Kikuchi-Fujimoto disease following SARS-CoV-2 infection: A rare disease with increased incidence during the COVID-19 pandemic?

Kikuchi-Fujimoto Disease (KFD), also known as Kikuchi disease or Kikuchi histiocytic necrotizing lymphadenitis, is a rare and self-limiting condition characterized by cervical lymphadenopathy and fever, primarily affecting young Asian adults. The aetiology of KFD remains unknown, although various infectious agents have been suggested as potential triggers. With the emergence of the COVID-19 pandemic, cases of post-COVID-19 KFD and post-COVID-19 vaccine KFD have been reported. In this article, we present the first case of post-COVID-19 KFD in Hong Kong. A 24-year-old man developed fever and painful neck swelling 1 month after recovering from COVID-19. Diagnostic evaluation, including ultrasound-guided fine needle aspiration cytology (FNAC), confirmed the diagnosis of KFD. The patient's symptoms resolved spontaneously with supportive care. This case underscores the importance of considering KFD as a potential differential diagnosis in patients presenting with cervical lymphadenopathy and fever following COVID-19 recovery or vaccination.

Improving Understanding of Visual Snow by Quantifying its Appearance and Effect on Vision.

Purpose: Visual snow is the hallmark of the neurological condition visual snow syndrome (VSS) but the characteristics of the visual snow percept remain poorly defined. This study aimed to quantify its appearance, interobserver variability, and effect on measured visual performance and self-reported visual quality. Methods: Twenty-three participants with VSS estimated their visual snow dot size, separation, luminance, and flicker rate by matching to a simulation. To assess whether visual snow masks vision, we compared pattern discrimination thresholds for textures that were similar in spatial scale to visual snow as well as more coarse than visual snow, in participants with VSS, and with and without external noise simulating visual snow in 23 controls. Results: Mean and 95% confidence intervals for visual snow appearance were: size (6.0, 5.8-6.3 arcseconds), separation (2.0, 1.7-2.3 arcmin), luminance (72.4, 58.1-86.8 cd/m2), and flicker rate (25.8, 18.9-32.8 frames per image at 120 hertz [Hz]). Participants with finer dot spacing estimates also reported greater visibility of their visual snow (τb = -0.41, 95% confidence interval [CI] = -0.62 to -0.13, P = 0.01). In controls, adding simulated fine-scale visual snow to textures increased thresholds for fine but not coarse textures (F(1, 22) = 4.98, P = 0.036, ηp2 = 0.19). In VSS, thresholds for fine and coarse textures were similar (t(22) = 0.54, P = 0.60), suggesting that inherent visual snow does not act like external noise in controls. Conclusions: Our quantitative estimates of visual snow constrain its likely neural origins, may aid differential diagnosis, and inform future investigations of how it affects vision. Methods to quantify visual snow are needed for evaluation of potential treatments.

Implementation of a Smart Teaching and Assessment System for High-Quality Cardiopulmonary Resuscitation.

The purpose of this study is to develop a smart training and assessment system called SmartCPR, for teaching and training cardiopulmonary resuscitation (CPR), based on human posture estimation techniques. In this system, trainees can automatically recognize and evaluate whether chest compressions during CPR meet the standard of high-quality CPR by simply using a device such as a smart phone. Through the system, trainees are able to obtain real-time feedback on the quality of compressions so that they can adjust the cycle, depth, frequency, and posture of compressions to meet the standard of high-quality CPR. In addition, the SmartCPR system is convenient for CPR trainers. Trainers can instantly and accurately assess whether the trainee's compressions meet the standard of high-quality CPR, which reduces the risk of manual assessment errors and also reduces the trainer's teaching pressures. Therefore, the SmartCPR system developed in this study can be an important tool for CPR teaching and training for physicians, which can provide training and guidance for high-quality CPR maneuvers and enable trainees to become more proficient in CPR and self-training.

Hyaluronic acid-based injectable formulation developed to mitigate metastasis and radiation-induced skin fibrosis in breast cancer treatment.

