AP39 through AMPK-ULK1-FUNDC1 pathway regulates mitophagy, inhibits pyroptosis, and improves doxorubicin-induced myocardial fibrosis.

Doxorubicin induces myocardial injury and fibrosis. Still, no effective interventions are available. AP39 is an H2S donor that explicitly targets mitochondria. This study investigated whether AP39 could improve doxorubicin-induced myocardial fibrosis. Doxorubicin induced significant myocardial fibrosis while suppressing mitophagy-related proteins and elevating pyroptosis-related proteins. Conversely, AP39 reverses these effects, enhancing mitophagy and inhibiting pyroptosis. In vitro experiments revealed that AP39 inhibited H9c2 cardiomyocyte pyroptosis, improved doxorubicin-induced impairment of mitophagy, reduced ROS levels, ameliorated the mitochondrial membrane potential, and upregulated AMPK-ULK1-FUNDC1 expression. In contrast, AMPK inhibitor (dorsomorphin) and ULK1 inhibitor (SBI-0206965) reversed AP39 antagonism of doxorubicin-induced FUNDC1-mediated impairment of mitophagy and secondary cardiomyocyte pyroptosis. These results suggest that mitochondria-targeted H2S can antagonize doxorubicin-induced pyroptosis and impaired mitophagy in cardiomyocytes via AMPK-ULK1-FUNDC1 and ameliorated myocardial fibrosis and remodeling.

Clinical Effects of Sugar Substitutes on Cariogenic Bacteria: A Systematic Review and Meta-Analysis.

BACKGROUND: The use of sugar substitutes in food products has recently increased. Limited information regarding the role of various sugar substitutes in caries prevention was found. This systematic review and meta-analysis was conducted to investigate the effects of sugar substitute consumption on reducing cariogenic bacteria in dental plaque and saliva. METHODS: We systematically searched PubMed, EMBASE, and Web of Science (inception to July 2023) for prospective controlled trials published in English and investigated the effects of sugar substitute consumption on cariogenic bacteria in dental plaque and saliva. The primary outcome was the changes in cariogenic bacteria. Two independent reviewers screened the papers. Quality was assessed using the Cochrane risk-of-bias tools. RESULTS: From 977 studies identified, 32 trials were included. Almost half (14/32, 44%) of the included studies had a high risk of bias. Almost all (31/32, 96.88%) were investigations of xylitol and other sugar alcohols (low-intensity sweeteners), such as sorbitol, erythritol, and maltitol. Only one trial investigated stevia, a high-intensity sweetener, whereas no studies on other high-intensity sweeteners, such as sucralose, saccharin, or aspartame, were found. Almost all studies (30/32, 93.75%) showed the consumption of low-intensity sweeteners led to a significant reduction of different types of cariogenic bacteria. The results of the meta-analysis showed that consumption of low-intensity sweeteners led to a significant reduction of cariogenic bacteria in both dental plaque and saliva compared to no treatment. CONCLUSION: The consumption of low-intensity sweeteners helps reduce cariogenic bacteria in dental plaque and saliva. There is limited clinical evidence regarding the role of high-intensity sweeteners in reducing cariogenic bacteria.

Attenuation of Polycyclic Aromatic Hydrocarbon (PAH)-Induced Carcinogenesis and Tumorigenesis by Omega-3 Fatty Acids in Mice In Vivo.

Lung cancer is the leading cause of cancer death worldwide. Polycyclic aromatic hydrocarbons (PAHs) are metabolized by the cytochrome P450 (CYP)1A and 1B1 to DNA-reactive metabolites, which could lead to mutations in critical genes, eventually resulting in cancer. Omega-3 fatty acids, such as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), are beneficial against cancers. In this investigation, we elucidated the mechanisms by which omega-3 fatty acids EPA and DHA will attenuate PAH-DNA adducts and lung carcinogenesis and tumorigenesis mediated by the PAHs BP and MC. Adult wild-type (WT) (A/J) mice, Cyp1a1-null, Cyp1a2-null, or Cyp1b1-null mice were exposed to PAHs benzo[a]pyrene (BP) or 3-methylcholanthrene (MC), and the effects of omega-3 fatty acid on PAH-mediated lung carcinogenesis and tumorigenesis were studied. The major findings were as follows: (i) omega-3 fatty acids significantly decreased PAH-DNA adducts in the lungs of each of the genotypes studied; (ii) decreases in PAH-DNA adduct levels by EPA/DHA was in part due to inhibition of CYP1B1; (iii) inhibition of soluble epoxide hydrolase (sEH) enhanced the EPA/DHA-mediated prevention of pulmonary carcinogenesis; and (iv) EPA/DHA attenuated PAH-mediated carcinogenesis in part by epigenetic mechanisms. Taken together, our results suggest that omega-3 fatty acids have the potential to be developed as cancer chemo-preventive agents in people.

