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Background and Objectives With the ongoing development of intraoral surgical treatment and invasive dental treatments such as implants, odontogenic rhinosinusitis (ORS) is on the rise. ORS related to dental implants accounts for 8% to 37% of cases. The purpose of this study is to define the characteristics of patients with ORS related to dental implants. Methods From 2015 to 2019, the medical records of 15 patients who developed maxillary sinus disease after receiving dental implants were retrospectively analyzed among patients who visited the ear nose and throat and dentistry departments. We reviewed the chief complaint, assessment, diagnosis, treatment and prognosis of these patients. Results Of the 15 patients, all were diagnosed with ORS. One patient with a post-operative cheek cyst, 1 with fungal sinusitis, 1 with an inverted papilloma, 1 with chronic rhinosinusitis, and 1 with a radicular cyst were diagnosed after surgery. Endoscopic sinus surgery was performed in 14 patients and 2 patients underwent a combined operation. One patient improved after medical treatment. The follow-up period was about 8.6 months. No recurrence was found in any of the patients. Conclusion If an implant problem is suspected based on history-taking and physical examination, active consultation with dentistry is needed to diagnose ORS.

Abstract Background Lateral sinus augmentation is necessary when the residual bone height is insufficient in the posterior maxilla. Immediate implant placement following tooth extraction with lateral sinus augmentation will shorten the number of operations and treatment time. Purpose To evaluate radiologic and clinical results for at least 1 year after loading in patients who underwent tooth extraction, implant placement, and lateral sinus augmentation at the same time. Materials and methods We retrospectively evaluated 35 implants placed in 25 patients. Preoperative and postoperative CBCT were compared and analyzed for residual bone height (RBH) and increased bone height (IBH), the initial torque value (ITV), and the implant stability quotient (ISQ). A comparative evaluation was performed between a 1-stage (non-submerged) group and a 2-stage (submerged) group. After loading for at least 1 year, clinical and radiological evaluations were performed to evaluate the survival rate. Results One of the 35 implants failed in osseointegration, and the remaining 34 showed successful results. The failure-free survival rate at 1 year was 97.06% (95% CI, 91.38-100.0%). The RBH ranged from 3.1 to 9.6 mm (mean, 5.62 ± 1.68 mm), and the IBH ranged from 3 to 15.3 mm (mean, 8.87 ± 2.74 mm). Among the RBH, ITV, ISQ, treatment period, final bone height, and failure evaluation by stage of implant placement, only ISQ showed statistical significance between the groups (p < .001). A comparison of RBH, ITV, and ISQ, regardless of group, showed that each value tended to increase, but there were no statistically significant differences. Conclusions Immediate implant placement following tooth extraction with simultaneous lateral sinus augmentation is considered reliable even though the procedures had been performed at the same time.

Background/purpose: Maxillary sinus lift without grafting is an alternative procedure that is used to lower the risk of infection and facilitate the surgical procedure. The objective of this study was to evaluate the tenting effect of the dental implant by measuring the amount and morphology of bone formation around it. Material and methods: 49 implants were placed in 26 patients by maxillary sinus lift without grafting. Radiographic images were taken preoperatively and at 6 months postoperatively and used to evaluate the height of the residual bone, the width of the maxillary sinus, the amount of bone formation, and the adjacent tooth. Results: The most common type of bone formed around the implant, as seen in 23 cases, was the same height as the apex of the implant; in 11 cases, it was 0–2 mm above the apex of the implant, and in 7 cases, 2 mm or more. Meanwhile, 5 cases showed defects. The tent type of bone formation, which showed more bone formation at the implant apex than in the surrounding bone, was overwhelmingly the most common. (80.4%) The amount of bone formation increased in proportion to the difference between the residual bone height and the implant length. (P

Abstract Background Individual and organizational factors correlate with perceived barriers to error reporting. Understanding medication administration errors (MAEs) reduces confusion about error definitions, raises perceptions of MAEs, and allows healthcare providers to report perceived and identified errors more frequently. Therefore, an emphasis must be placed on medication competence, including medication administration knowledge and decision-making. It can be helpful to utilize an organizational approach, such as collaboration between nurses and physicians, but this type of approach is difficult to establish and maintain because patient-safety culture starts at the highest levels of the healthcare organization. This study aimed to examine the canonical correlations of an individual self-efficacy/bottom-up organizational approach variable set with perceived barriers to reporting MAEs among nurses. Methods We surveyed 218 staff nurses in Korea. The measurement tools included a questionnaire on knowledge of high-alert medication, nursing decision-making, nurse-physician collaboration satisfaction, and barriers to reporting MAEs. Descriptive statistics, t-tests, analysis of variance (ANOVA), Pearson’s correlation coefficient, and canonical correlations were used to analyze results. Results Two canonical variables were significant. The first variate indicated that less knowledge about medication administration (− 0.83) and a higher perception of nurse-physician collaboration (0.42) were related to higher disagreement over medication error (0.64). The second variate showed that intuitive clinical decision-making (− 0.57) and a higher perception of nurse-physician collaboration (0.84) were related to lower perceived barriers to reporting MAEs. Conclusions Enhancing positive collaboration among healthcare professionals and promoting analytic decision-making supported by sufficient knowledge could facilitate MAE reporting by nurses. In the clinical phase, providing medication administration education and improving collaboration may reduce disagreement about the occurrence of errors and facilitate MAE reporting. In the policy phase, developing an evidence-based reporting system that informs analytic decision-making may reduce the perceived barriers to MAE reporting.

