Near-Perfect Synaptic Integration by Nav1.7 in Hypothalamic Neurons Regulates Body Weight.

Neurons are well suited for computations on millisecond timescales, but some neuronal circuits set behavioral states over long time periods, such as those involved in energy homeostasis. We found that multiple types of hypothalamic neurons, including those that oppositely regulate body weight, are specialized as near-perfect synaptic integrators that summate inputs over extended timescales. Excitatory postsynaptic potentials (EPSPs) are greatly prolonged, outlasting the neuronal membrane time-constant up to 10-fold. This is due to the voltage-gated sodium channel Nav1.7 (Scn9a), previously associated with pain-sensation but not synaptic integration. Scn9a deletion in AGRP, POMC, or paraventricular hypothalamic neurons reduced EPSP duration, synaptic integration, and altered body weight in mice. In vivo whole-cell recordings in the hypothalamus confirmed near-perfect synaptic integration. These experiments show that integration of synaptic inputs over time by Nav1.7 is critical for body weight regulation and reveal a mechanism for synaptic control of circuits regulating long term homeostatic functions.

[Coronary Artery-Left Atrial Fistula Complicated by a Left Atrial Myxoma:Report of a Case].

We report our experience with a case of a left atrial mass coexisting with a coronary artery-left atrial fistula. The abnormal vessels extended from the right coronary artery and left circumflex artery to the tumor in the left atrium and were aggregated within the tumor. An efflux of the contrast media was also noted from the tumor into the left atrium. Tumor resection and ligation of the abnormal vessels were performed as surgical interventions. The outcomes were favorable. The tumor was pathologically diagnosed as a myxoma, but its association with the abnormal vessels was unknown.

[CD5-positive diffuse large B-cell lymphoma with gastrointestinal infiltration presenting with protein-losing enteropathy].

Protein-losing enteropathy is rarely associated with malignant lymphoma. This report describes the case of a 67-year-old man with diffuse large B-cell lymphoma (DLBCL) and concomitant protein-losing enteropathy who was admitted to our hospital for evaluation of watery diarrhea, edema, and abdominal fullness. On admission, the patient reported a history of weight gain. Subsequent examination showed ascites, hepatosplenomegaly, and hypoalbuminemia. Notably, 99mTc-labeled human serum albumin scintigraphy revealed protein loss from the intestine, and the patient was diagnosed with protein-losing enteropathy. Endoscopy revealed erosive and edematous hyperplasia of the gastric-colonic mucosa, and histopathological evaluation of a biopsy specimen showed proliferation of CD20+ and CD5+ tumor cells. Thus, the diagnosis of DLBCL was histopathologically confirmed. Lymphomatous infiltration of the bone marrow was observed; however, no lymphadenopathy was detected. Based on these findings, the patient was diagnosed with protein-losing enteropathy associated with gastrointestinal infiltration of CD5+ DLBCL. Hypoalbuminemia and diarrhea improved following the initiation of R-CHOP regimen. The DLBCL showed a favorable response to treatment, and gastrointestinal lesions and hepatosplenomegaly improved, along with the resolution of protein-losing enteropathy.

Cascaded AMZ triplets: a class of demultiplexers having a monitor and control scheme enabling dense WDM on Si nano-waveguide PICs with ultralow crosstalk and high spectral efficiency.

We propose a class of wavelength-division multiplexing (WDM) demultiplexers having a novel monitor and control scheme enabling dense WDM on Si nano-waveguide (NW) photonic integrated circuits (PICs), which had been impossible due to the critically small fabrication tolerance of the extremely miniaturized waveguide structure. With a computer simulation, we show our proposed demultiplexers enable crosstalk in the range of -50 to -40 dB, flat-topped spectrum for high spectral efficiency, and channel counts as large as 64. We have experimentally evaluated the validity of this type of demultiplexers by using a 4-ch WDM demultiplexer, which has shown total crosstalk of < -49 dB as a result of fully automatic control of heaters. This technology is expected to drastically shrink the size of dense WDM transceivers, paving the way for future sustainable scalability in the capacity of optical transceiver systems.

Atypical extraventricular neurocytoma in a 3-year-old girl: case report with radiological-pathological correlation.