Exploring the Design of Upper Limb Strength Training Through High-Intensity Interval Training Combined With Exergaming: Usability Study.

Background: High-intensity interval training (HIIT) has become a popular exercise strategy in modern society, with the Tabata training method being the most popular. In the past, these training methods were mostly done without equipment, but incorporating exergaming into the training may provide a new option for muscle training. objectives: The aim of this study was to explore the differences in upper limb muscle activation using an HIIT program combined with exergaming. Methods: A total of 15 healthy male participants were recruited for the study, and the differences in muscle activation were compared between push-ups and exergaming (Nintendo Switch Ring Fit Adventure with the Ring-Con accessory) during HIIT. Prior to the tests, participants underwent pretests, including maximal voluntary contractions of various muscle groups, maximal push-up tests, and maximal movement tests using the exergaming device. The push-up and exergaming tests were conducted on separate days to avoid interference, with a warm-up period of 5 minutes on a treadmill before testing. Muscle activation in the lateral and anterior portions of the deltoid muscle, the sternal and clavicular heads of the pectoralis major muscle, and the latissimus dorsi muscle were measured during the maximal voluntary contractions and single-round tests for each exercise mode. A repeated measures ANOVA was used to assess the variations in muscle activation observed across the 2 distinct modes of exercise, specifically push-ups and exergaming. Results: In exergaming, the number of repetitions for push-ups was significantly fewer than for single-site exercises across both exhaustive (mean 23.13, SD 6.36 vs mean 55.67, SD 17.83; P=.001; effect size [ES]: 2.43) and single-round (mean 21.93, SD 7.67 vs mean 92.40, SD 20.47; P=.001; ES: 4.56) training. Heart rate differences were not significant (all P>.05), yet exergaming led to better muscle activation in specific muscle groups, particularly the right anterior deltoid (mean 48.00%, SD 7.66% vs mean 32.84%, SD 10.27%; P=.001; ES: 1.67) and right pectoralis major (sternal head: mean 38.99%, SD 9.98% vs mean 26.90%, SD 12.97%; P=.001; ES: 1.04; clavicular head: mean 43.54%, SD 9.59% vs mean 30.09%, SD 11.59%; P=.002; ES: 1.26) during exhaustive training. In single-round training, similar patterns were observed with the anterior deltoid (mean 51.37%, SD 11.76% vs mean 35.47%, SD 12.72%; P=.002; ES: 1.30) and pectoralis major (sternal head: mean 53.27%, SD 10.79% vs mean 31.56%, SD 16.92%; P=.001; ES: 1.53; clavicular head: mean 53.75%, SD 13.01% vs mean 37.95%, SD 14.67%; P=.006; ES: 1.14). These results suggest that exergaming may be more effective for targeted muscle activation. Conclusions: In conclusion, HIIT can increase muscle activation in the upper extremities and can be incorporated into exergaming strategies to provide a fun and engaging way to exercise.

Aggressive sperm immobilization improves reproductive outcomes in patients with suboptimal semen parameters and previous ICSI fertilization failure.

