Long-term exposure to particulate matter and all-cause and cause-specific mortality in an analysis of multiple Asian cohorts.

BACKGROUND: Exposure to ambient air pollution is associated with a significant number of deaths. Much of the evidence associating air pollution with adverse effects is from North American and Europe, partially due to incomplete data in other regions limiting location specific examinations. The aim of the current paper is to leverage satellite derived air quality data to examine the relationship between ambient particulate matter and all-cause and cause-specific mortality in Asia. METHODS: Six cohorts from the Asia Cohort Consortium provided residential information for participants, recruited between 1991 and 2008, across six countries (Bangladesh, India, Iran, Japan, South Korea, and Taiwan). Ambient particulate material (PM2·5) levels for the year of enrolment (or 1998 if enrolled earlier) were assigned utilizing satellite and sensor-based maps. Cox proportional models were used to examine the association between ambient air pollution and all-cause and cause-specific mortality (all cancer, lung cancer, cardiovascular and lung disease). Models were additionally adjusted for urbanicity (representing urban and built characteristics) and stratified by smoking status in secondary analyses. Country-specific findings were pooled via random-effects meta-analysis. FINDINGS: More than 300,000 participants across six cohorts were included, representing more than 4-million-person years. A positive relationship was observed between a 5 µg/m (Dockery et al., 1993) increase in PM2·5 and cardiovascular mortality (HR: 1·06, 95 % CI: 0.99, 1·13). The additional adjustment for urbanicity resulted in increased associations between PM2.5 and mortality outcomes, including all-cause mortality (1·04, 95 % CI: 0·97, 1·11). Results were generally similar regardless of whether one was a current, never, or ex-smoker. INTERPRETATION: Using satellite and remote sensing technology we showed that associations between PM2.5 and all-cause and cause-specific Hazard Ratios estimated are similar to those reported for U.S. and European cohorts. FUNDING: This project was supported by the Health Effects Institute. Grant number #4963-RFA/18-5. Specific funding support for individual cohorts is described in the Acknowledgements.

Toxic dinoflagellate Centrodinium punctatum (Cleve) F.J.R. Taylor: An examination on the responses in growth and toxin contents to drastic changes of temperature and salinity.

To understand environmental effects affecting paralytic shellfish toxin production of Centrodinium punctatum, this study examined the growth responses, and toxin contents and profiles of a C. punctatum culture exposed to drastic changes of temperature (5-30 °C) and salinity (15-40). C. punctatum grew over a temperature range of 15-25 °C, with an optimum of 20 °C., and over a salinity range of 25-40, with optimum salinities of 30-35. This suggests that C. punctatum prefers relatively warm waters and an oceanic habitat for its growth and can adapt to significant changes of salinity levels. When C. punctatum was cultivated at different temperature and salinity levels, the PST profile included four major analogs (STX, neoSTX, GTX1 and GTX4, constituted >80 % of the profile), while low amounts of doSTX and traces of dc-STX and dc-GTX2 were also observed. Interestingly, though overall toxin contents did not change significantly with temperature, increases in the proportion of STX, and decreases in proportions in GTX1 and GTX4 were observed with higher temperatures. Salinity did not affect either toxin contents or profile from 25 to 35. However, the total toxin content dropped to approximately half at salinity 40, suggesting this salinity may induce metabolic changes in C. punctatum.

Comparing Three Wearable Brassiere Braces Designed to Correct Rounded Posture.

