P1 Center Electron Spin Clusters Are Prevalent in Type Ib Diamonds.

Understanding the spatial distribution of the P1 centers is crucial for diamond-based sensors and quantum devices. P1 centers serve as polarization sources for dynamic nuclear polarization (DNP) quantum sensing and play a significant role in the relaxation of nitrogen vacancy (NV) centers. Additionally, the distribution of NV centers correlates with the distribution of P1 centers, as NV centers are formed through the conversion of P1 centers. We utilized DNP and pulsed electron paramagnetic resonance (EPR) techniques that revealed strong clustering of a significant population of P1 centers that exhibit exchange coupling and produce asymmetric line shapes. The 13C DNP frequency profile at a high magnetic field revealed a pattern that requires an asymmetric EPR line shape of the P1 clusters with electron-electron (e-e) coupling strengths exceeding the 13C nuclear Larmor frequency. EPR and DNP characterization at high magnetic fields was necessary to resolve energy contributions from different e-e couplings. We employed a two-frequency pump-probe pulsed electron double resonance technique to show cross-talk between the isolated and clustered P1 centers. This finding implies that the clustered P1 centers affect all of the P1 populations. Direct observation of clustered P1 centers and their asymmetric line shape offers a novel and crucial insight into understanding magnetic noise sources for quantum information applications of diamonds and for designing diamond-based polarizing agents with optimized DNP efficiency for 13C and other nuclear spins of analytes. We propose that room temperature 13C DNP at a high field, achievable through straightforward modifications to existing solution-state NMR systems, is a potent tool for evaluating and controlling diamond defects.

The neural representation of time distributed across multiple brain regions differs between implicit and explicit time demands.

Animals appear to possess an internal timer during action, based on the passage of time. However, the neural underpinnings of the perception of time, ranging from seconds to minutes, remain unclear. Herein, we considered the neural representation of time based on mounting evidence on the neural correlates of time perception. The passage of time in the brain is represented by two types of neural encoding as follows: (i) the modulation of firing rates in single neurons and (ii) the sequential activity in neural ensembles. Time-dependent neural activity reflects the relative time rather than the absolute time, similar to a clock. They emerge in multiple regions, including the hippocampus, medial and lateral entorhinal cortices, medial prefrontal cortex, and dorsal striatum. Moreover, they involve different brain regions, depending on an implicit or explicit event duration. Thus, the two types of internal timers distributed across multiple brain regions simultaneously engage in time perception, in response to implicit or explicit time demands.

Comparison of Lumbar Artery and Superior Gluteal Artery Perforator Flaps for Breast Reconstruction: Multislice CT-Based Anatomical Study.

BACKGROUND: Although the deep inferior epigastric artery perforator flap is the criterion standard for autologous breast reconstruction, lumbar artery perforator (LAP) and superior gluteal artery perforator (SGAP) flaps are recent trends as alternatives. The purpose of our study was to clarify differences of these flaps based on multislice CT findings of the same patient. METHODS: Retrospective study was conducted on 58 patients who underwent preoperative contrast-enhanced multislice CT for breast reconstruction using deep inferior epigastric artery perforator. Of these, 32 patients' data were evaluated excluding 26 patients' data either for the lumbar or gluteal fat being outside the imaging range or for nondepiction of the vascular pedicle origin of LAP or SGAP flap. Vascular pedicle diameter, pedicle length, and subcutaneous fat thickness were measured for LAP and SGAP flaps. RESULTS: The vascular pedicle diameter, pedicle length, and fat thickness were 2.1 (SD, 0.3) mm, 3.4 (SD, 0.4) cm, and 4.9 (SD, 1.0) cm, respectively, for LAP flaps; and 1.7 (SD, 0.2) mm, 5.6 (SD, 1.1) cm, and 2.7 (SD, 0.7) cm, respectively, for SGAP flaps. CONCLUSIONS: The LAP flaps had thicker subcutaneous fat and a larger vascular pedicle diameter, whereas the SGAP flaps had a longer vascular pedicle. As donor material for breast reconstruction, the LAP flap is indicated for cases where absolute volume is needed; otherwise, the SGAP flap is more advantageous as it facilitates vascular anastomosis with its longer vascular pedicle.

