Direct oral anticoagulants versus warfarin in people living with human immunodeficiency virus.

Human immunodeficiency virus (HIV) is associated with increased rates of cardiovascular disease and vascular events, and people living with HIV (PLWH) may often have indications for therapeutic anticoagulation. However, the ideal anticoagulant in PLWH remains unknown. This retrospective cohort evaluated the tolerability and effectiveness of oral anticoagulants in PLWH. The primary outcome was tolerability, defined as a composite of bleeding and/or discontinuation rates. The secondary outcomes included recurrent thromboembolism, bleeding, and discontinuations, independently. There were 92 patients included for analysis, 48 in the direct oral anticoagulant (DOAC) arm and 44 in the warfarin arm. There were 35 (38%) PLWH that did not tolerate oral anticoagulation therapy in the total cohort. Among these, 19 received a DOAC and 16 received warfarin. There were 16 (17%) PLWH that experienced a bleeding event: six in the DOAC arm and 10 in the warfarin arm. There were 15 (16%) PLWH that experienced recurrent thromboembolism, with similar rates between DOAC versus warfarin (10, 21% vs 5, 11%, respectively; p = 0.11). The most commonly prescribed HIV regimens were protease inhibitor and integrase inhibitor-based regimens. Overall, anticoagulation-related outcomes with either a DOAC or warfarin were poor in our cohort of PLWH, with high rates of bleeding, discontinuations, and recurrent thromboembolism. Further studies are necessary to validate and assess reasons for poor tolerability.

Do distribution and expansion of exotic invasive Asteraceae plants relate to leaf construction cost in a man-made wetland?

Exotic species especially Asteraceae plants severely invade wetlands in Shenzhen Bay, an important part of the coast wetland in Guangdong-Hong Kong-Macau Bay Area, China. However, the reasons causing their expansion are unclear. The leaf traits and expansion indices of six invasive Asteraceae plants from the Overseas Chinese Town (OCT) wetland were studied and the results showed that nearly 45% of the total plant species (31 out of 69 species) in the OCT wetland, belonging to 15 families and 27 genera, were exotic invasive species. The expansion indices of six Asteraceae species negatively correlated with their leaf construction cost based on mass (CCM), caloric values and carbon concentration, but their relations with ash content were positive. Multiple linear regression analysis revealed that CCM was the most important factor affecting the expansion of an exotic species, indicating CCM may be an important reason causing the expansion of exotic species in coastal wetlands.

Is Laguncularia racemosa more invasive than Sonneratia apetala in northern Fujian, China in terms of leaf energetic cost?

Laguncularia racemosa and Sonneratia apetala are fast-growing exotic mangrove species in Southern China and widely used for afforestation. However, the invasiveness of the two exotic species is still unclear. We compared structural and physiological traits and energy-use related traits between L. racemosa and S. apetala, and with two natives (Kandelia obovata and Aegiceras corniculatum) in northern Fujian. Results showed that leaf construction cost based on mass (CCM) and caloric values of L. racemosa were significantly lower than S. apetala, and the two natives had highest CCM. Because lower CCM, L. racemosa grew faster with a taller height (4.83 m) and wider ground diameter circumference (40.03 cm) than S. apetala (4.43 m tall and 35.63 cm wide) and the two natives (2.42 m tall and 26.78 cm wide). These findings indicated that L. racemosa could be more invasive than S. apetala in mangrove forests in northern Fujian, China where it still grew well, which deserves more attention.

The combined effects of elevated pCO2 and food availability on Tigriopus japonicus Mori larval development, reproduction, and superoxide dismutase activity.

Previous studies have shown that ocean acidification has little effect on adult Tigriopus japonicus copepods, and mainly impairs the early development and reproduction of females. This study investigated the possible interactive effect between CO2-induced seawater acidification and food availability on larval development and reproductive output in T. japonicus. Copepods were exposed to either pH8.1 or pH7.3 under different food concentrations (0.5×104-80.0×104cells/mL). Both the development of nauplii and copepodites was delayed at pH7.3 with a greater effect at lower food concentrations. The reproductive output followed a bell-shaped curve with the highest reproductive output at food concentrations between 30×104 and 40×104cells/mL. As an indicator of oxidative stress, the activity of superoxide dismutase increased at lower pH, with a greater increase at lower food concentrations. Therefore, the effect of elevated pCO2 on T. japonicus was food dependent.

