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The culture filtrate extract of golden bootleg (Phaeolepiota aurea) exhibited strong antifungal activity in a bioassay for volatile compounds. Purification of active compounds through silica gel column chromatography and high performance liquid chromatography isolated two compounds, 1 and 2, with molecular weights of 234 and 259, respectively, as confirmed by mass spectrometry. Nuclear magnetic resonance analysis identified these compounds as new sesquiterpenoids with the α-bourbonene skeleton. Both compounds had an aldehyde group, while 2 possessed a cyanohydrin group. These compounds were named phaeolep aldehydes A (1) and B (2). Phaeolep aldehyde A inhibited hyphae elongation of Penicillium citrinum, Aspergillus niger, Cladosporium sphaerospermum, and Alternaria brassicicola at 10 ppm, but did not exhibit any antibacterial activity. In contrast, phaeolep aldehyde B exhibited potent inhibitory effects on the spore germination of Pe. citrinum, achieving 58.2% inhibition at 0.25 ppm, outperforming phaeolep aldehyde A, which exhibited 25.7% inhibition at 10 ppm., (© The Author(s) 2024. Published by Oxford University Press on behalf of Japan Society for Bioscience, Biotechnology, and Agrochemistry.)

Red complex bacteria ( Porphyromonas gingivalis , Treponema denticola , and Tannerella forsythia ) have high virulence in periodontal disease. In the present study, we aimed to elucidate the detailed symbiotic relationships between the red complex and other oral bacteria in older Japanese individuals. Polymerase chain reaction was performed using dental plaque from 116 subjects and specific primers for ten periodontal pathogens. The detection rate of Prevotella intermedia and Capnocytophaga sputigena was significantly higher in P. gingivalis -positive subjects than in P. gingivalis -negative subjects ( p < 0.05). The detection rate of Campylobacter rectus , Prevotella nigrescens , Capnocytophaga ochracea , and Eikenella corrodens was significantly higher in T. forsythia -positive subjects than in T. forsythia -negative subjects ( p < 0.01). In a comprehensive analysis of oral microbiomes, three red complex species-positive subjects had significantly higher α-diversity than only P. gingivalis -positive subjects ( p < 0.05) and had significantly lower β-diversity than only T. forsythia -positive subjects ( p < 0.01). In the taxonomy analysis, Porphyromonas was significantly higher in three red complex species-positive subjects than in only P. gingivalis -positive and only T. forsythia -positive subjects ( p < 0.01). These results suggest that each red complex species forms a unique oral microbiome and individuals positive for all red complex bacteria may harbor oral bacteria that confer a significant advantage in developing periodontal disease.

Purpose: This prospective cohort study examined the effects of the number of present and functional teeth on mortality among older Japanese adults requiring nursing care in an environment of comprehensive oral hygiene and nutritional management., Methods: The study included 174 older adults (mean age: 84.4 ± 8.3 years; male/female: 49/125) in need of support or long-term care, who resided in either a local specialized healthcare facility or their own homes, and received daily oral hygiene and nutritional support at facilities in Okayama, Japan. The initial clinical oral examination along with assessment of general physical condition and nursing environment of the participants were performed in July 2013 and followed up for one year., Results: All-cause mortality occurred in 28 (mean age: 88.7 ±13.4 years; male/female: 6 /22) individuals during the follow-up period. Cox proportional hazard analysis indicated that older age, low performance in activities of daily living (Barthel Index <40), and underweight status (body mass index <18.5) were significant risk factors for mortality. The number of present and functional teeth were not found to be significant risk factors for mortality., Conclusions: During the one-year follow-up period, the number of present and functional teeth did not have a significant impact on mortality among older Japanese adults requiring nursing care in a well-managed environment of oral hygiene and nutritional status.

