Validation of dried blood spot sampling for detecting SARS-CoV-2 antibodies and total immunoglobulins in a large cohort of asymptomatic young adults.

BACKGROUND: Detecting antibody responses following infection with SARS-CoV-2 is necessary for sero-epidemiological studies and assessing the role of specific antibodies in disease, but serum or plasma sampling is not always viable due to logistical challenges. Dried blood spot sampling (DBS) is a cheaper, simpler alternative and samples can be self-collected and returned by post, reducing risk for SARS-CoV-2 exposure from direct patient contact. The value of large-scale DBS sampling for the assessment of serological responses to SARS-CoV-2 has not been assessed in depth and provides a model for examining the logistics of using this approach to other infectious diseases. The ability to measure specific antigens is attractive for remote outbreak situations where testing may be limited or for patients who require sampling after remote consultation. METHODS: We compared the performance of SARS-CoV-2 anti-spike and anti-nucleocapsid antibody detection from DBS samples with matched serum collected by venepuncture in a large population of asymptomatic young adults (N = 1070) living and working in congregate settings (military recruits, N = 625); university students, N = 445). We also compared the effect of self-sampling (ssDBS) with investigator-collected samples (labDBS) on assay performance, and the quantitative measurement of total IgA, IgG and IgM between DBS eluates and serum. RESULTS: Baseline seropositivity for anti-spike IgGAM antibody was significantly higher among university students than military recruits. Strong correlations were observed between matched DBS and serum samples in both university students and recruits for the anti-spike IgGAM assay. Minimal differences were found in results by ssDBS and labDBS and serum by Bland Altman and Cohen kappa analyses. LabDBS achieved 82.0% sensitivity and 98.2% specificity and ssDBS samples 86.1% sensitivity and 96.7% specificity for detecting anti-spike IgGAM antibodies relative to serum samples. For anti-SARS-CoV-2 nucleocapsid IgG there was qualitatively 100% agreement between serum and DBS samples and weak correlation in ratio measurements. Strong correlations were observed between serum and DBS-derived total IgG, IgA, and IgM. CONCLUSIONS: This is the largest validation of DBS against paired serum for SARS-CoV-2 specific antibody measurement and we have shown that DBS retains performance from prior smaller studies. There were no significant differences regarding DBS collection methods, suggesting that self-collected samples are a viable sampling collection method. These data offer confidence that DBS can be employed more widely as an alternative to classical serology.

Chemical characterisation of the vapour emitted by an e-cigarette using a ceramic wick-based technology.

Fourth-generation 'pod' e-cigarette devices have been driven by technological advances in electronic atomization of the e-liquid. Use of microporous ceramic as a wicking material improves heating efficiency, but how it affects the chemical emissions of these devices is unclear. We assessed the emissions of a pod e-cigarette with innovative ceramic wick-based technology and two flavoured e-liquids containing nicotine lactate and nicotine benzoate (57 and 18 mg mL-1 nicotine, respectively). Among the studied harmful and potentially harmful constituents (HPHCs) listed by the US FDA and/or WHO TobReg, only 5 (acetone, acetaldehyde, formaldehyde, naphthalene and nornicotine) were quantified at levels of 0.14 to 100 ng puff-1. In the combustible cigarette (Kentucky reference 1R6F), levels were from 0.131 to 168 µg puff-1. Nicotine levels ranged 0.10-0.32 mg puff-1 across the 3 study products. From the 19 proposed HPHCs specifically of concern in e-cigarettes, only 3 (glycerol, isoamyl acetate and propylene glycol) were quantified. The low/undetectable levels of HPHCs reflect not only the optimal operating conditions of the e-cigarette, including an efficient supply of e-liquid by the ceramic wick without overheating, but also the potential of the e-cigarettes to be used as an alternative to combustible cigarettes.

Quality of internet information to aid patient decision making in locally advanced and recurrent rectal cancer.

