Exploring the effects of antimicrobial treatment on the gut and oral microbiomes and resistomes from elderly long-term care facility residents via shotgun DNA sequencing.

Monitoring antibiotic-resistant bacteria (ARB) and understanding the effects of antimicrobial drugs on the human microbiome and resistome are crucial for public health. However, no study has investigated the association between antimicrobial treatment and the microbiome-resistome relationship in long-term care facilities, where residents act as reservoirs of ARB but are not included in the national surveillance for ARB. We conducted shotgun metagenome sequencing of oral and stool samples from long-term care facility residents and explored the effects of antimicrobial treatment on the human microbiome and resistome using two types of comparisons: cross-sectional comparisons based on antimicrobial treatment history in the past 6 months and within-subject comparisons between stool samples before, during and 2-4 weeks after treatment using a single antimicrobial drug. Cross-sectional analysis revealed two characteristics in the group with a history of antimicrobial treatment: the archaeon Methanobrevibacter was the only taxon that significantly increased in abundance, and the total abundance of antimicrobial resistance genes (ARGs) was also significantly higher. Within-subject comparisons showed that taxonomic diversity did not decrease during treatment, suggesting that the effect of the prescription of a single antimicrobial drug in usual clinical treatment on the gut microbiota is likely to be smaller than previously thought, even among very elderly people. Additional analysis of the detection limit of ARGs revealed that they could not be detected when contig coverage was <2.0. This study is the first to report the effects of usual antimicrobial treatments on the microbiome and resistome of long-term care facility residents.

Quantitative behavioral evaluation of a non-human primate stroke model using a new monitoring system.

Background: Recently, the common marmoset (Callithrix jacchus) has attracted significant interest as a non-human primate stroke model. Functional impairment in non-human primate stroke models should be evaluated quantitatively and successively after stroke, but conventional observational assessments of behavior cannot fully fit this purpose. In this paper, we report a behavioral analysis using MarmoDetector, a three-dimensional motion analysis, in an ischemic stroke model using photosensitive dye, along with an observational behavioral assessment and imaging examination. Methods: Ischemic stroke was induced in the left hemisphere of three marmosets. Cerebral infarction was induced by intravenous injection of rose bengal and irradiation with green light. The following day, the success of the procedure was confirmed by magnetic resonance imaging (MRI). The distance traveled, speed, activity time, and jumps/climbs were observed for 28 days after stroke using MarmoDetector. We also assessed the marmosets' specific movements and postural abnormalities using conventional neurological scores. Results: Magnetic resonance imaging diffusion-weighted and T2-weighted images showed hyperintense signals, indicating cerebral infarction in all three marmosets. MarmoDetector data showed that the both indices immediately after stroke onset and gradually improved over weeks. Neurological scores were the worst immediately after stroke and did not recover to pre-infarction levels during the observation period (28 days). A significant correlation was observed between MarmoDetector data and conventional neurological scores. Conclusion: In this study, we showed that MarmoDetector can quantitatively evaluate behavioral changes in the acute to subacute phases stroke models. This technique can be practical for research on the pathophysiology of ischemic stroke and for the development of new therapeutic methods.

Motor and sensory cortical processing of neural oscillatory activities revealed by human swallowing using intracranial electrodes.

Swallowing is attributed to the orchestration of motor output and sensory input. We hypothesized that swallowing can illustrate differences between motor and sensory neural processing. Eight epileptic participants fitted with intracranial electrodes over the orofacial cortex were asked to swallow a water bolus. Mouth opening and swallowing were treated as motor tasks, whereas water injection was treated as a sensory task. Phase-amplitude coupling between lower-frequency and high γ (HG) bands (75-150 Hz) was investigated. An α (10-16 Hz)-HG coupling appeared before motor-related HG power increases (burst), and a θ (5-9 Hz)-HG coupling appeared during sensory-related HG bursts. The peaks of motor-related coupling were 0.6-0.7 s earlier than that of HG power. The motor-related HG was modulated at the trough of the α oscillation, and the sensory-related HG amplitude was modulated at the peak of the θ oscillation. These contrasting results can help to elucidate the brain's sensory motor functions.

