bluuebunny/crossref_metadata_2025 huggingface dataset:
Spinal problems
Authors: Sivan Manoj , Phillips Margaret , Baguley Ian , Nott Melissa
Published: August 2019

Low back and neck pain are extremely common symptoms in modern societies. The pain may result from abnormalities occurring within the trunk muscles, the vertebrae, the intervertebral discs, the facet joints, and the ligaments and from the spinal canal and the nerve roots themselves. Pain may also be referred from distant sites—such as the abdomen—and in some cases may be functional or psychogenic in nature. Pain can be described as acute or chronic; pain present for more than 3 months is considered as chronic. This chapter describes the assessment and management of different types of back pain.
Opportunities and Challenges of the Phenotypic Heterogeneity of Major Depressive Disorder
Authors: Demyttenaere Koen
Published: August 2019

Major depressive disorder is a very heterogeneous disorder and the assessment tools most frequently used are at least as heterogeneous but, moreover, do not well represent the diagnostic criteria. This phenotypic heterogeneity could well be a barrier to a better neurobiological and psychopathological understanding of depression as well as to a better clinical understanding of which patient is better off with psychotherapy than with pharmacotherapy, or a better understanding of which patient is better off with which kind of psychotherapy or with which class of antidepressant. Finally, outcome with (or without) treatment is also much more heterogeneous than overall changes in scores on a depression scale or overall changes in response or remission rates suggest.
Clinical and Functional Characteristics of Cognitive Dysfunction in Major Depressive Disorder
Authors: Serra-Blasco Maria , Lam Raymond W.
Published: August 2019

Cognitive dysfunction is a cardinal symptom of depression that significantly contributes to the psychosocial and occupational impairment experienced by patients with major depressive disorder (MDD). This chapter examines the important clinical characteristics and functional impairments associated with cognitive dysfunction in patients with MDD. Although cognitive dysfunction can also be identified in first-episode MDD, depressed patients with greater illness burden (severity, recurrence) and specific subtypes (melancholic, psychotic) have more severe cognitive deficits and poorer functioning. Cognitive dysfunction can also persist during treatment of depression, even when other depressive symptoms are in remission, and can be a barrier to functional recovery. Clinicians should therefore assess, monitor, and target cognitive dysfunction in the treatment of patients with MDD to optimize their potential for full functional recovery.
The Neurobiology of Emotion–Cognition Interactions
Authors: Richter Thalia , Shackman Alexander J. , Aue Tatjana , Okon-Singer Hadas
Published: August 2019

Humans have long considered emotion and cognition as two separate mental capacities, depending on their subjective different emotional and cognitive experiences. However, evidence for the mutual modulatory relationships between emotional and cognitive functions, as well as for the neural circuits supporting these relationships, is growing substantially. In this chapter, we review the bidirectional interactions between the cognitive and emotional systems. We focus on threat-related cues and emotional states that influence a variety of attentional and executive functions, including working memory, cognitive control, and selective attention. We further elaborate on the flexibility of cognitive biases toward emotional information, as well as the plasticity of the neural connections supporting these biases. We discuss the influence of cognitive strategies on emotions. Finally, we highlight several limitations of existing research and suggest future scientific directions. Each of these themes is demonstrated among healthy individuals, at-risk populations, and patients with psychiatric disorders. Understanding the mutual influences between emotion and cognition is highly important for both theoretical and clinical knowledge. It may refine our expertise regarding the human mind, as well as contribute to the development of specific interventions for individuals with disorders involving disruption to emotional and cognitive systems.
Clinical Characteristics of Social Cognitive Processes in Major Depressive Disorder
Authors: Foerster Katharina , Joergens Silke , Baune Bernhard T.
Published: August 2019

Dysfunctional social cognition describes an important symptom of major depressive disorder (MDD). This dysfunction relates to various aspects of perception of emotional states in oneself and in others, but also applies to complex situations such as social communication. The majority of evidence supports a theory that patients with MDD show a negative bias towards ambiguous emotional information in all domains of social perception. It appears that social cognitive function varies in the course of MDD due to treatment and symptom severity. Therefore, social cognitive dysfunction often presents as a subtle phenomenon vulnerable to further disturbing influences by confounding variables. Analyses often do not consider important confounders such as symptom severity and type of treatment. Social cognitive research uses a broad spectrum of measurements with varying quality of standard psychometric criteria. Future investigations should use standardized measures with large normative samples to avoid distortions of results.
Pharmacological Interventions for Cognitive Dysfunction in Major Depressive Disorder
Authors: Solmi Marco , Bortolato Beatrice , Veronese Nicola , Stubbs Brendon , Herrmann Nathan , Carvalho Andre F.
Published: August 2019

