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Hsin-Yu Yang,1 Yu-Fan Chang,1,2 Chih-Chien Hsu,1,2 Yu-Chieh Ko,1–3 Catherine Jui-Ling Liu,1,3 Mei-Ju Chen1,3 1Department of Ophthalmology, Taipei Veterans General Hospital, Taipei, Taiwan; 2Institute of Clinical Medicine, National Yang-Ming University, Taipei, Taiwan; 3School of Medicine, National Yang-Ming University, Taipei, Taiwan Purpose: We evaluated macular ganglion cell asymmetry as a tool for diagnosing paracentral scotoma (PCS) in early glaucoma.Patients and methods: This prospective study compared 58 patients with early glaucoma and PCS to 58 age-matched control individuals. All glaucomatous eyes had scotoma within the central 12 degrees of fixation and confined to one hemifield. We measured circumpapillary retinal nerve fiber layer (cpRNFL) thickness, macular ganglion cell-inner plexiform layer (GCIPL) thickness, and optic nerve head (ONH) parameters with Cirrus spectral domain optical coherence tomography. Macular ganglion cell asymmetry was expressed as the absolute differences and the ratios between the inferior and superior hemispheres, inferotemporal (IT) and superotemporal (ST) areas, IT and superonasal (SN) areas, IT and inferonasal (IN) areas, and ST and IN areas. The asymmetry index was the absolute log10 of the ratio. The area under the receiver operating characteristics curve (AUROC) and partial AUROC (pAUROC, specificities ≥90%) were analyzed for each parameter.Results: All GCIPL parameters and most cpRNFL parameters were significantly lower in early glaucoma than in controls. The best discriminating parameters were inferior RNFL thickness, average RNFL thickness, and minimum GCIPL thickness. The macular ganglion cell asymmetry parameters with the largest AUROCs were the log IT/ST index, the absolute difference in IT-ST GCIPL thicknesses, and the log IT/SN index. Performance was comparable between the log IT/ST index and the cpRNFL (inferior RNFL thickness, P=0.129), GCIPL (minimum GCIPL thickness, P=0.358), and ONH parameters (vertical cup-to-disc ratio, P=0.475).Conclusion: The IT/ST asymmetry index may be useful as a new parameter for detecting structural changes in glaucoma patients with PCS.Keywords: macular ganglion cell, paracentral scotoma, glaucoma, optical coherence tomography

Rationale: Asthma is often work-related and can be classified as atopic or nonatopic on the basis of its pathogenesis. Few studies have reported an association between exposure to occupational asthmogens and asthma with and without atopy. Objectives: We investigated, in adults with asthma, whether occupational exposure to asthmogens influenced the risk of having atopic or nonatopic asthma, and their level of lung function. Methods: We recruited 504 hospital-based adults with current asthma, 504 community-based control subjects, and 504 hospital-based control subjects in southern Taiwan. Asthma with atopy was defined as having asthma in combination with an increase in total IgE (>=100 U/ml) or a positive Phadiatop test (>=0.35 Pharmacia arbitrary unit/L) (Pharmacia ImmunoCAP; Pharmacia, Uppsala, Sweden). Occupational exposure to asthmogens was assessed with an asthma-specific job exposure matrix. Measurements and Main Results: We found a significant association between atopic asthma and exposure to high molecular weight asthmogens (adjusted odds ratio [AOR], 4.0; 95% confidence interval [CI], 1.8-8.9). Nonatopic asthma was significantly associated with exposure to low molecular weight asthmogens (AOR, 2.6; 95% CI, 1.6-4.3), including industrial cleaning agents and metal sensitizers. Agriculture was associated with both atopic and nonatopic asthma (AOR, 7.8; 95% CI, 2.8-21.8; and AOR, 4.1; 95% CI, 1.3-13.0, respectively). The ratio of FEV(1) to FVC in the high-risk group was significantly lower than in the no-risk group (P = 0.026) in currently employed patients with asthma. Conclusions: In adults with asthma, occupational exposure to high and low molecular weight asthmogens appears to produce differential risks for atopic and nonatopic asthma. [ABSTRACT FROM AUTHOR]

Background: The crude extract of the fruit bearing plant, Physalis peruviana (golden berry), demonstrated anti-hepatoma and anti-inflammatory activities. However, the cellular mechanism involved in this process is still unknown.Methods: Herein, we isolated the main pure compound, 4beta-Hydroxywithanolide (4betaHWE) derived from golden berries, and investigated its antiproliferative effect on a human lung cancer cell line (H1299) using survival, cell cycle, and apoptosis analyses. An alkaline comet-nuclear extract (NE) assay was used to evaluate the DNA damage due to the drug.Results: It was shown that DNA damage was significantly induced by 1, 5, and 10 microg/mL 4betaHWE for 2 h in a dose-dependent manner (p < 0.005). A trypan blue exclusion assay showed that the proliferation of cells was inhibited by 4betaHWE in both dose- and time-dependent manners (p < 0.05 and 0.001 for 24 and 48 h, respectively). The half maximal inhibitory concentrations (IC50) of 4betaHWE in H1299 cells for 24 and 48 h were 0.6 and 0.71 microg/mL, respectively, suggesting it could be a potential therapeutic agent against lung cancer. In a flow cytometric analysis, 4betaHWE produced cell cycle perturbation in the form of sub-G1 accumulation and slight arrest at the G2/M phase with 1 microg/mL for 12 and 24 h, respectively. Using flow cytometric and annexin V/propidium iodide immunofluorescence double-staining techniques, these phenomena were proven to be apoptosis and complete G2/M arrest for H1299 cells treated with 5 microg/mL for 24 h.Conclusions: In this study, we demonstrated that golden berry-derived 4betaHWE is a potential DNA-damaging and chemotherapeutic agent against lung cancer. [ABSTRACT FROM AUTHOR]

This study used a large-scale cancer database in determination of prognostic factors for the survival of lung cancer subjects in Taiwan.~Background~Background~Total of 24,910 subjects diagnosed with lung cancer was analysed. Survival estimates by Kaplan-Meier methods. Cox proportional-hazards model estimated the death risk (hazard ratio (HR)) for various prognostic factors.~Methods~Methods~The prognostic indicators associated with a higher risk of lung cancer deaths are male gender (males versus females; HR = 1.07, 95% confidence intervals (CI): 1.03-1.11), males diagnosed in later periods (shown in 1991-1994 versus 1987-1990; HR = 1.13), older age at diagnosis, large cell carcinoma (LCC)/small cell carcinoma (SCC), and supportive care therapy over chemotherapy. The overall 5-year survival rate for lung cancer death was significantly poorer for males (21.3%) than females (23.6%). Subjects with squamous cell carcinoma (SQCC) and treatment by surgical resection alone had better prognosis. We find surgical resections to markedly increase 5-year survival rate from LCC, decreased risk of death from LCC, and no improved survival from SCC.~Results~Results~Gender and clinical characteristics (i.e. diagnostic period, diagnostic age, histological type and treatment modality) play important roles in determining lung cancer survival.~Conclusion~Conclusions [ABSTRACT FROM AUTHOR]

