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There are limited data on the fluid balance characteristics and fluid replenishment behaviors of high-performance adolescent athletes. The heterogeneity of hydration status and practices of adolescent athletes warrant efficient approaches to individualizing hydration strategies. This study aimed to evaluate and characterize the hydration status and fluid balance characteristics of high-performance adolescent athletes and examine the differences in fluid consumption behaviors during training. In total, 105 high-performance adolescent athletes (male: 66, female: 39, age 14.1 ± 1.0 y) across 11 sports had their hydration status assessed on three separate occasions—upon rising and before a low and a high-intensity training session (pre-training). The results showed that 20–44% of athletes were identified as hypohydrated, with 21–44% and 15–34% of athletes commencing low- and high-intensity training in a hypohydrated state, respectively. Linear mixed model (LMM) analyses revealed that athletes who were hypohydrated consumed more fluid (F (1.183.85)) = 5.91, (p = 0.016). Additional K-means cluster analyses performed highlighted three clusters: “Heavy sweaters with sufficient compensatory hydration habits,” “Heavy sweaters with insufficient compensatory hydration habits” and “Light sweaters with sufficient compensatory hydration habits”. Our results highlight that high-performance adolescent athletes with ad libitum drinking have compensatory mechanisms to replenish fluids lost from training. The approach to distinguish athletes by hydration characteristics could assist practitioners in prioritizing future hydration intervention protocols.

This study investigated the carbon (C) and nitrogen (N) gas emissions (N2O, NH3, CO2 and CH4) from solid pig manure management in China. Gas emissions were quantified from static piles over 60 days during summer in China's Yangtze River Basin, using Drager-Tube and static chamber-gas chromatography techniques. High emissions of NH3 and N2O were observed at the early stage of storage, but high emission of CH4 occured later during storage. Overall, 62% of the total C in the original pile was lost; CO2 and CH4 emissions accounted for 57 and 0.2% of C lost respectively. Over the same time, 41% of the total N in the original pile was lost; NH3 and N2O emissions accounted for 15 and 0.3% of N lost respectively. The volatilization of NH3 during storage in summer was 4.56 g NH3 per kg dry weight. The total greenhouse gas (GHG) emissions during storage accounted for 67.93 g CO2 equivalent per kg dry weight; N2O and CH4 contributed to 46 and 55% of total GHG emissions respectively. Given China's major role in pig production, further attention should given to pig manure management to mitigate its contribution to atmospheric pollution.

Recent studies demonstrated that lignite application in feedlot can mitigate ammonia (NH3) emission from intensive livestock production, which is an important source of environmental pollution. However, the use of lignite on feedlot requires mining and transport of lignite, which are themselves sources of greenhouse gas and other gaseous pollutants. There is a need for an integrated assessment on the gas emissions to determine the potential impact of those additions to the production chain. Using a case study in Victoria, Australia, carbon dioxide (CO2) and NH3 were identified as key emission changes compared to business as usual (BAU). Social costs and benefits analysis indicated that these changes in emissions translate to social benefits of AUD$11 - $151 and $18 - $256 per cattle per year at lignite application rate of 3 and 6 kg m-2 respectively, while the corresponding social costs of the additional gaseous emissions are AUD$2 - $19 and $3 - $28 per cattle per year per 200 km. Our results indicate that the use of lignite in feedlot to mitigate NH3 can be targeted at feedlots located in proximity to lignite source, population centre and/or vulnerable ecosystems to maximise social benefits and minimise social costs. More broadly, estimating the social costs and benefits of changing manure management practice to mitigate NH3 emission generates information that can be used to evaluate alternative policies for N management.