Purpose: This study aimed to evaluate the reliability and validity of a four-item questionnaire using a face rating scale to measure dental trait anxiety (DTA), dental trait fear (DTF), dental state anxiety (DSA), and dental state fear (DSF)., Materials and Methods: Participants were consecutively selected from patients undergoing scaling (S-group; n = 47) and implant placement (I-group; n = 25). The S-group completed the questionnaire both before initial and second scaling, whereas the I-group responded on the pre-surgery day (Pre-day), the day of implant placement (Imp-day), and the day of suture removal (Post-day)., Results: The reliability in the S-group was evaluated using the test-retest method, showing a weighted kappa value of DTA, 0.61; DTF, 0.46; DSA, 0.67; DSF, 0.52. Criterion-related validity, assessed using the State-Trait Anxiety Inventory's trait anxiety and state anxiety, revealed positive correlations between trait anxiety and DTA/DTF (DTA, ρ = 0.30; DTF, ρ = 0.27, ρ: correlation coefficient) and between state anxiety and all four items (DTA, ρ = 0.41; DTF, ρ = 0.32; DSA, ρ = 0.25; DSF, ρ = 0.25). Known-group validity was assessed using the initial data and Imp-day data from the S-group and I-group, respectively, revealing significantly higher DSA and DSF scores in the I-group than in the S-group. Responsiveness was gauged using I-group data, showing significantly lower DSA and DSF scores on post-day compared to other days., Conclusion: The newly developed questionnaire has acceptable reliability and validity for clinical use, suggesting its usefulness for research on dental anxiety and fear and for providing patient-specific dental care., (© 2024 The Korean Academy of Prosthodontics.)

Background: In older patients with progressive neurodegeneration, replacing fixed implant-supported prostheses (FIP) with implant overdentures (IOD) has been proposed to prevent future mucosal injury and create an oral environment that is easier for caregivers to clean. However, there have been no reports on the progress after replacing FIP with IOD. In this report, we present the progress of an older patient with Parkinson's disease in whom FIP was replaced with IOD., Case Presentation: An 81-year-old male patient with Parkinson's disease presented to our outpatient clinic with bruxism and crossbites. FIPs, with five Brånemark system implants, were placed in the bilateral lower molars. The FIP was replaced with an IOD with two locator attachments to create an oral environment that was easier for caregivers to clean and allow easy recovery of masticatory function if residual teeth were fractured in the care environment. As his systemic condition deteriorated, treatment was changed from outpatient to in-home visits. During dental care visits, professional oral cleaning and denture repair were continued, and good nutritional status was maintained. However, the patient developed cholecystitis and was hospitalized. During hospitalization, gastrostomy was performed because he developed aspiration pneumonia. After discharge from the hospital, the patient remained in bed all day and could not wear an IOD, resulting in buccal mucosa ulceration due to abrasion of the locator abutment. We decided to replace the abutment with cover screws; however, not all the implants could sleep submucosally. Although regular oral cleaning was resumed, new ulcers developed even when cover screws were installed. Additionally, swelling and drainage were observed at the peri-implant mucosal site where peri-implantitis had once occurred during an outpatient visit. The patient was readmitted to the hospital for a urinary tract infection, and subsequent visits were abandoned., Conclusions: By replacing FIP with IOD in an older patient with Parkinson's disease, we addressed a barrier to caregiver-provided oral management. The removable prosthesis facilitated smooth oral care by caregivers and functional recovery in the event of trouble with residual teeth. However, it could not completely avoid the recurrence of buccal mucosal ulcers or peri-implantitis., (© 2024. The Author(s).)

