Symptoms of Posttraumatic Stress Disorder Among Japanese Peacekeepers Deployed in South Sudan.

Importance: Peacekeepers in United Nations missions experience potentially traumatic events, resulting in increased risk for posttraumatic stress disorder (PTSD). Understanding the course and risk factors of PTSD symptom severity is crucial to ensure personnel safety. Objective: To investigate the incidence of PTSD, symptom severity trajectories, and potential risk factors associated with adverse trajectories among Japanese peacekeepers deployed in South Sudan. Design, Setting, and Participants: Data for this 6-year prospective cohort study were collected from December 2011 to December 2018 from Japan Ground Self-Defense Force personnel deployed at the United Nations Mission in South Sudan, corresponding to before and up to 78 months after deployment. Of 3799 potential participants, 80 were excluded because of multiple deployments and 757 because of missing data, incomplete responses, or not providing informed consent. Therefore, 2962 participants were included in the analysis. Data analysis was performed from February 2022 to February 2024. Exposure: The participants were deployed to United Nations Mission in South Sudan for 6 months. Main Outcomes and Measures: The 22-item Impact of Event Scale-Revised was used to assess PTSD symptoms, with 25 or more points indicating probable PTSD (p-PTSD). Sociodemographic data were collected, and the 30-item General Health Questionnaire was administered before deployment to identify risk factors for PTSD symptom severity. Results: In the 2962 participants studied (2901 [97.9%] male; mean [SD] age, 33.9 [7.2] years), the incidence of p-PTSD was 3.95%. Latent growth mixture models identified 4 symptom severity trajectories: resilient (2143 [72.3%]), recovery (479 [16.2%]), protracted (182 [6.1%]), and delayed (158 [5.3%]). Multinomial logistic regression showed that sleep disturbance was a common risk factor for the 2 most severe trajectories (protracted: odds ratio [OR], 1.29; 95% CI, 1.08-1.54; delayed: OR, 1.26; 95% CI, 1.03-1.53), whereas older age (OR, 1.25; 95% CI, 1.06-1.48), anxiety and dysphoria (OR, 1.45; 95% CI, 1.20-1.75), and general illness (OR, 1.30; 95% CI, 1.06-1.59) were associated with the protracted trajectory. Conclusions and Relevance: This cohort study found that approximately 4% of the participants developed p-PTSD and identified 4 distinct PTSD symptom trajectories. The findings suggest that addressing sleep disturbance and general health issues could effectively prevent PTSD symptoms among peacekeepers.

Multicenter prospective observational study to clarify the current status and clinical outcome in Japanese patients who have an indication for implantable cardioverter defibrillator (ICD) or wearable cardioverter defibrillator (WCD) (TRANSITION JAPAN-ICD/WCD study): Rationale and design of a prospective, multicenter, observational, comparative study.

Background: Despite the positive impact of implantable cardioverter defibrillators (ICDs) and wearable cardioverter defibrillators (WCDs) on prognosis, their implantation is often withheld especially in Japanese heart failure patients with reduced left ventricular ejection fraction (HFrEF) who have not experienced ventricular tachycardia (VT) or ventricular fibrillation (VF) for uncertain reasons. Recent advancements in heart failure (HF) medications have significantly improved the prognosis for HFrEF. Given this context, a critical reassessment of the treatment and prognosis of ICDs and WCDs is essential, as it has the potential to reshape awareness and treatment strategies for these patients. Methods: We are initiating a prospective multicenter observational study for HFrEF patients eligible for ICD in primary and secondary prevention, and WCD, regardless of device use, including all consenting patients. Study subjects are to be enrolled from 31 participant hospitals located throughout Japan from April 1, 2023, to December 31, 2024, and each will be followed up for 1 year or more. The planned sample size is 651 cases. The primary endpoint is the rate of cardiac implantable electronic device implementation. Other endpoints include the incidence of VT/VF and sudden death, all-cause mortality, and HF hospitalization, other events. We will collect clinical background information plus each patient's symptoms, Clinical Frailty Scale score, laboratory test results, echocardiographic and electrocardiographic parameters, and serial changes will also be secondary endpoints. Results: Not applicable. Conclusion: This study offers invaluable insights into understanding the role of ICD/WCD in Japanese HF patients in the new era of HF medication.