Recent developments in stress research have called for attention to how social structures influence the stress and coping processes. This paper examines the experience of work stress among professionals in Singapore and argues that workers' experiences in the workplace are influenced not only by individual personality and job nature, but also by structural forces shaping the profession, the social organization of work institutions and the development of the economy. Data were collected from a survey of professionals in Singapore conducted in 1989-1990. The sample consisted of 2570 men and women from six different professions and para-professions, namely general practitioners, lawyers, engineers, teachers, nurses and life insurance personnel. Results showed that performance pressure and work-family conflicts were perceived to be the most stressful aspects of work. These two stressors also significantly contributed to the experience of overall work stress. Further, stress arising from work-family conflicts, performance pressure and poor job prospects was negatively associated with the level of work satisfaction. These findings were discussed in the contexts of increasing professionalization and de-professionalization and the growing emphases on productivity and efficiency in a quickly developing economy. [ABSTRACT FROM AUTHOR]

Betel quid (BQ) use disorder (BUD) is prevalent in many Asian countries, impacting approximately 600 million people. We conducted a randomized clinical trial to analyze the impact of MAOA genetic variations on the severity of BQ craving. This was measured using DSM-5 criteria and the Yale-Brown Obsessive-Compulsive Scale modified for betel quid use (Y-BOCS-BQ). Participants were grouped according to the severity of BUD and MAOA gene single-nucleotide polymorphism (SNP) rs5953210 genotypes. The Y-BOCS-BQ scores were assessed at baseline (week 0) and during follow-up at weeks 2, 4, 6, and 8. The AA genotype group showed significantly greater reductions in Y-BOCS-BQ at weeks 2 ( p = 0.0194), 4 ( p = 0.0078), 6 ( p = 0.0277), and 8 ( p = 0.0376) compared to the GG genotype group. Additionally, within the antidepressant group, the AA genotype showed significant reductions in the Y-BOCS-BQ scores at weeks 2 ( p = 0.0313), 4 ( p = 0.0134), 6 ( p = 0.0061), and 8 ( p = 0.0241) compared to the GG genotype. The statistical analysis revealed a significant interaction between the treatment and placebo groups based on MAOA genotypes, with the AA genotype in the treatment group exhibiting a more pronounced decrease in Y-BOCS-BQ score ( p interaction <0.05) at week 6. Our study highlights the importance of considering genetic factors when developing personalized treatment plans for BUD.

Aim: This study investigated the adjunctive effect of polydeoxyribonucleotide (PDRN) on bone formation in alveolar ridge preservation (ARP) sockets., Materials and Methods: Both mandibular second, third and fourth premolars of eight beagle dogs were randomly divided into ARP and ARP/PDRN groups. Following tooth extraction, ARP procedures were conducted using collagenized alloplastic graft material and bilayer collagen membrane soaked with normal saline (ARP group) or PDRN (ARP/PDRN group) for 10 min before application. Both groups were also randomly allocated to 2-, 4- or 12-week healing subgroups. The primary endpoint of this study was to compare histomorphometric differences between ARP and ARP/PDRN. The secondary endpoints of this study were to compare micro-CT analysis and three-dimensional volumetric measurement between the two groups., Results: In the histomorphometric analysis, the ARP/PDRN group exhibited greater new bone formation at coronal, middle and total position compared with the ARP group at 2-week healing. The number of newly formed blood vessels was higher in the ARP/PDRN group than in the ARP group at 2- and 4-week healing. In micro-CT analysis, the mean new bone volume/total bone volume between ARP and ARP/PDRN was statistically significant at 2-week healing. Ridge volume alterations were significantly decreased in the ARP/PDRN group during entire healing time compared with the ARP group, especially on the buccal side., Conclusions: The application of PDRN in ARP might provide additional benefits for early bone regeneration and maintenance of buccal ridge volume., (© 2024 The Authors. Journal of Clinical Periodontology published by John Wiley & Sons Ltd.)

Background: Chest compression at a rate of 100-120 compressions per minute (cpm) during cardiopulmonary resuscitation (CPR) is associated with the highest survival rates. Performing compressions at a faster rate may exhaust the rescuers., Objectives: To compare a new cue of 'two compressions per second' to the traditional cue of '100-120 compressions per minute' on compression rate in CPR training., Methods: In this cluster-randomized study, students from two senior high schools were assigned into two groups. For the experimental group, the cue for the compression rate was 'two compressions per second'. For the control group, the cue was '100-120 cpm'. Except the different cues, all participants underwent the same standardized CPR training program. Verbal compression rate-related feedback was not obtained during practice. Quality indicators of chest compressions were recorded by a sensorized manikin. The primary outcome measure was mean compression rate at course conclusion. The secondary outcome measures were individual compression quality indicators at course conclusion and 3 months after training., Results: We included 164 participants (85 participants, experimental group; 79 participants, control group). Both groups had similar characteristics. The experimental group had a significantly lower mean compression rate at course conclusion (144.3 ± 16.17 vs. 152.7 ± 18.38 cpm, p = 0.003) and at 3 months after training (p = 0.09). The two groups had similar mean percentage of adequate compression rate (≥ 100 cpm), mean compression depth, and mean percentage of complete recoil at course conclusion and 3 months after training., Conclusion: The new cue of 'two compressions per second' resulted in participants having a lower compression rate, although it still exceeded 120 cpm., Competing Interests: Declaration of competing interest None., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Ambulance-based telestroke may be a promising solution to improving stroke care. We assessed the technical feasibility and reliability of prehospital evaluations using commercial mobile phones with fifth-generation wireless communication technology., Methods: Six standardized patients portrayed scripted stroke scenarios during ambulance transport in an urban city and were remotely evaluated by independent raters using tablets (three neurologists and three emergency physicians) in a hospital, assisted by paramedics (trained in National Institute of Health Stroke Scale [NIHSS] assessment) in the ambulance; commercial cellular networks were utilized for videoconferencing transmission. The primary outcomes were mean difference (MD) and correlation of NIHSS scores between the face-to-face and remote assessments. We also examined the Bland-Altman plot for itemized NIHSS components, and Kaplan-Meier curves were used to compare the differences in the duration of the two evaluations between neurologists and emergency physicians., Results: We conducted 32 ambulance runs and successfully completed all NIHSS examinations. No significant difference was found between the face-to-face and remote evaluations (MD, 0.782; 95% confidence interval [CI], -0.520-0.395). The correlation of NIHSS scores between the two methods was 0.994 (95% CI, 0.945-1.026), and three items exhibited the highest frequency of runs, with score differences between the two methods. There were no significant differences between neurologists and emergency physicians in the mean evaluation duration and NIHSS scores for the two methods., Conclusion: Prehospital evaluation using commercial mobile phones with fifth-generation wireless communication technology is feasible and reliable during ambulance transport in urban areas. Emergency physicians and neurologists performed similarly in stroke evaluations., Competing Interests: Declaration of competing interest None declared., (Copyright © 2024 Formosan Medical Association. Published by Elsevier B.V. All rights reserved.)

