•Wastewater-based epidemiology (WBE) was done for the first time in Africa.•The chiral signature and metabolite ratios suggest predominant consumption.•Methamphetamine was the primary drug of ...abuse.•Cocaine and MDMA were shown as secondary drugs of abuse.•Mephedrone and Heroin use was qualitatively confirmed within one study area.
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The current study is aimed to introduce a wastewater-based epidemiology (WBE) approach for the first time on the African continent where substance abuse data is limited. The study included the quantification of several drugs of abuse (DOA) in raw wastewater samples. Quantification of urinary metabolites as drug target residues (DTR), as well as enantiomeric profiling of chiral DOA was performed to distinguish between consumption and direct disposal into sewage. Monitoring campaigns were undertaken at two South African wastewater treatment works (WWTWs) located within two provinces of the country. The presence of non-racemic 3,4-methylenedioxymethamphetamine (MDMA) and methamphetamine, as well as the metabolite of cocaine, benzoylecgonine (BEG), confirmed their consumption within the areas investigated. Enantiomeric profiling further pointed to the abuse of methamphetamine as the primary DOA with use estimates calculated between 181.9 and 1184.8mg·day−1·1000inhabitants−1. Population-normalised mass loads for MDMA and cocaine confirmed their status as secondary DOA within the study sites. Use estimates for the new psychoactive substance (NPS) mephedrone were performed for one WWTW. The minor metabolite of heroin, O-6-monoacetylmorphine (O-6-MAM), was also detected at one WWTW and served as a qualitative indicator for heroin abuse within the area. These findings provide a novel comparison of the WBE approach in a developing-country with other global studies, with the aim to strengthen this approach as a tool to inform drug prevention strategies in countries where substance abuse data is limited due to financial constraints and lack of government structures to facilitate conventional monitoring.
Exercise, heat shock proteins and insulin resistance Archer, Ashley E.; Von Schulze, Alex T.; Geiger, Paige C.
Philosophical transactions of the Royal Society of London. Series B. Biological sciences,
01/2018, Letnik:
373, Številka:
1738
Journal Article
Recenzirano
Odprti dostop
Best known as chaperones, heat shock proteins (HSPs) also have roles in cell signalling and regulation of metabolism. Rodent studies demonstrate that heat treatment, transgenic overexpression and ...pharmacological induction of HSP72 prevent high-fat diet-induced glucose intolerance and skeletal muscle insulin resistance. Overexpression of skeletal muscle HSP72 in mice has been shown to increase endurance running capacity nearly twofold and increase mitochondrial content by 50%. A positive correlation between HSP72 mRNA expression and mitochondrial enzyme activity has been observed in human skeletal muscle, and HSP72 expression is markedly decreased in skeletal muscle of insulin resistant and type 2 diabetic patients. In addition, decreased levels of HSP72 correlate with insulin resistance and non-alcoholic fatty liver disease progression in livers from obese patients. These data suggest the targeted induction of HSPs could be a therapeutic approach for preventing metabolic disease by maintaining the body's natural stress response. Exercise elicits a number of metabolic adaptations and is a powerful tool in the prevention and treatment of insulin resistance. Exercise training is also a stimulus for increased HSP expression. Although the underlying mechanism(s) for exercise-induced HSP expression are currently unknown, the HSP response may be critical for the beneficial metabolic effects of exercise. Exercise-induced extracellular HSP release may also contribute to metabolic homeostasis by actively restoring HSP72 content in insulin resistant tissues containing low endogenous levels of HSPs.
This article is part of the theme issue ‘Heat shock proteins as modulators and therapeutic targets of chronic disease: an integrated perspective’.
The epidermal growth factor receptor variant III deletion mutation, EGFRvIII, is expressed in ∼30% of primary glioblastoma and linked to poor long-term survival. Rindopepimut consists of the unique ...EGFRvIII peptide sequence conjugated to keyhole limpet hemocyanin. In previous phase II trials (ACTIVATE/ACT II), rindopepimut was well tolerated with robust EGFRvIII-specific immune responses and promising progression-free and overall survival. This multicenter, single-arm phase II clinical trial (ACT III) was performed to confirm these results.
Rindopepimut and standard adjuvant temozolomide chemotherapy were administered to 65 patients with newly diagnosed EGFRvIII-expressing (EGFRvIII+) glioblastoma after gross total resection and chemoradiation.
Progression-free survival at 5.5 months (∼8.5 mo from diagnosis) was 66%. Relative to study entry, median overall survival was 21.8 months, and 36-month overall survival was 26%. Extended rindopepimut vaccination (up to 3.5+ years) was well tolerated. Grades 1-2 injection site reactions were frequent. Anti-EGFRvIII antibody titers increased ≥4-fold in 85% of patients, and increased with duration of treatment. EGFRvIII was eliminated in 4/6 (67%) tumor samples obtained after >3 months of therapy.