Interaction of left ventricular size with the outcome of cardiac resynchronization therapy in Japanese patients.

BACKGROUND: We analyzed the influence of the QRS duration (QRSd) to LV end-diastolic volume (LVEDV) ratio on cardiac resynchronization therapy (CRT) outcomes in heart failure patients classified as III/IV per the New York Heart Association (NYHA) and with small body size. HYPOTHESIS: We proposed the hypothesis that the QRSd/LV size ratio is a better index of the CRT substrate. METHODS: We enrolled 114 patients with advanced heart failure (NYHA class III/IV, and LV ejection fraction >35%) who received a CRT device, including those with left bundle branch block (LBBB) and QRSd ≥120 milliseconds (n = 60), non-LBBB and QRSd ≥150 milliseconds (n = 30) and non-LBBB and QRSd of 120-149 milliseconds (n = 24). RESULTS: Over a mean follow-up period of 65 ± 58 months, the incidence of the primary endpoint, a composite of all-cause death and hospitalization for heart failure, showed no significant intergroup difference (43.3% vs. 50.0% vs. 37.5%, respectively, p = .72). Similarly, among 104 patients with QRSd/LVEDV ≥ 0.67 (n = 54) and QRSd/LVEDV < 0.67 (n = 52), no significant differences were observed in the incidence of the primary endpoint (35.1% vs. 51.9%, p = .49). Nevertheless, patients with QRSd/LVEDV ≥ 0.67 showed better survival than those with QRSd/LVEDV < 0.67 (14.8% vs. 34.6%, p = .0024). CONCLUSION: Advanced HF patients with a higher QRSd/LVEDV ratio showed better survival in this small-body-size population. Thus, the risk is concentrated among those with a larger QRSd, and patients with a relatively smaller left ventricular size appeared to benefit from CRT.

Fear in action: Fear conditioning and alleviation through body movements.

Fear memories enhance survival especially when the memories guide defensive movements to minimize harm. Accordingly, fear memories and body movements have tight relationships in animals: Fear memory acquisition results in adapting reactive defense movements, while training active defense movements reduces fear memory. However, evidence in humans is scarce because their movements are typically suppressed in experiments. Here, we tracked adult participants' body motions while they underwent ecologically valid fear conditioning in a 3D virtual space. First, with body motion tracking, we revealed that distinct spatiotemporal body movement patterns emerge through fear conditioning. Second, subsequent training to actively avoid threats with naturalistic defensive actions led to a long-term (24 h) reduction of physiological and embodied conditioned responses, while extinction or vicarious training only transiently reduced the responses. Together, our results highlight the role of body movements in human fear memory and its intervention.

Long-term prognosis and prognostic factors after primary prophylactic implantable cardioverter-defibrillator therapy.

BACKGROUND: Little is known regarding which patients with ischemic cardiomyopathy (ICM) should be considered for prophylactic therapies, such as an implantable cardioverter-defibrillator (ICD), in the primary percutaneous intervention era. The aim of this study was to investigate the influence of non-sustained ventricular tachycardia (NSVT) on major adverse cardiac events (MACE) in heart failure with reduced ejection fraction (HFrEF) patients. METHODS: We retrospectively analyzed patients of ICM and non-ICM who underwent ICD implantation at our institute from October 2006 to August 2020. MACE were defined as composite outcome of cardiovascular death, heart failure hospitalization, and appropriate ICD therapies. RESULTS: A total of 167 patients were enrolled [male, 138 (83 %); age, 62.1 ±â€¯11.7 years; left ventricular ejection fraction, 23.5 ±â€¯6.1 %; left ventricular diastolic diameter, 67.4 ±â€¯9.0 mm; atrial fibrillation, 47 (28 %); NSVT, 124 (74 %); use of class III antiarrhythmic drugs, 55 (33 %); ischemic cardiomyopathy, 56 (34 %); cardiac resynchronization therapy, 73 (44 %)]. The median follow-up duration was 61 months. MACE occurred with 71 patients (43 %). When comparing baseline characteristics of the patients, left ventricular ejection fraction (p = 0.02) and atrial fibrillation (p = 0.04) were significantly associated with MACE. The multivariable Cox analysis for the target variable MACE identified atrial fibrillation (hazard ratio 2.00; 95 % confidence index 1.18-3.37; p = 0.01) as an independent predictor for MACE. CONCLUSIONS: Prior NSVT before ICD implantation was not an independent predictor of future MACE in patients with HFrEF with primary prophylactic ICD. In contrast, atrial fibrillation was associated with worse prognosis. To predict the prognosis of patients with primary prophylactic ICD, these factors should be assessed as comprehensive risk stratification factors for MACE.