Objective: To compare the effectiveness of intraosseous versus intravenous vascular access in the treatment of adult patients with out-of-hospital cardiac arrest., Design: Cluster randomised controlled trial., Setting: The VICTOR (Venous Injection Compared To intraOsseous injection during resuscitation of patients with out-of-hospital cardiac arrest) trial involved emergency medical service agencies with all four advanced life support ambulance teams in Taipei City, Taiwan. The enrolment period spanned 6 July 2020 to 30 June 2023 and was temporarily suspended between 20 May 2021 and 31 July 2021 owing to the covid-19 pandemic., Participants: Adult (age 20-80 years) patients with non-traumatic out-of-hospital cardiac arrest., Interventions: Biweekly randomised clusters of four participating advanced life support ambulance teams were assigned to insert either intravenous or intraosseous access., Main Outcome Measures: The primary outcome was survival to hospital discharge. Secondary outcomes included return of spontaneous circulation, sustained return of spontaneous circulation (≥2 hours), and survival with favourable neurological outcomes (cerebral performance category score ≤2) at hospital discharge., Results: Among 1771 enrolled patients, 1732 (741 in the intraosseous group and 991 in the intravenous group) were included in the primary analysis (median age 65.0 years; 1234 (71.2%) men). In the intraosseous group, 79 (10.7%) patients were discharged alive, compared with 102 (10.3%) patients in the intravenous group (odds ratio 1.04, 95% confidence interval 0.76 to 1.42; P=0.81). The odds ratio of intraosseous versus intravenous access was 1.23 (0.89 to 1.69; P=0.21) for pre-hospital return of spontaneous circulation, 0.92 (0.75 to 1.13; P=0.44) for sustained return of spontaneous circulation, and 1.17 (0.82 to 1.66; P=0.39) for survival with favourable neurological outcomes., Conclusions: Among adults with non-traumatic out-of-hospital cardiac arrest, initial attempts to establish vascular access through the intraosseous route did not result in different outcomes compared with intravenous access in terms of the proportion of patients surviving to hospital discharge, pre-hospital return of spontaneous circulation, sustained return of spontaneous circulation, and favourable neurological outcomes., Trial Registration: NCT04135547ClinicalTrials.gov NCT04135547., Competing Interests: Competing interests: All authors have completed the ICMJE uniform disclosure form at https://www.icmje.org/disclosure-of-interest/ and declare: this study was supported by the Taiwan Ministry of Science and Technology, National Science and Technology Council, and National Taiwan University Hospital, Yun-Lin Branch; no financial relationships with any organisations that might have an interest in the submitted work in the previous three years; no other relationships or activities that could appear to have influenced the submitted work., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Purpose: This study investigated the effect of implant vertical positioning within alveolar ridge preservation (ARP) sites on implant stability quotient (ISQ) values, which were measured 10 weeks post-implantation., Methods: Patients who underwent ARP using collagenized deproteinized bovine bone mineral, followed by implant placement in the posterior area, were divided into 2 groups: the within-ARP group and the beyond-ARP group. In the within-ARP group, osteotomy and implant placement occurred within the ARP boundary. In contrast, in the beyond-ARP group, these procedures were performed beyond the ARP boundary, incorporating 3 mm of pristine bone at the implant's apex. Bone quality was assessed by tactile sense, and both insertion torque during implant surgery and ISQ values at 10 weeks post-implant surgery were measured. Multiple linear regression analysis and Pearson correlation analysis were used to explore the relationship between insertion torque and ISQ values., Results: In total, 30 ARP sites in 28 patients were analyzed. There was no significant difference in bone quality, as determined by tactile sense, between the within-ARP and beyond-ARP groups. At the time of implant placement, the beyond-ARP group exhibited a higher insertion torque (33.33±13.39 Ncm) compared to the within-ARP group (17.08±11.17 Ncm). However, the ISQ values were similar between the 2 groups 10 weeks after implant placement. A positive correlation between insertion torque and ISQ values was confirmed at 10 weeks post-implant., Conclusions: The engagement of pristine bone may facilitate high insertion torque during the placement of implants in ARP sites. Nevertheless, by 10 weeks post-implantation, the ISQ values were found to be comparable, irrespective of the implant's position., Competing Interests: No potential conflict of interest relevant to this article was reported., (Copyright © 2024. Korean Academy of Periodontology.)

Brown root rot disease (BRRD) is a highly destructive tree disease. Early diagnosis of BRRD has been challenging because the first symptoms and signs are often observed after extensive tissue colonization. Existing molecular detection methods, all based on the internal transcribed spacer (ITS) region, were developed without testing against global Phellinus noxius isolates, other wood decay fungi, or host plant tissues. This study developed SYBR Green real-time quantitative PCR (qPCR) assays for P. noxius . The primer pair Pn&#95;ITS&#95;F/Pn&#95;ITS&#95;R targets the ITS, and the primer pair Pn&#95;NLR&#95;F/Pn&#95;NLR&#95;R targets a P. noxius -unique group of homologous genes identified through a comparative genomics analysis. The homologous genes belong to the nucleotide-binding-oligomerization-domain-like receptor (NLR) superfamily. The new primer pairs and a previous primer pair G1F/G1R were optimized for qPCR conditions and tested for specificity using 61 global P. noxius isolates, five other Phellinus species, and 22 non- Phellinus wood decay fungal species. While all three primer pairs could detect as little as 100 fg (about 2.99 copies) of P. noxius genomic DNA, G1F/G1R had the highest specificity and Pn&#95;NLR&#95;F/Pn&#95;NLR&#95;R had the highest efficiency. To avoid false positives, the cutoff Cq values were determined as 34 for G1F/G1R, 29 for Pn&#95;ITS&#95;F/Pn&#95;ITS&#95;R, and 32 for Pn&#95;NLR&#95;F/Pn&#95;NLR&#95;R. We further validated these qPCR assays using Ficus benjamina seedlings artificially inoculated with P. noxius , six tree species naturally infected by P. noxius , rhizosphere soil, and bulk soil. The newly developed qPCR assays provide sensitive detection and quantification of P. noxius , which is useful for long-term monitoring of BRRD status.

Background: The "chain of survival" was first systematically addressed in 1991, and its sequence still forms the cornerstone of current resuscitation guidelines. The term "chain of survival" is widely used around the world in literature, education, and awareness campaigns, but growing heterogeneity in the components of the chain has led to confusion. It is unclear which of these emerging chains is most suitable, or if adaptations are needed in particular contexts to depict key actions of resuscitation in the 21st century. This scoping review provides an overview of the variety of chains of survival described., Objectives: To identify published facets of the chain of survival, to assess views and strategies about adapting the chain, and to identify reports on how the chain of survival affects teaching, implementation, or patient outcomes., Methods Eligibility Criteria and Sources of Evidence: A scoping review as part of the continuous evidence evaluation process of the International Liaison Committee on Resuscitation (ILCOR) was conducted. MEDLINE(R) ALL (Ovid), Embase (Ovid), APA PsycINFO (Ovid), CINAHL (Ebscohost), ERIC (Ebscohost), Web of Science (Clarivate), Scopus (Elsevier), and Cochrane Library (Wiley Online) were searched. All publications in all languages describing chains of survival were eligible, without time restrictions. Due to the heterogeneity and publication types of the relevant studies, we did not pursue a systematic review or meta-analysis., Results: A primary search yielded 1713 studies and after screening we included 43 publications. Modified versions of the chain of survival for specific contexts were found (e.g., in-hospital cardiac arrest or paediatric resuscitation). There were also numerous versions with minor adaptations of the existing chain. Three publications suggested an impact of the use of the chain of survival on patient outcomes. No educational or implementation outcomes were reported., Conclusion: There is a vast heterogeneity of chain of survival concepts published. Future research is warranted, especially into the concept's importance concerning educational, implementation, and clinical outcomes., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

