bluuebunny/crossref_metadata_2025 huggingface dataset:
Arabidopsis glucosinolate storage cells transform into phloem fibres at late stages of development
Authors: Hunziker Pascal , Halkier Barbara Ann , Schulz Alexander
Published: April 2019

The phloem cap of Arabidopsis thaliana accumulates glucosinolates that yield toxic catabolites upon damage-induced hydrolysis. These defence compounds are stored in high concentrations in millimetre long S-cells. At early stages of development, S-cells initiate a process indicative of programmed cell death. How these cells are maintained in a highly turgescent state following this process is currently unknown. Here, we show that S-cells undergo substantial morphological changes during early differentiation. Vacuolar collapse and rapid clearance of the cytoplasm did not occur until senescence. Instead, smooth endoplasmic reticulum, Golgi bodies, vacuoles, and undifferentiated plastids were observed. Lack of chloroplasts indicates that S-cells depend on metabolite supply from neighbouring cells. Interestingly, TEM revealed numerous plasmodesmata between S-cells and neighbouring cells. Photoactivation of a symplasmic tracer showed coupling with neighbouring cells that are involved in glucosinolate synthesis. Hence, symplasmic transport might contribute to glucosinolate storage in S-cells. To investigate the fate of S-cells, we traced them in flower stalks from the earliest detectable stages to senescence. At late stages, S-cells were shown to deposit thick secondary cell walls and transform into phloem fibres. Thus, phloem fibres in the herbaceous plant Arabidopsis pass a pronounced phase of chemical defence during early stages of development.
AutoMLST: an automated web server for generating multi-locus species trees highlighting natural product potential
Authors: Alanjary Mohammad , Steinke Kat , Ziemert Nadine
Published: April 2019

Understanding the evolutionary background of a bacterial isolate has applications for a wide range of research. However generating an accurate species phylogeny remains challenging. Reliance on 16S rDNA for species identification currently remains popular. Unfortunately, this widespread method suffers from low resolution at the species level due to high sequence conservation. Currently, there is now a wealth of genomic data that can be used to yield more accurate species designations via modern phylogenetic methods and multiple genetic loci. However, these often require extensive expertise and time. The Automated Multi-Locus Species Tree (autoMLST) was thus developed to provide a rapid ‘one-click’ pipeline to simplify this workflow at: https://automlst.ziemertlab.com. This server utilizes Multi-Locus Sequence Analysis (MLSA) to produce high-resolution species trees; this does not preform multi-locus sequence typing (MLST), a related classification method. The resulting phylogenetic tree also includes helpful annotations, such as species clade designations and secondary metabolite counts to aid natural product prospecting. Distinct from currently available web-interfaces, autoMLST can automate selection of reference genomes and out-group organisms based on one or more query genomes. This enables a wide range of researchers to perform rigorous phylogenetic analyses more rapidly compared to manual MLSA workflows.
LitSense: making sense of biomedical literature at sentence level
Authors: Allot Alexis , Chen Qingyu , Kim Sun , Vera Alvarez Roberto , Comeau Donald C , Wilbur W John , Lu Zhiyong
Published: April 2019

Literature search is a routine practice for scientific studies as new discoveries build on knowledge from the past. Current tools (e.g. PubMed, PubMed Central), however, generally require significant effort in query formulation and optimization (especially in searching the full-length articles) and do not allow direct retrieval of specific statements, which is key for tasks such as comparing/validating new findings with previous knowledge and performing evidence attribution in biocuration. Thus, we introduce LitSense, which is the first web-based system that specializes in sentence retrieval for biomedical literature. LitSense provides unified access to PubMed and PMC content with over a half-billion sentences in total. Given a query, LitSense returns best-matching sentences using both a traditional term-weighting approach that up-weights sentences that contain more of the rare terms in the user query as well as a novel neural embedding approach that enables the retrieval of semantically relevant results without explicit keyword match. LitSense provides a user-friendly interface that assists its users to quickly browse the returned sentences in context and/or further filter search results by section or publication date. LitSense also employs PubTator to highlight biomedical entities (e.g. gene/proteins) in the sentences for better result visualization. LitSense is freely available at https://www.ncbi.nlm.nih.gov/research/litsense.
Postoperative Hearing Preservation in Patients Undergoing Retrosigmoid Craniotomy for Resection of Vestibular Schwannomas: A Systematic Review of 2034 Patients
Authors: Preet Komal , Ong Vera , Sheppard John P , Udawatta Methma , Duong Courtney , Romiyo Prasanth , Nguyen Thien , Kwan Isabelle , Yang Isaac
Published: April 2019

BACKGROUND

Vestibular schwannomas (VS) are benign tumors derived from Schwann cells ensheathing the vestibulocochlear nerve. The retrosigmoid (RS) surgical approach is useful to resect tumors of multiple sizes while affording the possibility of preserving postoperative hearing.

OBJECTIVE

To conduct a systematic review of published literature investigating hearing preservation rates in patients who underwent the RS approach for VS treatment.

METHODS

The PubMed, Scopus, and Embase databases were surveyed for studies that reported preoperative and postoperative hearing grades on VS patients who underwent RS treatment. Hearing preservation rates were calculated, and additional patient demographic data were extracted. Tumor size data were stratified to compare hearing preservation rates after surgery for intracanalicular, small (0-20 mm), and large (>20 mm) tumors.

