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The chest symptoms of the patient deteriorated with bilateral involvement and increased need for oxygen support, and she was transferred to the intensive care unit with use of a high-flow nasal cannula. There was significant improvement in inflammatory markers with C-reactive protein level decreased to 30.8 mg/L, ferritin level decreased to 4746 pmol/L, and lactate dehydrogenase level decreased to 526 IU/L at the end of treatment. Discussion The Centers for Disease Control and Prevention case definition for MIS-A was developed through expert opinion and states that the patient should be aged [greater than or equal to]21 years, have been hospitalised for at least 1 day or died as a result, and fulfilled certain clinical and laboratory criteria with no more likely alternative diagnosis.1 Case 1 did not fulfil these primary clinical criteria for MIS-A. Author contributions All authors contributed to the concept or design of the study, acquisition of the data, analysis or interpretation of the data, drafting of the manuscript, and critical revision of the manuscript for important intellectual content.

Krüppel-like factor 2 (KLF2) is expressed in endothelial cells in the developing heart, particularly in areas of high shear stress, such as the atrioventricular (AV) canal. KLF2 ablation leads to myocardial thinning, high output cardiac failure and death by mouse embryonic day 14.5 (E14.5) in a mixed genetic background. This work identifies an earlier and more fundamental role for KLF2 in mouse cardiac development in FVB/N mice. FVB/N KLF2-/- embryos die earlier, by E11.5. E9.5 FVB/N KLF2-/- hearts have multiple, disorganized cell layers lining the AV cushions, the primordia of the AV valves, rather than the normal single layer. By E10.5, traditional and endothelial-specific FVB/N KLF2-/- AV cushions are hypocellular, suggesting that the cells accumulating at the AV canal have a defect in endothelial to mesenchymal transformation (EMT). E10.5 FVB/N KLF2-/- hearts have reduced glycosaminoglycans in the cardiac jelly, correlating with the reduced EMT. However, the number of mesenchymal cells migrating from FVB/N KLF2-/- AV explants into a collagen matrix is reduced considerably compared to wild-type, suggesting that the EMT defect is not due solely to abnormal cardiac jelly. Echocardiography of E10.5 FVB/N KLF2-/- embryos indicates that they have abnormal heart function compared to wild-type. E10.5 C57BL/6 KLF2-/- hearts have largely normal AV cushions. However, E10.5 FVB/N and C57BL/6 KLF2-/- embryos have a delay in the formation of the atrial septum that is not observed in a defined mixed background. KLF2 ablation results in reduced Sox9, UDP-glucose dehydrogenase (Ugdh), Gata4 and Tbx5 mRNA in FVB/N AV canals. KLF2 binds to the Gata4, Tbx5 and Ugdh promoters in chromatin immunoprecipitation assays, indicating that KLF2 could directly regulate these genes. In conclusion, KLF2-/- heart phenotypes are genetic background-dependent. KLF2 plays a role in EMT through its regulation of important cardiovascular genes.

Objectives: This study developed a sol–gel tricalcium silicate/graphene oxide (TCS-GO) composite and examined its physicochemical properties, antimicrobial activity, and osteo/odontogenic effect on dental pulp stem cells. Methods: Tricalcium silicate was synthesized and combined with graphene oxide at three different concentrations, namely 0.02%, 0.04%, and 0.08% w/w, while tricalcium silicate and mineral trioxide aggregate served as controls. The setting time, compressive strength, pH, and calcium ion release of the composites were evaluated, as well as antimicrobial properties against Streptococcus mutans and Lactobacillus acidophilus. Additionally, the viability of dental pulp stem cells; apatite forming ability; and the gene expression of Alkaline phosphatase, Dentin sialophosphoprotein, and Runt-related transcription factor 2 were assessed. Results: TCS-GO (0.08%) showed a significantly shorter setting time and higher compressive strength when compared to MTA (p < 0.05). Additionally, tricalcium silicate and TCS-GO groups showed a higher release of Ca ions than MTA, with no significant difference in pH values among the different groups. TCS-GO (0.08%) also demonstrated a significantly stronger antimicrobial effect against Lactobacillus acidophilus compared to MTA (p < 0.05). ALP expression was higher in TCS-GO (0.08%) than MTA on days 3 and 7, while DSPP expression was higher in TCS-GO (0.08%) than MTA on day 3 but reversed on day 7. There was no significant difference in RUNX2 expression between TCS-GO (0.08%) and MTA on days 3 and 7. Conclusions: The TCS-GO (0.08%) composite demonstrated superior physicochemical characteristics and antimicrobial properties compared to MTA. Moreover, the early upregulation of ALP and DSPP markers in TCS-GO (0.08%) indicates that it has the potential to promote and enhance the osteo/odontogenic differentiation of DPSCs.

