He continued to have fever despite 2 weeks of broad-spectrum antibiotics, and was transferred to Barnes-Jewish Hospital/Washington University in St. Louis, MO, USA, for further evaluation. Our differential diagnosis included malaria, typhoid, typhus, leptospirosis, relapsing fever, and tuberculosis. On examination, the patient complained of chills, and thick and thin blood smears were immediately obtained. Both revealed 1% parasitemia with gametocytes of Ribociclib molecular weight Plasmodium vivax. The patient was treated with mefloquine 1,200 mg PO once and primaquine 15 mg PO daily for 2 weeks. At follow-up, his symptoms had completely resolved. Vector-borne

and environmentally acquired infections are a threat to all travelers to endemic locations, but military personnel are at

elevated risk because of the duration and intensity of environmental exposure. An analysis of 17,353 travelers revealed that the majority, around 64%, present with symptoms of infection within the first month of travel.1 However, this analysis did not signaling pathway include military personnel. When evaluating fever in military personnel, a careful history should include country and terrain of any deployments, both recent and distant. Malaria represents one of the most important infectious disease threats to deployed military forces; 15 of the last 17 major or minor military deployments were to malarious locations. Afghanistan has large endemic areas of malaria, especially below 2,000 m above sea-level.2 This disease has reemerged in the north-eastern river valleys used for

growing rice because of lapsed control measures, intensified agricultural activity, and returning refugees,3 with an annual incidence of 240 per 1,000 people around Jalalabad, where our patient was exposed.4 In 2004, the attack rate of troops deployed to Afghanistan was 52.4 cases per 1,000 soldiers.5 Malaria has also been reported in both British and German soldiers returning from Afghanistan.6,7 In 2004, P. vivax infection acquired in Afghanistan accounted for 25% of the 56 cases of malaria diagnosed among US Army soldiers. Soldiers presented for care weeks to 20 months after return to the United States.8 BCKDHB The median time to diagnosis of malaria in returning Army Rangers was 233 days.5 Vivax malaria presented in German soldiers as late as 9 months after return from Afghanistan.7 This report highlights the importance of a high index of suspicion for tropical infections in returning military personnel; it also underscores an important feature of malaria infection, the possibility of delayed presentation. Low index of suspicion in patients presenting long after exposure is further complicated by the poor sensitivity of malaria smears when trained and experienced microscopists are not readily available; malaria was suspected at the regional hospital but smears were read as negative, delaying the initiation of appropriate treatment.

These results demonstrate a sharp contrast in the responses of D. vulgaris to low and high levels of H2O2, by analogy to data between 0.1% oxygen exposure MG-132 mw and air stress (Fournier et al., 2006; Mukhopadhyay et al., 2007). Our results show that the primary response of D. vulgaris Hildenborough to H2O2 stress is finely regulated.

In addition to regulating genes directly involved in H2O2 detoxification such as the PerR regulon members, nigerythrin and thiol peroxidase-encoding genes, H2O2 also regulates the expression of sod and sor genes, involved in the elimination of superoxide anions. All these genes thus belong to the H2O2 stimulon and are directly involved in the defense mechanisms that allow cells to counterbalance the toxic effects of H2O2 and its derived chemical species in low concentrations. This mechanism thus allows cells to adapt successfully to temporary ROS presence and to survive in a variety of natural biotopes that undergo selleck chemicals llc periodic exposure to oxidative conditions. It is noteworthy that the expression of all these genes is inversely regulated depending on

the H2O2 concentration, suggesting subtle and complicated regulation mechanisms of oxidative stress responses in D. vulgaris that need further studies to be completely characterized. This work was supported by the FEMS Research Fellowship to A.L.B. The authors acknowledge Y. Denis from the IMM Transcriptomic facilities for the helpful discussion on qRT-PCR. Sequences of primers used in the study. Please note: Wiley-Blackwell is not responsible for the content or functionality of any supporting materials supplied by the authors. Any queries (other than missing material) should be directed to the corresponding author Rolziracetam for the article. “
“Vanadium is a contaminant from steel additive and ship fuel in coastal and port areas, and its effect

on marine microbes remains largely unknown. We showed that vanadium accelerates transfer of the tetracycline resistance gene tet(M) from Photobacterium to Escherichia coli, and found a positive correlation between the concentration of vanadium in natural marine sediment and the rate of oxytetracycline resistance. These results suggest the possibility that vanadium may play a role in the preservation and horizontal transfer of antibiotic resistance genes in the marine environment. Vanadium (V) is used as a steel additive (Moskalyk & Alfantazi, 2003) and is contained in jet and ship fuels, which may be released into the air and oceans (Viana et al., 2008; Pondolfi et al., 2011). Oil combustion alone accounts for 91% of total worldwide atmospheric V emissions.

