A significant consequence of Typhoon Morakot in August 2009 was the production of vast volumes of driftwood in Pacific Asia. We have quantified the flux of this coarse woody debris (CWD) to the ...oceans from typhoon-triggered landslides in Taiwan, where Morakot made landfall, by combining remote sensing (using FORMOSAT-2 imagery and aerial photography), analysis of forest biomass, and field observations. A total of 3.8–8.4 TgCWD was transported to the oceans, carrying 1.8–4.0 Tg of organic carbon. In addition to the local effects on the marine and coastal environment from such a highly concentrated flux of carbon and nutrients, storm-driven mobilization of CWD may represent a significant, if infrequent, transfer of terrestrial biomass to the oceans. If the frequency of relatively rare, extreme storms such as Morakot increases in a changing climate, this transport mechanism may play an important role in feedbacks between global climate, storm intensity, and carbon cycling.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NMLJ, NUK, OILJ, PNG, SAZU, SBCE, SBMB, UL, UM, UPUK
Traffic emissions are a significant source of airborne particulate matter (PM) in ambient environments. These emissions contain an abundance of toxic metals and thus pose adverse effects on human ...health. Size-fractionated aerosol samples were collected from May to September 2013 by using micro-orifice uniform deposited impactors (MOUDIs). Sample collection was conducted simultaneously at the inlet and outlet sites of Hsuehshan Tunnel in northern Taiwan, which is the second-longest freeway tunnel (12.9 km) in Asia. This endeavor aims to characterize the chemical constituents and size distributions, as well as fingerprinting ratios of particulate metals emitted by vehicle fleets. A total of 36 metals in size-resolved aerosols were determined through inductively coupled plasma mass spectrometry. Three major groups – namely, tailpipe emissions (Zn, Pb, and V in fine mode), wear debris (Cu, Cd, Fe, Ga, Mn, Mo, Sb, and Sn), and resuspended dust (Ca, Mg, K, and Rb) – of airborne PM metals were categorized on the basis of the results of enrichment factor, correlation matrix, and principal component analysis. Size distributions of wear-originated metals resembled the pattern of crustal elements, which were predominated by super-micron particulates (PM1–10). By contrast, tailpipe exhaust elements such as Zn, Pb, and V were distributed mainly in submicron particles. By employing Cu as a tracer of wear abrasion, several inter-metal ratios – including Fe / Cu (14), Ba / Cu (1.05), Sb / Cu (0.16), Sn / Cu (0.10), and Ga / Cu (0.03) – served as fingerprints for wear debris. However, the data set collected in this work is useful for further studies on traffic emission inventory and human health effects of traffic-related PM.
An ideal material has yet to be discovered that can completely treat dentin hypersensitivity; however, calcium phosphate precipitation has exhibited potential value for the treatment of dentin ...hypersensitivity by the occlusion of dentinal tubules. We hypothesized that a novel mesoporous silica biomaterial (nano CaO@mesoporous silica, NCMS) containing nano-sized calcium oxide particles mixed with 30% phosphoric acid can efficiently occlude dentinal tubules and significantly reduce dentin permeability, even with the presence of pulpal pressure. This highly supersaturated Ca2+-and HPO4
2−ion-containing NCMS paste was brushed onto dentin surfaces, and the ions diffused deeply into the dentinal tubules and formed a CaHPO4·2H2O precipitation with a depth of 100 μm. The results of the dentin permeability tests showed that the novel mesoporous material exhibited a significant reduction in dentin permeability (p < 0.05), even under simulated pulpal pressure, as compared with our previously developed material, DP-bioglass, and a commercial desensitizing material, Seal & Protect®.
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CMK, NUK, OILJ, SAZU, UKNU, UL, UM, UPUK
Objective
PANSS‐8 and PANSS‐6 are derived from the 30‐item Positive and Negative Syndrome Scale (PANSS‐30). We investigate whether PANSS‐8 or PANSS‐6 is a reliable, valid, sensitive to change ...measure, and scalable, and whether early improvement using them can predict response/remission.
Method
Data were from 3 trials for 270 schizophrenia inpatients receiving antipsychotics. Internal consistency, validity, sensitivity to change, and scalability using PANSS‐30, PANSS‐8, and PANSS‐6 at each assessment were examined. Early improvement was defined as at least 20% reduction of PANSS‐30, PANSS‐8, or PANSS‐6 scores at week 2. Response was defined as at least 40% reduction of PANSS‐30 and remission as a score of PANSS‐8 ≤ 3 on each item at endpoint. Receiver operating characteristic analysis was used to determine which rating scale had better discriminative capacity.
Results
PANSS‐8 and PANSS‐6 showed acceptable internal consistency, were highly correlated with PANSS‐30, and had sensitivity to change. PANSS‐8 and PANSS‐6 were scalable at each assessment, except for PANSS‐6 at baseline. Early improvement using PANSS‐8 or PANSS‐6 had comparable predictive values with that of PANSS‐30 for response/remission.
