High-performance Ge/Si electro-absorption optical modulator up to 85°C and its highly efficient photodetector operation.

We studied a high-speed Ge/Si electro-absorption optical modulator (EAM) evanescently coupled with a Si waveguide of a lateral p-n junction for a high-bandwidth optical interconnect over a wide range of temperatures from 25 °C to 85 °C. We demonstrated 56 Gbps high-speed operation at temperatures up to 85 °C. From the photoluminescence spectra, we confirmed that the bandgap energy dependence on temperature is relatively small, which is consistent with the shift in the operation wavelengths with increasing temperature for a Ge/Si EAM. We also demonstrated that the same device operates as a high-speed and high-efficiency Ge photodetector with the Franz-Keldysh (F-K) and avalanche-multiplication effects. These results demonstrate that the Ge/Si stacked structure is promising for both high-performance optical modulators and photodetectors integrated on Si platforms.

Incidentally Detected Extramedullary Plasmacytoma of the Gallbladder: A Case Report and Literature Review.

Extramedullary plasmacytoma (EMP) can rarely occur in conjunction with multiple myeloma (MM). EMPs are usually detected in the upper aerodigestive tract (UAD) but can also occur along the digestive tract. However, the involvement of gallbladder is uncommon. Gastrointestinal tract symptoms often lead to the diagnosis of EMP in the gallbladder. An 81-year-old man was referred to our hospital with suspected primary gallbladder carcinoma. He was subsequently operated on, and the pathological findings showed EMP of the gallbladder without MM.

Towards universal neural network potential for material discovery applicable to arbitrary combination of 45 elements.

Computational material discovery is under intense study owing to its ability to explore the vast space of chemical systems. Neural network potentials (NNPs) have been shown to be particularly effective in conducting atomistic simulations for such purposes. However, existing NNPs are generally designed for narrow target materials, making them unsuitable for broader applications in material discovery. Here we report a development of universal NNP called PreFerred Potential (PFP), which is able to handle any combination of 45 elements. Particular emphasis is placed on the datasets, which include a diverse set of virtual structures used to attain the universality. We demonstrated the applicability of PFP in selected domains: lithium diffusion in LiFeSO4F, molecular adsorption in metal-organic frameworks, an order-disorder transition of Cu-Au alloys, and material discovery for a Fischer-Tropsch catalyst. They showcase the power of PFP, and this technology provides a highly useful tool for material discovery.

Endoscopic Removal of Multiple Ingested Cylindrical Batteries.

Button battery ingestion accidents have been reported in multiple previous reports. However, ingestion of cylindrical-type batteries is significant less described in the literature. Cylindrical batteries can reportedly cause corrosive damage to the gastrointestinal mucosa after long-term retention, leading to ulceration and perforation. Here, we present a case of endoscopic removal of eight AA batteries that had been ingested and caused corrosive changes in the gastrointestinal mucosa. A 45-year-old man with mental retardation was brought to our hospital due to the suspicion of cylindrical battery ingestion. A plain abdominal x-ray revealed a total of eight cylindrical batteries. Esophagogastroduodenoscopy was performed approximately 24 hours after ingestion, and four AA batteries were removed using a polypectomy snare. The remaining four batteries were followed up and removed under colonoscopy after confirming that they had reached the rectum. Leaked components of retained cylindrical batteries can cause chemical mucosal damage in the gastrointestinal tract. Therefore, early extraction should be considered in case of cylindrical battery ingestion. On the other hand, when the cylindrical battery has passed the pyloric ring, conservative management with close monitoring is acceptable if there are no clinical symptoms. Additionally, a polypectomy snare is useful in the extraction of ingested cylindrical batteries.

Diagnostic Strategy of Early Stage Pancreatic Cancer via Clinical Predictor Assessment: Clinical Indicators, Risk Factors and Imaging Findings.

