma leakage and extravasation of immune cells as a defense mechanism. Thus, the dynamic but also simultaneously tight regulation of vascular permeability by endothelial cells is responsible for maintaining homeostasis and, as such, impairments of its underlying mechanisms result in hyperpermeability, leading to the development and progression of various diseases including coronavirus disease 2019 (COVID-19), a newly emerging infectious disease. Recently, increasing numbers of studies have been unveiling the important role of Rap1, a small guanosine 5'-triphosphatase (GTPase) belonging to the Ras superfamily, in the regulation of vascular permeability. Rap1 enhances VE-cadherin-mediated endothelial cell-cell junctions to potentiate vascular barrier functions via dynamic reorganization of the actin cytoskeleton. Importantly, Rap1 signaling activation reportedly improves vascular barrier function in animal models of various diseases associated with vascular hyperpermeability, suggesting that Rap1 might be an ideal target for drugs intended to prevent vascular barrier dysfunction. Here, we describe recent progress in understanding the mechanisms by which Rap1 potentiates VE-cadherin-mediated endothelial cell-cell adhesions and vascular barrier function. We also discuss how alterations in Rap1 signaling are related to vascular barrier dysfunction in diseases such as acute pulmonary injury and malignancies. In addition, we examine the possibility of Rap1 signaling as a target of drugs for treating diseases associated with vascular hyperpermeability.

Key Clinical Message Implantable collamer lenses (ICL) carry a risk of prolapse caused by direct ocular trauma, especially in mesopic conditions and when oversized ICLs are implanted. We recommend early surgical repositioning, as well as patient education that encourages goggle use during active sports.

This paper presents practical results of a snake-like robot with controllable side-thrust links, which is a novel snake-like robot proposed by the authors. This snake-like robot consists of multiple links connected by passive joints and each link has an active omni-directional wheel. Driving forces of the omni-directional wheels act only in the lateral directions, while the robot moves in the longitudinal direction. In this paper, the proposed snake-like robot is realized and a locomotion controller with an anti-slip controller is introduced. Development and experiment shows that the proposed snake-like robot not only looks good on paper.

A high-efficiency asymmetric Doherty power amplifier has been developed. This study proposed a harmonic suppressing technique at the second and the third harmonics and an impedance converting technique at a fundamental frequency with a T -shaped stub. Amplification efficiency was improved by a two-power-level impedance optimisation and harmonic treatment for the carrier amplifier and peaking amplifier on an asymmetric Doherty power amplifier circuit. The 10-W and 45-W GaN HEMTs released by Cree/Wolfspeed are respectively used for the carrier amplifier and the peaking amplifier. The fabricated asymmetric Doherty power amplifier with 58.6 % drain efficiency at a saturated output power of 46.3 dBm was achieved at 2.19 GHz. It achieved a 72.1 % drain efficiency at 8 dB output back-off condition from the saturation. Furthermore, the second and third harmonic spurious levels were reduced to −58.1 dBc and −62.8 dBc, respectively.

In this work, a 2-dimensional phased-array antenna is proposed for microwave power transfer. The purpose of this antenna design is to simplify the phase control system for beam steering. In this paper, we design and fabricate two-stage phase shifters and $3\times 3$ antenna array. The demonstration of 2-D beam steering based on only two dc sources was tried. According to a demonstration, the 2-D beam steering of 15.5° and 16.5° in azimuth and elevation axis are confirmed.

Introduction & Aim: Plaque micro-ruptures and associated thrombosis are a contributor to the progression of coronary artery disease (CAD). We sought to determine if disorders of haemostasis detectable by a global coagulation assay was a novel risk factor for CAD, or if hypercoagulation was associated with any of the traditional cardiac risk factors. Methods: Using the BioHEART biobank of clinical data, imaging data and pathology specimens, a cohort of patients (mean age 62.9 +/- 9.9 years, n=103 female, 103 male) had platelet poor plasma assessed by the overall haemostatic potential (OHP) assay. This assay measures the integrated effect of procoagulant, anticoagulant and fibrinolytic factors via calculation of area under a fibrin time curve. All patients had CT coronary angiograms scored; calcified plaque was identified by the coronary artery calcium score, and non-calcified plaque burden by a soft plaque score (SPS). Analysis was segregated by sex because of baseline differences in coagulation between males and females. Results: The OHP was found to be elevated in male patients who had non-calcified CAD [SPS>0 - 10.4 +/- 0.6 (n=62) vs SPS=0 - 8.78 +/- 0.5 (n=41), p=0.04], male patients with obesity [BMI >= 30 - 12.6 +/- 1.1 (n=26) vs BMI < 30 - 8.8 +/- 0.4 (n=77), p Conclusions: These results indicate that hypercoagulation is associated with more biologically active non-calcified plaque, and that disordered coagulation is associated with two significant cardiac risk factors in a sex-discrepant manner. These findings underscore the importance of global coagulation assessments as potential novel, sex-specific biomarker for subclinical atherosclerosis.