Intracytoplasmic sperm injection (ICSI) is the most effective procedure to resolve male infertility, enhancing overall fertilization and pregnancy outcomes. However, it is important to note that fertilization failure (FF) can still occur in a few cases after ICSI. This study aims to introduce a specialized technique of aggressive sperm immobilization for ICSI and evaluate its impact on reproductive outcomes in cases involving prior fertilization failure. All infertile couples with male partners having suboptimal semen samples and previous ICSI fertilization failure were evaluated using retrospective data from National Taiwan tertiary university hospital (NTUH) between January 2016 and February 2022. Fertilization failure in our study was defined as less than 30% fertilization rate (FR, the number of normally fertilized oocytes divided by the total number of injected mature oocytes). Data involving both standard (routine procedure) and aggressive sperm immobilization (SI) techniques during different ICSI cycles were included in this study. Standard and aggressive SI methods were performed by compressing the distal half tail of the spermatozoa ≦ 5 and 15 times prior to ICSI respectively. Generalized estimating equations analysis were applied to compare the clinical outcomes between two procedures. Overall, data from 23 infertile couples who had undergone 65 ICSI cycles (31 standard SI with low fertilization rate and 34 aggressive SI) were included in the study. The average FR in the ICSI cycles with standard SI and aggressive SI were 23.6 ± 23.1% and 49.5 ± 31.8 respectively (P = 0.0002). The majority of embryos were transferred at the day 3 stage, with an average number transferred of 2.6 ± 0.9 in the aggressive SI group and 1.9 ± 0.9 in the standard group. The number of embryos transferred per transfer cycle was higher in the aggressive SI (P = 0.015), whereas the number of good-quality embryos was similar between the two procedures (P = 0.44). There were one and seven live births from the standard SI cycles and aggressive SI cycles respectively. In conclusion, aggressive SI was associated with a significantly higher FR, resulting in more available embryos for transfer without compromising embryo quality. Therefore, this specialized technique improved pregnancy outcome among infertile couples with a previous ICSI-FF. It can be a safe, economic, and effective method to improve the assisted reproductive technologies outcomes for infertile patients affected by previous ICSI-FF.

Clinical evidence for silver diamine fluoride to reduce dentine hypersensitivity: A systematic review.

OBJECTIVE: To assess the clinical evidence for silver diamine fluoride (SDF) to reduce dentine hypersensitivity in adults. METHODS: Two independent researchers searched the English literature in five databases (Scopus, PubMed, Web of Science, EMBASE and the Cochrane Library) up to 15th July 2023 for clinical trials investigating the desensitising effect of professionally applied SDF to manage dentine hypersensitivity in adults aged 18 or above at any follow-up period. The primary outcome was the change in dentine hypersensitivity between baseline and follow-up visits after SDF application regarding any validated pain outcome measures. The Cochrane guidelines were used for the risk of bias assessment. RESULTS: Three hundred and thirty-one studies were identified, and four of them were finally included. Three of the included studies were rated as having a 'low risk' of bias. The SDF solution reduced dentine hypersensitivity in adults. The percentage reduction in dentine hypersensitivity ranged from 23 % to 56 % after a single application of SDF solution. Moreover, the SDF solution was more effective than potassium nitrate, potassium oxalate and glutaraldehyde plus hydroxyethyl methacrylate in reducing dentine hypersensitivity. Meta-analysis indicated a more significant reduction in visual analogue scales (1-10) by 1.35 (95 % CI:0.9-1.8; p<0.00001) after receiving the SDF application than controls. CONCLUSION: The included clinical trials showed that SDF solution reduced dentine hypersensitivity in adults. However, clinical trials are few, and their protocol varied from one another. Further well-designed clinical trials should be conducted to provide more evidence on its use to manage dentine hypersensitivity. CLINICAL SIGNIFICANCE: SDF is cleared as desensitizing agents by the US Food and Drug Administration to manage dentine hypersensitivity, which induces pain, limits food choice, and impacts the quality of life. Evidence from this systematic review informs clinicians and provides researchers insight for future research on SDF use for dentine hypersensitivity. THE INTERNATIONAL PROSPECTIVE REGISTER OF SYSTEMATIC REVIEWS (PROSPERO) REGISTRATION NUMBER: CRD42023462613.

Female showed favorable left ventricle hypertrophy regression during post-TAVR follow-up.

Transcatheter aortic valve replacement (TAVR) is a well-established procedure using a catheter-introduced valve prosthesis for patients with severe aortic stenosis (AS). This retrospective study investigated sex-related differences in pre- and post-TAVR clinical and hemodynamic outcomes and analyzed data of the first 100 cases at Kaohsiung Medical University Chung-Ho Memorial Hospital (KMUH) between December 2013 and December 2021. Baseline characteristics, procedural outcomes, mortality rates, and echocardiographic parameters were analyzed and compared between sexes. Among the 100 patients, male (46%) and female (54%) were of similar age (mean age, male 86.0 years vs. female 84.5 years) and of the same severity of AS (mean pressure gradient, male 47.5 mmHg vs. female 45.7 mmHg) at the time receiving the TAVR procedure. Women had smaller aortic valve areas calculated by continuity equation (0.8 ± 0.3 cm2 vs. 0.7 ± 0.2 cm2, p < 0.001). In addition, women had better left ventricle ejection fraction (59.6 ± 14.0% vs. men 54.7 ± 17.2%, p < 0.01). In the post-TAVR follow-up, regression of left ventricle mass and dimension was better in women than in men. None of the patient died within 30 days after the procedure, and women tended to have a more favorable survival than men (2-year mortality and overall mortality rate in 8.3 year, women 9.1% and 22.2% vs. men 22.2% and 34.8%; p = 0.6385 and 0.1277, respectively). In conclusion, the sex-based difference in post-TAVR regression of LV remodeling suggests a need for sex-based evaluation for patients with severe AS and their post TAVR follow-up.