Early detection of pancreatic ductal adenocarcinoma (PDAC) in the general population is difficult due to unknown clinical characteristics. This study was conducted to clarify the factors associated with early stage PDAC. Well-known symptoms and factors associated with PDAC were classified into clinical indicators, risk factors, and imaging findings concomitant with early stage PDAC. To analyze these factors for the detection of patients with early stage PDAC compared to patients without PDAC, we constructed new diagnostic strategies. The factors of 35 patients with early stage PDAC (stage 0 and IA) and 801 patients without PDAC were compared retrospectively. Clinical indicators; presence and number of indicators, elevated pancreatic enzyme level, tumor biomarker level, acute pancreatitis history, risk factors; familial pancreatic cancer, diabetes mellitus, smoking history, imaging findings; presence and number of findings, and main pancreatic duct dilation were significant factors for early stage PDAC detection. A new screening strategy to select patients who should be examined by imaging modalities from evaluating clinical indicators and risk factors and approaching a definitive diagnosis by evaluating imaging findings had a relatively high sensitivity, specificity, and areas under the curve of 80.0%, 80.8%, and 0.80, respectively. Diagnosis based on the new category and strategy may be reasonable for early stage PDAC detection.

Monomorphic epitheliotropic intestinal T-cell lymphoma presenting as melena with long-term survival: A case report and review of literature.

BACKGROUND: Monomorphic epitheliotropic intestinal T-cell lymphoma (MEITL) is a rare primary intestinal T-cell lymphoma, previously known as enteropathy-associated T-cell lymphoma type II. MEITL is an aggressive T-cell lymphoma with a poor prognosis and high mortality rate. The known major complications of MEITL are intestinal perforation and obstruction. Here, we present a case of MEITL that was diagnosed following upper gastrointestinal bleeding from an ulcerative duodenal lesion, with recurrence-free survival for 5 years. CASE SUMMARY: A 68-year-old female was admitted to our hospital with melena and mild anemia. An urgent esophagogastroduodenoscopy (EGD) revealed bleeding from an ulcerative lesion in the transverse part of the duodenum, for which hemostatic treatment was performed. MEITL was diagnosed following repeated biopsies of the lesion, and cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) chemotherapy was administered. She achieved complete remission after eight full cycles of CHOP therapy. At the last follow-up examination, EGD revealed a scarred ulcer and 18Fluorodeoxyglucose (18FDG) positron emission tomography/computed tomography showed no abnormal FDG accumulation. The patient has been in complete remission for 68 mo after initial diagnosis. CONCLUSION: To rule out MEITL, it is important to carefully perform histological examination when bleeding from a duodenal ulcer is observed.

High-speed Ge/Si electro-absorption optical modulator in C-band operation wavelengths.

We studied a high-speed electro-absorption optical modulator (EAM) of a Ge layer evanescently coupled with a Si waveguide (Si WG) of a lateral pn junction for high-bandwidth optical interconnect. By decreasing the widths of selectively grown Ge layers below 1 µm, we demonstrated a high-speed modulation of 56 Gbps non-return-to-zero (NRZ) and 56 Gbaud pulse amplitude modulation 4 (PAM4) EAM operation in the C-band wavelengths, in contrast to the L-band wavelengths operations in previous studies on EAMs of pure Ge on Si. From the photoluminescence and Raman analyses, we confirmed an increase in the direct bandgap energy for such a submicron Ge/Si stack structure. The operation wavelength for the Ge/Si stack structure of a Ge/Si EAM was optimized by decreasing the device width below 1-µm and setting the post-growth anneal condition, which would contribute to relaxing the tensile-strain of a Ge layer on a Si WG and broadening the optical bandwidths for Franz-Keldysh (FK) effect with SiGe alloy formation.

Preparation of Continuous Highly Hydrophobic Pure Silica ITQ-29 Zeolite Layers on Alumina Supports.

The preparation of continuous layers of highly hydrophobic pure silica ITQ-29 zeolite, potentially applicable as hydrophobic membranes for separation of molecules based on their polarity, has been investigated. Continuous layers of intergrown ITQ-29 zeolite crystals were successfully grown on porous alumina supports by optimization of the synthesis conditions, such as the appropriate selection of the seeds, the procedure for the gel preparation, and the calcination conditions. This resulted in the formation of all silica ITQ-29 zeolite layers without the presence of germanium required in previously reported ITQ-29 membranes, with the subsequent improvement in quality and stability, as verified by the absence of cracks after calcination. We have proved that the incorporation of aluminum from the support into the zeolite layer does not occur, neither during the secondary growth nor through migration of aluminum species during calcination.