RESULTS

Of 383 deduplicated articles, 26 studies (6.8%) met eligibility criteria for a total of 2034 patients with serviceable preoperative hearing, for whom postoperative hearing status was evaluated. Aggregate hearing preservation was 31% and 35% under a fixed and random effects model, respectively. A mixed effects model was used to determine hearing preservation rates depending on tumor size, which were determined to be 57%, 37%, and 12% for intracanalicular, small, and large tumors, respectively. Significant cross-study heterogeneity was found (I2 = 93%, τ2 = .964, P < .01; Q = 287.80, P = < .001), with rates of hearing preservation ranging from 0% to 100%.

CONCLUSION

Tumor size may have an effect on hearing preservation rates, but multiple factors should be considered. Discussion of a patient's expectations for hearing preservation is critical when deciding on VS treatment plans.
Weak Assertion
Authors: Incurvati Luca , Schlöder Julian J
Published: April 2019

We present an inferentialist account of the epistemic modal operator might. Our starting point is the bilateralist programme. A bilateralist explains the operator not in terms of the speech act of rejection; we explain the operator might in terms of weak assertion, a speech act whose existence we argue for on the basis of linguistic evidence. We show that our account of might provides a solution to certain well-known puzzles about the semantics of modal vocabulary whilst retaining classical logic. This demonstrates that an inferentialist approach to meaning can be successfully extended beyond the core logical constants.
Backlash: The Unintended Effects of Language Prohibition in U.S. Schools after World War I
Authors: Fouka Vasiliki
Published: April 2019

Do forced assimilation policies always succeed in integrating immigrant groups? This article examines how a specific assimilation policy—language restrictions in elementary school—affects integration and identification with the host country later in life. After World War I, several U.S. states barred the German language from their schools. Affected individuals were less likely to volunteer in World War II and more likely to marry within their ethnic group and to choose decidedly German names for their offspring. Rather than facilitating the assimilation of immigrant children, the policy instigated a backlash, heightening the sense of cultural identity among the minority.
Idiosyncratic Jump Risk Matters: Evidence from Equity Returns and Options
Authors: Bégin Jean-François , Dorion Christian , Gauthier Geneviève
Published: April 2019

The recent literature provides conflicting empirical evidence about the pricing of idiosyncratic risk. This paper sheds new light on the matter by exploiting the richness of option data. First, we find that idiosyncratic risk explains 28% of the variation in the risk premium on a stock. Second, we show that the contribution of idiosyncratic risk to the equity premium arises exclusively from jump risk. Third, we document that the commonality in idiosyncratic tail risk is much stronger than that in total idiosyncratic risk documented in the literature. Tail risk thus plays a central role in the pricing of idiosyncratic risk.

Received May 15, 2017; editorial decision September 12, 2018 by Editor Stijn Van Nieuwerburgh. Authors have furnished code and an Internet Appendix, which are available on the Oxford University PressWeb site next to the link to the final published paper online.
UNIVERSAL RADIATION PROTECTION SYSTEM (URPS); A NATURAL GLOBAL STANDARDISED TREND FOR HUMAN EXPOSURE CONTROL IN 21st CENTURY
Authors: Sohrabi M
Published: April 2019

In order to address the many deficiencies with current radiological protection system worldwide, this paper proposes a new Universal Radiation Protection System (URPS) Hypothesis with novel philosophy, concepts and methodologies of applying principles of equal human health-effect risks of an individual per unit radiation dose either from environmental natural background (NBG) or man-made sources; a ‘standardised integrated dose system’ for integrating all individual doses with emphasis on national NBG doses; considering worker as a member of public; and a ‘cause–effect conservation principle’ for epidemiology risk estimation. The URPS also a radiation hypothesises fractionation weighting factors (WF); a ‘URPS Model’ for bridging ‘linear no-threshold and hormesis models’; example dose limit for workers; as well as new terms and definitions. State-of-the-art developments on URPS hypothesis are presented and discussed with simple global natural trends for standardised human exposure control in order to protect workers, patients, public and environment by standardised methods independent of source and country of origin in the 21st century.
Relationship between Future Orientation and Pain Severity in Fibromyalgia Patients: Self-Compassion as a Coping Mechanism
Authors: Chang Edward C , Lucas Abigael G , Chang Olivia D , Angoff Harrison D , Li Mingqi , Duong Ashley H , Huang Judy , Perera Marisa J , Sirois Fuschia M , Hirsch Jameson K
Published: April 2019

The present study examined the relationship between future orientation and fibromyalgia-related pain severity in a sample of 287 adults with fibromyalgia. Specifically, authors examined dimensions of self-compassion (for example, self-kindness, isolation, mindfulness) as possible mechanisms through which future orientation might be associated with pain severity. Results of conducting a multiple mediator test with 10,000 bootstraps indicated that the significant negative association between future orientation and pain severity was mediated through one specific self-compassion dimension, namely, isolation. The article concludes with a discussion of the implications of the present findings for working with fibromyalgia patients, specifically the potential value of social workers working with fibromyalgia patients to build future orientation as a resilience factor to combat pain severity. Also discussed is the value of working with patients to develop a sustainable social support system that can disrupt experiences of social isolation and disconnectedness from others, and which appear to contribute to greater pain severity.
Nutrient availability alters the correlation between spring leaf-out and autumn leaf senescence dates
Authors: Fu Yongshuo H , Piao Shilong , Delpierre Nicolas , Hao Fanghua , Hänninen Heikki , Geng Xiaojun , Peñuelas Josep , Zhang Xuan , Janssens Ivan A , Campioli Matteo
Published: April 2019

