bluuebunny/crossref_metadata_2025 huggingface dataset:
Penetrating neck trauma with common carotid artery injury caused by a percussive drill
Authors: Wang Dong , Zhao Yi , Cha Bingshan , Fang Ping , Liu Yehai
Published: May 2019

Rationale:

Penetrating neck traumas are dangerous and have a high mortality rate, particularly in patients with common carotid artery injuries. Advances in diagnostic imaging technology have shifted management of penetrating neck injuries from mandatory exploration to selective management. The question is now regarding optimal selection of auxiliary examinations to assess “stability” rapidly and guide clinics in managing such patients.

Patient concerns:

A 56-year-old man suffered neck trauma with the right common carotid artery caused by a percussive drill. The carotid artery could not be clearly displayed in computed tomography (CT) angiography imaging.

Diagnoses:

Penetrating neck trauma due to percussive drill bit with common carotid artery injury.

Interventions:

X-ray and bedside duplex ultrasound with color Doppler flow imaging were used to assess the state of trauma and the foreign body was removed under general anesthesia.

Outcomes:

The patient was discharged at postoperative day 10 with no complication. The patient had no sequelae from this injury at 6-month follow up.

Lessons:

X-ray provides a comprehensive assessment of damage, and can efficiently detect foreign bodies in the skull and cervical vertebrae. Duplex ultrasound to be a viable method to exclude macrovascular injury in unstable patients who are not eligible for computed tomography angiography (CTA) or catheter angiography imaging. Widely available duplex ultrasound and x-ray should be considered in emergency situations.
Herbal medicine Banha-sasim-tang for the treatment of functional dyspepsia protocol for a systematic review of randomized controlled trials
Authors: Ko Seok-Jae , Cho Soo-ho , Kim Keum-Ji , Kim Jin-sung , Ha Na-yeon , Park Jae-Woo
Published: May 2019

Background:

Functional dyspepsia (FD) has a high prevalence rate. The dyspeptic symptoms are not easily cured despite the availability of various conventional Western medical treatments. Banha-sasim-tang (BST) is a traditional herbal medicine that has long been used for treating FD.

Methods:

The following databases will be searched from inception to January 2019: Medline via PubMed, the Cochrane Central Register of Controlled Trials, EMBASE, Allied and Complementary Medicine Database, National Digital Science Library, Korean Medical Database (KoreaMed), Oriental Medicine Advanced Searching Integrated System, Korean Studies Information Service System, China National Knowledge Infrastructure Database, and Citation Information by Nii. Randomized controlled trials (RCTs) that used BST or herbs-added BST for treating FD will be included in the systematic review. Control groups in these RCTs will be the placebo, no-treatment, and conventional Western medicine groups. RCTs that compared BST and Western medicine combination therapy with the conventional Western medicine will also be included in the systematic review to investigate the synergistic effect of BST and Western medicine. Data extraction and evaluation of risk of bias will be performed by 2 independent investigators. The primary outcome will be the total clinical effective rate and secondary outcomes will include gastrointestinal symptom scale, visual analog scale, FD-related quality of life, electrogastrography, plasma motilin, dyspepsia-related symptom score, gastric emptying, and adverse events. RevMan version 5.3 will be used for data integration and analysis.

Results:

This systematic review will provide a high-quality integration of current evidence of BST for treating FD from several aspects including total clinical effective rate, dyspepsia-related symptoms, quality of life, and adverse events.

Conclusions:

This systematic review will provide evidence of the effectiveness and safety of BST on FD.

Ethics and dissemination:

Identifying information of the participants will not be revealed; hence, this protocol does not need ethical approval. The systematic review will be published in a peer-reviewed journal and disseminated electronically.

Trial registration number:

PROSPERO CRD42019123285.
The diagnostic performance of serum LIM homeobox transcription factor 1 alpha in patients with gastric cancer
Authors: Li Dinuo , Li Chen
Published: May 2019

The study was conducted to investigate the diagnostic performance of serum LIM homeobox transcription factor 1 alpha (LMX1A) in patients with gastric cancer (GC).

The serum level of LMX1A in GC, benign, and healthy groups was measured using quantitative real time PCR (qRT-PCR) and compared with the student t test. The associations of serum LMX1A levels with clinical parameters were analyzed with chi-square test. The diagnostic value of serum LMX1A in GC was evaluated by receiver operating characteristic (ROC) curve.