Introduction: In 2020, patients with critical coronavirus disease 2019 (COVID-19) had a 28-day mortality rate of 30% to 50% worldwide; outcomes among such patients in Hong Kong were unknown. This study investigated 28-day mortality and corresponding risk factors among patients with severe or critical COVID-19 in Hong Kong.Methods: This retrospective cohort study included adult patients with severe or critical COVID-19 who were admitted to three public hospitals in Hong Kong from 22 January to 30 September 2020. Demographics, comorbidities, symptoms, treatment, and outcomes were examined.Results: Among 125 patients with severe or critical COVID-19, 15 (12.0%) died within 28 days. Overall, the median patient age was 64 years; 48.0% and 54.4% of patients had hypertension and obesity, respectively. Respiratory samples were confirmed severe acute respiratory syndrome coronavirus 2 RNA–positive after a median of 3 days. The most common presenting symptom was fever (80.0% of patients); 45.6% and 32.8% of patients received care in intensive care unit and required mechanical ventilation, respectively. In logistic regression analysis comparing 28-day survivors and non-survivors, factors associated with greater 28-day mortality were older age (odds ratio [OR] per 1-year increase in age=1.12, 95% confidence interval [CI]=1.04-1.21; P=0.002), history of stroke (OR=15.96, 95% CI=1.65-154.66; P=0.017), use of renal replacement therapy (OR=15.32, 95% CI=2.67- 87.83; P=0.002), and shorter duration of lopinavirritonavir treatment (OR per 1-day increase=0.82, 95% CI=0.68-0.98; P=0.034).Conclusion: The 28-day mortality rate among patients with severe or critical COVID-19 in Hong Kong was 12.0%. Older age, history of stroke, use of renal replacement therapy, and shorter duration of lopinavir-ritonavir treatment were independent predictors of 28-day mortality.

The development of biomaterials that exhibit profound bioactivity and stimulate stem cell differentiation is imperative for the success and prognosis of vital pulp therapies. The objectives were to (1) synthesize calcium strontium silicate (CSR) ceramic through the sol–gel process (2) investigate its physicochemical properties, bioactivity, cytocompatibility, and its stimulatory effect on the differentiation of human dental pulp stem cells (HDPSC). Calcium silicate (CS) and calcium strontium silicate (CSR) were synthesized by the sol–gel method and characterized by x-ray diffraction (XRD). Setting time, compressive strength, and pH were measured. The in vitro apatite formation was evaluated by SEM-EDX and FTIR. The NIH/3T3 cell viability was assessed using an MTT assay. The differentiation of HDPSC was evaluated using alkaline phosphatase activity (ALP), and Alizarin red staining (ARS). Ion release of Ca, Sr, and Si was measured using inductive coupled plasma optical emission spectroscopy (ICP-OES). XRD showed the synthesis of (CaSrSiO4). The initial and final setting times were significantly shorter in CSR (5 ± 0.75 min, 29 ± 1.9 min) than in CS (8 ± 0.77 min, 31 ± 1.39 min), respectively (p < 0.05). No significant difference in compressive strength was found between CS and CSR (p > 0.05). CSR demonstrated higher apatite formation and cell viability than CS. The ALP activity was significantly higher in CSR 1.16 ± 0.12 than CS 0.92 ± 0.15 after 14 d of culture (p < 0.05). ARS showed higher mineralization in CSR than CS after 14 and 21 d culture times. CSR revealed enhanced differentiation of HDPSC, physicochemical properties, and bioactivity compared to CS.