Leaf senescence (LS) affects tree fitness, species distribution and ecosystem structure and functioning. The drivers of LS and the processes underlying it have been studied, but the studies have mainly focused on environmental cues and have mainly been based on statistical analyses using in situ data sets. Experimental investigation and field verification of the processes and drivers are thus urgently needed. We conducted a nutrient-addition experiment after a spring-warming experiment in which an ~40-day range of leaf-out (LO) dates was induced in horse chestnut (Aesculus hippocastanum) and beech (Fagus sylvatica) saplings. We found that both increased nutrient supply and advanced LO date significantly affected the timing of LS, but their effects were opposite, as the former delayed and the latter advanced the senescence. The effects of nutrient supply and LO interacted species specifically. In chestnut, the delay of senescence caused by fertilization increased with the delay of LO and was thus stronger for individuals that flushed late in the spring. On the contrary, in beech the delay of senescence caused by fertilization decreased with the delay of LO and was insignificant for individuals with the latest LO. The experimental findings for beech were confirmed with mature trees at a regional scale. The interactive effect between nutrients and LO on senescence may be associated with variable sensitivity to photoperiod, growth sink limitation and/or direct effect of foliar nutrition on the timing of senescence. Our novel results show that the interactive effects of LO and nutrient supply on the timing of LS should be further addressed experimentally in forthcoming studies. It would also be interesting to consider our results in the further development of phenological models used in assessing the effects of climatic change. The differences found in the present study between horse chestnut and beech suggest that the results found for one species cannot necessarily be generalized to other species, so studies with different temperate tree species are called for.
Microbiota Associated with Sclerotia of Soilborne Fungal Pathogens – A Novel Source of Biocontrol Agents Producing Bioactive Volatiles
Authors: Mülner Pascal , Bergna Alessandro , Wagner Philipp , Sarajlić Dženana , Gstöttenmayr Barbara , Dietel Kristin , Grosch Rita , Cernava Tomislav , Berg Gabriele
Published: April 2019

Soilborne plant pathogens are an increasing problem in modern agriculture, and their ability to survive long periods in soil as persistent sclerotia makes control and treatment particularly challenging. To develop new control strategies, we explored bacteria associated with sclerotia of Sclerotinia sclerotiorum and Rhizoctonia solani, two soilborne fungi causing high yield losses. We combined different methodological approaches to get insights into the indigenous microbiota of sclerotia, to compare it to bacterial communities of the surrounding environment, and to identify novel biocontrol agents and antifungal volatiles. Analysis of 16S rRNA gene fragment amplicons revealed significant compositional differences in the bacterial microbiomes of Rhizoctonia sclerotia, the unaffected tuber surface and surrounding soil. Moreover, distinctive bacterial lineages were associated with specific sample types. Flavobacteriaceae and Caulobacteraceae were primarily found in unaffected areas, while Phyllobacteriaceae and Bradyrhizobiaceae were associated with sclerotia of R. solani. In parallel, we studied a strain collection isolated from sclerotia of the pathogens for emission of bioactive volatile compounds. Isolates of Bacillus, Pseudomonas, and Buttiauxella exhibited high antagonistic activity toward both soilborne pathogens and were shown to produce novel, not yet described volatiles. Differential imaging showed that volatiles emitted by the antagonists altered the melanized sclerotia surface of S. sclerotiorum. Interestingly, combinations of bacterial antagonists increased inhibition of mycelial growth up to 60% when compared with single isolates. Our study showed that fungal survival structures are associated with a specific microbiome, which is also a reservoir for new biocontrol agents.
Artificial Intelligence and Machine Learning in Anesthesiology
Authors: Connor Christopher W.
Published: April 2019

Commercial applications of artificial intelligence and machine learning have made remarkable progress recently, particularly in areas such as image recognition, natural speech processing, language translation, textual analysis, and self-learning. Progress had historically languished in these areas, such that these skills had come to seem ineffably bound to intelligence. However, these commercial advances have performed best at single-task applications in which imperfect outputs and occasional frank errors can be tolerated.

The practice of anesthesiology is different. It embodies a requirement for high reliability, and a pressured cycle of interpretation, physical action, and response rather than any single cognitive act. This review covers the basics of what is meant by artificial intelligence and machine learning for the practicing anesthesiologist, describing how decision-making behaviors can emerge from simple equations. Relevant clinical questions are introduced to illustrate how machine learning might help solve them—perhaps bringing anesthesiology into an era of machine-assisted discovery.
Compressive Pressure Versus Time in Cauda Equina Syndrome
Authors: Pronin Savva , Koh Chan Hee , Bulovaite Edita , Macleod Malcolm R. , Statham Patrick F.
Published: April 2019

Study Design.

Systematic review and meta-analysis.

Objective.

To examine the relationship between compressive pressure and its duration in cauda equina compression, and the effects of subsequent decompression, on neurophysiological function, and pathophysiology in animal studies. We further aim to investigate these relationships with systemic blood pressure to assess whether a vascular component in the underlying mechanism may contribute to the clinical heterogeneity of this disease.