Nosocomial coronavirus disease 2019 (COVID-19) had occurred at our hospital. We retrospectively analyzed the differences between patients with nosocomial COVID-19 and either hematological disease (n=40) or other diseases (n=57). The analysis was completed within 60 days for surviving patients. Among the patients with hematological disease and those with other diseases, there were 21 (52.5%) and 20 (35.1%) deaths, respectively. Although the patients with hematological disease received favipiravir more frequently than patients with other diseases (21 [52.5%] vs. 15 [35.3%], respectively; P0.05), their median overall survival was poor (29 days; P=0.078). Furthermore, the median duration from oxygen therapy initiation to death or intubation was significantly shorter in the patients with hematological disease (5 days [range, 1-17 days] vs. 10 days [1-24 days], respectively; P0.05). Furthermore, the patients with hematological disease and nosocomial COVID-19 exhibited more marked respiratory failure and poorer outcomes leading to death in a shorter time period than the patients with other diseases and nosocomial COVID-19.

The dependences of phase transition and luminescence properties upon both Eu 3+ concentration and heating temperature in air were investigated for GdTiNbO 6 :Eu 3+ fine crystals formed hydrothermally at 240 °C as aeschynite-type Eu x Gd 1-x TiNbO 6 solid solution. The as-prepared aeschynite solid solution in the concentration range x ≥ 0.70 did not show the phase transformation from an aeschynite- to an euxenite-type structure caused by heating at 1300 °C for 1 h in air. The present study suggested that the phase boundary between the aeschynite- and euxenite-type RETiNbO 6 in the EuTiNbO 6 -GdTiNbO 6 system, where RE was a rare earth, lay in the average RE 3+ ionic radius 0.1061 nm. The intense emissions attributed to the 5 D 0 → 7 F 1 and 5 D 0 → 7 F 2 transitions of Eu 3+ for the as-prepared samples were more improved by heating at 1100–1300°C in air. The material doped with 30 mol% Eu 3+ was preferred for UV-B excitation, in contrast, the material with 50 mol% Eu 3+ was preferred for visible light excitation.

This work targets microwave power transfer to a flying drone. The rf transmitter is assumed to use a magnetron unit array. Each magnetron transmitter is attached to large-aperture antennas. Beam steering is provided by phased-array systems or mechanical gimbals on each antenna. The beams generated by the phase-controlled magnetrons and radiated from the transmitters are combined in free space. This report discusses the 5.8 GHz phase-locked magnetron characteristics. 60 % dc-rf conversion efficiency and 1 kW output are confirmed in a demonstration if self-excited oscillation. The phase-locked magnetron demonstration also confirms phase shifting of the output signal by controlling the phase of the injection signal.

Stratospheric platform attracts attention as a new communication infrastructure for expanding the communication area in many countries. In stratospheric platform, the unmanned airplanes stay at the stratosphere(an altitude of about 20km) and use as a communication relay station. In this concept, it is important to get a light and stable power supply for long term operation. Microwave power transfer is proposed as one solution. By using radio waves, microwave power transfer can transmit wirelessly and efficiently even at long distances. However, considering the shape of the airplane, it is desirable for the receiving antenna to be an elongated rectangle. An antenna shape such as rectanglar or circular affects the transmission efficiency even though the antenna aperture area is even. Therefore, when the receiving antenna becomes rectangular, it is confirmed that the transmission efficiency improves if the transmitting antenna is elongated according to its shape. Furthermore, we estimate the transmission efficiency including the attenuation of the atmosphere and the rainfall. In addition, since the airplane is assumed to move along the flight path, it is necessary to obtain how much power can be obtained over the entire flight path. Therefore, we also examined the received power in the entire flight path.