The forced alignment of magnetic moments leads to a large change in entropy, which can be used to reduce the temperature of a material. Here, the authors show that this magnetic cooling effect occurs on a femtosecond time scale in cobalt–platinum nano-multilayers.

Abstract Background The purpose of this study is to analyze changes in mandibular width and frontal view ramus inclination using cone beam CT in patients with skeletal class III malocclusion who underwent BSSRO, with the removal of bone interference between segments. Methods For all 20 subjects, cone-beam CT imaging was performed prior to surgery (T1), immediately post-surgery (T2), and 6 months after surgery (T3). Reorientation was performed using R2GATE software (MegaGen, Seoul, Korea). The gonion and antegonial notch were used as reference points in the sagittal view, and the most lateral point of the condyle head was used as the reference point in the frontal view. All measurements were recorded in the frontal view. Results Inter-gonial width decreased by 2.64 mm at T3-T2 (P

Abstract Protocadherin 19 (Pcdh19) is a homophilic cell adhesion molecule and is involved in a variety of neuronal functions. Here, we tested whether Pcdh19 has a regulatory role in axon guidance using the developing Xenopus retinotectal system. We performed targeted microinjections of a translation blocking antisense morpholino oligonucleotide to knock down the expression of Pcdh19 selectively in the central nervous system. Knocking down Pcdh19 expression resulted in navigational errors of retinal ganglion cell (RGC) axons specifically at the optic chiasm. Instead of projecting to the contralateral optic tectum, RGC axons in the Pcdh19-depleted embryo misprojected ipsilaterally. Although incorrectly delivered into the ipsilateral brain hemisphere, these axons correctly reached the optic tectum. These data suggest that Pcdh19 has a critical role in preventing mixing of RGC axons originating from the opposite eyes at the optic chiasm, highlighting the importance of cell adhesion in bundling of RGC axons.

The aim of the present study was to delineate and evaluate the feasibility of a web-based error reporting system using the International Classification of Patient Safety (ICPS) in a Korean university hospital. Method: Seventy-five staff nurses were encouraged to complete error reports on the website during an 8-week period from December, 2008 to February, 2009. To solve the research question, χ2 test, t test and descriptive statistics were used. Results: Of the 75 enrolled participants, 36% (n = 27) completed at least one web-based report during the 8-week period. There were no significant mean differences in demographics and job-related characteristics between the two groups (compliance group vs. non-compliance group). Error reports were distinguished between those observed that involved others (77%) and those that involved themselves (23%). The majority of incident types involved medications (60.9%), in particular their administration (77.6% of the medication errors). About 90% of events caused “no harm and no change in monitoring” or “no harm, but monitoring initiated or increased”. About 45% percent of errors increased in required resource allocation for patients (13.1/10,000 patient-days) and 33.9% of errors augmented to a “formal complaint” (9.8/10,000 patient-days). Conclusion: The web-based error reporting system using ICPS proved to be an easy, feasible system for hospitals in Korea. This system will be helpful for inducing general agreement upon errors within clinical nursing practice and bring more attention to any errors made or near misses. Also, it will be able to ameliorate the punitive culture for errors and transform error reporting into a habit for healthcare providers.