Rounded shoulder posture (RSP) causes shoulder pain and can lead to shoulder impingement and thoracic outlet syndromes, ultimately resulting in a frozen shoulder. Altered scapular positions in RSP patients affect muscle activity. Many studies have explored methods to correct and prevent RSP, including shoulder braces, muscle strengthening, stretching, and inhibition techniques. Using a shoulder brace reduces RSP and improves shoulder discomfort and function, similar to conventional rehabilitation. However, despite their effectiveness, these braces are bulky and inconvenient, which makes continuous daily wear challenging. This is especially true for women who are sensitive to their appearance. To address this issue, methods have been developed to convert women's underwear bra straps into braces. This study aimed to evaluate the immediate effects of three underwear-mounted rounded shoulder braces and to identify the brace that is most effective in decreasing RSP and upper trapezius (UT) muscle activity and increasing lower trapezius (LT) muscle activity in patients with RSP. The study included 18 patients with an RSP. The RSP amount and UT and LT muscle activities were measured before and after three interventions. The interventions were scapular posterior tilting (SPT) exercises with the X strap, X + 8 strap, and inner brace. Compared with the baseline value, the RSP amount was significantly lower with the three braces. The RSP was significantly lower with the X + 8 strap and the inner brace than with the X strap. The inner brace showed significantly lower UT muscle activity than those with the X strap and X + 8 straps and significantly greater LT muscle activity than that with the X + 8 strap. These results show underwear-mounted braces as a potential RSP solution, but long-term sustainability and improving comfort, especially for those concerned about appearance, require further research and development.

Purification and Molecular Docking Study on the Angiotensin I-Converting Enzyme (ACE)-Inhibitory Peptide Isolated from Hydrolysates of the Deep-Sea Mussel Gigantidas vrijenhoeki.

The objective of this study was to prepare an angiotensin I-converting enzyme (ACE)-inhibitory peptide from the hydrothermal vent mussel, Gigantidas vrijenhoeki. The G. vrijenhoeki protein was hydrolyzed by various hydrolytic enzymes. The peptic hydrolysate exhibited the highest ACE-inhibitory activity and was fractionated into four molecular weight ranges by ultrafiltration. The <1 kDa fraction exhibited the highest ACE inhibitory activity and was found to have 11 peptide sequences. Among the analyzed peptides, KLLWNGKM exhibited stronger ACE inhibitory activity and an IC50 value of 0.007 µM. To investigate the ACE-inhibitory activity of the analyzed peptides, a molecular docking study was performed. KLLWNGKM exhibited the highest binding energy (-1317.01 kcal/mol), which was mainly attributed to the formation of hydrogen bonds with the ACE active pockets, zinc-binding motif, and zinc ion. These results indicate that G. vrijenhoeki-derived peptides can serve as nutritional and pharmacological candidates for controlling blood pressure.

Coscinoderines A-J: Trisubstituted Pyridinium-Containing Norterpenoids Isolated from Coscinoderma bakusi, a Tropical Marine Sponge.

Ten new norterpene alkaloids, coscinoderines A-J (1-10), were isolated from the marine sponge Coscinoderma bakusi. Each coscinoderine contains a 1,2,5-trisubstituted pyridinium moiety bearing a terpene unit at the C-2 position. Their structures were elucidated by analysis of NMR and HRMS data, and the absolute stereochemistry of 4 with a 2-methylbutyl group attached to the nitrogen was determined from a comparison of the calculated and measured ECD spectra. The isolation of coscinoderines expands the repertoire of pyridinium alkaloids isolated from marine sponges.

Stocking-only versus additional eccentric compression after below-the-knee truncal vein sclerotherapy: A SOVAECS prospective randomized within-person trial.

