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OBJECTIVE: This study aims to explore the perspectives and experiences of Australian caregivers and community pharmacists about pediatric melatonin use. METHODS: A convenience sample of caregivers with children (aged 11-16 years) using melatonin as a sleep aid and community pharmacists (including pharmacist interns) were recruited. Participants first completed an online survey followed by an online semi-structured interview. Interviews were guided by a schedule of questions for the respective participant groups, broadly exploring their beliefs about melatonin, experiences in using/supplying melatonin, and perceived facilitators/barriers for melatonin use. Interviews were digitally recorded, transcribed verbatim, and analyzed using the Framework Approach. RESULTS: Fourteen caregivers of predominantly neurodiverse adolescents and 24 community pharmacists were interviewed. While melatonin was perceived by caregivers of both typically developing and neurodiverse dependants as safer than pharmacological sleep aids, treatment was only initiated after trialling non-pharmacological strategies first. Pharmacists expressed concerns around the ambiguities in practice and the limited scope of existing resources for guiding pediatric melatonin use. Caregivers frequently deferred to the information available online to procure products or self-adjust doses and dosing schedules. Both pharmacists and caregivers emphasized the need for more affordable and age-appropriate proprietary formulations that are readily accessible. CONCLUSION: Melatonin is administered predominantly by caregivers of neurodiverse adolescents to address their sleep disturbances. The findings underscore the need for reliable, evidence-based information to guide safe and appropriate use of melatonin in pediatric populations. Patient education is also warranted to address maladaptive medication-administration practices. Lastly, there is a need for stronger regulatory oversight of melatonin products to ensure their quality and safety of use.

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Since the coronavirus pandemic, mRNA vaccines have revolutionized the field of vaccinology. Lipid nanoparticles (LNPs) are proposed to enhance mRNA delivery efficiency; however, their design is suboptimal. Here, a rational method for designing LNPs is explored, focusing on the ionizable lipid composition and structural optimization using machine learning (ML) techniques. A total of 213 LNPs are analyzed using random forest regression models trained with 314 features to predict the mRNA expression efficiency. The models, which predict mRNA expression levels post-administration of intradermal injection in mice, identify phenol as the dominant substructure affecting mRNA encapsulation and expression. The specific phospholipids used as components of the LNPs, as well as the N/P ratio and mass ratio, are found to affect the efficacy of mRNA delivery. Structural analysis highlights the impact of the carbon chain length on the encapsulation efficiency and LNP stability. This integrated approach offers a framework for designing advanced LNPs and has the potential to unlock the full potential of mRNA therapeutics.

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Clinically, prostate cancer is infamous for its histological and molecular heterogeneity, which causes great challenges to pinpoint therapy and pharmaceutical development. To overcome these difficulties, researchers are focusing on modulating tumor microenvironment and immune responses in addition to genetic alteration and epigenetic regulation. Here, we aimed to identify potential biomarkers or modulators of prostate cancer by investigating genes specifically altered in prostate cancer cells treated with established anti-cancer agents. Glycerol kinase 1 (GK1) is phosphotransferase encoded on the X chromosome, is associated with the synthesis of triglycerides and glycerophospholipids, and has been mainly studied for X-linked metabolic disorder GK deficiency (GKD). Interestingly, our DNA microarray analysis showed that several anti-cancer agents highly induced the expression of GK1, especially GK1a and GK1b isoforms, in human prostate cancer PC-3 cells. To elucidate the relationship between GK1 and cancer cell death, a human GK1b-specific expression vector was constructed and transfected into the PC-3 cells. Surprisingly, GK1b overexpression dramatically reduced cell viability and significantly accelerated apoptotic cell death. These findings suggest that GK1b may serve as a promising modulator and biomarker of cell death in prostate cancer, offering potential avenues for therapeutic intervention.