The level of serum LMX1A in GC group (1.309 ± 0.553) was significantly lower than that in the benign group (2.174 ± 0.676) and healthy group (2.598 ± 0.826) (P < .01 for both). The decreased level of LMX1A was associated with large tumor size (P = .009), positive lymph node metastasis (P = .027), and advanced TNM stages (P = .002). Receiver operating characteristic (ROC) analysis demonstrated that serum LMX1A could discriminate GC patients from the healthy individuals, with the area under the curve (AUC) of 0.889 (95% confidence interval [CI] = 0.838–0.938) combining with the sensitivity and specificity of 82.68% and 82.61%. Additionally, serum LMX1A also exhibited high accuracy in discriminating between GC patients and benign gastric disease cases (AUC = 0.842, 95% CI = 0.782–0.901), with the sensitivity of 81.89% and specificity of 72.41%.

Serum LMX1A may be an effective biomarker for early detection of GC.
Comparison of 2-point and 3-point point-of-care ultrasound techniques for deep vein thrombosis at the emergency department
Authors: Lee Ju Hyung , Lee Sun Hwa , Yun Seong Jong
Published: May 2019

Background:

To our knowledge, so far, no studies have comprehensively examined the performance of 2-point and 3-point point-of-care compression ultrasound (POCUS) in the diagnosis of lower extremity deep vein thrombosis (DVT). The aim of this meta-analysis was to compare the performance of 2-point and 3-point POCUS techniques for the diagnosis of DVT and evaluate the false-negative rate of each POCUS method.

Methods:

A computerized search of the PubMed, EMBASE, and Cochrane library databases was performed to identify relevant original articles. Bivariate modeling and hierarchical summary receiver operating characteristic modeling were performed to compare the diagnostic performance of 2-point and 3-point POCUS. The pooled proportions of the false-negative rate for each POCUS method were assessed using a DerSimonian–Laird random-effects model. Meta-regression analyses were performed according to the patient and study characteristics.

Results:

Seventeen studies from 16 original articles were included (2-point, 1337 patients in 9 studies; 3-point, 1035 patients in 8 studies). Overall, 2-point POCUS had similar pooled sensitivity [0.91; 95% confidence interval (95% CI), 0.68–0.98; P = .86) and specificity (0.98; 95% CI, 0.96–0.99; P = .60) as 3-point POCUS (sensitivity, 0.90; 95% CI, 0.83–0.95 and specificity, 0.95; 95% CI, 0.83–0.99). The false-negative rates of 2-point (4.0%) and 3-point POCUS (4.1%) were almost similar. Meta-regression analysis showed that high sensitivity and specificity tended to be associated with an initial POCUS performer (including attending emergency physician > only resident) and separate POCUS training for DVT (trained > not reported), respectively.

Conclusion:

Both 2-point and 3-point POCUS techniques showed excellent performance for the diagnosis of DVT. We recommend that POCUS-trained attending emergency physicians perform the initial 2-point POCUS to effectively and accurately diagnose DVT.
A case of Kawasaki disease presenting with parotitis
Authors: Li Yanchun , Yang Qingran , Yu Xiuhua , Qiao Hongmei
Published: May 2019

Rationale:

Kawasaki disease affects multiple organ systems. Its typical symptoms include fever, rash, oropharyngeal mucosal erythema, bilateral non-exudative conjunctivitis, cervical lymphadenopathy, extremity changes, and membranous desquamation of the fingers and toes. In severe cases, cardiovascular, respiratory, musculoskeletal, gastrointestinal, neurological, and genitourinary complications may occur. In the early stage, Kawasaki disease is often manifested by uncommon symptoms, such as pyuria, meningitis, shock, and retropharyngeal or parapharyngeal abscess, which may delay diagnosis and treatment. We have reported a case of Kawasaki disease presenting with mumps and reviewed the clinical features of 14 other similar cases, in order to facilitate the early diagnosis and treatment of this unusual presentation of Kawasaki disease.

Patient concerns:

A 10-year-old boy presented with persistent fever and parotitis and was diagnosed with suppurative parotitis. After antibiotic therapy, the parotid swelling reduced, but the fever persisted and other typical symptoms of Kawasaki disease appeared, including bilateral conjunctival hyperaemia, cervical lymphadenopathy, oropharyngeal mucosal erythema, membranous desquamation of the fingers, and left coronary artery widening.

Diagnoses:

The patient was diagnosed with Kawasaki disease 12 days after the onset of fever.

Interventions:

The patient was administered γ-globulin 1.0 g/kg·d for 2 consecutive days and oral aspirin 5 mg/kg·d.

Outcomes:

The left coronary artery returned to a width of 3.8 mm after 1 month and of 3.1 mm after 3 months. The dose of aspirin was reduced to 3 mg/kg·d after 2 months and to 1.5 mg/kg·d after 3 months.