Microwave AC Resonance Induced Phase Change in Sb2Te3 Nanowires.

Scaling information bits to ever smaller dimensions is a dominant drive for information technology (IT). Nanostructured phase change material emerges as a key player in the current green-IT endeavor with low power consumption, functional modularity, and promising scalability. In this work, we present the demonstration of microwave AC voltage induced phase change phenomenon at ∼3 GHz in single Sb2Te3 nanowires. The resistance change by a total of 6-7 orders of magnitude is evidenced by a transition from the crystalline metallic to the amorphous semiconducting phase, which is cross-examined by temperature dependent transport measurement and high-resolution electron microscopy analysis. This discovery could potentially tailor multistate information bit encoding and electrical addressability along a single nanowire, rendering technology advancement for neuro-inspired computing devices.

Understanding the Linewidth of the ESR Spectrum Detected by a Single NV Center in Diamond.

Spectral analysis of electron spin resonance (ESR) is a powerful technique for various investigations including characterization of spin systems, measurements of spin concentration, and probing spin dynamics. The nitrogen-vacancy (NV) center in diamond is a promising magnetic sensor enabling improvement of ESR sensitivity to the level of a single spin. Therefore, understanding the nature of the NV-detected ESR (NV-ESR) spectrum is critical for applications to nanoscale ESR. Within this work, we investigate the linewidth of NV-ESR from single substitutional nitrogen centers (called P1 centers). NV-ESR is detected by a double electron-electron resonance (DEER) technique. By studying the dependence of the DEER excitation bandwidth on the NV-ESR linewidth, we find that the spectral resolution is improved significantly and eventually limited by inhomogeneous broadening of the detected P1 ESR. Moreover, we show that the NV-ESR linewidth can be as narrow as 0.3 MHz.

A Clinical Significance of Intermittent Infusion Hemodiafiltration Using Backfiltration of Ultrapure Dialysis Fluid Compared to Hemodialysis: A Multicenter Randomized Controlled Crossover Trial.

BACKGROUND: Intermittent infusion hemodiafiltration -(I-HDF) using repeated infusion of ultrapure dialysis fluid through a dialysis membrane or sterile nonpyrogenic substitution fluid was developed to prevent a rapid decrease in blood pressure by increasing the patient's circulating blood volume, to enhance the plasma refilling rate by improving peripheral circulation, and to enhance solute transfer from the extravascular space to the intravascular space by enhancing the plasma refilling rate. Furthermore, the effect of fouling caused by attachment of proteins to the membrane as a result of ultrafiltration can be reduced by backflushing of the membrane with the purified dialysate in I-HDF. Although there have been several clinical trials of I-HDF, there have been no comparisons of the clinical significance of and indications for -I-HDF with those of conventional hemodialysis (HD). OBJECTIVE: The aim of this multicenter randomized controlled crossover trial was to compare the clinical significance of -I-HDF with that of HD in Japan. METHOD: Patients were randomized to receive HD, I-HDF, and HD (group A) or I-HDF, HD, and I-HDF (group B) in that order for 14 weeks each. The sample size of 70 was determined based on the operability and patient availability. Treatment outcomes were evaluated 5 and 14 weeks after the start of each treatment period. The patients received 4-h treatment sessions with no changes in session duration or anticoagulant therapy during the study. I-HDF was performed using a GC-110N dialysis machine. Two hundred milliliters of ultrapure dialysis fluid were infused at a rate of 150 mL/min by backfiltration every 30 min during treatment. The first and last infusions were performed 30 min after the start and 30 min before the end of treatment, respectively. The total estimated infusion volume per session was 1.4 L (i.e., 200 mL × 7 infusions). I-HDF is a type of online HDF with a small fluid replacement volume. An ABH-P polysulfone membrane hemodiafilter was used for -I-HDF and a class 1 or 2 hemodialyzer with a polysulfone membrane not coated with vitamin E and approved by the Japanese reimbursement system was used for HD. The primary outcomes were the Short Form-36 version 2 summary scores for quality of life and the visual analog scale scores for clinical symptoms. Secondary outcomes were vital signs, number of interventions, and pre-treatment blood test results. These variables were evaluated 1 week before at the start of the study, and at 5 and 14 weeks after the start of each treatment period. The removal characteristics of the various solutes were evaluated when possible on the first day of each treatment period. All patients provided written informed consent to participate. RESULTS: Thirty-two patients in group A and 32 patients in group B completed the trial. There were no differences in the primary or secondary outcomes between I-HDF and HD. Serum α1-microglobulin (MG) levels at 14 weeks were significantly lower for I-HDF than for HD. During treatment, the removal rates for urea and creatinine, which are low molecular weight substances, were significantly lower during I-HDF than during HD. In contrast, the ß2-MG and α1-MG removal rates were significantly higher during I-HDF than during HD. Furthermore, there was significantly less albumin leak during I-HDF than during HD. The solute removal results reflect the difference in pore size between the hemodiafilter used for I-HDF and the hemodialyzer used for HD and the difference in convective transport attributable to filtration between the 2 methods. CONCLUSIONS: These findings show that the removal rates of low molecular weight substances are significantly lower and those of medium to high molecular weight substances are significantly higher with I-HDF than with HD. They also indicate that there is significantly less albumin leak during I-HDF than during HD, meaning that I-HDF may be a particularly suitable dialysis modality for patients with malnutrition and the elderly in Japan.