Objective: Collaboration among medical facilities is crucial to deliver comprehensive epilepsy care to a diverse and large population of people with epilepsy. We conducted a survey among medical facilities of various sizes throughout Japan to investigate the status of epilepsy care delivery, functioning, and referral., Methods: With the cooperation of the Japan Neurological Society (1428 facilities), Japanese Neurosurgical Society (3489 specialists), and Epilepsy Care Network (948 facilities), a questionnaire was mailed to 5865 locations that provide epilepsy care in Japan. The facilities were classified into clinics (19 beds or less), small hospitals (SH, 20-199 beds), large hospitals (LH, 200 beds or more), and epilepsy centers (EC). The status of epilepsy care delivery, functioning, and referral was compared among the four groups., Results: Responses were received from 1014 facilities (17.3% response rate). After excluding duplicate responses, 957 facilities were analyzed (394 clinics, 149 SH, 388 LH, 26 EC). EC responded "manageable" in more items of epilepsy care functions in general, especially those related to epilepsy surgery, compared to LH with similar facility size. However, EC responded being less manageable in psychiatric service (61.5%), dietary therapy (46.2%), rehabilitation (53.8%), and patient employment support (61.5%). The percentage of facilities that responded "always able to refer" was highest in clinics (67.6%) and the lowest in EC (40%). Referral difficulties were more commonly encountered in EC, and less common in clinics. In EC, the most common reason for inability to refer was patient or family refusal (64%)., Significance: We have clarified the epilepsy care delivery, functioning, and referral in facilities of various sizes in Japan. This study highlights the issues of downward referral and patient stagnation in EC, which have not received much attention., Plain Language Summary: A nationwide survey of healthcare facilities ranging in size from small clinics to large hospitals in Japan examined medical care delivery and patient referrals related to epilepsy. Compared to other facilities, epilepsy centers provided a variety of medical services to people with epilepsy but were inadequate in addressing psychiatric symptoms, providing dietary therapy, rehabilitation, and patient employment support. Referrals from epilepsy centers to other medical facilities were often refused by patients and their families. This results in patient crowding at epilepsy centers., (© 2023 The Authors. Epilepsia Open published by Wiley Periodicals LLC on behalf of International League Against Epilepsy.)

Purpose: To compare the accuracy of the tooth morphology fusion (TMF) digital technique and customized impression transfer coping (conventional) technique when transferring the morphology of a provisional crown to a definitive screw-retained implant-supported crown., Methods: Six cases of partial edentulism (one anterior and five posterior) treated with oral implant placement in our clinic for the loss of three or fewer teeth in the maxilla or mandible between April 2017 and September 2018 were included. After implant placement and re-entry surgery, provisional restorations were made and adjusted to obtain the ideal morphology. Two definitive restorations were constructed by transferring the complete morphology of the provisional restorations, including the subgingival contour, using the TMF digital and conventional techniques. Three sets of surface morphological data were obtained using a desktop scanner. The three-dimensional total discrepancy volume (TDV) between the provisional restoration (reference) and the two definitive restorations was digitally measured by overlapping the surface data of the stone cast using the Boolean operation. Each TDV ratio (%) was calculated by dividing the TDV by the volume of provisional restoration. The median TDV ratios for TMF and conventional techniques were compared using the Wilcoxon signed-rank test., Results: The median TDV ratio between provisional and definitive restorations constructed using the TMF digital technique (8.05%) was significantly lower than that obtained using the conventional technique (13.56%, P < 0.05)., Conclusions: In this preliminary intervention study, the TMF digital technique was more accurate than the conventional technique for the transfer of morphology from provisional to definitive prosthesis.

Objective: The authors perform thorough, noninvasive presurgical evaluations for intractable epilepsy at their center and avoid unnecessary intracranial EEG when possible. The purpose of this study was to clarify the appropriateness of their lesion-oriented surgical strategy for localized focal cortical dysplasia (FCD) type II., Methods: Fifty-one patients with pathologically proven localized FCD type II who were followed for at least 1 year after surgery were included. Patients with FCD type II with lobar or multilobar distribution were excluded. The results of presurgical evaluations, including thin-slice 3-T MRI, FDG-PET, and ictal SPECT, as well as surgical procedures and postoperative seizure and functional outcomes, were examined retrospectively., Results: MRI was positive in 46 (90%) of 51 patients, and FDG-PET revealed localized hypo- or hypermetabolism in 47 (92%) of 51 patients. Ictal SPECT revealed concordant hyperperfusion in 37 of 42 patients examined. Intracranial EEG was used in only 13 patients (25%), including 5 with negative MRI results and 4 with subtle MRI findings. Of the 15 patients with FCD in the vicinity of eloquent (sensorimotor and language) areas, intracranial EEG was used in 4. Lesionectomy was performed in all 51 patients. Intraoperative electrocorticography (ECoG) was performed in 8 patients, but the findings were not used to tailor the extent of resection. Postoperative seizure outcomes were Engel class I in 47 patients (92%) and Ia in 45 (88%). In the 15 patients with FCD in the vicinity of eloquent areas, 13 (87%) achieved a class I outcome. Predictive factors for favorable seizure outcome were complete resection of the MRI lesion (p = 0.006) and frontal lobe surgery (p = 0.012). Postoperative neurological deficits were noted in only 4 (27%) of 15 patients with FCD in the vicinity of eloquent areas. All 5 MRI-negative patients achieved an Engel class I outcome., Conclusions: In most of the patients with localized FCD type II, MRI and/or FDG-PET detected the localized abnormality. Lesionectomy without intracranial EEG led to seizure freedom in most cases. Even when lesions were in the vicinity of eloquent areas, seizure and functional outcomes were favorable. Intraoperative ECoG may thus be unnecessary. Complete resection of the lesion is essential for favorable seizure outcome in MRI-positive patients. In MRI-negative patients, surgery with intracranial EEG guided by FDG-PET provided seizure-free outcomes.