Summary of Background Data.

The complex relationship between preoperative factors and outcomes in cauda equina syndrome (CES) suggests heterogeneity within CES which may inform better understanding of pathophysiological process, their effect on neurological function, and prognosis.

Methods.

Systematic review identified 17 relevant studies including 422 animals and reporting electrophysiological measures (EP), histopathology, and blood flow. Modeling using meta-regression analyzed the relationship between compressive pressure, duration of compression, and electrophysiological function in both compression and decompression studies.

Results.

Modeling suggested that electrophysiological dysfunction in acute cauda equina compression has a sigmoidal response, with particularly deterioration when mean arterial blood pressure is exceeded and, additionally, sustained for approximately 1 hour. Accounting for pressure and duration may help risk-stratify patients pre-decompression. Outcomes after decompression appeared to be related more to the degree of compression, where exceeding systolic blood pressure tended to result in an irreversible lesion, rather than duration of compression. Prognosis was most strongly associated with residual pre-decompression function.

Conclusion.

Compressive pressure influences effects and outcomes of cauda equina compression. We suggest the presence of two broad phenotypic groups within CES defined by the degree of ischaemia as a potential explanatory pathophysiological mechanism.

Level of Evidence: 1
Predictive Factors of Male Sexual Dysfunction After Traumatic Spinal Cord Injury
Authors: Ferro Josepha Karinne de Oliveira , Lemos Andrea , Silva Caroline Palácio da , Lima Claudia Regina Oliveira de Paiva , Raposo Maria Cristina Falcão , Cavalcanti Geraldo de Aguiar , Oliveira Daniella Araújo de
Published: April 2019

Study Design.

Observational study (Ethics Committee Number 973.648).

Objective.

Evaluating the social and clinical factors associated with sexual dysfunction in men with traumatic spinal cord injury, as well as predictive factors for sexual dysfunction.

Summary of Background Data.

Besides the motor and sensory loss, sexual function changes after spinal cord injury, ranging from decreased sexual desire to erectile disorders, orgasm, and ejaculation.

Methods.

Performed with 45 men, with traumatic spinal cord injury and sexually active. Sexual function was assessed by the International Index of Erectile Function and the level and degree of injury were determined following guidelines of International Standards for Neurological and Functional Examination Classification of Spinal Cord Injury. Bi and multivariate analysis was applied, with a 0.05 significance level.

Results.

Forty-five subjects with mean injury time of 7.5 years (CI 5.2–9.9) were evaluated. Having a fixed partner is a protective factor (OR: 0.25; 95% CI: 0.07–0.92) of erectile dysfunction. Sexual desire is associated with the fixed partner (OR: 0.12; 95% CI: 0.02–0.66), masturbation (OR: 0.13; 95% CI: 0.02–0.62), and sexual intercourse in the last month (OR: 0.13; 95% IC: 0.01–0.92). Ejaculation (OR: 0.01; 95% CI: 0.00–0.15) and erectile dysfunction (OR: 15.7; 95% CI: 1.38–178.58) are associated with orgasm. Psychogenic erection (OR: 0.07; 95% CI: 0.01–0.69), monthly frequency of sexual intercourse (OR: 11.3; 95% CI: 2.0–62.8), and orgasmic dysfunction (OR: 7.1; 95% CI: 1.1–44.8) are associated with satisfaction.

Conclusion.

Fixed partner, ejaculation, masturbation are protective factors for sexual dysfunction. Erectile dysfunction, orgasmic, and infrequent sex dysfunction are predictors of sexual dysfunction.

Level of Evidence: 3
Mentoring millennials in surgical education
Authors: Louie Michelle , Moulder Janelle K. , Wright Kelly , Siedhoff Matthew
Published: April 2019

Purpose of review

We seek to define the Millennial generation and identify strengths that can be employed to improve medical and surgical education and career development. We outline how generational traits can be incorporated into adult learning theory, offer suggestions for modernizing traditional teaching and mentorship models, and discuss why Millennials are ideally positioned to succeed in 21st century medicine.

Recent findings

Millennials (born ∼1981 to 1996) have several consistently identified traits that should be considered when teaching trainees and mentoring junior faculty. Millennials are technologically savvy, accustomed to accessing and assimilating large amounts of information quickly, using the electronic medical record with ease, and learning from a variety of media sources. They learn better with alternatives to traditional lectures, and respond well when given discrete goals, encouragement, and direct feedback early and often. Millennials prefer team-based learning and a flat hierarchy. Millennials are socially responsible, culturally diverse, and strive to promote diversity and work-life integration.

Although the individuals that make up the Millennial generation may not encompass each attribute associated with this cohort, collectively, this generation of physicians is positioned to usher medicine into a new era.
Online Survey of Nurses' Personal and Professional Praying
Authors: O'Connell-Persaud Shannon , Dehom Salem , Mamier Iris , Gober-Park Carla , Taylor Elizabeth Johnston
Published: April 2019

This study explored how nurses' prayer beliefs and practices are associated with their offering to pray with patients. Participants (N = 423) completed an online survey. Those with higher prayer experience scores were 9% more likely to offer prayer to patients; those working in religious settings were 2.5 times more likely offer prayer to patients.
RETINAL FLECKS IN STARGARDT DISEASE REVEAL CHARACTERISTIC FLUORESCENCE LIFETIME TRANSITION OVER TIME
Authors: Solberg Yasmin , Dysli Chantal , Escher Pascal , Berger Lisa , Wolf Sebastian , Zinkernagel Martin S.
Published: April 2019

Purpose:

Stargardt disease is the most common inherited juvenile macular dystrophy and is characterized by yellowish flecks across the posterior pole. The purpose of this study was to investigate fluorescence lifetime changes of retinal flecks over time using fluorescence lifetime imaging ophthalmoscopy.