Intracerebroventricular Treatment with Resiniferatoxin and Pain Tests in Mice.

The transient receptor potential vanilloid type 1 (TRPV1), a thermosensitive cation channel, is known to trigger pain in the peripheral nerves. In addition to its peripheral function, its involvement in brain functions has also been suggested. Resiniferatoxin (RTX), an ultrapotent TRPV1 agonist, has been known to induce long-term desensitization of TRPV1, and this desensitization has been an alternative approach for investigating the physiological relevance of TRPV1-expressing cells. Here we describe a protocol for intracerebroventricular (i.c.v.) treatment with RTX in mice. Procedures are described for testing nociception to peripheral TRPV1 stimulation (RTX test) and mechanical stimulation (tail pressure test) then follow. Although the nociceptive responses of mice that had been administered RTX i.c.v. were comparable to those of the control groups, RTX-i.c.v.-administered mice were insensitive to the analgesic effect of acetaminophen, suggesting that i.c.v. RTX treatment can induce supraspinal-selective TRPV1 desensitization. This mouse model can be used as a convenient experimental system for studying the role of TRPV1 in brain/supraspinal function. These techniques can also be applied to studies of the central actions of other drugs.

A case of ruptured mucinous cystadenoma of the pancreas with recurrence-free survival for 8 years.

BACKGROUND: Pancreatic mucinous cystic neoplasm (MCM) presenting with rupture is extremely rare, and very few studies have followed up patients over the long term after ruptured mucinous cystadenoma (MCA). We report a case of ruptured MCA of the pancreas with recurrence-free survival for 8 years. CASE PRESENTATION: A 28-year-old Japanese woman was admitted to the emergency department of a local hospital after experiencing acute abdominal pain. Abdominal computed tomography revealed massive ascites and the presence of a cystic tumor measuring 60 mm in diameter in the pancreatic tail. Conservative therapy with antibiotics and abdominal drainage were performed to treat peritonitis that occurred secondary to the ruptured pancreatic cystic tumor, after which the patient's symptoms improved. The patient was referred to our department for further examination and treatment. We diagnosed a ruptured MCN and performed laparoscopic spleen-preserving distal pancreatectomy. Histopathological findings revealed ovarian-type stroma, which tested positive for estrogen and progesterone receptors by immunohistochemistry. The histopathological diagnosis was MCA. The postoperative course was uneventful, and the patient remains alive without any evidence of recurrence at 8 years postoperatively. CONCLUSION: A good prognosis is possible even in cases of ruptured MCA. Because of the risk of peritoneal dissemination after ruptured MCA, long-term follow-up is important.

[Hypothermic Action of Oseltamivir Not Dependent on Its Anti-influenza Virus Action].

Although the anti-influenza virus drug oseltamivir ameliorates the fever of influenza, adverse events related to its hypothermic effect have been reported. We found that oseltamivir causes dose-dependent hypothermia in normal mice, and have been studying the pharmacological mechanisms responsible for 12 years. Oseltamivir blocks nicotinic cholinergic transmission at sympathetic ganglia and reduces sympathetic modulation of brown adipose tissue (BAT), a heat generator. Oseltamivir was found to target the ion channels of nicotinic acetylcholine receptors, as demonstrated by patch clamp experiments with cells expressing the human α3ß4 nicotinic receptor. Metabolized oseltamivir carboxylate, which inhibits the influenza virus neuraminidase, did not elicit hypothermia and ion channel suppression. Body temperature was decreased by intracerebroventricular administration of oseltamivir. Because this hypothermic effect was inhibited by dopamine D2 receptor blockade, it was suggested that oseltamivir centrally stimulates the D2 receptor. In Japan, the package inserts for oseltamivir and amantadine indicate very similar adverse neuropsychiatric reactions for the two drugs (abnormal behavior, consciousness disturbance, convulsion, delirium, delusion, hallucination). A literature search revealed that in some previous studies, oseltamivir and amantadine were shown to block the ion channel systems and activate the dopaminergic nervous system via several mechanisms. Therefore the similarity of the adverse reactions elicited by oseltamivir and amantadine was considered attributable to their similar pharmacological effects.