DNP-NMR of surface hydrogen on silicon microparticles.

Dynamic nuclear polarization (DNP) enhanced nuclear magnetic resonance (NMR) offers a promising route to studying local atomic environments at the surface of both crystalline and amorphous materials. We take advantage of unpaired electrons due to defects close to the surface of the silicon microparticles to hyperpolarize adjacent 1H nuclei. At 3.3 T and 4.2 K, we observe the presence of two proton peaks, each with a linewidth on the order of 5 kHz. Echo experiments indicate a homogeneous linewidth of ∼150-300 Hz for both peaks, indicative of a sparse distribution of protons in both environments. The high frequency peak at 10 ppm lies within the typical chemical shift range for proton NMR, and was found to be relatively stable over repeated measurements. The low frequency peak was found to vary in position between -19 and -37 ppm, well outside the range of typical proton NMR shifts, and indicative of a high-degree of chemical shielding. The low frequency peak was also found to vary significantly in intensity across different experimental runs, suggesting a weakly-bound species. These results suggest that the hydrogen is located in two distinct microscopic environments on the surface of these Si particles.

Similarity in Neuronal Firing Regimes across Mammalian Species.

UNLABELLED: The architectonic subdivisions of the brain are believed to be functional modules, each processing parts of global functions. Previously, we showed that neurons in different regions operate in different firing regimes in monkeys. It is possible that firing regimes reflect differences in underlying information processing, and consequently the firing regimes in homologous regions across animal species might be similar. We analyzed neuronal spike trains recorded from behaving mice, rats, cats, and monkeys. The firing regularity differed systematically, with differences across regions in one species being greater than the differences in similar areas across species. Neuronal firing was consistently most regular in motor areas, nearly random in visual and prefrontal/medial prefrontal cortical areas, and bursting in the hippocampus in all animals examined. This suggests that firing regularity (or irregularity) plays a key role in neural computation in each functional subdivision, depending on the types of information being carried. SIGNIFICANCE STATEMENT: By analyzing neuronal spike trains recorded from mice, rats, cats, and monkeys, we found that different brain regions have intrinsically different firing regimes that are more similar in homologous areas across species than across areas in one species. Because different regions in the brain are specialized for different functions, the present finding suggests that the different activity regimes of neurons are important for supporting different functions, so that appropriate neuronal codes can be used for different modalities.

Hippocampal-prefrontal theta phase synchrony in planning of multi-step actions based on memory retrieval.

