Anterograde transneuronal tracing and genetic control with engineered yellow fever vaccine YFV-17D.

Transneuronal viruses are powerful tools for tracing neuronal circuits or delivering genes to specific neurons in the brain. While there are multiple retrograde viruses, few anterograde viruses are available. Further, available anterograde viruses often have limitations such as retrograde transport, high neuronal toxicity or weak signals. We developed an anterograde viral system based on a live attenuated vaccine for yellow fever-YFV-17D. Replication- or packaging-deficient mutants of YFV-17D can be reconstituted in the brain, leading to efficient synapse-specific and anterograde-only transneuronal spreading, which can be controlled to achieve either monosynaptic or polysynaptic tracing. Moreover, inducible transient replication of YFV-17D mutant is sufficient to induce permanent transneuronal genetic modifications without causing neuronal toxicity. The engineered YFV-17D systems can be used to express fluorescent markers, sensors or effectors in downstream neurons, thus providing versatile tools for mapping and functionally controlling neuronal circuits.

Directed stepwise tracing of polysynaptic neuronal circuits with replication-deficient pseudorabies virus.

Brain functions are accomplished by polysynaptic circuits formed by neurons wired together through multiple orders of synaptic connections. Polysynaptic connectivity has been difficult to examine due to a lack of methods of continuously tracing the pathways in a controlled manner. Here, we demonstrate directed, stepwise retrograde polysynaptic tracing by inducible reconstitution of replication-deficient trans-neuronal pseudorabies virus (PRVΔIE) in the brain. Furthermore, PRVΔIE replication can be temporally restricted to minimize its neurotoxicity. With this tool, we delineate a wiring diagram between the hippocampus and striatum-two major brain systems for learning, memory, and navigation-that consists of projections from specific hippocampal domains to specific striatal areas via distinct intermediate brain regions. Therefore, this inducible PRVΔIE system provides a tool for dissecting polysynaptic circuits underlying complex brain functions.

Effect of right hemispheric damage on structured spoken conversation.

Patients with right hemisphere damage (RHD) occasionally complain of difficulties in conversation. A conversation is a type of communication between the speaker and listener, and several elements are required for a conversation to take place. However, it is unclear which of those elements affect communication in patients with RHD. Therefore, we prospectively enrolled 11 patients with right hemispheric damage due to acute cerebral infarction, within 1 week of onset. To evaluate patients' conversational abilities, we used a structured conversation task, namely, the "Hallym Conversation and Pragmatics Protocol". The topics of conversation were "family", "leisure", and "other/friends". The conversation characteristics were classified according to three indices: the "conversational participation index", "topic manipulation index", and "conversational breakdown index". Patients with RHD were compared with 11 age-, sex-, and years of education-matched healthy adults. The most common site of damage in the patients with RHD was the periventricular white matter. There was no significant difference in performance between the two groups according to the conversation participation index and in the discontinuance rate assessed with the conversational breakdown index. However, patients with RHD showed a lower topic maintenance rate and higher topic initiation and topic switching rates, according to the topic manipulation index. Therefore, we explored the characteristics of impaired conversation abilities in patients with RHD by assessing their ability to converse and manage topics during structured conversations, and found difficulties with pragmatics and communication discourse in these patients.

Small atypical cervical nodes detected on sonography in patients with squamous cell carcinoma of the head and neck: probability of metastasis.

OBJECTIVE: The purpose of this study was to assess the probability of metastasis of small atypical cervical lymph nodes detected on sonography in patients with squamous cell carcinoma (SCC) of the head and neck. METHODS: We reviewed, retrospectively and blindly, sonographic findings of 148 patients (118 men and 30 women; mean age, 58.2 years) who underwent curative neck dissection. Each lymph node was classified by using a 4-point scale: 1, definitely benign; 2, indeterminate (small [short-axis diameter <10 mm for levels I and II and <7 mm for levels III-VI] atypical node); 3, definitely metastatic; and 4, large (>3-cm) metastatic. Lymph nodes were considered atypical if they met at least 1 of the following criteria: a long- to short-axis diameter ratio of less than 2.0, absence of a normal echogenic hilum, and heterogeneous echogenicity of the cortex. These results were verified, on a level-by-level basis, with histopathologic findings. RESULTS: Small atypical nodes were found on sonography in 63 cervical levels of 48 patients, of which 18 (28.6%) were proved to have metastatic nodes. The probability of metastasis was significantly higher with than without a large (>3-cm) ipsilateral metastatic node (0.50 versus 0.20; P = .038) and marginally higher with than without an ipsilateral metastatic node (0.41 versus 0.16; P = .061) but not significantly associated with the T stage of the primary tumor (P = .238) or the presence of an ipsilateral tumor (P = .904). CONCLUSIONS: Metastasis was encountered in about 30% of small atypical cervical nodes on sonography in patients with SCC of the head and neck. Our results indicate that small atypical nodes must be interpreted with consideration of metastatic nodes in the ipsilateral neck.

Fibroma of the tympanic membrane.

A primary tumor of the tympanic membrane is very rare. Herein, we describe a patient with a thick tympanic membrane that caused progressive hearing loss. The patient was treated with total resection of the tympanic membrane and was diagnosed with fibroma after histopathologic examination. There was no evidence of recurrence 2 years after the operation, and the patient's hearing was normal. Fibroma may arise in the tympanic membrane and should be regarded as a possible cause of the mass of the tympanic membrane.

Facial canal dehiscence in the initial operation for chronic otitis media without cholesteatoma.