Swallowing-related neural oscillation: an intracranial EEG study.

OBJECTIVE: Swallowing is a unique movement due to the indispensable orchestration of voluntary and involuntary movements. The transition from voluntary to involuntary swallowing is executed within milliseconds. We hypothesized that the underlying neural mechanism of swallowing would be revealed by high-frequency cortical activities. METHODS: Eight epileptic participants fitted with intracranial electrodes over the orofacial cortex were asked to swallow a water bolus and cortical oscillatory changes, including the high γ band (75-150 Hz) and ß band (13-30 Hz), were investigated at the time of mouth opening, water injection, and swallowing. RESULTS: Increases in high γ power associated with mouth opening were observed in the ventrolateral prefrontal cortex (VLPFC) with water injection in the lateral central sulcus and with swallowing in the region along the Sylvian fissure. Mouth opening induced a decrease in ß power, which continued until the completion of swallowing. The high γ burst of activity was focal and specific to swallowing; however, the ß activities were extensive and not specific to swallowing. In the interim between voluntary and involuntary swallowing, swallowing-related high γ power achieved its peak, and subsequently, the power decreased. INTERPRETATION: We demonstrated three distinct activities related to mouth opening, water injection, and swallowing induced at different timings using high γ activities. The peak of high γ power related to swallowing suggests that during voluntary swallowing phases, the cortex is the main driving force for swallowing as opposed to the brain stem.

Autism-associated variants of neuroligin 4X impair synaptogenic activity by various molecular mechanisms.

BACKGROUND: Several genetic alterations, including point mutations and copy number variations in NLGN genes, have been associated with psychiatric disorders, such as autism spectrum disorder (ASD) and X-linked mental retardation (XLMR). NLGN genes encode neuroligin (NL) proteins, which are adhesion molecules that are important for proper synaptic formation and maturation. Previously, we and others found that the expression level of murine NL1 is regulated by proteolytic processing in a synaptic activity-dependent manner. METHODS: In this study, we analyzed the effects of missense variants associated with ASD and XLMR on the metabolism and function of NL4X, a protein which is encoded by the NLGN4X gene and is expressed only in humans, using cultured cells, primary neurons from rodents, and human induced pluripotent stem cell-derived neurons. RESULTS: NL4X was found to undergo proteolytic processing in human neuronal cells. Almost all NL4X variants caused a substantial decrease in the levels of mature NL4X and its synaptogenic activity in a heterologous culture system. Intriguingly, the L593F variant of NL4X accelerated the proteolysis of mature NL4X proteins located on the cell surface. In contrast, other variants decreased the cell-surface trafficking of NL4X. Notably, protease inhibitors as well as chemical chaperones rescued the expression of mature NL4X. LIMITATIONS: Our study did not reveal whether these dysfunctional phenotypes occurred in individuals carrying NLGN4X variant. Moreover, though these pathological mechanisms could be exploited as potential drug targets for ASD, it remains unclear whether these compounds would have beneficial effects on ASD model animals and patients. CONCLUSIONS: These data suggest that reduced amounts of the functional NL4X protein on the cell surface is a common mechanism by which point mutants of the NL4X protein cause psychiatric disorders, although different molecular mechanisms are thought to be involved. Furthermore, these results highlight that the precision medicine approach based on genetic and cell biological analyses is important for the development of therapeutics for psychiatric disorders.

The effects of chronic subthalamic stimulation on nonmotor symptoms in advanced Parkinson's disease, revealed by an online questionnaire program.