Prior studies suggest that the influenza vaccine is protective against some outcomes in hospitalized patients infected with influenza despite vaccination. We utilized surveillance data from Columbus, Ohio to investigate this association over multiple influenza seasons and age groups. Data on laboratory-confirmed influenza-associated hospitalizations were collected as a part of the Influenza Hospitalization Surveillance Project for the 2012–2013, 2013–2014, and 2014–2015 influenza seasons. The association between influenza vaccination status was examined in relation to the outcomes of severe influenza and diagnosis of pneumonia among patients receiving antiviral treatment. Data were analyzed using multivariable logistic regression. We observed no overall association between influenza vaccination status and severe influenza among hospitalized patients. During the 2013–2014 season, those who were vaccinated were 41% less likely to be diagnosed with pneumonia compared with those who were unvaccinated (OR = 0·59 95% CI 0·41–0·86). The influenza vaccine may provide a secondary preventive function against pneumonia among influenza cases requiring hospitalization. However, a protective effect was only observed in 2013–2014, an influenza H1N1 dominant year. Differences in circulating influenza virus strains and vaccine matching to the circulating strains during influenza seasons may impact this association.

Transcriptional regulation of ESR1, the gene that encodes for estrogen receptor α (ER), is critical for regulating the downstream effects of the estrogen signaling pathway in breast cancer such as cell growth. ESR1 is a large and complex gene that is regulated by multiple regulatory elements, which has complicated our understanding of how ESR1 expression is controlled in the context of breast cancer. Early studies characterized the genomic structure of ESR1 with subsequent studies focused on identifying intrinsic (chromatin environment, transcription factors, signaling pathways) and extrinsic (tumor microenvironment, secreted factors) mechanisms that impact ESR1 gene expression. Currently, the introduction of genomic sequencing platforms and additional genome-wide technologies has provided additional insight on how chromatin structures may coordinate with these intrinsic and extrinsic mechanisms to regulate ESR1 expression. Understanding these interactions will allow us to have a clearer understanding of how ESR1 expression is regulated and eventually provide clues on how to influence its regulation with potential treatments. In this review, we highlight key studies concerning the genomic structure of ESR1, mechanisms that affect the dynamics of ESR1 expression, and considerations towards affecting ESR1 expression and hormone responsiveness in breast cancer.

Effective antiviral therapy is important for tackling the coronavirus disease 2019 (COVID-19) pandemic. We assessed the efficacy and safety of combined interferon beta-1b, lopinavir–ritonavir, and ribavirin for treating patients with COVID-19. This was a multicentre, prospective, open-label, randomised, phase 2 trial in adults with COVID-19 who were admitted to six hospitals in Hong Kong. Patients were randomly assigned (2:1) to a 14-day combination of lopinavir 400 mg and ritonavir 100 mg every 12 h, ribavirin 400 mg every 12 h, and three doses of 8 million international units of interferon beta-1b on alternate days (combination group) or to 14 days of lopinavir 400 mg and ritonavir 100 mg every 12 h (control group). The primary endpoint was the time to providing a nasopharyngeal swab negative for severe acute respiratory syndrome coronavirus 2 RT-PCR, and was done in the intention-to-treat population. The study is registered with ClinicalTrials.gov, NCT04276688. Between Feb 10 and March 20, 2020, 127 patients were recruited; 86 were randomly assigned to the combination group and 41 were assigned to the control group. The median number of days from symptom onset to start of study treatment was 5 days (IQR 3–7). The combination group had a significantly shorter median time from start of study treatment to negative nasopharyngeal swab (7 days [IQR 5–11]) than the control group (12 days [8–15]; hazard ratio 4·37 [95% CI 1·86–10·24], p=0·0010). Adverse events included self-limited nausea and diarrhoea with no difference between the two groups. One patient in the control group discontinued lopinavir–ritonavir because of biochemical hepatitis. No patients died during the study. Early triple antiviral therapy was safe and superior to lopinavir–ritonavir alone in alleviating symptoms and shortening the duration of viral shedding and hospital stay in patients with mild to moderate COVID-19. Future clinical study of a double antiviral therapy with interferon beta-1b as a backbone is warranted. The Shaw-Foundation, Richard and Carol Yu, May Tam Mak Mei Yin, and Sanming Project of Medicine.