Background: This study compared the progression of experimental peri-implantitis between alveolar ridge preservation (ARP) and spontaneous healing (SH) sites in infected (IT) and noninfected tooth (NIT)., Methods: Bilateral mandibular third or fourth premolars of six beagle dogs were randomly assigned to IT and NIT groups. Before extraction, chronic dehiscence defects were created at the mesial root of mid-buccal area in IT group. Four weeks later, the mesial roots of the third and fourth premolars were extracted in all groups.ARP procedure was randomly conducted on one side of the extraction sockets using collagenated bovine bone substitutes and resorbable collagen membrane, and contralateral side was allowded spontaneous healing. After 12 weeks of healing, bone-level implants (ϕ 3.6 × 8.0 mm) were placed at the extraction sockets. Three months of ligature induced peri-implantitis and three months of spontaneous progression were allowed, with radiographs taken at each phase. Biopsies were retrieved at the implant site for histomorphometric, immunohistochemical, and polarized light-microscopic analyses., Results: Radiography demonstrated that the changes in the marginal bone level during the spontaneous progression period showed no significant differences between ARP and SH sites. Only small and/or nonsignificant differences in the progression of peri-implantitis were observed between ARP and SH sites in histomorphometric, immunohistochemical, and polarized light microscopic analyses. Additionally, the IT and NIT groups exhibited similar outcomes for most parameters., Conclusion: ARP with xenogenic bone substitutes might provide similarly robust results as SH sites regarding the progression of experimental peri-implantitis, irrespective of the infected or noninfected nature of the site before tooth extraction., (© 2024 The Authors. Journal of Periodontology published by Wiley Periodicals LLC on behalf of American Academy of Periodontology.)

Purpose: This study evaluated the implant stability, volumetric changes, and patient-reported outcome measures (PROMs) of hydroxyapatite (HA) nano-coated sandblasted/acid-etched (SLA) implants compared to uncoated SLA implants., Methods: Forty patients were recruited and randomly allocated to HA nano-coated SLA group (test, n = 20) and uncoated SLA group (control, n = 20) using single-blinded/block randomization. Implants were immediately placed in maxillary posterior region using a digital surgical guide. Insertion torque and implant stability quotient (ISQ) were measured at implant surgery and 1, 2, 3, and 4 months postoperatively. Intraoral scans, PROMs and soft tissue inflammation data were collected, and multivariable linear regression analysis of ISQ was performed., Results: In total, 48 implants (test; n = 24, control; n = 24) in 37 patients (test; n = 19, control; n = 18) were analyzed. Despite no significant between-group difference at surgery, the test group showed higher ISQ values than the control group at 2 (76.53 ± 4.17 vs. 71.32 ± 4.79, p < 0.01), 3 (77.45 ± 4.41 vs. 73.85 ± 4.69, p < 0.05), and 4 months (79.08 ± 2.96 vs. 73.43 ± 3.52, p < 0.0001) postoperatively. There were no significant differences in linear and volumetric changes, PROMs, and soft tissue inflammation analysis between two groups. The ISQ at implant surgery was influenced by age and diabetes mellitus (DM) at the implant level and DM and predicted total bone-to-implant contact area at the patient level., Conclusion: HA nano-coated SLA implants promoted favorable immediate implants stability during early osseointegration phase compared to uncoated SLA implants, but displayed similar dimensional changes, PROMs, and soft tissue inflammation outcomes., Trial Registration: Clinical Research Information Service (CRIS), KCT0006364. Registered 21 July 2021, https://cris.nih.go.kr/cris/search/detailSearch.do?seq=24221&search&#95;page=L ., (© 2024. The Author(s).)

Background/purpose: Blended learning offers the advantages of both instructor-led and self-instruction methods in basic life support (BLS). Our study aims to compare the effects of blended learning with those of traditional instructor-led methods on the performance of laypersons taking BLS courses., Methods: A total of 108 participants were randomly assigned to three groups: traditional instruction (group A, n = 36), blended learning with two rounds of practice (group B, n = 36), and blended learning with three rounds of practice (group C, n = 36). Group A received a 90-min lecture and a 30-min hands-on practice session using a manikin and a metronome. Participants in groups B and C received 18-min standardized online video lessons and performed hands-on practice twice and thrice, respectively. The primary outcome was chest compression at a correct speed (100-120 compressions per min) after the training course. Secondary outcomes included knowledge test scores, attitudes and confidence, and individual skill performance after training., Results: Patient characteristics were similar between the groups. Blended learning with practicing thrice resulted in the highest compressions at a correct speed (group A vs. B vs. C, 68.09 vs 80.03 vs 89.42, p = 0.015) and the shortest average hands-off time (group A vs. B vs. C, 1.12 vs 0.86 vs 0.17 s, p = 0.015). Both blended groups performed better in confirming environmental safety (p < 0.001). No differences in scores of the knowledge test, attitude, or confidence were noted among the three groups., Conclusion: Blended learning with three rounds of hands-on practice may be considered an alternative teaching method., Competing Interests: Declarations of interest None., (Copyright © 2023 Formosan Medical Association. Published by Elsevier B.V. All rights reserved.)

This study aimed to develop aptamers targeting LipL32, a most abundant lipoprotein in pathogenic Leptospira, to hinder bacterial invasion. The objectives were to identify high-affinity aptamers through SELEX and evaluate their specificity and inhibitory effects. SELEX was employed to generate LipL32 aptamers (L32APs) over 15 rounds of selection. L32APs' binding affinity and specificity for pathogenic Leptospira were assessed. Their ability to inhibit LipL32-ECM interaction and Leptospira invasion was investigated. Animal studies were conducted to evaluate the impact of L32AP treatment on survival rates, Leptospira colonization, and kidney damage. Three L32APs with strong binding affinity were identified. They selectively detected pathogenic Leptospira, sparing non-pathogenic strains. L32APs inhibited LipL32-ECM interaction and Leptospira invasion. In animal studies, L32AP administration significantly improved survival rates, reduced Leptospira colonies, and mitigated kidney damage compared to infection alone. This pioneering research developed functional aptamers targeting pathogenic Leptospira. The identified L32APs exhibited high affinity, pathogen selectivity, and inhibition of invasion and ECM interaction. L32AP treatment showed promising results, enhancing survival rates and reducing Leptospira colonization and kidney damage. These findings demonstrate the potential of aptamers to impede pathogenic Leptospira invasion and aid in recovery from Leptospira-induced kidney injury (190 words)., Competing Interests: Declaration of competing interest The authors have stated explicitly that there are no conflicts of interest in connection with this article., (Copyright © 2024 Institut Pasteur. Published by Elsevier Masson SAS. All rights reserved.)

Background/purpose: This review aimed to investigate the effect of crew ratios of on-scene advanced life support (ALS)-trained personnel on patients with out-of-hospital cardiac arrest (OHCA)., Methods: We systematically searched PubMed, Ovid EMBASE, and the Cochrane Central Register of Controlled Trials databases from the inception date until September 30, 2022, for eligible studies. Two reviewers independently screened the studies for relevance, extracted data, and quality. We compared the effect of the ratio of on-scene ALS-trained personnel >50 % to those with a ratio ≤50 % among prehospital personnel on the clinical outcomes of OHCA patients. The primary outcome was survival-to-discharge and secondary outcomes were any return of spontaneous circulation (ROSC), sustained ROSC (≥2 h), and favourable neurological outcome at discharge (cerebral performance category scores: 1 or 2). Pooled odds ratios (ORs) were calculated, and the certainty of evidence was assessed., Results: From 10,864 references, we identified four non-randomised studies, including 16,475 patients. Two studies were performed in Japan and two in Taiwan. There were significant differences in survival-to-discharge (OR: 1.24, 95 % confidence interval [CI]: 1.07-1.44, I 2 : 7 %), any ROSC (OR:1.22, 95 % CI: 1.04-1.43, I 2 : 74 %) and sustained ROSC (OR: 1.39, 95 % CI: 1.16-1.65, I 2 : 40 %), but insignificant differences in favourable neurological outcome at discharge. The overall certainty of evidence was rated as very low for all outcomes., Conclusion: Prehospital ALS care with a ratio of on-scene ALS-trained personnel >50 % could improve OHCA patient outcomes than crew ratios ≤50 %. Further studies are required to reach a robust conclusion., Competing Interests: Declaration of competing interest None., (Copyright © 2023 Formosan Medical Association. Published by Elsevier B.V. All rights reserved.)