Abstract Anti-tuberculosis (AT) medications, including isoniazid (INH), can cause drug-induced liver injury (DILI), but the underlying mechanism remains unclear. In this study, we aimed to identify genetic factors that may increase the susceptibility of individuals to AT-DILI and to examine genetic interactions that may lead to isoniazid (INH)-induced hepatotoxicity. We performed a targeted sequencing analysis of 380 pharmacogenes in a discovery cohort of 112 patients (35 AT-DILI patients and 77 controls) receiving AT treatment for active tuberculosis. Pharmacogenome-wide association analysis was also conducted using 1048 population controls (Korea1K). NAT2 and ATP7B genotypes were analyzed in a replication cohort of 165 patients (37 AT-DILI patients and 128 controls) to validate the effects of both risk genotypes. NAT2 ultraslow acetylators (UAs) were found to have a greater risk of AT-DILI than other genotypes (odds ratio [OR] 5.6 [95% confidence interval; 2.5–13.2], P = 7.2 × 10−6). The presence of ATP7B gene 832R/R homozygosity (rs1061472) was found to co-occur with NAT2 UA in AT-DILI patients (P = 0.017) and to amplify the risk in NAT2 UA (OR 32.5 [4.5–1423], P = 7.5 × 10−6). In vitro experiments using human liver-derived cell lines (HepG2 and SNU387 cells) revealed toxic synergism between INH and Cu, which were strongly augmented in cells with defective NAT2 and ATP7B activity, leading to increased mitochondrial reactive oxygen species generation, mitochondrial dysfunction, DNA damage, and apoptosis. These findings link the co-occurrence of ATP7B and NAT2 genotypes to the risk of INH-induced hepatotoxicity, providing novel mechanistic insight into individual AT-DILI susceptibility. Yoon et al. showed that individuals who carry NAT2 UAs and ATP7B 832R/R genotypes are at increased risk of developing isoniazid hepatotoxicity, primarily due to the increased synergistic toxicity between isoniazid and copper, which exacerbates mitochondrial dysfunction-related apoptosis.

Background Post-transplant diabetes mellitus (PTDM) is one of the most significant complications after transplantation. Patients with end-stage liver diseases requiring transplantation are prone to sarcopenia, but the association between sarcopenia and PTDM remains to be elucidated. We aimed to investigate the effect of postoperative muscle mass loss on PTDM development. Methods A total of 500 patients who underwent liver transplantation at a tertiary care hospital between 2005 and 2020 were included. Skeletal muscle area at the level of the L3–L5 vertebrae was measured using computed tomography scans performed before and 1 year after the transplantation. The associations between the change in the muscle area after the transplantation and the incidence of PTDM was investigated using a Cox proportional hazard model. Results During the follow-up period (median, 4.9 years), PTDM occurred in 165 patients (33%). The muscle mass loss was greater in patients who developed PTDM than in those without PTDM. Muscle depletion significantly increased risk of developing PTDM after adjustment for other confounding factors (hazard ratio, 1.50; 95% confidence interval, 1.23 to 1.84; P=0.001). Of the 357 subjects who had muscle mass loss, 124 (34.7%) developed PTDM, whereas of the 143 patients in the muscle mass maintenance group, 41 (28.7%) developed PTDM. The cumulative incidence of PTDM was significantly higher in patients with muscle loss than in patients without muscle loss (P=0.034). Conclusion Muscle depletion after liver transplantation is associated with increased risk of PTDM development.

There is still need for representative models of intrahepatic cholangiocarcinoma (ICC) subtypes. Here, the authors develop organoids for two recently suggested ICC subtypes and identify distinct transcriptional profiles and potential therapeutic targets.

Abstract Tubby mice exhibit hearing impairment due to the loss of stereocilin from the tip regions that connect the tallest stereocilia of the outer hair cells (OHCs) to the tectorial membrane. Stereocilin is an essential stereociliary protein in the OHCs, the mutation of which in humans causes autosomal recessive non-syndromic deafness. Map1a is a modifier of tubby hearing (moth1), and its wild-type allele, rather than the moth1 allele from the C57BL/6 J strain, restores stereocilin localization to the stereocilia and rescues the hearing impairment of tubby mice. The mechanism by which MAP1A accomplishes this is unclear, partly due to ambiguity regarding whether the tubby mutation is a true null. We therefore generated Tub-null (Tub −/−) mice by deleting exon 3 and found that they exhibit hearing impairment like that of tubby mice, suggesting the tubby mutation is a loss-of-function mutation with regard to hearing. When we crossed Tub −/− mice with AKR mice that have wild-type Map1a alleles, we found that wild-type MAP1A restores stereocilin localization to the tips of stereocilia and rescues hearing impairment. These data suggest MAP1A does not require interaction with tubby protein in maintaining stereocilin at the tips of stereocilia and that OHCs use two independent molecules—MAP1A and tubby—to doubly ensure proper stereocilin localization.