Methods:

Longitudinal fluorescence lifetime data of 12 patients with Stargardt disease (mean age ± SEM, 42.25 ± 2.1 years; range, 28–58 years) were acquired using a fluorescence lifetime imaging ophthalmoscope based on a Heidelberg Engineering Spectralis system. Retinal autofluorescence was excited with a 470-nm laser. The emitted fluorescence was detected in two wavelength channels: a short spectral channel (498–560 nm) and a long spectral channel (560–720 nm). The mean retinal autofluorescence lifetimes were calculated and further analyzed with corresponding color fundus images, autofluorescence intensity images, and spectral domain optical coherence tomography. Patients were classified into three subtypes.

Results:

All patients with Stargardt disease displayed characteristic autofluorescence lifetime patterns. Mean fluorescence lifetime values within areas of yellow flecks were significantly prolonged (long spectral channel 484 ps) compared with the surrounding tissue (long spectral channel 297 ps). In 91.6% of the eyes, flecks with short fluorescence lifetimes (long spectral channel 255 ps) were identified. Short lifetime flecks progressed to flecks with characteristic long lifetimes in 75.1% of eyes within a mean interval of 29.2 months (range 3–45 months). Between baseline and follow-up, the rate of newly developed short lifetime flecks (number/per year) based on subtypes was 2.62 in Group 1, 1.43 in Group 2, and 0.81 in Group 3.

Conclusion:

Recent onset flecks in Stargardt disease display short fluorescence lifetimes and convert into longer fluorescence lifetime flecks over time. This transition may represent a change in the composition of retinal deposits with accumulation of lipofuscin and retinoid by-products from the visual cycle. With emerging treatment options, these findings may prove useful to monitor disease progression and therapeutic effects.
pH of Mitomycin-C Formulations for Filtration Surgery
Authors: Klifto Meredith R. , Fleischman David
Published: April 2019

Precis:

The use of mitomycin-C as a mixed formulation with lidocaine and epinephrine for filtration surgery may alter its pH and consequently affect clinical effectivity.
Exploring Hygienic Behaviors and Vulvodynia
Authors: Klann Alexandra M. , Rosenberg Jessica , Wang Tanran , Parker Samantha E. , Harlow Bernard L.
Published: April 2019

Objectives

Vulvodynia is common and characterized by vulvar discomfort and pain. However, few studies have assessed hygienic practices in relation to onset. We investigated whether hygienic behaviors were associated with the onset of vulvodynia.

Materials and Methods

We assessed a self-reported history of personal hygienic behaviors, including wearing tight-fitting clothing, vulva care and genital washing, pubic hair removal, douching, and powdering, a year before first reported onset of vulvar pain among 213 clinically confirmed cases and a similar time period among 221 general population controls.

Results

Compared with women who reported never wearing tight-fitting jeans or pants, women wearing tight-fitting jeans or pants 4 or more times per week had twice the odds of vulvodynia (95% CI = 1.14–3.95). Relative to controls, women with vulvodynia were substantially less likely to report use of soaps and gels to cleanse the vulva (95% CI = 0.17–0.63). Among women who chose to remove pubic hair, those who removed pubic hair from the mons pubis compared with bikini-area only hair removal, were 74% more likely to have vulvodynia (95% CI = 1.05–2.89). Finally, compared with women who reported bikini-area only hair removal less than monthly, those who removed hair from the mons pubis weekly or more were nearly 2 times more likely to be vulvodynia cases (95% CI = 0.83–3.49).

Conclusions

Wearing tight-fitting jeans or pants and removing hair from the mons pubis area were associated with increased odds of vulvodynia. Research on how hygienic practices could influence vulvar pain in larger and more temporally addressed populations is warranted.
Utility of mean platelet volume to predict the prevalence of coronary artery disease on coronary angiography in patients with stable angina
Authors: Lin Yangyi , Chen Xia , Xu Xiangdong
Published: April 2019

Background

Approximately 50% of patients with stable angina have coronary artery disease (CAD) on coronary angiography. The mean platelet volume (MPV) has been proposed as a marker that reflects platelet size and reactivity. This study investigated the predictive value of high MPV in patients with stable angina for diagnosing stable CAD.

Patients and methods

A total of 491 patients with chest pain who underwent selective coronary angiography for suspected CAD were enrolled. The patients were divided into the CAD group and non-CAD group according to angiography. All demographic, laboratory, and angiographic data were collected.