Background: Optimal timing for initiating maintenance dialysis in patients with chronic kidney disease (CKD) stages 3-5 is challenging. This study aimed to develop and validate a machine learning (ML) model for early personalised prediction of maintenance dialysis initiation within 1-year and 3-year timeframes among patients with CKD stages 3-5., Methods: Retrospective electronic health record data from the Taipei Medical University clinical research database were used. Newly diagnosed patients with CKD stages 3-5 between 2008 and 2017 were identified. The observation period spanned from the diagnosis of CKD stages 3-5 until the maintenance dialysis initiation or a maximum follow-up of 3 years. Predictive models were developed using patient demographics, comorbidities, laboratory data and medications. The dataset was divided into training and testing sets to ensure robust model performance. Model evaluation metrics, including area under the curve (AUC), sensitivity, specificity, positive predictive value, negative predictive value and F1 score, were employed., Results: A total of 6123 and 5279 patients were included for 1 year and 3 years of the model development. The artificial neural network demonstrated better performance in predicting maintenance dialysis initiation within 1 year and 3 years, with AUC values of 0.96 and 0.92, respectively. Important features such as baseline estimated glomerular filtration rate and albuminuria significantly contributed to the predictive model., Conclusion: This study demonstrates the efficacy of an ML approach in developing a highly predictive model for estimating the timing of maintenance dialysis initiation in patients with CKD stages 3-5. These findings have important implications for personalised treatment strategies, enabling improved clinical decision-making and potentially enhancing patient outcomes., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY. Published by BMJ.)

Background: Tourniquets (TQ) have been increasingly adopted in pre-hospital settings recently. This study examined the effectiveness and safety of applying TQ in the pre-hospital settings for civilian patients with traumatic vascular injuries to the extremities., Materials and Methods: We systematically searched the Ovid Embase, PubMed, and Cochrane Central Register of Controlled Trials databases from their inception to June 2023. We compared pre-hospital TQ (PH-TQ) use to no PH-TQ, defined as a TQ applied after hospital arrival or no TQ use at all, for civilian vascular extremity trauma patients. The primary outcome was overall mortality rate, and the secondary outcomes were blood product use and hospital stay. We analyzed TQ-related complications as safety outcomes. We tried to include randomized controlled trials (RCTs) and non-randomized studies (including non-RCTs, interrupted time series, controlled before-and-after studies, cohort studies, and case-control studies), if available. Pooled odds ratios (ORs) were calculated and the certainty of evidence was assessed using Grading of Recommendations Assessment, Development, and Evaluation (GRADE) methodology., Results: Seven studies involving 4,095 patients were included. In the primary outcome, pre-hospital TQ (PH-TQ) use significantly decrease mortality rate in patients with extremity trauma (odds ratio [OR], 0.48, 95% confidence interval [CI] 0.27-0.86, I 2  = 47%). Moreover, the use of PH-TQ showed the decreasing trend of utilization of blood products, such as packed red blood cells (mean difference [MD]: -2.1 [unit], 95% CI: -5.0 to 0.8, I 2  = 99%) or fresh frozen plasma (MD: -1.0 [unit], 95% CI: -4.0 to 2.0, I 2  = 98%); however, both are not statistically significant. No significant differences were observed in the lengths of hospital and intensive care unit stays. For the safety outcomes, PH-TQ use did not significantly increase risk of amputation (OR: 0.85, 95% CI: 0.43 to 1.68, I 2  = 60%) or compartment syndrome (OR: 0.94, 95% CI: 0.37 to 2.35, I 2  = 0%). The certainty of the evidence was very low across all outcomes., Conclusion: The current data suggest that, in the pre-hospital settings, PH-TQ use for civilian patients with vascular traumatic injury of the extremities decreased mortality and tended to decrease blood transfusions. This did not increase the risk of amputation or compartment syndrome significantly., (© 2024. The Author(s).)

Background: Major trauma is a leading cause of unexpected death globally, with increasing age-adjusted death rates for unintentional injuries. Field triage schemes (FTSs) assist emergency medical technicians in identifying appropriate medical care facilities for patients. While full FTSs may improve sensitivity, step-by-step field triage is time-consuming. A simplified FTS (sFTS) that uses only physiological and anatomical criteria may offer a more rapid decision-making process. However, evidence for this approach is limited, and its performance in identifying all age groups requiring trauma center resources in Asia remains unclear., Methods: We conducted a multinational retrospective cohort study involving adult trauma patients admitted to emergency departments in the included countries from 2016 to 2020. Prehospital and hospital data were reviewed from the Pan-Asia Trauma Outcomes Study database. Patients aged ≥18 years transported by emergency medical services were included. Patients lacking data regarding age, sex, physiological criteria, or injury severity scores were excluded. We examined the performance of sFTS in all age groups and fine-tuned physiological criteria to improve sFTS performance in identifying high-risk trauma patients in different age groups., Results: The sensitivity and specificity of the physiological and anatomical criteria for identifying major trauma (injury severity score ≥ 16) were 80.6% and 58.8%, respectively. The modified sFTS showed increased sensitivity and decreased specificity, with more pronounced changes in the young age group. Adding the shock index further increased sensitivity in both age groups., Conclusions: sFTS using only physiological and anatomical criteria is suboptimal for Asian adult patients with trauma of all age groups. Adjusting the physiological criteria and adding a shock index as a triage tool can improve the sensitivity of severely injured patients, particularly in young age groups. A swift field triage process can maintain acceptable sensitivity and specificity in severely injured patients., Competing Interests: Declaration of Competing Interest This study received no financial support and there are no conflicts of interest., (Copyright © 2023 Elsevier Inc. All rights reserved.)

The surface-enhanced Raman scattering (SERS) technique has garnered significant interest due to its ultrahigh sensitivity, making it suitable for addressing the growing demand for disease diagnosis. In addition to its sensitivity and uniformity, an ideal SERS platform should possess characteristics such as simplicity in manufacturing and low analyte consumption, enabling practical applications in complex diagnoses including cancer. Furthermore, the integration of machine learning algorithms with SERS can enhance the practical usability of sensing devices by effectively classifying the subtle vibrational fingerprints produced by molecules such as those found in human blood. In this study, we demonstrate an approach for early detection of breast cancer using a bottom-up strategy to construct a flexible and simple three-dimensional (3D) plasmonic cluster SERS platform integrated with a deep learning algorithm. With these advantages of the 3D plasmonic cluster, we demonstrate that the 3D plasmonic cluster (3D-PC) exhibits a significantly enhanced Raman intensity through detection limit down to 10 -6 M (femtomole-(10 -17 mol)) for p -nitrophenol (PNP) molecules. Afterward, the plasma of cancer subjects and healthy subjects was used to fabricate the bioink to build 3D-PC structures. The collected SERS successfully classified into two clusters of cancer subjects and healthy subjects with high accuracy of up to 93%. These results highlight the potential of the 3D plasmonic cluster SERS platform for early breast cancer detection and open promising avenues for future research in this field.