BACKGROUND: This study was designed to detect and assess the frequency and severity of nonmotor symptoms (NMSs) in advanced Parkinson's disease (PD) and to investigate the effects of subthalamic nucleus deep brain stimulation (STN-DBS) on NMSs. METHODS: We developed an online PC-based questionnaire program to assess NMSs in PD. Twenty-six PD patients who underwent bilateral STN-DBS were assessed. The NMS questionnaire consisted of 54 NMSs in three categories, based on Witjas et al. (2002). For each NMS, the patients were asked whether or not it was present, whether or not the fluctuating manifestations correlated with the timing of levodopa-induced motor fluctuations, and how severe the NMS was. Patients were assessed by this system before surgery and at the follow-up visit, 3 to 6 months after surgery. At the postoperative assessment, patients were also assessed on preoperative NMSs using recall. RESULTS: The most frequent preoperative NMSs were constipation and visual disorders, while the most frequent postoperative NMSs were difficulty in memorizing and pollakiuria. The ranking of most frequent NMSs changed from before to after surgery. NMSs of drenching sweats, dysphagia, and constipation were significantly ameliorated, while NMSs of dyspnea and slowness of thinking were significantly deteriorated after surgery. The preoperative assessment by postoperative recall gave very different results from that of the preoperative assessment. CONCLUSION: An online questionnaire system to assess NMSs in patients with advanced PD suggested that STN-DBS might influence the frequencies of some kinds of NMSs.

Predictive Factors of Antiparkinsonian Drug Reduction after Subthalamic Stimulation for Parkinson's Disease.

Subthalamic nucleus deep brain stimulation (STN-DBS) improves motor symptoms in individuals with advanced Parkinson's disease (PD) and enables physicians to reduce doses of antiparkinsonian drugs. We investigated possible predictive factors for the successful reduction of antiparkinsonian drug dosage after STN-DBS. We evaluated 33 PD patients who underwent bilateral STN-DBS. We assessed rates of reduction of the levodopa-equivalent daily dose (LEDD) and levodopa daily dose (LDD) by comparing drug doses before vs. 6-months post-surgery. We used correlation coefficients to measure the strength of the relationships between LEDD and LDD reduction rates and preoperative factors including age, disease duration, preoperative LEDD and LDD, unified Parkinson's Disease Rating Scale part-II and -III, levodopa response rate, Mini-Mental State Examination score, dyskinesia score, Hamilton Rating Scale for depression, and the number of non-motor symptoms. The average LEDD and LDD reduction rates were 61.0% and 70.4%, respectively. Of the variables assessed, only the number of psychiatric/cognitive symptoms was significantly correlated with the LEDD reduction rate. No other preoperative factors were correlated with the LEDD or LDD reduction rate. A wide range of preoperative psychiatric and cognitive symptoms may predict the successful reduction of antiparkinsonian drugs after STN-DBS.

Long-Term Implantable, Flexible, and Transparent Neural Interface Based on Ag/Au Core-Shell Nanowires.

Neural interfaces enabling light transmittance rely on optogenetics to control and monitor specific neural activity, thereby facilitating deeper understanding of intractable diseases. This study reports the material strategy underlying an optogenetic neural interface comprising stretchable and transparent conductive tracks and capable of demonstrating high biocompatibility after long-term (5-month) implantation. Ag/Au core-shell nanowires contribute toward improving track performance in terms of stretchability (<60% strain), transparency (<83%), and electrical resistance (15 Ω sq-1 ). The neural interface integrated with gel-coated exterior microelectrodes preserves low impedance (1.1-3.2 Ω cm2 ) in a saline solution over the evaluated 5-month period. Besides the use of efficient conductive materials, surface treatment using antithrombogenic polymer tends to prevent the growth of granulation tissue, thereby facilitating clear monitoring of electrocorticograms (ECoG) in a rodent during chronic implantation. The flexible and transparent neural interface pathologically exhibits noncytotoxicity and low inflammatory response while efficiently recording evoked ECoG in a nonhuman primate via optogenetic stimulation. The proposed highly reliable interface can be employed in multifaceted approaches for translational research based on chronic implants.

MarmoDetector: A novel 3D automated system for the quantitative assessment of marmoset behavior.