Purpose: The aim of this study is to compare dental implant placement accuracy of three surgical guide fabrication methods: single (SCT) and double computed tomography (DCT), and a newly developed modified SCT (MSCT) scan method., Methods: A total of 183 cases (183 surgical guides, and 485 implants) of static-guide-assisted implant placement surgery using the SCT, DCT, or MSCT methods in a dental clinic were included in the study. Three-dimensional (3D) deviations (mm) at the entry and tip of the implant body between preoperative simulation and actual placement were measured as surrogate endpoints of implant placement accuracy. The following survey details were collected from medical records and CT data: sex, age at implant placement surgery, surgical guide fabrication method, number of remaining teeth, implant length, implant location, alveolar bone quality, and bone surface inclination at implant placement site in preoperative simulation, etc. Risk factors for reducing implant placement accuracy were investigated using generalized estimating equations., Results: The SCT and DCT methods (odds ratios [ORs] vs. MSCT method: 1.438, 1.178, respectively), posterior location (OR: 1.114), bone surface buccolingual inclination (OR: 0.997), and age at implant placement surgery (OR: 0.995) were significant risk factors for larger 3D deviation at the entry; the SCT (OR: 1.361) and DCT methods (OR: 1.418), posterior location (OR: 1.190), implant length (OR: 1.051), and age at implant placement surgery (OR: 0.995) were significant risk factors for larger 3D deviation at the tip of the implant body., Conclusions: Implant placement accuracy was better using the MSCT method compared to the SCT and DCT methods., (© 2023. The Author(s).)

Mahjong is one of the most popular Chinese tile games played in Japan. Mahjong-related seizures (MRS) are rare praxis-induced seizures. We identified three patients with MRS from February 2000 to February 2021. All cases were men, with a middle-age onset, generalized convulsive seizures, and lack of non-provoked, myoclonic, and absence seizures. All patients had no or non-specific neuroimaging or electroencephalogram abnormalities. They did not have features linked to idiopathic generalized epilepsy. All patients were seizure-free after behavioral adjustments, although one patient required anti-seizure medication and avoided long duration games. These changes may help other patients with MRS continue playing Mahjong.

Objective: Periictal water drinking (PIWD), which is a rare seizure-related autonomic behavior, has been reported in temporal lobe epilepsy (TLE) but only rarely in extra-TLE. Additionally, the lateralizing value of PIWD is controversial. We aimed to clarify the occurrence and lateralizing value of PIWD in patients with focal epilepsy., Methods: This retrospective study included 240 focal epilepsy patients aged >10 years with a favorable postoperative seizure outcome (Engel class I). PIWD was defined as water drinking behavior during a seizure or within 2 min in the postictal phase. The occurrence of PIWD documented on video-electroencephalogram monitoring was assessed. The lateralizing value of PIWD was analyzed among patients whose language dominant hemisphere was identified., Results: Twenty-three (9.5%) patients exhibited PIWD. PIWD occurred more frequently in frontal lobe epilepsy (FLE; eight of 41 patients, 19.5%) than in TLE (15 of 188 patients, 8%). The occurrence of PIWD was significantly different between FLE and extra-FLE (P = 0.035), with a low positive predictive value (34.8%). In FLE with PIWD, all but one patient underwent resective surgery involving the medial frontal lobe. In 194 patients whose language dominant hemisphere was determined, the lateralizing value of PIWD in FLE and TLE showed no statistical significance (P = 0.69 and P = 0.27, respectively)., Significance: Periictal water drinking occurred more often in FLE than TLE. Thus, PIWD might not be a specific periictal symptom in TLE. There was no evidence for the lateralizing value of PIWD in FLE and TLE. These findings can provide useful clinical clues for preoperative evaluations to estimate the epileptogenic zone based on seizure semiology and allow for a better understanding of pathophysiological insights into PIWD., (© 2023 The Authors. Epilepsia Open published by Wiley Periodicals LLC on behalf of International League Against Epilepsy.)