Reactive nitrogen (Nr; all species of nitrogen other than N2 gas) is a major cause of air and water pollution, with worldwide costs of billions in human health and ecosystem damages. The nitrogen (N) footprint, which quantifies the anthropogenic release of Nr from the production and consumption of both food and energy, has been used as an indicator of sustainability at individual and national levels. Here, we present the first institutional N footprint in Australia – the N footprint for The University of Melbourne (UoM) in 2015, and projections to 2020 under four scenario families. The total N footprint of UoM in 2015 was 139 tonnes N; food production (36.7%), utilities (32.4%), and transport (28.1%) were the major contributors while food consumption and fertilizer usage made up the remaining 2.8%. Under a businessasusual scenario, the N footprint of UoM would grow by 13% to 157 tonnes N in 2020 due to increase in student and staff population and infrastructure development. However, UoM has the potential to reduce its N footprint by 59% relative to the 2015 baseline if it implements changes to food purchases and energy use by 2020. The mitigation strategies with the largest potential reduction should be prioritized, including shifting purchased electricity fuel sources to wind or solar (26% reduction) and reducing air travel emissions (25% reduction). We demonstrate the potential of the N footprint as a tool for an institution to assess and monitor the sustainability of its operations and governance. Universities are leading the way in sustainable development, and the calculation of N footprint for UoM is the starting point for future work on sustainable institutional Nr management in Australia.

The potential effect of herbicides on soil functions, including nitrogen (N) transformations, is of interest to farmers, advisers, regulators and the community, yet comparisons of herbicides with different modes of action in a range of soil types are scarce. We applied seven commonly used herbicides (glyphosate acid, 2,4-dichlorophenoxyacetic acid [2,4-D], metsulfuron-methyl, trifluralin, diuron, atrazine and diflufenican) and one fungicide (tebuconazole) to five different Australian cropping soils at a recommended and five times recommended rate. Mineral N levels and the activities of eight enzymes involved organic matter cycling, including β-N-acetylglucosaminidase and leucine aminopeptidase contributing to organic N transformation, were monitored over a 28-d period. Only one herbicide (atrazine) at a recommended rate statistically (P 25% inhibition cf. control treatment) reduced NO3− formation in one soil type at the end of the incubation. The remaining herbicides at recommended rates had inconsistent, transitory or negligible effects on enzyme activities and mineral N levels. However, five times the recommended rate of metsulfuron-methyl or 2,4-D caused alterations to mineral N levels, either as reduced NO3− or increased NH4+, across multiple soil types. This study suggests that N-transformation assays were at least, if not, more sensitive to herbicides than enzyme assays. Overall, our study confirms that single recommended rate applications of herbicides typically have limited effects on soil functions such as N-transformation and soil enzyme activities involved in organic matter and nutrient cycling. The observation of significant effects at higher-than-label rates highlights the need to follow label instructions and prevent herbicide accumulation in soil.

Microplastics and nanoplastics are emerging pollutants of global importance. They are small enough to be ingested by a wide range of organisms and at nano-scale, they may cross some biological barriers. However, our understanding of their ecological impact on the terrestrial environment is limited. Plastic particle loading in agroecosystems could be high due to inputs of some recycled organic waste and plastic film mulching, so it is vital that we develop a greater understanding of any potentially harmful or adverse impacts of these pollutants to agroecosystems. In this article, we discuss the sources of plastic particles in agroecosystems, the mechanisms, constraints and dynamic behaviour of plastic during aging on land, and explore the responses of soil organisms and plants at different levels of biological organisation to plastic particles of micro and nano-scale. Based on limited evidence at this point and understanding that the lack of evidence of ecological impact from microplastic and nanoplastic in agroecosystems does not equate to the evidence of absence, we propose considerations for addressing the gaps in knowledge so that we can adequately safeguard world food supply.

Plastic pollution is a global concern given its prevalence in aquatic and terrestrial ecosystems. Studies have been conducted on the distribution and impact of plastic pollution in marine ecosystems, but little is known on terrestrial ecosystems. Plastic mulch has been widely used to increase crop yields worldwide, yet the impact of plastic residues in cropland soils to soil health and crop production in the long term remained unclear. In this paper, using a global meta-analysis, we found that the use of plastic mulch can indeed increase crop yields on average by 25%-42% in the immediate season due to the increase of soil temperature (+8%) and moisture (+17%). However, the unabated accumulation of film residues in the field negatively impacts its physicochemical properties linked to healthy soil and threatens food production in the long term. It has multiple negative impacts on plant growth including crop yield (at the mean rate of -3% for every additional 100 kg/ha of film residue), plant height (-2%) and root weight (-5%), and soil properties including soil water evaporation capacity (-2%), soil water infiltration rate (-8%), soil organic matter (-0.8%) and soil available phosphorus (-5%) based on meta-regression. Using a nationwide field survey of China, the largest user of plastic mulch worldwide, we found that plastic residue accumulation in cropland soils has reached 550,800 tonnes, with an estimated 6%-10% reduction in cotton yield in some polluted sites based on current level of plastic residue content. Immediate actions should be taken to ensure the recovery of plastic film mulch and limit further increase in film residue loading to maintain the sustainability of these croplands.