BACKGROUND: Extraventricular neurocytoma (EVN) is a rare neuronal tumor histologically similar to central neurocytoma but arising in the brain parenchyma outside the ventricles. The minority of EVNs show atypical features including increased proliferative index, microvascular proliferation, or necrosis, and are called atypical EVN. Most of atypical EVNs occur in adults, and the tumors in children are extremely rare. A radiological-pathological correlation and radiological clue to atypical EVNs have not been clarified. CASE REPORT: We report a case of atypical EVN in a 3-year-old girl. Magnetic resonance imaging (MRI) revealed an extraventricular intraparenchymal tumor in the left frontal lobe, which was composed of homogeneous well-demarcated cystic component and peripheral ill-delineated solid component with enhancement. Angiography demonstrated vascular proliferation and arteriovenous shunting in the tumor. Histologically, the resected tumor was diagnosed as atypical EVN. Types of the tumor borders (well-circumscribed or infiltrative) and MRI findings correlated closely. Morphology of the tumor vasculature was remarkable for microvascular proliferation and dilated, thickened veins, which corresponded to the angiographic features. CONCLUSION: Although rare, atypical EVN should be included in the differential diagnosis of a cystic mass in the cerebral hemispheres in children. Radiological evaluation of tumor borders and angiographic characteristics might be useful for predicting atypicality of the tumor.

Long-term potentiation of inhibitory synaptic transmission onto cerebellar Purkinje neurons contributes to adaptation of vestibulo-ocular reflex.

Synaptic plasticity in the cerebellum is thought to contribute to motor learning. In particular, long-term depression (LTD) at parallel fiber (PF) to Purkinje neuron (PN) excitatory synapses has attracted much attention of neuroscientists as a primary cellular mechanism for motor learning. In contrast, roles of plasticity at cerebellar inhibitory synapses in vivo remain unknown. Here, we have investigated the roles of long-lasting enhancement of transmission at GABAergic synapses on a PN that is known as rebound potentiation (RP). Previous studies demonstrated that binding of GABAA receptor with GABAA receptor-associated protein (GABARAP) is required for RP, and that a peptide that blocks this binding suppresses RP induction. To address the functional roles of RP, we generated transgenic mice that express this peptide fused to a fluorescent protein selectively in PNs using the PN-specific L7 promoter. These mice failed to show RP, although they showed no changes in the basal amplitude or frequency of miniature IPSCs. The transgenic mice also showed no abnormality in gross cerebellar morphology, LTD, or other excitatory synaptic properties, or intrinsic excitability of PNs. Next, we attempted to evaluate their motor control and learning ability by examining reflex eye movements. The basal dynamic properties of the vestibulo-ocular reflex and optokinetic response, and adaptation of the latter, were normal in the transgenic mice. In contrast, the transgenic mice showed defects in the adaptation of vestibulo-ocular reflex, a model paradigm of cerebellum-dependent motor learning. These results together suggest that RP contributes to a certain type of motor learning.

Non-sebaceous lymphadenoma of the salivary gland with serous acinic cell differentiation, a first case report in the literature.

We report an atypical case of non-sebaceous lymphadenoma (NSL) of the parotid gland showing serous acinic cell differentiation. NSL is a rare benign salivary gland tumor with intermingled lymphoid and epithelial tissues without sebaceous differentiation. Since the first description of a case designated by Auclair et al. as 'non-sebaceous lymphadenoma' in 1991, to our best knowledge, only 37 cases have been reported, and no differentiation of tumor cells into serous acinic cell lineage has been described so far. In this paper, we present a case of NSL with serous acinic cell differentiation. The patient was a 78-year-old female with the complaint of a painless mass in the left parotid gland. The surgically resected tumor was encapsulated and measured 13 × 9 × 9 mm. Histologically, the tumor had the features of NSL, and an unusual finding of this case was the presence of epithelial cells with serous acinic cell differentiation. Dense cytoplasm packed with basophilic granules in those cells was positive in periodic acid Schiff reaction after diastase digestion (D-PAS), which was compatible with the feature of serous acinic cell differentiation. Possible differentiation of the epithelial component into serous acinic cell in this rare entity is warranted to avoid confusion in the diagnosis.

[A case of rectal carcinoid tumor with lymph node and liver metastasis 5 years after curative resection].

A 65-year-old man was diagnosed with a rectal carcinoid tumor (10 mm in diameter) in July 2007. We performed low anterior resection with lymph node dissection. Histological depth of penetration of the rectal wall by the primary tumor was up to the submucosa, and lymph node metastasis was observed at station 251 (Japanese Classification of Colorectal Carcinoma, seventh Edition). Five years later, abdominal enhanced computed tomography (CT) revealed multiple liver tumors and swelling of the right obturator lymph nodes. During surgery, ultrasonography revealed 10 hypoechoic masses in both hepatic lobes. We performed right pelvic lymph node dissection, partial hepatectomy (S5/6, S7, and S8), and microwave coagulation therapy. After surgery, the patient was treated with octreotide long-acting repeatable( LAR). The patient remained disease-free for 10 months after surgery. Our findings suggest that careful monitoring is necessary for metachronous lymph node and liver metastasis during follow-up treatment for rectal carcinoid tumors.

