Subcutaneous inoculation of a whole virus particle vaccine prepared from a non-pathogenic virus library induces protective immunity against H7N7 highly pathogenic avian influenza virus in cynomolgus macaques

Development of H7N7 highly pathogenic avian influenza virus (HPAIV) vaccines is an urgent issue since human cases of infection with this subtype virus have been reported and most humans have no immunity against H7N7 viruses. We made an H7N7 vaccine combining components from an influenza virus library of non-pathogenic type A influenza viruses. Antibody and T cell recall responses specific against the vaccine strain were elicited by subcutaneous inoculation with the whole virus particle vaccine with or without alum as an adjuvant in cynomolgus macaques. No significant difference was observed in magnitude of antibody responses between vaccination with alum and vaccination without alum, though vaccination with alum induced longer recall responses of CD8⁺ T cells than did vaccination without alum. After challenge with a subtype of H7N7 HPAIV, the virus was detected in nasal swabs of unvaccinated macaques for 8 days but only for 1 day in the animals vaccinated either with or without alum, although the macaques vaccinated with alum showed elevated body temperature more briefly after infection. These findings demonstrated that this H7N7 HPAIV strain is pathogenic to macaques and that the vaccine conferred protective immunity to macaques against H7N7 HPAIV infection.     

Pancreatic acinar cell carcinoma with extensive tumor embolism at the trunk of portal vein and pancreatic intraductal infiltration

A 59-year-old man was admitted to the hospital with acute pancreatitis. The cause was suggested to be a pancreatic tumor based on computed tomography (CT). The pancreatic tumor was 45 mm with an extensive tumor embolism at the trunk of the portal vein and intraductal infiltration of the main pancreatic duct (MPD). The pancreatic tumor was diagnosed as acinar cell carcinoma (ACC) by endoscopic ultrasound guided fine needle aspiration. Therefore, the cause of acute pancreatitis was diagnosed to be intraductal infiltration of ACC in the MPD. Chemotherapy was initially performed because it was difficult to perform surgery due to extensive tumor embolism at the trunk of the portal vein. Degeneration and reduction of ACC and tumor embolism of the portal vein was noted on CT after chemotherapy, and extended distal pancreatectomy with portal vein reconstruction was performed. There has been no relapse for 5 years postoperative follow-up. This is an interesting and rare case because ACC with intraductal infiltration of MPD is low in frequency; most ACCs are asymptomatic when they are found, and many cases tend to have poor prognosis in spite of surgical cases.     

The efficacy and safety of left atrial low‐voltage area guided ablation for recurrence prevention compared to pulmonary vein isolation alone in patients with persistent atrial fibrillation trial: Design and rationale

Recurrence rates of atrial fibrillation (AF) after pulmonary vein isolation (PVI) are higher in patients with a left atrial low‐voltage area (LVA) than those without. However, the efficacy of LVA guided ablation is still unknown. The purpose of this study—the Efficacy and Safety of Left Atrial Low‐voltage Area Guided Ablation for Recurrence Prevention Compared to Pulmonary Vein Isolation Alone in Patients with Persistent Atrial Fibrillation trial (SUPPRESS‐AF trial)—is to elucidate whether LVA guided ablation in addition to PVI is superior to PVI alone in patients with persistent AF. The Osaka Cardiovascular Conference will conduct a multicenter, randomized, open‐label trial aiming to examine whether LVA guided ablation in addition to PVI is superior to PVI alone in patients with persistent AF and LVAs. The primary outcome is the recurrence of AF documented by scheduled or symptom‐driven electrocardiography (ECG) during the 1 year follow‐up period after the index ablation. The key secondary endpoints include all‐cause death, symptomatic stroke, bleeding events, and other complications related to the procedure. A total of 340 patients with an LVA will be enrolled and followed up to 1 year. The SUPPRESS‐AF trial is a randomized controlled trial designed to assess whether LVA guided ablation in addition to PVI is superior to PVI alone for patients with persistent AF and LVAs detected while undergoing their first catheter ablation.     

Intranasal administration of a live non-pathogenic avian H5N1 influenza virus from a virus library confers protective immunity against H5N1 highly pathogenic avian influenza virus infection in mice: Comparison of formulations and administration routes of vaccines

Outbreaks of highly pathogenic avian influenza viruses (HPAIVs) would cause disasters worldwide. Various strategies against HPAIVs are required to control damage. It is thought that the use of non-pathogenic avian influenza viruses as live vaccines will be effective in an emergency, even though there might be some adverse effects, because small amounts of live vaccines will confer immunity to protect against HPAIV infection. Therefore, live vaccines have the advantage of being able to be distributed worldwide soon after an outbreak. In the present study, we found that intranasal administration of a live H5N1 subtype non-pathogenic virus induced antibody and cytotoxic T lymphocyte responses and protected mice against H5N1 HPAIV infection. In addition, it was found that a small amount (100 PFU) of the live vaccine was as effective as 100 μg (approximately 10^10–11 PFU of virus particles) of the inactivated whole particle vaccine in mice. Consequently, the use of live virus vaccines might be one strategy for preventing pandemics of HPAIVs in an emergency.     

