Ingestion of soapberry fruit toxins hypoglycin A and methylenecyclopropylglycine has been linked to public health challenges worldwide. In 1976, over 100 years after Jamaican vomiting sickness (JVS) ...was first reported, the cause of JVS was linked to the ingestion of the toxin hypoglycin A produced by ackee fruit. A structural analogue of hypoglycin A, methylenecyclopropylglycine (MCPG), was implicated as the cause of an acute encephalitis syndrome (AES). Much of the evidence linking hypoglycin A and MCPG to these diseases has been largely circumstantial due to the lack of an analytical method for specific metabolites. This study presents an analytical approach to identify and quantify specific urine metabolites for exposure to hypoglycin A and MCPG. The metabolites are excreted in urine as glycine adducts methylenecyclopropylacetyl-glycine (MCPA-Gly) and methylenecyclopropylformyl-glycine (MCPF-Gly). These metabolites were processed by isotope dilution, separated by reverse-phase liquid chromatography, and monitored by electrospray ionization tandem mass spectrometry. The analytical response ratio was linearly proportional to the concentration of MCPF-Gly and MCPA-Gly in urine from 0.10 to 20 μg/mL with a correlation coefficient of r > 0.99. The assay demonstrated accuracy ≥80% and precision ≤20% RSD across the calibration range. This method has been applied to assess exposure to hypoglycin A and MCPG as part of a larger public health initiative and was used to provide the first reported identification of MCPF-Gly and MCPA-Gly in human urine.
This study examines factors influencing HIV sero-status disclosure to sex partners among a sample of 630 HIV-infected men and women with recent sexual contact attending anti-retroviral therapy (ART) ...clinics in Cape Town, South Africa, with a focus on sex partner type, HIV-related stigma, and ART as potential correlates. About 20% of the sample had not disclosed their HIV status to their most recent sex partners. HIV disclosure to sex partner was more likely among participants who had a steady sex partner Adjusted odds ratio (AOR) = 2.7; 95% CI: 1.6–4.6, had a partner with known-HIV status AOR = 7.8; 95% CI: 3.2–18.7; perceived less stigma AOR = 1.9; 95% CI: 1.2–2.9; and were on ART AOR = 1.6; 95% CI: 1.1–2.3. Stratified analyses by the type of sex partner further reveals that stigma and ART were significantly associated with HIV disclosure within steady relationships but were not significant correlates of HIV disclosure with casual sex partners. The findings support a positive prevention strategy that emphasizes increased access to ART, and behavioral interventions to reduce casual sex partnerships for persons who are HIV-positive. Mitigating the influence of HIV stigma on HIV status disclosure particularly within steady sex partnerships is also important and may be accomplished through individual and couple counseling.
•Quantitates MCPG and HGA levels in soapberry seeds.•Adapts previous platform used to quantitate MCPG and HGA levels in soapberry arils.•Enables public health investigators to determine how ripeness ...affects MCPG and HGA.•Provides first quantitation of HGA in litchi, mamoncillo, and longan seeds.
Methylenecyclcopropylglycine (MCPG) and hypoglycin A (HGA) are naturally occurring amino acids found in various soapberry (Sapindaceae) fruits. These toxins have been linked to illnesses worldwide and were recently implicated in Asian outbreaks of acute hypoglycemic encephalopathy. In a previous joint agricultural and public health investigation, we developed an analytical method capable of evaluating MCPG and HGA concentrations in soapberry fruit arils as well as a clinical method for the urinary metabolites of the toxins. Since the initial soapberry method only analyzed the aril portion of the fruit, we present here the extension of the method to include the fruit seed matrix. This work is the first method to quantitate both MCPG and HGA concentrations in the seeds of soapberry fruit, including those collected during a public health investigation. Further, this is the first quantitation of HGA in litchi seeds as well as both toxins in mamoncillo and longan seeds.
BACKGROUND:The HIV continuum of care paradigm uses a single viral load test per patient to estimate the prevalence of viral suppression. We compared this single-value approach with approaches that ...used multiple viral load tests to examine the stability of suppression.