BACKGROUND: To review whether online decision aids are available for patients contemplating pelvic exenteration (PE) for locally advanced and recurrent rectal cancer (LARC and LRRC). METHODS: A grey literature review was carried out using the Google Search™ engine undertaken using a predefined search strategy (PROSPERO database CRD42019122933). Written health information was assessed using the DISCERN criteria and International Patient Decision Aids Standards (IPDAS) with readability content assessed using the Flesch-Kincaid reading ease test and Flesch-Kincaid grade level score. RESULTS: Google search yielded 27, 782, 200 results for the predefined search criteria. 131 sources were screened resulting in the analysis of 6 sources. No sources were identified as a decision aid according to the IPDAS criteria. All sources provided an acceptable quality of written health information, scoring a global score of 3 for the DISCERN written assessment. The median Flesch-Kincaid reading ease was 50.85 (32.5-80.8) equating to a reading age of 15-18 years and the median Flesch-Kincaid grade level score was 7.65 (range 3-9.7), which equates to a reading age of 13-14. CONCLUSIONS: This study has found that there is a paucity of online information for patients contemplating PE. Sources that are available are aimed at a high health literate patient. Given the considerable morbidity associated with PE surgery there is a need for high quality relevant information in this area. A PDA should be developed to improve decision making and ultimately improve patient experience.

Circulating and Endometrial Regulatory T Cell and Related Populations in Endometriosis and Infertility: Endometriosis Is Associated with Blunting of Endometrial Cyclical Effects and Reduced Proportions in Moderate-Severe Disease.

Evidence to date supports regulatory T cell (Treg) alterations in endometriosis; however, the relationship remains unclear, and Tregs have not previously been investigated with respect to infertility in endometriosis. This prospective cross-sectional cohort study details circulating and endometrial tissue-specific disturbances in Tregs and broader gated populations in women of reproductive age with and without endometriosis (n = 57 and 29, respectively) using flow cytometry and immunohistochemistry. Participants were characterised by menstrual cycle phase, r-ASRM endometriosis disease stage and fertility status.In the endometrium of women with endometriosis, endometrial Tregs and CD4+ lymphocyte proportions did not change between the proliferative and secretory phases, while in women without the disease, they significantly decreased (p = 0.045 and p = 0.039, respectively). In women with endometriosis, endometrial Tregs were lower than in women without endometriosis overall (p = 0.050 as a proportion of all CD45+ immune cells). We have shown for the first time that proportions of CD4+ lymphocytes (p = 0.021), overall lymphocytes (p = 0.034) and non-granulocytes (p = 0.027) were significantly decreased in the endometrium of women with moderate-severe (r-ASRM stages III and IV) compared to minimal-mild (r-ASRM stages I and II) endometriosis. During the secretory phase, circulating Treg proportions were significantly increased in infertile compared to fertile women (p = 0.049). This study confirms differences in endometrial Tregs in women with endometriosis, with blunting of normal menstrual cyclical variations, reduced proportions during the proliferative phase and disease stage-specific relationships.

Intestinal microbiota and their metabolic contribution to type 2 diabetes and obesity.

Obesity and type 2 diabetes mellitus (T2DM) are common, chronic metabolic disorders with associated significant long-term health problems at global epidemic levels. It is recognised that gut microbiota play a central role in maintaining host homeostasis and through technological advances in both animal and human models it is becoming clear that gut microbiota are heavily involved in key pathophysiological roles in the aetiology and progression of both conditions. This review will focus on current knowledge regarding microbiota interactions with short chain fatty acids, the host inflammatory response, signaling pathways, integrity of the intestinal barrier, the interaction of the gut-brain axis and the subsequent impact on the metabolic health of the host.

The Chemical Complexity of e-Cigarette Aerosols Compared With the Smoke From a Tobacco Burning Cigarette.