Lessons:

Physicians should be aware that Kawasaki disease may develop after parotitis.
Fatty liver increases gallstone disease risk in younger Chinese patients
Authors: Li Xu , Gao Pujun
Published: May 2019

We investigated possible associations between fatty liver and gallstone disease (GD) in a Chinese population.

This cross-sectional study included 897 people who visited the clinical center and underwent ultrasonography at The First Hospital of Jilin University between January 2018 and June 2018.

The overall prevalence of GD was 8.8%; the between-sex difference (9.3% in men, 8.4% in women) was not statistically significant. The risk of GD was similar for men and women across all age groups. GD prevalence increased steadily with increasing age, from 2.1% in patients ≤30 years of age to 15.4% in those >70 years of age. Older age (≥50 years) and fatty liver were associated with GD development. Diabetes mellitus (adjusted odds ratio [AOR]: 3.066; 95% confidence interval [CI]: 1.563–6.013) was associated with GD in female but not in male subjects. In younger patients (<50 years), fatty liver (AOR: 5.268; 95% CI: 1.832–15.147) was associated with GD development.

The factors older age and fatty liver predicted GD risk in Chinese individuals. Further studies are required to explore differences in lithogenesis according to sex.
Opioid Use and Outcomes in Hospitalized Older Patients With Heart Failure Receiving and Not Receiving Hospice Referrals
Authors: Sheriff Helen M. , Arundel Cherinne , Gill Gauravpal S. , Tummala Lakshmi S. , Zeng Qing , Theisen-Toupal Jesse C. , Morgan Charity J. , Faselis Charles , Allman Richard M. , Singh Steven , Ahmed Ali
Published: May 2019

Background:

The use of opioids is associated with poor outcomes. Less is known about this association in patients with heart failure (HF) and whether it varies by the receipt of hospice care.

Methods:

Of the 7467 patients hospitalized for HF without previous opioid use, 124 received discharge opioids. We matched 123 of these patients with 123 not receiving opioids based on their propensity scores for opioid use, thus assembling a matched cohort of 246 patients balanced on 30 baseline characteristics (mean age, 76 years, 60% women, and 11% African American). We repeated the process in hospice (n = 155; 20 received opioids) and nonhospice (n = 7298; 104 received opioids) subgroups, thus assembling 2 matched cohorts of 22 and 208 patients, respectively. Hazard ratios (HRs) and 95% confidence intervals (CIs) associated with opioid use were estimated from matched cohorts.

Results:

During 8.6 (median, 1.4) years of follow-up, all-cause mortality occurred in 80% and 68% of matched patients in the opioid and nonopioid groups, respectively (HR, 1.49; 95% CI, 1.11–1.99; P = 0.008). There was evidence of heterogeneity in this association between hospice and nonhospice patients (P for interaction, 0.027). Among matched hospice and nonhospice patients, HRs (95% CIs) for mortality were 6.37 (2.06–19.69; P = 0.001) and 1.42 (1.03–1.96; P = 0.035), respectively. HRs (95% CIs) for 30-day and 1-year mortality were 1.98 (1.06–3.70; P = 0.033) and 1.72 (1.18–2.49; P = 0.004), respectively. HRs (95% CIs) for all-cause, HF, and non-HF readmissions were 1.31 (0.97–1.76; P = 0.079), 1.03 (0.71–1.49; P = 0.866), and 1.75 (1.05–2.91; P = 0.031), respectively. Readmission associations were similar among matched nonhospice patients. There was no readmission among matched hospice patients receiving opioids.

Conclusions:

In older patients with HF, opioid use is associated with a higher risk of mortality, which is greater in the hospice subgroup, and a higher risk of non-HF readmission in the nonhospice subgroup.
Antimicrobial stewardship in transplant patients
Authors: Hand Jonathan , Patel Gopi
Published: May 2019

Purpose of review

To provide an update on the current landscape of antimicrobial stewardship in solid organ transplant (SOT) recipients.

Recent findings

Constructing personalized antimicrobial prescribing approaches to avoid untoward consequences of antimicrobials while improving outcomes is an emerging and critical aspect of transplant medicine. Stewardship activities encompassing the specialized interests of transplant patients and programs are evolving. New literature evaluating strategies to optimize antimicrobial agent selection, dosing, and duration have been published. Additionally, consensus guidance for certain infectious clinical syndromes is available and should inform institutional clinical practice guidelines. Novel metrics for stewardship-related outcomes in transplantation are desperately needed. Though exciting new molecular diagnostic technologies will likely be pivotal in the care of immunocompromised patients, optimal clinical adaptation and appropriate integration remains unclear. Important studies understanding the behaviors influencing antimicrobial prescribing in organizational transplant cultures are needed to optimize interventions.