Abstract Herein, an unprecedented report is presented on the incorporation of size-dependent gold nanoparticles (AuNPs) with polyvinylpyrrolidone (PVP) capping into a conventional hole transport layer, poly(3,4-ethylenedioxythiophene):poly(styrenesulfonate) (PEDOT:PSS). The hole transport layer blocks ion-diffusion/migration in methylammonium-lead-bromide (MAPbBr3)-based perovskite light-emitting diodes (PeLEDs) as a modified interlayer. The PVP-capped 90 nm AuNP device exhibited a seven-fold increase in efficiency (1.5%) as compared to the device without AuNPs (0.22%), where the device lifetime was also improved by 17-fold. This advancement is ascribed to the far-field scattering of AuNPs, modified work function and carrier trapping/detrapping. The improvement in device lifetime is attributed to PVP-capping of AuNPs which prevents indium diffusion into the perovskite layer and surface ion migration into PEDOT:PSS through the formation of induced electric dipole. The results also indicate that using large AuNPs (> 90 nm) reduces exciton recombination because of the trapping of excess charge carriers due to the large surface area.

Abstract In the CNS, pericytes are important for maintaining the blood–brain barrier (BBB) and for controlling blood flow. Recently, several methods were suggested for the differentiation of human pluripotent stem cells (hPSCs) into brain mural cells, specifically pericytes or vascular smooth muscle cells (vSMCs). Unfortunately, identifying the pericytes from among such hPSC-derived mural cells has been challenging. This is due both to the lack of pericyte-specific markers and to the loss of defining anatomical information inherent to culture conditions. We therefore asked whether NeuroTrace 500/525, a newly developed dye that shows cell-specific uptake into pericytes in the mouse brain, can help identify human induced pluripotent stem cell (hiPSC)-derived brain pericyte-like cells. First, we found that NeuroTrace 500/525 specifically stains primary cultured human brain pericytes, confirming its specificity in vitro. Second, we found that NeuroTrace 500/525 specifically labels hiPSC-derived pericyte-like cells, but not endothelial cells or vSMCs derived from the same hiPSCs. Last, we found that neuroectoderm-derived vSMCs, which have pericyte-like features, also take up NeuroTrace 500/525. These data indicate NeuroTrace 500/525 is useful for identifying pericyte-like cells among hiPSC-derived brain mural cells.

Abstract Background The purpose of this retrospective study was to evaluate the postoperative change in the position and stability of the mandibular condyle after bilateral sagittal split ramus osteotomy (BSSRO) and BSSRO with distal segmental ostectomy (DSO) in patients with facial asymmetry using 3D computed tomography. Methods The condyles of the patient diagnosed with facial asymmetry were divided into the deviated side (DS) and the non-deviated side (NDS). Group I, which was treated with BSSRO only, and Group II, which additionally received DSO along with BSSRO, were superimposed on the condyle using the pre-and postoperative 3D CT. The amount of condylar change in anteroposterior displacement, mediolateral displacement, and rotation was measured. The clinical symptoms of temporomandibular joint were also evaluated before and after surgery for each patient. Results Between Groups I and II, there was no statistically significant difference in the anteroposterior condylar position on both DS and NDS. And also, there was no statistical difference between the two groups in the mediolateral change on DS but, statistically significant difference on NDS. The change in the rotation of the condyle was observed to rotate inward from both condylar heads of Groups I and II, and a statistically significant difference was observed between the two groups on both DS and NDS. Moreover, no difference in clinical temporomandibular joint symptoms was observed after surgery in each DS and NDS condyle of the two groups. Conclusions As a result of analyzing the condylar position change of the group treated with BSSRO alone and the group treated with BSSRO and DSO in patients with facial asymmetry, there were statistically significant differences in the mediolateral displacement of NDS and the condyle rotation of NDS and DS. However, the anteroposterior condylar position did not show any difference in the bilateral condyles. In addition, since worsening clinical symptoms of bilateral temporomandibular joint were not observed before and after surgery in both groups, it is concluded that it is not necessary to accompany DSO in patients with facial asymmetry (minimum 3 mm, maximum 7 mm).

A transparent twistable and stretchable MoO3/Au/MoO3 electrode is demonstrated by Choi et al. for organic light-emitting diodes. The device fabricated on thin elastomer shows enhanced EQE with minimum efficiency roll-off owing to the improved charge injection and heat dissipation from the substrate.

Bone metabolism: Regulation by brain protein A protein that is highly expressed in brain cells plays a vital role in maintaining balanced energy expenditure and bone health. Recent research indicates that protein activity within brain cells can directly influence energy and bone metabolism. Disruption to these proteins may therefore be associated with obesity and osteoporosis. In experiments on mice, Seok Jun Moon at Yonsei University College of Dentistry in Seoul, South Korea and co-workers found that the protein calsyntenin-3 is expressed at high levels in brain cells. Mice lacking the protein had reduced body mass and growth rate, increased energy expenditure, and lower overall bone mass. This was true regardless of their diet, suggesting they were resistant to diet-induced obesity. The team believe calsyntenin-3 is one of several key brain-based regulators of energy and bone metabolism.