Background: As e-cigarette popularity has increased, there is growing evidence to suggest that while they are highly likely to be considerably less harmful than cigarettes, their use is not free of risk to the user. There is therefore an ongoing need to characterise the chemical composition of e-cigarette aerosols, as a starting point in characterising risks associated with their use. This study examined the chemical complexity of aerosols generated by an e-cigarette containing one unflavored and three flavored e-liquids. A combination of targeted and untargeted chemical analysis approaches was used to examine the number of compounds comprising the aerosol. Contributions of e-liquid flavors to aerosol complexity were investigated, and the sources of other aerosol constituents sought. Emissions of 98 aerosol toxicants were quantified and compared to those in smoke from a reference tobacco cigarette generated under two different smoking regimes. Results: Combined untargeted and targeted aerosol analyses identified between 94 and 139 compounds in the flavored aerosols, compared with an estimated 72-79 in the unflavored aerosol. This is significantly less complex (by 1-2 orders of magnitude) than the reported composition of cigarette smoke. Combining both types of analysis identified 5-12 compounds over and above those found by untargeted analysis alone. Gravimetrically, 89-99% of the e-cigarette aerosol composition was composed of glycerol, propylene glycol, water and nicotine, and around 3% comprised other, more minor, constituents. Comparable data for the Ky3R4F reference tobacco cigarette pointed to 58-76% of cigarette smoke "tar" being composed of minor constituents. Levels of the targeted toxicants in the e-cigarette aerosols were significantly lower than those in cigarette smoke, with 68.5->99% reductions under ISO 3308 puffing conditions and 88.4->99% reductions under ISO 20778 (intense) conditions; reductions against the WHO TobReg 9 priority list were around 99%. Conclusion: These analyses showed that the e-cigarette aerosols contain fewer compounds and at significantly lower concentrations than cigarette smoke. The chemical diversity of an e-cigarette aerosol is strongly impacted by the choice of e-liquid ingredients.

Gut microbiota influence in type 2 diabetes mellitus (T2DM).

A strong and expanding evidence base supports the influence of gut microbiota in human metabolism. Altered glucose homeostasis is associated with altered gut microbiota, and is clearly associated with the development of type 2 diabetes mellitus (T2DM) and associated complications. Understanding the causal association between gut microbiota and metabolic risk has the potential role of identifying susceptible individuals to allow early targeted intervention.

Measuring interoception: The phase adjustment task.

Interoception, perception of one's bodily state, has been associated with mental health and socio-emotional processes. However, several interoception tasks are of questionable validity, meaning associations between interoception and other variables require confirmation with new measures. Here we describe the novel, smartphone-based Phase Adjustment Task (PAT). Tones are presented at the participant's heart rate, but out of phase with heartbeats. Participants adjust the phase relationship between tones and heartbeats until they are synchronous. Data from 124 participants indicates variance in performance across participants which is not affected by physiological or strategic confounds. Associations between interoception and anxiety, depression and stress were not significant. Weak associations between interoception and mental health variables may be a consequence of testing a non-clinical sample. A second study revealed PAT performance to be moderately stable over one week, consistent with state effects on interoception.

A review on gut microbiota: a central factor in the pathophysiology of obesity.

Obesity and its complications constitute a substantial burden. Considerable published research describes the novel relationships between obesity and gut microbiota communities. It is becoming evident that microbiota behave in a pivotal role in their ability to influence homeostatic mechanisms either to the benefit or detriment of host health, the extent of which is not fully understood. A greater understanding of the contribution of gut microbiota towards host pathophysiology is revealing new therapeutic avenues to tackle the global obesity epidemic. This review focuses on causal relationships and associations with obesity, proposed central mechanisms encouraging the development of obesity and promising prospective methods for microbiota manipulation.

From forest to pharmacy: Should we be depressed about a sustainable Griffonia simplicifolia (Fabaceae) seed supply chain?