Planning of multi-step actions based on the retrieval of acquired information is essential for efficient foraging. The hippocampus (HPC) and prefrontal cortex (PFC) may play critical roles in this process. However, in rodents, many studies investigating such roles utilized T-maze tasks that only require one-step actions (i.e., selection of one of two alternatives), in which memory retrieval and selection of an action based on the retrieval cannot be clearly differentiated. In monkeys, PFC has been suggested to be involved in planning of multi-step actions; however, the synchrony between HPC and PFC has not been evaluated. To address the combined role of the regions in planning of multi-step actions, we introduced a task in rats that required three successive nose-poke responses to three sequentially illuminated nose-poke holes. During the task, local field potentials (LFP) and spikes from hippocampal CA1 and medial PFC (mPFC) were simultaneously recorded. The position of the first hole indicated whether the following two holes would be presented in a predictable sequence or not. During the first nose-poke period, phase synchrony of LFPs in the theta range (4-10 Hz) between the regions was not different between predictable and unpredictable trials. However, only in trials of predictable sequences, the magnitude of theta phase synchrony during the first nose-poke period was negatively correlated with latency of the two-step ahead nose-poke response. Our findings point to the HPC-mPFC theta phase synchrony as a key mechanism underlying planning of multi-step actions based on memory retrieval rather than the retrieval itself.

The Kidney Early Evaluation Program (KEEP) of Japan.

The International Kidney Evaluation Association Japan (IKEAJ) was created to improve public health awareness of chronic kidney disease (CKD) by screening high-risk CKD populations. This study aimed to retrospectively examine data from KEEP Japan and detect the CKD risk factors for the onset and the progression of CKD. A total of 1,947 participants (mean age: 56.9 ± 16.4 years) to KEEP Japan were enrolled. More than 70% of the participants had no CKD. However, 7.5% of the participants were classified as high risk. The participants with a history of hypertension and older than 60 years had significantly higher odds ratio for occurrence of CKD. In addition, the participants with history of diabetes or cardiovascular disease, high blood pressure (BP), anemia, and low HDL-C had high odds ratios. It is therefore suggested that the appropriate control of BP, blood glucose, anemia, and HDL-C is important for populations with CKD risk factors to reduce the likelihood of CKD.

Sex differences in the prevalence, progression, and improvement of chronic kidney disease.

BACKGROUND/AIMS: We examined sex differences in prevalence, progression, and improvement in early-stage chronic kidney disease (CKD). METHODS: We analyzed data from 533 participants who took 4 consecutive annual CKD detection tests. RESULTS: Urine albumin-creatinine ratio (ACR), estimated glomerular filtration rate (eGFR), and hemoglobin (Hb) at baseline in men with and without CKD and in women with and without CKD were 8.3±6.1, 149.2±310.4, 10.2±5.8, and 96.7±246.8 mg/g Cr; 83.4±14.7, 63.8±18.8, 79.9±13.0, and 69.4±20.0 mL/min/1.73 m2; and 14.8±1.2, 14.3±1.4, 13.0±1.0, and 13.0±1.2 mg/dL, respectively. ACR levels decreased significantly over time in men and women with CKD and they increased significantly over time in men and women without CKD. eGFR levels in men and women with CKD did not significantly change over time, but they decreased significantly over time in men and women without CKD. CKD prevalence and progression rate were not significantly different between sexes. Among the CKD participants, significantly more women had a "cured" status at 3 years (39.1% vs. 19.4%, P<0.01). Most whose eGFR increased to >60 mL/min/1.73 m2 at 3 years had values just below those at baseline. Regression analysis showed that change in eGFR correlated significantly with ACR in men with CKD (change in eGFR = -1.707+0.022×ACR, P<0.001, r2=0.201) and with Hb and ACR in women with CKD (change in eGFR = 48.870-3.803×Hb + 0.018×ACR, P<0.05, r2=0.134). CONCLUSIONS: These results suggest that the slight decrease of Hb within a normal range and mild anemia can be managed in women with early-stage CKD. The key baseline for eGFR is 60 mL/min/1.73 m2.

Accurate measurement of the bond stress between rebar and concrete in reinforced concrete using FBG sensing technology.