The standard treatment for early-stage breast cancer involves breast-conserving surgery followed by adjuvant radiotherapy. However, approximately 20 % of patients experience distant metastasis, and adjuvant radiotherapy often leads to radiation-induced skin fibrosis (RISF). In this study, we develop an on-site injectable formulation composed of selenocystamine (SeCA) and hyaluronic acid (HyA), referred to as SeCA cross-linked HyA (SCH) agent, and investigate its potential to mitigate metastasis and prevent RISF associated with breast cancer therapy. SCH agents are synthesized using the nanoprecipitation method to modulate cell-cell tight junctions and tissue inflammation. The toxicity assessments reveal that SCH agents with a higher Se content (Se payload 17.4 µg/mL) are well tolerated by L929 cells compared to SeCA (Se payload 3.2 µg/mL). In vitro, SCH agents significantly enhance cell-cell tight junctions and effectively mitigate migration and invasion of breast cancer cells (4T1). In vivo, SCH agents mitigate distant lung metastasis. Furthermore, in animal models, SCH agents reduce RISF and promote wound repair. These findings highlight the potential of SCH agents as a novel therapeutic formulation for effectively mitigating metastasis and reducing RISF. This holds great promise for improving clinical outcomes in breast cancer patients undergoing adjuvant radiotherapy.

The neddylation inhibitor MLN4924 inhibits proliferation and triggers apoptosis of oral cancer cells but not for normal cells.

Increased neddylation benefits the survival of several types of cancer cells. The inhibition of neddylation has the potential to exert anticancer effects but is rarely assessed in oral cancer cells. This study aimed to investigate the antiproliferation potential of a neddylation inhibitor MLN4924 (pevonedistat) for oral cancer cells. MLN4924 inhibited the cell viability of oral cancer cells more than that of normal oral cells (HGF-1) with 100% viability, that is, IC50 values of oral cancer cells (CAL 27, OC-2, and Ca9-22) are 1.8, 1.4, and 1.9 µM. MLN4924 caused apoptotic changes such as the subG1 accumulation, activation of annexin V, pancaspase, and caspases 3/8/9 of oral cancer cells at a greater rate than in normal oral cells. MLN4924 induced greater oxidative stress in oral cancer cells compared to normal cells by upregulating reactive oxygen species and mitochondrial superoxide and depleting the mitochondrial membrane potential and glutathione. In oral cancer cells, preferential inductions also occurred for DNA damage (γH2AX and 8-oxo-2'-deoxyguanosine). Therefore, this investigation demonstrates that MLN4924 is a potential anti-oral-cancer agent showing preferential inhibition of apoptosis and promotion of DNA damage with fewer cytotoxic effects on normal cells.

Data-Driven Design for Metamaterials and Multiscale Systems: A Review.

Metamaterials are artificial materials designed to exhibit effective material parameters that go beyond those found in nature. Composed of unit cells with rich designability that are assembled into multiscale systems, they hold great promise for realizing next-generation devices with exceptional, often exotic, functionalities. However, the vast design space and intricate structure-property relationships pose significant challenges in their design. A compelling paradigm that could bring the full potential of metamaterials to fruition is emerging: data-driven design. This review provides a holistic overview of this rapidly evolving field, emphasizing the general methodology instead of specific domains and deployment contexts. Existing research is organized into data-driven modules, encompassing data acquisition, machine learning-based unit cell design, and data-driven multiscale optimization. The approaches are further categorized within each module based on shared principles, analyze and compare strengths and applicability, explore connections between different modules, and identify open research questions and opportunities.

Structural brain feature is associated with changes of masticatory performance in healthy elderly people: Evidence from longitudinal neuroimaging research over two years.