Conclusion
PANSS‐8 and PANSS‐6 are clinically useful measures. Early improvement, regardless of whether PANSS‐30, PANSS‐8, or PANSS‐6 is used, is a statistically significant predictor of response/remission.
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BFBNIB, DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, SIK, UILJ, UKNU, UL, UM, UPUK
Metastasis is the predominant cause of death in breast cancer patients. Several lines of evidence have shown that microRNAs (miRs) can have an important role in cancer metastasis. Using isogenic ...pairs of low and high metastatic lines derived from a human breast cancer line, we have identified miR-149 to be a suppressor of breast cancer cell invasion and metastasis. We also identified GIT1 (G-protein-coupled receptor kinase-interacting protein 1) as a direct target of miR-149. Knockdown of GIT1 reduced migration/invasion and metastasis of highly invasive cells. Re-expression of GIT1 significantly rescued miR-149-mediated inhibition of cell migration/invasion and metastasis. Expression of miR-149 impaired fibronectin-induced focal adhesion formation and reduced phosphorylation of focal adhesion kinase and paxillin, which could be restored by re-expression of GIT1. Inhibition of GIT1 led to enhanced protein degradation of paxillin and α5β1 integrin via proteasome and lysosome pathways, respectively. Moreover, we found that GIT1 depletion in metastatic breast cancer cells greatly reduced α5β1-integrin-mediated cell adhesion to fibronectin and collagen. Low level of miR-149 and high level of GIT1 was significantly associated with advanced stages of breast cancer, as well as with lymph node metastasis. We conclude that miR-149 suppresses breast cancer cell migration/invasion and metastasis by targeting GIT1, suggesting potential applications of the miR-149-GIT1 pathway in clinical diagnosis and therapeutics.
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DOBA, EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, IZUM, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UILJ, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
The particulate methane monooxygenase (pMMO) is the first enzyme in the C1 metabolic pathway in methanotrophic bacteria. As this enzyme converts methane into methanol efficiently near room ...temperature, it has become the paradigm for developing an understanding of this difficult C1 chemistry. pMMO is a membrane-bound protein with three subunits (PmoB, PmoA, and PmoC) and 12–14 coppers distributed among different sites. X-ray crystal structures that have revealed only three mononuclear coppers at three sites have neither disclosed the location of the active site nor the catalytic mechanism of the enzyme. Here we report a cyro-EM structure of holo-pMMO from Methylococcus capsulatus (Bath) at 2.5 Å, and develop quantitative electrostatic-potential profiling to scrutinize the nonprotein densities for signatures of the copper cofactors. Our results confirm a mononuclear CuI at the A site, resolve two CuIs at the B site, and uncover additional CuI clusters at the PmoA/PmoC interface within the membrane (D site) and in the water-exposed C-terminal subdomain of the PmoB (E clusters). These findings complete the minimal set of copper factors required for catalytic turnover of pMMO, offering a glimpse of the catalytic machinery for methane oxidation according to the chemical principles underlying the mechanism proposed earlier.
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IJS, KILJ, NUK, PNG, UL, UM
Summary
Background: Statins are the most commonly prescribed agents for hypercholesterolemia because of their efficacy and tolerability. As the number of patients in need of statin therapy continues ...to increase, information regarding the relative efficacy and safety of statins is required for decision‐making.
Objective: This study will use systematic review to compare the efficacy and safety profiles of different statins at different doses and determine the therapeutically equivalent doses of statins to achieve a specific level of low‐density lipoprotein cholesterol (LDL‐C) lowering effect.
Methods: Publications of head‐to‐head randomized controlled trials (RCTs) of statins were retrieved from the Oregon state database (1966–2004), MEDLINE (2005‐April of 2006), EMBASE (2005‐April of 2006), and the Cochrane Controlled Trials Registry (up to the first quarter of 2006). The publications were evaluated with predetermined criteria by a reviewer before they were included in the review. The mean change in cholesterol level of each statin was calculated and weighted by number of subjects involved in each RCT. Where possible, meta‐analysis was performed to generate pooled estimates of the cholesterol lowering effect of statins and the difference between statins.
Results: Seventy‐five studies reporting RCTs of head‐to‐head comparisons on statins were included. Most studies had similar baseline characteristics, except the rosuvastatin related studies. A daily dose of atorvastatin 10 mg, fluvastatin 80 mg, lovastatin 40–80 mg, and simvastatin 20 mg could decrease LDL‐C by 30–40%, and fluvastatin 40 mg, lovastatin 10–20 mg, pravastatin 20–40 mg, and simvastatin 10 mg could decrease LDL‐C by 20–30%. The only two statins that could reduce LDL‐C more than 40% were rosuvastatin and atorvastatin at a daily dose of 20 mg or higher. Meta‐analysis indicated a statistically significant but clinically minor difference (<7%) between statins in cholesterol lowering effect. Comparisons of coronary heart disease prevention and safety could not be made because of insufficient data.