Results

Patients with MPV in the highest tertile were more likely to have CAD (66.9 vs. 51.0 vs. 35.7% for the highest, middle, and lowest tertiles; P = 0.001), had lower platelet counts (186 ± 48 vs. 199 ± 52 vs. 223 ± 63; P < 0.001), and had higher hemoglobin A1c levels (6.8 ± 1.5 vs. 6.5 ± 1.5 vs. 6.2 ± 1.1; P < 0.001). MPV had a positive correlation with hemoglobin A1c (r = 0.16; P < 0.001). Patients with CAD (n = 248) had higher MPV than those without CAD (n = 243) (11.0 ± 1.0 vs. 10.5 ± 0.9; P < 0.001). MPV was an independent predictor of CAD in patients with stable angina, with an adjusted odds ratio of 1.820 (95% confidence interval: 1.453–2.279; P < 0.001).

Conclusion

The presence of high MPV predicts the prevalence of CAD on coronary angiography in patients with stable angina, and this result may ultimately reduce unnecessary invasive coronary angiography.
Desensitization for sensitized patients awaiting heart transplant
Authors: Byku Mirnela , Chang Patricia P.
Published: April 2019

Purpose of review

This review summarizes contemporary desensitization strategies for patients awaiting cardiac transplantation in an era when specific management is still somewhat controversial.

Recent findings

The number of sensitized patients awaiting heart transplantation is rising. Clinical assessment of antibody levels is mostly focused on human leukocyte antigen (HLA) antibodies. Sensitization to HLA antigens increases the risk of antibody medicated rejection and cardiac allograft vasculopathy after transplant, thus translates to reduced access to compatible donors and increased wait time to transplant. Desensitization therapy is commonly considered in listed patients with cPRA more than 50%, to either decrease the amount of circulating anti-HLA antibodies, reduce the antibody production, or a combination of both. Despite promising results on specific therapies (e.g., plasmapheresis, intravenous immunoglobulin, rituximab, bortezomib), there is a significant gap in knowledge on desensitization therapies in heart transplantation. Most data are from small observational studies and extrapolated from nonheart solid organ transplants.

Management of the sensitized patient awaiting heart transplant is individualized. Desensitization can facilitate negative cross-match and successful transplantation, but is associated with significant cost and potential adverse effects. The long-term outcomes of desensitization therapy remain to be determined, further emphasizing the importance of personalizing the treatment approach to each patient.
Recent Insights Into the Pathogenic Mechanism of Pancreatitis
Authors: Gukovskaya Anna S. , Gorelick Fred S. , Groblewski Guy E. , Mareninova Olga A. , Lugea Aurelia , Antonucci Laura , Waldron Richard T. , Habtezion Aida , Karin Michael , Pandol Stephen J. , Gukovsky Ilya
Published: April 2019

Acute pancreatitis (AP) is a potentially lethal inflammatory disease that lacks specific therapy. Damaged pancreatic acinar cells are believed to be the site of AP initiation. The primary function of these cells is the synthesis, storage, and export of digestive enzymes. Beginning in the endoplasmic reticulum and ending with secretion of proteins stored in zymogen granules, distinct pancreatic organelles use ATP produced by mitochondria to move and modify nascent proteins through sequential vesicular compartments. Compartment-specific accessory proteins concentrate cargo and promote vesicular budding, targeting, and fusion. The autophagy-lysosomal-endosomal pathways maintain acinar cell homeostasis by removing damaged/dysfunctional organelles and recycling cell constituents for substrate and energy. Here, we discuss studies in experimental and genetic AP models, primarily from our groups, which show that acinar cell injury is mediated by distinct mechanisms of organelle dysfunction involved in protein synthesis and trafficking, secretion, energy generation, and autophagy. These early AP events (often first manifest by abnormal cytosolic Ca2+ signaling) in the acinar cell trigger the inflammatory and cell death responses of pancreatitis. Manifestations of acinar cell organelle disorders are also prominent in human pancreatitis. Our findings suggest that targeting specific mediators of organelle dysfunction could reduce disease severity.
Patient satisfaction with information on chemotherapy
Authors: Oosterhof Piter , Sombroek Melissa , Crul Mirjam
Published: April 2019

Introduction:

Patients, who are starting systemic treatment for an oncological disease, receive a large amount of information on their treatment at multiple time points from several different healthcare professionals. In the OLVG hospital in Amsterdam, the information provision was harmonized in a multiprofessional treatment team. Afterward, the satisfaction with drug information was measured in ambulatory patients.

Methods:

The clinical care pathway of the oncology patient who receives antineoplastic drug treatment was mapped out, identifying the different moments where information can be given and by whom. In 3 multidisciplinary meetings, the different time points for patient contact were assigned to one of the healthcare professionals and the content of the information to be given was agreed upon by the team. For measurement of patient satisfaction, the validated Satisfaction with Information about Medicines Scale (SIMS) questionnaire was used during a 1-week period at the oncology day-care department.

Results:

Information at each contact with the patient was standardized in a map of the patients’ clinical care pathway. Forty-eight patients returned a SIMS questionnaire showing a high overall satisfaction rate of 81%.

Conclusion:

This study has shown that harmonizing information provision to patients on anticancer drug treatment is feasible and results in high levels of information satisfaction in oncology patients.
Amphetamine and Clonidine Toxicity Resulting in Posterior Reversible Encephalopathy Syndrome
Authors: Minhaj Faisal Syed , Schult Rachel F. , Dvorak Peter , Nacca Nicholas
Published: April 2019

Amphetamine toxicity typically presents with hypertension and tachycardia. Conversely, clonidine acts as an agonist at central α2 and imidazoline receptors, which may cause brief initial hypertension followed by hypotension and bradycardia in overdose. We report a case of mixed ingestion resulting in posterior reversible encephalopathy syndrome (PRES) successfully treated with phentolamine.