2b and c). The hot spring isolates, on the other hand, showed almost no variation; only

3 of the 12 occurring polymorphisms were present, with a preference for 14 repeat units (Fig. 2d). It was also observed that strains that had the same seven-gene SBT could still have a different copy number for the lcl VNTR region (data not shown). As addition of the seventh gene neuA to the previously used six-gene SBT scheme enhanced the discriminatory power (Ratzow et al., 2007), it is possible that additional genes can even further discriminate the presently established SBT types. Therefore, our sequencing data reinforce the observation made by Pourcel et al. (2007) that the VNTR region of lcl (lpms31) is very diverse and could be an additional tool to distinguish among isolates. However, we have to be cautious about its genetic variability. If this genetic variability is extremely large, the chance of DNA Damage inhibitor two isolates of the same population being different is almost equal to the EPZ-6438 cell line chance of two isolates of different locations being different. This problematic genetic variability was previously shown for three other L. pneumophila loci: fliC, proA and mompS (Coscolláet al., 2006). This emphasizes that attention

has to be paid when selecting a gene for discrimination purposes. More specifically, the genetic variability of the gene has to be high enough to discriminate between different isolates, but small enough to be stable in the period between the outbreak and epidemiological typing. Based on the knowledge that very mammalian collagen plays a role in cell adhesion (Kadler

et al., 2007), the role of Lcl in the adhesion of L. pneumophila Philadelphia to host cells was examined. For this, we attempted to prepare an Lcl-negative mutant. Notwithstanding many attempts, using (1) homologous recombination with a resistance cassette with flanking regions of the lcl gene of different sizes; (2) point mutagenesis; and (3) different resistance cassettes and shuttle vectors, a correct insertion was never obtained, even after screening thousands of colonies. Whether the failure of obtaining a deletion mutant is due to the presence of the VNTR regions present in the lcl gene is not known, but VNTR regions are known to have greater instability. Because we were not able to obtain an Lcl-negative mutant, the role of Lcl in L. pneumophila adhesion and invasion of host cells was determined indirectly by comparing the Philadelphia WT cells and the same cells preincubated with Lcl-specific antibodies. The preincubation of 5 × 107L. pneumophila Philadelphia-1 cells with 20 μg Lcl-specific antibodies for 30 min decreased the adhesion to A549 and macrophage-like cells by 59% (P=0.0015) and 39% (P=0.006), respectively (Fig. 3a and b). In contrast, adhesion and invasion of the amoebae A.

The strategy

has shown efficacy in HIV-seronegative individuals [71–73], though specific data from HIV-seropositive individuals is more limited. Antiviral therapy should be initiated during the prodrome or early in an attack and aciclovir 200–400 mg orally five times daily for 5 days is recommended [47]. Alternative regimens are aciclovir 400 mg orally three times a day for 5 days; valaciclovir 500 mg orally twice daily for 3–5 days; valaciclovir 1 g orally, twice daily for 5 days; famciclovir 500 mg orally twice daily CYC202 clinical trial for 5 days. There is no evidence of clear superiority of the alternative regimens over standard doses of aciclovir. In more immunocompromised HIV-seropositive persons, episodes may be prolonged and more severe, requiring a longer duration of antiviral treatment. In HIV negative individuals, discontinuation of suppressive or episodic antiviral therapy after 12 months is recommended in order to assess the ongoing frequency of recurrences. In an HIV-seropositive individual with a low CD4 cell count, the interruption may be delayed. The timing of this treatment

interruption should be agreed with the patient and they should be given a supply of antiviral therapy to enable prompt administration of episodic treatment if recurrences recur. 6.3.5.3 Non-mucosal (or systemic) herpes. There is limited data on the treatment selleck chemicals of systemic HSV disease in HIV-seropositive individuals. Recommendations