ETHNOPHARMACOLOGICAL RELEVANCE: Griffonia simplicifolia D.C (Baill.) (Fabaceae) seeds are unusually high (6-20% wet weight) in 5-HTP (5-Hydroxytryptophan), a serotonin precursor widely used to treat depression. Consequently, this species is regarded as a herbal "Prozac®". Contemporary use as an anti-depressant contrasts with traditional uses for insecticides, arachnicides, fodder, dyes, mordants and chewing-sticks. G. simplicifolia seeds are wild-harvested for the export trade. Over the past 15 years, use of 5-HTP extracted from G. simplicifolia in cosmetics has added to global demand. Wild populations in West Africa are the sole commercial source of G. simplicifolia seed. AIMS OF THE STUDY: Were to (i) assess the scale of the global trade in G. simplicifolia seeds and (ii) produce a synthesis of the challenges facing sustainable harvest of G. simplicifolia. MATERIALS AND APPROACH: Firstly, we analysed global trade data for G. simplicifolia, taking into account historical trends over the past 40 years. Secondly, we reviewed published studies on the distribution, population biology and harvest impacts of wild G. simplicifolia populations. RESULTS AND CONCLUSION: s: Wild G. simplicifolia populations have been the focus of commercial harvest of their pods (for seeds) for international trade from West Africa for almost 50 years. In the late 1980's, when Ghana exported 75-80 metric tonnes (MT) of G. simplicifolia seed to Europe, this species was already Ghana's main medicinal plant export. Currently, 5 West African countries export G. simplicifolia seeds (Cote d'Ivoire, Ghana, Liberia, Nigeria and Togo). Although in the 1980's, most seed exports were to Europe, today China is the main importer of G. simplicifolia seed. These seeds are value-added for production of 5-HTP extracts, and then re-exported, particularly to North America (c.48% of exports). The low habitat specificity and vigorous re-sprouting of G. simplicifolia after cutting, plus its occurrence in forest reserves and national parks confer some resilience on wild populations. Sustaining future supply chains faces six future challenges, however: (1) Rapid loss of forest habitats; (2) Declining populations of understorey birds and disruption of G. simplicifolia pollination in this bird pollinated species; (3) Negative effects of introduced invasive plant species (Broussonetia papyrifera, Chromolaena odorata) on G. simplicifolia regeneration; (4) Grazing by livestock and use of G. simplicifolia leaves as forage; (5) The long-term impact of industrial scale seed "predation": Over a 9-year period (2005-2013), G. simplicifolia exports from Ghana totalled at least 5550 metric tonnes (or between 9.1 billion to 13.5 billion seeds). This could affect the long-term population dynamics of this species, which produces a low number of seeds per pod (1-4 seeds) and has short distance (ballistic) seed dispersal; and (6) Destructive harvest methods, when plants are cut to harvest get the seed pods. Improved resource management, monitoring, quality control and careful pricing are important if supply chains from wild stocks are to be maintained. If wild populations decline, then 5-HTP biosynthesis may compete with low G. simplicifolia seed yields, leading to loss of income to West African harvesters and traders.

Validation of a combined ELISA to detect IgG, IgA and IgM antibody responses to SARS-CoV-2 in mild or moderate non-hospitalised patients.

BACKGROUND: Frequently SARS-CoV-2 results in mild or moderate disease with potentially lower concentrations of antibodies compared to those that are hospitalised. Here, we validated an ELISA using SARS-CoV-2 trimeric spike glycoprotein, with targeted detection of IgG, IgA and IgM (IgGAM) using serum and dried blood spots (DBS) from adults with mild or moderate disease. METHODS: Targeting the SARS-CoV-2 trimeric spike, a combined anti-IgG, IgA and IgM serology ELISA assay was developed using 62 PCR-confirmed non-hospitalised, mild or moderate COVID-19 samples, ≥14 days post symptom onset and 624 COVID-19 negative samples. The assay was validated using 73 PCR-confirmed non-hospitalised, mild or moderate COVID-19 samples, ≥14 days post symptom onset and 359 COVID-19 negative serum samples with an additional 81 DBSs. The assay was further validated in 226 PCR-confirmed non-hospitalised, mild or moderate COVID-19 samples, ≥14 days post symptom onset and 426 COVID-19 negative clinical samples. RESULTS: A sensitivity and specificity of 98.6% (95% CI, 92.6-100.0), 98.3% (95% CI, 96.4-99.4), respectively, was observed following validation of the SARS-CoV-2 ELISA. No cross-reactivities with endemic coronaviruses or other human viruses were observed, and no change in results were recorded for interfering substances. The assay was stable at temperature extremes and components were stable for 15 days once opened. A matrix comparison showed DBS to correlate with serum results. Clinical validation of the assay reported a sensitivity of 94.7% (95% CI, 90.9-97.2%) and a specificity of 98.4% (95% CI, 96.6-99.3%). CONCLUSIONS: The human anti-IgGAM SARS-CoV-2 ELISA provides accurate and sensitive detection of SARS-CoV-2 antibodies in non-hospitalised adults with mild or moderate disease. The use of dried blood spots makes the assay accessible to the wider community.

Comprehensive analysis utilizing flow cytometry and immunohistochemistry reveals inflammatory changes in local endometrial and systemic dendritic cell populations in endometriosis.