Comparison between dynamic versus static models and real-time monitoring of neuronal dysfunction in an amyloid-ß induced neuronal toxic model on a chip platform.

Microfluidics-based organs-on-a-chip offer a promising method for dynamic and 3-dimensional (3D) cell culture to evaluate the cell behaviors within the biomimetic environment. The purpose of this study was to establish neural network connections in a 3D neural stem cell (NSC)-based system with an interstitial level of flow for simulating the brain microenvironment toward a dynamic amyloid-ß (Aß) induced neuronal toxic model on a chip and to compare the biological effects and neurite dysfunction between static and dynamic systems. The brain-on-a-chip system consisted of an impedance analyzing layer, a structured well with a connected channel, and an interface coating with polypeptide films fabricated with modification based on our previous study. The cytotoxicity and percentage of neuron/astrocyte differentiation were all compared in both static and dynamic brain-on-a-chip systems. Reactive oxygen species production, neuron marker expression and neurotransmitter-acetylcholine release were all compared to evaluate functional neurite losses in both static and dynamic systems with/without Aß addition. Moreover, real-time impedance recording was used to consecutively monitor the neurite connection/disconnection in both static and dynamic brain-on-a-chip systems. The NSC-based dynamic brain-on-a-chip may enable the application of different neurodegenerative disease in vitro models for pathogenesis studies, drug discovery and novel therapeutic method development.

The interactions and biological pathways among metabolomics products of patients with coronary heart disease.

BACKGROUND: Through bioinformatics analysis, this study explores the interactions and biological pathways involving metabolomic products in patients diagnosed with coronary heart disease (CHD). METHODS: A comprehensive search for relevant studies focusing on metabolomics analysis in CHD patients was conducted across databases including CNKI, Wanfang, VIP, CBM, PubMed, Cochrane Library, Nature, Web of Science, Springer, and Science Direct. Metabolites reported in the literature underwent statistical analysis and summarization, with the identification of differential metabolites. The pathways associated with these metabolites were examined using the Kyoto Encyclopedia of Genes and Genomes (KEGG). Molecular annotation of metabolites and their relationships with enzymes or transporters were elucidated through analysis with the Human Metabolome Database (HMDB). Visual representation of the properties related to these metabolites was achieved using Metabolomics Pathway Analysis (metPA). RESULTS: A total of 13 literatures satisfying the criteria for enrollment were included. A total of 91 metabolites related to CHD were preliminarily screened, and 87 effective metabolites were obtained after the unrecognized metabolites were excluded. A total of 45 pathways were involved. Through the topology analysis (TPA) of pathways, their influence values were calculated, and 13 major metabolic pathways were selected. The pathways such as Phenylalanine, tyrosine, and tryptophan biosynthesis, Citrate cycle (TCA cycle), Glyoxylate and dicarboxylate metabolism, and Glycine, serine, and threonine metabolism primarily involved the regulation of processes and metabolites related to inflammation, oxidative stress, one-carbon metabolism, energy metabolism, lipid metabolism, immune regulation, and nitric oxide expression. CONCLUSION: Multiple pathways, including Phenylalanine, tyrosine, and tryptophan biosynthesis, Citrate cycle (TCA cycle), Glyoxylate and dicarboxylate metabolism, and Glycine, serine, and threonine metabolism, were involved in the occurrence of CHD. The occurrence of CHD is primarily associated with the regulation of processes and metabolites related to inflammation, oxidative stress, one-carbon metabolism, energy metabolism, lipid metabolism, immune regulation, and nitric oxide expression.

The Effect of the COVID-19 Pandemic on Non-COVID-19 Deaths: Population-Wide Retrospective Cohort Study.