The impact of microplastic pollution on terrestrial biota is an emerging research area, and this is particularly so for soil biota. In this study, we addressed this knowledge gap by examining the impact of aged low-density polyethylene (LDPE) and polyester fibres (i.e. polyethylene terephthalate, PET) on a forest microbiome composition and activity. We also measured the corresponding physicochemical changes in the soil. We observed that bacteria community composition diverged in PET and LDPE treated soils from that of the control by day 42. These changes occurred at 0.2% and 0.4% (w/w) of PET and at 3% LDPE. Additionally, soil respiration was 8-fold higher in soil that received 3% LDPE compared to other treatments and control. There were no clear patterns linking these biological changes to physicochemical changes measured. Taken together, we concluded that microplastics aging in the environment may have evolutionary consequences for forest soil microbiome and there is immediate implication for climate change if the observed increase in soil respiration is reproducible in multiple ecosystems.

Today's ecosystems are influenced by different factors that could evolve into stressors. Effects of pesticides, especially in agricultural areas, may interact with environmental factors, such as soil moisture fluctuation caused by global climate change. In this contribution, two semi-field studies conducted in Germany and Portugal with terrestrial model ecosystems are presented. Their aim was to assess the effects of the fungicide pyrimethanil under different soil moisture levels on Enchytraeidae. In Portugal a no observed effect concentration design was chosen, using two concentration levels: the maximum application rate (MAR) according to the safe use registration within the European Union and five times the MAR (1.82 and 9.09 mg/kg dry soil, respectively). Both concentrations did neither affect the total enchytraeid abundance nor single populations. In Germany an ECx design (effect concentration) was conducted, using 11 concentrations. In general, 14 EC50 values for different combinations of single species, moisture level and sampling date were determined. The strongest effects were found in dry soil, particularly for Fridericia connata (EC50: 3.48 mg/kg dry soil after 8 weeks of exposure). The advantages and challenges of these test designs are discussed with regard to the registration process of pesticides in the European Union. In any case, enchytraeids are suitable test organisms in such higher tier studies for the combined evaluation of chemical and climatic stressors due to their usually high diversity and abundances and their close contact with the soil solution.

Grassland ecosystems in south-eastern Australia are important for dairy and livestock farming. Their productivity relies heavily on water availability, as well as the ecosystem services provided by soil microbial communities including carbon and nutrient cycling. Management practices such as compost application are being encouraged as a means to improve both soil water holding capacity and fertility, thereby buffering against the impacts of increasing climate variability. Such buffering consists of two complementary processes: resistance, which measures the ability of an ecosystem to maintain community structure and function during a period of stress (such as drying); and resilience, which measures the ability of an ecosystem to recover community structure and function post-stress. We investigated the effects of compost on the resistance and resilience of the grassland soil ecosystem under drying and drying with rewetting events, in a terrestrial model ecosystem. Overall, compost addition led to an increase in soil moisture, greater plant available P and higher plant δ15N. Soil C:nutrient ratios, mineral N content (NH4+ and NO3−) and soil microbial PLFA composition were similar between amended and unamended soils. Rainfall treatment led to differences in soil moisture, plant above-ground and below-ground biomass, plant δ15N, soil mineral N content (NH4+ and NO3−) and microbial biomass C, N and P composition but had no effects on soil C:nutrient ratios, plant available P and soil microbial PLFA composition. There was little interaction between rainfall and compost. Generally, the soil microbial community was resistant and resilient to fluctuations in rainfall regardless of compost amendment. However, these properties of the soil microbial community were translated to resilience and not resistance in soil functions. Overall, the results below-ground showed much greater response to rainfall than compost amendment. Water was the key factor shaping the soil microbial community, and nutrients were not strong co-limiting factors. Future projections of increasing rainfall variability will have important below-ground functional consequences in the grassland, including altered nutrient cycling.