Recent earthquakes in several developing countries have shown that reinforced concrete (RC) buildings with improper structural detailing experience severe damage under seismic motions. Using low-quality construction materials such as brick aggregates, resulting in low-strength concrete, significantly impacts the bond between rebar and concrete. Accurate evaluation of the bond performance of such low-strength concrete is one of the key issues for seismic safety assessment of RC buildings, especially in Bangladesh; thus, the bond performance is usually evaluated through laboratory tests. However, conventional measurements of bond stress based on rebar strains measured by electrical resistance strain gauges are likely to negatively impact the bond behavior/performance because of the reduced total contact area between rebar and concrete as well as the changing rebar surface boundary conditions. Under the above social and academic backgrounds, in this study, a new measurement technique that applies fiber Bragg grating (FBG) sensors embedded in optical fiber to rebar strain measurements is developed, and its effectiveness is investigated to realize more accurate measurements of the bond stress between rebar and concrete. Two 70% scaled RC beam-column joint specimens in which the beam rebar was anchored in a straight manner were constructed with identical detailing, except for the beam rebar strain measuring methods. The specimens were then subjected to cyclic lateral loading until failure. By comparing the experimental data acquired by the above two different devices (the FBG sensors and conventional strain gauges), it was found that the experimental bond strength on the beam rebar based on the strain data measured by the FBG sensors was much higher than that from the data measured using conventional strain gauges. Which negatively impacted the test data on the beam-column joint's capacity in the specimen applied the conventional measuring method, indicating the necessity of the presented method not only for accurate evaluation of the bond stress between rebar and concrete but also for seismic safety assessments of RC buildings.

Conditioned enhancement of firing rates and synchrony of hippocampal neurons and firing rates of motor cortical neurons in rats.

The aim of this study was to examine the potential ability of neuronal groups to enhance their activities by conditioning without behaviors. We employed a method of neuronal operant conditioning in which increments in the firing rates and synchrony of closely neighboring neurons in the motor cortex and hippocampus were rewarded in the absence of behaviors. Rats were trained to engage in a free-operant task in which nose-poke behaviors were rewarded in session 1, and firing rates and synchrony above preset criteria were rewarded in sessions 2 and 3, respectively. The firing rates of motor cortical and hippocampal neuron groups were found to increase rapidly in session 2 similarly to the nose-poke behavior in session 1. Placing contingency of reward on firing synchrony resulted in selective enhancement of firing synchrony of only hippocampal neurons in session 3. Control experiments revealed that the enhancement of neuronal firing was not attributable to increments of superstitious behaviors or excitation caused by reward delivery. Analysis of the firing rates and synchrony of individual neurons and neuron pairs in each group revealed that the firing rates and synchrony of some but not all neurons and neuron pairs increased in each group. No enhancement was observed in any neurons and neuron pairs recorded by neighboring electrodes not used for conditioning. These results suggest that neuronal operant conditioning enhances the firing rates and synchrony of only some neurons in small restricted areas. The present findings are expected to contribute to further research into neurorehabilitation and neuroprosthesis.

Grafting nitroxide radicals on nanodiamond surface using click chemistry.

We demonstrate grafting of nitroxide radicals on the surface of nanodiamonds (NDs). The surface of NDs is functionalized by azide groups. Nitroxide radicals are covalently bonded using Cu(I)-catalyzed azide/alkyne-click chemistry approach. The reaction is confirmed by infrared spectroscopy. The grafting of nitroxides is also verified by studying the rotational correlational time using electron paramagnetic resonance (EPR) spectroscopy. EPR study estimates that a few hundreds (tens) of nitroxide radicals are grafted on the surface of NDs with 100 nm (25 nm) of the average diameter.

Aging and chronic kidney disease.