This study confirms, in a multicenter setting, the preliminary results seen in previous phase II trials of rindopepimut. A pivotal, double-blind, randomized, phase III trial ("ACT IV") is under way.
Regenerative stem cell-like memory (T
) CD8
T cells persist longer and produce stronger effector functions. We found that MEK1/2 inhibition (MEKi) induces T
that have naive phenotype with ...self-renewability, enhanced multipotency and proliferative capacity. This is achieved by delaying cell division and enhancing mitochondrial biogenesis and fatty acid oxidation, without affecting T cell receptor-mediated activation. DNA methylation profiling revealed that MEKi-induced T
cells exhibited plasticity and loci-specific profiles similar to bona fide T
isolated from healthy donors, with intermediate characteristics compared to naive and central memory T cells. Ex vivo, antigenic rechallenge of MEKi-treated CD8
T cells showed stronger recall responses. This strategy generated T cells with higher efficacy for adoptive cell therapy. Moreover, MEKi treatment of tumor-bearing mice also showed strong immune-mediated antitumor effects. In conclusion, we show that MEKi leads to CD8
T cell reprogramming into T
that acts as a reservoir for effector T cells with potent therapeutic characteristics.
A Statistical Analysis of STEVE Gallardo‐Lacourt, Bea; Nishimura, Y.; Donovan, E. ...
Journal of geophysical research. Space physics,
November 2018, 2018-11-00, 20181101, Letnik:
123, Številka:
11
Journal Article
Recenzirano
Odprti dostop
There has been an exciting recent development in auroral research associated with the discovery of a new subauroral phenomenon called STEVE (Strong Thermal Emission Velocity Enhancement). Although ...STEVE has been documented by amateur night sky watchers for decades, it is as yet an unidentified upper atmosphere phenomenon. Observed first by amateur auroral photographers, STEVE appears as a narrow luminous structure across the night sky over thousands of kilometers in the east‐west direction. In this paper, we present the first statistical analysis of the properties of 28 STEVE events identified using Time History of Events and Macroscale Interactions during Substorms (THEMIS) all‐sky imager and the Redline Emission Geospace Observatory (REGO) database. We find that STEVE occurs about 1 hr after substorm onset at the end of a prolonged expansion phase. On average, the AL index magnitude is larger and the expansion phase has a longer duration for STEVE events compared to subauroral ion drifts or substorms. The average duration for STEVE is about 1 hr, and its latitudinal width is ~20 km, which corresponds to ~¼ of the width of narrow auroral structures like streamers. STEVE typically has an equatorward displacement from its initial location of about 50 km and a longitudinal extent of 2,145 km.
Plain Language Summary
Strong Thermal Emission Velocity Enhancement (STEVE) is an atmospheric phenomenon that manifests across the night sky as an extremely thin yet long ribbon of vibrant purple and white hues. Although STEVE has been well documented by amateur auroral photographers for several decades, the scientific community only recently stumbled upon this phenomenon. In this paper, we report on the first statistical analysis of STEVE's optical characteristics using ground‐based all‐sky imagery and examined satellite data to determine the geomagnetic conditions favorable for the formation of STEVE. Our results verify that STEVE is narrow in the north‐south direction, but it extends over a wider east‐west region. We have also determined that STEVE displaces southward over its lifetime in most observations. More interestingly, all 28 STEVE events identified in this study were observed at the end of a prolonged substorm expansion phase.
Key Points
The first statistical study of the subauroral optical phenomenon known as STEVE, featuring 28 events identified with all‐sky imagers, is performed
STEVE is a latitudinally narrow optical structure: ~20 km in meridional spread and spanning over 2,000 km zonally
STEVE is strongly linked to substorms: It is observed subsequently to a prolonged (~1 hr) substorm expansion phase
Immunologic targeting of tumor-specific gene mutations may allow precise eradication of neoplastic cells without toxicity. Epidermal growth factor receptor variant III (EGFRvIII) is a constitutively ...activated and immunogenic mutation not expressed in normal tissues but widely expressed in glioblastoma multiforme (GBM) and other neoplasms.
A phase II, multicenter trial was undertaken to assess the immunogenicity of an EGFRvIII-targeted peptide vaccine and to estimate the progression-free survival (PFS) and overall survival (OS) of vaccinated patients with newly diagnosed EGFRvIII-expressing GBM with minimal residual disease. Intradermal vaccinations were given until toxicity or tumor progression was observed. Sample size was calculated to differentiate between PFS rates of 20% and 40% 6 months after vaccination.