[Similarity of Clinically Significant Neuropsychiatric Adverse Reactions Listed in Package Inserts between the Anti-influenza Drugs Oseltamivir and Amantadine (Possibility Attributable to Common Pharmacological Effects)].

　The anti-influenza virus drug oseltamivir has been reported to have several pharmacological actions including blocking of nicotinic acetylcholine receptor channels and activation of the dopaminergic system. These pharmacological actions highly overlap those of amantadine, another anti-influenza virus drug authorized in Japan, and ester-type local anesthetics. Moreover, oseltamivir and amantadine can clinically induce similar adverse neuropsychiatric reactions. In the present study, from the database of the Pharmaceuticals and Medical Devices Agency (PMDA), we surveyed 2576 drugs for which neuropsychiatric side effects similar to those of oseltamivir, amantadine and local anesthetics (abnormal behavior, confusion, consciousness disturbance, convulsion, delirium, delusion, hallucination, myoclonus, tremor) are listed as "clinically significant adverse reactions", and found 327 that had at least one of these adverse reactions. Other neuraminidase inhibitors (laninamivir, peramivir and zanamivir) did not elicit such adverse reactions. By discussing the pharmacological effects of drugs that elicit these adverse reactions, we propose that the similarity of adverse neuropsychiatric reactions between oseltamivir and amantadine is possibly attributable to their common pharmacological effects.

The anti-influenza drug oseltamivir evokes hypothermia in mice through dopamine D2 receptor activation via central actions.

Oseltamivir has a hypothermic effect in mice when injected intraperitoneally (i.p.) and intracerebroventricularly (i.c.v.). Here we show that the hypothermia evoked by i.c.v.-oseltamivir is inhibited by non-selective dopamine receptor antagonists (sulpiride and haloperidol) and the D2-selective antagonist L-741,626, but not by D1/D5-selective and D3-selective antagonists (SCH-23390 and SB-277011-A, respectively). The hypothermic effect of i.p.-administered oseltamivir was not inhibited by sulpiride, haloperidol, L-741,626 and SCH-23390. In addition, neither sulpiride, haloperidol nor SCH-23390 blocked hypothermia evoked by i.c.v.-administered oseltamivir carboxylate (a hydrolyzed metabolite of oseltamivir). These results suggest that oseltamivir in the brain induces hypothermia through activation of dopamine D2 receptors.

Supraspinal-selective TRPV1 desensitization induced by intracerebroventricular treatment with resiniferatoxin.

The transient receptor potential vanilloid type 1 (TRPV1) is a thermosensitive cation channel that triggers heat pain in the periphery. Long-term desensitization of TRPV1, which can be induced by excess amounts of agonists, has been a method for investigating the physiological relevance of TRPV1-containing neuronal circuits, and desensitization induced by various routes of administration, including systemic, intrathecal and intraganglionic, has been demonstrated in rodents. In the present study, we examined the effect of intracerebroventricular (i.c.v.) treatment with an ultrapotent TRPV1 agonist, resiniferatoxin (RTX), on nociception and the analgesic effect of acetaminophen, which is known to mediate the activation of central TRPV1. I.c.v. administration of RTX a week before the test did not affect the licking/biting response to intraplantar injection of RTX (RTX test), suggesting that such i.c.v. treatment spares the function of TRPV1 at the hindpaw. Mice that had been i.c.v.-administered RTX also exhibited normal nociceptive responses in the formalin test and the tail pressure test, but acetaminophen failed to induce analgesia in those mice in any of the tests. These results suggest that i.c.v. administration of RTX leads to brain-selective TRPV1 desensitization in mice.

Serotonergic System Does Not Contribute to the Hypothermic Action of Acetaminophen.

