Listeria Meningitis, one of your five a day? A case report of Listeria Monocytogenes Meningitis in a fit and well 62-year-old woman.

Listeria Monocytogenes is transmitted via ingestion of contaminated food products and can cause invasive disease in susceptible hosts. Risk factors include immunocompromise; pregnancy; being elderly; and new-born. Listeriosis is uncommon but can occur in immunocompetent individuals and has a high mortality rate. We report a case of a 62-year-old female with no obvious risk factors who presented with atypical meningism. The patient was subsequently diagnosed with listeria meningitis and made a good recovery. The patient was a gardener regularly handling soil and ingested vegetables from her allotment patch; this case is reported to highlight less common risk factors and atypical ways in which listeria may present to the acute medical take.

Developing priorities for quality improvement in acute medicine using a modified Delphi method A consensus process hosted by the Society for Acute Medicine Quality Improvement Committee (SAM-QI).

INTRODUCTION: The SAM Quality Improvement Committee (SAM-QI), set up in 2016, has worked over the last year to determine the priority Acute Medicine QI topics. They have also discussed and put forward proposals to improve QI training for Acute Medicine professionals. METHODS: A modified Delphi process was completed over four rounds to determine priority QI topics. Online meetings were also used to develop proposals for QI training. RESULTS: Same Day Emergency Care (SDEC) was chosen as the priority topic for QI work within Acute Medicine. CONCLUSION: The SAM-QI group settled on SDEC being the priority topic for Acute Medicine QI development. Throughout the Delphi process SAM-QI has also developed proposals for QI training that will help Acute Medicine professionals deliver coordinated meaningful improvements in care.

A Qualitative Evaluation of a Simulation Training Initiative for Registrars Working in Acute Medicine.

INTRODUCTION: We evaluated a simulation-based training day for medical registrars to define the hidden curriculum of the training. METHODS: We interviewed participants to explore their reflections about the day, what they had learned and how it had influenced their practice. Interviews were conducted iteratively and analysed in accordance with content thematic analysis. RESULTS: We established four themes: sharing (collaborative learning), sensing (comparing one's practice against peers'), transforming (development or change in practice based on learning from the day), and endorsing (appreciating authenticity in the simulation and psychological safety in debriefing). CONCLUSION: This evaluation furthered our understanding of the self-reported learning outcomes of our participants. We encourage other institutions to perform similar evaluations to build a collaborative understanding of simulationbased education for medical registrars.

Opioid analgesia and the somatosensory memory of neonatal surgical injury in the adult rat.

BACKGROUND: Nociceptive input during early development can produce somatosensory memory that influences future pain response. Hind-paw incision during the 1st postnatal week in the rat enhances re-incision hyperalgesia in adulthood. We now evaluate its modulation by neonatal analgesia. METHODS: Neonatal rats [Postnatal Day 3 (P3)] received saline, intrathecal morphine 0.1 mg kg-1 (IT), subcutaneous morphine 1 mg kg-1 (SC), or sciatic levobupivacaine block (LA) before and after plantar hind-paw incision (three×2 hourly injections). Six weeks later, behavioural thresholds and electromyography (EMG) measures of re-incision hyperalgesia were compared with an age-matched adult-only incision (IN) group. Morphine effects on spontaneous (conditioned place preference) and evoked (EMG sensitivity) pain after adult incision were compared with prior neonatal incision and saline or morphine groups. The acute neonatal effects of incision and analgesia on behavioural hyperalgesia at P3 were also evaluated. RESULTS: Adult re-incision hyperalgesia was not prevented by neonatal peri-incision morphine (saline, IT, and SC groups > IN; P<0.05-0.01). Neonatal sciatic block, but not morphine, prevented the enhanced re-incision reflex sensitivity in adulthood (LA < saline and morphine groups, P<0.01; LA vs IN, not significant). Morphine efficacy in adulthood was altered after morphine alone in the neonatal period, but not when administered with neonatal incision. Morphine prevented the acute incision-induced hyperalgesia in neonatal rats, but only sciatic block had a preventive analgesic effect at 24 h. CONCLUSIONS: Long-term effects after neonatal injury highlight the need for preventive strategies. Despite effective analgesia at the time of neonatal incision, morphine as a sole analgesic did not alter the somatosensory memory of early-life surgical injury.