Major depressive disorder (MDD) is a severe, chronic, and recurring mental disorder, which is frequently accompanied by co-occurring mental and somatic illnesses. Compelling evidence indicates that patients with MDD exhibit cognitive impairment encompassing several domains, including but not limited to, executive function, verbal memory, and attention. In addition, cognitive impairment may be evident even during remission and appears to play a major role in the persistence of psychosocial dysfunction (including impairment in workforce). Therefore, several compounds have been tested as putative cognitive enhancers for MDD. Although antidepressant treatment may be associated with modest improvements in some cognitive domains (namely psychomotor speed and delayed recall), evidence thus far remains unclear owing to methodological limitations across clinical trials. These methodological limitations include: (i) lack of adequate screening for cognitive dysfunction at baseline; (ii) the inclusion of samples that were not in remission at baseline; pseudospecificity (i.e. observed effects on cognition could be due to secondary improvement in mood); (iii) cognitive function was not the primary outcome in some trials; and (iv) lack of standardization of cognitive measures employed across studies. Replicated evidence from randomized controlled trials (RCTs) indicates that vortioxetine and duloxetine may have procognitive effects. Furthermore, data from RCTs suggest that lisdexamfetamine, modafinil, metformin, and erythropoietin may also have beneficial cognitive effects. In conclusion, the achievement of cognitive remission remains an unmet goal in the treatment of MDD. Future research directions, including methodological improvements in the conduct of RCTs targeting MDD-related cognitive dysfunction, are discussed.
Head and neck surgical oncology
Authors: Breeze Johno , Parmer Sat , McLeod Niall
Published: August 2019

This chapter contains eight clinical vivas on the subject of head and neck surgical oncology. This will provide candidates sitting the vivas component of the Oral and Maxillofacial Surgery FRCS examination with practical knowledge in the assessment and treatment of cancer presenting in the head, face, and neck region. It will also provide insight for clinicians in allied specialties, such as otolaryngology and plastic surgery, in how to engage in a debate with a senior clinician in the contemporary management of such complex cases.
Head and neck trauma
Authors: Breeze Johno , Parmer Sat , McLeod Niall
Published: August 2019

This chapter contains eight clinical vivas on the subject of head, face, and neck trauma. This will provide candidates sitting the vivas component of the Oral and Maxillofacial Surgery FRCS examination with practical knowledge in the assessment and treatment of trauma presenting in the head, face, and neck region. It will also provide insight for clinicians in allied specialties, such as otolaryngology and plastic surgery, in how to engage in a debate with a senior clinician in the contemporary management of such complex cases.
Craniofacial surgery
Authors: Breeze Johno , Parmer Sat , McLeod Niall
Published: August 2019

This chapter contains eight clinical vivas on the subject of congenital and craniofacial surgery. This will provide candidates sitting the vivas component of the Oral and Maxillofacial Surgery FRCS examination with practical knowledge in the assessment and treatment of congenital conditions presenting in the craniofacial region. These include craniosynostosis and predisposing conditions, hemifacial microsomia, and vascular anomalies. It will also provide insight for clinicians in allied specialties, such as otolaryngology and plastic surgery, in how to engage in a debate with a senior clinician in the contemporary management of such complex cases.
Implants
Authors: Breeze Johno , Parmer Sat , McLeod Niall
Published: August 2019

This chapter contains eight clinical vivas on the subject of oral implantology. This will provide candidates sitting the vivas component of the Oral and Maxillofacial Surgery FRCS examination with practical knowledge in the assessment of alveolar ridge deficiency and treatment using bone grafts and osseointegrated implants. It will also provide insight for clinicians in allied specialties, such as otolaryngology and plastic surgery, in how to engage in a debate with a senior clinician in the contemporary management of such complex cases.
On the triple-star origin of the planetary nebula Sh 2-71
Authors: Jones David , Pejcha Ondřej , Corradi Romano L M
Published: August 2019

Recent studies have indicated that triple-star systems may play a role in the formation of an appreciable number of planetary nebulae, however, only one triple central star is known to date (and that system is likely too wide to have had much influence on the evolution of its component stars). Here, we consider the possibility that Sh 2-71 was formed by a triple system that has since broken apart. We present the discovery of two regions of emission, seemingly aligned with the proposed tertiary orbit (i.e. in line with the axis formed by the two candidate central star systems previously considered in the literature). We also perform a few simple tests of the plausibility of the triple hypothesis based on the observed properties (coordinates, radial velocities, distances, and proper motions) of the stars observed close to the projected centre of the nebula, adding further support through numerical integrations of binary orbits responding to mass loss. Although a number of open questions remain, we conclude that Sh 2-71 is currently one of the best candidates for planetary nebula formation influenced by triple-star interactions.
ESTE ANNUAL IMPACTS—SYSTEM FOR ASSESSMENT OF RADIOLOGICAL IMPACTS OF OPERATIONAL DISCHARGES FROM NUCLEAR FACILITIES
Authors: Lipták Ľudovít , Fojcíková Eva , Krpelanová Monika , Chylý Miroslav , Čarný Peter
Published: August 2019

Described are models and approaches of the software tool ESTE Annual Impacts, a system for analyzes of radiological impacts of operational discharges to the atmosphere and hydrosphere from nuclear facilities. As a result, evaluated are radiological impacts to the population (to representative person and collective doses) and the environment (plants and animals). Described are models applied for calculation of dispersion in the atmosphere and hydrosphere (river, dam, sea). Method of application of sea currents for dispersion calculation in marine environment is also presented. The system is used by operators of the operated and decommissioned nuclear facilities at the site Bohunice (Slovakia), by regulatory authority of the Czech Republic for facilities at the sites Dukovany and Temelín and by operator of the Bushehr Nuclear Power Plant (Iran). In addition, the system is tool for analyses of environmental impacts assessments, applied in environmental impacts assessments process for newly prepared nuclear sources in Slovakia and Czech Republic.
EMERGENCY PREPAREDNESS OF GAMMA SPECTROMETRY LABORATORIES
Authors: Sloboda Michal , Malá Helena , Rulík Petr , Bečková Věra
Published: August 2019

