A Potential Strategy for Atherosclerosis Prevention in Modernizing China - Hyperhomocysteinemia, MTHFR C677T Polymorphism and Air Pollution (PM2.5) on Atherogenesis in Chinese Adults.

BACKGROUND: Atherosclerosis is one of the most important global health hazards and air pollution (AP, PM2.5) has been implicated. In addition to traditional risk factors hyperhomocysteinemia (HC) has been recognized in many parts of China related to risk of stroke. METHODS: To evaluate the impact of HC (homocysteine >14µmol/l) and PM2.5 air pollution on atherogenesis in modernizing China, we studied 756 asymptomatic Chinese in China from 1998-2007. PM2.5 exposure, HC, folate, and methylenetetrahydrofolate reductase (MTHFR) C/T genotype were evaluated. Brachial flow-mediated dilation (FMD) and carotid intima-media thickness (IMT) were measured by ultrasound. Locations were categorized as zones 1, 2 and 3, with increasing PM2.5 exposure. RESULTS: HC was higher (19.4±13.1 and 27.1±25.1µmol/l) in high PM2.5-polluted zones 2 and 3 than in zone 1 (9.7±4.5µmol/l, p<0.0015). The top HC tertile was characterized by lower folate and vitamin B12, but a higher proportion of the MTHFR TT genotype, Metabolic Syndrome (MS) and PM2.5 level (p=0.0018). FMD was significantly lower (7.3±2.3%) and carotid IMT thicker (0.63±0.12mm) in the top HC tertile, compared with low HC tertile (8.4±2.5%, p<0.0001; 0.57±0.1mm, p<0.0001 respectively). Similar differences in FMD and IMT were seen in zones 2 and 3, compared with zone 1 (p<0.0001). On multivariate regression, HC was related to male gender (beta=0.106, p=0.021), MTHFR-TT (beta=0.935, p<0.0001), locations (beta=0.230, p<0.0001) and folate-MTHFR interaction (beta=-0.566, p<0.0001). FMD was related to age (beta= -0.221; p<0.0001), male gender (beta= -0.194, p=0.001) PM2.5 and location (beta=-0.285 to -0.303, p<0.0001). Carotid IMT was related to PM2.5 (beta=0.173, p<0.0001), HC (0.122, p=0.006) but not to MTHFR or location, independent of age, gender, MS, and LDL-C. No significant HC-PM2.5 interaction effect on FMD and IMT was observed. CONCLUSION: HC and PM2.5 pollution but not MTHFR genotype were both related to carotid IMT, independent of other traditional risk factors. This has potential implications in dietary and AP strategies for atherosclerosis prevention in China.

Effects of strict public health measures on seroprevalence of anti-SARS-CoV-2 antibodies during pregnancy.

INTRODUCTION: A substantial number of people infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) remain asymptomatic throughout the course of infection. Nearly half of pregnant women with coronavirus disease 2019 (COVID-19) are asymptomatic upon diagnosis; these cases are not without risk of maternal morbidity. Here, we investigated the seroprevalence of anti-SARS-CoV-2 antibodies in an unselected sample of pregnant women in Hong Kong. METHODS: This prospective cohort study included pregnant women who presented for routine Down syndrome screening (DSS) between November 2019 and October 2020; all women subsequently delivered at the booking hospitals. Serum antibodies against SARS-CoV-2 were analysed using a qualitative serological assay in paired serum samples taken at DSS and delivery for all participants. RESULTS: In total, 1830 women were recruited. Six women (0.33%) were seropositive at the DSS visit; this seropositivity persisted until delivery. Of the six women, none reported relevant symptoms during pregnancy; one reported a travel history before DSS and one reported relevant contact history. The interval between sample collections was 177 days (range, 161-195). Among women with epidemiological risk factors, 1.79% with travel history, 50% with relevant contact history, and 0.77% with community SARS-CoV-2 testing history, were seropositive. CONCLUSION: The low seroprevalence in this study suggests that strict public health measures are effective for preventing SARS-CoV-2 transmission. However, these measures cannot be maintained indefinitely. Until a highly effective therapeutic drug targeting SARS-CoV-2 becomes available, vaccination remains the best method to control the COVID-19 pandemic.

Impact of the Mechanical Properties of a Functionalized Cross-Linked Binder on the Longevity of Li-S Batteries.

One of the very challenging aspects of Li-S battery development is the fabrication of a sulfur electrode with high areal loading using conventional Li-ion binders. Herein, we report a new multifunctional polymeric binder, synthesized by the free-radical cross-linking polymerization of [2-(acryloyloxy)ethyl]trimethylammonium chloride (AETMAC) and ethylene glycol diacrylate (EGDA) to form poly(AETMAC- co-EGDA), that not only helps to confine the soluble polysulfide species but also has the desired mechanical properties to allow stable cycling of high-sulfur loading cathodes. Through a combination of spectroscopic and electrochemical studies, we elucidate the chemical interactions that inhibit polysulfide shuttling. We also show that extensive cross-linkage enables this polymeric binder to exhibit a low degree of swelling as well as high tensile modulus and toughness. These attributes are essential to maintain the architectural integrity of the sulfur cathode during extended cycling. Using this material, Li-S cells with a high-sulfur loading (6.0 mg cm-2) and a low-intermediate electrolyte/sulfur ratio (7 µL:1 mg) achieve an areal capacity of 5.4 mA h cm-2 and can be (dis)charged for 300 cycles with stable reversible redox behavior after the initial cycles.