A recent report has dealt with geriatric nephrology, including epidemiology and pathophysiology of chronic kidney disease (CKD), attempting to get nephrologists to pay more attention to elderly CKD patients. The aims of this article are to summarize the morphological and functional properties of the aging kidney, and to better understand nephrology care for elderly CKD patients. The kidneys are affected by the aging process, which results in numerous effects on the renal system. In addition, the elderly population is hetereogenous - some have a decline in GFR explained by diseases that complicate aging such as arteriosclerosis with hypertension, whereas in the most of healthy adults the decline in GFR is much more modest and not inevitable. The values for normal estimated glomerular filtration rate (eGFR) in aging population have important implications for the diagnosis of CKD in the elderly. However, the MDRD equation underestimates mean eGFR by 25% and the CKD-EPI equation underestimates mean GFR by 16%. This bias may lead to misclassifying healthy older persons as having CKD. It is also still unknown whether and how age influences the predictive role of other risk factors for end-stage renal disease (ESRD) and death in referred as well as unreferred patients. The risk of ESRD was reported to be higher than the risk of death without ESRD for ages <60 years, and independent of eGFR. Proteinuria significantly increased the risk of ESRD with advancing age. In older patients on nephrology care, the risk of ESRD prevailed over mortality even when eGFR was not severely impaired. Proteinuria increases the risk of ESRD, while the predictive role of other modifiable risk factors was unchanged compared with younger patients. The decision to initiate renal replacement therapy in the elderly is complicated by more challenges than in younger patients. Calorie restriction and Klotho deficiency may be a candidate therapeutic target for attenuating kidney aging. © 2014 S. Karger AG, Basel.

Cost-effectiveness analysis of on-line hemodiafiltration in Japan.

BACKGROUND/AIMS: Evaluation of the socioeconomic value of medical intervention and establishment of the resources necessary for clinical practice are important for new developments in medical technology. The aim of this study was to determine the socioeconomic value of on-line hemodiafiltration (HDF). METHODS: The subjects were 24 patients who underwent hemodialysis (HD) (9 HDF, 15 HD) for chronic renal failure. A total of 288 dialysis interventions were observed for 4 weeks in three clinics. Cost-effectiveness was evaluated based on quality-adjusted life years (Qaly) and a visual analog scale. RESULTS: EuroQOL-5D (0.776 ± 0.015) and visual analog scale (67.9 ± 1.2) in the HDF group were higher than those in the HD group at baseline. The incremental cost utility ratio for HDF was 641.7 (JPY 10,000/Qaly) based on Qaly (0.776 ± 0.015) and reimbursement for medical fees (JPY 4,982,736 ± 7,852), and was lower than the incremental cost utility ratio for HD. CONCLUSION: These results suggest that on-line HDF could be cost-effective.

Effects of CPAP treatment interruption due to disasters: patients with sleep-disordered breathing in the Great East Japan Earthquake and tsunami area.

INTRODUCTION: The 2011 Great East Japan Earthquake caused major disruptions in the provision of health care, including that for patients with sleep-disordered breathing (SDB) using a nasal continuous positive airway pressure (nCPAP) device. This study investigated the ability of SDB patients to continue using the nCPAP device in the weeks immediately following the earthquake, whether inability to use the nCPAP device led to symptom relapse, and measures that should be taken to prevent disruptions in nCPAP therapy during future disasters. Hypothesis If nCPAP devices cannot be used during disasters, SDB patients' health will be affected negatively. METHODS: Within 14 days of the disaster, 1,047 SDB patients completed a questionnaire that collected data regarding ability to use, duration of inability to use, and reasons for inability to use the nCPAP device; symptom relapse while unable to use the nCPAP device; ability to use the nCPAP device use at evacuation sites; and recommendations for improvement of the nCPAP device. RESULTS: Of the 1,047 patients, 966 (92.3%) had been unable to use the nCPAP device in the days immediately following the earthquake. The most common reason for inability to use the nCPAP device was power failure, followed by anxiety about sleeping at night due to fear of aftershocks, involvement in disaster-relief activities, loss of the nasal CPAP device, and fear of being unable to wake up in case of an emergency. Among the 966 patients, 242 (25.1%) had experienced relapse of symptoms, the most common of which was excessive daytime sleepiness (EDS), followed by insomnia, headache, irritability, and chest pain. CONCLUSION: Developing strategies for the continuation of nCPAP therapy during disasters is important for providing healthy sleeping environments for SDB patients in emergency situations.