Currently, the territorial Radiation Monitoring Network (RMN) of the Czech Republic consists of seven laboratories equipped with gamma spectrometry High Purity Germanium (HPGe) detectors. From 2007 to 2018, five emergency exercises were carried out to test the sample throughput of these facilities and their staff. The main objective was to identify weaknesses and problem areas in the whole process from the moment of obtaining the samples to logging the results into the central RMN database. The long-term aim of these exercises is to optimize emergency response procedures. The most important factor limiting laboratory capacity is the lack of qualified personnel. The exercises showed that in the current state, these laboratories would be able to operate in 12-hour shifts for 14 days and analyze 1700 samples per day. Emergency exercises have highlighted the fact that this type of exercise should be repeated periodically in order to monitor the performance and analytical capabilities of RMN.
Population Genetics of Fusarium graminearum at the Interface of Wheat and Wild Grass Communities in New York
Authors: Fulcher Michael R. , Winans James B. , Quan Menchus , Oladipo Eniola D. , Bergstrom Gary C.
Published: August 2019

Fusarium graminearum is primarily understood as an agricultural pathogen affecting cereal crops, but its host range also includes diverse, noncultivated grasses ubiquitous across agricultural and natural environments. Wild grasses may select for the production of diverse toxin variants (chemotypes) and serve as reservoirs of genetic diversity or sources of disease-inciting inoculum. Populations at the intersection of wheat and wild grass communities were described using 909 isolates collected from wheat spikes, wild grass spikes, and overwintered wild grass stems found at natural and agricultural sites in regions of high and low crop production. Trichothecene (TRI) genotypes correlated to pathogen chemotype were predicted from two loci, and multilocus genotypes (MLGs) were determined using eight microsatellite loci. The genetic diversity of wild grass and wheat-derived populations was comparable, and their differentiation was low. Duplicate MLGs were rare even in samples collected from a single square meter, although they could be found in multiple hosts, environments, regions, and years. TRI genotype frequencies differed between region and land use. Admixture between TRI genotype-defined populations, which correspond to three previously described sympatric North American populations, was detected and was highest in a region with remote host communities and little agricultural production. Nonagricultural environments may maintain different pathogen TRI genotypes than wheat fields and provide an opportunity for recombination between isolates from different F. graminearum populations. A lack of structural barriers suggests that pathogen gene flow is uninhibited between wheat and wild grass communities, and the recovery of putative clones from multiple hosts and environments provides initial evidence that noncultivated grasses are a source of local and regional inoculum.
Characterizing the Risk of Long-Term Opioid Utilization in Patients Undergoing Lumbar Spine Surgery
Authors: Wright Anna K. , Sikora Matt , Leveque Jean-Christophe
Published: August 2019

Study Design.

Single-institution retrospective cohort study.

Objective.

To determine whether prescribing practices at discharge are associated with opioid dependence (OD) in patients undergoing discectomy or laminectomy procedures for degenerative indications.

Summary of Background Data.

Long-term opioid use in spine surgery is associated with higher healthcare utilization and worse postoperative outcomes. The impact of prescribing practices at discharge within this surgical population is poorly understood.

Methods.

A query of an administrative database was conducted to identify all patients undergoing discectomy or laminectomy procedures at our high-volume tertiary referral center between 2007 and 2016. For patients included in the analysis, opioid prescription data on admission and discharge were manually abstracted from the electronic health record, including opioid type, frequency, route, and dose, and then converted to daily morphine equivalent dose (MED) values. We defined OD as a consecutive narcotic prescription lasting for at least 90 days within the first 12 months after the index surgical procedure.

Results.

Of the 819 total patients, 499 (60.9%) patients had an active opioid prescription before surgery. Postoperatively, 813 (99.3%) received at least one narcotic prescription within 30 days of index surgery, and 162 (19.8%) continued with sustained opioid use in the 12 months after surgery. In adjusted analysis, patients with OD had a higher incidence of preoperative depression (P = 0.012) and preoperative opioid use (P < 0.001), as well as a higher frequency of preoperative benzodiazepine prescriptions (P = 0.009), and discharge MED value exceeding 120 mg/day (P = 0.013). Postoperative OD was observed in 7.5% of previously opioid-naïve patients.

Conclusion.

This is the first study to test for an association between MED values prescribed at discharge and sustained opioid use after lumbar spine surgery. In addition to previously reported risk factors, discharge prescription dose exceeding 120 mg/day is independently associated with OD after spine surgery.

Level of Evidence: 3
Recurrent Proximal Junctional Kyphosis
Authors: Kim Han Jo , Wang Shan-Jin , Lafage Renaud , Iyer Sravisht , Shaffrey Christopher , Mundis Gregory , Hostin Richard , Burton Douglas , Ames Christopher , Klineberg Eric , Gupta Munish , Smith Justin , Schwab Frank , Lafage Virginie
Published: August 2019

Study Design.

Retrospective comparative cohort study.

Objective.