Right ventricular systolic function as a predictor of appropriate ICD therapy.

BACKGROUND: Recent studies have shown that right ventricular dysfunction is associated with a significantly increased risk of sudden cardiac death. The purpose of this study was to evaluate the association of the right ventricular fractional area change (RVFAC) and appropriate implantable cardioverter-defibrillator (ICD) therapy to determine the cutoff value of the RVFAC. METHODS: Consecutive patients who underwent initial ICD implantations except those with hypertrophic cardiomyopathy, Brugada syndrome, and long QT syndrome were retrospectively enrolled. The primary endpoint was defined as any appropriate ICD therapy. The right ventricular dimensions and function on transthoracic echocardiography were measured for analysis. RESULTS: In total, 172 patients (60.3 ± 13.6 years, 131 males) were enrolled. Ninety patients received an ICD as a secondary prophylaxis. The mean LV ejection fraction and RVFAC were 38.3 ± 14.3% and 35.8 ± 8.8%, respectively. Regarding appropriate ICD therapy events, the best cutoff value of the RVFAC was 34.8%, while 74 patients had an RVFAC < 34.8%. Regarding the primary endpoint, the hazard ratio of a low RVFAC was 2.73 (95% CI 1.46-5.12, P < 0.01). In the multivariate analysis, a low RVFAC was an independent predictor of appropriate ICD therapy (HR: 3.40, 95% CI 1.74-6.64, P < 0.01). The secondary prophylactic cohort with a low RVFAC had the highest incidence of appropriate ICD therapy. Among the patients with RV dysfunction, the RVFAC normalized in 39% of patients during follow-up. This recovered RVFAC group had a significantly lower incidence of appropriate ICD therapy than the unrecovered RVFAC group (P = 0.043). CONCLUSION: A low RVFAC might be associated with increased appropriate ICD therapy.

PTSD Symptom dynamics after the great east japan earthquake: mapping the temporal structure using Dynamic Time Warping.

Background: After the Great East Japan Earthquake [GEJE], approximately 70,000 Japan Ground Self Defense Force [JGSDF] personnel were deployed, risking Post-Traumatic Stress Disorder [PTSD]. The network approach to psychopathology suggests that symptoms may cause and exacerbate each other, resulting in the emergence and maintenance of disorders, including PTSD. It is therefore important to further explore the temporal interplay between symptoms. Most studies assessing the factor structure of the Impact of Event Scale-Revised [IES-R] have used cross-sectional designs. In this study, the structure of the IES-R was re-evaluated while incorporating the temporal interplay between symptoms.Methods: Using Dynamic Time Warping [DTW] the distances between PTSD symptoms on the IES-R were modelled in 1120 JGSDF personnel. Highly correlated symptoms were clustered at the group level using Distatis three-way principal component analyses of the distance matrices. The resulting clusters were compared to the original three subscales of the IES-R using a Confirmatory Factor Analysis (CFA).Results: The DTW analysis yielded four symptom clusters: Intrusion (five items), Hyperarousal (six items), Avoidance (six items), and Dissociation (five items). CFA yielded better fit estimates for this four-factor solution (RMSEA = 0.084, CFI = 0.918, TLI = 0.906), compared to the original three subscales of the IES-R (RMSEA = 0.103, CFI = 0.873, TLI = 0.858).Conclusions: DTW offers a new method of modelling the temporal relationships between symptoms. It yielded four IES-R symptom clusters, which may facilitate understanding of PTSD as a complex dynamic system.