BACKGROUND: Human neuroimaging studies have revealed the association between brain structure and masticatory function. However, the majority of the studies adopted a cross-sectional design, which hardly reveals the change in masticatory function and brain structure between different timepoints, and the dynamical association between changes in masticatory function and changes in brain structure has not been elucidated. OBJECTIVE: With a longitudinal design, we assessed the association between changes in masticatory performance (MP) and regional brain volume. METHODS: Twenty-two elderly participants received assessments of the number of missing teeth and MP (via colour-changeable chewing gum) when they entered the study (i.e. the initial stage, T0 ), approximately 6 months later (T0.5 ), and approximately 1-2 years later (T1 ). Difficulty of food intake was assessed using a questionnaire. The participants received magnetic resonance imaging (MRI) at T0 and T1 . The brain volume of the motor-related area was estimated using FreeSurfer for MRI data. The associations between different stages were analysed using Spearman's rho correlation coefficients. RESULTS: (1) Individually, a smaller volume of right primary motor cortex at T0 was associated with increased MP from T0 to T1 , suggesting the brain's role in changing oral functions; (2) higher MP at T0 was associated with an increased volume of the left superior frontal cortex from T0 to T1 p, suggesting a potential effect on brain plasticity, and (3) increased difficulty to eat was associated with decrease MP but not brain volume of motor-related area. CONCLUSIONS: The preliminary findings revealed a complicated pattern of structural brain features and masticatory function in elderly people, and either the hypothesis that the brain predisposes masticatory function or the hypothesis that mastication reshapes the brain is oversimplified.

Highly selective Cu2+ detection with a naphthalimide-functionalised pillar[5]arene fluorescent chemosensor.

Ligand 1, a rim-differentiated pillar[5]arene macrocycle modified with five naphthalimide groups through click chemistry, serves as an effective ratiometric fluorescent chemosensor for Cu2+. In contrast to the monomeric naphthalimide control compound 2, which shows only monomer emission, ligand 1 demonstrates dual emission characteristics encompassing both the monomer and excimer of the naphthalimide moieties. The binding properties of ligand 1 toward 15 different metal ions were systematically investigated in CH2Cl2/CH3CN (v/v, 1 : 1) by UV-vis and fluorescence spectroscopy. Remarkably, ligand 1 exhibits exceptional selectivity for Cu2+ ions. Upon complexation with Cu2+, the excimer emission of ligand 1 diminishes, concomitant with an enhancement of its monomer emission. The binding ratio for 1·Cu2+ was determined to be 1 : 1, with an association constant of (3.39 ± 0.40) × 105 M-1 calculated using a nonlinear least-squares curve-fitting method. Furthermore, the limit of detection (LOD) was found to be 185 ± 7 nM. Our results from 1H NMR titration, high-resolution mass spectrometry analysis and density functional theory calculations of 1·Cu2+ suggest synergistic coordination between Cu2+ and the triazole groups on ligand 1.

The Pulse of Singapore: Short-Term HRV Norms.

Short-term heart rate variability (HRV) is increasingly used to assess autonomic nervous system activity and found to be useful for monitoring and providing care due to its quick measurement. With evidence of low HRV associated with chronic diseases, mental disorders, and an increased risk of cardiovascular disease, having normative data of HRV across the age spectrum would be useful for monitoring health and well-being of a population. This study examines HRV of healthy Singapore sample, with ages ranging from 10 to 89 years. Short-term HRV of five minutes was measured from 2,143 participants. 974 males and 1,169 females, and overall HRV was found to be 42.4ms (RMSSD) and 52.0 ms (SDNN) with a further breakdown of HRV by age and gender. Overall HRV declined with age and gender, although gender differences dissipated in the 60s age range onwards, with the 50s age range having the sharpest decline in HRV. Short-term HRV norms were similar to Nunan et al.'s (2010) systematic review in various populations and less similar to Choi et al.'s (2020) study on Koreans.

A non-socially-sensitive predictive model of prostate cancer for Asian males with benign prostatic hyperplasia: A multi-site cross-sectional case-control study.