Assess the incidence, risk factors, and outcomes of recurrent proximal junctional kyphosis (r-PJK) in PJK revision patients.

Summary of Background Data.

Several studies have identified the incidence and risk factors for PJK after primary surgery. However, few studies have reported on PJK recurrence after revision for PJK.

Methods.

A multicenter database of patients who underwent PJK revision surgery with minimum 2-year follow-up was analyzed. Demographic, operative, and radiographic outcomes were compared in patients with r-PJK and patients without recurrence no-Proximal Junctional Kyphosis (n-PJK). Postoperative Scoliosis Research Society-22r, Short Form-36, and Oswestry Disability Index were compared. Preoperative and most recent spinopelvic, cervical, and cervicothoracic radiographic parameters were compared. Univariate and multivariate analyses were used to determine r-PJK risk factors. A predictive model was formulated based on our logistic regression analysis.

Results.

A total of 70 patients met the inclusion criteria with an average follow-up of 21.8 months. The mean age was 66.3 ± 9.4 and 80% of patients were women. Before revision, patients had a proximal junctional angle angle of −31.7° ± 15.9°. The rate of recurrent PJK was 44.3%. Logistic regression showed that pre-revision thoracic pelvic angle (odds ratio [OR]: 1.060 95% confidence interval [CI] 1.002; 1.121; P = 0.042) and prerevision C2-T3 sagittal vertical axis (SVA; OR: 1.040 95% CI [1.007; 1.073] P = 0.016) were independent predictors of r-PJK. Classification with these parameters yielded an accuracy of 72.7%, precision of 80.6%, and recall of 73.5%. When examining correction, or change in alignment with revision surgery, we found that change in SVA (OR: 0.981 95% CI [0.968; 0.994] P = 0.005) was the only predictor of r-PJK with accuracy of 66.7%, precision of 74.2%, and recall of 69.7%.

Conclusion.

Patients after PJK revision surgery had a recurrence rate of 44%. Logistic regression based on the prerevision variables showed that prerevision thoracic pelvic angle and prerevision C2-T3 SVA were independent predictors of r-PJK.

Level of Evidence: 4
Ultrasound-guided intra-articular triamcinolone acetonide injection for treating refractory small joints arthritis of rheumatoid arthritis patients
Authors: Wang Shaokun , Wang Xianbin , Liu Ying , Sun Xiaofeng , Tang Yanchun
Published: August 2019

To investigate the efficiency and clinical safety of intra-articular triamcinolone acetonide (TA) injection under the guide of ultrasonography combined with standard treatment for treating refractory small joints arthritis in rheumatoid arthritis (RA) patients.

TA was injected upon confirmation of the needle inserting into the articular cavity. The dose was 40 mg for the wrist, 20 mg for the metacarpophalangeal (MCP) joint and 20 mg for the proximal interphalangeal (PIP) joint, respectively. Visual analogue scale (VAS) for joint pain, swelling, tenderness, synovial hyperplasia and power Doppler signal scores were evaluated at pretreatment, and post-treatment 24 hours, 1 week, 4 weeks as well as 12 weeks.

The VAS for pain and tenderness scores showed gradual improvement at 24 hours, 1 week, 4 weeks and 12 weeks after treatment compared with the baseline levels (P’ < .005). The swelling showed no changes at 24 hours after treatment compared with the baseline, and showed gradual improvement at 1 week, 4 weeks and 12 weeks after treatment (P’ < .005). Significant decrease was noticed in the synovial hyperplasia score at 4 weeks and 12 weeks compared with the baseline level. Power Doppler signal score showed significant decrease at post-treatment 24 hours, which showed further decrease at 1 week and 4 weeks.

Ultrasound-guided intra-articular TA injection is effective for treating RA patients with refractory small joints arthritis without changing the original treatment plan.
Immune adjuvant therapy using Bacillus Calmette–Guérin cell wall skeleton (BCG-CWS) in advanced malignancies
Authors: Nishida Sumiyuki , Tsuboi Akihiro , Tanemura Atsushi , Ito Toshinori , Nakajima Hiroko , Shirakata Toshiaki , Morimoto Soyoko , Fujiki Fumihiro , Hosen Naoki , Oji Yusuke , Kumanogoh Atsushi , Kawase Ichiro , Oka Yoshihiro , Azuma Ichiro , Morita Satoshi , Sugiyama Haruo
Published: August 2019

The cell wall skeleton of Bacillus Calmette–Guérin (BCG-CWS) is a bioactive component that is a strong immune adjuvant for cancer immunotherapy. BCG-CWS activates the innate immune system through various pattern recognition receptors and is expected to elicit antigen-specific cellular immune responses when co-administered with tumor antigens. To determine the recommended dose (RD) of BCG-CWS based on its safety profile, we conducted a phase I dose-escalation study of BCG-CWS in combination with WT1 peptide for patients with advanced cancer.

The primary endpoint was the proportion of treatment-related adverse events (AEs) at each BCG-CWS dose. The secondary endpoints were immune responses and clinical effects. A BCG-CWS dose of 50, 100, or 200 μg/body was administered intradermally on days 0, 7, 21, and 42, followed by 2 mg of WT1 peptide on the next day. For the escalation of a dose level, 3 + 3 design was used.