Consequences of antimicrobial use, such as Clostridiodes difficile and infections with multidrug-resistant organisms disproportionately affect SOT recipients and are associated with poor allograft and patient outcomes. Application of ASP interventions tailored to SOT recipients is recommended though further studies are needed to provide guidance for best practice.
Community-acquired respiratory viruses in solid organ transplant
Authors: Nam Hannah H. , Ison Michael G.
Published: May 2019

Purpose of review

Respiratory viruses are common in solid organ transplant (SOT) recipients and recognized as a significant cause of mortality and morbidity. This review examines the literature on influenza and noninfluenza viruses in the SOT recipient.

Recent findings

Advances in immunosuppression and antimicrobial prophylaxis have led to improved patient and graft survival, yet respiratory viruses continue to be a common cause of disease in this population. Influenza viruses have received top priority regarding prevention and treatment, whereas advances in molecular diagnostic tests detecting an array of other respiratory viruses have expanded our knowledge about the epidemiology and impact of these viruses in both the general population and SOT patients. Effective treatment and prevention for noninfluenza respiratory viruses are only emerging.

Respiratory viruses can contribute to a wide array of symptoms in SOT, particularly in lung transplant recipients. The clinical manifestations, diagnosis, and treatment options for influenza and noninfluenza viruses in SOT patients are reviewed. PCR and related molecular techniques represent the most sensitive diagnostic modalities for detection of respiratory viruses. Early therapy is associated with improved outcomes. Newer classes of antivirals and antibodies are under continuous development for many of these community acquired respiratory viruses.
Emergence of a Ph-negative Clone in a Child With Ph+ ALL
Authors: Mehrhoff Casey J. , Hemenway Charles S. , Suh Eugene
Published: May 2019

The addition of tyrosine kinase inhibitors to conventional chemotherapy has improved outcomes for pediatric patients with Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL). However, the rate of relapse is still higher compared with many other types of pediatric ALL, with many possible mechanisms for resistance. We describe an 8-year-old boy with Ph+ ALL relapsing with ALL without the Ph following treatment with dasatinib as a part of Children’s Oncology Group trial AALL1122. This emphasizes the polyclonal nature of ALL at diagnosis and indicates that the BCR-ABL fusion oncogene is not always an essential “driver” mutation.
Neurodevelopment and Exposure to Cannabis
Authors: Pressman Peter , Clemens Roger A.
Published: May 2019

This article discusses human brain development and what is known about the effects of exposure to cannabis to it. It summarizes the differences between traditional uses of cannabis and more recent uses as a drug rather than in a social context and their possible health implications. It discusses the Farm Bill’s provisions on hemp. The next article in the series will discuss the risk in the use of cannabis in food.
Prevalence of Trichomonas vaginalis Among Civilian, Noninstitutionalized Male and Female Population Aged 14 to 59 Years: United States, 2013 to 2016
Authors: Flagg Elaine W. , Meites Elissa , Phillips Christi , Papp John , Torrone Elizabeth A.
Published: May 2019

Among the US civilian noninstitutionalized population aged 14 to 59 years in 2013 to 2016, prevalence of Trichomonas vaginalis infection in urine was 1.3% overall. Prevalence was 2.1% among females, 0.5% among males, and highest at 9.6% among non-Hispanic black females. Estimate instability limited analysis of factors beyond sex, age, and race/Hispanic ethnicity.
Diagnostic Utility and Limitations of Immunohistochemistry of p16, CDK4, and MDM2 and Automated Dual-color In Situ Hybridization of MDM2 for the Diagnosis of Challenging Cases of Dedifferentiated Liposarcoma
Authors: Kobayashi Anna , Sakuma Toshiko , Fujimoto Masayo , Jimbo Naoe , Hirose Takanori
Published: May 2019