BACKGROUND: Benign prostatic hyperplasia (BPH) is common in aging Asian males and is associated with an excess risk of developing prostate cancer (PCa). However, discussions about socially-sensitive experiences such as sexual activity, which can significantly predict PCa risk, may be considered stigmatized in Asian culture. This study aimed to develop a predictive model for PCa risk in Asian males with BPH using non-socially-sensitive information. METHODS: A cross-sectional case-control study, with PCa patients as the cases and remaining as the controls, was conducted on a cohort of Taiwanese males with BPH from four medical institutions. Patients who met the inclusion criteria were enrolled, excluding those aged over 86 years or who had received human papillomavirus (HPV) vaccination. Non-socially-sensitive variables such as obesity, occupational exposure, HPV infection, and PCa family history score (FH score) were included in a fully adjusted logistic regression model, and depicted using a nomogram. RESULTS: Among 236 BPH patients, 45.3% had PCa. Obesity, occupational exposure, HPV infection, and family history of PCa were significantly associated with PCa risk. The FH score (OR = 1.89, 95% CI = 1.03-3.47, P = 0.041) had the highest impact, followed by HPV infection (OR = 1.47, 95% CI = 1.03-2.11, P = 0.034), occupational exposure (OR = 1.32, 95% CI = 1.15-1.51, P <0.001), and obesity (OR = 1.22, 95% CI = 1.07-1.41, P = 0.005). The nomogram accurately depicted the predictive risk, and the model demonstrated robust performance compared to individual factors. In addition, the subgroup analysis results showed elderly age group could obtain more favorable predictive performance in our proposed model (AUC = 0.712). CONCLUSION: This non-socially-sensitive predictive model for PCa risk in Taiwanese males with BPH integrates multiple factors that could provide acceptable PCa risk-predictive performance, especially for elderly BPH patients over 70 years, aiding clinical decision-making and early cancer detection.

Case Report: One heart with two lobes: a rare infantile congenital giant left atrial appendage aneurysm.

Left atrial appendage aneurysm (LAAA) is an extremely rare congenital heart abnormality, with varying degrees of symptoms, ranging from asymptomatic to arrhythmia, thromboembolic event or airway obstruction. Most infantile cases were incidentally found by echocardiography. Contrast-enhanced chest tomography can confirm the diagnosis and inform surgical plan. We describe an asymptomatic young female infant who had a unique extreme cardiomegaly on a chest x-ray and received surgical aneurysmectomy. Her heart was restored to a normal cardiac size after the heart surgery.

ISGF3 and STAT2/IRF9 Control Basal and IFN-Induced Transcription through Genome-Wide Binding of Phosphorylated and Unphosphorylated Complexes to Common ISRE-Containing ISGs.

In addition to the canonical ISGF3 and non-canonical STAT2/IRF9 complexes, evidence is emerging of the role of their unphosphorylated counterparts in IFN-dependent and -independent ISG transcription. To better understand the relation between ISGF3 and U-ISGF3 and STAT2/IRF9 and U-STAT2/IRF9 in IFN-I-stimulated transcriptional responses, we performed RNA-Seq and ChIP-Seq, in combination with phosphorylation inhibition and antiviral experiments. First, we identified a group of ISRE-containing ISGs that were commonly regulated in IFNα-treated WT and STAT1-KO cells. Thus, in 2fTGH and Huh7.5 WT cells, early and long-term IFNα-inducible transcription and antiviral activity relied on the DNA recruitment of the ISGF3 components STAT1, STAT2 and IRF9 in a phosphorylation- and time-dependent manner. Likewise, in ST2-U3C and Huh-STAT1KO cells lacking STAT1, delayed IFN responses correlated with DNA binding of phosphorylated STAT2/IRF9 but not U-STAT2/IRF9. In addition, comparative experiments in U3C (STAT1-KO) cells overexpressing all the ISGF3 components (ST1-ST2-IRF9-U3C) revealed U-ISGF3 (and possibly U-STAT2/IRF9) chromatin interactions to correlate with phosphorylation-independent ISG transcription and antiviral activity. Together, our data point to the dominant role of the canonical ISGF3 and non-canonical STAT2/IRF9, without a shift to U-ISGF3 or U-STAT2/IRF9, in the regulation of early and prolonged ISG expression and viral protection. At the same time, they suggest the threshold-dependent role of U-ISFG3, and potentially U-STAT2/IRF9, in the regulation of constitutive and possibly long-term IFNα-dependent responses.