METHODS:The retrospective analysis included HIV patients who had at least 2 viral load tests during a 12-month observation period. We assessed the (1) percent with suppressed viral load (<200 copies/mL) based on a single test during observation, (2) percent with suppressed viral loads on all tests during observation, (3) percent who maintained viral suppression among patients whose first observed viral load was suppressed, and (4) change in viral suppression status comparing first with last measurement occasions. Prevalence ratios compared demographic and clinical subgroups.
RESULTS:Of 10,942 patients, 78.5% had a suppressed viral load based on a single test, whereas 65.9% were virally suppressed on all tests during observation. Of patients whose first observed viral load was suppressed, 87.5% were suppressed on all subsequent tests in the next 12 months. More patients exhibited improving status (13.3% went from unsuppressed to suppressed) than worsening status (5.6% went from suppressed to unsuppressed). Stable suppression was less likely among women, younger patients, black patients, those recently diagnosed with HIV, and those who missed ≥1 scheduled clinic visits.
CONCLUSIONS:Using single viral load measurements overestimated the percent of HIV patients with stable suppressed viral load by 16% (relative difference). Targeted clinical interventions are needed to increase the percent of patients with stable suppression.
An experiential curriculum exposing medical students to the clinic early has many benefits but comes with the emotional stress this environment engenders. Schwartz rounds (SR) are an effective means ...to combat emotional stress and increasingly used in UK and USA hospitals. Recent studies show that the SR format may also provide benefits for medical students. This study aimed to investigate whether the guidance of SR in second year medical students provides the same benefits as to healthcare professionals.
SR assessment involved 83 s year MBChB students in facilitated groupwork sessions. Topics discussed were "change and resilience" and "duty of candour". Students completed a Likert Scale questionnaire evaluating outcomes proffered by the Point of Care Foundation in collaboration with the Schwartz Foundation, with freeform feedback.
There was an 86% completion rate with 25% providing written feedback. Participants were more likely to agree than disagree that SR were beneficial. SR effectiveness in enhancing students' working relationship awareness and skills was strongly correlated with understanding the purpose of, and engagement with, the SR (P < 0.001). Similarly, engagement with the SR was strongly correlated with self-reporting of enhanced patient-centredness (P < 0.001). Freeform feedback could be grouped into five themes that revolved around understanding of the SR and engagement with the process. Many positive comments regarded the SR as a forum not only to "learn experientially" but to so in a "safe environment". Many negative comments stemmed from students not seeing any benefits of engagement with the SR, in that sharing experiences was "unbeneficial", "empathy is inherent and not learnt", or that sharing emotional problems is simply "moaning".
SRs are an effective way of fostering empathy and understanding towards patients and colleagues. However, for the students to benefit fully from the SR it is necessary for them to engage and understand the process. Therefore, for the successful implementation of SR into pre-clinical medical education, it is important to help students realise that SR are not merely a "facilitated whinge".
Metabolomics is a rapidly growing field of research used in the identification and quantification of the small molecule metabolites within an organism, thereby providing insights into cell metabolism ...and bioenergetics as well as processes important in clinical medicine, such as disposition of pharmaceutical compounds. It offers comprehensive information about thousands of low-molecular mass compounds (<1500 Da) that represent a wide range of pathways and intermediary metabolism. Because of its vast expansion in the past two decades, mass spectrometry has become an indispensable tool in “omic” analyses. The use of different ionization techniques such as the more traditional electrospray and matrix-assisted laser desorption, as well as recently popular desorption electrospray ionization, has allowed the analysis of a wide range of biomolecules (e.g., peptides, proteins, lipids, and sugars), and their imaging and analysis in the original sample environment in a workup free fashion. An overview of the current state of the methodology is given, as well as examples of application.