The transformation of organic matter amendments in the soil is regulated by soil microbial communities. We examined the utility of ecological and functional stoichiometry theories to explain microbial transformation of organic amendments in the soil and examined the key relationships between soil microbial community composition, biomass and activity with resource elemental composition (soil and organic input) and nutrient availability. Using two contrasting soils amended with raw green waste, its compost or biochar, we found that microbial PLFA composition was distinct for each soil and organic amendment. Microbial activity was strongly influenced by organic amendment. Further, we observed that changes in the soil stoichiometry with inputs were accompanied by changes in total PLFA and bacteria: fungal ratio, but the relationships between them were inconsistent and changed over time. Microbial activities involved in C, N and P cycling were generally correlated, but the relationship between hydrolase β-glucosidase (BGL) and microbial N and P activities was stronger and more consistent than that between oxidases (phenol oxidase PPO, peroxidase POX) and microbial N and P activities. These microbial activity relationships translated to a consistent relationship between log(BGL):log(nutrient) and soil C:nutrient but a weaker and inconsistent relationship between log(PPO + POX):log(nutrient) and soil C:nutrient. Our analyses indicate that microbial composition can be different, but stoichiometric invariance of microbial activity constrained microbial community response to organic input.

The transformation of organic amendments (OA) in soil is in large part performed by soil microbial communities. These processes are strongly affected by the carbon composition of the OAs. We examined microbial community responses to three types of OA: green waste, composted green waste and pyrolysed green waste added to two contrasting agricultural soils. We investigated the relationship between the soil carbon composition (as determined by 13 C-solid state NMR), microbial community composition (as determined by phospholipid fatty acid analysis) and microbial activity (as determined by soil enzyme assays). We found that alkyl-C, O-aryl-C, aryl-C and carbonyl-C were able to explain most of the variations (≥50%) in soil microbial community composition and activity. Aryl-C content (reflecting relatively stable carbon forms) strongly influenced microbial composition, while carbonyl-C content (reflecting relatively labile carbon forms) strongly influenced the microbial activity. Our results confirm that there is a tight relationship between carbon composition and soil microbial community composition and function. Results are discussed in the context of examining the relationship between carbon forms, microbial community composition and activity following the addition of different OAs to the soil.

Soil is central to human wellbeing through its provision of critical ecosystem services, including food and clean water. These services emerge through the self-organising nature of the soil system. Here, we consider the lessons learnt from the evolution of the understanding of human and ecosystem health for the conceptualisation and application of soil health. We share the fundamental and practical challenges of managing the land with respect to soil health, and the need for policy to drive the protection of soil as one of our most important non-renewable natural resources.

Background Thrombocytopenia is a hallmark of dengue infection, and bleeding is a dreaded complication of dengue fever. Prophylactic platelet transfusion has been used to prevent bleeding in the management of dengue fever, although the evidence for its benefit is lacking. In adult dengue patients with platelet count 50,000/mm3 and increasing length of hospitalization., Author Summary Thrombocytopenia is one of the most prominent clinical features in dengue infection. This may manifest clinically as bleeding, which carries significant morbidity and mortality. For many years, clinicians have given dengue patients platelet transfusion in a bid to increase their platelet counts to prevent hemorrhagic manifestations. However, this practice has not been proven to reduce the risk of bleeding in dengue. Conversely, transfusion of blood products may be detrimental to patients as it can carry risks of fluid overload, transmission of infectious diseases and transfusion reactions. In this study, the authors found that platelet transfusion in the absence of bleeding in adult dengue patients did not prevent bleeding. Instead, this practice is associated with a slower platelet recovery and increased length of hospitalisation. These findings may contribute to better clinical management of thrombocytopenia in dengue patients and limit the use of these precious blood products.

To reflect the microbial ecology techniques being applied currently, this chapter aims to explore how the phospholipid fatty acids can be used to determine how biochar affects the structural, compositional, and functional capacities of microbial communities in different soil ecosystems. Used in combination with natural isotope or radioisotope (13C or 14C)-labeled substrates, it has the potential to determine soil organic matter cycling rate, monitor C flows from plants to soil microbes, and identify below-ground trophic relationships. Insights into biochar effects on soil phospholipid fatty acids, alternatives to data analysis, its limitations, and knowledge gaps are highlighted.