Betel quid (BQ) is the fourth most popular psychoactive substance in the world, and BQ use disorder (BUD) is prevalent in Asian countries. Although the mechanisms underlying BUD remain unclear, studies have reported influences from monoamine oxidase inhibitor. We enrolled 50 patients with BUD and assessed their BQ consumption habits, emotional conditions, and the clinical severity of addiction-assessed using the Diagnostic and Statistical Manual of Mental Disorders [Fifth Edition] ( DSM-5 ) criteria, Substance Use Severity Rating Scale, and Yale-Brown Obsessive Compulsive Disorder Rating Scale for BQ. Patients were categorized into the severe group when showing six or more symptoms defined by DSM-5 . A genome-wide association study was conducted for single nucleotide polymorphisms in BRCA1 , COL9A1 , NOTCH1 , HSPA13 , FAT1 , and MAOA by using patients' blood samples. More severe BUD symptoms were associated with younger age of using BQ and poor oral hygiene and with severe craving for and more anxiety toward BQ use. The MAOA rs5953210 polymorphism was significantly associated with severe BUD (odds ratio, 6.43; 95% confidence interval, 5.12-7.74; p < 0.01) and might contribute to BQ-associated cancer risk. Further studies are required to investigate the addictive properties of BQ and the development of novel diagnostic tools and pharmacotherapeutic alternatives to BUD treatment.

Renal fibrosis is a common pathway leading to progressive renal function loss in various forms of chronic kidney disease. Many fibrogenic factors regulate renal fibrosis; two key players are post-injury inflammation and transforming growth factor-β1 (TGF-β1)-induced myofibroblast differentiation. Myofibroblast differentiation is tightly regulated by the microtubule polymerization. Noscapine, an antitussive plant alkaloid, is a potent microtubule-interfering agent previously identified as a potential anticancer compound. Here, we examined how noscapine affects renal fibrogenesis in an in vitro renal fibroblast model and an in vivo unilateral ureteral obstruction (UUO) model. UUO mice were intraperitoneally treated with noscapine at 1 day before UUO surgery and daily thereafter. At 7 days post-surgery, kidneys were collected for further analysis. To analyze whether noscapine inhibits downstream TGF-β1-related signaling, we pre-incubated NRK-49F fibroblasts with noscapine and then performed TGF-β1 stimulation. In UUO mice, noscapine attenuated extracellular matrix protein deposition and the expression levels of type I collagen, type IV collagen, α-smooth muscle actin, and fibronectin. In addition, noscapine decreased tubulointerstitial inflammation in UUO kidneys by reducing TLR2 expression, modulating NLRP3 inflammasome activation, reducing macrophage infiltration, and antagonizing the M2 macrophage phenotype. Furthermore, noscapine pre-incubation suppressed the TGF-β1-induced fibroblast-myofibroblast transformation by downregulating the TGF-β/Smads signaling pathways in NRK-49F cells. These results suggest that noscapine reduces tubulointerstitial inflammation and fibrosis in the kidneys of UUO mice and inhibits the fibroblast-myofibroblast transformation induced by TGF-β1. Noscapine is an over-the-counter antitussive that has been used safely for several decades. Therefore, noscapine is an attractive therapeutic agent for inhibiting renal tubulointerstitial fibrosis., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Objective: Recently, matrix metalloproteinase-8 (MMP-8) has been used to diagnose periodontal disease in a point-of-care (POC) test in order to save time and cost relative to the traditional diagnostic workflow. This study aimed to investigate the diagnostic performance of INCLIX TRF MMP-8, a POC testing device for periodontitis using the area under the receiver operating characteristic curve, sensitivity, specificity, and predictive values., Materials and Methods: Full-mouth periodontal examination and radiographic analysis were used for evaluating periodontal condition based on the 2018 classification of periodontal disease. A dichotomous diagnosis of clinical periodontal condition was performed using the POC device. The relationships among periodontal condition and the concentration of MMP-8, tooth loss (TL), gingival index (GI), plaque index (PI), and alveolar bone loss (ABL) were assessed by the Spearman rank correlations (r s )., Results: In all, 108 cases of non-periodontitis (NP) and 191 cases of periodontitis (P), including 38 cases of periodontitis stage I, 42 cases of periodontitis stage II, 99 cases of periodontitis stage III, and 11 cases of periodontitis stage IV, were enrolled in this study. Diagnostic accuracy in assessing periodontal condition with the POC device improved when it was used with participants aged ≥ 40 years. There were weak positive correlations between periodontal condition and MMP-8 and between periodontal condition and GI (r s 2 = 0.1124 and r s 2 = 0.0906, respectively), whereas a strong positive correlation between periodontal condition and alveolar bone loss (r s 2 = 0.6877) was observed., Conclusion: The POC device investigated in this study is a potential tool to distinguish between NP and P in individuals ≥ 40 years of age., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: To investigate the incidence of and risk factors for bleb-related infection (BRI) in patients who underwent mitomycin C-augmented primary trabeculectomy., Methods: We reviewed the medical charts of consecutive patients who had received primary trabeculectomy in Taipei Veterans General Hospital. We recorded the demographic and clinical characteristics of patients before, during and after surgery. Furthermore, we recorded the time interval between surgery and infection onset, clinical manifestations and visual outcomes of patients with BRI. The cumulative incidence of BRI was estimated using the Kaplan-Meier method. A Cox proportional hazards model was used to explore factors associated with BRI., Results: In total, 1663 eyes were postoperatively followed up for 94.57±65.23 months. The cumulative incidence of BRI was 1.86 per 1000 person-years during the 28-year follow-up period: 24 (1.44%) patients developed BRI and 6 (0.36%) patients additionally developed endophthalmitis. A multivariate analysis revealed a significant association of BRI with wound manipulation, high myopia and hyperlipidaemia. Patients younger than 60 years were more likely to receive wound manipulation than their elderly counterparts (<0.001). One year after BRI, the best corrected visual acuity of the eyes with blebitis did not change significantly, whereas that of the eyes with endophthalmitis worsened significantly., Conclusion: Risk factors for BRI after trabeculectomy include wound manipulation, high myopia and hyperlipidaemia. Considering myopia is highly prevalent throughout the world and is a risk factor for glaucoma, the lifelong risk of BRI after trabeculectomy in eyes with high myopia warrants the attention of ophthalmologists., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Aim: This study aimed to investigate factors influencing the survival of replaced dental implants., Materials and Methods: Charts from 2005 to 2021 were reviewed. Replaced implants after removal for the first time were identified. Depending on their survival, the replaced group was divided into the surviving and second-removal groups. Risk factors affecting survival of replaced implants were evaluated considering clustering of multiple implants within patients., Results: The present study included 464 replaced implants of 370 patients, of which 429 and 35 implants were categorized into the surviving group and the second-removal group. The 5-year survival rate was 90.2 ± 0.18% in replaced implants at sites with a periodontitis history and 97.0 ± 0.15% at sites without a periodontitis history (p = 0.008). The 5-year survival rate was 89.1 ± 0.27% in replaced implants with guided bone regeneration (GBR) at first implant placement and 93.9 ± 0.14% at non-GBR (p = 0.032). The 5-year survival rate was 97.6 ± 0.13% in replaced implants with GBR and 90.3 ± 0.17% in replaced implants without GBR (p = 0.026). In the multivariable analysis adjusted for clinical variables, periodontitis history (adjusted hazard ratio [aHR] = 3.417; 95% confidence interval [CI] = 1.161-10.055), GBR at first implant placement (aHR = 2.152; 95% CI = 1.052-4.397) and non-GBR at primary implant replacement (aHR = 0.262; 95% CI = 0.088-0.778) were identified as independent risk factors for second implant removal., Conclusions: Periodontitis history, GBR at first implant placement and non-GBR at primary implant replacement were identified as risk factors affecting the survival of replaced implants., (© 2023 Wiley Periodicals LLC.)