A 17-year-old male adolescent presented to the emergency department 2 hours after ingesting up to 25 each of clonidine 0.1-mg tablets and dextroamphetamine 10 mg extended-release capsules. He reported nausea and fatigue with initial blood pressure (BP) 145/95 mm Hg and heart rate (HR) 52 beats per minute (bpm). Nine hours postingestion (HPI), the patient developed headache, photophobia, and confusion with BP 182/111 mm Hg and HR 48 bpm. A computed tomography scan of the head revealed generalized fullness of the cerebellum, upward bulging of the tentorial leaflets, effacement of the fourth ventricle, and crowding of the foramen magnum, suspicious for an atypical presentation of PRES. The patient's systolic BP rose over 200 mm Hg and treated with 2 mg of intravenous phentolamine at 14 HPI. Blood pressure decreased to 133/82 mm Hg, and HR increased to 56 bpm with improvements in headache. Following repeat doses of phentolamine, nicardipine was initiated and increased to 2.5 mg/h for 12 hours. The patient was stable with normal vital signs at 36 HPI.

The delayed presentation of hypertensive emergency with PRES may have been due to the actions of extended-release dextroamphetamine and the α2-agonistic effects of clonidine. Phentolamine was chosen for its α1-antagonism and was effective in managing symptoms.
Adherence to PrEP Among Young Men Who Have Sex With Men Participating in a Sexual Health Services Demonstration Project in Alameda County, California
Authors: Myers Janet J. , Kang Dufour Mi-Suk , Koester Kimberly A. , Udoh Ifeoma , Frazier Remi , Packard Rebecca , Kennedy Kristin , Erguera Xavier , Horowitz Jessica , Grant Robert , Burack Jeffrey H.
Published: April 2019

Background:

Young men of color who have sex with men face a continual increase in rates of HIV infection. Pre-exposure prophylaxis (PrEP) is an important prevention method for these young men.

Setting:

The Connecting Resources for Urban Sexual Health (CRUSH) demonstration project provided sexual health services, including PrEP, to young men who have sex with men aged 18–29 years. We report on adherence and factors influencing it.

Methods:

Participants were offered HIV and sexually transmitted infection testing, prevention counseling, PrEP, and when appropriate, sexually transmitted infection treatment and postexposure prophylaxis. Participants taking PrEP had erythrocyte tenofovir diphosphate and emtricitabine levels measured through dried blood spot testing at 4, 12, and 24 weeks to estimate medication adherence. Participants also completed surveys to assess demographic and psychosocial measures.

Results:

From February 2014 to November 2015, CRUSH enrolled 257 participants. Ninety-three percent started PrEP, 81% of whom initiated it at their first visit. Twelve percent required postexposure prophylaxis before starting PrEP. Adherence at protective levels was initially high with 87% demonstrating levels consistent with at least 4 doses per week at week 4, compared with 77% at the 48-week follow-up. African American race, exposure to violence, and having survival needs were associated with significantly lower levels of adherence [odds ratio (OR): 0.33; confidence interval (CI): 0.11 to 0.97, P < 0.04; OR: 0.79; CI: 0.59 to 1.04, P < 0.10; OR: 0.51; CI: 0.24 to 1.05, P < 0.07].

Conclusions:

Most young men who initiate PrEP adhere at levels that confer protection against HIV infection. Interventions should account for differences in life experiences, particularly addressing the structural challenges facing young African American men.
High Incidence of Intended Partner Pregnancy Among Men Living With HIV in Rural Uganda: Implications for Safer Conception Services
Authors: Kaida Angela , Kabakyenga Jerome , Bwana Mwebesa , Bajunirwe Francis , Muyindike Winnie , Bennett Kara , Kembabazi Annet , Haberer Jessica E. , Boum Yap , Martin Jeffrey N. , Hunt Peter W. , Bangsberg David R. , Matthews Lynn T.
Published: April 2019

Background:

Many men with HIV express fertility intentions and nearly half have HIV-uninfected sexual partners. We measured partner pregnancy among a cohort of men accessing antiretroviral therapy in Uganda.

Methods:

Self-reported partner pregnancy incidence and bloodwork (CD4, HIV-RNA) were collected quarterly. Interviewer-administered questionnaires assessed men's sexual and reproductive health annually and repeated at time of reported pregnancy (2011–2015). We measured partner pregnancy incidence overall, by pregnancy intention and by reported partner HIV serostatus. We assessed viral suppression (≤400 copies/mL) during the periconception period. Cox proportional hazard regression with repeated events identified predictors of partner pregnancy.

Results:

Among 189 men, the baseline median age was 39.9 years (interquartile range: 34.7–47.0), years on antiretroviral therapy was 3.9 (interquartile range: 0.0–5.1), and 51% were virally suppressed. Over 530.2 person-years of follow-up, 63 men reported 85 partner pregnancies (incidence = 16.0/100 person-years); 45% with HIV-serodifferent partners. By 3 years of follow-up, 30% of men reported a partner pregnancy, with no difference by partner HIV serostatus (P = 0.75). Sixty-nine percent of pregnancies were intended, 18% wanted but mistimed, and 8% unwanted. Seventy-eight percent of men were virally suppressed before pregnancy report. Men who were younger [adjusted hazard ratio (aHR): 0.94/yr; 95% confidence interval (CI): 0.89 to 0.99], had incomplete primary education (aHR: 2.95; 95% CI: 1.36 to 6.40), and reported fertility desires (aHR: 2.25; 95% CI: 1.04 to 4.85) had higher probability of partner pregnancy.