Study subjects were 18 patients with advanced WT1-expressing cancers refractory to standard anti-cancer therapies (7 melanoma, 5 colorectal, 4 hepatobiliary, 1 ovarian, and 1 lung). Dose-limiting toxicity occurred in the form of local skin reactions in 2 patients at a dose of 200 μg although no serious treatment-related systemic AEs were observed. Neutrophils and monocytes transiently increased in response to BCG-CWS. Some patients demonstrated the induction of the CD4+ T cell subset and its differentiation from the naïve to memory phenotype, resulting in a tumor response.

The RD of BCG-CWS was determined to be 100 μg/body. This dose was well tolerated and showed promising clinical effects with the induction of an appropriate immune response.
Identifying the superior surgical procedure for endometrial cancer
Authors: Yin Min , Cai Yitong , Zhou Li
Published: August 2019

Background:

Endometrial cancer (EC) is one of the most common gynecologic tumors, with a high incidence in developed countries. Although the overall prognosis is good, some women have invasive tumors, the risk of recurrence, and death is high. The common surgical methods used in EC are total-abdominal hysterectomy (TAH), total-vaginal hysterectomy (TVH), laparoscopic-assisted vaginal hysterectomy (LAVH), and total-laparoscopic hysterectomy (TLH) including both conventional and robotically assisted.

Methods:

The literature search was performed in The Cochrane Central Register of Controlled Trials, PubMed, Web of Science, and Embase. The randomized controlled trials (RCTs) will be included. The search date is until June 2019. The risk of bias of included RCTs was assessed by 2 investigators according to the Cochrane Collaboration's tool. Network meta-analysis will be conducted by R software.

Results:

This study is ongoing and the results will be submitted to a peer-reviewed journal for publication.

Conclusion:

This network meta-analysis will provide clinical staff with current and reliable information on the best surgical approach for EC. Ethical approval is not applicable, since this is a network mate-analysis based on published articles. The protocol has been registered on PROSPERO under the number CRD42019128094.
Angiotensin axis blockade, acute kidney injury, and perioperative morbidity in patients undergoing colorectal surgery
Authors: Bonavia Anthony , Javaherian Milad , Skojec Alexander J. , Chinchilli Vernon M. , Mets Berend , Karamchandani Kunal
Published: August 2019

Patients undergoing surgery and taking angiotensin converting enzyme inhibitors (ACEi) or angiotensin receptor blockers (ARB) are susceptible to complications related to intraoperative hypotension. Perioperative continuation of such medications in patients undergoing colorectal surgery may be associated with more harm than benefit, as these patients are often exposed to other risk factors which may contribute to intraoperative hypotension. Our objectives were to assess the incidence and severity of postinduction hypotension as well as the rates of acute kidney injury (AKI), 30-day all-cause mortality, 30-day readmission, and hospital length of stay in adult patients undergoing colorectal surgery who take ACEi/ARB.

We performed a retrospective chart review of patients undergoing colorectal surgery of ≥4 hour duration at a tertiary care academic medical center between January 2011 and November 2016. The preoperative and intraoperative characteristics as well as postoperative outcomes were compared between patients taking ACEi/ARB and patients not taking these medications.

Of the 1020 patients meeting inclusion criteria, 174 (17%) were taking either ACEi or ARB before surgery. Patients taking these medications were more likely to receive both postinduction and intraoperative phenylephrine and ephedrine. The incidences of postoperative AKI (P 
= .35), 30-day all-cause mortality (P 
= .36), 30-day hospital readmission (P 
= .45), and hospital length of stay (P 
= .25), were not significantly different between the 2 groups.

Our results support the current recommendation that ACEi/ARB use is probably safe within the colorectal surgery population during the perioperative period. Intraoperative hypotension should be expected and treated with vasopressors.
Portal Use Among Patients With Chronic Conditions
Authors: Reed Mary E. , Huang Jie , Millman Andrea , Graetz Ilana , Hsu John , Brand Richard , Ballard Dustin W. , Grant Richard
Published: August 2019

Background:

Personal health records offer patients access to view their own health information and to manage their care online through secure patient portal tools. Little is known about the patient-reported experience in using health portals to manage chronic conditions.

Objective:

In a patient-centered research study, we examined how using portal tools affects patient health care experiences among patients with chronic conditions. We also examined barriers among nonportal users.

Research Design:

A cross-sectional patient survey.

Subjects:

Patients with a chronic condition in an integrated delivery system offering a patient portal.

Measures:

Respondents reported barriers, preferences, and experiences in using the patient portal, and whether using the portal changed their overall health.

Results:

Among all the 1824 respondents (70% response rate), portal nonusers reported preferring in-person health care (54%) or experiencing internet access barriers (41%). Portal users reported that using the portal was convenient (90%), the information available was useful (92%), and that it integrated well with other health care (92%). Among users, 31% reported that using the portal had improved their overall health. After adjustment, patients were significantly more likely to report that portal use improved their health if they had also reported convenience, information usefulness, or integration with other care (P<0.05). Reassuringly, patient-reported impacts on overall health did not vary by patient characteristics (including age, race, sex, education, income, complex conditions).