Background: Continuous positive airway pressure (CPAP) therapy is the first-line treatment for obstructive sleep apnea (OSA). However, the low acceptance rate of CPAP remains a challenging clinical issue. This study aimed to determine the factors that influence the acceptance rate of CPAP., Methods: This retrospective cohort study was conducted at the sleep center of Shuang-Ho Hospital. Initially, 1186 OSA patients who received CPAP therapy between December 2013 and December 2017 were selected, and finally, 1016 patients were analyzed. All patients with OSA received CPAP therapy for at least 1 week, and their acceptance to treatment was subsequently recorded. Outcome measures included patients' demographic and clinical characteristics (sex, age, BMI, comorbidities, history of smoking, and the medical specialist who prescribed CPAP treatment), polysomnography (PSG) results, and OSA surgical records., Results: Patients with a lower CPAP acceptance rate were referred from otolaryngologists (acceptance rate of otolaryngology vs. others: 49.6% vs. 56.6%, p = .015), in addition to having a lower apnea-hypopnea index (AHI) (acceptance vs. non-acceptance: 55.83 vs. 40.79, p = .003), rapid eye movement AHI (REM-AHI) (acceptance vs. non-acceptance: 51.21 vs. 44.92, p = .014), and arousal index (acceptance vs. non-acceptance: 36.80 vs. 28.75, p = .011). The multiple logistic regression model showed that patients referred from otolaryngology had a lower CPAP acceptance rate (odds ratio 0.707, p = .0216) even after adjusting for age, sex, BMI, AHI, REM-AHI, arousal index, comorbidities, and smoking status., Conclusions: Before their initial consultation, patients may already have their preferred treatment of choice, which is strongly linked to the type of medical specialists they visit, and consequently, affects their rate of acceptance to CPAP therapy. Therefore, physicians should provide personalized care to patients by exploring and abiding by their preferred treatment choices., (© 2023. The Author(s).)

Background: The aim of this scoping review was to identify factors that would enable or hinder the opportunity for laypersons to undertake resuscitation education., Methods: We searched PubMed, Ovid EMBASE, CINAHL, and the Cochrane Central Register of Controlled Trials (CENTRAL) to identify studies published from January 1, 1966 to December 31, 2022 including factors that could influence laypersons to undertake resuscitation education. Data regarding participant characteristics, interventions, and design and outcomes of included studies were extracted., Results: Of the initially identified 6627 studies, 23 studies (20 cross-sectional and 3 cohort studies) were finally included. Among them, a wide variety of enablers and barriers were identified. High heterogeneity among studies was observed. We categorized factors into three themes: personal factors (age, sex, race, family status, language, prior experience of resuscitation, and immigration status), socioeconomic and educational factors (income, societal status, occupation and legislation, and educational attainment), and geographic factors (birthplace and habitancy). Several barriers were identified that affect laypersons from participating in resuscitation training, such as personal factors like advanced age, lower socioeconomic and educational status, as well as being part of marginalized groups due to race or language barriers. On the other hand, several enablers identified in the study included prior experiences of witnessing someone collapsing, awareness of automated external defibrillators in public locations, certain occupations, or legal requirements for training., Conclusions: Various barriers and enablers were found to influence laypersons to participate in resuscitation training. To enhance layperson response to cardiac arrest, targeted initiatives that aim to eliminate barriers need to be initiated, and further research is required to explore factors relating to populations with special needs., Competing Interests: Declaration of Competing Interest R.G. is chair, A.C. is vice-chair of the ILCOR Task Force on Education, Implementation and Teams. All other authors are members of that committee., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Leptospirosis is a commonly overlooked zoonotic disease that occurs in tropical and subtropical regions. Recent studies have divided the Leptospira spp. into three groups based on virulence, including pathogenic, intermediate, and saprophytic species. Pathogenic species express a protein family with leucine-rich repeat (LRR) domains, which are less expressed or absent in nonpathogenic species, highlighting the importance of this protein family in leptospirosis. However, the role of LRR domain proteins in the pathogenesis of leptospirosis is still unknown and requires further investigation. In this study, the 3D structure of LSS&#95;01692 (rLRR38) was obtained using X-ray crystallography at a resolution of 3.2 Å. The results showed that rLRR38 forms a typical horseshoe structure with 11 α-helices and 11 β-sheets and an antiparallel dimeric structure. The interactions of rLRR38 with extracellular matrix and cell surface receptors were evaluated using ELISA and single-molecule atomic force microscopy. The results showed that rLRR38 interacted with fibronectin, collagen IV, and Toll-like receptor 2 (TLR2). Incubating HK2 cells with rLRR38 induced two downstream inflammation responses (IL-6 and MCP-1) in the TLR2 signal transduction pathway. The TLR2-TLR1 complex showed the most significant upregulation effects under rLRR38 treatment. Inhibitors also significantly inhibited nuclear factor κB and mitogen-activated protein kinases signals transduction under rLRR38 stimulation. In conclusion, rLRR38 was determined to be a novel LRR domain protein in 3D structure and demonstrated as a TLR2-binding protein that induces inflammatory responses. These structural and functional studies provide a deeper understanding of the pathogenesis of leptospirosis., (© 2023 Federation of European Biochemical Societies.)

Background: Guided bone regeneration (GBR) is the most widely used technique for overcoming the deficiency of alveolar bone. However, the progression of peri-implantitis in regenerative and pristine bone sites has not been fully investigated. The aim of this study is to compare experimental peri-implantitis around implants placed in pristine bone and GBR sites., Methods: Bilateral  mandibular first molars were extracted from six beagle dogs, and standardized horizontal ridge defect was simultaneously created at predetermined site in unilateral mandible. After 8 weeks, guided bone regeneration procedure was conducted at the defect site. After 16 weeks, implants (ϕ 3.6×8.0 mm) were placed at both extracted sites. This study included 3 months of active breakdown and another 3 months of spontaneous progression period. Radiographs were taken at each phase and specimens were obtained for histological, immunohistochemical, and polarized light microscopic analysis., Results: Marginal bone loss around implant did not show the significant differences between pristine bone and GBR sites during spontaneous progression period. In immunohistochemical analysis, inflammatory and immune-related cells were predominantly detected in peri-implantitis-affected area rather than unaffected area. In the polarized light microscopic analysis, substantial reductions in the amount and thickness of collagen fibers were observed in peri-implantitis-affected area compared with unaffected tissues. However, there were no significant differences in histological, immunohistochemical, polarized light microscopic outcomes between pristine bone and GBR sites., Conclusion: Previous hard tissue grafting at the implant sites did not affect experimental peri-implantitis and exhibited similar radiographic, histological, immunohistochemical, and polarized light microscopic outcomes compared with those of pristine bone sites., (© 2023 American Academy of Periodontology.)