A high-energy-density lithium-oxygen battery based on a reversible four-electron conversion to lithium oxide.

Lithium-oxygen (Li-O2) batteries have attracted much attention owing to the high theoretical energy density afforded by the two-electron reduction of O2 to lithium peroxide (Li2O2). We report an inorganic-electrolyte Li-O2 cell that cycles at an elevated temperature via highly reversible four-electron redox to form crystalline lithium oxide (Li2O). It relies on a bifunctional metal oxide host that catalyzes O-O bond cleavage on discharge, yielding a high capacity of 11 milliampere-hours per square centimeter, and O2 evolution on charge with very low overpotential. Online mass spectrometry and chemical quantification confirm that oxidation of Li2O involves transfer of exactly 4 e-/O2 This work shows that Li-O2 electrochemistry is not intrinsically limited once problems of electrolyte, superoxide, and cathode host are overcome and that coulombic efficiency close to 100% can be achieved.

High aspect ratio sharp nanotip for nanocantilever integration at CMOS compatible temperature.

In this paper, we demonstrate a novel low temperature nanofabrication approach that enables the formation of ultra-sharp high aspect ratio (HAR) and high density nanotip structures and their integration onto nanoscale cantilever beams. The nanotip structure consists of a nanoscale thermally evaporated Cr Spindt tip on top of an amorphous silicon rod. An apex radius of the tip, as small as 2.5 nm, has been achieved, and is significantly smaller than any other Spindt tips reported so far. 100 nm wide tips with aspect ratio of more than 50 and tip density of more than 5 × 109 tips cm-2 have been fabricated. The HAR tips have been integrated onto an array of 460 nm wide cantilever beams with high precision and yield. In comparison with other approaches, this approach allows the integration of HAR sharp nanotips with nano-mechanical structures in a parallel and CMOS compatible fashion for the first time to our knowledge. Potential applications include on-chip high-speed atomic force microscopy and field emission devices.

Micromechanical Origin of Particle Size Segregation.

We computationally study the micromechanics of shear-induced size segregation and propose distinct migration mechanisms for individual large and small particles. While small particles percolate through voids without enduring contacts, large particles climb under shear through their crowded neighborhoods with anisotropic contact network. Particle rotation associated with shear is necessary for the upward migration of large particles. Segregation of large particles can be suppressed with inadequate friction, or with no rotation; increasing interparticle friction promotes the migration of large particles, but has little effect on the percolation of small particles.

Characterization of base roughness for granular chute flows.

Base roughness plays an important role in the dynamics of granular flows but is still poorly understood due to the difficulty of its quantification. For a bumpy base made of spheres, at least two factors should be considered in order to characterize its geometric roughness, namely, the size ratio of flow to base particles and the packing arrangement of base particles. In this paper, we propose an alternative definition of base roughness, R_{a}, as a function of both the size ratio and the distribution of base particles. This definition is generalized for random and regular packings of multilayered spheres. The range of possible values of R_{a} is presented, and optimal arrangements for maximizing base roughness are studied. Our definition is applied to granular chute flows in both two- and three-dimensional configurations, and is shown to successfully predict whether slip occurs at the base. A transition is observed from slip to nonslip conditions as R_{a} increases. Critical values of R_{a} are identified for the construction of a nonslip base at various angles of inclination.

Transport Properties of Polysulfide Species in Lithium-Sulfur Battery Electrolytes: Coupling of Experiment and Theory.

A comprehensive experimental and theoretical analysis of the isothermal transport of species for the two model ternary-electrolytes with LiTFSI-Li2S4/dioxolane (DOL)-dimethoxyethane (DME) and LiTFSI-Li2S6/DOL-DME formulations is presented. An unambiguous picture of the polysulfide's mobility is set forth after a detailed investigation of the macroscopic transference number and diffusion coefficients. The new findings of incongruent diffusion for Li2S4 species and high significance of cross-term diffusion coefficients reformulate a fledgling view of the prevalent redox-shuttle phenomena. The practical implications of this complex mechanism are discussed in detail.

Identification of a tumor suppressive critical region mapping to 3p14.2 in esophageal squamous cell carcinoma and studies of a candidate tumor suppressor gene, ADAMTS9.