BACKGROUND: Health care avoidance in the COVID-19 pandemic has been widely reported. Yet few studies have investigated the dynamics of hospital avoidance behavior during pandemic waves and inferred its impact on excess non-COVID-19 deaths. OBJECTIVE: This study aimed to measure the impact of hospital avoidance on excess non-COVID-19 deaths in public hospitals in Hong Kong. METHODS: This was a retrospective cohort study involving 11,966,786 patients examined between January 1, 2016, and December 31, 2021, in Hong Kong. All data were linked to service, treatment, and outcomes. To estimate excess mortality, the 2-stage least squares method was used with daily tallies of emergency department (ED) visits and 28-day mortality. Records for older people were categorized by long-term care (LTC) home status, and comorbidities were used to explain the demographic and clinical attributes of excess 28-day mortality. The primary outcome was actual excess death in 2020 and 2021. The 2-stage least squares method was used to estimate the daily excess 28-day mortality by daily reduced visits. RESULTS: Compared with the prepandemic (2016-2019) average, there was a reduction in total ED visits in 2020 of 25.4% (548,116/2,142,609). During the same period, the 28-day mortality of non-COVID-19 ED deaths increased by 7.82% (2689/34,370) compared with 2016-2019. The actual excess deaths in 2020 and 2021 were 3143 and 4013, respectively. The estimated total excess non-COVID-19 28-day deaths among older people in 2020 to 2021 were 1958 (95% CI 1100-2820; no time lag). Deaths on arrival (DOAs) or deaths before arrival (DBAs) increased by 33.6% (1457/4336) in 2020, while non-DOA/DBAs increased only by a moderate 4.97% (1202/24,204). In both types of deaths, the increases were higher during wave periods than in nonwave periods. Moreover, non-LTC patients saw a greater reduction in ED visits than LTC patients across all waves, by more than 10% (non-LTC: 93,896/363,879, 25.8%; LTC: 7,956/67,090, 11.9%). Most of the comorbidity subsets demonstrated an annualized reduction in visits in 2020. Renal diseases and severe liver diseases saw notable increases in deaths. CONCLUSIONS: We demonstrated a statistical method to estimate hospital avoidance behavior during a pandemic and quantified the consequent excess 28-day mortality with a focus on older people, who had high frequencies of ED visits and deaths. This study serves as an informed alert and possible investigational guideline for health care professionals for hospital avoidance behavior and its consequences.

Effects of gas signaling molecule SO2 in cardiac functions of hyperthyroid rats.

Sulfur dioxide (SO2), a novel endogenous gas signaling molecule, is involved in the regulation of cardiac function. Exerting a key role in progression of hyperthyroidism-induced cardiomyopathy (HTC), myocardial fibrosis is mainly caused by myocardial apoptosis, leading to poor treatment outcomes and prognoses. This study aimed to investigate the effect of SO2 on the hyperthyroidism-induced myocardial fibrosis and the underlying regulatory mechanisms. Elisa, Masson staining, Western-Blot, transmission electron microscope, and immunofluorescence were employed to evaluate the myocardial interstitial collagen deposition, endoplasmic reticulum stress (ERS), apoptosis, changes in endogenous SO2, and Hippo pathways from in vitro and in vivo experiments. The study results indicated that the hyperthyroidism-induced myocardial fibrosis was accompanied by decreased cardiac function, and down-regulated ERS, apoptosis, and endogenous SO2-producing enzyme aspartate aminotransferase (AAT)1/2 in cardiac myocytes. In contrast, exogenous SO2 donors improved cardiac function, reduced myocardial interstitial collagen deposition, up-regulated AAT1/2, antagonized ERS and apoptosis, and inhibited excessive activation of Hippo pathway in hyperthyroid rats. In conclusion, the results herein suggested that SO2 inhibited the overactivation of the Hippo pathway, antagonized ERS and apoptosis, and alleviated myocardial fibrosis in hyperthyroid rats. Therefore, this study was expected to identify intervention targets and new strategies for prevention and treatment of HTC.

ILT2 and ILT4 drive myeloid suppression via both overlapping and distinct mechanisms.