Abstract Clozapine is thought to induce obsessive compulsive symptoms (OCS) in schizophrenic patients. However, because OCS are often comorbid with schizophrenia regardless of clozapine treatment, it remains unclear whether clozapine can generate OCS de novo. Thus, it has been difficult to establish a causal link between clozapine and OCS in human studies. To address this question, we asked whether chronic treatment with clozapine can induce obsessive compulsive disorder (OCD)-like behavior in mice. We injected mice with long-term continuous release pellets embedded with clozapine four times at 60-day intervals and then monitored the mice for signs of OCD-like behavior up to 40 wk. of age. We found clozapine increases grooming behavior as early as 30 wk. of age. We also investigated the effect clozapine on grooming behavior in Sapap3 knockout (KO) mice, which are a well-known animal model of OCD. In Sapap3 heterozygous KO mice, clozapine increases grooming behavior much earlier than in wild-type mice, suggesting a clozapine-OCD gene interaction. Fluoxetine, which is often used in the treatment of OCS and OCD, reduced the grooming behavior induced by clozapine. These data demonstrate that chronic clozapine treatment can generate OCD-like behavior in mice and support the hypothesis that clozapine produces de novo OCS regardless of schizophrenia status.

Abstract Increasing evidence suggests there is a relationship between cognitive impairment and metabolic dysfunction. Diabetes is a chronic disease, and metabolic factors affecting brain metabolisms, such as serum glucose, insulin, and glucagon, are altered according to disease progression. In our previous study, we applied hyperpolarized [1-13C] pyruvate magnetic resonance spectroscopy in prediabetic mice after feeding them a 60% high-fat diet (HFD) for 6 months. Ultimately, we detected significantly increased [1-13C]lactate conversion in the whole brain and an almost five-fold increased [1-13C]lactate/pyruvate ratio in the hippocampal region. In the present study, we induced diabetes in mice by injecting streptozotocin and feeding them an HFD for 6 months. Unlike in prediabetic mice, [1-13C]lactate conversion in the diabetic mice did not differ from that in the control group, but [1-13C]lactate/total 13C ratio showed an almost 1.4-fold increase in the hippocampal region. We measured the amount of the lactate and mRNA levels of glucose transporters from isolated hippocampus and cortex samples. In the hippocampus, significantly decreased GLUT1 mRNA levels and increased lactate were detected, suggesting an inconsistency between glucose and pyruvate metabolism. Pyruvate can be produced from oxaloacetate as well as glucose. We investigated ATP citrate lyase (ACLY) because it cleaves citrate into oxaloacetate and acetyl CoA. Phosphorylated ACLY (Ser455), the active form, was increased in both hippocampus and cortex samples of mice injected with streptozotocin and fed an HFD. Also, phosphorylated ACLY/total ACLY showed a positive correlation with lactate amount in the hippocampus. Our results suggest that the brain has different responses to diabetic progression, but, in the hippocampus, maintains metabolic alteration toward increasing lactate production from the prediabetic to the diabetic stage. We suggest that ACLY-mediated pyruvate be used to support lactate levels in the hippocampus in cases of limited glucose availability.

Purpose To investigate the relationship between carotid arterial calcium score (CarACS) and silent cerebrovascular lesions in patients with obstructive sleep apnea (OSA). Materials and Methods This study involved retrospective evaluation of 60 OSA patients who underwent both upper airway CT and brain MRI. Using polysomnography, several indicators, including apnea index (AI), were used to evaluate the relationship between OSA and silent cerebrovascular lesions. The CarACS was quantified on CT imaging using the modified Agatston method. Silent cerebrovascular lesions were evaluated on brain MRI by grading periventricular hyperintensity (PVH). Various clinical characteristics, including age, were analyzed in each patient. Results The number of patients per PVH grade 0, 1, 2, 3, and 4 was 26 (43.3%), 14 (23.3%), 14 (23.3%), 4 (6.7%), and 2 (3.3%), respectively. The mean age, hypertension, smoking status, AI, and CarACS were significantly different among PVH groups (Ps < 0.05). In univariate analysis, the presence of carotid arterial calcification (β = 0.483, p < 0.01), CarACS (β = 0.482, p < 0.01), and age (β = 0.360, p < 0.01) showed a significant association with PVH grade. The mean AI and lowest O2 saturation had statistically weak associations with PVH grade (β = 0.267, p < 0.01; β = -0.219, p < 0.14, respectively). In multivariate analysis, CarACS was the only factor affecting PVH grade (p < 0.04). Conclusion CarACS is associated with the severity of silent cerebrovascular lesions. Therefore, additional analysis of CarACS in OSA patients may provide more information on their cerebrovascular status.