Vasculitis mimicking immunoglobulin-G4-related disease with involvement of the submandibular and lacrimal glands and periaortitis: A case report.

INTRODUCTION: Vasculitis does not usually induce glandular tissue lesions. Herein, we present a case of vasculitis with a distribution similar to that of immunoglobulin-G4-related disease (IgG4-RD), including that of the submandibular and lacrimal glands, and periaortitis. CASE REPORT: A 70-year-old man presented with shortness of breath. Laboratory findings revealed an IgG4 level of 191 mg/dL, negative antineutrophil cytoplasmic antibody test, and C-reactive protein level of 8.33 mg/dL. Magnetic resonance imaging of the head and computed tomography of the neck revealed bilaterally enlarged submandibular and lacrimal glands. Neck-to-pelvis computed tomography revealed bilateral infiltrative shadows in the lower lobes of both lungs, mass shadows in both lungs, and periaortitis of the abdominal aorta extending to the common iliac artery. Thus, the patient was diagnosed with IgG4-related respiratory disease and periaortitis/periarteritis. Prednisolone was administered at a dose of 35 mg (0.6 mg/kg daily). The dose was gradually tapered while observing the effects of the treatment. Imaging findings indicated an improvement and the C-reactive protein and IgG4 levels decreased, indicating a successful treatment course. However, after reexamination of the pathological findings, the diagnosis changed from IgG4-RD to vasculitis. One year after treatment initiation, the patient symptoms have stabilized. CONCLUSION: Vasculitis can present with lesions and pathological findings similar to those of IgG4-RD.

Optogenetic activation of the ventral tegmental area-hippocampal pathway facilitates rapid adaptation to changes in spatial goals.

Animal adaptation to environmental goals to pursue rewards is modulated by dopamine. However, the role of dopamine in the hippocampus, involved in spatial navigation, remains unclear. Here, we studied dopaminergic inputs from the ventral tegmental area (VTA) to the hippocampus, focusing on spatial goal persistence and adaptation. Mice with VTA dopaminergic lesions struggled to locate and update learned reward locations in a circular maze with dynamic reward locations, emphasizing the importance of VTA dopaminergic neurons in the persistence and adaptation of spatial memory. Further, these deficits were accompanied by motor impairments or motivational loss even when dopamine receptors in the dorsal hippocampus were selectively blocked. Stimulation of VTA dopaminergic axons within the dorsal hippocampus enhanced the mice's ability to adapt to changing reward locations. These findings provide insights into the contribution of dopaminergic inputs within the hippocampus to spatial goal adaptation.

Identification of novel kynurenine production-inhibiting benzenesulfonamide derivatives in cancer cells.

Kynurenine (Kyn), a metabolite of tryptophan (Trp), is known to be a key regulator of human immune responses including cancer immune tolerance. Therefore, abrogation of Kyn production from cancer cells by small molecules may be a promising approach to anticancer therapy. Indeed, several small molecule inhibitors of indoleamine 2,3-dioxygenase (IDO), a rate-limiting enzyme in the catabolism of Trp to Kyn, exert antitumor effects in animal models. We screened our chemical libraries using a cell-based Kyn production assay to identify a new type of small molecules that regulate Kyn production, and for the first time identified a benzenesulfonamide derivative (compound 1) as a hit with the ability to inhibit Kyn production in interferon-γ (IFN-γ)-stimulated A431 and HeLa cells. Unlike the previously identified S-benzylisothiourea derivative, compound 2, compound 1 had little effect on the enzymatic activity of recombinant human IDO in vitro but suppressed the expression of IDO at the mRNA level in cells. Furthermore, compound 1 suppressed STAT1-dependent transcriptional activity and DNA binding, whereas no decrement in either the expression or phosphorylation level of STAT1 was observed. The inhibition of IDO expression by several benzenesulfonamide derivatives is associated with the suppression of STAT1. Thus, compound 1 and its analogs might be useful for analyzing the regulation of IDO activation, and STAT1-targeting could be an alternative to the IDO-directed approach for the regulation of Kyn levels by small molecules in the tumor microenvironment.