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Genetic factors significantly affect the pathogenesis of psychiatric disorders. However, the specific pathogenic mechanisms underlying these effects are not fully understood. Recent extensive genomic studies have implicated the protocadherin-related 15 (PCDH15) gene in the onset of psychiatric disorders, such as bipolar disorder (BD). To further investigate the pathogenesis of these psychiatric disorders, we developed a mouse model lacking Pcdh15. Notably, although PCDH15 is primarily identified as the causative gene of Usher syndrome, which presents with visual and auditory impairments, our mice with Pcdh15 homozygous deletion (Pcdh15-null) did not exhibit observable structural abnormalities in either the retina or the inner ear. The Pcdh15-null mice showed very high levels of spontaneous motor activity which was too disturbed to perform standard behavioral testing. However, the Pcdh15 heterozygous deletion mice (Pcdh15-het) exhibited enhanced spontaneous locomotor activity, reduced prepulse inhibition, and diminished cliff avoidance behavior. These observations agreed with the symptoms observed in patients with various psychiatric disorders and several mouse models of psychiatric diseases. Specifically, the hyperactivity may mirror the manic episodes in BD. To obtain a more physiological, long-term quantification of the hyperactive phenotype, we implanted nano tag® sensor chips in the animals, to enable the continuous monitoring of both activity and body temperature. During the light-off period, Pcdh15-null exhibited elevated activity and body temperature compared with wild-type (WT) mice. However, we observed a decreased body temperature during the light-on period. Comprehensive brain activity was visualized using c-Fos mapping, which was assessed during the activity and temperature peak and trough. There was a stark contrast between the distribution of c-Fos expression in Pcdh15-null and WT brains during both the light-on and light-off periods. These results provide valuable insights into the neural basis of the behavioral and thermal characteristics of Pcdh15-deletion mice. Therefore, Pcdh15-deletion mice can be a novel model for BD with mania and other psychiatric disorders, with a strong genetic component that satisfies both construct and surface validity.

The overarching goal of the third scientific oral health symposium was to introduce the concept of a learning health system to the dental community and to identify and discuss cutting-edge research and strategies using data for improving the quality of dental care and patient safety. Conference participants included clinically active dentists, dental researchers, quality improvement experts, informaticians, insurers, EHR vendors/developers, and members of dental professional organizations and dental service organizations. This report summarizes the main outputs of the third annual OpenWide conference held in Houston, Texas, on October 12, 2022, as an affiliated meeting of the American Dental Association (ADA) 2022 annual conference.

BACKGROUND: Dental Patient Reported Outcomes (PROs) relate to a dental patients subjective experience of their oral health. How practitioners and patients value PROs influences their successful use in practice. METHODS: Semi-structured interviews were conducted with 22 practitioners and 32 patients who provided feedback on using a mobile health (mHealth) platform to collect the pain experience after dental procedures. A themes analysis was conducted to identify implementation barriers and facilitators. RESULTS: Five themes were uncovered: (1) Sense of Better Care. (2) Tailored Follow-up based on the dental procedure and patients pain experience. (3) Effective Messaging and Alerts. (4) Usable Digital Platform. (5) Routine mHealth Integration. CONCLUSION: Frequent automated and preferably tailored follow-up messages using an mHealth platform provided a positive care experience for patients, while providers felt it saved them time and effort. Patients thought that the mHealth questionnaires were well-developed and of appropriate length. The mHealth platform itself was perceived as user-friendly by users, and most would like to continue using it. PRACTICAL IMPLICATIONS: Patients are prepared to use mobile phones to report their pain experience after dental procedures. Practitioners will be able to close the post-operative communication gap with their patients, with little interruption of their workflow.

Abstract Background Low-grade systemic inflammation may be a key player in the immune activation that has been reported for mental health deterioration. We hypothesised that elevated serum levels of inflammatory cytokines increase neuroinflammation and exacerbate depressive symptoms. Methods The participants were part of a cohort study for whom data was available for both 2015 and 2019. In 2015, blood samples were collected from 232 participants. Their depressive symptoms were assessed both 2015 and 2019 using the Centre for Epidemiologic Studies Depression Scale (CES-D) (n = 33). The multiplex immunoassay system (Luminex® 200) was used to measure the serum concentrations of IL-6, IL-10, IL-12, IL-17A and TNFα. Data were analysed using linear models with the level of significance considered to be p

Background/Aims Dilation of the tract before stent deployment is a challenging step in endoscopic ultrasound-guided pancreatic duct drainage (EUS-PDD). In this study, we examined the effectiveness and safety of a novel spiral dilator, Tornus ES (Asahi Intec), for EUS-PDD. Methods This was a retrospective, single-arm, observational study at Aichi Cancer Center Hospital. The punctured tract was dilated using a Tornus ES dilator in all EUS-PDD cases. Our primary endpoint was the technical success rate of initial tract dilation. Technical success was defined as successful fistula dilation using a Tornus ES followed by successful stent insertion. Secondary endpoints were procedure times and early adverse events. Results A total of 12 patients were included between December 2021 and March 2023. EUS-PDD was performed in 11 patients for post-pancreaticoduodenectomy anastomotic strictures and one patient with pancreatitis with duodenal perforation. The technical success rates of stent insertion and fistula dilation using a Tornus ES dilator was 100%. The median procedure time was 24 minutes. No remarkable adverse events related to the procedure were observed, apart from fever, which occurred in 2 patients. Conclusions Tract dilation in EUS-PDD using a Tornus ES is effective and safe.