Abstract Mutations in protocadherin 19 (PCDH19), which is on the X-chromosome, cause the brain disease Epilepsy in Females with Mental Retardation (EFMR). EFMR is also often associated with autism-like symptoms. In mice and humans, epilepsy occurs only in heterozygous females who have a mixture of PCDH19 wild-type (WT) and mutant cells caused by random X-inactivation; it does not occur in hemizygous PCDH19 mutant males. This unique inheritance pattern strongly suggests the underlying disease mechanism operates via interference between WT and mutant cells rather than being a result of complete loss of PCDH19 functions. Although it remains unclear whether the other symptoms of EFMR also conform to this unique genotype-phenotype relationship, PCDH19 mutant males were recently reported to demonstrate autism-like symptoms. We, therefore, used a Pcdh19 knockout (KO) mouse model to ask whether a complete lack of PCDH19 causes autism-like behaviors. Consistent with the autism observed in EFMR females, we found Pcdh19 heterozygous KO female mice (with mosaic expression of PCDH19) show defects in sociability in the 3-chamber test. Surprisingly, hemizygous Pcdh19 KO male mice (without any PCDH19 expression) exhibit impaired sociability in the 3-chamber test and reduced social interactions in the reciprocal social interaction test. We also observed that, compared to WT mice, mutant mice display more repetitive behaviors, including self-grooming and rearing. These findings indicate that hemizygous Pcdh19 KO male mice show autism-like phenotypes.

The co-facially stacked dyes on semiconductor films serve as an alternative model to elucidate the photo-driven exciton dynamics occurring in a molecular assembly. In this study, we report the unique emission properties of coumarin dye adsorbed on the surface of the semiconductor film, measured by ultrafast time-resolved fluorescence. When a rigid coumarin derivative, 7-hydroxycoumarin-3-carboxylic acid (OHCCA), is anchored on the Al2O3 film, the dye manifests dual emissions from the two lowest excited states. Various anchoring modes of a carboxylic acid group on the Al2O3 surface are invoked to account for the unusual emission process. Additionally, we identified characteristic transition dipole interactions in the well-stacked dye aggregates, which leads to discernible excitonic splitting in the electronic transitions. Femtosecond time-resolved fluorescence reveals that the excimer formation in the aggregate occurs with the time constant of 550 fs. Picosecond time-resolved emission spectra confirm the subsequent structural relaxations of the nascent excimer. The enhanced transition dipole via the electronic coupling between OHCCA and metal oxide can be responsible for the dual emission and the ultrafast excimer formation.

Abstract Genetic and pharmacological manipulations targeting metabotropic glutamate receptor 5 (mGluR5) affect performance in behavioural paradigms that depend on cognitive flexibility. Many of these studies involved exposing mice to highly stressful conditions including electric foot shocks or water immersion and forced swimming. Because mGluR5 is also implicated in resilience and stress responses, however, apparent impairments in inhibitory learning may have been an artifact of manipulation-induced changes in affective state. To address this, we present here a characterization of cognitive flexibility in mGluR5 knockout (KO) mice conducted with a rodent touchscreen cognitive assessment apparatus in which the animals experience significantly less stress. Our results indicate a significant reversal learning impairment relative to wild-type (WT) controls in the two-choice Visual Discrimination-Reversal (VDR) paradigm. Upon further analysis, we found that this deficit is primarily driven by a prolonged period of perseveration in the early phase of reversal. We also observed a similar perseveration phenotype in the KO mice in the Extinction (EXT) paradigm. In addition, mGluR5 KO mice show higher breakpoints in the touchscreen Progressive Ratio (PR) and altered decision making in the Effort-related Choice (ERC) tasks. Interestingly, this impairment in PR is an additional manifestation of an increased propensity to perseverate on the emission of relatively simplistic behavioural outputs. Together, these findings suggest that under conditions of low stress, mGluR5 KO mice exhibit a pronounced perseverative phenotype that blunts cognitive flexibility.