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As the global population ages, the death and prevalence of atrial fibrillation (AF) continue to rise, posing significant concerns due to its strong association with stroke-related disabilities. Detecting AF early before a stroke occurs has become paramount. However, existing methods face challenges in achieving quick, easy, and affordable detection in complex environments characterized by motion interference and varying light conditions. To address these challenges, we propose a system that is employable for edge computing devices like smartphones, tablets, or laptops. Meanwhile, to ensure that the dataset reflects real-world scenarios, we collect 7,216 30-second segments from 452 subjects, categorized into Atrial Fibrillation (AF), Normal Sinus Rhythm (NSR), and Other Arrhythmias (Others), with a subject ratio of 105:116:231. Our lightweight non-contact facial rPPG atrial fibrillation detection system utilizes a Convolution Neural Network (CNN) with a large receptive field and a bidirectional spatial mapping augmented attention module (BiSME-ATT) coupled with a bidirectional feature pyramid network layer (BiFPN), optimized for deployment on mobile devices by reducing model parameters and floating-point operations per second (FLOPs). Our approach significantly improves AF detection accuracy, sensitivity, specificity, positive predictive value, and negative predictive value to 94.39%, 91.57%, 95.44%, 88.06%, and 96.93%, respectively, in AF vs. Non-AF scenarios. Furthermore, the results demonstrate notable enhancements in AF detection across various motion and light intensity levels.

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The aim of this study was to evaluate the distance between the maxillary central incisor root and the incisive canal based on skeletal malocclusion classification and to analyze the morphology of the incisive canal using cone-beam computed tomography (CBCT). Skeletal malocclusion was categorized into Class I, II, and III using lateral cephalometric analysis. Measurements of the distance between the maxillary central incisor root and the incisive canal were taken at two levels: 2 mm (L1) and 4 mm (L2) superior to the labial cementoenamel junction of the maxillary central incisor. At L1, the distance was found to be closer in the Class II group compared to the Class I or Class III groups. Similarly, at L2, the Class II group exhibited a closer distance than the Class III group. Interestingly, females showed a closer distance compared to males at both L1 and L2. Further analysis revealed a significant gender difference in the Class I and III groups, but not in the Class II group. These findings emphasize the significance of evaluating the distance between the maxillary central incisor root and the incisive canal in patients with skeletal Class II malocclusion, regardless of gender.

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BACKGROUND: In intracranial stenting, good stent apposition is crucial, and high-resolution C-arm computer tomography (CT) is utilized to assess whether stent apposition is complete. This study was aimed at finding optimal hypertonic or isotonic contrast media injection concentration for high-resolution C-arm CT to assess apposition of flow diversion (FD) after carotid artery stenting in swine. METHODS: Twelve FD stents were implanted into the left carotid artery of Bama swine through the endovascular method. During high-resolution C-arm CT scanning, 6%, 8%, 10%, 12%, and 14% dilution percentages of hypertonic contrast media (iopromide 370 mg/ml) and 10%, 12%, 14%, 16%, and 18% dilution percentages of isotonic contrast media (iodixanol 320 mg/ml) were separately injected. A radiologist and a neuro-interventional specialist evaluated and qualitatively scored the post-processed images, and intravascular ultrasound (IVUS) was used to verify the accuracy of these images. RESULTS: Overall, 12 FD stents were implanted into the left common carotid artery of 12 swine, with a technical success rate of 100%. The best reconstructed images used to observe stent apposition were achieved with iopromide diluted to a concentration of 12% (all P < .05) or iodixanol diluted to a concentration of 16% (all P < .05). Malapposition was noted in one case, and good apposition was noted in 11 cases. These results were consistent with IVUS observations. CONCLUSION: Injecting iopromide or iodixanol diluted to 12% or 16% during high-resolution C-arm CT scanning, respectively, can help evaluate FD stent apposition and obtain optimal image quality.

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The rapid development of messenger RNA (mRNA) vaccines formulated with lipid nanoparticles (LNPs) has contributed to control of the COVID-19 pandemic. However, mRNA vaccines have raised concerns about their potential toxicity and clinical safety, including side effects, such as myocarditis, anaphylaxis, and pericarditis. In this study, we investigated the potential of trehalose glycolipids-containing LNP (LNP S050L) to reduce the risks associated with ionizable lipids. Trehalose glycolipids can form hydrogen bonds with polar biomolecules, allowing the formation of a stable LNP structure by replacing half of the ionizable lipids. The efficacy and safety of LNP S050L were evaluated by encapsulating the mRNA encoding the luciferase reporter gene and measuring gene expression and organ toxicity, respectively. Furthermore, mice immunized with an LNP S050L-formulated mRNA vaccine expressing influenza hemagglutinin exhibited a significant reduction in organ toxicity, including in the heart, spleen, and liver, while sustaining gene expression and immune efficiency, compared to conventional LNPs (Con-LNPs). Our findings suggest that LNP S050L, a trehalose glycolipid-based LNP, could facilitate the development of safe mRNA vaccines with improved clinical safety.