Although phthalate esters contribute to airway remodeling by increasing bronchial cells' migration and proliferation, the relationship between human exposure to phthalates and asthma is not understood. We measured phthalate exposure in the human body and evaluated its effect on asthma. Asthma ( n = 123) and asthma-free ( n = 139) participants were, respectively, recruited from an asthma clinic and the community in Taiwan. The urine levels of six phthalate metabolites were determined by liquid chromatography tandem mass spectrometry. Compared with the controls, male asthma patients had higher means of mono-(2-ethylhexyl) phthalate (MEHP) (116.3 nmol/g), monobutyl phthalate (MBP) (850.3 nmol/g) and monoethyl phthalate (MEP) (965.8 nmol/g), and female patients had greater MBP (2902.4 nmol/g). Each 10-fold increase in the level of these phthalate metabolites was correspondingly associated with a 5.0-, 5.8-, 4.2- and 5.3-fold risk of contracting asthma. Male asthma patients were identified to have a higher proportion of MEHP exposure (32.5%) than the controls (25.3%). In asthma patients, an increase in urine MEHP levels and the total phthalate metabolite concentration were notably linked to increased risks of emergency room visits and being hospitalized. For the occurrence and acute clinical events of adult asthma, phthalate exposures and MEHP retention may contribute to higher risks of contracting this respiratory disorder.

The diagnosis of oral epithelial dysplasia is based on the degree of architectural and cytologic atypia in the squamous epithelium. The conventional grading system of mild, moderate, and severe dysplasia is considered by many the gold standard in predicting the risk of malignant transformation. Unfortunately, some low-grade lesions, with or without dysplasia, progress to squamous cell carcinoma (SCC) in short periods. As a result, we are proposing a new approach to characterize oral dysplastic lesions that will help identify lesions at high risk for malignant transformation. We included a total of 203 cases of oral epithelial dysplasia, proliferative verrucous leukoplakia, lichenoid, and commonly observed mucosal reactive lesions to evaluate their p53 immunohistochemical (IHC) staining patterns. We identified 4 wild-type patterns, including scattered basal, patchy basal/parabasal, null-like/basal sparing, mid-epithelial/basal sparing, and 3 abnormal p53 patterns, including overexpression basal/parabasal only, overexpression basal/parabasal to diffuse, and null. All cases of lichenoid and reactive lesions exhibited scattered basal or patchy basal/parabasal patterns, whereas human papillomavirus-associated oral epithelial dysplasia demonstrated null-like/basal sparing or mid-epithelial/basal sparing patterns. Of the oral epithelial dysplasia cases, 42.5% (51/120) demonstrated an abnormal p53 IHC pattern. p53 abnormal oral epithelial dysplasia was significantly more likely to progress to invasive SCC when compared to p53 wild-type oral epithelial dysplasia (21.6% vs 0%, P < .0001). Furthermore, p53 abnormal oral epithelial dysplasia was more likely to have dyskeratosis and/or acantholysis (98.0% vs 43.5%, P < .0001). We propose the term p53 abnormal oral epithelial dysplasia to highlight the importance of utilizing p53 IHC stain to recognize lesions that are at high risk of progression to invasive disease, irrespective of the histologic grade, and propose that these lesions should not be graded using the conventional grading system to avoid delayed management., (Copyright © 2023 United States & Canadian Academy of Pathology. Published by Elsevier Inc. All rights reserved.)

Aim: The mobile network quality in ambulances can be variable and limited. This pilot study aimed to identify a suitable network setting for recognizing agonal respiration under limited network conditions., Methods: We recruited five emergency medical technicians, and each participant viewed 30 real-life videos with different resolutions, frame rates, and network scenarios. Thereafter, they reported the respiration pattern of the patient and identified agonal respiration cases. The time at which agonal respiration was identified was also recorded. The answers provided by the five participants were compared with those of two emergency physicians to compare the accuracy and time delay in breathing pattern recognition., Results: The overall accuracy for initial respiratory pattern recognition was 80.7% (121/150). The accuracy for normal breathing was 93.3% (28/30), for not breathing was 96% (48/50), and for agonal breathing was 64.3% (45/70). There was no significant difference in successful recognition between video resolutions. However, the rate of time delay in recognizing agonal respiration less than 10 seconds between 15-fps group and 30-fps group had statistical significance (21% vs 52%, p  = 0.041)., Conclusion: The frame rate emerges as one of critical factors in agonal respiration recognition through telemedicine, outweighing the significance of video resolution., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Author(s).)

Identifying and treating tumors early is the key to secondary prevention in cancer control. At present, prevention of oral cancer is still challenging because the molecular drivers responsible for malignant transformation of the 11 clinically defined oral potentially malignant disorders are still unknown. In this review, we focused on studies that elucidate the epigenetic alterations demarcating malignant and nonmalignant epigenomes and prioritized findings from clinical samples. Head and neck included, the genomes of many cancer types are largely hypomethylated and accompanied by focal hypermethylation on certain specific regions. We revisited prior studies that demonstrated that sufficient uptake of folate, the primary dietary methyl donor, is associated with oral cancer reduction. As epigenetically driven phenotypic plasticity, a newly recognized hallmark of cancer, has been linked to tumor initiation, cell fate determination, and drug resistance, we discussed prior findings that might be associated with this hallmark, including gene clusters (11q13.3, 19q13.43, 20q11.2, 22q11-13) with great potential for oral cancer biomarkers, and successful examples in screening early-stage nasopharyngeal carcinoma. Although one-size-fits-all approaches have been shown to be ineffective in most cancer therapies, the rapid development of epigenome sequencing methods raises the possibility that this nonmutagenic approach may be an exception. Only time will tell.

Purpose: Glioblastoma (GBM) has a poor prognosis after standard treatment. Recently, metformin has been shown to have an antitumor effect on glioma cells. We performed the first randomized prospective phase II clinical trial to investigate the clinical efficacy and safety of metformin in patients with recurrent or refractory GBM treated with low-dose temozolomide., Methods: Included patients were randomly assigned to a control group [placebo plus low-dose temozolomide (50 mg/m 2 , daily)] or an experimental group [metformin (1000 mg, 1500 mg, and 2000 mg per day during the 1st, 2nd, and 3rd week until disease progression, respectively) plus low-dose temozolomide]. The primary endpoint was progression-free survival (PFS). Secondary endpoints were overall survival (OS), disease control rate, overall response rate, health-related quality of life, and safety., Results: Among the 92 patients screened, 81 were randomly assigned to the control group (43 patients) or the experimental group (38 patients). Although the control group showed a longer median PFS, the difference between the two groups was not statistically significant (2.66 versus 2.3 months, p = 0.679). The median OS was 17.22 months (95% CI 12.19-21.68 months) in the experimental group and 7.69 months (95% CI 5.16-22.67 months) in the control group, showing no significant difference by the log-rank test (HR: 0.78; 95% CI 0.39-1.58; p = 0.473). The overall response rate and disease control rate were 9.3% and 46.5% in the control group and 5.3% and 47.4% in the experimental group, respectively., Conclusions: Although the metformin plus temozolomide regimen was well tolerated, it did not confer a clinical benefit in patients with recurrent or refractory GBM. Trial registration NCT03243851, registered August 4, 2017., (© 2023. The Author(s).)