Abstract Higher dietary intakes of saturated fatty acid increase the risk of developing Alzheimer’s disease and dementia, and even in people without diabetes higher glucose levels may be a risk factor for dementia. The mechanisms causing neuronal dysfunction and dementia by consuming high-fat diet degrading the integrity of the blood-brain barrier (BBB) has been suggested but are not yet fully understood, and metabolic state of the brain by this type of insult is still veiled. The objective of this study was to investigate the effect of high-fat diet on the brain metabolism by a multimodal imaging method using the hyperpolarizedcarbon 13 (13C)-pyruvate magnetic resonance (MR) spectroscopy and dynamic contrast-enhanced MR imaging in conjunction with the biochemical assay and the behavior test in a mouse model fed high-fat diet (HFD). In mice were fed 60% HFD for 6 months, hyperpolarized [1-13C] pyruvate MR spectroscopy showed decreased perfusion (p

Acute myocardial infarction (AMI) is lethal and causes myocardial necrosis via time-dependent ischemia due to prolonged occlusion of the infarct-related artery. No effective therapy or potential therapeutic targets can prevent myocardial ischemia/reperfusion (I/R) injury. Targeted temperature management (TTM) may reduce peri-infarct regions by inhibiting the extracellular release of high mobility group box-1 (HMGB1) as a primary mediator of the innate immune response. We used a rat left anterior descending (LAD) coronary artery ligation model to determine if TTM at 33°C and 36°C had similar myocardial protective effects. Rats were divided into sham, LAD I/R+37°C normothermia, LAD I/R+33°C TTM, and LAD I/R+36°C TTM groups (n = 5 per group). To verify the cardioprotective effect of TTM by specifically inhibiting HMGB1, rats were assigned to sham, LAD I/R, and LAD I/R after pre-treatment with glycyrrhizin (known as a pharmacological inhibitor of HMGB1) groups (n = 5 per group). Different target temperatures of 33°C and 36°C caused equivalent reductions in infarct volume after myocardial I/R, inhibited the extracellular release of HMGB1 from infarct tissue, and suppressed the expression of inflammatory cytokines from peri-infarct regions. TTM at 33°C and 36°C significantly attenuated the elevation of cardiac troponin, a sensitive and specific marker of heart muscle damage, after injury. Similarly, glycyrrhizin alleviated myocardial damage by suppressing the extracellular release of HMGB1. TTM at 33°C and 36°C had equivalent myocardial protective effects by similar inhibiting HMGB1 release against myocardial I/R injury. This is the first study to suggest that a target core temperature of 36°C is applicable for cardioprotection.

Abstract Reliable and reproducible assessment of animal learning and behavior is a central aim of basic and translational neuroscience research. Recent developments in automated operant chamber technology have led to the possibility of universal standard protocols, in addition to increased translational potential, reliability and accuracy. However, the impact of regional and national differences in the supplies of available reinforcers in this system on behavioural performance and inter-laboratory variability is an unknown and at present uncontrolled variable. Therefore, we aimed to identify which constituent(s) of the reward determines reinforcer strength to enable improved standardization of this parameter across laboratories. Male C57BL/6 mice were examined in the touchscreen-based fixed ratio (FR) and progressive ratio (PR) schedules, reinforced with different kinds of milk-based reinforcers to directly compare the incentive values of plain milk (PM, high-calorie: high-fat/low-sugar), strawberry-flavored milk (SM, high-calorie: low-fat/high-sugar), and semi-skimmed low-fat milk (LM, low-calorie: low-fat/low-sugar) on the basis of differences in caloric content, sugar/fat content, and flavor. Use of a higher caloric content reward was effective in increasing operant training acquisition rate. Total trial number completed in FR and breakpoint in PR were higher using the two isocaloric milk products (PM and SM) than the lower caloric LM, with comparable outcomes between PM and SM conditions, suggesting that total caloric content determines reward strength. Analysis of within-session changes in response rate revealed that overall outputs in FR and PR primarily depend on the response rate at the initial phase of a session, which itself was dependent on reinforcer caloric content. Interestingly, the rate of satiation, indicated by decay in response rate within a FR session, was highest when reinforced with SM, suggesting a rapid satiating effect of sugar. The key contribution of reward caloric content to operant performance was confirmed in a multi-laboratory study using the touchscreen 5-choice serial reaction time task (5-CSRTT) reinforced by two isocaloric milk-based liquid rewards with different countries of origin, which yielded consistent performance parameters across sites. Our results indicate that milk-based liquid reinforcer standardization can be facilitated by matching caloric content across laboratories despite regional or national differences in other non-caloric aspects of the reinforcers.

Cilia are highly specialized antennae-like cellular organelles. Inositol polyphosphate 5-phosphatase E (INPP5E) converts PI(4,5)P2 into PI4P and is required for proper ciliary function. Although Inpp5e mutations are associated with ciliopathies in humans and mice, the precise molecular role INPP5E plays in cilia remains unclear. Here, we report that Drosophila INPP5E (dINPP5E) regulates ciliary protein trafficking by controlling the phosphoinositide composition of ciliary membranes. Mutations in dInpp5e lead to hearing deficits due to the mislocalization of dTULP and mechanotransduction channels, Inactive and NOMPC, in chordotonal cilia. Both loss of dINPP5E and ectopic expression of the phosphatidylinositol-4-phosphate 5-kinase Skittles increase PI(4,5)P2 levels in the ciliary base. The fact that Skittles expression phenocopies the dInpp5e mutants confirms a central role for PI(4,5)P2 in the regulation of dTULP, Inactive, and NOMPC localization. These data suggest that the spatial localization and levels of PI(4,5)P2 in ciliary membranes are important regulators of ciliary trafficking and function.