OBJECTIVE: To evaluate the risk of the facial nerve injury during operations for chronic otitis media without cholesteatoma by analysis of the intraoperative findings of the facial canal dehiscence. METHODS: We retrospectively reviewed operative findings of 152 patients who underwent tympanoplasty with mastoidectomy for chronic otitis media. We examined every segment of the facial canal from the geniculate ganglion to the mastoid segment. Facial canal dehiscence was confirmed by palpation with a Rosen pick after inspection with a surgical microscope. RESULTS: The rate of facial canal dehiscence was 8.6% (13 of 152 cases), and the tympanic segment was the most commonly found region at 84.6% (11 of 13 cases). Of the 11 cases of tympanic segment dehiscence, 9 cases were involved the lateral aspect of the facial canal in the oval window area. There was one case each of facial canal dehiscence in the geniculate ganglion and the mastoid segment, respectively. CONCLUSION: The rate of facial canal dehiscence of 8.6% is not a low incidence rate, so even though performing a routine chronic ear operation, surgeons may encounter facial canal dehiscence at any time and should be prepared for the emergence of such a situation.

Emulating Host-Microbiome Ecosystem of Human Gastrointestinal Tract in Vitro.

The human gut microbiome performs prodigious physiological functions such as production of microbial metabolites, modulation of nutrient digestion and drug metabolism, control of immune system, and prevention of infection. Paradoxically, gut microbiome can also negatively orchestrate the host responses in diseases or chronic disorders, suggesting that the regulated and balanced host-gut microbiome crosstalk is a salient prerequisite in gastrointestinal physiology. To understand the pathophysiological role of host-microbiome crosstalk, it is critical to recreate in vivo relevant models of the host-gut microbiome ecosystem in human. However, controlling the multi-species microbial communities and their uncontrolled growth has remained a notable technical challenge. Furthermore, conventional two-dimensional (2D) or 3D culture systems do not recapitulate multicellular microarchitectures, mechanical dynamics, and tissue-specific functions. Here, we review recent advances and current pitfalls of in vitro and ex vivo models that display human GI functions. We also discuss how the disruptive technologies such as 3D organoids or a human organ-on-a-chip microphysiological system can contribute to better emulate host-gut microbiome crosstalks in health and disease. Finally, the medical and pharmaceutical significance of the gut microbiome-based personalized interventions is underlined as a future perspective.

A case of dysplastic nevus of the external auditory canal presenting with conductive hearing loss.

A nevus which is a benign melanocytic neoplasm rarely occurs within the external auditory canal (EAC). A dysplastic nevus presents atypical features both clinically and histologically, and is important as a potential precursor for melanoma. We present a case of a 33-year-old female patient with a dysplastic nevus in her EAC. Physical examination revealed a protruding mass arising from the posterior wall of the left cartilaginous EAC. The mass showed clinically characteristic findings of a melanocytic nevus. The patient underwent excisional biopsy via a transcanal approach under local anesthesia. Histopathological examination revealed an intradermal nevus with atypical melanocytes without pleomorphism. There was no evidence of recurrence two years after surgical excision.

Analysis of axial temporal bone computed tomography scans for performing a safe posterior tympanotomy.

A posterior tympanotomy is a procedure performed to access the posterior mesotympanum to remove pathologic lesions through a mastoid exposure. In this study, we aimed to evaluate and classify the anatomical relationships between the vertical segment of the facial nerve and the mastoid antrum in an axial temporal bone CT to prevent facial nerve injury when performing a posterior tympanotomy. We performed retrospective analysis of temporal bone CT scans. A cohort of 102 patients who underwent tympanomastoidectomy for chronic otitis media, and 43 patients with sensorineural hearing loss with normal temporal bone, were included. All patients had preoperative and diagnostic computed tomography of the temporal bone from January to December 2006. Anatomical relationships were evaluated according to several parameters: protrusion of the facial nerve into the mastoid antrum, status of the facial canal, new bone formation over the facial canal, and size of the mastoid antrum. Anatomical relationships between the vertical segment and the mastoid antrum were classified into six types. Type 1 has no protrusion of the facial nerve with a regular facial canal, and Type 2 has no protrusion with a partly thin facial canal. Type 3 has protrusion into the antrum with a regular facial canal, and Type 4 has protrusion with a partly thin facial canal. Type 5 has new bone formation around the facial canal, and Type 6 has new bone formation with a small or contracted antrum. These results may enable preoperative assessment of the facial nerve's status, and provide background knowledge to prevent facial nerve injury when performing a posterior tympanotomy.

Functional benefit after modification of radial forearm free flap for soft palate reconstruction.

OBJECTIVES: To compare the velopharyngeal function, swallowing and speech of the conventional and modified radial forearm free flap (RFFF) for soft palate reconstruction. METHODS: Retrospective clinical study. Twenty-eight patients who underwent oropharyngeal reconstruction with RFFF were divided into two groups: 10 patients had conventional folded RFFF and 18 patients underwent modified method. RESULTS: The average speech intelligibility score in modified RFFF group was 8.0+/-2.4, and 6.2+/-2.2 in conventional RFFF group (P<0.05). The nasalance was 27.4+/-7.8% in modified group and 38.6+/-2.7% in conventional group during no nasal passage reading and 43.6+/-7.3% in modified group, 55.2+/-7.6% in conventional group during high nasal passage reading (P<0.05). The subjective swallowing functional score was 2.8 in modified group and 2.1 in conventional group. CONCLUSION: The speech assessment and nasalance demonstrate a more favorable outcome in modified group than conventional group.

Multiple osteomas in the middle ear.

Osteomas in the middle ear are extremely rare and are generally solitary and small. We present a case of a 28-year-old female patient with multiple middle ear osteomas which arose from the promontory, epitympanum, and lateral semicircular canal. The osteomas were successfully removed by tympanomastoidectomy. This is the first reported case of a patient with middle ear osteomas arising from multiple sites.