Direction and distance dependency of reaching movements of lower limb.

Efficient body movement is required in our daily lives, as it facilitates responding to the external environment and producing movements in various directions and distances. While numerous studies have reported on goal-directed movements in the frontal direction during gait initiation, there is limited research on the efficient movement of the lower limbs in multiple directions and distances. Therefore, we aimed to examine changes in the kinematics of lower-limb reaching movements to determine skilled motor ability in terms of direction and distance. Sixteen adults (10 male participants) were requested to reach targets projected on the floor in seven directions and at three distances for a total of 21 points. The reaching time slowed down for the contralateral side (right foot to left-sided target) and was caused by a slower start of the toe movement. To identify the cause of this delay, we analyzed the onset of movement at each joint and found that movement to the contralateral side starts from the hip, followed by the knee, and subsequently the toe. The time-to-peak velocity was also calculated, and the motion required to reach the target in the shortest time varied depending on direction and distance. These results suggested that movement kinematics vary with direction and distance, resulting in a slower reaching time on the contralateral side. The results of our study hold promise for potential applications in sports and rehabilitation.

Dissociation of perception and motor execution of lower limb in multi-directional movements.

Estimating the action capability is vital for humans to move their bodies successfully. Researchers have proposed reachability as an overestimation of motor abilities by judging unreachable distances as reachable. The existing literature has mainly investigated the sagittal direction, but multi-directional reachability is unexplored. This study examined the relationship between perception and motor using the reaching of the lower limbs in multiple directions. We asked 16 adults to reach targets projected onto the floor at 21 locations (seven directions and three distances) to estimate the reaching time. We found that the reaching time slowed as the direction increased toward the contralateral side, but the subjective reaching time did not change with direction. Multiple regression analysis showed that the subjective reaching time could be calculated accurately, mainly using the duration from the toe leaving the ground to movement completion. These results suggest that changes in direction may not be perceived precisely by the motor system of the lower limbs and that the subjective reaching time was strongly affected by the time after the toe left the ground. Our findings provide novel insights into the relationship between motor and perception in multiple directions, which may provide a new strategy for the maximal performance of lower-limb movement.

Volitional activation of remote place representations with a hippocampal brain-machine interface.

The hippocampus is critical for recollecting and imagining experiences. This is believed to involve voluntarily drawing from hippocampal memory representations of people, events, and places, including maplike representations of familiar environments. However, whether representations in such "cognitive maps" can be volitionally accessed is unknown. We developed a brain-machine interface to test whether rats can do so by controlling their hippocampal activity in a flexible, goal-directed, and model-based manner. We found that rats can efficiently navigate or direct objects to arbitrary goal locations within a virtual reality arena solely by activating and sustaining appropriate hippocampal representations of remote places. This provides insight into the mechanisms underlying episodic memory recall, mental simulation and planning, and imagination and opens up possibilities for high-level neural prosthetics that use hippocampal representations.

High-output-power, single-wavelength silicon hybrid laser using precise flip-chip bonding technology.

An Si/III-V hybrid laser oscillating at a single wavelength was developed for use in a large-scale Si optical I/O chip. The laser had an InP-based reflective semiconductor optical amplifier (SOA) chip integrated with an Si wavelength-selection-mirror chip in a flip-chip configuration. A low coupling loss of 1.55 dB at the Si-SOA interface was accomplished by both mode-field-matching between Si-SOA waveguides and accurately controlling the bonding position. The fabricated Si hybrid laser exhibited a very low threshold current of 9.4 mA, a high output power of 15.0 mW, and a high wall-plug efficiency of 7.6% at 20 °C. Moreover, the device maintained a high output power of >10 mW up to 60°C due to the high thermal conductance between the SOA chip and Si substrate. The short cavity length of the flip-chip bonded laser expanded the longitudinal mode spacing. This resulted in temperature-stable single longitudinal mode lasing and a low RIN level of <-130 dB/Hz.

Flat-topped and low loss silicon-nanowire-type optical MUX/DeMUX employing multi-stage microring resonator assisted delayed Mach-Zehnder interferometers.