Lysosomes serve key degradative functions for the turnover of membrane lipids and protein components. Its biogenesis is principally dependent on exocytic traffic from the late endosome via the trans-Golgi network, and it also receives cargo to be degraded from the endocytic pathway. Membrane trafficking to the late endosome-lysosome is tightly regulated to maintain the amplitude of signalling events and cellular homeostasis. Key coordinators of lysosomal traffic include members of the Rab small GTPase family. Amongst these, Rab7, Rab9 and the more recently studied Rab22B/31 have all been reported to regulate membrane trafficking processed at the late endosome-lysosome system. We discuss what is known about the roles of these Rab proteins and their interacting partners on the regulation of traffic of important receptor proteins such as the epidermal growth factor receptor (EGFR) and the mannose 6-phosphate receptor (M6PR), in association with the late endosome-lysosome system. Better knowledge of EGFR and M6PR traffic in this regard may aid in understanding the pathological processes, such as oncogenic transformations associated with these receptors.

The small GTPase Rab22B (or Rab31) has been suspected to be involved in trafficking at trans-Golgi network. However, its exact cellular localization, tissue expression profile, and functions have not been uncharacterized. Specific antibody raised against Rab22B's protein revealed that Rab22B is brain-enriched, but is also present in substantial levels in spleen and intestine. In HeLa cells, endogenous Rab22B is largely associated with the trans-Golgi network (TGN). Over-expression of a GDP-binding mutant (Rab22BSN), but not wild-type Rab22B, specifically disrupts the TGN localization of TGN46, a dynamic marker which cycles between the TGN and the plasma membrane. The TGN resident membrane protein syntaxin 16, cis-Golgi markers such as GM130 and syntaxin 5, as well as the TGN/late endosome marker mannose 6-phosphate receptor (M6PR) are not affected by Rab22BSN, neither was endosomal-TGN transport of the Shiga toxin B subunit. The disruption of TGN46 staining by Rab22BSN could be specifically attributed to a domain at the C-terminal portion of Rab22B, where its sequence deviates the most from Rab22A. Over-expression of Rab22BSN inhibits the cell surface transport of the vesicular stomatitis virus G protein. Thus, Rab22B may have a role in anterograde exit from the TGN.

Background/Purpose Bacteremia in dengue may occur with common exposure to pathogens in association with severe organ impairment or severe dengue, which may result in death. Cohort studies identifying risk factors for concurrent bacteremia among patients with dengue are rare. Methods We conducted a retrospective case–control study of adult patients with dengue who were admitted to the Department of Infectious Diseases at Tan Tock Seng Hospital, Singapore from 2004 to 2008. For each case of dengue with concurrent bacteremia (within the first 72 hours of admission), we selected four controls without bacteremia, who were matched on year of infection and dengue confirmation method. Conditional logistic regression was performed to identify risk factors for concurrent bacteremia. Results Among 9,553 patients with dengue, 29 (0.3%) had bacteremia. Eighteen of these patients (62.1%) had concurrent bacteremia. The predominant bacteria were Staphylococcus aureus , one of which was a methicillin-resistant strain. Dengue shock syndrome occurred more frequently and hospital stay was longer among cases than among controls. Three cases did not survive, whereas none of the controls died. In multivariate analysis, being critically ill at hospital presentation was independently associated with 15 times the likelihood of a patient with dengue having concurrent bacteremia. Conclusion Concurrent bacteremia in adult patients with dengue is uncommon but presents atypically and results in more deaths and longer hospital stay. Given the associated mortality, collection of blood cultures and empiric antibiotic therapy may be considered in patients who are critically ill.

The addition of compost to the soil can increase C and nutrient levels, but how these are affected by different rainfall regimes remain unknown. This study determines the carbon (C), nitrogen (N) and phosphorus (P) stocks after drying and rewetting events in a compost-amended grassland ecosystem at 3 depths (0-5, 5-10, 10-30cm). Compost addition consistently increased C, N and P stocks despite altered rainfall but these improvements can only be detected by careful consideration of soil depths.