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Nasopharyngeal carcinoma (NPC) is a malignant tumor originated from the nasopharynx epithelial cells and has been linked with Epstein-Barr virus (EBV) infection, dietary habits, environmental and genetic factors. It is a common malignancy in Southeast Asia, especially with gender preference among men. Due to its non-specific symptoms, NPC is often diagnosed at a late stage. Thus, the molecular diagnosis of NPC plays a crucial role in early detection, treatment selection, disease monitoring, and prognosis prediction. This review aims to provide a summary of the current state and the latest emerging molecular diagnostic techniques for NPC, including EBV-related biomarkers, gene mutations, liquid biopsy, and DNA methylation. Challenges and potential future directions of NPC molecular diagnosis will be discussed.

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There is no consensus on the definition of sleep hygiene and its components. We examined the definition of sleep hygiene based on its use in published studies. Four databases (Medline, EMBASE, PsycINFO and CINAHL) were searched from inception until December 31, 2021 for the phrase 'sleep hygiene' in the title or abstract. We identified 548 relevant studies in adults: 250 observational and 298 intervention studies. A definition of sleep hygiene was provided in only 44% of studies and converged on three themes: behavioural factors, environmental factors, and an aspect of control. Sleep hygiene components were explicitly defined in up to 70% of observational studies, but in only 35% of intervention studies. The most commonly considered components of sleep hygiene were caffeine (in 51% of studies), alcohol (46%), exercise (46%), sleep timing (45%), light (42%), napping (39%), smoking (38%), noise (37%), temperature (34%), wind-down routine (33%), stress (32%), and stimulus control (32%), although the specific details of each component varied. Lack of consistency in definitions of sleep hygiene and its components may hinder communication between researchers, clinicians, and the public, and likely limits the utility of sleep hygiene as an intervention.

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Aim: Recent data have identified specific symptom and polysomnographic profiles associated with cardiovascular disease (CVD) in patients with obstructive sleep apnoea (OSA). Our aim was to determine whether these profiles were present at diagnosis of OSA in patients with established CVD and in those with high cardiovascular risk. Participants in the Sydney Sleep Biobank (SSB) database, aged 30-74 years, self-reported presence of CVD (coronary artery disease, cerebrovascular disease, or heart failure). In those without established CVD, the Framingham Risk Score (FRS) estimated 10-year absolute CVD risk, categorised as "low" (<6%), "intermediate" (6-20%), or "high" (>20%). Groups were compared on symptom and polysomnographic variables. Results: 629 patients (68% male; mean age 54.3 years, SD 11.6; mean BMI 32.3 kg/m2, SD 8.2) were included. CVD was reported in 12.2%. A further 14.3% had a low risk FRS, 38.8% had an intermediate risk FRS, and 34.7% had a high risk FRS. Groups differed with respect to age, sex and BMI. OSA severity increased with established CVD and increasing FRS. The symptom of waking too early was more prevalent in the higher FRS groups (p=0.004). CVD and FRS groups differed on multiple polysomnographic variables; however, none of these differences remained significant after adjusting for age, sex, and BMI. Conclusion: Higher CVD risk was associated with waking too early in patients with OSA. Polysomnographic variations between groups were explained by demographic differences. Further work is required to explore the influence of OSA phenotypic characteristics on susceptibility to CVD.

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This study aimed to evaluate the physiological role of NAMPT associated with MDPC-23 odontoblast cell proliferation. Cell viability was measured using the (DAPI) staining, caspase activation analysis and immunoblotting were performed. Visfatin promoted MDPC-23 odontoblast cell growth in a dose-dependent manner. Furthermore, the up-regulation of Visfatin promoted odontogenic differentiation and accelerated mineralization through an increase in representative odontoblastic biomarkers in MDPC-23 cells. However, FK-866 cell growth in a dose-dependent manner induced nuclear condensation and fragmentation. FK-866-treated cells showed H&E staining and increased apoptosis compared to control cells. The expression of anti-apoptotic factors components of the mitochondria-dependent intrinsic apoptotic pathway significantly decreased following FK-866 treatment. The expression of pro-apoptotic increased upon FK-866 treatment. In addition, FK-866 activated caspase-3 and PARP to induce cell death. In addition, after treating FK-866 for 72 h, the 3/7 activity of MDPC-23 cells increased in a concentration-dependent manner, and the IHC results also confirmed that Caspase-3 increased in a concentration-dependent. Therefore, the presence or absence of NAMPT expression in dentin cells was closely related to cell proliferation and formation of extracellular substrates.