Personnel from the Japan Ground Self-Defense Force responded to the aftermath of the 2011 Great East Japan Earthquake, putting them at increased risk of developing symptoms of Post-Traumatic Stress Disorder.In recent years, psychological research has focused increasingly on methods to map the ways in which symptoms of psychopathology cause and exacerbate each other.The Dynamic Time Warping algorithm seems to be an appropriate and useful tool to analyse the interaction between post-traumatic stress symptoms over time, especially if these are not instantaneous or linear. This can improve our understanding of psychopathology and help move towards personalized medicine.

Junctional rhythm during cryoablation for typical atrioventricular nodal reentrant tachycardia.

INTRODUCTION: Cryoablation is being used as an alternative to radiofrequency (RF) ablation for atrioventricular nodal reentrant tachycardia (AVNRT) owing to the lower risk of atrioventricular block (AVB) compared to RF ablation. Junctional rhythm often occurs during successful application of RF ablation for AVNRT. In contrast, junctional rhythm has rarely been reported to occur during cryoablation. This retrospective study evaluated the characteristics of junctional rhythm during cryoablation for typical AVNRT. METHODS AND RESULTS: This retrospective study included 127 patients in whom successful cryoablation of typical AVNRT was performed. Patients diagnosed with atypical AVNRT were excluded. Junctional rhythm appeared during cryofreezing in 22 patients (17.3%). These junctional rhythms appeared due to cryofreezing at the successful site in the early phase within 15 s of commencement of cooling. Transient complete AVB was observed in 10 of 127 patients (7.9%), and it was noted that atrioventricular conduction improved immediately after cooling was stopped in these 10 patients. No junctional rhythm was observed before the appearance of AVB. No recurrence of tachycardia was confirmed in patients in whom junctional rhythm occurred by cryofreezing at the successful site. CONCLUSION: Occurrence of junctional rhythms during cryoablation is not so rare and can be considered a criterion for successful cryofreezing. Furthermore, junctional rhythm may be associated with low risk of recurrent tachycardia.

Antithrombotic Regimen After Percutaneous Left Atrial Appendage Closure　- A Real-World Study.

BACKGROUND: Antithrombotic therapy after left atrial appendage closure (LAAC) in patients at high risk of bleeding remains controversial. We present real-world clinical outcomes of LAAC.Methods and Results: Data from 74 consecutive patients who received LAAC therapy between January 2020 and June 2022 were analyzed. Patients received 1 of 3 antithrombotic therapies according to the bleeding risk category or clinical event. Regimen 1 was based on a prior study, regimen 2 comprised a lower antiplatelet drug dose without dual antiplatelet therapy, and regimen 3 was antiplatelet drug administration for as long as possible to patients with uncontrollable bleeding who were required to stop anticoagulant drugs. Overall, 73 (98.6%) procedures were successful. Of them, 16 (21.9%) patients were selected for regimen 1, 46 (63.0%) for regimen 2, and 11 (15.1%) for regimen 3. Device-related thrombosis (13% vs. 0% vs. 0%, P=0.0257) only occurred with regimen 1. There was no difference in major bleeding event rates (6% vs. 2% vs. 9%, P=0.53). CONCLUSIONS: The post-LAAC antithrombotic regimen was modified without major concerns.

Concomitant use and interaction of a subcutaneous implantable defibrillator and epicardial pacemaker.

A concomitant use of S-ICD and epicardial pacemaker was established to avoid tricuspid valve dysfunction. DFT test confirmed that any bipolar pacing did no interference on the S-ICD function.