STUDY QUESTION: What are the detailed endometrial tissue specific and systemic dendritic cell (DC) subset disturbances in endometriosis? SUMMARY ANSWER: This study confirms myeloid DC (mDC) and plasmacytoid DC subsets are readily identified in endometrial tissue and shows both endometrial and circulating differences in DC populations in women with endometriosis, with disease stage-specific relationships evident locally in the endometrium. WHAT IS KNOWN ALREADY: Immune factors in the uterus, the peritoneal environment and systemically are implicated in the pathogenesis and progression of both endometriosis and infertility. While there is some evidence that endometrial DC populations are altered in endometriosis, DC subset involvement in both the endometrium and peripheral blood have not been comprehensively investigated so the functional consequences have been unknown. STUDY DESIGN, SIZE, DURATION: This prospective cross-sectional cohort study compares circulating and endometrial DC populations in women of reproductive age with and without endometriosis (n = 55 and 30, respectively), wherein each participant donated samples at a single time point. Study participants were surveyed for menstrual cycle phase, American Society for Reproductive Medicine (ASRM) endometriosis disease stage and fertility status (where possible). PARTICIPANTS/MATERIALS, SETTING, METHODS: Peripheral blood samples were processed into mononuclear cells for analysis by flow cytometry, and endometrial samples were analysed by immunohistochemistry and dissociated into single-cell suspension for flow cytometry. MAIN RESULTS AND THE ROLE OF CHANCE: In the endometrium of women with endometriosis, IRF-8+ cells were increased during the proliferative phase (P = 0.014), total DC proportions increased in the secretory phase (P = 0.038) and normal menstrual cyclical fluctuations in CD1c+ and IRF-8+ cells blunted; indicative of a consistently inflammatory tissue environment. The inflammatory changes in CD141+ and IRF-8+ populations in the endometrium of women with endometriosis were particularly evident in more advanced ASRM stages of the disease (respective P-values 0.032 and 0.045). There was also evidence of systemic inflammation in women with endometriosis, with increased circulating CD141+ mDC proportions (overall P = 0.040, secretory phase P = 0.021). LARGE SCALE DATA: N/A. LIMITATIONS, REASONS FOR CAUTION: As is common in this type of study, one of the main limitations was small sample numbers, particularly during the menstrual phase of the cycle. WIDER IMPLICATIONS OF THE FINDINGS: Further phenotyping of local and circulating immune cell subtypes is critical to improving understanding of endometriosis pathogenesis and immune contributions to infertility associated with the disease. STUDY FUNDING/COMPETING INTEREST(S): This research was financially supported by a Sydney Medical School and Balnaves Foundation Kick Start Grant and the Department of Obstetrics, Gynaecology and Neonatology at The University of Sydney. The authors have no conflicts of interest to declare.

Running out of time to smell the roseroots: Reviewing threats and trade in wild Rhodiola rosea L.

ETHNOPHARMACOLOGICAL RELEVANCE: Rhodiola rosea L. has a circumpolar distribution and is used in ethnomedicines of Arctic peoples, as well as in national systems of traditional medicine. Since the late 20th century, global demand for R. rosea has increased steadily, in part due to clinical research supporting new uses in modern phytotherapy. Global supply has been largely obtained from wild populations, which face threats from poorly regulated and destructive exploitation of the rootstocks on an industrial scale. AIM OF THE STUDY: To evaluate (i) the conservation status, harvesting and trade levels of R. rosea, in order to determine whether international trade should be monitored, (ii) the current state of experimental and commercial farming and whether cultivation may play a role to take pressure off wild stocks, and (iii) evidence of substitution of other Rhodiola species for R. rosea as an indicator of overexploitation and rarity. MATERIALS AND METHODS: We reviewed published studies on R. rosea biology and ecology, as well as information on impacts of wild harvest, on management measures at the national and regional levels, and on the current level of cultivation from across the geographic range of this species. Production and trade data were assessed and analysed from published reports and trade databases, consultations with R. rosea farmers, processors of extracts, and trade experts, but also from government and news reports of illegal harvesting and smuggling. RESULTS AND CONCLUSIONS: Our assessment of historical and current data from multiple disciplines shows that future monitoring and protection of R. rosea populations is of time-sensitive importance to the fields of ethnobotany, ethnopharmacology, phytochemistry and phytomedicine. We found that the global demand for R. rosea ingredients and products has been increasing in the 21st century, while wild populations in the main commercial harvesting areas continue to decrease, with conservation issues and reduced supply in some cases. The level of illegal harvesting in protected areas and cross border smuggling is increasing annually coupled with increasing incidences of adulteration and substitution of R. rosea with other wild Rhodiola species, potentially negatively impacting the conservation status of their wild populations, but also an indicator of scarcity of the genuine article. The current data suggests that the historical primary reliance on sourcing from wild populations of R. rosea should transition towards increased sourcing of R. rosea from farms that are implementing conservation oriented sustainable agricultural methods, and that sustainable wild collection standards must be implemented for sourcing from wild populations.