Purpose: The aim of this study was to introduce rating criteria to evaluate student performance in a newly developed, digital wax-up preclinical program for computer-aided design (CAD) of full-coverage crowns and preliminarily investigate the reliability and internal consistency of the rating system., Materials and Methods: This study, conducted in 2017, enrolled 47 fifth-year dental students of Okayama University Dental School. Digital wax-up training included a fundamental practice using computer graphics (CG), multipurpose CAD software programs, and an advanced practice to execute a digital wax-up of the right mandibular second molar (#47). Each student's digital wax-up work (stereolithography data) was evaluated by two instructors using seven qualitative criteria. The total qualitative score (0-90) of the criteria was calculated. The total volumetric discrepancy between each student's digital wax-up work and a reference prepared by an instructor was automatically measured by the CAD software. The inter-rater reliability of each criterion was analyzed using a weighted kappa index. The relationship between the total volume discrepancy and the total qualitative score was analyzed using Spearman's correlation., Results: The weighted kappa values for the seven qualitative criteria ranged from 0.62 - 0.93. The total qualitative score and the total volumetric discrepancy were negatively correlated (ρ = -0.27, P = .09, respectively); however, this was not statistically significant., Conclusion: The established qualitative criteria to evaluate students' work showed sufficiently high inter-rater reliability; however, the digitally measured volumetric discrepancy could not sufficiently predict the total qualitative score., (© 2022 The Korean Academy of Prosthodontics.)

Objective: The impact of the coronavirus disease 2019 (COVID-19) pandemic on epilepsy care across Japan was investigated by conducting a multicenter retrospective cohort study., Methods: This study included monthly data on the frequency of (1) visits by outpatients with epilepsy, (2) outpatient electroencephalography (EEG) studies, (3) telemedicine for epilepsy, (4) admissions for epilepsy, (5) EEG monitoring, and (6) epilepsy surgery in epilepsy centers and clinics across Japan between January 2019 and December 2020. We defined the primary outcome as epilepsy-center-specific monthly data divided by the 12-month average in 2019 for each facility. We determined whether the COVID-19 pandemic-related factors (such as year [2019 or 2020], COVID-19 cases in each prefecture in the previous month, and the state of emergency) were independently associated with these outcomes., Results: In 2020, the frequency of outpatient EEG studies (-10.7%, p<0.001) and cases with telemedicine (+2,608%, p=0.031) were affected. The number of COVID-19 cases was an independent associated factor for epilepsy admission (-3.75*10 -3 % per case, p<0.001) and EEG monitoring (-3.81*10 -3 % per case, p = 0.004). Further, the state of emergency was an independent factor associated with outpatient with epilepsy (-11.9%, p<0.001), outpatient EEG (-32.3%, p<0.001), telemedicine for epilepsy (+12,915%, p<0.001), epilepsy admissions (-35.3%; p<0.001), EEG monitoring (-24.7%: p<0.001), and epilepsy surgery (-50.3%, p<0.001)., Significance: We demonstrated the significant impact that the COVID-19 pandemic had on epilepsy care. These results support those of previous studies and clarify the effect size of each pandemic-related factor on epilepsy care., (This article is protected by copyright. All rights reserved.)