Multiple time measurements of multidimensional psychiatric states from immediately before the COVID-19 pandemic to one year later: a longitudinal online survey of the Japanese population.

The coronavirus disease 2019 (COVID-19) pandemic has profoundly affected the mental health of both infected and uninfected people. Although most psychiatric disorders have highly overlapping genetic and pathogenic backgrounds, most studies investigating the impact of the pandemic have examined only single psychiatric disorders. It is necessary to examine longitudinal trajectories of factors that modulate psychiatric states across multiple dimensions. About 2274 Japanese citizens participated in online surveys presented in December 2019 (before the pandemic), August 2020, Dec 2020, and April 2021. These surveys included nine questionnaires on psychiatric symptoms, such as depression and anxiety. Multidimensional psychiatric time-series data were then decomposed into four principal components. We used generalized linear models to identify modulating factors for the effects of the pandemic on these components. The four principal components can be interpreted as a general psychiatric burden, social withdrawal, alcohol-related problems, and depression/anxiety. Principal components associated with general psychiatric burden and depression/anxiety peaked during the initial phase of the pandemic. They were further exacerbated by the economic burden the pandemic imposed. In contrast, principal components associated with social withdrawal showed a delayed peak, with human relationships as an important risk modulating factor. In addition, being female was a risk factor shared across all components. Our results show that COVID-19 has imposed a large and varied burden on the Japanese population since the commencement of the pandemic. Although components related to the general psychiatric burden remained elevated, peak intensities differed between components related to depression/anxiety and those related to social withdrawal. These results underline the importance of using flexible monitoring and mitigation strategies for mental problems, according to the phase of the pandemic.

Prevalence and risk factors of internet gaming disorder and problematic internet use before and during the COVID-19 pandemic: A large online survey of Japanese adults.

Internet gaming disorder (IGD) and problematic internet use (PIU) are becoming increasingly detrimental to modern society, with serious consequences for daily functioning. IGD and PIU may be exacerbated by lifestyle changes imposed by the coronavirus 2019 (COVID-19) pandemic. This study investigated changes in IGD and PIU during the pandemic and risk factors for them. This study is a part of a larger online study of problematic smartphone use in Japan, originally planned in 2019, and expanded in August 2020 to include the impact of COVID-19. 51,246 adults completed an online survey during the pandemic (August 2020), in Japan. Of these, 3,938 had also completed the survey before the onset of the pandemic (December 2019) and were used as the study population to determine how the pandemic has influenced IGD and PIU. IGD was assessed using the Internet Gaming Disorder Scale (IGDS). PIU was measured using the Compulsive Internet Use Scale (CIUS). The prevalence of probable IGD during COVID-19 was 4.1% overall [95%CI, 3.9%-4.2%] (N = 51,246), and 8.6% among younger people (age < 30), 1-2.5% higher than reported before the pandemic. Probable PIU was 7.8% overall [95%CI, 7.6%-8.1%], and 17.0% [95%CI, 15.9%-18.2%] among younger people, 3.2-3.7% higher than reported before the pandemic. Comparisons before and during the pandemic, revealed that probable IGD prevalence has increased 1.6 times, and probable PIU prevalence by 1.5 times (IGD: χ2= 619.9, p < .001, PIU: χ2= 594.2, p < .001). Youth (age < 30) and COVID-19 infection were strongly associated with IGD exacerbation (odds ratio, 2.10 [95%CI, 1.18 to 3.75] and 5.67 [95%CI, 1.33 to 24.16]). Internet gaming disorder and problematic internet use appear to be aggravated by the pandemic. In particular, younger persons and people infected with COVID-19 are at higher risk for Internet Gaming Disorder. Prevention and treatment of these problems are needed.

Pathophysiological background and prognosis of common atrial flutter in non-elderly patients: Comparison to Atrial Fibrillation.