are based on evidence from studies in both immunocompetent and immunocompromised patient populations. Systemic infection should be treated with intravenous aciclovir 5–10 mg/kg every 8 h for 10–21 days. HSV meningitis can be treated with 10 mg/kg every 8 h [74]. For HSV encephalitis, aciclovir 10 mg/kg every 8 h for 14–21 days is recommended [75] and quantitative PCR in the CSF may be helpful in monitoring response to treatment. Mortality and morbidity is high. Joint care with a neurologist is essential and there should be a low threshold for referral to a brain ITU. Patients with HSV keratoconjunctivitis or acute retinal necrosis should be seen urgently by an ophthalmologist and managed jointly. 6.3.5.4 Antiviral-resistant HSV infection. HA-1077 purchase In prospective studies, aciclovir-resistant HSV variants have been described in up to 7% of isolates from HIV-seropositive patients [76,77]. The threshold for resistance is a greater than 1–3 mg/mL aciclovir concentration for viral inhibition. This is most usually due to a mutation affecting the gene encoding viral thymidine kinase (TK), the enzyme that phosphorylates aciclovir in HSV-infected cells. TK-deficient strains are of reduced pathogenesis in immunocompetent individuals but cause significant clinical disease in immunosuppressed patients. Although partial resistance can occur, most TK mutants are resistant to aciclovir, valaciclovir and ganciclovir and the majority to famciclovir.

After one or two baseline treatments, eight patients

had skin indurations (defined as papules, lumpiness, clumping or hard mass). Skin indurations were still present at 12 months in three of these patients. Thirteen patients were re-treated at 12 months, one patient had a touch-up treatment, and three patients had skin indurations after treatment at 12 months. One of these skin indurations was palpable and was still present at the 24-month study visit. Vismodegib Thirteen patients were treated again at 24 months. Six of these patients had a touch-up treatment. After the 24-month treatment, three patients had skin indurations and in one of these patients the induration was still present at 36 months. A total of six patients, who did not present with skin indurations at one of the 6-week ICG-001 manufacturer post-treatment consultations, went on to develop palpable indurations in the next 12 months. At the 24 month visit, four patients were treated by injection with hyaluronidase, an enzyme that has a temporary and reversible depolymerizing effect on the polysaccharide hyaluronic acid, to remove the palpable indurations. One of the treated papules was c. 1.5 cm in diameter. Approximately 0.5 mL of hyaluronidase (Hyalase 1500 IU diluted in 15 mL normal saline

solution) was injected directly into the papule without local anaesthetic. There was a sense of perforating a thin capsule as the needle was injected. All four patients reported that the treated papules had disappeared completely within a few hours of receiving the hyaluronidase injections. Massaging the papules did not appear to have any effect. Each patient required approximately 6mL of Restylane SubQ Leukotriene-A4 hydrolase per treatment including touch-up. With the full price for 1 mL of Restylane SubQ being €160 (including taxes and blunt-tip application cannulas; no discount), the yearly cost of filling material (approximately 6 mL) can be estimated to be approximately €950 per patient. In our study using the temporary dermal filler

Restylane SubQ, mean total cutaneous thickness increased from 6 ± 1 mm at baseline to 12 ± 2 mm at 24 months and 12 ± 1 mm at 36 months. Response rate, defined as total cutaneous thickness >10 mm, was 85% at 24 months and 70% at 36 months (intention-to-treat analysis). In comparison, a 96-week study using polylactic acid treatment reported proportions of patients with total cutaneous thickness >10 mm as 52% at week 72 and 43% at week 96 [17]. Fifteen out of 17 patients (88%) classified their facial appearance as very much improved or moderately improved when compared with a pre-operative photograph at the 36-month study visit, which was at least 12 months after their last treatment with Restylane SubQ. Similarly, a significant increase in self-esteem scores and visual analogue scores, measuring patient satisfaction with their appearance, was found between baseline and 36 months.