Thermal pattern of Tatun volcanic system by satellite-observed temperatures and its correlation with earthquake magnitudes.

The land surface temperature (LST) of volcanoes detected from satellite sensors reflects the thermal status of heat sources in the subsurface. Volcanic earthquakes occur as magma and volcanic fluids transport to the surface from depth. Thus, both LST and earthquake magnitude are key parameters to the study of active volcanoes. Here we investigate the volcanic status of Tatun Volcanic Group (TVG) based on LST and seismic observations. The Earth-observing satellites onboard thermal sensor derived land surface temperature, and the seismic records retrieved volcanic earthquake magnitude are used to delineate the past and current pattern of volcanic activity plus the future trend of the TVG. The spatiotemporal distribution of LST and volcanic earthquake magnitude in TVG are analyzed. The high-similarity trends of the 4-decade LST time series and 3-decade earthquake magnitude time series are inspected. The retrieved surface thermal pattern shows the non-steady-state nature of the subsurface thermal sources at this volcanic complex. The LST trend exhibits a rather positive correlation with the energy released from volcanic earthquakes and consequently, the presumption on the connection between LSTs and earthquakes is validated.

Ultrasonographic cervical length screening at 20-24 weeks of gestation in twin pregnancies for prediction of spontaneous preterm birth: A 10-year Taiwanese cohort.

BACKGROUND: Shortened cervical length is one of the primary predictors for spontaneous preterm deliveries in twin pregnancies. However, there is lack of consensus regarding cut-off values. Recent evidence highlights that established cut-offs for cervical length screening might not always apply across different populations. This study aims to present the distribution of cervical length in Taiwanese twin pregnancies and to assess its predictive value for spontaneous preterm birth during mid-trimester screening. MATERIALS AND METHODS: This retrospective analysis of cervical length screening in Taiwan evaluated 469 twin pregnancies between 20-24 weeks of gestation. Outcome data were obtained directly from the medical records of the delivery hospital. The study explored the predictive value of cervical length screening for spontaneous preterm birth and the characteristics of cervical length distribution in Taiwanese twin pregnancies. RESULTS: The average gestational age at screening was 22.7 weeks. Cervical length values displayed a non-normal distribution (p-value <0.001). The median, 5th and 95th centiles were 37.5 mm 25.1 mm, and 47.9 mm, respectively. Various cut-off values were assessed using different methods, yielding positive [negative] likelihood ratios for spontaneous preterm births between 32-37 weeks of gestational age (GA) (1.3-30.1 and [0.51-0.92]) and for very preterm births between 28-32 weeks GA (5.6-51.1 and [0.45-0.64]). CONCLUSIONS: The findings from our analysis of Taiwanese twin pregnancies uphold the moderate predictive potential of cervical length screening, consistent with prior investigations. The presented likelihood ratios for predicting preterm birth at different gestational ages equip clinicians with valuable tools to enhance their diagnostic rationale and resource utilization. By fine-tuning screening parameters according to the spontaneous preterm birth prevalence and clinical priorities of the particular population, healthcare providers can enhance patient care. Our data implies that a cervical length below 20 mm might provide an optimal balance between minimizing false negatives and managing false positives when predicting spontaneous preterm birth.

Calix[4]arene-based Supramolecular Gels for Mercury Ion Removal in Water.

A calix[4]arene-based gelator 1, with lower-rim mono triazolylpyridine group, capable of spontaneous self-assembly into microspheres in different ethanol/H2 O mixtures, is synthesized. The concentration-dependent 1 H NMR spectra and X-ray single-crystal structure of 1 provided evidence for self-assembly of gelator 1 via cooperative interactions of intermolecular noncovalent forces. Furthermore, metallogels by self-assembly of 1 was found to exhibit remarkable selectivity toward Hg2+ ions. 1 H NMR spectra support that Hg2+ ion was bound to the nitrogen atoms of two coordination sites of 1, which composed of triazole and pyridine. Moreover, the results of field emission scanning electron microscopy and rheology experiments indicated that Hg2+ ions not only enhanced the gelling ability of gelator 1 in ethanol but also led to morphological change of its self-assembly through metal-ligand interactions. Finally, the in situ gelation, triggered by mixing a gelator solution of 1 in ethanol with water samples such as deionized (DI), tap, and lake water, leads to the effective removal of Hg(II) from a water sample which reduced from 400 to 1.6 ppm.