A gene critical to esophageal cancer has been identified. Functional studies using microcell-mediated chromosome transfer of intact and truncated donor chromosomes 3 into an esophageal cancer cell line and nude mouse tumorigenicity assays were used to identify a 1.61 Mb tumor suppressive critical region (CR) mapping to chromosome 3p14.2. This CR is bounded by D3S1600 and D3S1285 microsatellite markers. One candidate tumor suppressor gene, ADAMTS9, maps to this CR. Further studies showed normal expression levels of this gene in tumor-suppressed microcell hybrids, levels that were much higher than observed in the recipient cells. Complete loss or downregulation of ADAMTS9 gene expression was found in 15 out of 16 esophageal carcinoma cell lines. Promoter hypermethylation was detected in the cell lines that do not express this gene. Re-expression of ADAMTS9 was observed after demethylation drug treatment, confirming that hypermethylation is involved in gene downregulation. Downregulation of ADAMTS9 was also found in 43.5 and 47.6% of primary esophageal tumor tissues from Hong Kong and from the high-risk region of Henan, respectively. Thus, this study identifies and provides functional evidence for a CR associated with tumor suppression on 3p14.2 and provides the first evidence that ADAMTS9, mapping to this region, may contribute to esophageal cancer development.

Clinical experience of trainee anaesthesiologists: logbook analysis.

OBJECTIVE: To study the clinical experience acquired by trainee anaesthesiologists after 6 years of training in Hong Kong. DESIGN: Retrospective observational study. SETTING: Recognised anaesthesiology training posts in the Hong Kong Hospital Authority. PARTICIPANTS: All anaesthesiology trainees who sat the Exit Assessment between January 2001 and June 2002 after completing more than 48 months of anaesthetic training. MAIN OUTCOME MEASURES: Anaesthetic experience of trainees. RESULTS: All data provided by 25 trainees were computed for analysis. Each trainee administered a mean of 2668 anaesthetics over a 6-year period, including 57 anaesthetics for thoracic surgery, 15 for cardiac surgery, 213 for caesarian section (34% under general anaesthesia), and 100 for neurosurgical operations. The paediatric anaesthesia exposure involved a mean of 12 neonates and 180 children who were younger than 4 years. Apart from cardiac and thoracic anaesthesia, there was no statistical difference in subspecialty anaesthetic experience among trainees from different parent hospitals. CONCLUSION: The current training system provides sufficient anaesthetic experience in terms of case variety and subspecialty case numbers. There was uneven exposure to cardiac, thoracic, and paediatric anaesthesia. An accurate logbook that is reviewed regularly by a supervisor will help ensure adequate subspecialty exposure. An electronic logbook will facilitate a more comprehensive reviewing process.

Securinine induced apoptosis in human leukemia HL-60 cells.

AIM: To study whether securinine might induce apoptosis in human leukemia HL-60 cells. METHODS: Inhibition of proliferation was measured using MTT assay. The amount of apoptotic cells was measured by flow cytometry. DNA fragmentation was visualized by DNA agarose gel electrophoresis and the cellular changes were observed by electron microscope. RESULTS: Securinine 5-80 mg.L-1 elicited typical apoptosis morphological changes and DNA fragmentation in a concentration-dependent manner in HL-60 cells. Securinine inhibited HL-60 cell proliferation in a time- and concentration-dependent manner. The IC50 and 95% confidence limits were 27 (15-47) mg.L-1 after 12-h treatment with securinine. CONCLUSION: Securinine induced apoptosis in HL-60 cells.

Elemene induces apoptosis and regulates expression of bcl-2 protein in human leukemia K562 cells.

AIM: To study the antitumor action of elemene (Ele) and its mechanism. METHODS: Inhibition of proliferation was measured with a colorimetric 3-[4,5-dimethyl thiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) assay. Morphological assessment of apoptosis was performed with fluorescence microscope. DNA fragmentation was assessed by agarose gel electrophoresis and flow cytometry. The levels of bcl-2 protein was measured with flow cytometry. RESULTS: Exposure of exponentially growing K562 cells to Ele 65-520 mumol. L-1 for 48 h resulted in growth arrest. The values of IC50 and 95% confidence limits were 220 (152-319) mumol.L-1. After treatment of K562 cells with Ele 130 mumol.L-1, marked morphological changes including "Apo bodies" reduction in volume were observed with fluorescence microscope. Agarose gel electrophoresis of DNA from cells treated with Ele for 48 h revealed "ladder" pattern. The levels of bcl-2 protein in K562 cells treated with Ele for 48 h were obviously decreased. CONCLUSION: Ele induces apoptosis of K562 cells, which is related with the down-regulation of bcl-2 protein in K562 cells.

Atrophie blanche--a special form of vasculopathy.

Although atrophie blanche is classified as a vasculitis, its presentation and management differ from the classical vasculitis. We present a patient with idiopathic atrophie blanche and discuss its management.

Retrospective study of the epidemiology of nodular vasculitis followed up in the National Skin Centre, Singapore.

A seven-year retrospective study was done on histologically proven nodular vasculitis presenting at the National Skin Centre, Singapore. We collected 25 patients and found that they differed from the classical European model. They most commonly involved the shins and did not ulcerate. A tuberculous aetiology accounted for 28% of cases. Useful indicators of tuberculosis were a past history of tuberculosis, an abnormal chest X-ray and a strongly positive Mantoux test.