Purpose: Myelin oligodendrocyte glycoprotein (MOG) antibodies (Abs) are associated with various central nervous system demyelinating disorders. Recently, they were detected in cerebral cortical encephalitis (CCE), which often causes seizures. We performed a literature review to elucidate the electroclinical features of CCE. In addition to the published cases, we describe a new, illustrative case of MOG-Ab-associated CCE (MOG-CCE) with multifocal seizures documented by video electroencephalograph (EEG)., Methods: We searched PubMed with the keywords "[MOG] AND [encephalitis]" and reviewed relevant articles. The articles included reports of patients with CCE (as demonstrated by magnetic resonance imaging) and serum MOG Ab positivity. Cases were excluded if no epileptic seizures were reported or if details of the seizures were unavailable., Results: Our literature review identified 34 patients with MOG-CCE. An analysis of these 34 cases and the new case showed that 20 patients were male (57.1%), and the median age at presentation was 23 years (range, 6 to 46 years). Focal to bilateral tonic-clonic seizure was the most common seizure type, followed by focal motor seizure in the face or an arm or leg. EEG findings were available for 26 patients. Interictal epileptiform discharges (IEDs) and ictal EEG patterns were seen in 10 (38.5%) and 5 (19.2%) patients, respectively. Focal EEG abnormalities, including slow waves and IEDs, were observed in the central, parietal, occipital, or posterior temporal region., Conclusion: MOG-CCE has distinctive electroclinical features that differ from those of other autoimmune encephalitides. Careful electroclinical analysis of seizures can be helpful for diagnosing MOG-CCE., (Copyright © 2022 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.)

Purpose: We aimed to determine root caries annual incidence (RCAI) and root caries annual progression (RCAP) and risk factors for them among older people requiring nursing care., Methods: The target population comprised 186 dentate individuals aged ≥ 65 years who required nursing care while living in nursing homes (NHs) or their own homes (OHs) in Okayama, Japan. Survey items included presence/absence and severity of root caries, age, sex, living environment (NH or OH), the Clinical Dementia Rating, and the Barthel Index (BI). Baseline surveys were conducted from 2015 to 2017; subjects were followed up for one year. RCAI and RCAP per tooth and per person were calculated, and risk factors for them were identified using generalized estimating equations., Results: In total, 104 individuals (mean age: 82.0 ± 12.4 years) completed the follow-up survey. RCAIs per tooth and per person were 14.6% (173/1188) and 59.6% (62/104), respectively. RCAP per tooth was 22.5% (51/227 teeth with root caries at baseline). Significant risk factors for RCAI were living environment (OH, odds ratio [OR]: 2.14), sex (male, OR: 1.84), clasped tooth (OR: 1.82), and older age (OR: 1.05) at baseline. Significant risk factors for RCAP were sex (male, OR: 5.20), regular dental checkup (OR: 2.74), and high BI score (OR: 1.02) at baseline., Conclusion: At one-year follow-up, 59.6% of the subjects developed at least one root caries. Risk factors for RCAI were living environment (OH), male, clasped tooth, and older age, whereas those for RCAP were male, regular dental checkup, and high BI score.

Lysocin E is a lipopeptide with antibiotic activity against methicillin-resistant Staphylococcus aureus. For unclear reasons, the antibacterial activity of lysocin E in a mouse systemic infection model is higher than expected from in vitro results, and the in vitro activity is enhanced by addition of bovine serum. Here, we confirm that serum from various species, including humans, increases lysocin E antimicrobial activity, and identify apolipoprotein A-I (ApoA-I) as an enhancing factor. ApoA-I increases the antibacterial activity of lysocin E when added in vitro, and the antibiotic displays reduced activity in ApoA-I gene knockout mice. Binding of ApoA-I to lysocin E is enhanced by lipid II, a cell-wall synthesis precursor found in the bacterial membrane. Thus, the antimicrobial activity of lysocin E is potentiated through interactions with host serum proteins and microbial components., (© 2021. The Author(s).)