Rab23 is the product of the gene mutated in the mouse open brain1 phenotype, which displays neural tube defects. It appears to antagonize sonic hedgehog (Shh)-mediated signaling during mouse development, presumably by regulating the intracellular trafficking of one or more of Shh's-signaling components. The Shh receptor Patched1 (Ptch1) and its downstream effector Smoothened (Smo) were initial prime suspects as they are membrane proteins whose cellular dynamics are modulated by the Shh signal. However, Rab23 mutants do not appear to affect the localization and dynamics of either protein. Genetic analyses have now shown that Rab23 functions downstream of Smo and affects the function of the Shh-regulated Gli family of transcription factors in a more direct manner than previously thought. A plethora of proteins that influence Shh signaling and whose cellular trafficking could potentially be regulated by Rab23 has also emerged. These include members of the intraflagellar transport complex, as well as motor proteins responsible for their assembly at the cilia. Rab23 is also expressed in adult mouse neurons and may thus have functions beyond embryonic developmental stages and Shh signaling. We discuss these new findings and explore the myriad of possibilities whereby Rab23 may function.

In this century, agroecosystems are subjected to multiple global change stressors acting in concert such as alterations in rainfall regimes and pesticide use. Alterations in rainfall regimes, characterised by more extreme intra-annual rainfall regimes, have been forecasted for the Mediterranean region. At the same time, the use of pesticides continues to rise. Here, we report the responses of soil microbial community to a model pesticide, i.e., fungicide pyrimethanil (PYR) under altered rainfall regimes (i.e., drought and heavy rainfall) two and eight weeks after PYR application. We measured the functional responses as enzyme activities, potential nitrification and BIOLOG carbon substrate utilisation. We also characterised the soil bacterial communities using polymerase chain reaction–denaturing gradient gel electrophoresis (PCR–DGGE) method. After two weeks, enzyme activities were mainly responsive to PYR and kinetic parameters, calculated from BIOLOG carbon substrate utilisation, indicated interaction effects from PYR and rain treatments. Bacterial band richness increased with PYR treatment under normal rain and drought regimes, but bacterial band richness was higher at 1X than 5X PYR under heavy rainfall. Bacterial community structure was also different with the PYR and rainfall treatments. By week eight, PYR treated soils remained functionally different from untreated soils. Bacterial band richness was consistent across PYR treatment regardless of rain regime. However, the bacterial community structure remained significantly different among the PYR treatments under different rain regimes. We conclude that rainfall extremes can alter the effect of PYR on the soil microbial community structure without altering PYR effects on soil functions (measured as enzyme activities, potential nitrification and BIOLOG carbon substrate utilisation).

The behavioral variable employment-related motivational distortion (EMD) was defined and measured. In Study 1, a sample of 250 undergraduates completed the California Psychological Inventory (CPI), Form 434, on two separate occasions in which they responded (a) honestly and (b) as if applying for a job they valued. Four different change measures indexed participants’ response changes between the two conditions on a CPI-based scale measuring counter productivity (CPI-Cp). A composite of these four measures provided an EMD criterion, which enabled the development, in Study 2, of a 56-item CPI-based EMD predictor scale. On the basis of eight samples comprising a total Nof 2,074, internal consistency and test-retest reliability estimates for the CPI-EMD scale ranged between .72 and .86. Correlations with NEO PI-R domain and facet scales provided construct information about EMD. In Study 3, CPI-Cp scale scores adjusted for EMD manifested (a) reliability ranging from .71 to .87 over eight samples and (b) somewhat different correlations than for the unadjusted scale with Big Five personality scales. In addition, some evidence was found for gains in criterion correlations with EMD adjustments.

Background Pain is a prominent feature of acute dengue as well as a clinical criterion in World Health Organization guidelines in diagnosing dengue. We conducted a prospective cohort study to compare levels of pain during acute dengue between different ethnicities and dengue severity. Methods Demographic, clinical and laboratory data were collected. Data on self-reported pain was collected using the 11-point Numerical Rating Scale. Generalized structural equation models were built to predict progression to severe disease. Results A total of 499 laboratory confirmed dengue patients were recruited in the Prospective Adult Dengue Study at Tan Tock Seng Hospital, Singapore. We found no statistically significant differences between pain score with age, gender, ethnicity or the presence of co-morbidity. Pain score was not predictive of dengue severity but highly correlated to patients’ day of illness. Prevalence of abdominal pain in our cohort was 19%. There was no difference in abdominal pain score between grades of dengue severity. Conclusion Dengue is a painful disease. Patients suffer more pain at the earlier phase of illness. However, pain score cannot be used to predict a patient’s progression to severe disease.