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BACKGROUND/AIMS: Since the coronavirus disease 2019 (COVID-19) outbreak, hospitals have implemented infection control measures to minimize the spread of the virus within facilities. This study aimed to investigate the impact of COVID-19 on the incidence of healthcare-associated infections (HCAIs) and common respiratory virus (cRV) infections in hematology units. METHODS: This retrospective study included all patients hospitalized in Catholic Hematology Hospital between 2019 and 2020. Patients infected with vancomycin-resistant Enterococci (VRE), carbapenemase-producing Enterobacterales (CPE), Clostridium difficile infection (CDI), and cRV were analyzed. The incidence rate ratio (IRR) methods and interrupted time series analyses were performed to compare the incidence rates before and after the pandemic. RESULTS: The incidence rates of CPE and VRE did not differ between the two periods. However, the incidence of CDI increased significantly (IRR: 1.41 [p = 0.002]) after the COVID-19 pandemic. The incidence of cRV infection decreased by 76% after the COVID-19 outbreak (IRR: 0.240 [p < 0.001]). The incidence of adenovirus, parainfluenza virus, and rhinovirus infection significantly decreased in the COVID-19 period (IRRs: 0.087 [p = 0.003], 0.031 [p < 0.001], and 0.149 [p < 0.001], respectively). CONCLUSION: The implementation of COVID-19 infection control measures reduced the incidence of cRV infection. However, CDI increased significantly and incidence rates of CPE and VRE remained unchanged in hematological patients after the pandemic. Infection control measures suitable for each type of HCAI, such as stringent hand washing for CDI and enough isolation capacities, should be implemented and maintained in future pandemics, especially in immunocompromised patients.

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SUMMARY: Failure to locate a complete canal system affects the prognosis of root canal treatment. A missed root canal is one of the most common reasons for failed root canal treatment. The prevalence of the second mesiobuccal canal in the maxillary second molar is relatively high and has a variety of configurations. Therefore, knowledge of its morphology is required in clinical endodontics. This review presented the canal in terms of its prevalence, classification, anatomical features, and the method for locating the second mesiobuccal canal in the maxillary second molar. Root canal treatment requires knowledge of tooth morphology, appropriate access preparation, and a thorough examination of the tooth's interior. Thus, clinicians should carefully employ various methods for assessing the anatomy of the entire root canal system to prevent failure in locating the second mesiobuccal canal. This canal can be located by modifying the access cavity design and utilizing specific instruments to improve the second mesiobuccal canal system visualization.

La falta de localización de un sistema completo de canal afecta el pronóstico del tratamiento de éste. La omisión de un tratamiento de canal es uno de los motivos más frecuentes por las que el tratamiento de canal fracasa. La prevalencia del segundo canal mesiovestibular en el segundo molar superior es relativamente alta y tiene una variedad de configuraciones. Por tanto, el conocimiento de su morfología es necesario en endodoncia clínica. Esta revisión presentó el canal en términos de su prevalencia, clasificación, características anatómicas y el método para localizar el segundo canal mesiovestibular en el segundo molar superior. El tratamiento de canal requiere conocimiento de la morfología del diente, una preparación adecuada del acceso y un examen exhaustivo del interior del diente. Por lo tanto, los dentistas deben emplear cuidadosamente varios métodos para evaluar la anatomía de todo el sistema de canales radiculares para evitar fallas en la localización del segundo canal mesiovestibular. Este canal se puede localizar modificando el diseño de la cavidad de acceso y utilizando instrumentos específicos para mejorar la visualización del sistema del segundo canal mesiovestibular.