Conclusions:

A high incidence of intended partner pregnancy highlights the need to address men's reproductive goals within HIV care. Nearly half of pregnancy partners were at-risk for HIV, and one-quarter of men were not virally suppressed during periconception. Safer conception care provides opportunity to support men's health and reproductive goals, while preventing HIV transmission to women and infants.
Monoclonal antibody-based therapies for bacterial infections
Authors: Motley Michael P. , Banerjee Kasturi , Fries Bettina C.
Published: April 2019

Purpose of review

This review highlights recent developments in the development of monoclonal antibodies to treat bacterial disease, including preclinical advances and the status of current clinical trials.

Recent findings

Monoclonal antibody (mAb) therapy is becoming increasingly promising in the infectious disease field. Though bacterial exotoxins continue to be a mainstay of mAb targets, searches for protein targets on the surface of bacteria have uncovered new mechanisms of antibody-mediated action against bacteria. Additionally, surveys of the polysaccharide serotype prevalence among antibiotic-resistant bacterial populations have yielded opportunities to leverage human selective pressures to our clinical advantage. Several mAb candidates are progressing through clinical development with great promise, especially those with structures altered to provide maximum benefit. Although other clinical trials have recently proved unsuccessful, these failures and lessons from immune profiling provide opportunities to understand how vulnerabilities of certain targets may change in different disease states.

Despite the hurdles of identifying effective targets and understanding how mAbs provide protection within different infections, we show that the progress made in these fields is a positive indication of mAbs becoming more widely accepted as the future for treating bacterial infections.
Infectious causes of stroke
Authors: Jillella Dinesh V. , Wisco Dolora R.
Published: April 2019

Purpose of review

Stroke continues to be a leading cause of debility in the world. Infections have been associated with stroke, but are not considered as directly causal, and so they are not often included in the traditional stroke workup and management. They are especially important in patients with stroke of undetermined etiology, and in certain patient populations, such as young patients without traditional risk factors and immunocompromised patients.

Recent findings

There has been strong evidence for infectious conditions, such as endocarditis, and pathogens, such as varicella zoster in stroke causation, and more supportive evidence is surfacing in recent years of several organisms increasing the stroke risk or being directly causal in stroke. The evidence also seems to be pointing to the role of inflammation in increasing the risk of stroke via accelerated atherosclerosis, vasculitis and vasculopathy.

Infectious causes should be considered in the differential and work up of stroke in certain patient populations and appropriate treatments need to be initiated to minimize adverse stroke-related outcomes.
Age, But Not Repeated Exposure to Gadoterate Meglumine, Is Associated With T1- and T2-Weighted Signal Intensity Changes in the Deep Brain Nuclei of Pediatric Patients
Authors: Pozeg Polona , Forget Joachim , Meuli Reto A. , Maeder Philippe
Published: April 2019

Objectives

Current findings on gadolinium deposition in the pediatric brain due to repeated exposure to macrocyclic contrast agents are inconclusive and possibly confounded by brain maturation processes. We evaluated the longitudinal effects of repeated gadoterate meglumine exposure (Dotarem; Guerbet, Villepinte, France) on the T1- and T2-weighted signal intensity (SI) in pediatric patients, and assessed the magnitude of age-related increase in T1-weighted (and decrease in T2-weighted) SI in a control cohort without prior gadolinium exposure.

Materials and Methods

In this retrospective, double-cohort study, magnetic resonance imaging (MRI) data of 24 patients (0.7–16.4 years, M = 5.74, SD = 4.15) who received at least 10 doses of exclusively gadoterate meglumine were included in the longitudinal study. The MRI data of 190 controls (age range, 1–20 years; 10 patients/bin; bin width, 1 year) without any prior gadolinium-based contrast exposure were included in the control, cross-sectional study to assess the age-dependent SI changes in the regions of interest (ROIs). We measured SI (native), T1-weighted gradient echo, and T2-weighted fast spin-echo of 12 deep brain nuclei. The ROIs were measured at each of the first 11 MRI examinations of the contrast-exposed patients and in the control subject's MRI. Regions of interest's SIs, normalized by the pons, were analyzed with mixed effects models, accounting for the potential confounding factors, such as radiotherapy and chemotherapy.

Results

The number of gadoterate meglumine administrations had no effect on the SI increase in any of the ROIs (all P > 0.05), but age significantly correlated with increased SI in T1-weighted globus pallidus (GP; P < 0.01) and caudate (P < 0.05), and with decreased SI in T2-weighted GP (P < 0.001) and dentate nucleus (P < 0.005) in the contrast-exposed group. The cross-sectional analyses of the control cohort showed a significant age-dependent T1-weighted SI increase in multiple ROIs, including the GP and caudate, and decrease in the T2-weighted GP and dentate nucleus (P < 0.05).

Conclusions

Repeated exposure to gadoterate meglumine was not associated with brain hyperintensity in the pediatric patients, whereas age importantly contributed to the SI changes in several deep brain nuclei.