Conclusion:

Patients with chronic conditions using the portal reported convenience, information usefulness, and integration of the patient portal with their health care; these may act as potential pathways improving health.
Development and Pilot Testing of MyGoutCare
Authors: Khanna Puja , Berrocal Veronica , An Larry , Khanna Dinesh
Published: August 2019

Background

Management guidelines have identified unmet educational needs in gout patients. Our objective was to develop and pilot test MyGoutCare (MGC©)—a web-based, interactive educational resource for gout patients, tailored to improve knowledge.

Methods

The website was developed with input from patients and experts. A health informatics expert tailored content areas so the patient could walk through a journey to learn various aspects of gout. During the pilot study, patients completed baseline demographics and a 10-item validated gout knowledge questionnaire. After reviewing the website, patients completed a post-survey within 2 weeks of their physician visit. Data were analyzed using paired t-tests and effect size (ES) was calculated for the changed scores.

Results

Gout patients and experts agreed on these content areas—triggers of flares, comorbidities, pharmacologic and non-pharmacologic treatment, healthy gout diet, and lifestyle choices. In the pilot study, 50 patients (mean age of 54 years, mean disease duration of 9.5 years, and mean 3–5 flares/year) were recruited. Their post-survey scores (0–10) on knowledge questions improved significantly when compared to pre-survey scores with mean (SD) of 1.95 (1.76) p < 0.0001, ES = 0.95. Patients identified actionable changes moving forward after reviewing the website—decision to continue lifelong urate-lowering therapy, complying with periodic monitoring of serum urate, and making dietary changes.

Conclusions

Web-based platforms that offer patient-focused materials can serve as a practical tool to address ongoing educational needs of gout patients. Additional studies are needed to evaluate if the website can improve patient–physician communication and lead to better long-term outcomes.
First report of Lasiodiplodia pseudotheobromae keratitis susceptible to voriconazole in an Indian mango grower
Authors: Vanam Hari Pankaj , Ather Mohammed , Madhura K. S. , Rudramurthy Shivprakash Mandya
Published: August 2019

The family Botriosphaeriacea comprises cosmopolitan endophytic fungi and many of the genera have frequently been implicated in causing human infections, including subcutaneous infection, sinusitis, invasive mycoses and keratitis. Among them, the genus Lasiodiplodia, which contains >30 species, is grouped as coelomycetous fungi with prototype species Lasiodiplodia theobromae as an important cause of keratitis. Several cryptic species morphologically resembling L. theobromae exist, one of which is Lasiodiplodia pseudotheobromae. We present a rare case of mycotic keratitis in an Indian mango grower following penetrating trauma to the left eye. Direct microscopy revealed retractile hyphal elements, and fungal cultures yielded a dematiaceous mould which was confirmed by sequencing as L. pseudotheobromae. Antifungal susceptibility testing revealed low MICs to amphotericin B and voriconazole and increased MICs to itraconazole and posaconazole. This is the first report of phytopathogenic L. pseudotheobromae keratitis, successfully treated with 2 % voriconazole without keratoplasty.
Diet-derived fruit and vegetable metabolites suggest sex-specific mechanisms conferring protection against osteoporosis in humans
Authors: Mangano Kelsey M. , Noel Sabrina E. , Lai Chao-Qiang , Christensen Jacob J. , Ordovas Jose M. , Dawson-Hughes Bess , Tucker Katherine L. , Parnell Laurence D.
Published: August 2019

The impact of nutrition on the metabolic profile of osteoporosis is incompletely characterized. The objective of this cross-sectional study was to detangle the association of fruit and vegetable (FV) intakes with osteoporosis prevalence. Dietary, anthropometric and blood plasma metabolite data were examined from the Boston Puerto Rican Osteoporosis Study, a cohort of 600 individuals (age 46-79yr). High FV intake was protective against osteoporosis prevalence. Associations of 525 plasma metabolites were assessed with fruit and vegetable intake, and separately with osteoporosis status. Several biological processes affiliated with the FV-associating metabolites, including caffeine metabolism, carnitines and fatty acids, and glycerophospholipids. For osteoporosis-associated metabolites, important processes were steroid hormone biosynthesis in women, and branched-chain amino acid metabolism in men. In all instances, the metabolite patterns differed greatly between sexes, arguing for a stratified nutrition approach in recommending FV intakes to improve bone health. Factors derived from principal components analysis of the FV intakes were correlated with the osteoporosis-associated metabolites, with high intake of dark leafy greens and berries/melons appearing protective in both sexes. These data warrant investigation into whether increasing intakes of dark leafy greens, berries and melons causally affect bone turnover and BMD among adults at risk for osteoporosis via sex-specific metabolic pathways, and how gene-diet interactions alter these sex-specific metabolomic-osteoporosis links.
Genetic Background Dictates Aortic Fibrosis in Hypertensive Mice
Authors: Spronck Bart , Latorre Marcos , Mehta Sameet , Caulk Alexander W. , Ramachandra Abhay B. , Murtada Sae-Il , Rojas Alexia , He Chang-Shun , Jiang Bo , Wang Mo , Bersi Matthew R. , Tellides George , Humphrey Jay D.
Published: August 2019