Predator-prey interaction between muricid gastropods and mussels under ocean acidification.

Predation of the muricid gastropod Thais clavigera on two-sized groups of the mussel Brachidontes variabilis was studied under three pCO2 levels, 380, 950, and 1250µatm. At 950µatm pCO2 level, the prey handling time decreased significantly and large-sized B. variabilis were preferred by T. clavigera. However, the prey consumption rate was independent of pCO2 levels, although the prey searching time increased significantly at elevated pCO2. These findings indicated that the predator-prey interaction between T. clavigera and B. variabilis was altered under ocean acidification, which will have a long-term impact on the population dynamics of the interacting species.

Microplastic ingestion reduces energy intake in the clam Atactodea striata.

The effects of microplastic concentrations (10itemsl-1 and 1000itemsl-1) on the physiological responses of Atactodea striata (clearance rate, absorption efficiency, respiration rate) were investigated. The fates of ingested microplastics and the efficiency of depuration in removing ingested microplastics were also studied. A. striata ingested microplastics and the clearance rate was reduced at high concentration of microplastics. Since the respiration rate and absorption efficiency remained unchanged in exposed A. striata, reduction in the clearance rate would reduce the energy intake. Ingestion and retention of microplastics in the body were further limited by the production of pseudofaeces and faeces, and depuration in clean water, resulting in a very small amount of microplastics stored in the body of the clam.

Isolation and mRNA expression of hypoxia-inducible factor α (HIF-α) in two sublittoral nassariid gastropods: Nassarius siquijorensis and Nassarius conoidalis.

Hypoxia-inducible factor (HIF) is commonly found in vertebrates as an adaptation against hypoxia. In this study, partial sequences of HIF were first reported for subtidal nassariid gastropods, Nassarius siquijorensis and Nassarius conoidalis. The phylogenetic tree of HIF-α among various animal groups was inferred. Adults of both N. siquijorensis and N. conoidalis were exposed to 24 h and 1 week hypoxia (1.5 mg O2 l(-1)) and the change of HIF-α mRNA level was determined in gill, foot muscle and hepatopancreas by using quantitative real-time PCR. The expression profile of HIF-α was also investigated in veliger larvae after 1 and 24 h hypoxia exposure. The HIF-α mRNA from gills of N. siquijorensis was 2.22-fold elevated after 24 h of exposure but returned back to the baseline level after 1 week of exposure. In contrast to N. siquijorensis, both short-term and long-term exposure to hypoxia significantly enhanced the mRNA level of HIF-α in the gill of N. conoidalis. Both 24 h and 1 week of exposure resulted in a significantly higher degree of expression of mRNA of HIF-α in the foot muscle of N. siquijorensis and N. conoidalis. For hepatopancreas, the mRNA level of HIF-α remained unchanged in N. siquijorensis after both 24 h and 1 week of exposure to hypoxia but a significant enhancement was observed in N. conoidalis after 1 week of exposure to hypoxia. The mRNA level of HIF-α significantly reduced after 24 h of exposure to hypoxia in the larvae of N. siquijorensis. The different expression patterns of HIF-α mRNA between the two species reflected their different adaptation abilities to hypoxia, which will further explain the differences in the distribution of these species in Hong Kong waters with N. siquijorensis being predominant in regions suffered from summer hypoxia.

Effects of hypoxia on biofilms and subsequently larval settlement of benthic invertebrates.

Biofilms on submerged surfaces are important in determining larval settlement of most marine benthic invertebrates. We investigated if exposure of biofilms to hypoxia would alter the larval settlement pattern and result in a shift in benthic invertebrate community structure in the field. Biofilms were first exposed to hypoxia or normoxia in laboratory microcosms for 7 days, and then deployed in the field for another 7 days to allow for larval settlement and recruitment to occur. Using terminal-restriction fragment length polymorphism of the 16S rRNA gene, this study showed that hypoxia altered the biofilm bacterial community composition, and the difference between the hypoxic and normoxic treatments increased with the time of exposure period. This study also demonstrated significantly different benthic invertebrate community structures as a result of biofilm exposure to hypoxia and that the hypoxic and normoxic treatments were dominated by Hydroides sp. and Folliculina sp., respectively.

Effects of salinity on anatomical features and physiology of a semi-mangrove plant Myoporum bontioides.