Background/Aims This study aimed to examine the synergistic effect of independent risk factors on post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis (PEP). Methods This multicenter retrospective study included 1,273 patients with native papillae who underwent ERCP for bile duct stones in Japan. Independent PEP risk factors were identified using univariate and multivariate analyses. Significant risk factors for PEP in the multivariate analysis were included in the final analysis to examine the synergistic effect of independent risk factors for PEP. Results PEP occurred in 45 of 1,273 patients (3.5%). Three factors including difficult cannulation ≥10 minutes, pancreatic injection, and normal serum bilirubin level were included in the final analysis. The incidences of PEP in patients with zero, one, two, and three factors were 0.5% (2/388), 1.9% (9/465), 6.0% (17/285), and 12.6% (17/135), respectively. With increasing risk factors for PEP, the incidence of PEP significantly increased (1 factor vs. 2 factors, p=0.006; 2 factors vs. 3 factors, p=0.033). Conclusions As the number of risk factors for PEP increases, the risk of PEP may not be additive; however, it may multiply. Thus, aggressive prophylaxis for PEP is strongly recommended in patients with multiple risk factors.

OBJECTIVE: This study assessed contributing factors associated with dental adverse events (AEs). METHODS: Seven electronic health record-based triggers were deployed identifying potential AEs at 2 dental institutions. From 4106 flagged charts, 2 reviewers examined 439 charts selected randomly to identify and classify AEs using our dental AE type and severity classification systems. Based on information captured in the electronic health record, we analyzed harmful AEs to assess potential contributing factors; harmful AEs were defined as those that resulted in temporary moderate to severe harm, required hospitalization, or resulted in permanent moderate to severe harm. We classified potential contributing factors according to (1) who was involved (person), (2) what were they doing (tasks), (3) what tools/technologies were they using (tools/technologies), (4) where did the event take place (environment), (5) what organizational conditions contributed to the event? (organization), (6) patient (including parents), and (7) professional-professional collaboration. A blinded panel of dental experts conducted a second review to confirm the presence of an AE. RESULTS: Fifty-nine cases had 1 or more harmful AEs. Pain occurred most frequently (27.1%), followed by nerve injury (16.9%), hard tissue injury (15.2%), and soft tissue injury (15.2%). Forty percent of the cases were classified as temporary not moderate to severe harm. Person (training, supervision, and fatigue) was the most common contributing factor (31.5%), followed by patient (noncompliance, unsafe practices at home, low health literacy, 17.1%), and professional-professional collaboration (15.3%). CONCLUSIONS: Pain was the most common harmful AE identified. Person, patient, and professional-professional collaboration were the most frequently assessed factors associated with harmful AEs.

Understanding kidney disease relies on defining the complexity of cell types and states, their associated molecular profiles and interactions within tissue neighbourhoods1. Here we applied multiple single-cell and single-nucleus assays (>400,000 nuclei or cells) and spatial imaging technologies to a broad spectrum of healthy reference kidneys (45 donors) and diseased kidneys (48 patients). This has provided a high-resolution cellular atlas of 51 main cell types, which include rare and previously undescribed cell populations. The multi-omic approach provides detailed transcriptomic profiles, regulatory factors and spatial localizations spanning the entire kidney. We also define 28 cellular states across nephron segments and interstitium that were altered in kidney injury, encompassing cycling, adaptive (successful or maladaptive repair), transitioning and degenerative states. Molecular signatures permitted the localization of these states within injury neighbourhoods using spatial transcriptomics, while large-scale 3D imaging analysis (around 1.2 million neighbourhoods) provided corresponding linkages to active immune responses. These analyses defined biological pathways that are relevant to injury time-course and niches, including signatures underlying epithelial repair that predicted maladaptive states associated with a decline in kidney function. This integrated multimodal spatial cell atlas of healthy and diseased human kidneys represents a comprehensive benchmark of cellular states, neighbourhoods, outcome-associated signatures and publicly available interactive visualizations.