Impact of Diverse Parameters on the Physicochemical Characteristics of Green-Synthesized Zinc Oxide-Copper Oxide Nanocomposites Derived from an Aqueous Extract of Garcinia mangostana L. Leaf.

Compared to conventional metal oxide nanoparticles, metal oxide nanocomposites have demonstrated significantly enhanced efficiency in various applications. In this study, we aimed to synthesize zinc oxide-copper oxide nanocomposites (ZnO-CuO NCs) using a green synthesis approach. The synthesis involved mixing 4 g of Zn(NO3)2·6H2O with different concentrations of mangosteen (G. mangostana) leaf extract (0.02, 0.03, 0.04 and 0.05 g/mL) and 2 or 4 g of Cu(NO3)2·3H2O, followed by calcination at temperatures of 300, 400 and 500 °C. The synthesized ZnO-CuO NCs were characterized using various techniques, including a UV-Visible spectrometer (UV-Vis), photoluminescence (PL) spectroscopy, Fourier Transform Infrared (FTIR) spectroscopy, X-ray powder diffraction (XRD) analysis and Field Emission Scanning Electron Microscope (FE-SEM) with an Energy Dispersive X-ray (EDX) analyzer. Based on the results of this study, the optical, structural and morphological properties of ZnO-CuO NCs were found to be influenced by the concentration of the mangosteen leaf extract, the calcination temperature and the amount of Cu(NO3)2·3H2O used. Among the tested conditions, ZnO-CuO NCs derived from 0.05 g/mL of mangosteen leaf extract, 4 g of Zn(NO3)2·6H2O and 2 g of Cu(NO3)2·3H2O, calcinated at 500 °C exhibited the following characteristics: the lowest energy bandgap (2.57 eV), well-defined Zn-O and Cu-O bands, the smallest particle size of 39.10 nm with highest surface area-to-volume ratio and crystalline size of 18.17 nm. In conclusion, we successfully synthesized ZnO-CuO NCs using a green synthesis approach with mangosteen leaf extract. The properties of the nanocomposites were significantly influenced by the concentration of the plant extract, the calcination temperature and the amount of precursor used. These findings provide valuable insights for researchers seeking innovative methods for the production and utilization of nanocomposite materials.

Use of high flow nasal cannula oxygen therapy for patients infected with SARS-CoV-2 outside intensive care setting.

Background: In early 2022, there was a sudden surge of patients infected by the Omicron variant of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) in Hong Kong (HK), resulting in 9,163 deaths as of 29 May 2022. Many of the local population had not been vaccinated before this wave. The number of patients who developed coronavirus disease 2019 (COVID-19) related respiratory failure outnumbered the capacity of intensive care unit (ICU) beds. Some of these patients had to be supported with high flow nasal cannula (HFNC) therapy outside ICU setting. HK was in crisis situation. The primary objective of this study is to assess the 28-day mortality of this group of patients. The secondary objective is to explore any predictors of non-survivors to help clinical decision-making in future crisis. Methods: This is a retrospective observational study of patients suffering from COVID-19 related respiratory failure who received HFNC therapy in general medical wards of two hospitals during the period of 17 Mar to 30 Apr 2022. Survival and risk factors were reviewed. Results: Forty-nine patients were recruited. Twenty-six patients (53%) survived at 28-day after initiation of HFNC support. Three clinical parameters were found to be significantly associated with mortality at 28-day: (I) SpO2/FiO2 (SF) ratio <160 at 48 hours; (II) SF ratio <191 at 72 hours; (III) serial SF ratio at 48 or 72 hours showing no improvement over that at the time of initiation of HFNC therapy. Conclusions: Use of HFNC outside ICU setting showed benefit to patients suffering from COVID-19 related acute hypoxemic respiratory failure (AHRF). Serial SF ratio monitoring at 48 and 72 hours after therapy initiation might serve as predictors of outcome and thus guide clinical decision-making for medical resource allocation in outbreak situation.