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Analyzing the correlation between cephalometric measurements is important for improving our understanding of the anatomy in the oral and maxillofacial region. To minimize bias resulting from the design of the input data and to establish a reference for malocclusion research, the aims of this study were to construct the input set by integrating nine cephalometric analyses and to study the correlation structure of cephalometric variables in Korean adults with normal occlusion. To analyze the complex correlation structure among 65 cephalometric variables, which were based on nine classical cephalometric analyses, network analysis was applied to data obtained from 735 adults (368 males, 367 females) aged 18-25 years with normal occlusion. The structure was better revealed through weighted network analysis and minimum spanning tree. Network analysis revealed cephalometric variable clusters and the inter- and intra-correlation structure. Some metrics were divided based on their geometric interpretation rather than their clinical significance. It was confirmed that various classical cephalometric analyses primarily focus on investigating nine anatomical features. Investigating the correlation between cephalometric variables through network analysis can significantly enhance our understanding of the anatomical characteristics in the oral and maxillofacial region, which is a crucial step in studying malocclusion using artificial intelligence.

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Causal effect estimation of individual heterogeneity is a core issue in the field of causal inference, and its application in medicine poses an active and challenging problem. In high-risk decision-making domain such as healthcare, inappropriate treatments can have serious negative impacts on patients. Recently, machine learning-based methods have been proposed to improve the accuracy of causal effect estimation results. However, many of these methods concentrate on estimating causal effects of continuous outcome variables under binary intervention conditions, and give less consideration to multivariate intervention conditions or discrete outcome variables, thus limiting their scope of application. To tackle this issue, we combine the double machine learning framework with Light Gradient Boosting Machine (LightGBM) and propose a double LightGBM model. This model can estimate binary causal effects more accurately and in less time. Two cyclic structures were added to the model. Data correction method was introduced and improved to transform discrete outcome variables into continuous outcome variables. Multivariate Cyclic Double LightGBM model (MCD-LightGBM) was proposed to intelligently estimate multivariate treatment effects. A visual human-computer interaction system for heterogeneous causal effect estimation was designed, which can be applied to different types of data. This paper reports that the system improved the Logarithm of the Minimum Angle of Resolution (LogMAR) of visual acuity change after Vascular Endothelial Growth Factor (anti-VEGF) treatment in patients with diabetic macular degeneration. The improvement was observed in two clinical problems, from 0.05 to 0.33, and the readmission rate of diabetic patients after cure was reduced from 48.4% to 10.5%. The results above demonstrate the potential of the proposed system in predicting heterogeneous clinical drug treatment effects.

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INTRODUCTION: Understanding how persons with narcolepsy conceptualize symptoms, daily impact and illness experience is key to facilitating dialogue between patients and healthcare professionals. These concepts are usually explored from the perspective of healthcare professionals/researchers and rarely from the perspective of those with narcolepsy. METHODS: 127 self-reported persons with narcolepsy were recruited from an Australian patient support group. A short demographic survey was completed. All agreed to participate in a subsequent 1:1 semi-structured interview. Saturation was reached after 24 interviews (mean age = 33 years (SD 11) with 44% reporting cataplexy). A multidisciplinary team of researchers/clinicians analyzed interview transcripts using thematic analysis. RESULTS: Participants perceived physical fatigue, sleepiness, and two separate experiences of 'falling asleep/sleep attacks' as distinct symptoms rather than a multidimensional construct (i.e. excessive daytime sleepiness). We also identified two experiences of cataplexy, one triggered by acute emotion and another by a stressor. Participants determined their narcolepsy to be 'well-managed' by the level of functional impairment rather than the frequency of any symptom. Almost all participants described experiencing anticipated stigma and internalized or 'self-' stigma, likely stemming from societal devaluation of sleep and the conflation of sleepiness with laziness. CONCLUSION: Descriptions of common symptoms often differed between participants and the existing literature. These differences likely impact patient-physician communication, with both parties utilizing the same terminology to communicate different concepts. The characterization of stigma in narcolepsy presents opportunities for future research exploring the impact and possible development of interventions to reduce the substantial psychological comorbidity in persons with narcolepsy.