Acetaminophen (AcAP), a widely-used antipyretic and analgesic drug, has been considered to exert its effects via central mechanisms, and many studies have demonstrated that the analgesic action of AcAP involves activation of the serotonergic system. Although the serotonergic system also plays an important role in thermoregulation, the contribution of serotonergic activity to the hypothermic effect of AcAP has remained unclear. In the present study, we examined whether the serotonergic system is involved in AcAP-induced hypothermia. In normal mice, AcAP (300 mg/kg, intraperitoneally (i.p.)) induced marked hypothermia (ca. -4°C). The same dose of AcAP reduced pain response behavior in the formalin test. Pretreatment with the serotonin synthesis inhibitor DL-p-chlorophenylalanine (PCPA, 300 mg/kg/d, i.p., 5 consecutive days) substantially decreased serotonin in the brain by 70% and significantly inhibited the analgesic, but not the hypothermic action of AcAP. The same PCPA treatment significantly inhibited the hypothermia induced by the selective serotonin reuptake inhibitor fluoxetine hydrochloride (20 mg/kg, i.p.) and the serotonin 5-HT2 receptor antagonist cyproheptadine hydrochloride (3 mg/kg, i.p.). The lower doses of fluoxetine hydrochloride (3 mg/kg, i.p.) and cyproheptadine hydrochloride (0.3 mg/kg, i.p.) did not affect the AcAP-induced hypothermia. These results suggest that, in comparison with its analgesic effect, the hypothermic effect of AcAP is not mediated by the serotonergic system.

N- and L-type calcium channels blocker cilnidipine ameliorates neuropathic pain.

Cilnidipine is a dihydropyridine derivative that inhibits N-type and L-type voltage-gated Ca2+ channels (VDCCs). We recently reported that a selective N-type VDCC blocker attenuated the spinal long-term potentiation (LTP) of C-fiber-evoked field potentials recorded in the spinal dorsal horn of rats, which served as a model for examining synaptic function during central pain sensitization. In this study, we investigated the effects of cilnidipine on the changes related to neuropathic pain induced by nerve injury. Mechanical allodynia and hyperalgesia were evaluated by von Frey test and pin prick test, respectively. Spinal LTP of C-fiber-evoked field potentials were evaluated by in vivo electrophysiology. Intrathecally administrated cilnidipine attenuated mechanical allodynia and hyperalgesia in the spared nerve injury mouse model. Using in vivo electrophysiology in rats, cilnidipine (10µm) administered spinally inhibited the induction and maintenance of high-frequency stimulation-induced LTP of C-fiber-evoked field potentials, while basal C-fiber-evoked field potentials in naïve rats were unaffected. The basal C-fiber-evoked field potentials in nerve-injured rats were strongly inhibited by cilnidipine. Treatment with a specific N-type VDCC blocker, ω-conotoxin GVIA, which reportedly attenuates C-fiber-evoked field potentials both before and after the induction of LTP, attenuated mechanical allodynia and hyperalgesia in nerve-injured mice. By contrast, an L-type VDCC blocker, nicardipine attenuated only mechanical hyperalgesia, but not mechanical allodynia in nerve-injured mice, and also attenuated the established LTP of C-fiber-evoked field potentials in rats. These results suggested that N-type and L-type VDCC blockers may effectively alleviate the hyperalgesia and allodynia associated with neuropathic pain without affecting normal pain perception.

Oxaliplatin treatment changes the function of sensory nerves in rats.