Forward [f] and reverse [r] primer pairs: CB58 [f] and CB57 [r] (icmW–CBU1651–icmX), CB59 [f] and CB60 [r] (icmV–dotA), CB718 [f] and CB716 [r] (dotA–CBU1647), CB603 [f] and CB602 [r] (dotB–CBU1646), selleck chemical CB63 [f] and CB64 [r] (dotD–dotC–dotB), and CB62 [f] and CB61 [r] (icmT–icmS–dotD), were used to demonstrate transcriptional linkage. RT-PCR analysis of icmT, icmV, and icmW ORFs was performed using CB78 [f] and CB79 [r], CB70 [f] and CB71 [r], and CB40 [f] and CB41 [r], respectively. Oligonucleotide primers

(Table 1) for RT-qPCR analysis of icmX, icmW, icmV, dotA, dotB, and icmT were designed using primer3plus (Andreas Untergasser et al., 2007). The primer efficiency of all primer sets were within the efficiency window for the calculation method (Livak & Schmittgen, 2001; Schmittgen & Livak, 2008). Single-step RT-qPCR analysis using SuperScript III (Invitrogen) reverse transcriptase and the SYBR Green Master Mix Kit (Applied Biosystems) was performed on an ABI 7500 cycler. Each reaction contained 15 μL total volume and 20 ng total RNA. To calculate the relative temporal RNA

expression fold changes over the time course, to each individual gene was used, respectively. For each gene, the respective mean time-zero cycle threshold (CT) value was used as Copanlisib chemical structure the baseline reference point for all other (respective) mean time point CT values over the evaluation period. Therefore, for each individual gene, their relative fold expression at each time point is internally referenced to time zero RNA levels. Each time-zero point

has been referenced to themselves, resulting in a calculated fold value of 1. Statistical significance between the time points was evaluated by single-factor anova with a 95% confidence interval using ms excel 2007 (Microsoft). A P-value of <0.05 was considered significant. Recombinant C. burnetii IcmT  and protein-specific antibody were the same as described previously (Morgan et al., 2010). Briefly, to ensure specificity, the rabbit sera against recombinant C. burnetii IcmT were absorbed against Vero cell lysates as well as the Escherichia coli DH5α expression strain to remove cross-reactive antibodies. This antibody was designated RαIcmT. For immunoblot analysis, purified C. burnetii NMII was pelleted and resuspended in protein lysis/running buffer [Tris-HCl, pH 6.8, 62.5 mM, Idoxuridine sodium dodecyl sulfate (SDS) 2%, glycerol 25%, bromophenol blue 0.01%, and 2-mercaptoethanol 5% added before loading]. Protein representing 108C. burnetii genome equivalents and 104 Vero cells, respectively, was separated by 16% SDS-polyacrylamide gel electrophoresis and transferred to a nitrocellulose membrane (Whatman, Dassel, Germany) along with a protein ladder (Bio-Rad, Hercules, CA). Immunoblot analysis was carried out using a Pico Western Chemilluominescent Kit (Pierce, Rockford, IL) following the manufacturer’s directions using the RαIcmT primary antibody at a 1 : 1000 dilution in a hybridization buffer.

As a whole, this study describes the composition of the endophytic bacterial communities of tomato leaves, identifying a variety of genera that could exert multiple effects on growth and health of tomato plants. “
“Lactococcus lactis IL1403 is a lactic acid bacterium that is used widely for food fermentation. Copper homeostasis in this organism chiefly involves copper secretion by the CopA copper ATPase. This enzyme is under the control of the CopR transcriptional regulator. AZD9291 in vivo CopR not only controls its own expression and that of CopA, but also that of an additional three operons and two monocistronic genes. One of the genes under the control of CopR, yahD,

encodes an α/β-hydrolase. YahD expression was induced by copper and cadmium, but not by other metals or oxidative or nitrosative stress. The three-dimensional structure of YahD was determined by X-ray crystallography to a resolution of 1.88 Å. The protein was found to adopt an α/β-hydrolase fold with the characteristic Ser-His-Asp catalytic triad. Functional testing of YahD for a wide range of substrates for esterases, lipases, epoxide

hydrolases, phospholipases, amidases and proteases was, however, unsuccessful. Y-27632 mouse A copper-inducible serine hydrolase has not been described previously and YahD appears to be a new functional member of this enzyme family. Lactococcus lactis IL1403 is a Gram-positive lactic acid bacterium used Proteases inhibitor extensively in the manufacture of food, in the dairy industry and for an increasing number of biotechnological applications. Its genome has been sequenced (Bolotin et al., 2001) and its proteome has been characterized (Guillot et al., 2003). For these reasons, it represents a good model organism for molecular studies. In industrial processes, bacteria are often exposed to a variety of stress conditions, including extreme pH and temperature, osmotic shock and metal stress (van de Guchte et al., 2002). For example, in the traditional production of Swiss cheese in copper vats, L. lactis is exposed to copper leaching from the vats. Copper is an essential biological