The diagnosis of dedifferentiated liposarcoma (DDLPS) is challenging when an atypical lipomatous tumor component is absent or obscure. To analyze the utility and limitations of ancillary techniques, we studied 11 cases of DDLPS in challenging conditions and 17 cases of nonlipogenic high-grade sarcomas with immunohistochemistry (IHC) for p16, CDK4, and MDM2 and automated dual-color in situ hybridization (DISH) for MDM2 amplification. All DDLPS specimens lacked clear lipogenic components and were immunoreactive for p16, CDK4, and MDM2. DISH analyses also revealed high-level amplification of MDM2 in all DDLPS. In contrast, among nonlipogenic sarcomas, p16, CDK4, and MDM2 were expressed in 8, 9, and 3 cases, respectively. MDM2 amplification was detected in 3 of 8 studied. The MDM2-amplified tumors were the same as the MDM2-immunoreactive tumors. After careful reevaluation of these 3 sarcomas, 2 were reclassified as DDLPS because small areas of lipogenic components were detected in the original specimens. The respective sensitivities and specificities of these markers were as follows: p16 IHC (100% and 60%), CDK4 IHC (100% and 53.3%), MDM2 IHC (100% and 93.3%), and MDM2 DISH (100% and 83.3%). The results of MDM2 IHC completely coincided with those of MDM2 DISH. The present study confirmed the substantial utility of MDM2 IHC and MDM2 DISH in the diagnosis of DDLPS, especially when lipogenic components were indistinct compared with IHC for p16 and CDK4. Furthermore, automated DISH was more practical than fluorescent in situ hybridization.
The Rehabilitation Research Experience for Medical Students
Authors: Mohan Manoj , Schnappinger Amy , Dicianno Brad E.
Published: May 2019

The aim of this project was to evaluate the 10-yr outcomes from the Rehabilitation Research Experience for Medical Students. A target benchmark was one high-quality output per student. Students were required to devise a research project and work full time with a mentor at an approved sponsor site for 8 wks. Longitudinal surveys were used to collect data about research outputs, match results, and decisions about whether to pursue academic careers. From 2008 to 2017, 73 (48%) of 153 applicants were awarded summer externships. Residency match results included the following: physical medicine and rehabilitation (45%), internal medicine (17%), emergency medicine (8%), orthopedic surgery (6%), neurology (6%), psychiatry (6%), OBGYN (6%), pediatrics (4%), and anesthesia (2%). The Rehabilitation Research Experience for Medical Students was successful in exceeding the target benchmark for quality scholarly output, which included 73 oral presentations at the Association of Academic Physiatrists meeting, 63 published and 20 in-review articles directly related to summer research, 5 book chapters, and 51 published and 20 in-review articles that were indirectly related to summer research. A total of 77% reported that the Rehabilitation Research Experience for Medical Students positively influenced their decision to pursue research in their future career, and 70% endorsed interest in becoming a clinician scientist.
A New Threshold for Appendicular Lean Mass Discriminates Muscle Weakness in Women With Hip Fracture
Authors: Di Monaco Marco , Castiglioni Carlotta , Bardesono Francesca , Milano Edoardo , Massazza Giuseppe
Published: May 2019

Objective

The aim of the study was to investigate the relationship between measures of muscle mass and grip strength in women with subacute hip fracture. Firstly, we aimed to assess the capability of the current thresholds for appendicular lean mass, appendicular lean mass/body mass index ratio and appendicular lean mass/height2 to separate weak and nonweak women. Secondly, we aimed to explore alternative thresholds for the three measures of muscle mass to discriminate weakness.

Design

This is cross-sectional study of 160 women with hip fracture admitted to a rehabilitation hospital. We assessed appendicular lean mass by dual-energy x-ray absorptiometry and grip strength by a Jamar hand dynamometer. Weakness was defined as grip strength of less than 16 kg.

Results

Weakness was not significantly associated with appendicular lean mass of less than 15.02 kg, appendicular lean mass/body mass index ratio of less than 0.512 or appendicular lean mass/height2 of less than 5.67 kg/m2. For appendicular lean mass (but not for the other 2 measures of muscle mass), an alternative threshold (11.87 kg instead of 15.02 kg) significantly discriminated weakness: χ2 (1, n = 160) = 10.77 (P = 0.001). The association between appendicular lean mass of less than 11.87 kg and grip strength of less than 16 kg persisted after adjustment for age and body mass index (odds ratio = 2.50, 95% confidence interval = 1.17–5.34, P = 0.018).

Conclusions

Data suggest that the current thresholds for measures of muscle mass do not discriminate weakness in women with subacute hip fracture. For appendicular lean mass, an alternative cutoff point actually separated weak and nonweak women.
The Association Between Perceived Discrimination and Allostatic Load in the Boston Puerto Rican Health Study
Authors: Cuevas Adolfo G. , Wang Kaipeng , Williams David R. , Mattei Josiemer , Tucker Katherine L. , Falcon Luis M.
Published: May 2019

Objective

Perceived discrimination is a risk factor for poor health among ethnic and racial minority groups. However, few studies have examined the association between major lifetime and everyday perceived discrimination and allostatic load (AL), a preclinical indicator of disease. We examine the association between two measures of discrimination and AL among Puerto Rican adults.