Relationship between vitamin D knowledge and 25-hydroxyvitamin D levels amongst pregnant women.

BACKGROUND: Pregnant women living at northerly latitudes are at risk of suboptimal vitamin D status. There is a paucity of studies correlating knowledge, attitudes and practices of vitamin D with serum levels amongst pregnant women. We aimed to determine the prevalence of suboptimal vitamin D status in pregnant women of various ethnicities attending two Dublin maternity hospitals and to assess levels of knowledge, attitudes and practices concerning vitamin D. METHODS: We conducted a cross-sectional study of 116 pregnant women of Irish, Asian, Sub-Saharan African and Middle Eastern and North African (MENA) origin. Vitamin D status was determined by measurement of serum 25-hydroxyvitamin D (25OHD). We examined knowledge, attitudes and practices concerning vitamin D using an interview-assisted questionnaire. RESULTS: The median (interquartile range) 25OHD level was 25.9 (16.5-44.7) nmol L(-1). Using a cut-off point of <30 nmol L(-1) , the proportion at risk of deficiency was significantly higher among MENA (88%; P < 0.001) and Sub-Saharan African women (68%; P = 0.019) than Irish women (36%). Eighty-two women (71%) reported they had insufficient knowledge about vitamin D and its sources. Vitamin D containing supplement usage was the strongest predictor of 25OHD levels ≥30 nmol L(-1) (odds ratio = 18.03, 95% confidence interval = 5.7256.8, P < 0.001). CONCLUSIONS: Suboptimal vitamin D status is common in this cohort of pregnant women, especially among those of Sub-Saharan African and MENA origin. Awareness of vitamin D dietary sources is poor among all subgroups. Recommending vitamin D containing supplements may be the best strategy at present for improving vitamin D status with a need for increased vitamin D education.

Attitudes of women with gestational diabetes toward diet and exercise: a qualitative study.

OBJECTIVE: Gestational diabetes (GDM) refers to glucose intolerance of varying severity first occurring in pregnancy. Following a diagnosis of GDM, exercise and dietary modification has a positive effect on improving glycemic control. Lifestyle changes affected in pregnancies affected by GDM have beneficial effects on long-term health if continued following birth. In addition, the psychological impact of a diagnosis of GDM should not be overlooked. Reports of maternal stress, anxiety, and fear are commonly reported issues in the literature. Support, both socially and from health care professionals, is also linked with higher rates of success in GDM management. Research to date had focused on women's reaction to a diagnosis of GDM, their mood and quality of life following a diagnosis, and their knowledge or opinions on the management of GDM. This qualitative study explored the attitudes of women with GDM toward these lifestyle changes, specifically diet and exercise. Women were also asked to identify advice that would be useful for other women newly diagnosed with GDM. METHODS: With ethical approval a qualitative study was conducted using semi-structured interviews which were examined using Thematic Analysis. Patients were invited to participate and gave written consent after a discussion with a study researcher. The question plan for semi-structured interviews was designed with the advice of patient advocates. Recurrent themes were developed until the saturation of data. RESULTS: Thirty-two women took part in the study. Time, convenience, and lack of educational awareness were common barriers to healthy eating and physical activity plans. Enablers for change included meal planning and organization. Women regarded their diets pre-diagnosis as healthy, with small "tweaks" (such as portion control) required to comply with recommendations. Another significant facilitator to change was support from the woman's partner. This also set a benchmark for plans of diet maintenance within the family structure after pregnancy. Unlike dietary changes, a consistent theme was that exercise was considered a "chore" in managing GDM and was unlikely to be continued in the long term. Practical advice offered by participants for other women with GDM included organization, realistic approaches, and lack of self-blame. CONCLUSION: Women reported that changes in diet would be more achievable in the long term than changes in exercise patterns. Partners and the clinical team were significant sources of support. Women's views are crucial to providing clinicians with a comprehensive and holistic understanding of disease management. Involving women in self-care decisions and empowering women to manage their own health are key contributors to long-term behavior change as well as service provision and policy implementation.