OBJECTIVE: After foam sclerotherapy in the truncal saphenous vein, the clinical effects of additional eccentric compression has not yet been explored. METHODS: Between April 2020 and February 2021, we enrolled 42 patients (84 limbs) who underwent bilateral endovenous combined therapy for great saphenous vein (GSV) reflux. Each patient received the same type of endovenous ablation in both above-the-knee GSVs (laser, radiofrequency, cyanoacrylate glue), and combined foam sclerotherapy was performed on both below-the-knee GSVs. Subsequently, we conducted a prospective randomized, single-blind, within-person study in which each patient's bilateral truncal saphenous vein of the calves underwent two different compression therapies: wearing of a regular class II compression stocking on one side (RC group) and additional eccentric compression on the other side (AC group). The primary end point was the occlusion range (score, 0-10) of the below-the-knee truncal GSV after foam sclerotherapy. The secondary outcomes were the pain score (visual analog scale score range, 0-10) of the paired limb, the required number of additional foam sclerotherapy sessions, compliance with compression therapy, and procedure-related complications. RESULTS: For the above-the-knee GSV, endovenous laser treatment (n = 44), endovenous radiofrequency ablation (n = 14), and endovenous cyanoacrylate glue ablation (n = 26) were performed. The mean subcompression pressure of the medial calf in the supine and standing positions were 16.7 ± 2.34 mm Hg and 24.5 ± 6.6 mm Hg in the RC group and 38.5 ± 5.5 mm Hg and 45.3 ± 8.2 mm Hg in the AC group, respectively (P = .000). The secondary outcomes of pain score, number of additional foam sclerotherapy sessions, and pigmentation were not significantly different statistically between the two groups. The patient-reported satisfaction scores (range, 0-10) on compression at 24 hours postoperatively were 8.03 ± 1.9 for the AC group and 7.98 ± 1.9 for the RC group (P = .317; Wilcoxon signed ranks test). In both groups, the closure rate of the above-the-knee GSV at 1 month postoperatively was 100%. No procedure-related complications were identified within 1 month postoperatively, including no deep vein thrombosis, numbness, or skin necrosis requiring additional medical attention. CONCLUSIONS: The 24 hours of additional eccentric compression on the truncal GSV compared with the use of a conventional knee-level stocking only did not yield any clinical advantages in terms of the occlusion range, postoperative pain, need for additional sclerotherapy, or skin pigmentation after foam sclerotherapy. The decision on which type of compression therapy to perform after foam sclerotherapy in the truncal vein should be comprehensively determined.

Incidence and Clinical Impact of Endovenous Glue-Induced Hypersensitivity Among Patients Who Underwent Endovenous Cyanoacrylate Ablation Procedures: A Registry-Based Cohort Study.

BACKGROUND: The characteristics of endovenous glue-induced hypersensitivity (EGIH) remain unclear. OBJECTIVE: To assess the clinical impacts on patients with EGIH after endovenous cyanoacrylate-glue ablation (CA). MATERIALS AND METHODS: A prospectively designed endovenous CA-specific registry was created, and a total of 335 limbs from 173 patients who underwent endovenous CA were enrolled for a cohort study. RESULTS: Symptomatic EGIH was observed in 55 (31.8%) patients. Beyond the target vein area, systemic side effects were noted in 5.8% of the treated patients after CA. The median onset time was 13 postoperative days (range: 1-35 days). The median duration was 7 days, but about 10.9% of the affected patients experienced symptoms lasting longer than 4 weeks. In the EGIH and non-EGIH groups, significant improvements in venous clinical severity score and Chronic Venous Insufficiency Quality of Life Questionnaire-14 scores were observed 3 months postoperatively. The development of EGIH did not affect the postoperative patient-reported satisfaction scores ( p = .524). CONCLUSION: EGIH is observed in a substantial proportion of patients. The side effects do not affect the clinical outcomes and patient-reported outcome measures. Further studies are required on the detailed pathogenesis and definition of EGIH.

Bloom development of toxic dinoflagellate Alexandrium catenella (Group I) in Jinhae-Masan Bay, Korea: Germination strategy of resting cysts in relation to temperature and salinity.

To better understand the role of resting cysts in the outbreak of paralytic shellfish poisoning and bloom dynamics in Jinhae-Masan Bay, Korea, this study investigated the germination features of ellipsoidal Alexandrium cysts isolated from sediments collected in winter and summer under different combinations of temperature and salinity. Morphology and phylogeny of germling cells revealed that the ellipsoidal Alexandrium cysts belong to Alexandrium catenella (Group I). The cysts could germinate across a wide range of temperature (5-25 °C) with germination success within 5 days, indicating that continuous seeding for the maintenance of vegetative cells in the water column may occur through the year without an endogenous clock to regulate germination timing. In addition, the cyst germination of A. catenella (Group I) was not controlled by seasonal salinity changes. Based on the results, this study provides a schematic scenario of the bloom development of A. catenella (Group I) in Jinhae-Masan Bay, Korea.

Biocompatible 7-nitro-2,1,3-benzoxadiazole-embedded naphthalimide for exploring endogenous H2S in living cells.