Methods

Using primarily wave 3 data from the longitudinal Boston Puerto Rican Health Study, we examined the association between major lifetime and everyday perceived discrimination and AL (multisystem dysregulation of 11 physiological components) among Puerto Rican adults residing in the Boston metro area (N = 882). Five models were tested using multivariable regression. The final model adjusted for demographic factors, migration factors, socioeconomic status and work history, health behaviors/risk factors, and depressive symptom.

Results

Respondents had a M (SD) AL score of 5.11 (1.76; range = 0–11). They had an average score of 0.21 (0.42) for major lifetime perceived discrimination (0–3) and 0.29 (0.49) for everyday perceived discrimination (0–3). In a fully adjusted model, major lifetime perceived discrimination was associated with greater AL (b = 0.56; 95% CI = 0.19 to 0.92), whereas greater everyday perceived discrimination was marginally, but not significantly, associated with lower AL (b = −0.42; 95% CI = −0.87 to 0.04).

Conclusions

Perceived discrimination remains a common stressor and may be a determinant of AL for Puerto Ricans, although the type of perceived discrimination may have differing effects. Further research is needed to better understand the ways in which major lifetime and everyday perceived discrimination operate to effect physiological systems among Puerto Ricans.
A Safety Evaluation of the Impact of Maternity-Orientated Human Factors Training on Safety Culture in a Tertiary Maternity Unit
Authors: Ansari Sophia P. , Rayfield Malissa E. , Wallis Victoria A. , Jardine Jennifer E. , Morris Edward P. , Prosser-Snelling Edward
Published: May 2019

Background

Human factors have risen to attention in maternity as key contributors to patient harm. Despite national recommendation for multidisciplinary human factors training, there is a lack of guidance and healthcare-orientated training.

Objectives

The aim of the study was to evaluate the impact of maternity-orientated human factors training program on safety culture in a tertiary maternity unit.

Methods

This prospective observational cohort study was conducted for 6 months in a tertiary maternity unit. Participants involved in high-risk intrapartum care completed the Hospital Survey of Patient Safety Culture before and after intervention. Statistical analysis was performed using the χ2 test with statistical significance at 5% (P = 0.05).

Intervention

The human factors curriculum included situational awareness, communication, decision-making, conflict resolution, teamwork, and leadership. A train-the-trainer approach generated a faculty to disseminate multidisciplinary training. Traditional classroom teaching, social media content, and cognitive activities provided theoretical foundations. Forum theater and behavioral simulation taught complex communication issues. Regular labor ward simulations helped embed training into clinical practice.

Results

The results demonstrated statistically significant improvement in safety culture domains of communication openness, handover, nonpunitive response to error, and overall safety perception. Participants felt more able to challenge decisions or actions of those in authority, 33% responded “most of the time or always” in August increasing to 42% in January with a reduction of 50% in those responding “never” (P = 0.02). No change was found relating to team working, staffing or manager expectations promoting patient safety.

Conclusions

This study is proof-of-concept that maternity-orientated human factors training can improve safety culture.
Effect of a Dynamic Exercise Program in Combination With Mediterranean Diet on Quality of Life in Women With Rheumatoid Arthritis
Authors: García-Morales José Manuel , Lozada-Mellado Mariel , Hinojosa-Azaola Andrea , Llorente Luis , Ogata-Medel Midori , Pineda-Juárez Juan Antonio , Alcocer-Varela Jorge , Cervantes-Gaytán Rocío , Castillo-Martínez Lilia
Published: May 2019

Objective

To assess the effect of a dynamic exercise program (DEP) in combination with a Mediterranean diet (MD) on health-related quality of life in women with rheumatoid arthritis (RA).

Method

A randomized clinical trial including 144 women with RA diagnosis was performed. Patients were randomized into 4 groups: (1) MD + DEP (n = 36), (2) DEP (n = 37), (3) MD (n = 40), and (4) control (n = 31). All patients received conventional disease-modifying antirheumatic drugs. Health-related quality of life was assessed with 36-item Short Form Health Survey v2 (0–100 score) and disability with Health Assessment Questionnaire Disability Index at enrollment and after 24 weeks. Between-groups comparisons of the change in the quality of life scores from baseline to follow-up were performed using analysis of covariance in which baseline–to–follow-up was the dependent variable, and the intervention group was the independent variable.

Results

All patients had low disease activity at the time of enrollment, with a mean 28-joint Disease Activity Score of less than 3.2. Patients who were included in the MD + DEP and DEP groups showed 15 points of increase in health-related quality of life global punctuation versus 3.5 in the MD group and −4.6 in the control group (p= 0.01). Also the scores in the physical component after 24 weeks of intervention in the MD + DEP group improved (15.5), in the DEP group (12) and MD group as well (5.1), whereas the control group showed a decrease of the score (−1.7) (p= 0.03 between groups).