Background The recommendation from the 2009 World Health Organization guidelines for managing dengue suggests that patients with any warning sign can be hospitalized for observation and management. We evaluated the utility of using warning signs to guide hospital admission and predict disease progression in adults. Methods We conducted a prospective cohort study from January 2010 to September 2012. Daily demographic, clinical and laboratory data were collected from adult dengue patients. Warning signs were recorded. The proportion of admitted patients using current admission criteria and warning signs was compared. The sensitivity, specificity, positive and negative predictive values of warning signs in predicting disease progression were also evaluated. Results Four hundred and ninety-nine patients with confirmed dengue were analyzed. Using warning signs instead of the current admission criteria will lead to a 44% and 31% increase in admission for DHF II-IV and SD cases respectively. The proportion of non-severe dengue cases which were admitted also increased by 32% for non DHF II-IV and 33% for non-SD cases. Absence of any warning signs had a NPV of 91%, 100% and 100% for DHF I-IV, DHF II-IV and SD. Of those who progressed to severe illness, 16.3% had warning signs on the same day while 51.3% had warning signs the day before developing severe illness, respectively. Conclusions Our findings demonstrated that patients without any warning signs can be managed safely with ambulatory care to reduce hospital resource burden. No single warning sign can independently predict disease progression. The window from onset of warning sign to severe illness in most cases was within one day.

Lysosomes serve key degradative functions for the turnover of membrane lipids and protein components. Its biogenesis is principally dependent on exocytic traffic from the late endosome via the trans-Golgi network, and it also receives cargo to be degraded from the endocytic pathway. Membrane trafficking to the late endosome-lysosome is tightly regulated to maintain the amplitude of signalling events and cellular homeostasis. Key coordinators of lysosomal traffic include members of the Rab small GTPase family. Amongst these, Rab7, Rab9 and the more recently studied Rab22B/31 have all been reported to regulate membrane trafficking processed at the late endosome-lysosome system. We discuss what is known about the roles of these Rab proteins and their interacting partners on the regulation of traffic of important receptor proteins such as the epidermal growth factor receptor (EGFR) and the mannose 6-phosphate receptor (M6PR), in association with the late endosome-lysosome system. Better knowledge of EGFR and M6PR traffic in this regard may aid in understanding the pathological processes, such as oncogenic transformations associated with these receptors.

The expression profile and functions of the brain-enriched Rab22B/Rab31 small GTPase had remained uncharacterized. Using specific antibodies against Rab22B, we found the protein to be exceptionally enriched in nestin and RC2-positive radial glia of the embryonic mouse brain. In the adult brain, Rab22B is rather specifically expressed in glial fibrillary acidic protein (GFAP)-positive mature astrocytes, but is not clearly detectable in either 2',3'-cyclic nucleotide 3'-phosphodiesterase (CNPase)-positive mature oligodendrocytes or betaIII-tubulin (TuJ)-positive neurons. In probing for specific functions of Rab22B, we found that Rab22B silencing in A431 cells resulted in abnormal trafficking of the epidermal growth factor receptor (EGFR), Texas-red-labeled EGF, and the cation-independent mannose 6-phosphate receptor (M6PR). Affinity pull-down assays and co-immunoprecipitation analysis indicated that Rab22B could associate with EGFR in a GTP-dependent manner. Rab22B is thus a Rab protein specifically expressed in the astroglia lineage and may have a role in regulating EGFR trafficking in some cell types. Given that EGFR signaling modulates astrocyte development and oncogenesis of multiple cell types, Rab22B may thus have specific developmental or pathophysiological roles in cell types which it is enriched in.

The Rab family of small GTPases functions in regulating vesicular transport in all eukaryotes. In the past few years, several important reports have linked some members of the Rab family to intriguing mechanistic aspects of cancer cell migration and invasiveness. Rab5 and Rab21 associate with alpha-integrin subunits and modulate their endosomal traffic and subcellular localization. Expression of the latter enhances adhesion and migration of certain cancer cell types. Rab25 has been functionally linked to tumor progression and the invasiveness of some epithelial cancers. Rab25 promotes invasive migration of cells in three-dimensional microenvironments by associating with alpha5beta1 integrin, and directing its recycling to dynamic ruffling protrusions at the migrating cell front. Acting directly, or through its effector, the Rab-coupling protein, Rab25 could potentially engage both integrin and epidermal growth factor receptor and enhance their oncogenic recycling and signaling. Tumor invasiveness may also be modulated by Rab8-mediated exocytic traffic of MT1-matrix metalloproteinase, with the latter's activity likely influenced by interaction with the mammalian suppressor of Sec4 (Mss4), a Rab8 guanine nucleotide exchange factor, and integrin. We discuss highlights in the recent literature that point towards a role for Rab-mediated membrane traffic in cancer cell migration and invasion.