Many genetic mutations affect aortic structure and function in mice, but little is known about the influence of background strain. We phenotyped aortas from C57BL/6J and 129SvEv mice before and after continuous infusion of angiotensin II (AngII) for two weeks, which elevated blood pressure similarly in both strains (1.34-fold vs. 1.32-fold, systolic). Excised thoracic aortas were characterized functionally using isobaric vasoactive and cyclic passive stiffness tests whereas immunohistological studies quantified altered medial and adventitial composition as well as the infiltration of pan-inflammatory CD45+ cells. Baseline aortic geometry, composition, and biomechanical properties were similar across strains, consistent with mechanical homeostasis. Yet, aortic remodeling in response to AngII-induced hypertension differed dramatically between strains, with gross maladaptive remodeling in C57BL/6J but not in 129SvEv mice. CD45+ cell density was markedly higher in C57BL/6J than 129SvEv aortas while vasoconstrictive responses to AngII were greater in 129SvEv than C57BL/6J both before and after hypertension; importantly, smooth muscle mediated vasoconstriction reduces pressure-induced wall stress. Bulk RNA sequencing, layer-specific biomechanical modeling, and growth and remodeling simulations support the emergent hypothesis that mechanical stress-mediated immune processes promote maladaptive remodeling while smooth muscle contractile processes reduce wall stress and thereby protect against fibrosis. Differentially expressed mechano-sensitive genes thus play key roles in the distinct hypertensive aortic remodeling in C57BL/6J and 129SvEv mice and must be considered when comparing studies in different background strains, particularly mixed strains that are often used to generate mice with targeted mutations.

Graphical Abstract
Rapid Detection of Genetic Engineering, Structural Variation, and Antimicrobial Resistance Markers in Bacterial Biothreat Pathogens by Nanopore Sequencing
Authors: Gargis A. S. , Cherney B. , Conley A. B. , McLaughlin H. P. , Sue D.
Published: August 2019

Widespread release of Bacillus anthracis (anthrax) or Yersinia pestis (plague) would prompt a public health emergency. During an exposure event, high-quality whole genome sequencing (WGS) can identify genetic engineering, including the introduction of antimicrobial resistance (AMR) genes. Here, we developed rapid WGS laboratory and bioinformatics workflows using a long-read nanopore sequencer (MinION) for Y. pestis (6.5h) and B. anthracis (8.5h) and sequenced strains with different AMR profiles. Both salt-precipitation and silica-membrane extracted DNA were suitable for MinION WGS using both rapid and field library preparation methods. In replicate experiments, nanopore quality metrics were defined for genome assembly and mutation analysis. AMR markers were correctly detected and >99% coverage of chromosomes and plasmids was achieved using 100,000 raw sequencing reads. While chromosomes and large and small plasmids were accurately assembled, including novel multimeric forms of the Y. pestis virulence plasmid, pPCP1, MinION reads were error-prone, particularly in homopolymer regions. MinION sequencing holds promise as a practical, front-line strategy for on-site pathogen characterization to speed the public health response during a biothreat emergency.
MKPV (aka MuCPV) and related chapparvoviruses are nephro-tropic and encode novel accessory proteins p15 and NS2
Authors: Jolly Christopher J. , Lee Quintin , Padula Matthew P. , Pinello Natalia , Williams Simon H. , O’Rourke Matthew B. , Fumagalli Marcilio Jorge , Orkin Joseph D. , Shaban Babak , Brenner Ori , Weninger Wolfgang , de Souza William Marciel , Melin Amanda D. , Wong Justin J.-L. , Crim Marcus J. , Monette Sébastien , Roediger Ben
Published: August 2019

Mouse kidney parvovirus (MKPV) is a member of the provisionalChapparvovirusgenus that causes renal disease in immune-compromised mice, with a disease course reminiscent of polyomavirus-associated nephropathy in immune-suppressed kidney transplant patients. Here we map four MKPV transcripts, created by alternative splicing, to a common transcription initiation region, and use mass spectrometry to identify “p10” and “p15” as novel chapparvovirus accessory proteins produced in MKPV-infected kidneys. p15 and a splicing-dependent putative accessory protein NS2 are conserved in all near-complete tetrapod chapparvovirus genomes currently available (from mammals, birds and a reptile). In contrast, p10 may be encoded only by viruses with >60% amino acid identity to MKPV. We show that MKPV is kidney-tropic and that the bat chapparvovirus DrPV-1 and a non-human primate chapparvovirus, CKPV, are also found in the kidneys of their hosts. We propose, therefore, that chapparvoviruses with >60% VP1 amino acid identity to MKPV be classified into a genus dubbedNephroparvovirus, which is consistent with nomenclature for the genusErythroparvovirus.
Unique transcriptional signatures of sleep loss across independently evolved cavefish populations
Authors: McGaugh Suzanne E. , Passow Courtney N. , Jaggard James Brian , Stahl Bethany A. , Keene Alex C.
Published: August 2019