Abstract Introduction Nocturnal swallowing and cortical arousals from sleep both produce rapid transient heartrate increases driven by autonomic activation. Obstructive Sleep Apnoea (OSA) is associated with autonomic dysfunction and cardiovascular diseases, however, the underpinning mechanisms remain unclear. Here, we examine autonomic activation associated with swallowing and arousals during sleep in OSA. Methods Overnight sleep with epiglottic pressure data from a previous study were analyzed using custom semi-automated analysis scripts to extract variables for swallows and arousals during sleep. The following variables were extracted: average heartrate 30 seconds prior to a swallow or arousal and, peak heartrate 10 seconds afterwards, plus data on associated arousals and arousal duration, respiratory events preceding the swallow(s). Results 53 datasets were analyzed, including 6 controls, 12 mild, 17 moderate and 18 severe OSA subjects, in total: 2794 swallows and 9147 arousals. Across all samples, heartrate elevation was greater when swallows occurred in close succession (21.4bpm vs 14.7bpm, p<0.0001). Arousals with swallows produced larger heartrate elevations (17.0bpm vs 10.7bpm, p<0.0001) and prolonged duration by 6 seconds compared to arousals without swallows. Arousals during Rapid Eye Movement (REM) sleep also produced a higher heartrate increase (16.4bpm vs 12bpm, p<0.0001). Notably, the severe OSA group exhibited reduced magnitude of swallow and arousal heartrate increases (18.4bpm vs 22.3bpm and 11.9bpm vs 12.9bpm, p<0.0001). Discussion Individuals with severe OSA exhibited diminished magnitude of heartrate elevation responses to swallows and arousals. This finding potentially advances our comprehension of the underlying mechanisms of OSA with association with cardiovascular diseases.

Objectives: The objectives of the study were (1) to develop a novel multi-element-doped porous 58S bioactive glass coating for titanium implants and (2) to investigate the physiochemical, cell cytotoxic and antibacterial properties of this novel coating for titanium implants. Methods: This study employed the sol–gel method to develop a silver-, cobalt (II) oxide- and titanium dioxide-doped 58S bioactive glass coating. The surface topography and in vitro bioactivity of the new bioactive glass-coated implants were studied using scanning electron microscopy (SEM) and energy-dispersive X-ray spectroscopy. The surface nanohardness and coating degradation were evaluated using atomic force microscopy (AFM) and inductively coupled plasma atomic emission spectroscopy (ICP-AES), respectively. The cell cytotoxicity was assessed using cell viability of osteoblast-like mouse cells. The antibacterial property was examined using colony-forming units (CFUs) of the implant coating against Porphyromonas gingivalis. Results: The multi-element-doped porous 58S bioactive glass-coated titanium implant was synthesized. SEM showed that calcium phosphate was formed on the novel coating but not on the 58S bioactive glass coating. The mean surface nanohardness of the novel coating and the 58S coating were 124 ± 24 and 50 ± 17 MPa, respectively (p < 0.001). ICP-AES showed that the releases of Si, Ca and P ions of the novel coating were significantly higher than that of a 58S bioactive glass-coated implant. No significant difference in cell cytotoxicity was found between the novel coating and the 58S coating (p > 0.1). The mean CFUs of the novel coating and the conventional coating were 120 × 106 and 49 × 106 /mL. Conclusion: A novel multielement-doped porous bioactive glass coating for titanium implants was developed. The coating displays promising biocompatibility and antibacterial activity. Clinical significance: the coating can be used to improve the clinical success of dental implants for patient care if it shows success in clinical trials.