Solid tumors are dense three-dimensional (3D) multi-cellular structures that enable efficient receptor-ligand trans interactions via close cell-cell contact. Immunoglobulin-like transcript (ILT)2 and ILT4 are related immune suppressive receptors that play a role in the inhibition of myeloid cells within the tumor microenvironment. The relative contributions of ILT2 and ILT4 to immune inhibition in the context of solid tumor tissue has not been fully explored. We present evidence that both ILT2 and ILT4 contribute to myeloid inhibition. We found that while ILT2 inhibits myeloid cell activation in the context of trans-engagement by MHC-I, ILT4 efficiently inhibits myeloid cells in the presence of either cis- or trans-engagement. In a 3D spheroid tumor model, dual ILT2/ILT4 blockade was required for optimal activation of myeloid cells, including the secretion of CXCL9 and CCL5, upregulation of CD86 on dendritic cells, and downregulation of CD163 on macrophages. Humanized mouse tumor models showed increased immune activation and cytolytic T cell activity with combined ILT2 and ILT4 blockade, including evidence of the generation of immune niches, which have been shown to correlate with clinical response to immune checkpoint blockade. In a human tumor explant histoculture system, dual ILT2/ILT4 blockade increased CXCL9 secretion, downregulated CD163 expression, and increased the expression of M1 macrophage, IFN-γ, and cytolytic T cell gene signatures. Thus, we have revealed distinct contributions of ILT2 and ILT4 to myeloid cell biology and provide proof-of-concept data supporting the combined blockade of ILT2 and ILT4 to therapeutically induce optimal myeloid cell reprogramming in the tumor microenvironment.

Improving oral health of older adults for healthy ageing.

The objective of this article is to discuss the importance of oral health in achieving healthy ageing and the role of all stakeholders in improving oral health for older adults. The World Health Organization defined healthy ageing as the process of developing and maintaining the functional ability that enables well-being in older age. It recognized healthy ageing as an important goal and the key to turn population ageing from a challenge to an opportunity. Healthy ageing has positive impacts on individual older adults, their families and societies. It enhances quality of life of older adults, strengthen family bonding of families and reduce resource demand of the societies. Maintaining oral health and function is essential in healthy ageing. Oral health affects systemic health, cognitive health and psychological health. Oral functions such as eating ensure nutritional health in older adults. Most oral diseases are preventable and oral function decline can be recovered by intervention. Unfortunately, oral diseases remain prevalent and oral function decline is being neglected in older adults. Policy makers, national dental associations, academics and healthcare professionals should collaborate to provide a patient-centred, comprehensive and integrated care to older adults. Health policy reforms are needed to reduce the global oral health inequalities in older adults. Population-wide prevention should be accessible, affordable and available to older adults. Universal oral health coverage is crucial for integration of oral health into general health care.

Global prevalence of early childhood dental fear and anxiety: A systematic review and meta-analysis.

OBJECTIVE: The objective of this review is to determine the global prevalence of dental fear and anxiety (DFA) in early childhood and identify its related factors. METHODS: The systematic review utilized three common English-language databases (PubMed, EMBASE, and Web of Science). Two independent researchers performed a systematic search to include observational studies on young children published from 2000 to 2023. They extracted information on prevalence of DFA, assessment tools used, study sites, respondents, and children's dental visit experiences. RESULTS: A total of 2,895 studies were identified, and 25 studies met the inclusion criteria for analysis. The pooled prevalence of DFA among 2- to 6- year-old children was estimated to be 30 % (95 % CI=25, 36). Children without dental visit experience (OR=1.37, 95 % CI=1.18, 1.59) and children with caries experiences (OR=1.18, 95 % CI=1.09, 1.27) had higher odds of experiencing DFA compared to those with dental visit experience or caries-free status. The most commonly used assessment tools in the included studies were the Frankl Behaviour Rating Scale (32 %, 8/25), Children's Fear Survey Schedule-Dental Subscale (20 %, 5/25), and Dental Anxiety Question (20 %, 5/25). CONCLUSIONS: This systematic review reveals that approximately one-third of young children globally experience DFA. Children who lack dental visit experience or have caries experiences are at increased risk of DFA. Clinicians can use this information to make informed decisions regarding dental care provision for young children. CLINICAL SIGNIFICANCE: This study provides comprehensive information on the global prevalence of dental fear and anxiety and its associated factors in early childhood. The findings can assist clinicians in understanding and addressing DFA in their dental care approach for young children. REGISTRATION: PROSPERO (CRD42023446464).

Tooth Wear in Older Adults: A Review of Clinical Studies.