BACKGROUND: It is unclear whether there is any difference in the background and prognosis between non-elderly patients who undergo catheter ablation of atrial fibrillation (AF) and common atrial flutter (CAFL). PURPOSE: To investigate the difference between the patient background of both CAFL and AF in the non-elderly. METHODS: In 526 consecutive patients who underwent catheter ablation of clinical paroxysmal/persistent CAFL or AF in our hospital, we enrolled only patients under 60 years old. Cases harboring both AFL and AF were excluded. We analyzed the patient characteristics, echocardiographic findings, electrocardiographic (ECG) abnormalities during sinus rhythm, and clinical course after ablation. RESULTS: In total, 196 patients (Cohort 1: 142 males, 156 AF cases) were analyzed. AFL patients were younger than AF patients (47.4 ± 10.6 vs. 50.2 ± 6.4years, p = 0.031) and organic heart disease (OHD) was significantly more common in AFL patients than AF patients (42.5% vs. 11.5%, p<0.001). In 161 patients excluding OHD (Cohort 2), ECG abnormalities were more frequent in AFL than in AF patients (78.3% vs. 39.1%, p = 0.001). There were no significant differences in all-cause death, onset of heart failure, and cerebral strokes. On the other hand, the number of cases that required a pacemaker was significantly higher in the CAFL group than AF group (0.0% vs. 26.1%, p-value <0.001). These results suggested that CAFL may reflect occurrence of any atrial myocardial damage, even if it does not lead to heart failure. CONCLUSIONS: Our present study suggested that CAFL may be associated with a broader atrial myocardial disorder in non-elderly patients.

A reciprocal inhibition model of alternations between under-/overemotional modulatory states in patients with PTSD.

Patients with posttraumatic stress disorder (PTSD) appear to manifest two opposing tendencies in their attentional biases and symptoms. However, whether common neural mechanisms account for their opposing attentional biases and symptoms remains unknown. We here propose a model in which reciprocal inhibition between the amygdala and ventromedial prefrontal cortex (vmPFC) predicts synchronized alternations between emotional under- and overmodulatory states at the neural, behavioral, and symptom levels within the same patients. This reciprocal inhibition model predicts that when the amygdala is dominant, patients enter an emotional undermodulatory state where they show attentional bias toward threat and manifest re-experiencing symptoms. In contrast, when the vmPFC is dominant, patients are predicted to enter an emotional overmodulatory state where they show attentional bias away from threat and avoidance symptoms. To test the model, we performed a behavioral meta-analysis (total N = 491), analyses of own behavioral study (N = 20), and a neuroimaging meta-analysis (total N = 316). Supporting the model, we found the distributions of behavioral attentional measurements to be bimodal, suggesting alternations between the states within patients. Moreover, attentional bias toward threat was related to re-experiencing symptoms, whereas attentional bias away from threat was related with avoidance symptoms. We also found that the increase and decrease of activity in the left amygdala activity was related with re-experiencing and avoidance symptoms, respectively. Our model may help elucidate the neural mechanisms differentiating nondissociative and dissociative subtypes of PTSD, which usually show differential emotional modulatory levels. It may thus provide a new venue for therapies targeting each subtype.

Current Status of Neurofeedback for Post-traumatic Stress Disorder: A Systematic Review and the Possibility of Decoded Neurofeedback.