Aflatoxin and ochratoxin A residues in supplementary foods used for wild birds.

Provision of supplementary food for garden birds is practiced on a large scale in multiple countries. While this resource has benefits for wild bird populations, concern has been expressed regarding the potential for contamination of foodstuffs by mycotoxins, and the implications this might have for wildlife health. We investigated whether aflatoxin (AF) and ochratoxin A (OA) residues are present in foodstuffs sold for wild bird consumption at point of sale in Great Britain using high pressure liquid chromatography analyses. The hypothesis that production of these mycotoxins occurs in British climatic conditions, or under storage conditions after the point of sale, was tested under experimental conditions but was not proved by our study. While the majority of peanut samples were negative for AF residues, 10% (10/98) of samples at point of sale and 11% (13/119) of those across the storage and climate exposure treatment replicates contained AFB1 that exceeded the maximum permitted limit of 20 µg/kg. No significant difference was found in the detection of either mycotoxin between branded and non-branded products. The clinical significance, if any, of exposure of wild birds to mycotoxins requires further investigation. Nevertheless, the precautionary principle should be adopted and best practice steps to reduce the likelihood of wild bird exposure to mycotoxins are recommended.

There "ain't no mountain high enough"?: The drivers, diversity and sustainability of China's Rhodiola trade.

ETHNOPHARMACOLOGICAL RELEVANCE: Across Asia, Rhodiola species have been used in Bhutanese, Mongolian, Nepalese, Kazakh, Kyrgyz and Uzbek traditional medical systems. China is globally significant in terms of Rhodiola species diversity, with over 60% (55 species) of the world's 90 Rhodiola species, including 16 species found nowhere else in the world. Since the late 1980's there has been a shift from relatively low demand for infusions using chopped dried Rhodiola roots, to high 21st century demand for a wide variety of processed products. China's trade in Rhodiola products is now very diverse, with use in cosmetics and foods in addition to herbal products. Rhodiola crenulata (Hook.f. & Thomson) H.Ohba is the most widely traded species in China. In addition to R. crenulata and Rhodiola rosea L., 19 Rhodiola other species are used. AIMS OF THE STUDY: These were to: (i) better understand why adulteration occurs in Rhodiola products; (ii) become more aware of what drives the growing market demand for Rhodiola products in China; (iii) find out whether increased demand is reflected in wholesale prices for Rhodiola raw materials traditional medicine markets; (iv) to examine Rhodiola supply chains and (v) given that wild populations are the primary supply source, to review the implications of growing demand for conservation and sustainable use. MATERIALS AND METHODS: Firstly, we assessed growth in the diversity of Rhodiola products using three approaches: (i) by assessing patent applications for Rhodiola products in China (1990-2019); (ii) in 2018, through on-line searches of CFDA (China Food and Drug Administration) records for medicines and dietary supplements that had Rhodiola as an ingredient and (iii) by visiting retail stores in 2018 and 2019 to assess the diversity of commercial Rhodiola based products in trade. Secondly, we visited traditional medicine markets in Yunnan, Sichuan, and Qinghai provinces to investigate the trade in Rhodiola (folk taxonomy, trade names, prices, source areas, levels of processing and grading). Thirdly, we analysed the wholesale price data for Rhodiola raw materials in trade over a 16-year period (2002-2018). Fourthly, as most products come from wild collected Rhodiola species, we documented the extent of Rhodiola cultivation in China. RESULTS: International exports of Rhodiola products from China, particularly extracts, is a major driver of commercial trade. One proxy indicator of Rhodiola product diversification in China has been the rapid rise in patent applications from single applications in 1990 and 1991, to a peak of 1017 patent applications in 2015. Wholesale price data from 2002 to 2018 shows a steady increase in wholesale prices. As the growing market for Rhodiola products in China is currently supplied entirely from wild collection, there are justifiable concerns about sustainability. Commercial cultivation needs to expand to meet future demand. CONCLUSIONS: In contrast to Europe and North America, where R. rosea is the focal species in commerce, the trade in Rhodiola products in China is much more diverse. In the face of growing demand, both effective conservation of wild populations and cultivation are needed.