INTRODUCTION: Tooth wear is a prevalent dental condition among older adults, leading to pain and adversely affecting aesthetics, functionality, and their overall quality of life. This review aims to update the information on tooth wear in older adults from the past five years and to provide guidance on the clinical management of tooth wear in older adults. METHODS: A literature search was conducted in three electronic databases, Scopus, Pubmed, and Embase, for English publications from January 2019 to December 2023 on clinical studies with participants aged 65 or above on tooth wear. A total of 307 articles were retrieved and 14 articles were finally included as references for this study. RESULTS: This review highlights the common causes of tooth wear and various risk factors, such as medical conditions, hyposalivation, dietary habits, oral hygiene practices, parafunctional habits, and occlusal factors, associated with tooth wear. It is crucial for oral health care professionals to diagnose and manage tooth wear at an early stage through a risk assessment and a clinical examination to avoid complex restorative procedures. Tooth wear management should prioritize prevention, aiming to control etiological and risk factors while employing non-restorative treatments. Restorative intervention, if indicated, should be simple, minimally invasive, and cost-effective. Tooth wear progression should be monitored regularly to determine if a further intervention is needed. CONCLUSION: Since the clinical studies on tooth wear in older adults over the past five years are limited and mainly cross-sectional, more interventional clinical studies are warranted to provide more clinical guidance on tooth wear management in older adults.

Erosive tooth wear among non-institutionalised older adults in Hong Kong: a cross-sectional study.

BACKGROUND: Non-institutionalised older adults is the majority of older adults in Hong Kong. The study aimed to examine erosive tooth wear (ETW) and its association with dental conditions and oral hygiene habits among non-institutionalised older adults in Hong Kong. METHODS: This cross-sectional study recruited dentate adults aged 60 or above from nine elderly daycare centres in the five main districts of Hong Kong. The study consists of a questionnaire survey and a clinical examination. A researcher used a questionnaire to collected the participants' demographic information, oral hygiene habits such as toothbrushing habits and dental visit behaviour. A calibrated examiner performed an oral examination in the daycare elderly centre to assess the ETW using basic erosive wear (BEWE) criteria. Oral hygiene was recorded using visible plaque index. Prosthetic status was recorded using the World Health Organization criteria. Logistic regression was used to examine the correlation between ETW and the dental conditions and oral hygiene habits. RESULTS: This study recruited 433 dentate adults and 333 adults were female (77%). Their age ranged from 60 to 99 years and their mean age was 74 years (SD = 7). They all had ETW (BEWE > 0). Over half of them (57%) had BEWE score of 3, indicating severe ETW. Analysis showed increasing age (OR = 1.030, p = 0.029) and older adults with untreated dental caries had higher odds (OR = 1.822, p = 0.002) of presenting severe ETW. No other associations were found between the ETW and the factors studied. CONCLUSION: Hong Kong non-institutionalised older adults aged 60 or above had ETW and more than half of them had severe ETW. Increasing age and having untreated dental caries were associated with severe ETW.

Lanthanide Doping into All-Inorganic Heterometallic Halide Layered Double Perovskite Nanocrystals for Multimodal Visible and Near-Infrared Emission.

The introduction of lanthanide ions (Ln3+) into all-inorganic lead-free halide perovskites has captured significant attention in optoelectronic applications. However, doping Ln3+ ions into heterometallic halide layered double perovskite (LDP) nanocrystals (NCs) and their associated doping mechanisms remain unexplored. Herein, we report the first colloidal synthesis of Ln3+ (Yb3+, Er3+)-doped LDP NCs utilizing a modified hot-injection method. The resulting NCs exhibit efficient near-infrared (NIR) photoluminescence in both NIR-I and NIR-II regions, achieved through energy transfer down-conversion mechanisms. Density functional theory calculations reveal that Ln3+ dopants preferentially occupy the Sb3+ cation positions, resulting in a disruption of local site symmetry of the LDP lattices. By leveraging sensitizations of intermediate energy levels, we delved into a series of Ln3+-doped Cs4M(II)Sb2Cl12 (M(II): Cd2+ or Mn2+) LDP NCs via co-doping strategies. Remarkably, we observe a brightening effect of the predark states of Er3+ dopant in the Er3+-doped Cs4M(II)Sb2Cl12 LDP NCs owing to the Mn component acting as an intermediate energy bridge. This study not only advances our understanding of energy transfer mechanisms in doped NCs but also propels all-inorganic LDP NCs for a wider range of optoelectronic applications.

TGFB1I1 promotes cell proliferation and migration in urothelial carcinoma.