The effect of different concentrations of NaCl, 0, 100, 200, 300 and 400 mM, on the anatomical features and physiology of Myoporum bontioides was investigated. The photosynthetic rates (Pn) were significantly reduced by salt stress, with the lowest values at 400 mM NaCl. The content of malondialdehyde (MDA), proline and soluble sugar, as well as the activities of peroxidase (POD) and catalase (CAT) increased at the beginning, but became similar to the control as the experiment proceeded. The NaCl effect on superoxide dismutase (SOD) was different from the other parameters, with a significant reduction at 400 mM NaCl at Day 7. Salt glands were found in both upper and lower epidermis, and the ratios of the thickness of palisade to spongy mesophyll tissues increased with NaCl concentrations. The medullary ray was clearly damaged by NaCl at levels of 200 and 300 mM. These results demonstrated that M. bontioides could adapt to a relatively low salinity, and was not a halophilous species.

Comparisons of the metabolic responses of two subtidal nassariid gastropods to hypoxia and re-oxygenation.

Changes in the levels of carbohydrate, lipid, protein and anaerobic metabolites (succinate, lactate, acetate, fumarate and propionate), upon exposure to hypoxia (1.5 mg O2 l(-1)) and after reoxygenation in subtidal gastropods Nassarius siquijorensis and N. conoidalis, were compared. A significant decrease of the glycogen content was observed under hypoxia in N. conoidalis but not in N. siquijorensis. A greater increase in the concentrations of anaerobic metabolites was observed in N. conoidalis under hypoxia, and their levels did not return to baseline after returning to normoxia for 24h. In contrast, a lower rate of accumulation of the metabolites was observed in N. siquijorensis, and complete recovery from anaerobic metabolism was observed after reoxygenation. The results lend further support to the role of hypoxia in governing the different distributional patterns between the two subtidal gastropods in Hong Kong waters.

Structure and function of soil microbial community in artificially planted Sonneratia apetala and S. caseolaris forests at different stand ages in Shenzhen Bay, China.

The present study examined the relationships between soil characteristics, microbial community structure and function in the forests artificially planted with exotic Sonneratia apetala at stand ages of 1-, 2-, 7-, 10- and 14-years and Sonneratia caseolaris of 1-, 4-, 7-, 10- and 14-years in Futian National Nature Reserve, Shenzhen Bay, China. The 7-years old forests of both Sonneratia species reached peak growth and had the highest content of nitrogen and phosphorus, enzymatic activities, including dehydrogenase, cellulase, phosphatase, urease and ß-glucosidase, except arylsulphatase which increased continuously with stand ages. The microbial community structure reflected by phospholipid fatty acid (PLFA) profiles also reached the maximum value in the 7-years old forests and soil bacterial PLFAs in both forests were significantly higher than fungal PLFAs. The canonical correlation analysis revealed that differences in microbial structural variables were significantly correlated to the differences in their functional variables, and the highest correlation was found between the soil enzymatic activities and the content of carbon and nitrogen.

Acute hypoxic exposure affects gamete quality and subsequent fertilization success and embryonic development in a serpulid polychaete.

Hypoxia likely compromises the reproductive success of those marine organisms carrying out external fertilization because their gametes and embryos are inevitably exposed to the external environment. Hydroides elegans, a dominant serpulid polychaete in Hong Kong waters, can spawn throughout the year but the number of recruits drops during summer when hypoxia commonly occurs. This study attempted to explain such observation by investigating the gamete quality, including sperm motility, egg size, complexity and viability, after 1-h hypoxic exposure (1 mg O2 l(-1)). In addition, how gamete quality affects fertilization success and embryonic development was examined. After 1-h hypoxic exposure, sperm motility was significantly reduced, compromising fertilization success. Although the eggs remained viable, more malformed embryos and retarded embryonic development were observed. We interpreted that the harmful effect of hypoxia on embryonic development was attributed to the teratogenicity and induced oxidative stress, ultimately causing the reduction in recruitment during summer.

Hypoxia induces abnormal larval development and affects biofilm-larval interaction in the serpulid polychaete Hydroides elegans.