Patients: The patient was a 55-year-old woman with left upper molar free-end edentulism and 9 full cast metal crowns in her mouth. Three three-dimensional (3D) images were superimposed: a computed tomography (CT) image with the patient wearing the CT-matching template (CTMT) with six glass ceramic markers, which hardly generate any artifacts, on the template surface, and oral plaster model surfaces with and without CTMTs. Metal artifacts were automatically removed by a Boolean operation identifying unrealistic images outside the oral plaster model surface. After the preoperative simulation, fully guided oral implant surgery was performed. Two implant bodies were placed in the left upper edentulism. The placement errors calculated by comparing the preoperative simulation and actual implant placement were then assessed by a software program using the 3D-CT bone morphology as a reference. The 3D deviations between the preoperative simulation and actual placement at the entry of the implant body were a maximum 0.48 mm and minimum 0.26 mm. Those at the tip of the implant body were a maximum 0.56 mm and a minimum 0.25 mm., Discussion: In this case, the maximum 3D deviations at the entry and tip section were less than in previous studies using double CT., Conclusions: Accurate image fusion utilizing CTMT with new reference markers was possible for a patient with many metal restorations. Using a surgical guide manufactured by the new matching methodology (modified single CT scan method), implant placement deviation can be minimized in patients with many metal restorations.

A 49-year-old woman with hepatic failure owing to alcoholic liver cirrhosis went into a deep coma. Her serum ammonia concentration was elevated at 436 μg/dl, and she had a generalized convulsion. Electroencephalogram and cerebrospinal fluid examination did not suggest encephalitis and epilepsy. Hyperammonemia may be occur because of generalized convulsions; however, it can spontaneously resolve if the convulsions are stopped. If hyperammonemia is the primary cause of generalized convulsion, the serum ammonia concentration will remain high until the cause is eliminated. However, despite stopping the convulsions, her ammonia concentration remained high. Diffusion-weighted brain MRI revealed symmetric high-intensity lesions in the frontal, temporal, and parietal cortices, especially the cingulate and insular cortices of the bilateral hemispheres. These findings were in line with those of previous reports that revealed symmetric cortical lesions, including cingulate and insula cortices that are distinctive in acute hyperammonemic encephalopathy. Therefore, we diagnosed that the coma, generalized convulsions, and abnormal brain MRI findings were caused by acute hyperammonemic encephalopathy.

Lysocin E, a 37-membered natural depsipeptide, induces rapid bacteriolysis in methicillin-resistant Staphylococcus aureus via a unique menaquinone-dependent mechanism, presenting a promising therapeutic lead. Despite the great medical importance, exploring the potential utility of its derivatives as new platform structures for antibiotic development has remained a significant challenge. Here, we report a high-throughput strategy that enabled the preparation of thousands of analogues of lysocin E and large-scale structure-activity relationship analyses. We integrate 26-step total synthesis of 2401 cyclic peptides, tandem mass spectrometry-sequencing, and two microscale activity assays to identify 23 candidate compounds. Re-synthesis of these candidates shows that 11 of them (A1-A11) exhibit antimicrobial activity superior or comparable to that of lysocin E, and that lysocin E and A1-A11 share L-Leu-6 and L-Ile-11. Therefore, the present strategy allows us to efficiently decipher biologically crucial residues and identify potentially useful agents for the treatment of infectious diseases.

WAP-8294A2 (lotilibcin, 1) is a potent antibiotic with superior in vivo efficacy to vancomycin against methicillin-resistant Staphylococcus aureus (MRSA). Despite the great medical importance, its molecular mode of action remains unknown. Here we report the total synthesis of complex macrocyclic peptide 1 comprised of 12 amino acids with a β-hydroxy fatty-acid chain, and its deoxy analogue 2. A full solid-phase synthesis of 1 and 2 enabled their rapid assembly and the first detailed investigation of their functions. Compounds 1 and 2 were equipotent against various strains of Gram-positive bacteria including MRSA. We present evidence that the antimicrobial activities of 1 and 2 are due to lysis of the bacterial membrane, and their membrane-disrupting effects depend on the presence of menaquinone, an essential factor for the bacterial respiratory chain. The established synthetic routes and the menaquinone-targeting mechanisms provide valuable information for designing and developing new antibiotics based on their structures.