Differentiating between memory and effector CD8 T cells by altered expression of cell surface O-glycans.

Currently there are few reliable cell surface markers that can clearly discriminate effector from memory T cells. To determine if there are changes in O-glycosylation between these two cell types, we analyzed virus-specific CD8 T cells at various time points after lymphocytic choriomeningitis virus infection of mice. Antigen-specific CD8 T cells were identified using major histocompatibility complex class I tetramers, and glycosylation changes were monitored with a monoclonal antibody (1B11) that recognizes O-glycans on mucin-type glycoproteins. We observed a striking upregulation of a specific cell surface O-glycan epitope on virus-specific CD8 T cells during the effector phase of the primary cytotoxic T lymphocyte (CTL) response. This upregulation showed a strong correlation with the acquisition of effector function and was downregulated on memory CD8 T cells. Upon reinfection, there was again increased expression of this specific O-glycan epitope on secondary CTL effectors, followed once more by decreased expression on memory cells. Thus, this study identifies a new cell surface marker to distinguish between effector and memory CD8 T cells. This marker can be used to isolate pure populations of effector CTLs and also to determine the proportion of memory CD8 T cells that are recruited into the secondary response upon reencounter with antigen. This latter information will be of value in optimizing immunization strategies for boosting CD8 T cell responses.

Differences in development, glycogen, and lipid content associated with cytochrome P450-mediated permethrin resistance in Culex pipiens quinquefasciatus (Diptera: Culicidae).

Insecticide resistance in populations of mosquitoes is an escalating problem that can directly affect disease prevalence. Determining the fitness associated with an insecticide resistance mechanism (allele) will provide for greater understanding of the evolution of resistance, and help inform effective vector management programs. Previously, a population cage experiment in which the alleles of two highly related strains of Culex pipiens quinquefasciatus (Say) SLAB (susceptible) and ISOP450 (permethrin resistant because of cytochrome P450-mediated detoxification) were placed in direct competition in the absence of insecticide revealed that the P450 resistance allele frequency decreased over time. In the current study, SLAB and ISOP450 development, mortality and energetic resources derived from glycogen, other sugars and lipids were measured to identify biological parameters that might explain the previously observed fitness cost. SLAB exhibited shorter egg-to-adult female development time and larger body size when reared in groups when compared with ISOP450. ISOP450 female adults provided 20% sugar water lived longer than 20% sugar water fed females of the SLAB strain. No significant differences in larval development time, larval mortality, pupal stage duration time, pupal mortality, longevity of male and female adults provided with distilled water and males provided sugar water were found between the strains. The caloric content from glycogen and lipids were significantly higher in SLAB relative to ISOP450 in adults. The slower female emergence time and smaller body size when reared in groups combined with lower energy reserves (glycogen and lipids) associated with the resistance allele (in ISOP450) are likely fitness costs associated with the resistance allele of P450-mediated detoxification.

AeDES: a next-generation monitoring and forecasting system for environmental suitability of Aedes-borne disease transmission.

Aedes-borne diseases, such as dengue and chikungunya, are responsible for more than 50 million infections worldwide every year, with an overall increase of 30-fold in the last 50 years, mainly due to city population growth, more frequent travels and ecological changes. In the United States of America, the vast majority of Aedes-borne infections are imported from endemic regions by travelers, who can become new sources of mosquito infection upon their return home if the exposed population is susceptible to the disease, and if suitable environmental conditions for the mosquitoes and the virus are present. Since the susceptibility of the human population can be determined via periodic monitoring campaigns, the environmental suitability for the presence of mosquitoes and viruses becomes one of the most important pieces of information for decision makers in the health sector. We present a next-generation monitoring and forecasting system for [Formula: see text]-borne diseases' environmental suitability (AeDES) of transmission in the conterminous United States and transboundary regions, using calibrated ento-epidemiological models, climate models and temperature observations. After analyzing the seasonal predictive skill of AeDES, we briefly consider the recent Zika epidemic, and the compound effects of the current Central American dengue outbreak happening during the SARS-CoV-2 pandemic, to illustrate how a combination of tailored deterministic and probabilistic forecasts can inform key prevention and control strategies .