Hydrogen sulfide (H2S) is a central signaling and antioxidant biomolecule involved in various biological processes. As inappropriate levels of H2S in the human body are closely related to various diseases, including cancer, a tool capable of detecting H2S with high selectivity and sensitivity in living systems is urgently required. In this work, we intended to develop a biocompatible and activatable fluorescent molecular probe for detecting H2S generation in living cells. The 7-nitro-2,1,3-benzoxadiazole-imbedded naphthalimide (1) probe presented here responds specifically to H2S and produces readily detectable fluorescence at 530 nm. Interestingly, probe 1 exhibited significant fluorescence responses to changes in endogenous H2S levels as well as high biocompatibility and permeability in living HeLa cells. This allowed for the real-time monitoring of endogenous H2S generation as an antioxidant defense response in the oxidatively stressed cells.

Isolation of Scalimides A-L: ß-Alanine-Bearing Scalarane Analogs from the Marine Sponge Spongia sp.

A chemical investigation of a methanol extract of Spongia sp., a marine sponge collected from the Philippines, identified 12 unreported scalarane-type alkaloids-scalimides A-L (1-12)-together with two previously described scalarin derivatives. The elucidation of the structure of the scalaranes based on the interpretation of their NMR and HRMS data revealed that 1-12 featured a ß-alanine-substituted E-ring but differed from each other through variations in their oxidation states and substitutions occurring at C16, C24, and C25. Evaluation of the antimicrobial activity of 1-12 against several Gram-positive and Gram-negative bacteria showed that 10 and 11 were active against Micrococcus luteus and Bacillus subtilis, respectively, with MIC values ranging from 4 to 16 µg/mL.

Incidence of tick-borne spotted fever group Rickettsia species in rodents in two regions in Kazakhstan.

Records on the distribution of Rickettsia spp. in their natural hosts in Central Asia are incomplete. Rodents and small mammals are potential natural reservoirs for Rickettsiae in their natural lifecycle. Studies about the maintenance of Rickettsia in wild animals are available for Western nations, but-to our knowledge-no studies and data are available in the Republic of Kazakhstan so far. The first case description of Rickettsioses in Kazakhstan was made in the 1950ies in the Almaty region and now Kyzylorda, East Kazakhstan, Pavlodar and North Kazakhstan are endemic areas. The existence of murine and endemic typhus was proven in arthropod vectors in the regions Kyzylorda and Almaty. Here we show for the first time investigations on tick-borne Rickettsia species detected by a pan-rickettsial citrate synthase gene (gltA) real-time PCR in ear lobes of small mammals (n = 624) in Kazakhstan. From all analysed small mammals 2.72% were positive for Rickettsia raoultii, R. slovaca or R. conorii. Sequencing of the rickettsial gene OmpAIV and the 23S-5S interspacer region revealed a similar heritage of identified Rickettsia species that was observed in ticks in previous studies from the region. In summary, this study proves that rodents in Kazakhstan serve as a natural reservoir of Rickettsia spp.

Transcriptional and toxic responses to saxitoxin exposure in the marine copepod Tigriopus japonicus.

Saxitoxin (STX) is a highly toxic marine neurotoxin produced by phytoplankton and a growing threat to ecosystems worldwide due to the spread of toxic algae. Although STX is an established sodium channel blocker, the overall profile of transcriptional levels in STX-exposed organisms has yet to be described. Here, we describe a toxicity assay and transcriptome analysis of the copepod Tigriopus japonicus exposed to STX. The half-maximal lethal concentration of STX was 12.35 µM, and a rapid mortality slope was evident at concentrations between 12 and 13 µM. STX induced changes in swimming behavior among the copepods after 10 min of exposure. In transcriptome analysis, gene ontology revealed that the genes involved in nervous system and gene expression were highly enriched. In addition, the congenital neurological disorder and nuclear factor erythroid 2-related factor 2-mediated oxidative stress pathways were identified to be the most significant in network analysis and toxicity pathway analysis, respectively. This study provides valuable information about the effects of STX and related transcriptional responses in T. japonicus.

Early line-probe assay using DNA specimens in patients with pulmonary TB.