A series of dopant-free D-π-A structural hole-transporting materials (HTMs), named as SGT-460, SGT-461, and SGT-462, incorporating a planner-type triazatruxene (TAT) core, thieno[3,2-b]indole (TI) π-bridge and three different acceptors, 3-ethylthiazolidine-2,4-dione (ED), 3-(dicyano methylidene)indan-1-one (DI), and malononitrile (MN), were designed and synthesized for application in perovskite solar cells (PrSCs). The effect of three acceptor units in star-shaped D-π-A structured dopant-free HTMs on the photophysical and electrochemical properties and the photovoltaic performance were investigated compared to the reference HTM of 2,2′,7,7′-tetrakis[N,N-di(4-methoxyphenyl)amino]-9,9′-spirobifluorene (spiro-OMeTAD). Their highest occupied molecular orbital (HOMO) energy levels were positioned for efficient hole extraction from a MAPbCl3−xIx layer (5.43 eV). The hole mobility values of the HTMs without dopants were determined to be 7.59 × 10−5 cm2 V−1 s−1, 5.13 × 10−4 cm2 V−1 s−1, and 7.61 × 10−4 cm2 V−1 s−1 for SGT-460-, SGT-461-, and SGT-462-based films. The glass transition temperature of all HTMs showed higher than that of the spiro-OMeTAD. As a result, the molecular engineering of a planer donor core, π-bridge, and end-capped acceptor led to good hole mobility, yielding 11.76% efficiency from SGT-462-based PrSCs, and it provides a useful insight into the synthesis of the next-generation of HTMs for PrSC application.

We investigated the effects of environmental enrichment (EE) on the function of transplanted adipose stem cells (ASCs) and the combined effect of EE and ASC transplantation on neurobehavioral function in an animal model of chronic hypoxic-ischemic (HI) brain injury. HI brain damage was induced in 7-day-old mice by unilateral carotid artery ligation and exposure to hypoxia (8% O 2 for 90 min). At 6 weeks of age, the mice were randomly injected with either ASCs or PBS into the striatum and were randomly assigned to either EE or standard cages (SC), comprising ASC-EE ( n = 18), ASC-SC ( n = 19), PBS-EE ( n = 12), PBS-SC ( n = 17), and untreated controls ( n = 23). Rotarod, forelimb-use asymmetry, and grip strength tests were performed to evaluate neurobehavioral function. The fate of transplanted cells and the levels of endogenous neurogenesis, astrocyte activation, and paracrine factors were also measured. As a result, EE and ASC transplantation synergistically improved rotarod latency, forelimb-use asymmetry, and grip strength compared to those of the other groups. The number of engrafted ASCs and βIII-tubulin + neurons derived from the transplanted ASCs was significantly higher in mice in EE than those in SC. EE and ASC transplantation also synergistically increased BrdU + βIII-tubulin + neurons, GFAP + astrocytic density, and fibroblast growth factor 2 (FGF2) level but not the level of CS-56 + glial scarring in the striatum. In conclusion, EE and ASC transplantation synergistically improved neurobehavioral functions. The underlying mechanisms of this synergism included enhanced repair processes such as higher engraftment of the transplanted ASCs, increased endogenous neurogenesis and astrocytic activation coupled with upregulation of FGF2.

Mechanically gated ion channels convert sound into an electrical signal for the sense of hearing. In Drosophila melanogaster, several transient receptor potential (TRP) channels have been implicated to be involved in this process. TRPN (NompC) and TRPV (Inactive) channels are localized in the distal and proximal ciliary zones of auditory receptor neurons, respectively. This segregated ciliary localization suggests distinct roles in auditory transduction. However, the regulation of this localization is not fully understood. Here we show that the Drosophila Tubby homolog, King tubby (hereafter called dTULP) regulates ciliary localization of TRPs. dTULP-deficient flies show uncoordinated movement and complete loss of sound-evoked action potentials. Inactive and NompC are mislocalized in the cilia of auditory receptor neurons in the dTulp mutants, indicating that dTULP is required for proper cilia membrane protein localization. This is the first demonstration that dTULP regulates TRP channel localization in cilia, and suggests that dTULP is a protein that regulates ciliary neurosensory functions.