element for many organisms, but at elevated concentrations, it becomes toxic to cells. Because of its ability to cycle between Cu2+ and Cu+ at relevant biological redox potentials, copper has been adopted as a cofactor by >30 known enzymes (Karlin, 1993), such as lysyl oxidase, superoxide dismutase and cytochrome c oxidase (Linder & Hazegh Azam, 1996). On the other hand, the redox properties of copper can lead to the formation of toxic reactive oxygen species via a Fenton-type reaction, which may result in cellular damage (Magnani & Solioz, 2007). Recent findings suggest that an important in vivo toxicity mechanism of copper also consists of the displacement of iron from iron–sulfur clusters of proteins (Macomber & Imlay, 2009; Chillappagari et al., 2010).

Here, we showed that all Sfp-type

PPTases may have the potential to promote the biosynthesis of long-chain n-3 polyunsaturated fatty acids. “
“Research on audiovisual speech integration has reported high levels of individual variability, especially among young infants. In the present study we tested Alisertib cell line the hypothesis that this variability results from individual differences in the maturation of audiovisual speech processing during infancy. A developmental shift in selective attention to audiovisual speech has been demonstrated between 6 and 9 months with an increase in the time spent looking to articulating mouths as compared to eyes (Lewkowicz & Hansen-Tift. (2012) Proc. Natl Acad. Sci. USA, 109, 1431–1436; Tomalski et al. (2012) Eur. J. Dev. Psychol., 1–14). In the present study we tested whether these changes in behavioural maturational level are associated with differences in brain responses to audiovisual speech across this age range. We measured high-density event-related potentials (ERPs) in response to videos of audiovisually matching and mismatched syllables /ba/ and /ga/, and subsequently examined visual scanning of the same stimuli with eye-tracking. There were no clear age-specific changes in ERPs, but the amplitude of audiovisual CHIR99021 mismatch response (AVMMR) to the combination of visual /ba/ and auditory /ga/

was strongly negatively associated with looking time to the mouth in the same condition. These results have significant implications for our understanding of individual differences in neural signatures of audiovisual speech processing in infants, suggesting that they are not strictly related to chronological age but instead associated with Selleck Vorinostat the maturation of looking behaviour, and develop

at individual rates in the second half of the first year of life. Audiovisual (AV) speech integration as demonstrated originally by McGurk & MacDonald (1976) is a phenomenon in which seeing non-matching lip articulation interferes with the perception of a speech sound. In this study, two types of speech illusions were observed, a ‘fusion’, in which visual (V) /ga/ dubbed onto auditory (A) /ga/ (VgaAba) was perceived as /da/, and a ‘combination’, in which a visual /ba/ dubbed onto auditory /ga/ was perceived as /bga/. Subsequent studies have indicated that infants also may perceive VgaAba stimuli as a ‘fusion’ (Rosenblum et al., 1997; Burnham & Dodd, 2004; but see Desjardins & Werker, 2004). Less investigated in infancy is the ‘combination’ condition. Recent evidence from electrophysiological studies suggests that infants as young as 5 months old process differently these two types of audiovisually incongruent stimuli that lead to combination and fusion effects. In a study by Kushnerenko et al. (2008) an AV mismatch response (AVMMR) was found in response to the VbaAga-combination, but not for a VgaAba-fusion.

burgdorferi with Triton X-100 (Fig. 2b, lanes 1 and 2). In the presence of Triton X-100, all three proteins were completely digested by proteinase K at final concentrations

of 40, 400 (Fig. 2b, lanes 4 and 6) and 4000 (not shown) μg mL−1. In the absence of Triton X-100, BmpA and OspA were digested by proteinase K at final concentrations of STA-9090 solubility dmso 40 and 400 μg mL−1 (Fig. 2b, lanes 3 and 5); FlaB was not (Fig. 2b, lanes 3 and 5). The susceptibility of BmpA and OspA to proteinase K in intact B. burgdorferi indicates that BmpA, like OspA, is exposed on the surface of B. burgdorferi. The insensitivity of FlaB to proteinase K in intact organisms is consistent with its location in the periplasmic space below the surface membrane (Bunikis & Barbour, 1999). The surface exposure of BmpA in B. burgdorferi B31 was further confirmed by dual-label indirect immunofluorescence. Intact borrelia cells were double labeled in solution with optimal dilutions of monospecific anti-rBmpA and anti-OspA antisera or anti-rBmpA and anti-FlaB antisera. Similar dilutions of preimmunization rabbit Ig were used