The Telomerase/vault-associated protein TEP1 is required for vault RNA stability and its association with the vault particle.

Vaults and telomerase are ribonucleoprotein (RNP) particles that share a common protein subunit, TEP1. Although its role in either complex has not yet been defined, TEP1 has been shown to interact with the mouse telomerase RNA and with several of the human vault RNAs in a yeast three-hybrid assay. An mTep1(-/-) mouse was previously generated which resulted in no apparent change in telomere length or telomerase activity in six generations of mTep1-deficient mice. Here we show that the levels of the telomerase RNA and its association with the telomerase RNP are also unaffected in mTep1(-/-) mice. Although vaults purified from the livers of mTep1(-/-) mice appear structurally intact by both negative stain and cryoelectron microscopy, three-dimensional reconstruction of the mTep1(-/-) vault revealed less density in the cap than previously observed for the intact rat vault. Furthermore, the absence of TEP1 completely disrupted the stable association of the vault RNA with the purified vault particle and also resulted in a decrease in the levels and stability of the vault RNA. Therefore, we have uncovered a novel role for TEP1 in vivo as an integral vault protein important for the stabilization and recruitment of the vault RNA to the vault particle.

A mammalian telomerase-associated protein.

The telomerase ribonucleoprotein catalyzes the addition of new telomeres onto chromosome ends. A gene encoding a mammalian telomerase homolog called TP1 (telomerase-associated protein 1) was identified and cloned. TP1 exhibited extensive amino acid similarity to the Tetrahymena telomerase protein p80 and was shown to interact specifically with mammalian telomerase RNA. Antiserum to TP1 immunoprecipitated telomerase activity from cell extracts, suggesting that TP1 is associated with telomerase in vivo. The identification of TP1 suggests that telomerase-associated proteins are conserved from ciliates to humans.

Influence of container size, location, and time of day on oviposition patterns of the dengue vector, Aedes aegypti, in Thailand.

We conducted a study to determine the effect of container size and location on oviposition site selection by Ae. aegypti in large outdoor field enclosures (10 x 10 x 4 m high). There was a strong positive relationship between increasing container diameter, container volume, and water surface area with egg numbers over both high (rainy, July) and low (cool-dry, January) dengue transmission seasons. Location of containers (indoors versus immediately outdoors and underneath houses) did not influence the number of eggs deposited for containers 5-32 cm in diameter in either season. No trends based on container color (black, brown, or grey) were observed. A slight trend with a greater numbers of eggs laid outdoors in the largest containers (42 cm diameter) during the dry season was observed. Three separate models were run using the mixed model procedure in SAS for each container attribute. Controlling for season, time, and date, the most important container attribute predicting total egg numbers was container volume (total capacity) explaining 88% of the variation, followed by water surface area (85%), and container diameter opening (83%). Oviposition peaked in the afternoon at 1600 hrs and 2000 hrs in the dry and rainy seasons, respectively. Few eggs were laid overnight (2000 hrs-0600 hrs). Our results indicate that physical attributes of oviposition sites, such as size, light-dark contrasts, and specular reflectance from water surfaces, play a significant role in oviposition site selection.

Flushing effect of rain on container-inhabiting mosquitoes Aedes aegypti and Culex pipiens (Diptera: Culicidae).

We investigated the role of heavy rain on container-inhabiting mosquito (Diptera: Culicidae) populations, and how different species may have adapted to such conditions. Rains were created with a rain simulator calibrated to natural rain intensities in the habitats of two important vector species: Aedes aegypti (L.) from northern Thailand and Culex pipiens L. from New York state, USA. Immature stages of Ae. aegypti were able to resist the flushing effect of rain better than Cx. pipiens. This difference was most dramatic during the pupal stage. Fourth instars of Ae. aegypti were not affected by flushing when exposed for longer rain intervals (30 versus 60 min) or at a colder water temperature (24 versus 16 degrees C). In contrast, significantly more Cx. pipiens larvae flushed out with longer rain exposure. Warmer water temperatures also increased the proportion of Cx. pipiens flushed out, but mostly at the longest exposure time. Container position (tilted at a 7 degrees angle or level) did not affect proportions of fourth instars flushed out for both species. More accurate models of vector-borne diseases can be developed by incorporating the described effects of rain on container-breeding mosquito populations. Such models may provide more realistic assessments of disease risk and ensure optimal use of limited financial resources of mosquito control agencies.