Hydroides elegans, a worldwide fouling polychaete, can spawn throughout the year, but its recruitment drops during summer when hypoxia prevails. Here, the influence of hypoxia on larval development and settlement of H. elegans was investigated. Results showed that larval development was compromised at 1mg O2 l(-1) with a lower proportion of competent larvae and a higher proportion of malformed larvae, probably due to reduction in clearance rate. Regarding larval settlement, although most of the larvae were reluctant to settle at 1mg O2 l(-1), regardless of the biofilm nature, they settled quickly within 24h in response to the resumption of dissolved oxygen. Furthermore, only about 5% of the larvae settled on the biofilms developed under hypoxia, regardless of dissolved oxygen levels of the seawater. The delayed larval development and potential alteration of biofilm nature owing to hypoxia explained why the recruitment of H. elegans declines during summer.

Effect of parental hypoxic exposure on embryonic development of the offspring of two serpulid polychaetes: Implication for transgenerational epigenetic effect.

Sperm production and motility, fecundity, and egg size, complexity and viability of serpulid polychaetes Hydroides elegans and Hydroides diramphus after 2-week treatment to hypoxia (2 mg O2 l(-1)) was compared with those under normoxia (6 mg O2 l(-1)). Despite reduced fecundity, the effect of parental hypoxic exposure on gamete quality was not discernible for both species. However, regardless of their subsequent dissolved oxygen environment, eggs spawned by H. elegans after hypoxic exposure were found to have lower fertilization success, slower embryonic development and a significantly higher yield of malformed embryos than those with a parental normoxic treatment. In contrast, neither fertilization success nor rate of embryonic development was affected for H. diramphus. The results implied that hypoxia was a potential stress reducing the recruitment of H. elegans through non-adaptive epigenetic effect, whereas H. diramphus was a more tolerant species to survive hypoxic events.

A baseline study of benthic community associated with Amphioxus Sand in subtropical Hong Kong.

An annual investigation on the seasonal changes of benthic community structure associated with Amphioxus Sand was conducted at two sites in the eastern waters of subtropical Hong Kong, where three species of amphioxus, Branchiostoma belcheri, B. japonicum and B. malayanum coexist. A total of 84 species and 4169 individuals were recorded at Tai Long Wan, whereas a total of 87 species and 3915 individuals were recorded at Pak Lap Wan. Benthic polychaetes were dominant, including high abundance of Onuphis eremita and Prionospio malmgreni. Results of cluster analysis showed significant community structures between the two areas because of difference in sediment granulometry. However, temporal changes within these Amphioxus Sand communities were minimal. In general, the Amphioxus Sand communities in Hong Kong showed higher species richness of Polychaeta as compared with similar studies elsewhere, possibly implying an increased level of organic pollution in Hong Kong waters.

Chronic hypoxia and low salinity impair anti-predatory responses of the green-lipped mussel Perna viridis.

The effects of chronic hypoxia and low salinity on anti-predatory responses of the green-lipped mussel Perna viridis were investigated. Dissolved oxygen concentrations ranged from hypoxic to normoxic (1.5 ± 0.3 mg l(-1), 3.0 ± 0.3 mg l(-1) and 6.0 ± 0.3 mg l(-1)), and salinities were selected within the variation during the wet season in Hong Kong coastal waters (15‰, 20‰, 25‰ and 30‰). The dissolved oxygen and salinity significantly affected some anti-predatory responses of mussel, including byssus production, shell thickness and shell weight, and the adductor diameter was only significantly affected by salinity. Besides, interactive effects of dissolved oxygen and salinity on the byssus production and shell thickness were also observed. In hypoxic and low salinity conditions, P. viridis produced fewer byssal threads, thinner shell and adductor muscle, indicating that hypoxia and low salinity are severe environmental stressors for self-defence of mussel, and their interactive effects further increase the predation risk.

Characterization of subpopulations and immune-related parameters of hemocytes in the green-lipped mussel Perna viridis.

The green-lipped mussel Perna viridis is distributed widely in the estuarine and coastal areas of the Indo-Pacific region and extensively cultured as an inexpensive protein source. Morphology and immunological activities of hemocytes of P. viridis were investigated using flow cytometry and light and electron microscopy. Three major types of hemocytes were identified in the hemolymph, including dense-granulocyte, semi-granulocyte (small and large size) and hyalinocyte. Other hemocytes, which occurred in low numbers, included granulocytes with different electron-dense/lucent granules and hemoblast-like cells. Based on flow cytometry, two subpopulations were identified. Granulocytes were larger cells, and the more abundant, containing numerous granules in the cytoplasm, and hyalinocytes were the smaller and less abundant with the fewest granules. Flow cytometry revealed that the granulocytes were more active in cell phagocytosis, contained the higher lysosomal content, and showed higher esterase activity and reactive oxygen species (ROS) generation compared with hyalinocytes. Immune functions assessed by the flow cytometry indicated that the granulocytes were the main hemocytes involved in the cellular defence in P. viridis.