Urothelial carcinoma (UC) is common cancer worldwide with a high prevalence in Taiwan, especially in the upper urinary tract, including the renal pelvis and ureter, also classifying as upper urinary tract urothelial carcinoma. Here, we aim to find a representative prognostic marker that strongly correlates to this type of carcinoma. Transforming growth factor beta-1-induced transcript 1 (TGFB1I1) is a cofactor of cellular TGF-ß1 and interacts with various nuclear receptors. The previous study showed that TGFB1I1 promotes focal adhesion formation, contributing to the epithelial-mesenchymal transition (EMT) with actin cytoskeleton and vimentin through TGFB1I1 regulation. We aim to reveal the role of TGFB1I1 in the tumorigenesis of UC. In silico and clinicopathological data of upper urinary tract urothelial carcinoma (UTUC) and urinary bladder urothelial carcinoma (UBUC) were accessed and analyzed for IHC staining regarding tumor characteristics, including survival outcome. Finally, an in vitro study was performed to demonstrate the biological changes of UC cells. In UTUC, overexpression of TGFB1I1 was significantly correlated with advanced tumor stage, papillary configuration, and frequent mitosis. Meanwhile, overexpression of TGFB1I1 was significantly correlated with advanced tumor stage and histological grade in UBUC. Moreover, the in vitro study shows that TGFB1I1 affects cell proliferation, viability, migration and wound healing. The EMT markers also decreased upon TGFB1I1 knockdown. In this study, we identified that TGFB1I1 regulates UC cell proliferation and viability and induces the EMT to facilitate cell migration in vitro, leading to its essential role in promoting tumor aggressiveness in both UTUC and UBUC.

Tools Evaluating Child Oral Health-Related Quality of Life.

OBJECTIVES: This study aimed to systemically review the tools developed for evaluating oral health-related quality of life (OHRQoL) in preschool children. METHODS: Two reviewers systematically searched English-language publications within PubMed, Embase, Scopus, and Web of Science. They screened the titles and abstracts and retrieved the full texts of the selected publications. Studies which developed, validated, or culturally adapted an OHRQoL tool used in preschool children were included. They recorded information regarding tool characteristics, item configuration, discriminative validation, the aim of assessment, and the target group. RESULTS: The study included 59 publications and identified 12 tools for assessing OHRQoL in preschool children. Seven tools were tailored for preschool ages. Most of the scales were generic oral health measures. Dental caries was the most commonly used oral condition for assessing a tool's discriminative validity. Eight tools required parental proxy reports. Three tools were both child-administrated and parent-administrated. One tool was designed to be answered solely by children. Ten tools assessed the oral health-related impact on children, including oral condition-related, functioning, environmental, and emotional/social domains. Four tools included items regarding the impact on both children and family. CONCLUSIONS: This review identified 12 tools developed for evaluating OHRQoL in preschool children, 7 of which were tailored for preschool age. The 12 tools were validated but incomprehensive due to the subjective and multidimensional nature of the OHRQoL concept. Researchers can choose a suitable tool for their studies by understanding the basic characteristics and item setting of the tools. Researchers can have an overview of the tools developed for evaluating OHRQoL in preschool children. They can use the findings from this review to choose a suitable tool for their studies regarding the OHRQoL in preschool children.

Early Childhood Caries and Dental Public Health Programmes in Hong Kong.

The objective of this study was to investigate the relationship amongst early childhood caries (ECC), economic development, and dental public health programmes in Hong Kong. We searched exhaustively qualitative and quantitative data on the oral health policy, dental service, public health strategies of caries control and epidemiologic surveys on ECC. We then performed meta-regression to explore the impact of the Human Development Index (HDI), gross domestic product (GDP) growth, water fluoridation, oral health promotion, dental school establishment, free education, and dental workforce on ECC prevalence in 5-year-olds. We found that the first government oral health survey was conducted in 1960, when Hong Kong experienced significant growth, as the HDI indicated. The survey revealed that 97% of 6- to 8-year-old children experienced ECC. Water fluoridation was implemented in 1961 at 0.7 ppm (0.9 ppm in winter) to prevent caries. The government offered free 9-year education in 1978. In 1981, the government established a dental school to improve a low dentist-to-population ratio of 1:9000. The ECC prevalence amongst 5- to 6- year-old children was reduced from 84% in 1968 to 63% in 1986. The Department of Health created an oral health education division in 1989. The ECC prevalence for 5-year-old children was further reduced to 44% in 1997. The ECC prevalence amongst 5-year-old children was stabilised at 51% both in 2001 and 2011. However in 2021, the prevalence of untreated ECC increased to 57% during the outbreak of COVID-19. Meta-regression analysis showed that ECC prevalence was not linked to GDP growth but decreased with improvements in HDI, the provision of 9-year free education, the establishment of a dental school, fluoridation of water supply, and implementation of territory-wide oral health promotion. In conclusion, better education, living conditions, and dental public health programmes have improved children's oral health in Hong Kong.