Introduction Patients with mixed connective tissue disease (MCTD) have higher rates of pulmonary arterial hypertension (PAH) than the general population. PAH is a risk for perioperative respiratory and heart failure, and marked edema of colonic stoma after sigmoidectomy. We report a case of sigmoidectomy for sigmoid colon cancer in a patient with PAH associated with MCTD for whom perioperative treatment was planned to control pulmonary arterial pressure (PAP), and a surgical strategy to avoid complications attributable to PAH and MCTD was employed. Case presentation A 52-year-old woman with sigmoid cancer and severe PAH associated with MCTD underwent surgery. We controlled PAH by using intravenous epoprostenol. We selected open surgery without laparoscopy and Hartmann's operation. After surgery, severe perioperative complications were not detected, and the patient discharged from hospital 17 days after the operation. Discussion During surgery under general anesthesia, the mortality rate of PAH is high because of heart and respiratory failure. We planned to switch the PAH treatment from an oral agent to intravenous epoprostenol only in the preoperative period, and selected open surgery. We ligated the inferior mesenteric artery (IMA) and inferior mesenteric vein (IMV) below the branch of LCA to avoid marked edema of stoma. Consequently, we could avoid severe intraoperative and postoperative complications. Conclusions Controlling PAP using epoprostenol, open surgery, stoma and the ligation level for the IMA and IMV preventing are important to avoid perioperative complications of sigmoid colon cancer complicated by severe PAH., Highlights • The patient with PAH complicated by MCTD underwent Hartman’s operation for sigmoid colon cancer. • Control of PAH by epoprostenol preoperatively is important to prevent perioperative cardiac complications. • The level of ligation of the IMA and the LCA is important to avoid severe edema of stoma.

Introduction Antithrombin resistance (ATR) prothrombinemia is an inherited thrombophilic disorder caused by missense mutations in prothrombin gene (F2) at Arg596 of the sodium-binding region. Previously, prothrombin mutants Yukuhashi (Arg596Leu), Belgrade (Arg596Gln), and Padua 2 (Arg596Trp) were reported as ATR-prothrombins possessing a risk of familial venous thrombosis. To identify additional F2 mutations causing the ATR-phenotype, we investigated the coagulant properties of recombinant prothrombins mutated at amino acid residues within the sodium-binding region by single nucleotide substitutions (Thr540, Arg541, Glu592, and Lys599). Materials and methods We constructed expression vectors of prothrombin mutants, established stably transfected HEK293 cells, and isolated the recombinant prothrombin proteins. We evaluated procoagulant activity and ATR-phenotypes of those mutants in reconstituted plasma by mixing with prothrombin deficient plasma. Results The secreted quantity of all prothrombin mutants was the same as that of the wild-type prothrombin. Procoagulant activity of each mutant varied from 1.7% to 79.5% in a one-stage clotting assay and from 2.0% to 104.5% in a two-stage chromogenic assay. Most prothrombin mutants tested presented with a severe ATR-phenotype. To estimate the thrombosis risk of these mutations, we determined the residual clotting activity (RCA) after 30 min inactivation with antithrombin. RCA scores, normalized to the wild-type, revealed that prothrombin mutants Lys599Arg (5.35) and Glu592Gln (4.71) had high scores, which were comparable with prothrombins Yukuhashi (4.36) and Belgrade (5.19). Conclusions Mutation of prothrombin at the sodium-binding site caused ATR-phenotypes. Of those tested, Lys599Arg and Glu592Gln may possess a thrombosis risk as large as the known pathogenic prothrombins Yukuhashi and Belgrade.

The two-dimensional phased-array antenna for microwave-power transfer is proposed in this work. The antenna designed in small-scale units based on traveling-wave feed technique contributes to scalably expand the antenna aperture. In addition, the number of phase control systems for beam steering is drastically reduced by the proposed feed technique contributes. In this paper, we compare and clear the circuit loss of the parallel and traveling-wave feed line and the limited number of series elements. In addition, we calculate and analyze the beam angle of two-way antenna units in circuit and EM cooperation simulation.