A re-appraisal of lactose intolerance.

BACKGROUND: Lactose, beta-galactose-1,4-glucose, is hydrolysed by the enzyme lactase. Lactose intolerance occurs when lactase deficiency causes clinical symptoms. AIMS: To provide an overview of lactose intolerance, including definition, aetiology and epidemiology, the clinical symptoms and diagnostic testing and management. METHODS: A literature review was carried out to meet the aims of this paper. This resulted in the analysis of a database of patients tested for lactose intolerance to provide examples of the consequences of problems of terminology identified. CONCLUSIONS: The terminology relating to lactose intolerance is confusing for clinicians and researchers. Clinicians need to ensure that these problematic terms do not cause diagnostic mistakes and inappropriate treatment. Researchers should be aware of inconsistent terminology in studies and resultant problems with the interpretation of results.

Age and Body Size Influence Sperm Quantity in Male Aedes albopictus (Diptera: Culicidae) Mosquitoes.

Aedes albopictus (Skuse) (Diptera: Culicidae) is a vector of several arboviruses impacting human health, including dengue, chikungunya, and potentially Zika. Vector control strategies that deploy modified males into the field are in use or under development and require a solid understanding of male biology; unfortunately, there has been limited effort to understand male Ae. albopictus reproductive biology, including sperm production and capacity. We tested whether body size and age affect spermatogenesis in Ae. albopictus. In general, older and larger males produced more sperm than their younger or smaller counterparts. Large males continued spermatogenesis well after 10-d post-eclosion (dpe), augmenting their reserves by 39%. By contrast, small males stopped producing sperm at 10 dpe. These results contribute to a deeper understanding of Ae. albopictus reproductive physiology. We discuss the usefulness of these findings in the context of Ae. albopictus life history and their utility in optimizing male mosquito release strategies.

Reduction in physical function in women after venous thromboembolism.

Essentials The association of venous thromboembolism (VTE) with subsequent physical function remains unclear. We prospectively evaluated this relationship among women from the Nurses' Health Studies. We found a decline in physical function over four years in women with incident VTE. This decline was somewhat greater among women specifically reporting a pulmonary embolism. SUMMARY: Background Physical function is integral to healthy aging; however, limited research has examined the association of venous thromboembolism(VTE) with subsequent physical function. Objectives To prospectively evaluate the relationship between VTE and decline in physical function among 80 836 women from the Nurses' Health Study(NHS), ages 46-72 in 1992, and 84 304 women from the Nurses' Health Study II(NHS II), ages 29-48 in 1993. Methods Physical function was measured by the Medical Outcomes Short Form-36 physical function scale, administered every 4 years. We compared change in physical function for women with vs. without an incident VTE in each 4-year follow-up period using multivariable linear regression. Results We observed a decline in physical function over 4 years when comparing women with vs. those without incident VTE in both older (NHS) and younger (NHS II) women (multivariable-adjusted mean difference NHS, -6.5 points [95% CI -7.4, -5.6] per 4 years; NHS II, -3.8 [95% CI -5.6, -2.0]). This difference appeared greater among women specifically reporting a pulmonary embolism (NHS, -7.4 [95% CI -8.7, -6.1]; NHS II, -4.8 [95% CI -6.8, -2.8]), and was equivalent to 6.2 years of aging. Whereas longer-term slopes of physical function decline following a VTE were not different from the slopes of decline in women without a VTE, the absolute level of physical function of women with VTE was worse at the end of follow-up compared to women without VTE. Conclusions In this prospective cohort, incident VTE was strongly associated with an acute decline in physical function. These results suggest it may be clinically important to consider approaches to ameliorating functional deficits shortly after VTE diagnosis.