Conclusions

The combination of MD + DEP could improve the quality of life in RA patients with low disease activity receiving conventional disease-modifying antirheumatic drugs.
Beyond Lactulose
Authors: Said Vickey J. , Garcia-Trujillo Edith
Published: May 2019

Hepatic encephalopathy is a complication of liver failure characterized by neuropsychiatric dysfunction ranging from disorientation to coma. There is a need for more treatment options and preventive care interventions to reduce the incidence of hepatic encephalopathy and mitigate its socioeconomic impact on families and strain on healthcare resources. Currently, there is no consensus on a single pathophysiological mechanism responsible for the development of this neurocognitive disorder. Ammonia toxicity remains a significant factor, but there is now increased recognition that hyperammonemia acts synergistically with systemic inflammation, oxidative stress, and gut microbiota imbalance in the development of hepatic encephalopathy. This article provides an overview of current and emerging therapies that target these factors in the treatment and management of this condition. Because of its complex pathogenesis, a multipronged approach to treating hepatic encephalopathy may be highly beneficial.
A brief history of bird flu
Authors: Lycett Samantha J. , Duchatel Florian , Digard Paul
Published: May 2019

In 1918, a strain of influenza A virus caused a human pandemic resulting in the deaths of 50 million people. A century later, with the advent of sequencing technology and corresponding phylogenetic methods, we know much more about the origins, evolution and epidemiology of influenza epidemics. Here we review the history of avian influenza viruses through the lens of their genetic makeup: from their relationship to human pandemic viruses, starting with the 1918 H1N1 strain, through to the highly pathogenic epidemics in birds and zoonoses up to 2018. We describe the genesis of novel influenza A virus strains by reassortment and evolution in wild and domestic bird populations, as well as the role of wild bird migration in their long-range spread. The emergence of highly pathogenic avian influenza viruses, and the zoonotic incursions of avian H5 and H7 viruses into humans over the last couple of decades are also described. The threat of a new avian influenza virus causing a human pandemic is still present today, although control in domestic avian populations can minimize the risk to human health.

This article is part of the theme issue ‘Modelling infectious disease outbreaks in humans, animals and plants: approaches and important themes’. This issue is linked with the subsequent theme issue ‘Modelling infectious disease outbreaks in humans, animals and plants: epidemic forecasting and control’.
Adequacy of SEIR models when epidemics have spatial structure: Ebola in Sierra Leone
Authors: Getz Wayne M. , Salter Richard , Mgbara Whitney
Published: May 2019

Dynamic SEIR (Susceptible, Exposed, Infectious, Removed) compartmental models provide a tool for predicting the size and duration of both unfettered and managed outbreaks—the latter in the context of interventions such as case detection, patient isolation, vaccination and treatment. The reliability of this tool depends on the validity of key assumptions that include homogeneity of individuals and spatio-temporal homogeneity. Although the SEIR compartmental framework can easily be extended to include demographic (e.g. age) and additional disease (e.g. healthcare workers) classes, dependence of transmission rates on time, and metapopulation structure, fitting such extended models is hampered by both a proliferation of free parameters and insufficient or inappropriate data. This raises the question of how effective a tool the basic SEIR framework may actually be. We go some way here to answering this question in the context of the 2014–2015 outbreak of Ebola in West Africa by comparing fits of an SEIR time-dependent transmission model to both country- and district-level weekly incidence data. Our novel approach in estimating the effective-size-of-the-populations-at-risk (
N
eff
) and initial number of exposed individuals (
E
0
) at both district and country levels, as well as the transmission function parameters, including a time-to-halving-the-force-of-infection (
t
f/2
) parameter, provides new insights into this Ebola outbreak. It reveals that the estimate
R
0
≈ 1.7 from country-level data appears to seriously underestimate
R
0
≈ 3.3 − 4.3 obtained from more spatially homogeneous district-level data. Country-level data also overestimate
t
f/2
≈ 22 weeks, compared with 8–10 weeks from district-level data. Additionally, estimates for the duration of individual infectiousness is around two weeks from spatially inhomogeneous country-level data compared with 2.4–4.5 weeks from spatially more homogeneous district-level data, which estimates are rather high compared with most values reported in the literature.