The CA2 region is unique in the hippocampus; it receives direct synaptic innervations from several hypothalamic nuclei and expresses various receptors of neuromodulators, including adenosine, vasopressin, and oxytocin. Furthermore, the CA2 region may have distinct brain functions, such as the control of instinctive and social behaviors; however, little is known about the dynamics of the subthreshold membrane potentials of CA2 neurons in vivo. We conducted whole-cell current-clamp recordings from CA2 pyramidal cells in urethane-anesthetized mice and monitored the intrinsic fluctuations in their membrane potentials. The CA2 pyramidal cells emitted spontaneous action potentials at mean firing rates of ∼0.8 Hz. In approximately half of the neurons, the subthreshold membrane potential oscillated at ∼3 Hz. In two neurons, we obtained simultaneous recordings of local field potentials from the CA1 stratum radiatum and demonstrated that the 3-Hz oscillations of CA2 neurons were not correlated with CA1 field potentials. In tetrodotoxin-perfused acute hippocampal slices, the membrane potentials of CA2 pyramidal cells were not preferentially entrained to 3-Hz sinusoidal current inputs, which suggest that intracellular 3-Hz oscillations reflect the neuronal dynamics of the surrounding networks. © 2016 Wiley Periodicals, Inc.

Introduction Use of combined oral contraceptives (COCs) results in acquired protein S (PS) deficiency, a well-established risk factor for venous thromboembolism (VTE). The risk of VTE due to COCs containing newer-generation progestins is double compared with COCs containing older-generation progestins, although there is little difference in estrogen contents between the generations. In contrast, progestin-only contraceptives do not confer an increased risk of VTE. In this study, we aimed to investigate how different isoforms of progestin in COCs affect the risk of VTE by measuring PS expression. Materials and methods The effect of progestin, levonorgestrel (LNG) or drospirenone (DRSP), on PS mRNA expression in HepG2 cells was measured using reverse transcription-quantitative PCR; PS level was determined using Western blot analysis. PROS1 promoter activity, PS mRNA stability, and de novo synthesis of PS mRNA were examined in HepG2 cells after treatment with progestin. Results and conclusions In the presence of progestins, PS mRNA and protein expressions were significantly upregulated in HepG2 cells due to the augmentation of de novo PS mRNA expression modulated by RNA polymerase II (Pol II), thereby facilitating PS transcription elongation. Moreover, the transcription elongation inhibitor blocked progestin-mediated de novo PS mRNA expression. Conversely, progestin did not affect PROS1 promoter activity and PS mRNA stability. Pol II elongation efficiency in the newer-generation progestin (DRSP) treatment was not as strong compared with older-generation progestin (LNG), suggesting the difference in VTE risk between COC generations.

A non-syndromic, congenital bifid tongue is an extremely rare malformation, the details of which are largely unknown. A female neonate was referred to our division presenting with a bifid tongue. The cleft was located in the right anterior part of the tongue. In addition, 2 tumors (10 mm and 2 mm) were located at the base of the cleft. Seven days after birth, the tumors were excised and primary closure of the cleft was performed for correction of the bifid tongue. The postoperative course was uneventful, and follow-up examination 20 months later showed no functional disturbance. Furthermore, all published cases were carefully reviewed to improve our understanding of the etiology of congenital bifid tongue. Formation of a congenital neoplasm during the early stages of tongue development could be the main etiology of a bifid tongue.

Here, we report an electrochemical biosensor aimed at daily self-check of salivary uric acid (UA). For this purpose, a paper-based sampling device and an amperometric biosensor with a reaction chamber designed for inserting the sampling device were employed. Our sampling device was made of a flexible material based on filter paper and it is possible to collect certain amount of saliva with sufficient reproducibility by gently putting it on the salivary gland for about 5 seconds. The biosensor measures UA contained in the sampling device by inserting it into the reaction chamber, filled with phosphate buffer saline (PBS). The output current of the biosensor was proportional to the concentration of UA, which contained in the solution collected by the sampling device, from 10 μM – 400 μM. As a real sample test, the biosensor was used for the measurement of UA levels of a healthy male volunteer. The output current increased immediately when the sampling device containing saliva was inserted to the reaction chamber. Concentration of salivary UA was estimated to 150 μM, which value was compatible to the reported UA levels in saliva.