Observation of the esophagus, pharynx and lingual root by gastrointestinal endoscopy with a percutaneous retrograde approach

AIM: To evaluate the efficacy of retrograde observation of the esophagus, pharynx, larynx and lingual root.METHODS: With the beagle dog under anesthesia, the anterior wall of the stomach was fixed on the abdominal wall in a similar way to percutaneous endoscopic gastrostomy. The gastrointestinal scope was inserted via a 12 mm laparoscopic port for subsequent retrograde observation from stomach to the oral cavity.RESULTS: With this technique, direct observation of gastric cardia was possible without restriction. The cervical esophagus was dilated well, also allowing clear observation of the hypopharyngo-esophageal junction. If the tongue was manually pulled out forward, observation of the lingual root was possible.CONCLUSION: This procedure is easy and effective for pre-treatment evaluation of the feasibility of endoscopic resection in cases of superficial carcinoma of head and neck.     

Hepatic encephalopathy with status epileptics： A case report

A 62-year-old male with decompensated liver cirrhosis due to hepatitis C virus developed severe hepatic encephaiopathy with status epileptic us. The blood ammonia level on admission was more than twice the normal level. Brain computed tomography and magnetic resonance imaging were normal. In addition, electroencephalogram showed diffuse sharp waves, consistent with hepatic encephaiopathy. The status epilepticus was resolved after antiepileptic therapy (phenytoin sodium) and treatment for hepatic encephaiopathy (Branched chain amino acids). The blood ammonia level normalized with the clinical improvement and the patient did not have a recurrence of status epilepticus after the end of the antiepileptic treatment. Additionally, the electroencephalogram showed normal findings. Thus, we diagnosed the patient as hepatic encephaiopathy with status epilepticus. We consider the status epilepticus of this patient to a rare and interesting finding in hepatic encephaiopathy.     

A volumetric analysis of the brain and hippocampus of rats rendered perinatal hypothyroid

The thyroid hormone is essential for the proper development of the central nervous system (CNS). Hormone deficiency during CNS development causes neurological abnormalities in the brain. The hippocampus is one of the brain regions vulnerable to hormone deficiency, and the volume of dentate gyrus (DG) and cornu ammonis (CA) are reduced by transient hypothyroidism during CNS development. However, it remains unclear whether transient hypothyroidism specifically reduces the whole hippocampal volume. In the present study, we used magnetic resonance imaging (MRI) to examine the effects of perinatal hypothyroidism on the ratio of hippocampal volume to brain volume as well as brain and hippocampal volumes overall. Perinatal hypothyroidism was induced by adding the anti-thyroid drug, methimazole, to the drinking water of pregnant dams from gestational day 15 to postnatal day 21. The MRI experiment was conducted when the rats were between 7 and 11 months old. The results showed reductions of the hippocampal and brain volume of the treated group. However, the ratio of hippocampal volume to brain volume was comparable between the control and treated groups. These results indicate that perinatal hypothyroidism minimizes the brain as a whole, but does not minimize the hippocampus in particular.     

Centrifugal regulation of a task-relevant somatosensory signal triggering voluntary movement without a preceding warning signal

A warning signal followed by an imperative signal generates anticipatory and preparatory activities, which regulate sensory evoked neuronal activities through a top-down centrifugal mechanism. The present study investigated the centrifugal regulation of neuronal responses evoked by a task-relevant somatosensory signal, which triggers a voluntary movement without a warning signal. Eleven healthy adults participated in this study. Electrical stimulation was delivered to the right median nerve at a random interstimulus interval (1.75–2.25 s). The participants were instructed to extend the second digit of the right hand as fast as possible when the electrical stimulus was presented (ipsilateral reaction condition), or extend that of the left hand (contralateral reaction condition). They also executed repetitively extension of the right second digit at a rate of about 0.5 Hz, irrespective of electrical stimulation (movement condition), to count silently the number of stimuli (counting condition). In the control condition, they had no task to perform. The amplitude of short-latency somatosensory evoked potentials, the central P25, frontal N30, and parietal P30, was significantly reduced in both movement and ipsilateral reaction conditions compared to the control condition. The amplitude of long-latency P80 was significantly enhanced only in the ipsilateral reaction condition compared to the control, movement, contralateral reaction, and counting conditions. The long-latency N140 was significantly enhanced in both movement and ipsilateral reaction conditions compared to the control condition. In conclusion, short- and long-latency neuronal activities evoked by task-relevant somatosensory signals were regulated differently through a centrifugal mechanism even when the signal triggered a voluntary movement without a warning signal. The facilitation of activities at a latency of around 80 ms is associated with gain enhancement of the task-relevant signals from the body part involved in the action, whereas that at a latency of around 140 ms is associated with unspecific gain regulation generally induced by voluntary movement. These may be dissociated from the simple effect of directing attention to the stimulation.