Oxaliplatin (L-OHP) is a platinum-based chemotherapy drug, used in standard treatment of colorectal cancer. L-OHP frequently causes acute peripheral neuropathies. These adverse effects limit cancer therapy with L-OHP. The present study was designed to reveal the changes in sensory nerve function in L-OHP-injected rats. Mechanical static allodynia, dynamic allodynia, and cold allodynia were evaluated using the von Frey test, brush test, and acetone test, respectively. Sensory nerve fiber responsiveness was measured using a Neurometer. The fifth lumbar ventral root was sectioned to record multi-unit efferent discharges. Single intraperitoneal administration of L-OHP induced mechanical static allodynia, dynamic allodynia, and cold allodynia in Wistar/ST rats. The thresholds for paw withdrawal induced by 2000 Hz (Aß-fiber) and 5 Hz (C-fiber), but not 250 Hz (Aδ-fiber) sine-wave electrical stimulation were reduced in L-OHP-treated rats. Multi-unit efferent discharges were increased by mechanical stimulation using a von Frey filament applied to the plantar surface of the hindpaw. The discharges during and after stimulation were increased in the L-OHP-treated rats. Cold stimulation, but not brush stimulation, increased the discharges in L-OHP-treated rats. These results suggest that sensitization of Aß- and C-fibers, but not Aδ-fibers, contributes to the development of L-OHP-induced mechanical and cold allodynia.

Oseltamivir produces hypothermic and neuromuscular effects by inhibition of nicotinic acetylcholine receptor functions: comparison to procaine and bupropion.

Oseltamivir, an anti-influenza virus drug, induces marked hypothermia in normal mice. We have proposed that the hypothermic effect arises from inhibition of the nicotinic acetylcholine receptor function of sympathetic ganglion neurons which innervate the brown adipose tissue (a heat generator). It has been reported that local anesthetics inhibit nicotinic acetylcholine receptor function by acting on its ionic channels, and that bupropion, a nicotinic antagonist, induces hypothermia. In this study, we compared the effects of oseltamivir, procaine and bupropion on body temperature, cardiovascular function and neuromuscular transmission. Intraperitoneal administration of oseltamivir (100mg/kg), procaine (86.6mg/kg) and bupropion (86.7mg/kg) lowered the core body temperature of normal mice. At lower doses (10-30mg/kg oseltamivir, 8.7-26mg/kg procaine and bupropion), when administered subcutaneously, the three drugs antagonized the hypothermia induced by intraperitoneal injection of nicotine (1mg/kg). In anesthetized rats, intravenous oseltamivir (30-100mg/kg), procaine (10mg/kg) and bupropion (10mg/kg) induced hypotension and bradycardia. Oseltamivir alone (100mg/kg) did not inhibit neuromuscular twitch contraction of rats, but at 3-30mg/kg it augmented the muscle-relaxing effect of d-tubocurarine. Similar effects were observed when lower doses of procaine (10-30mg/kg) and bupropion (3-10mg/kg) were administered, suggesting that systemic administration of oseltamivir inhibits muscular nicotinic acetylcholine receptors. These results support the idea that the hypothermic effect of oseltamivir is due to its effects on sympathetic ganglia which innervate the brown adipose tissue, and suggest that oseltamivir may exert non-selective ion channel blocking effects like those of ester-type local anesthetics.

Oseltamivir blocks human neuronal nicotinic acetylcholine receptor-mediated currents.

The effects of oseltamivir, a neuraminidase inhibitor, were tested on the function of neuronal nicotinic acetylcholine receptors (nAChRs) in a neuroblastoma cell line IMR32 derived from human peripheral neurons and on recombinant human α3ß4 nAChRs expressed in HEK cells. IMR32 cells predominately express α3ß4 nAChRs. Nicotine (nic, 30 µm)-evoked currents recorded at -90 mV in IMR32 cells using the whole-cell patch clamp technique were reversibly blocked by oseltamivir in a concentration-dependent manner. In contrast, an active metabolite of oseltamivir, oseltamivir carboxylate (OC) at 30 µm had little effect on the nic-evoked currents. Oseltamivir also blocked nic-evoked currents derived from HEK cells with recombinant α3ß4 nAChRs. This blockade was voltage-dependent with 10, 30 and 100 µm oseltamivir inhibiting ~50% at -100, -60 and -40 mV, respectively. Non-inactivating currents in IMR32 cells and in HEK cells with α3ß4 nAChRs, which were evoked by an endogenous nicotinic agonist, ACh (5 µm), were reversibly blocked by oseltamivir. These data demonstrate that oseltamivir blocks nAChRs, presumably via binding to a site in the channel pore.