BACKGROUND: Callithrix jacchus, generally known as the common marmoset, has recently garnered interest as an experimental primate model for better understanding the basis of human social behavior, architecture and function. Modelling human neurological and psychological diseases in marmosets can enhance the knowledge obtained from rodent research for future pre-clinical studies. Hence, comprehensive and quantitative assessments of marmoset behaviors are crucial. However, systems for monitoring and analyzing marmoset behaviors have yet to be established. NEW METHOD: In this paper, we present a novel multimodal system, MarmoDetector, for the automated 3D analysis of marmoset behavior under freely moving conditions. MarmoDetector allows the quantitative assessment of marmoset behaviors using computerised tracking analysis techniques that are based on a Kinect system equipped with video recordings, infrared images and depth analysis. RESULTS: Using MarmoDetector, we assessed behavioral circadian rhythms continuously over several days in home cages. In addition, MarmoDetector detected acute, transient complex behaviors of alcohol injected marmosets. COMPARISON TO EXISTING METHOD: Compared to 2D recording, MarmoDetector detects activities more precisely and is very sensitive as we could detect behavioral defects specifically induced by alcohol administration. CONCLUSION: MarmoDetector facilitates the rapid and accurate analysis of marmoset behavior and will enhance research on the neural basis of brain disorders.

NrCAM is a marker for substrate-selective activation of ADAM10 in Alzheimer's disease.

The metalloprotease ADAM10 is a drug target in Alzheimer's disease, where it cleaves the amyloid precursor protein (APP) and lowers amyloid-beta. Yet, ADAM10 has additional substrates, which may cause mechanism-based side effects upon therapeutic ADAM10 activation. However, they may also serve-in addition to APP-as biomarkers to monitor ADAM10 activity in patients and to develop APP-selective ADAM10 activators. Our study demonstrates that one such substrate is the neuronal cell adhesion protein NrCAM ADAM10 controlled NrCAM surface levels and regulated neurite outgrowth in vitro in an NrCAM-dependent manner. However, ADAM10 cleavage of NrCAM, in contrast to APP, was not stimulated by the ADAM10 activator acitretin, suggesting that substrate-selective ADAM10 activation may be feasible. Indeed, a whole proteome analysis of human CSF from a phase II clinical trial showed that acitretin, which enhanced APP cleavage by ADAM10, spared most other ADAM10 substrates in brain, including NrCAM Taken together, this study demonstrates an NrCAM-dependent function for ADAM10 in neurite outgrowth and reveals that a substrate-selective, therapeutic ADAM10 activation is possible and may be monitored with NrCAM.

Non-invasive quantification of human swallowing using a simple motion tracking system.

The number of patients with dysphagia is rapidly increasing due to the ageing of the population. Therefore, the importance of objectively assessing swallowing function has received increasing attention. Videofluoroscopy and videoendoscopy are the standard clinical examinations for dysphagia, but these techniques are not suitable for daily use because of their invasiveness. Here, we aimed to develop a novel, non-invasive method for measuring swallowing function using a motion tracking system, the Kinect v2 sensor. Five males and five females with normal swallowing function participated in this study. We defined three mouth-related parameters and two larynx-related parameters and recorded data from 2.5 seconds before to 2.5 seconds after swallowing onset. Changes in mouth-related parameters were observed before swallowing and reached peak values at the time of swallowing. In contrast, larynx-related parameters showed little change before swallowing and reached peak values immediately after swallowing. This simple swallow tracking system (SSTS) successfully quantified the swallowing process from the oral phase to the laryngeal phase. This SSTS is non-invasive, wireless, easy to set up, and simultaneously measures the dynamics of swallowing from the mouth to the larynx. We propose the SSTS for use as a novel and non-invasive swallowing assessment tool in the clinic.

Real-Time Neurofeedback to Modulate ß-Band Power in the Subthalamic Nucleus in Parkinson's Disease Patients.