Secretion-mediated STAT3 activation promotes self-renewal of glioma stem-like cells during hypoxia.

High-grade gliomas (HGGs) include the most common and the most aggressive primary brain tumor of adults and children. Despite multimodality treatment, most high-grade gliomas eventually recur and are ultimately incurable. Several studies suggest that the initiation, progression, and recurrence of gliomas are driven, at least partly, by cancer stem-like cells. A defining characteristic of these cancer stem-like cells is their capacity to self-renew. We have identified a hypoxia-induced pathway that utilizes the Hypoxia Inducible Factor 1α (HIF-1α) transcription factor and the JAK1/2-STAT3 (Janus Kinase 1/2 - Signal Transducer and Activator of Transcription 3) axis to enhance the self-renewal of glioma stem-like cells. Hypoxia is a commonly found pathologic feature of HGGs. Under hypoxic conditions, HIF-1α levels are greatly increased in glioma stem-like cells. Increased HIF-1α activates the JAK1/2-STAT3 axis and enhances tumor stem-like cell self-renewal. Our data further demonstrate the importance of Vascular Endothelial Growth Factor (VEGF) secretion for this pathway of hypoxia-mediated self-renewal. Brefeldin A and EHT-1864, agents that significantly inhibit VEGF secretion, decreased stem cell self-renewal, inhibited tumor growth, and increased the survival of mice allografted with S100ß-v-erbB/p53-/- glioma stem-like cells. These agents also inhibit the expression of a hypoxia gene expression signature that is associated with decreased survival of HGG patients. These findings suggest that targeting the secretion of extracellular, autocrine/paracrine mediators of glioma stem-like cell self-renewal could potentially contribute to the treatment of HGGs.

Alcohol consumption and the risk of incident pulmonary embolism in US women and men.

Essentials The association of moderate alcohol consumption with pulmonary embolism (PE) risk remains unclear. In three large US cohorts, we evaluated the association of alcohol consumption with PE risk. We found no evidence of an association of alcohol consumption amount or frequency with PE risk. Secondary analyses of type and heavy episodic drinking also yielded null findings. SUMMARY: Background Moderate alcohol consumption has been variably associated with hemostatic and fibrinolytic factor levels, but the association between alcohol consumption and the risk of incident pulmonary embolism (PE) remains uncertain. Objective To evaluate alcohol consumption amount and frequency in relation to PE risk. Methods Nurses' Health Study (NHS), NHS II and Health Professionals Follow-Up Study participants free of venous thromboembolism (VTE) at baseline (n = 217 442) reported alcohol consumption by type, quantity and frequency, every 2-4 years. Incident PE cases were identified by self-report and confirmed for participants without cancer. In this cohort study, we used Cox proportional hazards models to estimate multivariable-adjusted hazard ratios (HRs) for PE associated with alcohol consumption amount and, separately, frequency. Secondary analyses evaluated alcohol type and heavy episodic drinking in relation to PE risk, and amount and frequency in relation to medical record-confirmed idiopathic PE and any self-reported VTE risk. Cohort-specific analyses were pooled using random-effects meta-analysis. Results During ≥ 20 years of follow-up, we identified 1939 PE events. We found no strong evidence of an association between PE risk and alcohol consumption amount (pooled HRadj for 5.0-14.9 g day-1 vs. abstention = 0.97 [95% CI, 0.79, 1.20]) or frequency (pooled HRadj for 5-7 drinking days per week vs. abstention = 1.04 [95% CI, 0.88, 1.23]). Secondary analyses of type, heavy episodic drinking, idiopathic PE and VTE also yielded null findings. Conclusions Among three large prospective cohorts of US men and women, we found no evidence of an association between the amount or frequency of alcohol consumption and PE risk.

Metabolomic analysis of 92 pulmonary embolism patients from a nested case-control study identifies metabolites associated with adverse clinical outcomes.