We propose a novel silicon-nanowire-type multiplexer (MUX) / demultiplexer (DeMUX) based on multi-stage microring resonator assisted delayed Mach-Zehnder interferometers. It is theoretically shown that spectral flatness of DeMUX spectra can be accomplished by incorporating nonlinear phase behaviors of microring resonators into the multi-stage delayed Mach-Zehnder interferometers. We experimentally demonstrate flat-topped 400GHz-spacing 1 × 4Ch demultiplexing operation in the fabricated device with silicon-nanowire waveguides. Furthermore, by integrating the micro-heaters on the top cladding layer of the fabricated device, the DeMUX performance is upgraded in terms of excess loss (<0.8dB) and crosstalk (<-10dB) without any degradation of filter spectral flatness at each channel grid.

Robotic multi-probe single-actuator inchworm neural microdrive.

A wide range of techniques in neuroscience involve placing individual probes at precise locations in the brain. However, large-scale measurement and manipulation of the brain using such methods have been severely limited by the inability to miniaturize systems for probe positioning. Here, we present a fundamentally new, remote-controlled micropositioning approach composed of novel phase-change material-filled resistive heater micro-grippers arranged in an inchworm motor configuration. The microscopic dimensions, stability, gentle gripping action, individual electronic control, and high packing density of the grippers allow micrometer-precision independent positioning of many arbitrarily shaped probes using a single piezo actuator. This multi-probe single-actuator design significantly reduces the size and weight and allows for potential automation of microdrives. We demonstrate accurate placement of multiple electrodes into the rat hippocampus in vivo in acute and chronic preparations. Our robotic microdrive technology should therefore enable the scaling up of many types of multi-probe applications in neuroscience and other fields.

Usefulness of Practitioner-Led Pancreatic Cancer Screening.

The 5-year survival rate for pancreatic cancer has improved (10%) but remains worse than that for other cancers. Early pancreatic cancer diagnosis is challenging, and delayed diagnosis can delay treatment, which impairs survival. Practitioners do not promptly refer cases to a general hospital, causing delayed discovery. Herein, we aimed to examine the usefulness of the Pancreatic Cancer Project in Matsue, whose objective is to detect pancreatic cancer in patients presenting at any medical institution in Matsue City. Clinical data were extracted from medical records, and abdominal ultrasonography and tumor marker blood level assessments were performed (n = 234; median age, 71 [range, 41-94] years; 51% male). Cases with abnormal abdominal ultrasonography or blood test findings were referred for specialist imaging and followed up. The pancreatic cancer detection rate was 6.0% (n = 14); all cases were referred to a general hospital by practitioners within 1 month. Patients had stage IA (n = 1), IIA (n = 6), IIB (n = 2), III (n = 1), and IV (n = 4) disease. Overall, pancreatic cancer could be detected at an earlier stage (I-II), but referral to a general hospital by visiting practitioners should be prompt. The Pancreatic Cancer Project in Matsue may help improve the detection and prognosis of pancreatic cancer.

[A case of hepatic angiosarcoma detected as a small lesion].

A 72-year-old man visited for imaging examination of alcoholic cirrhosis in April 2007. Enhanced CT images were revealed a 7 mm early enhanced lesion in segment 6 of the liver. The lesion was increased gradually to 40 mm on MRI images 21 months later. We performed ultrasound liver biopsy 3 times. Histology showed angiosarcoma with high-grade atypia and it was positive for CD31, CD34 and factor VIII-related antigen. The doubling time of this tumor was 42-108 days. Although we performed transarterial chemoembolization and interleukin-2 therapy, the patient died 34 months after the initial detection of tumor. We observed the clinical course with periodic imaging examination from the early stage of hepatic angiosarcoma and obtained a pathologic diagnosis by liver biopsy.

[A case of AFP-producing gastric cancer responding to the combination of systemic chemotherapy, transcatheter arterial embolization and hepatic infusion chemotherapy].

We report a case of a 64-year-old male with a-fetoprotein(AFP)-producing gastric cancer accompanied by large liver metastases and multiple lymph node metastases. The patient's serum AFP level was 42,307 ng/mL and a biopsy specimen showed AFP-positive tumor cells immunohistochemically. Systemic chemotherapy by tegafur gimeracil oteracil potassium(S-1)and local therapy for the hepatic metastases consisting of transcatheter arterial embolization (TAE)and infusion of epirubicin(EPI)to the hepatic arteries decreased the serum AFP level and reduced the gastric cancer and metastases. Due to the increase of AFP and lymph node metastases, we had to successively change the regimen to paclitaxel(PTX), a combination of cisplatin(CDDP)/irinotecan(CPT-11)and S-1. Continuous systemic chemotherapy in combination with various drugs for gastric cancer treatment followed by TAE and hepatic infusion chemotherapy for hepatic metastases proved effective. The patient survived for 3 years and 2 months.