The ß-band oscillation in the subthalamic nucleus (STN) is a therapeutic target for Parkinson's disease. Previous studies demonstrated that l-DOPA decreases the ß-band (13-30 Hz) oscillations with improvement of motor symptoms. However, it has not been elucidated whether patients with Parkinson's disease are able to control the ß-band oscillation voluntarily. Here, we hypothesized that neurofeedback training to control the ß-band power in the STN induces plastic changes in the STN of individuals with Parkinson's disease. We recorded the signals from STN deep-brain stimulation electrodes during operations to replace implantable pulse generators in eight human patients (3 male) with bilateral electrodes. Four patients were induced to decrease the ß-band power during the feedback training (down-training condition), whereas the other patients were induced to increase (up-training condition). All patients were blinded to their assigned condition. Adjacent contacts that showed the highest ß-band power were selected for the feedback. During the 10 min training, patients were shown a circle whose diameter was controlled by the ß-band power of the selected contacts. Powers in the ß-band during 5 min resting sessions recorded before and after the feedback were compared. In the down-training condition, the ß-band power of the selected contacts decreased significantly after feedback in all four patients (p < 0.05). In contrast, the ß-band power significantly increased after feedback in two of four patients in the up-training condition. Overall, the patients could voluntarily control the ß-band power in STN in the instructed direction (p < 0.05) through neurofeedback.

Near-Infrared Fluorescent Proteins Engineered from Bacterial Phytochromes in Neuroimaging.

Several series of near-infrared (NIR) fluorescent proteins (FPs) were recently engineered from bacterial phytochromes but were not systematically compared in neurons. To fluoresce, NIR FPs utilize an enzymatic derivative of heme, the linear tetrapyrrole biliverdin, as a chromophore whose level in neurons is poorly studied. Here, we evaluated NIR FPs of the iRFP protein family, which were reported to be the brightest in non-neuronal mammalian cells, in primary neuronal culture, in brain slices of mouse and monkey, and in mouse brain in vivo. We applied several fluorescence imaging modes, such as wide-field and confocal one-photon and two-photon microscopy, to compare photochemical and biophysical properties of various iRFPs. The iRFP682 and iRFP670 proteins exhibited the highest brightness and photostability under one-photon and two-photon excitation modes, respectively. All studied iRFPs exhibited efficient binding of the endogenous biliverdin chromophore in cultured neurons and in the mammalian brain and can be readily applied to neuroimaging.

Noninvasive spatiotemporal imaging of neural transmission in the subcortical visual pathway.

Spatiotemporal signal transmission in the human subcortical visual pathway has not been directly demonstrated to date. To delineate this signal transmission noninvasively, we investigated the early latency components between 45 ms (P45m) and 75 ms (N75m) of visually-evoked neuromagnetic fields (VEFs). Four healthy volunteers participated in this study. Hemi-visual field light flash stimuli were delivered a total of 1200 times. Neuromagnetic responses were measured with a 160-channel whole-head gradiometer. In three participants, averaged waveforms indicated a subtle but distinct component that peaked with a very early latency at 44.7 ± 2.1 ms with an initial rise latency of 36.8 ± 3.1 ms, followed by a typical prominent cortical component at 75 ms. The moving equivalent current dipoles continuously estimated from P45m to N75m were first localized in the vicinity of the contralateral lateral geniculate body, then rapidly propagated along the optic radiation and finally terminated in the contralateral calcarine fissure. This result indicates that the source of P45m is the lateral geniculate body and that the early latency components P45m-N75m of the VEFs reflect neural transmission in the optic radiation. This is the first report to noninvasively demonstrate the neurophysiological transmission of visual information through the optic radiation.

High Spatiotemporal Resolution ECoG Recording of Somatosensory Evoked Potentials with Flexible Micro-Electrode Arrays.