Essentials Risk-stratification often fails to predict clinical deterioration in pulmonary embolism (PE). First-ever high-throughput metabolomics analysis of risk-stratified PE patients. Changes in circulating metabolites reflect a compromised energy metabolism in PE. Metabolites play a key role in the pathophysiology and risk stratification of PE. SUMMARY: Background Patients with acute pulmonary embolism (PE) exhibit wide variation in clinical presentation and outcomes. Our understanding of the pathophysiologic mechanisms differentiating low-risk and high-risk PE is limited, so current risk-stratification efforts often fail to predict clinical deterioration and are insufficient to guide management. Objectives To improve our understanding of the physiology differentiating low-risk from high-risk PE, we conducted the first-ever high-throughput metabolomics analysis (843 named metabolites) comparing PE patients across risk strata within a nested case-control study. Patients/methods We enrolled 92 patients diagnosed with acute PE and collected plasma within 24 h of PE diagnosis. We used linear regression and pathway analysis to identify metabolites and pathways associated with PE risk-strata. Results When we compared 46 low-risk with 46 intermediate/high-risk PEs, 50 metabolites were significantly different after multiple testing correction. These metabolites were enriched in the following pathways: tricarboxylic acid (TCA) cycle, fatty acid metabolism (acyl carnitine) and purine metabolism, (hypo)xanthine/inosine containing. Additionally, energy, nucleotide and amino acid pathways were downregulated in intermediate/high-risk PE patients. When we compared 28 intermediate-risk with 18 high-risk PE patients, 41 metabolites differed at a nominal P-value level. These metabolites were enriched in fatty acid metabolism (acyl cholines), and hemoglobin and porphyrin metabolism. Conclusion Our results suggest that high-throughput metabolomics can provide insight into the pathophysiology of PE. Specifically, changes in circulating metabolites reflect compromised energy metabolism in intermediate/high-risk PE patients. These findings demonstrate the important role metabolites play in the pathophysiology of PE and highlight metabolomics as a potential tool for risk stratification of PE.

Vasomotor symptoms and the risk of incident venous thrombosis in postmenopausal women.

Essentials Vasomotor symptoms have been proposed as markers of changing cardiovascular risk. In this cohort study, we evaluated these symptoms as markers of venous thrombosis (VT) risk. We found no evidence that vasomotor symptom presence or severity were associated with VT risk. Among these postmenopausal women, vasomotor symptoms are not a useful marker of VT risk. SUMMARY: Background Vasomotor symptoms may be markers of changes in cardiovascular risk, but it is unknown whether these symptoms are associated with the risk of venous thrombosis (VT). Objective To evaluate the association of vasomotor symptom presence and severity with incident VT risk among postmenopausal women, independent of potential explanatory variables. Methods This cohort study included participants of the Women's Health Initiative (WHI) Hormone Therapy Trials (n = 24 508) and Observational Study (n = 87 783), analyzed separately. At baseline, women reported whether hot flashes or night sweats were present and, if so, their severity. Using Cox proportional hazards models, we estimated the VT risk associated with vasomotor symptom presence and severity, adjusted for potential explanatory variables: age, body mass index, smoking status, race/ethnicity, and time-varying current hormone therapy use. Results At baseline, WHI Hormone Therapy Trial participants were aged 64 years and WHI Observational Study participants were aged 63 years, on average. In the WHI Hormone Therapy Trials over a median of 8.2 years of follow-up, 522 women experienced a VT event. In the WHI Observational Study, over 7.9 years of follow-up, 1103 women experienced a VT event. In adjusted analyses, we found no evidence of an association between vasomotor symptom presence (hazard ratio [HR]adj  0.91, 95% confidence interval [CI] 0.75-1.1 in the WHI Hormone Therapy Trials; HRadj  1.1, 95% CI 0.99-1.3 in the WHI Observational Study) or severity (HRadj for severe versus mild 0.99, 95% CI 0.53-1.9 in the WHI Hormone Therapy Trials; HRadj  1.3, 95% CI 0.89-2.0) in the WHI Observational Study) and the risk of incident VT. Conclusions Although vasomotor symptoms have been associated with the risk of other cardiovascular events in published studies, our findings do not suggest that vasomotor symptoms constitute a marker of VT risk.