Randomized, double-blind, placebo-controlled trial of ezogabine (retigabine) in partial epilepsy.

OBJECTIVE: To evaluate the efficacy and safety of ezogabine (United States adopted name)/retigabine (international nonproprietary name) (EZG[RTG]) 1,200 mg/day as adjunctive treatment in adults with drug-resistant epilepsy with partial-onset seizures with or without secondary generalization. METHODS: RESTORE 1 was a multicenter, randomized, double-blind, parallel-group trial. Following a prospective 8-week baseline phase, patients entered an 18-week double-blind treatment period (6-week forced dose titration to EZG[RTG] 1,200 mg/day in 3 equally divided doses or placebo, followed by a 12-week maintenance phase). Results were analyzed on an intent-to-treat basis for the entire 18-week period and for patients reaching the maintenance phase. RESULTS: In 306 patients randomized, 305 received EZG(RTG) 1,200 mg/day (n = 153) or placebo (n = 152). Median percent reduction in total partial-seizure frequency was 44.3% vs 17.5% (p < 0.001) for EZG(RTG) and placebo, respectively, during the 18-week double-blind period; responder rates (≥50% reduction in total partial-seizure frequency from baseline) were 44.4% vs 17.8% (p < 0.001). In 256 patients (EZG[RTG], 119; placebo, 137) entering the 12-week maintenance phase, median percent reduction in seizure frequency for EZG(RTG) vs placebo was 54.5% and 18.9% (p < 0.001), respectively; responder rates were 55.5% vs 22.6% (p < 0.001). The proportion of patients discontinuing due to treatment-emergent adverse events (TEAEs) was 26.8% (EZG[RTG]) vs 8.6% (placebo). Dizziness, somnolence, fatigue, confusion, dysarthria, urinary tract infection, ataxia, and blurred vision were the most common TEAEs reported by more patients treated with EZG(RTG) than placebo. CONCLUSIONS: This study demonstrates that EZG(RTG) is effective as add-on therapy for reducing seizure frequency in patients with drug-resistant partial-onset seizures. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that EZG(RTG) 1,200 mg/day is effective as adjunctive therapy in adults with partial-onset seizures with or without secondary generalization.

Respiration rate and swimming activity of larvae of two sub-tidal nassariid gastropods under reduced oxygen levels: implications for their distributions in Hong Kong waters.

The effects of hypoxia on the larvae of two sub-tidal nassariid gastropods, Nassarius siquijorensis and N. conoidalis were compared so as to understand how the species-specific tolerance to hypoxia might have resulted in changes in the abundance and distribution of these two species in the hypoxic Tolo Harbour, Hong Kong, since the 1980s. Respiration rates of N. siquijorensis and N. conoidalis larvae were reduced at 4.5 mg O2 l(-1), or below, as compared with the normoxic control. Significant reduction in swimming velocity was also observed for 10-day old larvae which were exposed to <2.0 mg O2 l(-1) for N. siquijorensis and <1.0 mg O2 l(-1) for N. conoidalis. The 48 h LC50 values of N. siquijorensis and N. conoidalis larvae were 0.7 and 1.7 mg O2 l(-1), respectively. The results suggested that N. siquijorensis are more tolerant to hypoxia than N. conoidalis.

Impact of hypoxia on the structure and function of benthic epifauna in Tolo Harbour, Hong Kong.

In Tolo Harbour, Hong Kong, where hypoxia occurs periodically, a large amount of benthic epifauna was found to be absent in the summer but become abundant again in the winter. This observation may indicate that some species are sensitive in detecting low dissolved oxygen (DO) levels and are able to escape from the harbour to more oxygenated, open waters when conditions deteriorate and return when DO levels are improved. Analysis of biological traits of these animals showed that 58% of the categories showed significant differences between the community structure in summer and winter. The significant biological traits of the few species, which remained in the harbour under the summer's hypoxic conditions suggested adaptation rather than opportunism to the low DO levels. Our data also showed that trawling can increase DO at the bottom and may benefit the less sensitive species that remained in the habitat during the summer.