Electrocorticogram (ECoG) has great potential as a source signal, especially for clinical BMI. Until recently, ECoG electrodes were commonly used for identifying epileptogenic foci in clinical situations, and such electrodes were low-density and large. Increasing the number and density of recording channels could enable the collection of richer motor/sensory information, and may enhance the precision of decoding and increase opportunities for controlling external devices. Several reports have aimed to increase the number and density of channels. However, few studies have discussed the actual validity of high-density ECoG arrays. In this study, we developed novel high-density flexible ECoG arrays and conducted decoding analyses with monkey somatosensory evoked potentials (SEPs). Using MEMS technology, we made 96-channel Parylene electrode arrays with an inter-electrode distance of 700 µm and recording site area of 350 µm2. The arrays were mainly placed onto the finger representation area in the somatosensory cortex of the macaque, and partially inserted into the central sulcus. With electrical finger stimulation, we successfully recorded and visualized finger SEPs with a high spatiotemporal resolution. We conducted offline analyses in which the stimulated fingers and intensity were predicted from recorded SEPs using a support vector machine. We obtained the following results: (1) Very high accuracy (~98%) was achieved with just a short segment of data (~15 ms from stimulus onset). (2) High accuracy (~96%) was achieved even when only a single channel was used. This result indicated placement optimality for decoding. (3) Higher channel counts generally improved prediction accuracy, but the efficacy was small for predictions with feature vectors that included time-series information. These results suggest that ECoG signals with high spatiotemporal resolution could enable greater decoding precision or external device control.

Protein-retention expansion microscopy of cells and tissues labeled using standard fluorescent proteins and antibodies.

Expansion microscopy (ExM) enables imaging of preserved specimens with nanoscale precision on diffraction-limited instead of specialized super-resolution microscopes. ExM works by physically separating fluorescent probes after anchoring them to a swellable gel. The first ExM method did not result in the retention of native proteins in the gel and relied on custom-made reagents that are not widely available. Here we describe protein retention ExM (proExM), a variant of ExM in which proteins are anchored to the swellable gel, allowing the use of conventional fluorescently labeled antibodies and streptavidin, and fluorescent proteins. We validated and demonstrated the utility of proExM for multicolor super-resolution (∼70 nm) imaging of cells and mammalian tissues on conventional microscopes.

Differences between oral cancer and cancers of the pharynx and larynx on a molecular level.

In order to elucidate differences between oral cancers and cancers of the pharynx and larynx, we investigated the genetic and epigenetic changes in these tumors using molecular biology methods. Methylation of the promoter region of the p16 tumor suppressor gene was examined using methylation-specific polymerase chain reaction in specimens from 47 oral, 39 pharyngeal and 35 laryngeal squamous cell carcinomas. These specimens were also characterized for allelic loss of certain areas of the genome, i.e., 3p22, 9p21 and 17p13 (TP53). The frequency of methylation of the promoter region of the p16 gene in tongue cancers (35.3%) was significantly higher than in pharyngeal (12.8%) and laryngeal cancers (11.4%) (p=0.046 and p=0.039, respectively). The frequency of methylation in tumors of female patients (47.1%) was significantly higher compared to tumors of male patients (15.4%) (p=0.0067). In contrast, the frequency of the loss of heterozygosity (LOH) at 3p21 in pharyngeal cancers (66.7%) was significantly higher than in oral cancers (20.0%) (p=0.0006). The frequencies of LOH at 17p13 in pharyngeal (71.0%) and laryngeal cancers (73.1%) were also significantly higher than in oral cancers (36.1%) (p=0.009 and p=0.009, respectively). Our results indicate that there are marked differences in the frequencies of the hypermethylation of genes and allelic loss between oral cancers and cancer of the pharynx and larynx. Although all of these tumors were diagnosed as squamous cell carcinomas, the process of carcinogenesis may be different in tumors located in various parts of the head and neck. Loss of function of tumor suppressor genes by allelic loss gives rise to tumors in the pharynx and larynx, while loss of function due to methylation of the promoter regions of those genes is related to carcinogenesis in the oral cavity.

Clinical safety of brain magnetic resonance imaging with implanted deep brain stimulation hardware: large case series and review of the literature.