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STUDY OBJECTIVES: Recent studies suggest that sleepy patients with obstructive sleep apnea (OSA) are at higher risk for incident cardiovascular disease. This study assessed cardiac autonomic function in sleepy versus non-sleepy patients with OSA using heart rate variability (HRV) analysis. We hypothesized that HRV profiles of sleepy patients would indicate higher cardiovascular risk. METHODS: Electrocardiograms (ECG) derived from polysomnograms (PSG) collected by the Sydney Sleep Biobank were used to study HRV in groups of sleepy (ESS ≥ 10) and non-sleepy OSA patients (ESS < 10). HRV parameters were averaged across available ECG signals during N2 sleep. RESULTS: A total of 421 patients were evaluated, with a mean age of 54 (14) years, body mass index of 33 (9) kg/m2, apnea-hypopnea index of 21 (28) events/h, and 66% male. The sleepy group consisted of 119 patients and the non-sleepy group 302 patients. Sleepy patients exhibited lower HRV values for: root mean square successive difference (RMSSD, p = 0.028), total power (TP, p = 0.031), absolute low frequency (LF, p = 0.045), and high-frequency (HF, p = 0.010) power compared to non-sleepy patients. Sleepy patients with moderate-to-severe OSA exhibited lower HRV values for: (RMSSD, p = 0.045; TP, p = 0.052), absolute LF (p = 0.051), and HF power (p = 0.025). There were no differences in other time and frequency domain HRV markers. CONCLUSIONS: This study shows a trend toward parasympathetic withdrawal in sleepy OSA patients, particularly in moderate-to-severe cases, lending mechanistic support to the link between the sleepy phenotype and CVD risk in OSA.

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An 82-year-old woman presented with a 6-month history of an enlarging brow mass that developed after trauma. Clinical and MRI appearance of the lesion appeared consistent with epidermal inclusion cyst. However, excisional biopsy demonstrated invasive squamous cell carcinoma, which recurred 6 weeks later and required repeat surgical excision. To our knowledge, this represents the first case of squamous cell carcinoma arising from a posttraumatic epidermal inclusion cyst.

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Background: Postoperative atrial fibrillation (A-fib) is a serious complication of cardiac surgery that is associated with increased mortality and morbidity. Traditional 24-hour Holter monitors have limitations, which have prompted the development of innovative wearable electrocardiogram (ECG) monitoring devices. This study assessed a patch-type wearable ECG device (MobiCARE-MC100) for monitoring A-fib in patients undergoing cardiac surgery and compared it with 24-hour Holter ECG monitoring. Methods: This was a single-center, prospective, investigator-initiated cohort study that included 39 patients who underwent cardiac surgery between July 2021 and June 2022. Patients underwent simultaneous monitoring with both conventional Holter and patchtype ECG devices for 24 hours. The Holter device was then removed, and patch-type monitoring continued for an additional 48 hours, to determine whether extended monitoring provided benefits in the detection of A-fib. Results: This 72-hour ECG monitoring study included 39 patients, with an average age of 62.2 years, comprising 29 men (74.4%) and 10 women (25.6%). In the initial 24 hours, both monitoring techniques identified the same number of paroxysmal A-fib in 7 out of 39 patients. After 24 hours of monitoring, during the additional 48-hour assessment using the patch-type ECG device, an increase in A-fib burden (9%→38%) was observed in 1 patient. Most patients reported no significant discomfort while using the MobiCARE device. Conclusion: In patients who underwent cardiac surgery, the mobiCARE device demonstrated diagnostic accuracy comparable to that of the conventional Holter monitoring system.

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The implications of administration of mRNA vaccines to individuals with chronic inflammatory diseases, including myocarditis, rheumatoid arthritis (RA), and inflammatory bowel disease (IBD), are unclear. We investigated mRNA vaccine effects in a chronic inflammation mouse model implanted with an LPS pump, focusing on toxicity and immunogenicity. Under chronic inflammation, mRNA vaccines exacerbated cardiac damage and myocarditis, inducing mild heart inflammation with heightened pro-inflammatory cytokine production and inflammatory cell infiltration in the heart. Concurrently, significant muscle damage occurred, with disturbances in mitochondrial fusion and fission factors signaling impaired muscle repair. However, chronic inflammation did not adversely affect muscles at the vaccination site or humoral immune responses; nevertheless, it partially reduced the cell-mediated immune response, particularly T-cell activation. These findings underscore the importance of addressing mRNA vaccine toxicity and immunogenicity in the context of chronic inflammation, ensuring their safe and effective utilization, particularly among vulnerable populations with immune-mediated inflammatory diseases.