Rab23 is the product of the gene mutated in the mouse open brain1 phenotype, which displays neural tube defects. It appears to antagonize sonic hedgehog (Shh)-mediated signaling during mouse development, presumably by regulating the intracellular trafficking of one or more of Shh's-signaling components. The Shh receptor Patched1 (Ptch1) and its downstream effector Smoothened (Smo) were initial prime suspects as they are membrane proteins whose cellular dynamics are modulated by the Shh signal. However, Rab23 mutants do not appear to affect the localization and dynamics of either protein. Genetic analyses have now shown that Rab23 functions downstream of Smo and affects the function of the Shh-regulated Gli family of transcription factors in a more direct manner than previously thought. A plethora of proteins that influence Shh signaling and whose cellular trafficking could potentially be regulated by Rab23 has also emerged. These include members of the intraflagellar transport complex, as well as motor proteins responsible for their assembly at the cilia. Rab23 is also expressed in adult mouse neurons and may thus have functions beyond embryonic developmental stages and Shh signaling. We discuss these new findings and explore the myriad of possibilities whereby Rab23 may function.

The gene mutated in the mouse open brain (opb) phenotype antagonizes sonic hedgehog-mediated signaling and encodes a small GTPase of the Rab family, Rab23. To date, the brain expression profile and exact mechanism of function of the Rab23 protein has remained unknown. Specific antibodies generated against Rab23 showed that the protein is highly enriched in the adult rodent brain and present in low levels in multiple tissues of the adult rodent. Rab23 is found in the cytosol as well as being associated with the plasma and endosomal membranes. In the adult mouse brain, Rab23 is found in βIII tubulin (TuJ) positive neuronal cell bodies and are most prominent in the cortex, hypothalamus and the cerebellum. It is, however, absent from glial fibrillary acidic protein (GFAP) positive astrocytes or CNPase positive oligodendrocytes. Despite the plasma membrane/endosomal membrane localization of Rab23, neither overexpression of the GTP-restricted nor the GDP-bound mutant forms affect internalization of transferrin or epidermal growth factor. Exogenous overexpression of Rab23 or its mutants also did not affect the morphological differentiation of thalamic neurons in culture. Expression of Rab23 in the adult brain is suggestive, however, of having a postnatal function beyond its role in embryonic development. © 2006 Wiley-Liss, Inc.

Results There were 217 patients of Asian ethnicity who had ever received a bDMARD, of whom 30 (13.8%) had received more than 1 bDMARD. These comprised rituximab (78, 35.9%), infliximab (59, 27.2%), etanercept (51, 23.5%), adalimumab (41, 18.9%), golimumab (8, 3.7%), anakinra (4, 1.8%), abatacept and tocilizumab (3, 1.4% each). HSR occurred in 4 female patients following previous exposure to an anti-tumour necrosis factor inhibitor (TNFi) (2) and rituximab (2) respectively. A 67-year-old Chinese female with rheumatoid arthritis developed fever and hypotension without rash or other organ-specific involvement, within 1 hour of the second dose of infliximab 200 mg 2 weeks later. She switched to adalimumab without adverse reaction. Another 34-year-old Malay female with psoriatic arthritis developed optic neuritis following the third dose of adalimumab 40 mg every other week. She recovered and switched to abatacept without adverse reaction. A 28-year-old female with systemic lupus erythematosus (SLE) developed acute urticaria following the second dose of the third course of rituximab 500 mg given 2 weeks apart. Another 27-year old female with SLE developed anaphylaxis with flushing, facial angioedema, dyspnoea and wheeze, following the second dose of the second course of rituximab 500 mg 5 years later. None of the patients with immediate reactions to infliximab/ rituximab agreed to have diagnostic skin testing in view of costs. The patient with anaphylaxis declined desensitization to rituximab. There were no HSR to any of the other bDMARDs. Exposure to more than 1 bDMARD within/across different classes did not increase the risk of HSR. There were no deaths from HSR.