as controls. Intact B. burgdorferi showed dual labeling of their surface with anti-rBmpA and anti-OspA antibodies (Fig. 3), but remained unlabeled by anti-FlaB (Fig. 3) or preimmunization Ig (Fig. 3). After permeabilization of the outer membrane by methanol fixation, B. burgdorferi cells were labeled by all three antibodies (Fig. 3), but not find protocol by preimmunization Ig (Fig. 3). These results confirm the results of cell fractionation and proteinase K treatment experiments and indicate that BmpA is exposed on the surface of B. burgdorferi cells (Cox et al., 1996). Previous work with monoclonal anti-BmpA antibodies

indicated that BmpA was resistant to treatment with proteinase K in intact borrelia and suggested its lack of exposure on the surface of these cells (Bunikis & Barbour, 1999). However, it was not clear from this earlier study whether the epitopes recognized by this monoclonal antibody were potentially exposed on the surface of borrelial cells and whether the epitopes it recognized were only found on BmpA. Experiments with Masitinib (AB1010) a different monoclonal anti-BmpA antibody and biotin-labeled intact borrelia suggested that BmpA was probably associated with the cytoplasmic membrane (Sullivan et al., 1994). Here again, the epitope recognized was not identified and the reactivity of this antibody with the other Bmp proteins was not determined. A third series of experiments concluded that BmpA and FlaB were detected with rat antisera only when the outer membrane was disrupted, but again, the specificity of the antisera against other Bmp proteins was not examined (Cox & Radolf, 2001). The monospecificity of our anti-rBmpA reagent and its lack of reactivity with BmpB, BmpC and BmpD in dot immunobinding and 2D-NEPHGE is the probable explanation for the differences between our results and those of previous workers (Sullivan et al.

The net result would be akin to the phenomena of surround inhibition reported in the motor cortex that enhances motor ability (Hallett, 2004; Beck & Hallett, 2010), the visual cortex that enhances visual perception (Angelucci et al., 2002) and the somatosensory cortex that enhances tactile acuity (Drevets et al., 1995). State dependency would also explain the lack screening assay of effect elicited by 5 Hz rTMS where both the sequence-related and non-sequence-related neural activity would be facilitated. However, given the already elevated excitability in the neurons involved with the repeated sequence representation, the effects of the rTMS would be more

pronounced in the less active neural pathways representing the random sequence compared with the already excited neural pathways representing the repeated sequence (Bienenstock et al., 1982; Kuo et al., 2008). The net result would be a reduction in the difference between the signal (repeated sequence neural activity) and the noise (random sequence neural activity). One limitation to the current work is that we are unable to directly assess changes in cortical excitability of the PMd itself. Future work is needed to determine whether rTMS following practice of interleaved random and repeated

sequences can elicit state dependency during the period of early offline consolidation. Our data highlight the potential differential roles for the PMd in implicit buy Trametinib motor learning and early offline motor memory consolidation of a novel motor task. The results confirm past work demonstrating that with practice participants can

implicitly learn a repeated sequence (Brashers-Krug et al., 1996; Shadmehr & Holcomb, 1997; Meehan et al., 2011) and that sequence-specific learning can be altered via rTMS (Boyd & Linsdell, 2009). Importantly, we found that 1 Hz rTMS over the PMd during early consolidation improved sequence-specific implicit motor learning, probably by reducing competition between consolidation of motor parameters and action selection following interleaved practice. Applying rTMS during early consolidation DNA Damage inhibitor may be an adjunctive mechanism to enhance gains associated with practice through consolidation of specific elements of motor memory. Support was provided to S.K.M. by the Canadian Institutes of Health Research and the Michael Smith Foundation for Health Research and to L.A.B. by the Canada Research Chairs and the Michael Smith Foundation for Health Research. This work was also supported by awards from the Natural Sciences and Engineering Research Council of Canada (Award #401890) and the Vancouver Coastal Health Research Institute to L.A.B.