BACKGROUND: We investigated the feasibility of early line-probe assay (LPA) using remnant DNA of Mycobacterium tuberculosis from polymerase chain reaction (PCR) test.METHODS: M. tuberculosis DNA specimens with cycle threshold (Ct) values reported and collected from patients with known results for both LPA with culture isolates and phenotype drug susceptibility testing (pDST) were selected. The diagnostic performance of DNA-based LPA according to the Ct value was investigated.RESULTS: A total of 143 respiratory specimens were included. For isoniazid resistance, the accuracy in subgroups with Ct value <25, 25-29 and ≥29 was respectively 96.8%, 65.7% and 13.3%. For rifampicin resistance, accuracy in subgroups with Ct values <29 and ≥29 was respectively 87.8% and 13.3%. When compared to the pDST results, sensitivity, specificity, positive predictive value and negative predictive value in specimens with Ct values <25 was respectively 1.00 (95% CI 0.69-1.00), 0.95 (95% CI 0.76-1.00), 0.91 (95% CI 0.59-1.00) and 1.00 (95% CI 0.83-1.00) for isoniazid resistance. For rifampicin resistance, corresponding values in subgroups with Ct values <29 were respectively 0.89 (95% CI 0.52-1.00), 0.98 (95% CI 0.91-1.00), 0.80 (95% CI 0.50-0.94) and 0.99 (95% CI 0.92-1.00).CONCLUSIONS: DNA-based early LPA with remnant DNA from respiratory samples was feasible and accurate when the Ct values were low.

Chirality-driven self-assembly: application toward renewable/exchangeable resin-immobilized catalysts.

Resin-immobilized catalysts were prepared through chirality-driven self-assembly. The method allows the resin-immobilized catalyst to be regenerated under mild conditions and in situ catalyst exchange to be carried out quantitatively. The uniqueness of the methodology was demonstrated by the preparation of a catalyst for TEMPO oxidation as well as a two-step sequential TEMPO oxidation/aldol condensation sequence enabled by facile catalyst exchange.

Effects of dinoflagellate Gymnodinium catenatum on swimming behavior and expression of heat shock protein (hsp) genes in the brine shrimp Artemia franciscana.

To understand the effects of the toxic marine dinoflagellate, Gymnodinium catenatum, on the brine shrimp, Artemia franciscana, we examined the acute toxicity and swimming behavior parameters such as swimming speed, swimming distance, and swimming path trajectory with transcriptional regulation of heat shock protein (hsp) genes in response to G. catenatum exposure. Mortality was not observed in response to G. catenatum. In the case of swimming behavior parameters, swimming speed and swimming distance were significantly decreased (P < 0.05) for 5 min at three concentrations (240, 360, and 600 cells/mL) of G. catenatum, whereas no significant change in swimming path trajectory was observed, suggesting that G. catenatum has potential adverse effects on the swimming behavior of A. franciscana. Additionally, the four A. franciscana-hsp genes (hsp26, hsp40, hsp70, and hsp90) were upregulated in response to G. catenatum. In particular, A. franciscana-hsp40 was significantly upregulated in response to 600 cells/mL G. catenatum, suggesting that A. franciscana-hsp genes are highly associated with cellular defense mechanisms and that A. franciscana-hsp40 is a potential biomarker for G. catenatum exposure. Overall, this study improves our understanding of the effects of G. catenatum on the swimming behavior and cellular defense mechanisms of A. franciscana.

Alexandrium catenella (Group I) and A. pacificum (Group IV) cyst germination, distribution, and toxicity in Jinhae-Masan Bay, Korea.