Extension of the known distribution of a novel clade C betacoronavirus in a wildlife host.

Disease surveillance in wildlife populations presents a logistical challenge, yet is critical in gaining a deeper understanding of the presence and impact of wildlife pathogens. Erinaceus coronavirus (EriCoV), a clade C Betacoronavirus, was first described in Western European hedgehogs (Erinaceus europaeus) in Germany. Here, our objective was to determine whether EriCoV is present, and if it is associated with disease, in Great Britain (GB). An EriCoV-specific BRYT-Green® real-time reverse transcription PCR assay was used to test 351 samples of faeces or distal large intestinal tract contents collected from casualty or dead hedgehogs from a wide area across GB. Viral RNA was detected in 10.8% (38) samples; however, the virus was not detected in any of the 61 samples tested from Scotland. The full genome sequence of the British EriCoV strain was determined using next generation sequencing; it shared 94% identity with a German EriCoV sequence. Multivariate statistical models using hedgehog case history data, faecal specimen descriptions and post-mortem examination findings found no significant associations indicative of disease associated with EriCoV in hedgehogs. These findings indicate that the Western European hedgehog is a reservoir host of EriCoV in the absence of apparent disease.

Prospective evaluation of the cardiac safety of HER2-targeted therapies in patients with HER2-positive breast cancer and compromised heart function: the SAFE-HEaRt study.

PURPOSE: HER2-targeted therapies have substantially improved the outcome of patients with breast cancer, however, they can be associated with cardiac toxicity. Guidelines recommend holding HER2-targeted therapies until resolution of cardiac dysfunction. SAFE-HEaRt is the first trial that prospectively tests whether these therapies can be safely administered without interruptions in patients with cardiac dysfunction. METHODS: Patients with stage I-IV HER2-positive breast cancer candidates for trastuzumab, pertuzumab or ado-trastuzumab emtansine (TDM-1), with left ventricular ejection fraction (LVEF) 40-49% and no symptoms of heart failure (HF) were enrolled. All patients underwent cardiology visits, serial echocardiograms and received beta blockers and ACE inhibitors unless contraindicated. The primary endpoint was completion of the planned HER2-targeted therapies without developing either a cardiac event (CE) defined as HF, myocardial infarction, arrhythmia or cardiac death or significant asymptomatic worsening of LVEF. The study was considered successful if planned oncology therapy completion rate was at least 30%. RESULTS: Of 31 enrolled patients, 30 were evaluable. Fifteen patients were treated with trastuzumab, 14 with trastuzumab and pertuzumab, and 2 with TDM-1. Mean LVEF was 45% at baseline and 46% at the end of treatment. Twenty-seven patients (90%) completed the planned HER2-targeted therapies. Two patients experienced a CE and 1 had an asymptomatic worsening of LVEF to ≤ 35%. CONCLUSION: This study provides safety data of HER2-targeted therapies in patients with breast cancer and reduced LVEF while receiving cardioprotective medications and close cardiac monitoring. Our results demonstrate the importance of collaboration between cardiology and oncology providers to allow for delivery of optimal oncologic care to this unique population.

The vector ecology of introduced Culex quinquefasciatus populations, and implications for future risk of West Nile virus emergence in the Galápagos archipelago.