Background Left ventricular noncompaction (LVNC) is a hereditary type of cardiomyopathy characterized by prominent trabeculations. Detailed characteristics of biventricular noncompaction (BiVNC) remain unknown. This study aimed to elucidate the clinical characteristics and genetic landscape of BiVNC. Methods and Results We recruited children with left ventricular noncompaction from Japanese multi‐institutional centers from 2013 to 2021. Left ventricular noncompaction was classified as BiVNC, congenital heart disease, arrhythmia, dilated cardiomyopathy, or normal function. In these patients, cardiomyopathy‐associated genes were screened. A total of 234 patients (127 male; mean age, 4 months [range, 0–6.6 years]) were enrolled in this study, of whom 25 had BiVNC; 55, normal function; 84, dilated cardiomyopathy; 38, congenital heart disease; and 32, arrhythmia. BiVNC was diagnosed during the perinatal period in 10 patients, in whom the prevalence was higher than that in other patients. A total of 14 patients in the group with BiVNC had congenital heart disease, but not necessarily right heart lesions. Left ventricular dyskinesis was frequently observed in the lateral wall (24%) and apex (28%). Eleven pathogenic variants were found in 11 patients with BiVNC (44.0%). The group with BiVNC had a higher ratio of mitochondrial and developmental gene variants than the other groups. Among all groups, the group with BiVNC had the worst survival rate (P=0.0009). Conclusions Pediatric patients with BiVNC had a high rate of ventricular dyskinesis and poor outcome. A comprehensive and careful screening for disease‐causing genes and phenotype may help identify specific patients with left ventricular noncompaction and mortality‐related cardiac phenotypes.

Background:. Craniosynostosis is a common diagnosis requiring early referral to a pediatric plastic surgeon; however, disparities in healthcare may influence presentation timing and affect treatment options and outcomes. This study aimed to explore sociodemographic factors contributing to delay in craniosynostosis surgical consultation. Methods:. A retrospective cohort study of 694 California-based craniosynostosis patients at a tertiary children’s hospital was performed from 2006 to 2023. State-specific Area Deprivation Index (ADI) and distance to the hospital were calculated using ZIP codes. Multivariate linear and logistic regressions considered race, insurance type, syndromic status, suture type, and ZIP code-based socioeconomic factors. Results:. Median age of presentation was 4.5 [interquartile range: 2.6–7.6] months with racial/ethnic breakdown of Hispanic/Latinx (41.2%), White (23.6%), Asian (3.7%), Black/African American (2.0%), or other/unreported (29.5%) with 58.4% having public insurance and an average distance to the hospital of 48.3 km. Median ADI was 5.4 [interquartile range: 4.0–7.1]. By linear regression, public insurance (P < 0.001) and higher ADI decile (P < 0.001) independently contributed to an older age of presentation. Patients with public insurance (odds ratio 1.90; P = 0.002) were more likely to present after 4 months of age. Conclusions:. Patients who had public insurance or resided in more disadvantaged areas presented later for craniosynostosis surgical consultation. Eliminating disparities in these populations ensures more equitable access to surgical options and can improve patient outcomes.

Understanding the structures of phosphate glasses is important to many of their technological applications. Molecular dynamics simulations are commonly used to generate structure models of sodium phosphate glasses, and those with partial charge pairwise potentials have been successfully applied for modeling other network glasses, such as silicate and aluminosilicate glasses. In this work, we show that the addition of a three-body term is essential in regulating the intertetrahedral bond angles, as well as Qn speciation in comparison to experiments. Simulation results with and without three-body terms were compared and validated with experimental results, including neutron structure factors. Further comparison with glass structures fully relaxed with first-principles density functional theory was performed to evaluate the simulation results. The results show that the addition of three-body terms is vital for the modeling of phosphate glasses, and it can significantly improve the description of short- and medium-range structures and properties. [ABSTRACT FROM AUTHOR]

Lithium-ion conducting borate glasses are suitable for solid-state batteries as an interfacial material between a crystalline electrolyte and an electrode, thanks to their superior formability. Chlorine has been known to improve the electron conductivity of borate glasses as a secondary anion. To examine the impact of chlorine on lithium dynamics, molecular dynamics (MD) simulations were performed with a machine-learning interatomic potential (MLIP). The accuracy of the MLIP in modeling chlorine-doped lithium borate (LBCl) and borosilicate (LBSCl) glasses was verified by comparing with available experimental data on density, neutron diffraction S(q), and glass transition temperatures (Tg). While the MLIP-MD simulations underestimated the density when an isobaric–isothermal (NPT) ensemble was used, the glass models relaxed using the NPT ensemble after a melt-quench simulation employing a canonical (NVT) ensemble possessed reasonable density. The LBCl and LBSCl glass models exhibited increased lithium ion diffusion, and the ions were found to travel longer distances with an increase in the chlorine content. According to the structural analyses, it was observed that chlorine ions primarily interacted with lithium ions rather than the network formers. Consequently, lithium ions that interacted with a higher amount of chlorine showed a moderate increase in mobility. In summary, the MLIP demonstrated reasonable accuracy in modeling chlorine-containing borate glasses and enabled the investigation of the effect of chlorine on electron conductivity. In contrast, the first sharp diffraction peaks in S(q) deviated from the experimental diffractions, suggesting that additional efforts are required to accurately model the middle-range structure of the glasses. [ABSTRACT FROM AUTHOR]