To better understand the outbreaks of paralytic shellfish poisoning and bloom dynamics caused by Alexandrium species in Jinhae-Masan Bay, Korea, the germination and distributions of ellipsoidal Alexandrium cysts were investigated, and paralytic shellfish toxins (PSTs) profiles and contents were determined using strains established from germling cells. The phylogeny and morphological observations revealed that the germinated vegetative cells from ellipsoidal cysts collected from the surface sediments in Jinhae-Masan Bay belong to Alexandrium catenella (Group I) and A. pacificum (Group IV) nested within A. tamarense species complex. Cyst germinations of A. catenella (Group I) were observed at only 10 °C, whereas cysts of A. pacificum (Group IV) could germinate at temperature ranges of 10 to 25 °C. Maximum germination success (85%) for isolated cysts occurred at 15 °C, and the germling cells were A. pacificum (Group IV). The results indicate that the variation in water temperature in Jinhae-Masan Bay can control the seasonal variations in germination of cysts of A. catenella (Group I) and A. pacificum (Group IV). The germination rates of ellipsoidal Alexandrium cysts were different among sampling sites in Jinhae-Masan Bay, probably because of differences in distribution and abundance of A. catenella (Group I) and A. pacificum (Group IV) in the sediments. The ellipsoidal Alexandrium cyst concentrations were much higher in February than in August, however the distributions were similar. Gonyautoxins 3 and 4 (GTX-3 and GTX-4) contributed a large proportion (>90%) of the toxins produced by strains A. catenella (Group I) and A. pacificum (Group IV) established from germling cells, and the total cellular contents were higher in A. catenella (Group I) than in A. pacificum (Group IV).

Isolation of Scalarane-Type Sesterterpenoids from the Marine Sponge Dysidea sp. and Stereochemical Reassignment of 12-epi-Phyllactone D/E.

The chemical investigation of the marine sponge Dysidea sp., which was collected from Bohol province in the Philippines, resulted in the identification of 15 new scalarane-type sesterterpenoids (1-14, 16), together with 15 known compounds. The chemical structures of the new compounds were elucidated based on NMR spectroscopy and HRMS. The structure of 12-epi-phyllactone D/E (15) isolated during this study was originally identified in 2007. However, careful inspection of our experimental 13C NMR spectrum revealed considerable discrepancies with the reported data at C-9, C-12, C-14, and C-23, leading to the correction of the reported compound to the C-12 epimer of 15, phyllactone D/E. The biological properties of compounds 1-16 were evaluated using the MDA-MB-231 cancer cell line. Compound 7, which bears a pentenone E-ring, exhibits significant cytotoxicity with a GI50 value of 4.21 µM.

Cell-specific activation of gemcitabine by endogenous H2S stimulation and tracking through simultaneous fluorescence turn-on.

The endogenous H2S-driven theranostic H2S-Gem has been invented. The theranostic prodrug H2S-Gem is selectively activated in cancer cells, releasing active gemcitabine with a simultaneous fluorescence turn-on. H2S-Gem selectively inhibited cancer cell growth compared to the mother chemotherapeutic gemcitabine. Overall, it is a unique protocol for tracking and transporting chemotherapeutic agents to tumor areas without the guidance of tumor-directive ligands.

Strategies of Detecting Bacteria Using Fluorescence-Based Dyes.

Identification of bacterial strains is critical for the theranostics of bacterial infections and the development of antibiotics. Many organic fluorescent probes have been developed to overcome the limitations of conventional detection methods. These probes can detect bacteria with "off-on" fluorescence change, which enables the real-time imaging and quantitative analysis of bacteria in vitro and in vivo. In this review, we outline recent advances in the development of fluorescence-based dyes capable of detecting bacteria. Detection strategies are described, including specific interactions with bacterial cell wall components, bacterial and intracellular enzyme reactions, and peptidoglycan synthesis reactions. These include theranostic probes that allow simultaneous bacterial detection and photodynamic antimicrobial effects. Some examples of other miscellaneous detections in bacteria have also been described. In addition, this review demonstrates the validation of these fluorescent probes using a variety of biological models such as gram-negative and -positive bacteria, antibiotic-resistant bacteria, infected cancer cells, tumor-bearing, and infected mice. Prospects for future research are outlined by presenting the importance of effective in vitro and in vivo detection of bacteria and development of antimicrobial agents.

Construction of Janus dendrimers through a self-assembly approach involving chiral discrimination at a focal point.

A strategy to build Janus dendrimers via the chirality-directed self-assembly of heteroleptic Zn(ii) BOX complexes is reported. The method allows quantitative synthesis of Janus dendrimers in situ without the need for purifications. Each dendritic domain of the Janus dendrimers can be recycled upon disassembly at the focal point.