Parental Postoperative Pain Management Perceptions, Attitudes, and Practices in Pediatric Limb Fractures.

BACKGROUND: Post-surgical pain in children is common, severe, and inadequately controlled. An effective model should involve the participation of parents. AIMS: To investigate parental perceptions, attitudes, and practices in postoperative pain management in children with limb fractures and analyze the factors affecting parental practices. DESIGN: This was a descriptive cross-sectional study. SETTINGS: Research was conducted at a tertiary Children's Hospital Affiliated with Soochow University. PARTICIPANTS: Parents whose children (age, 6-18 years) underwent orthopedic fracture surgery between January 1, 2020, and August 31, 2020, were recruited using purposive sampling. METHODS: The parents were asked to complete self-report questionnaires: "Pain Management Knowledge and Attitudes Questionnaire" and "Parents' Use of Pain Relief Strategies Questionnaire." The Wong-Baker Faces Scale was used to measure pain intensity in children. The Mann-Whitney U test, Kruskal-Wallis H test, and correlation and regression analyses were used for statistical analyses. RESULTS: Data of 180 parents were collected. Of the participants, 80.6%, 78.3%, and 71.7% had low-to-moderate scores for knowledge, general attitudes, and use of pain relief strategies, respectively. Moreover, 93.9% of parents had moderate-to-high scores for negative attitudes toward medication, despite 89.5% of them reporting moderate-to-high pain intensities in their children (median proxy-report of pain intensity, 7.0 [3.00]). Multivariate linear stepwise regression showed that parents' use of pain-relief strategies was related to their general attitudes, knowledge, and sex. CONCLUSIONS: Most parents had low-to-moderate scores for perceptions and general attitudes toward children's postoperative pain management, and use of pain relief strategies. Moreover, they lacked knowledge of and had negative attitudes toward pain assessment and analgesics, which significantly impacted their practices. CLINICAL IMPLICATIONS: Clinical pediatric nurses should provide appropriate support for the entire family of the child. Moreover, to enhance parental practices, they should develop targeted parental education programs for pain management, particularly regarding pain assessment tools and pain medications.

Hepatitis C Virus Down-Regulates the Expression of Ribonucleotide Reductases to Promote Its Replication.

Ribonucleotide reductases (RRs or RNRs) catalyze the reduction of the OH group on the 2nd carbon of ribose, reducing four ribonucleotides (NTPs) to the corresponding deoxyribonucleotides (dNTPs) to promote DNA synthesis. Large DNA viruses, such as herpesviruses and poxviruses, could benefit their replication through increasing dNTPs via expression of viral RRs. Little is known regarding the relationship between cellular RRs and RNA viruses. Mammalian RRs contain two subunits of ribonucleotide reductase M1 polypeptide (RRM1) and two subunits of ribonucleotide reductase M2 polypeptide (RRM2). In this study, expression of cellular RRMs, including RRM1 and RRM2, is found to be down-regulated in hepatitis C virus (HCV)-infected Huh7.5 cells and Huh7 cells with HCV subgenomic RNAs (HCVr). As expected, the NTP/dNTP ratio is elevated in HCVr cells. Compared with that of the control Huh7 cells with sh-scramble, the NTP/dNTP ratio of the RRM-knockdown cells is elevated. Knockdown of RRM1 or RRM2 increases HCV replication in HCV replicon cells. Moreover, inhibitors to RRMs, including Didox, Trimidox and hydroxyurea, enhance HCV replication. Among various HCV viral proteins, the NS5A and/or NS3/4A proteins suppress the expression of RRMs. When these are taken together, the results suggest that HCV down-regulates the expression of RRMs in cultured cells to promote its replication.