Abstract Genetic factors significantly affect the pathogenesis of psychiatric disorders. However, the specific pathogenic mechanisms underlying these effects are not fully understood. Recent extensive genomic studies have implicated the protocadherin-related 15 (PCDH15) gene in the onset of psychiatric disorders, such as bipolar disorder (BD). To further investigate the pathogenesis of these psychiatric disorders, we developed a mouse model lacking Pcdh15. Notably, although PCDH15 is primarily identified as the causative gene of Usher syndrome, which presents with visual and auditory impairments, our mice with Pcdh15 homozygous deletion (Pcdh15-null) did not exhibit observable structural abnormalities in either the retina or the inner ear. The Pcdh15-null mice showed very high levels of spontaneous motor activity which was too disturbed to perform standard behavioral testing. However, the Pcdh15 heterozygous deletion mice (Pcdh15-het) exhibited enhanced spontaneous locomotor activity, reduced prepulse inhibition, and diminished cliff avoidance behavior. These observations agreed with the symptoms observed in patients with various psychiatric disorders and several mouse models of psychiatric diseases. Specifically, the hyperactivity may mirror the manic episodes in BD. To obtain a more physiological, long-term quantification of the hyperactive phenotype, we implanted nano tag® sensor chips in the animals, to enable the continuous monitoring of both activity and body temperature. During the light-off period, Pcdh15-null exhibited elevated activity and body temperature compared with wild-type (WT) mice. However, we observed a decreased body temperature during the light-on period. Comprehensive brain activity was visualized using c-Fos mapping, which was assessed during the activity and temperature peak and trough. There was a stark contrast between the distribution of c-Fos expression in Pcdh15-null and WT brains during both the light-on and light-off periods. These results provide valuable insights into the neural basis of the behavioral and thermal characteristics of Pcdh15-deletion mice. Therefore, Pcdh15-deletion mice can be a novel model for BD with mania and other psychiatric disorders, with a strong genetic component that satisfies both construct and surface validity.

Abstract In pancreatic ductal adenocarcinoma (PDAC) patients, the importance of peritoneal lavage cytology, which indicates unresectability, remains controversial. This study sought to determine whether positive peritoneal lavage cytology (CY+) precludes pancreatectomy. Furthermore, we propose a novel liquid biopsy using peritoneal lavage fluid to detect viable peritoneal tumor cells (v-PTCs) with TelomeScan F35, a telomerase-specific replication-selective adenovirus engineered to express green fluorescent protein. Resectable cytologically or histologically proven PDAC patients (n = 53) were enrolled. CY was conducted immediately following laparotomy. The resulting fluid was examined by conventional cytology (conv-CY; Papanicolaou staining and MOC-31 immunostaining) and by the novel technique (Telo-CY; using TelomeScan F35). Of them, 5 and 12 were conv-CY+ and Telo-CY+, respectively. All underwent pancreatectomy. The two double-CY+ (conv-CY+ and Telo-CY+) patients showed early peritoneal recurrence (P-rec) postoperatively, despite adjuvant chemotherapy. None of the three conv-CY+ Telo-CY− patients exhibited P-rec. Six of the 10 Telo-CY+ conv-CY− patients (60%) relapsed with P-rec. Of the remaining 38 double-CY− [conv-CY−, Telo-CY−, conv-CY± (Class III)] patients, 3 (8.3%) exhibited P-rec. Although conv-CY+ status predicted poor prognosis and a higher risk of P-rec, Telo-CY was more sensitive for detecting v-PTC. Staging laparoscopy and performing conv-CY and Telo-CY are needed to confirm the indication for pancreatectomy.

Abstract A 63‐year‐old woman was admitted to our department for the investigation of superior vena cava (SVC) syndrome. Computed tomography revealed an azygos tumor extending into the SVC. Video‐assisted thoracic surgery (VATS) was performed to remove the distal end of the azygos vein in the left lateral position, followed by complete resection of the entire tumor under median sternotomy in the supine position. The histological diagnosis was a primary angiosarcoma of the azygos vein. The patient was discharged without any complications and is now alive and tumor‐free 24 months after surgery. In addition, contrast‐enhanced computed tomography revealed no graft occlusion in the two reconstructed brachiocephalic veins. Thoracoscopic surgery in the lateral position is useful for safe and reliable complete resection of a tumor arising from the azygos vein.