Culex quinquefasciatus Say (Diptera: Culicidae), an important vector of West Nile virus (WNV) in the U.S.A., was first detected on the Galápagos Islands (Ecuador) in the 1980s. However, little is known of its ecology, distribution or capacity for arbovirus transmission in the Galápagos. We characterize details of lifecycle (including gonotrophic period), temporal abundance, spatial distribution, vector competence and host-feeding behaviour. Culex quinquefasciatus was detected on five islands of the Galápagos during 2006-2011. A period of 7-14 days was required for egg-adult emergence; water salinity above 5 ppt was demonstrated to hinder larval development. Blood-meal analysis indicated feeding on reptiles, birds and mammals. Assessment of WNV vector competency of Galápagos C. quinquefasciatus showed a median infectious dose of 7.41 log10 plaque-forming units per millilitre and evidence of vertical transmission (minimal filial infection rate of 3.7 per 1000 progeny). The distribution of C. quinquefasciatus across the archipelago could be limited by salt intolerance, and its abundance constrained by high temperatures. Feeding behaviour indicates potential to act as a bridge vector for transmission of pathogens across multiple taxa. Vertical transmission is a potential persistence mechanism for WNV on Galápagos. Together, our results can be used for epidemiological assessments of WNV and target vector control, should this pathogen reach the Galápagos Islands.

Linking resource supplies and price drivers: Lessons from Traditional Chinese Medicine (TCM) price volatility and change, 2002-2017.

ETHNOPHARMACOLOGICAL RELEVANCE: Worldwide, one of the drivers of substitution and adulteration is the cost of the natural resources (plants, animals, fungi) that are ingredients of traditional medicines. Relatively few studies have been done that link prices of traditional medicine ingredients to what drives changes in price, yet this is an important topic. Theoretically, prices have been widely considered as an economic indicator of resource scarcity. Rare, slow growing medicinal plants sell for high prices and common, less popular species for low prices. Price levels also influence the viability of farming vs. wild harvest (and incentives to overharvest high value species when tenure is weak). Prices can also influence the harvesting or buying behaviour of harvesters, traders or manufacturers. When prices are high, then there is a greater incentive to use cheaper substitute species or adulterants. As previous studies on herbal medicine ingredients have shown, adulteration applies in a wide variety of cases, including to some Traditional Chinese Medicine (TCM) species. AIM OF THE STUDY: The aim of this study was to gain a better understanding of which factors influenced changes in the market prices of document prices for four popular, but very different traditional Chinese medicine (TCM) species (2002 - 2017). MATERIALS AND METHODS: Fluctuations in market prices were followed over a 15-year period (2002-2017) for four very different TCM ingredients: two plant species (one wild harvested for fruits (Schisandra sphenanthera Rehder & E.H. Wilson) the other in a transition from wild harvest to cultivation (Paris polyphylla Smith), an animal species (the Tokay gecko (Gekko gecko L.)) and the entomophagous "caterpillar fungus" (Ophiocordyceps sinensis (Berk). G.H. Sung, J.M. Sung, Hywel-Jones & Spatafora). RESULTS: High prices of medicinal plants are widely considered to reflect resource scarcity. Real-time market prices for three of the four very different TCM species we studied all showed major price fluctuations. The exception was P. polyphylla, whose wild populations are widely known to be increasingly scarce, where there was a steady increase in price, with few fluctuations in the upward price trend. The three other species showed significant price fluctuations. These were driven by multiple factors. Ecological and biogeographic factors that influence abundance or scarcity of supply certainly played a role. But other factors were also influential. These included both national and global economic factors (the influence of the Global Financial Crisis (GFC)), national policy changes that in turn influenced businessmen giving expensive gifts (that included O. sinensis)), climate change (influencing fruiting success of S. sphenanthera), price speculation by traders and lack of information (e.g: reduction in G. gecko prices due to traders incorrectly believing that domestication would increase supplies). CONCLUSIONS: Price fluctuations in the four TCM species we examined are influenced by many factors and not just resource scarcity. And the situation is more complex than the trajectory based on Homma's (1992) model, where he predicted that higher prices would result in a shift to cultivation, thus replacing wild harvest. In case of both O. sinensis and P. polyphylla, Homma (1992, 1996) was right in terms of scarcity and high prices stimulating a major investment in cultivation (P. polyphylla) and artificial production (O. sinensis). But in both cases, intensive production through cultivation or artificial propagation do not yet occur on a large enough scale to reduce harvest of wild stocks. Substitution and adulteration occur with all four species. Improving information to medicinal plant traders on the supply status of TCM stocks, whether from wild harvest or from cultivation could benefit product quality, cultivation initiatives and conservation efforts.