There were no symptomatic autoimmune reactions. The 6-month PFS rate after vaccination was 67% (95% CI, 40% to 83%) and after diagnosis was 94% (95% CI, 67% to 99%; n = 18). The median OS was 26.0 months (95% CI, 21.0 to 47.7 months). After adjustment for age and Karnofsky performance status, the OS of vaccinated patients was greater than that observed in a control group matched for eligibility criteria, prognostic factors, and temozolomide treatment (hazard ratio, 5.3; P = .0013; n = 17). The development of specific antibody (P = .025) or delayed-type hypersensitivity (P = .03) responses to EGFRvIII had a significant effect on OS. At recurrence, 82% (95% CI, 48% to 97%) of patients had lost EGFRvIII expression (P < .001).
EGFRvIII-targeted vaccination in patients with GBM warrants investigation in a phase III, randomized trial.
Background. The concept of empathy in students has gained significant attention in medical education. Whether implementing formal educational interventions to promote long-term and effective empathy ...levels leads to sustained increased empathy levels in students, is however less clear.
Objectives. The study aimed to evaluate the trajectory of medical students’ self-perceived empathy levels during their 6-year MB ChB degree.
Methods. A longitudinal, prospective study was conducted over 4 years. A cohort of 292 medical students was invited to participate. Participants completed the Jefferson Scale of Empathy for Students (JSE-S) at three intervals during their studies. The students attended two workshops related to empathic patient interactions during this time. The JSE-S mean score by age and gender was compared, making use of a linear regression model.
Results. A total of 119 students completed the study. Students’ total empathy levels were similar during the first and the last measuring point (110), but there was a significant rise in the intermediate measuring point (113.3). When the male and female cohorts’ scores were interpreted separately, both genders demonstrated a similar pattern to the total score, although females’ JSE-S scores were higher than the males.
Conclusion. The results of the study confirm that educational interventions can increase students’ self-perceived empathy levels; however, we suggest that students require reinforcement and multiple opportunities to practise and observe empathic communication with patients to sustain high levels of empathy. Follow-up sessions to specifically target the promotion of empathy should be implemented; otherwise the long-term effect of educational interventions might be limited.
Little is currently known about the optical phenomenon known as Steve. The first scientific publication on the subject suggests that Steve is associated with an intense subauroral ion drift (SAID). ...However, additional inquiry is warranted as this suggested relationship as it is based on a single case study. Here we present eight occurrences of Steve with coincident or near‐coincident measurements from the European Space Agency's Swarm satellites and show that Steve is consistently associated with SAID. When satellite observations coincident with Steve are compared to that of typical SAID, we find the SAID associated with Steve to have above average peak ion velocities and electron temperatures, as well as extremely low plasma densities.
Key Points
Eight Steve events were identified in all‐sky imager measurements with coincident or near‐coincident measurements from the Swarm satellites
In all cases, evidence of subauroral ion drifts are observed in Swarm measurements
All measurements of SAID overlapping with Steve have very fast ion flows, high electron temperatures, and extremely low plasma densities
We compiled and standardized sediment trap data below 1000 m depth from 52 locations around the globe to infer the implications of the Armstrong et al. 2002 “ballast” model to the ratio of organic ...carbon to calcium carbonate in the deep sea (the rain ratio). We distinguished three forms of mineral ballast: calcium carbonate, opal, and lithogenic material. We concur with Armstrong et al. 2002 that organic carbon sinking fluxes correlate tightly with mineral fluxes. Based on the correlations seen in the trap data, we conclude that most of the organic carbon rain in the deep sea is carried by calcium carbonate, because it is denser than opal and more abundant than terrigenous material. This analysis explains the constancy of the organic carbon to calcium carbonate rain ratio in the deep sea today, and argues against large changes in the mean value of this ratio in the past. However, sediment trap data show variability in the ratio in areas of high relative calcium carbonate export (mass CaCO3/mass ratio > 0.4), unexplainable by the model, leaving open the possibility of regional variations in the rain ratio in the past.
Compared to other types of livestock, poultry is widely owned by rural households in developing countries. Rural poultry production is not a primary agricultural activity per se, but rather serves to ...supplement other farming activities in resource-poor rural communities, and thus contributes significantly as a source of scarce animal protein and income. Rural poultry farming is, however, faced with several challenges, including inherent slow growth rates, high rearing mortalities and susceptibility to diseases, poor nutrition and housing, and insufficient health care, which may impede production. An added concern is that unprecedented climate warming may compound some of these challenges. This paper reviews the potential impact of such climate warming on rural poultry farming, which may then provide knowledge to help inform intervention strategies to assist sustainable production. Particular focus is on how climate-warming trends have impacted on heat stress experienced by livestock, the importance of rural poultry, and challenges faced in rural poultry production in developing countries. Although these birds are generally known to be hardy, it appears that some losses experienced in rural poultry farming may be a direct or indirect consequence of climate-related stresses. There is a clear need for urgent research attention in this domain, so as to improve appropriate management strategies and responses to rising temperatures.
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