Hypoglycin A (HGA) and methylenecyclopropylglycine (MCPG) are naturally-occurring amino acids known to cause hypoglycemia and encephalopathy. Exposure to one or both toxins through the ingestion of ...common soapberry (Sapindaceae) fruits are documented in illness outbreaks throughout the world. Jamaican Vomiting Sickness (JVS) and seasonal pasture myopathy (SPM, horses) are linked to HGA exposure from unripe ackee fruit and box elder seeds, respectively. Acute toxic encephalopathy is linked to HGA and MCPG exposures from litchi fruit. HGA and MCPG are found in several fruits within the soapberry family and are known to cause severe hypoglycemia, seizures, and death. HGA has been directly quantified in horse blood in SPM cases and in human gastric juice in JVS cases. This work presents a new diagnostic assay capable of simultaneous quantification of HGA and MCPG in human plasma, and it can be used to detect patients with toxicity from soapberry fruits. The assay presented herein is the first quantitative method for MCPG in blood matrices.
Since the establishment of the brown marmorated stink bug,
Halyomorpha halys
(Stål) (Hemiptera: Pentatomidae) in North America and Europe, there has been a large, multi-group effort to characterize ...the composition and impact of the indigenous community of arthropod natural enemies attacking this invasive pest. In this review, we combine 98 indigenous natural enemy datasets spanning a variety of sampling methods, habitats, and geographic areas. To date, the vast majority of
H. halys
biological control research has focused on the egg stage, using sentinel egg masses to characterize indigenous parasitoid and predator communities and their contribution to
H. halys
egg mortality. Although egg parasitism and predation levels by indigenous natural enemies are low (typically <10% each) in most surveys, total egg mortality attributable to natural enemies can be higher (typically between 5 and 25%; up to 83%)—even though these values were likely underestimated in most cases because some mortality due to biological control was not recognized. In North America, where the most data are available, it appears that the relative prevalence of different indigenous parasitoid species varies among habitat types, particularly between crop and non-crop habitats. Predator species responsible for egg mortality are much less commonly identified, but appear to include a wide variety of generalist chewing and sucking predators. To date, studies of natural enemies attacking
H. halys
nymphs and adults are relatively rare. Based on our review, we identify a number of key research gaps and suggest several directions for future research.
Measurement of nitrotyrosine levels in biological fluids can serve as a biomarker for oxidative/nitrative damage arising from formation of reactive nitrogen species, including peroxynitrite. ...Peroxynitrite is formed by the reaction of the superoxide radical
(
O
2
.
-
)
with the nitric oxide radical (
.NO) that is generated by nitric oxide synthase (NOS). This article describes an immunoaffinity liquid chromatography–tandem mass spectrometry (LC–MS/MS) method to measure 3-nitrotyrosine at very low (picomolar) levels. Incorporation of a pronase digestion step prior to the immunoaffinity LC–MS/MS allowed for measuring not only free amino acid but also protein 3-nitrotyrosine in biological fluids. The use of an in-line antibody column allowed for increased specificity as compared with previously reported assays. The assay is linear over a range of 5 to 500 pg/ml (0.022–2.20 nM,
r
2
=
0.9987), with the lower detection limit being 5 pg/ml. In addition to its increased sensitivity and specificity, this assay showed great nitrotyrosine recovery from biological fluids when either nitrotyrosine or nitrotyrosine-containing peptides were added exogenously. The utility of this assay for nitrotyrosine as a clinically translatable biomarker was demonstrated by quantifying both free and total nitrotyrosine levels in various biological fluids, including urine, plasma, serum, cerebrospinal fluid (CSF), and synovial fluid (SF) from both preclinical species and human subjects. Thus, whether in an animal model of human disease or in a clinical setting, the quantification of nitrotyrosine levels should provide support for NOS-driven pathology and its blockade following therapeutic intervention.
Sphingosine 1-phosphate (S1P), a potent phospholipid growth and trophic factor, is synthesized in vivo by two sphingosine kinases. Thus these kinases have been proposed as important drug targets for ...treatment of hyperproliferative diseases and inflammation. We report here a new class of amidine-based sphingosine analogues that are competitive inhibitors of sphingosine kinases exhibiting varying degrees of enzyme selectivity. These inhibitors display K I values in the submicromolar range for both sphingosine kinases and, in cultured vascular smooth muscle cells, decrease S1P levels and initiate growth arrest.
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