Actual resuscitation actions after the training of chest compression-only CPR and AED use among new university students.

BACKGROUND: Although cardiopulmonary resuscitation (CPR) training is recommended in schools, there are few attempts to train all students at universities and no reports showing actual resuscitation actions at emergency settings after the training. We surveyed how many students encountered a collapsed person, whether they performed any resuscitation actions, and any reasons why they could not do any resuscitation actions. METHODS: We have provided chest compression-only CPR and automated external defibrillator (AED) use training for 3000 new university students every April since 2015 and followed up on their subsequent emergency actions to collapsed persons in the real world. We carried out a questionnaire survey for 2nd through 4th-year students during the annual student health checkup period in 2018. RESULTS: A total of 7595 students underwent the annual health checkup and 5549 of them (73.1%) responded to the survey. The rates of encountering collapsed persons and out-of-hospital cardiac arrest (OHCA) patients were 2.5 and 1.1 per 100 person-years, respectively. Of the 264 students who encountered a collapsed person, 82 (53.6%) who encountered non-OHCA collapsed persons and 54 (48.6%) who encountered OHCA persons performed at least one resuscitation action including either chest compression, AED use, or any other various resuscitation actions. CONCLUSIONS: The incidence rate of encountering OHCA patients was 1.1 per 100 person-years and half of them who encountered a collapsed person performed at least one resuscitation action. Hands-on mass training would encourage university students to perform any resuscitation actions on the emergency scene.

Ruptured distal middle cerebral artery aneurysm filled with tumor cells in a patient with intravascular large B-cell lymphoma.

The authors describe a very rare case of intravascular large B-cell lymphoma in a woman whose ruptured distal middle cerebral artery (MCA) aneurysms were filled with lymphoma cells. A 69-year-old woman who had undergone artificial graft replacement for an aortic aneurysm presented with transient left hemiparesis. Magnetic resonance imaging demonstrated a small fresh cerebral infarction in the right frontal lobe, although major cervical and cerebral arteries were shown to be intact on MR angiography. Antiplatelet and anticoagulation treatments commenced. On the 21st day after onset, the patient suffered a subarachnoid hemorrhage, and a digital subtraction angiogram revealed aneurysmal lesions in the distal MCA. Based on the histological examination of the resected aneurysms, proliferation of large B-cell lymphoma was identified in the dilated arterial lumen. On the 71st day after ischemic onset, intracranial hemorrhage recurred, and she died. Postmortem examination revealed similar lymphoma cells only in the intimal layer that had grown on the artificial graft, and it was decided that the patient had had intravascular large B-cell lymphoma. The preceding cerebral infarction was thought to be due to occlusion of the distal MCA by tumor embolus, which may be the initial pathological stage in aneurysm formation. For patients with incomprehensible ischemic cerebral stroke, neoplasm must be taken in consideration.

The effect of combination therapy with an L/N-Type Ca(2+) channel blocker, cilnidipine, and an angiotensin II receptor blocker on the blood pressure and heart rate in Japanese hypertensive patients: an observational study conducted in Japan.

Recently, the use of combination therapy with a calcium channel blocker (CCB) and an angiotensin II receptor blocker (ARB) has been rapidly increasing. Although this combination therapy is accepted as a standard treatment hypertension, there have been few large-scale, multicenter studies examining its safety and efficacy. The present study was designed to investigate the safety and efficacy of adding cilnidipine, a dual L/N-type CCB, to the regimen of patients whose blood pressure had been poorly controlled (systolic blood pressure [SBP] >140 mmHg or diastolic blood pressure [DBP] >90 mmHg) by antihypertensive monotherapy with an ARB. The percentage achievement of the blood pressure goals recommended by the JSH 2000 guidelines was also assessed for at least 12 weeks of treatment. A total of 2,920 patients were enrolled in the study at 471 institutions in Japan from February 2003 to July 2004. The incidence of adverse reactions related to cilnidipine was as low as 2.5%. A significant reduction from the baseline was found both in SBP (from 164.1 +/- 15.3 to 139.2 +/- 15.3 mmHg, p<0.0001) and DBP (from 91.7 +/- 11.4 to 79.3 +/- 10.7 mmHg, p<0.0001). A total of 31.5% of the patients achieved the blood pressure goals recommended by the JSH 2000 guidelines. Moreover, the heart rate also significantly decreased in these patients, particularly in those with a higher baseline heart rate. Our results indicate that cilnidipine can be used in combination with an ARB to control blood pressure without any significant adverse effects, and also that cilnidipine successfully reduces elevated heart rate, which is a possible risk factor for cardiovascular events.