Background: Post-traumatic stress disorder (PTSD) is a neuropsychiatric affective disorder that can develop after traumatic life-events. Exposure-based therapy is currently one of the most effective treatments for PTSD. However, exposure to traumatic stimuli is so aversive that a significant number of patients drop-out of therapy during the course of treatment. Among various attempts to develop novel therapies that bypass such aversiveness, neurofeedback appears promising. With neurofeedback, patients can unconsciously self-regulate brain activity via real-time monitoring and feedback of the EEG or fMRI signals. With conventional neurofeedback methods, however, it is difficult to induce neural representation related to specific trauma because the feedback is based on the neural signals averaged within specific brain areas. To overcome this difficulty, novel neurofeedback approaches such as Decoded Neurofeedback (DecNef) might prove helpful. Instead of the average BOLD signals, DecNef allows patients to implicitly regulate multivariate voxel patterns of the BOLD signals related with feared stimuli. As such, DecNef effects are postulated to derive either from exposure or counter-conditioning, or some combination of both. Although the exact mechanism is not yet fully understood. DecNef has been successfully applied to reduce fear responses induced either by fear-conditioned or phobic stimuli among non-clinical participants. Methods: Follows the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, a systematic review was conducted to compare DecNef effect with those of conventional EEG/fMRI-based neurofeedback on PTSD amelioration. To elucidate the possible mechanisms of DecNef on fear reduction, we mathematically modeled the effects of exposure-based and counter conditioning separately and applied it to the data obtained from past DecNef studies. Finally, we conducted DecNef on four PTSD patients. Here, we review recent advances in application of neurofeedback to PTSD treatments, including the DecNef. This review is intended to be informative for neuroscientists in general as well as practitioners planning to use neurofeedback as a therapeutic strategy for PTSD. Results: Our mathematical model suggested that exposure is the key component for DecNef effects in the past studies. Following DecNef a significant reduction of PTSD severity was observed. This effect was comparable to those reported for conventional neurofeedback approach. Conclusions: Although a much larger number of participants will be needed in future, DecNef could be a promising therapy that bypasses the unpleasantness of conscious exposure associated with conventional therapies for fear related disorders, including PTSD.

Towards an unconscious neural reinforcement intervention for common fears.

Can "hardwired" physiological fear responses (e.g., for spiders and snakes) be reprogramed unconsciously in the human brain? Currently, exposure therapy is among the most effective treatments for anxiety disorders, but this intervention is subjectively aversive to patients, causing many to drop out of treatment prematurely. Here we introduce a method to bypass the subjective unpleasantness in conscious exposure, by directly pairing monetary reward with unconscious occurrences of decoded representations of naturally feared animals in the brain. To decode physiological fear representations without triggering excessively aversive reactions, we capitalize on recent advancements in functional magnetic resonance imaging decoding techniques, and use a method called hyperalignment to infer the relevant representations of feared animals for a designated participant based on data from other "surrogate" participants. In this way, the procedure completely bypasses the need for a conscious encounter with feared animals. We demonstrate that our method can lead to reliable reductions in physiological fear responses, as measured by skin conductance as well as amygdala hemodynamic activity. Not only do these results raise the intriguing possibility that naturally occurring fear responses can be "reprogrammed" outside of conscious awareness, importantly, they also create the rare opportunity to rigorously test a psychological intervention of this nature in a double-blind, placebo-controlled fashion. This may pave the way for a new approach combining the appealing rationale and proven efficacy of conventional psychotherapy with the rigor and leverage of clinical neuroscience.

Expression of a human NPT1/SLC17A1 missense variant which increases urate export.

Human sodium-dependent phosphate cotransporter type 1 (NPT1/SLC17A1) is one of the urate transporters in the kidney. Our recent study revealed that a common missense variant, I269T (rs1165196), of NPT1 decreases the risk of renal underexcretion gout. Moreover, we demonstrated that human NPT1 is localized to the apical membrane of the renal proximal tubule, and that I269T is the gain-of-function variant which increases the NPT1-mediated urate export. However, the mechanism by which I269T variant increases the urate export remains to be clarified. Thus, we performed immunostaining and functional analysis of human NPT1 using the Xenopus oocyte expression system. For comparison of human NPT1 expression levels of oocyte membrane between 269I (wild type) and 269T (variant), immunostaining was performed with anti-human NPT1 antibodies. As a result, we showed that NPT1 I269T variant did not change the human NPT1 membrane expression levels, although NPT1 I269T variant increased the urate transport compared with NPT1 wild type. Combined with the previous report that I269T variant did not induce Km changes but increased the Vmax of urate transport in a proteoliposome system, our findings suggest that I269T variant increases NPT1-mediated urate export without increase of NPT1 expression levels on the membrane. Thus, I269T, a common missense variant of NPT1, might have faster conformation changes than NPT1 wild type in terms of the alternating-access model of transporters, and increases renal urate export in humans.