Conclusions: At comparable doses, statins are therapeutically equivalent in reducing LDL‐C.
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BFBNIB, DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, SIK, UILJ, UKNU, UL, UM, UPUK, VSZLJ
Background
Pulsed radiofrequency (PRF) has been widely used to treat chronic pain, but the effectiveness and mechanisms in preventing early neuropathic pain have not been well explored. Even fewer ...knowledge is available in its impact on glia‐mediated nociceptive sensitization. This study aims to elucidate the modulation of PRF on nerve injury‐induced pain development and activation of spinal mitogen‐activated protein kinases (MAPKs).
Methods
In a rat spinal nerve ligation (SNL) model, a low‐volt PRF treatment was applied to the L5 dorsal root ganglion after nerve injury. Nociceptive behaviours were measured by von Frey and heat withdrawal tests at multiple time points. MAPK activations, including p‐ERK and p‐p38, as well as TNF‐α level in the spinal dorsal horn were assessed and the cell types that expressed MAPK activation were identified by double immunofluorescence staining.
Results
We found that SNL promptly induced neuropathic pain in the affected hind limb for over 1 week as well as increased p‐ERK and p‐p38 in the spinal dorsal horn. PRF significantly attenuated SNL‐induced mechanical allodynia and thermal hyperalgesia for 5–7 days. PRF also inhibited ERK and p38 activations, which were found majorly located within neurons and microglia, respectively. Besides, PRF significantly suppressed expression of TNF‐α in the spinal dorsal horn throughout the course.
Conclusions
Low‐volt PRF significantly ameliorated SNL‐induced acute pain. Inferentially, PRF may inhibit spinal sensitization by down‐regulating spinal MAPK activations and activation‐mediated cytokine release. We demonstrated that early PRF treatment in acute nerve injury helps to ameliorate neuropathic pain development.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Abstract Nanohybrids, synthesized via silver nitrate reduction in the presence of silicate clay, exhibit a high potency against bacterial growth. The plate-like clay, due to its anionic surface ...charges and a large surface area, serves as the support for the formation of silver nanoparticles (AgNPs) ∼30 nm in diameter. The nanohybrid consisting of Ag/silicate at a 7/93 weight ratio inhibited the growth of dermal pathogens including Staphylococcus aureus ( S. aureus ), Pseudomonas aeruginosa and Streptococcus pyrogens , as well as the methicillin- and oxacillin-resistant S. aureus (MRSA and ORSA). Scanning electron microscope revealed that these nanohybrids were adherent on the surface of individual bacteria. The thin silicate plates provide a surface for immobilizing AgNPs in one highly concentrated area but prevent them from entering the cell membrane. Subsequent cytotoxicity studies indicated that surface contact with the reduced AgNPs on clay is sufficient to initiate cell death. This toxicity is related to a loss in membrane integrity due to reactive oxygen species (ROS) generation. The hybridization of AgNPs on clay surface is viable for generating a new class of nanohybrids exhibiting mild cytotoxicity but high efficacy for battling drug-resistant bacteria.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Abstract
Background
The impact of SARS-CoV-2 variants of concern (VOCs) on disease severity is unclear. In this retrospective study, we compared the outcomes of patients infected with B.1.1.7, ...B.1.351, and B.1.617.2 with wild-type strains from early 2020.
Methods
National surveillance data from January to May 2021 were obtained and outcomes in relation to VOCs were explored. Detailed patient-level data from all patients with VOC infection admitted to our center between December 2020 and May 2021 were analyzed. Clinical outcomes were compared with a cohort of 846 patients admitted from January to April 2020.
Results
A total of 829 patients in Singapore in the study period were infected with these 3 VOCs. After adjusting for age and sex, B.1.617.2 was associated with higher odds of oxygen requirement, intensive care unit admission, or death (adjusted odds ratio aOR, 4.90; 95% confidence interval CI: 1.43-30.78). Of these patients, 157 were admitted to our center. After adjusting for age, sex, comorbidities, and vaccination, the aOR for pneumonia with B.1.617.2 was 1.88 (95% CI: .95-3.76) compared with wild-type. These differences were not seen with B.1.1.7 and B.1.351. Vaccination status was associated with decreased severity. B.1.617.2 was associated with significantly lower polymerase chain reaction cycle threshold (Ct) values and longer duration of Ct value ≤30 (median duration 18 days for B.1.617.2, 13 days for wild-type).
Conclusions
B.1.617.2 was associated with increased severity of illness, and with lower Ct values and longer viral shedding. These findings provide impetus for the rapid implementation of vaccination programs.
In this retrospective cohort study we found an association between infection with B.1.617.2 (Delta) and increased disease severity. B.1.617.2 was also associated with higher viral loads and prolonged duration of viral shedding. Vaccination remained protective.
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