BACKGROUND: Over 75,000 patients have undergone deep brain stimulation (DBS) procedures worldwide. Magnetic resonance imaging (MRI) is an important clinical and research tool in analyzing electrode location, documenting postoperative complications, and investigating novel symptoms in DBS patients. Functional MRI may shed light on the mechanism of action of DBS. MRI safety in DBS patients is therefore an important consideration. METHODS: We report our experience with MRI in patients with implanted DBS hardware and examine the literature for clinical reports on MRI safety with implanted DBS hardware. RESULTS: A total of 262 MRI examinations were performed in 223 patients with intracranial DBS hardware, including 45 in patients with an implanted pulse generator. Only 1 temporary adverse event occurred related to patient agitation and movement during immediate postoperative MR imaging. Agitation resolved after a few hours, and an MRI obtained before implanted pulse generator implantation revealed edema around both electrodes. Over 4000 MRI examinations in patients with implanted DBS hardware have been reported in the literature. Only 4 led to adverse events, including 2 hardware failures, 1 temporary and 1 permanent neurological deficit. Adverse neurological events occurred in a unique set of circumstances where appropriate safety protocols were not followed. MRI guidelines provided by DBS hardware manufacturers are inconsistent and vary among devices. CONCLUSIONS: The importance of MRI in modern medicine places pressure on industry to develop fully MRI-compatible DBS devices. Until then, the literature suggests that, when observing certain precautions, cranial MR images can be obtained with an extremely low risk in patients with implanted DBS hardware.

Feasibility of intraoperative motor-evoked potential monitoring for skull base tumors with a high risk of postoperative motor deterioration.

OBJECTIVE: To establish the validity and utility of motor-evoked potential (MEPs) monitoring for skull base tumor resection, we explored the relationship between MEP monitoring results and postoperative motor function. METHODS: MEPs were successfully monitored during 76 operations in 68 patients with a high risk of motor morbidity. MEP monitoring data were correlated with perioperative clinical motor function. RESULTS: MEPs remained stable in 56 operations (73.7%), and no postoperative motor deterioration was observed. Transient or permanent deterioration of MEPs (<50% of the initial amplitude before surgery) occurred in 20 operations (26.3%). This deterioration was reversible after intervention in seven cases (9.2%). Irreversible deterioration in MEPs was seen in 13 cases (17.1%). In five cases, the final amplitude was greater than 10%. Two of these patients experienced transient loss of MEPs and moderate to severe hemiparesis. Both patients showed full recovery within 6 months after the operation. The other three patients experienced no postoperative worsening of motor function. The final MEP amplitude was less than 10% in the other eight patients, including five with permanent MEP loss. All of these patients experienced severe postoperative motor dysfunction. Recovery of motor function was worse in most participants in this group compared with those in the other groups. CONCLUSION: Intraoperative MEP monitoring is a valid indicator of pyramidal tract pathway function for skull base tumor surgery.

[Chronic and acute hypersensitivity pneumonitis in a dairy farmer and his son].

We encountered a dairy farmer and his son with farmer's lung who had worked on the same farm for 25 years and 5 years, respectively. The son was admitted to our hospital because of cough, sputum, and shortness of breath. Chest computed tomography (CT) on admission revealed diffuse ground-glass opacities in both lung fields. Following admission, the clinical symptoms and radiological findings improved spontaneously without specific treatment. A provocation test (following return to work on the farm) elicited recurrence of the symptoms and radiological findings. He was diagnosed with acute hypersensitivity pneumonitis (HP) based on the clinical findings. After quitting his job, no reccurence was noted. The farther was admitted to our hospital complaining of repeated episodes of cough and high fever. He had been diagnosed with lung fibrosis 10 years previously. Chest CT on admission revealed progression of thin-walled cystic changes over ten years. Following admission, his symptoms improved without medication. However, because he has continued working on the farm, his radiological findings have gradually deteriorated. He was diagnosed with chronic HP based on his clinical features. These cases are suggestive of farmer's lung with familial occurrence, difference between acute HP and chronic HP, and long-term prognosis.