Animals respond to sleep loss with compensatory rebound sleep, and this is thought to be critical for the maintenance of physiological homeostasis. Sleep duration varies dramatically across animal species, but it is not known whether evolutionary differences in sleep duration are associated with differences in sleep homeostasis. The Mexican cavefish,Astyanax mexicanus, has emerged as a powerful model for studying the evolution of sleep. While eyed surface populations ofA. mexicanussleep approximately eight hours each day, multiple blind cavefish populations have converged on sleep patterns that total as little as two hours each day, providing the opportunity to examine whether the evolution of sleep loss is accompanied by changes in sleep homeostasis. Here, we examine the behavioral and molecular response to sleep deprivation across four independent populations ofA. mexicanus. Our behavioral analysis indicates that surface fish and all three cavefish populations display robust recovery sleep during the day following nighttime sleep deprivation, suggesting sleep homeostasis remains intact in cavefish. We profiled transcriptome-wide changes associated with sleep deprivation in surface fish and cavefish. While the total number of differentially expressed genes was not greater for the surface population, the surface population exhibited the highest number of uniquely differentially expressed genes than any other population. Strikingly, a majority of the differentially expressed genes are unique to individual cave populations, suggesting unique expression responses are exhibited across independently evolved cavefish populations. Together, these findings suggest sleep homeostasis is intact in cavefish despite a dramatic reduction in overall sleep duration.
Cancer causes metabolic perturbations associated with reduced insulin-stimulated glucose uptake in peripheral tissues and impaired muscle microvascular perfusion
Authors: Han Xiuqing , Raun Steffen H. , Carlsson Michala , Sjøberg Kim A. , Henriquez-Olguín Carlos , Ali Mona , Lundsgaard Annemarie , Fritzen Andreas M. , Møller Lisbeth L. V. , Li Zhen , Li Jinwen , Jensen Thomas E. , Kiens Bente , Sylow Lykke
Published: August 2019

Background

Redirecting glucose from skeletal muscle and adipose tissue, likely benefits the tumor’s energy demand to support tumor growth, as cancer patients with type 2 diabetes have 30% increased mortality rates. The aim of this study was to elucidate tissue-specific contributions and molecular mechanisms underlying cancer-induced metabolic perturbations.

Methods

Glucose uptake in skeletal muscle and white adipose tissue (WAT), as well as hepatic glucose production, were determined in control and Lewis lung carcinoma (LLC) tumor-bearing C57BL/6 mice using isotopic tracers. Skeletal muscle microvascular perfusion was analyzed via a real-time contrast-enhanced ultrasound technique. Finally, the role of fatty acid turnover on glycemic control was determined by treating tumor-bearing insulin-resistant mice with nicotinic acid or etomoxir.

Results

LLC tumor-bearing mice displayed reduced insulin-induced blood-glucose-lowering and glucose intolerance, which was restored by etomoxir or nicotinic acid. Insulin-stimulated glucose uptake was 30-40% reduced in skeletal muscle and WAT of mice carrying large tumors. Despite compromised glucose uptake, tumor-bearing mice displayed upregulated insulin-stimulated phosphorylation of TBC1D4Thr642 (+18%), AKTSer474 (+65%), and AKTThr309 (+86%) in muscle. Insulin caused a 70% increase in muscle microvascular perfusion in control mice, which was abolished in tumor-bearing mice. Additionally, tumor-bearing mice displayed increased (+45%) basal (not insulin-stimulated) hepatic glucose production.

Conclusions

Cancer can result in marked perturbations on at least six metabolically essential functions; i) insulin’s blood-glucose-lowering effect, ii) glucose tolerance, iii) skeletal muscle and WAT insulin-stimulated glucose uptake, iv) intramyocellular insulin signaling, v) muscle microvascular perfusion, and vi) basal hepatic glucose production in mice. The mechanism causing cancer-induced insulin resistance may relate to fatty acid metabolism.
The Metabolic Effects of Angiopoietin-like protein 8 (ANGPLT8) are Differentially Regulated by Insulin and Glucose in Adipose Tissue and Liver and are Controlled by AMPK Signaling
Authors: Zhang Lu , Shannon Chris E. , Bakewell Terry M. , Abdul-Ghani Muhammad A. , Fourcaudot Marcel , Norton Luke
Published: August 2019

Objective

The angiopoietin-like protein (ANGPTL) family represents a promising therapeutic target for dyslipidemia, which is a feature of obesity and type 2 diabetes (T2DM). The aim of the present study was to determine the metabolic role of ANGPTL8 and to investigate its nutritional, hormonal and molecular regulation in key metabolic tissues.

Methods

The metabolism of ANGPTL8 knockout mice (ANGPTL8−/−) was examined in mice following chow and high-fat diets (HFD). The regulation of ANGPTL8 expression by insulin and glucose was quantified using a combination of in vivo insulin clamp experiments in mice and in vitro experiments in hepatocytes and adipocytes. The role of AMPK signaling was examined, and the transcriptional control of ANGPTL8 was determined using bioinformatic and luciferase reporter approaches.

Results

The ANGPTL8−/−mice had improved glucose tolerance and displayed reduced fed and fasted plasma triglycerides. However, there was no reduction in steatosis in ANGPTL8−/−mice after the HFD. Insulin acutely activated ANGPTL8 expression in liver and adipose tissue, which was mediated by C/EBPβ. Using insulin clamp experiments we observed that glucose further enhanced ANGPTL8 expression in the presence of insulin in adipocytes only. The activation of AMPK signaling potently suppressed the effect of insulin on ANGPTL8 expression in hepatocytes.

Conclusion

These data show that ANGPTL8 plays an important metabolic role in mice that may extend beyond triglyceride metabolism. The finding that insulin and glucose have distinct roles in regulating ANGPTL8 expression in liver and adipose tissue may provide important clues about the function of ANGPTL8 in these tissues.