This article is part of the theme issue ‘Modelling infectious disease outbreaks in humans, animals and plants: approaches and important themes’. This issue is linked with the subsequent theme issue ‘Modelling infectious disease outbreaks in humans, animals and plants: epidemic forecasting and control’.
Chryseobacterium pennipullorum sp. nov., isolated from poultry feather waste
Authors: Oosthuizen Lize , Charimba George , Hitzeroth Arina , Nde Adeline Lum , Steyn Laurinda , Newman Jeff , Hugo Celia
Published: May 2019

Strain 7_F195T was previously isolated from chicken feather waste collected from an abattoir in Bloemfontein, South Africa. A polyphasic approach was followed to determine if strain 7_F195T belongs to the genus

Chryseobacterium

and if the organism can be classified as a new species. The nearest neighbours, based on 16S rRNA gene sequence similarity values (indicated in parentheses), were

Chryseobacterium flavum

KCTC 12877T (98.42 %),

Chryseobacterium indologenes

LMG 8337T (98.24 %) and

Chryseobacterium gleum

ATCC 35910T (97.71 %). Genome sequencing revealed a genome size of 4 796 535 bp and a DNA G+C content of 38.6 mol%. The ANI values of strain 7_F195T compared to

C. flavum
,
C. indologenes

and C. gleum were 81.45, 81.86 and 82.38 %, respectively. The digital DNA–DNA hybridization values for strain 7_F195T with

C. flavum

,

C. indologenes

and

C. gleum

were 23.7, 23.7 and 24.9 %, respectively. Notable phenotypic differences include the presence of urease activity in C. indologenes LMG 8337T and

C. gleum

NCTC 11432T, but not in strain 7_F195T or

C. flavum

KCTC 12877T. The predominant fatty acids of strain 7_F195T were iso-C15 : 0, iso-C17 : 1
ω9c and iso-C17 : 0 3-OH and the most abundant polar lipid was phosphatidylethanolamine. Menaquinone-6 was the only respiratory quinone. Based on the data generated from this polyphasic study, strain 7_F195T represents a novel

Chryseobacterium

species for which the name

Chryseobacterium
pennipullorum sp. nov. is proposed. The type strain is 7_F195T (=LMG 30781T=KCTC 62760T).
Clinically-relevant cell type cross-talk identified from a human lung tumor microenvironment interactome
Authors: Gentles Andrew J , Hui Angela Bik-Yu , Feng Weiguo , Azizi Armon , Nair Ramesh V. , Knowles David A. , Yu Alice , Jeong Youngtae , Bejnood Alborz , Forgó Erna , Varma Sushama , Xu Yue , Kuong Amanda , Nair Viswam S. , West Rob , van de Rijn Matt , Hoang Chuong D. , Diehn Maximilian , Plevritis Sylvia K.
Published: May 2019

Tumors comprise a complex microenvironment of interacting malignant and stromal cell types. Much of our understanding of the tumor microenvironment comes from in vitro studies isolating the interactions between malignant cells and a single stromal cell type, often along a single pathway. To develop a deeper understanding of the interactions between cells within human lung tumors we performed RNA-seq profiling of flow-sorted malignant cells, endothelial cells, immune cells, fibroblasts, and bulk cells from freshly resected human primary non-small-cell lung tumors. We mapped the cell-specific differential expression of prognostically-associated secreted factors and cell surface genes, and computationally reconstructed cross-talk between these cell types to generate a novel resource we call the Lung Tumor Microenvironment Interactome (LTMI). Using this resource, we identified and validated a prognostically unfavorable influence of Gremlin-1 production by fibroblasts on proliferation of malignant lung adenocarcinoma cells. We also found a prognostically favorable association between infiltration of mast cells and less aggressive tumor cell behavior. These results illustrate the utility of the LTMI as a resource for generating hypotheses concerning tumor-microenvironment interactions that may have prognostic and therapeutic relevance.

RNA-seq profiling of sorted populations from primary lung cancer samples identifies prognostically relevant cross-talk between cell types in the tumor microenvironment.
Fluorescent reporters for functional analysis in rice leaves
Authors: Luginbuehl Leonie H. , El-Sharnouby Sherif , Wang Na , Hibberd Julian M.
Published: May 2019

Fluorescent reporters have facilitated non-invasive imaging in multiple plant species and thus allowed analysis of processes ranging from gene expression and protein localization through to cellular patterning. However, in rice, a globally important crop and model species, there are relatively few reports of fluorescent proteins being used in leaves. Fluorescence imaging is particularly difficult in the rice leaf blade, likely due to a high degree of light scattering in this tissue. To address this, we investigated approaches to improve deep imaging in mature rice leaf blades. We found that ClearSee treatment, which has previously been used to visualise fluorescent reporters in whole tissues of plants, led to improved imaging in rice. Removing epidermal and subtending mesophyll cell layers was faster than ClearSee, and also reduced light scattering such that imaging of fluorescent proteins in deeper leaf layers was possible. To expand the range of fluorescent proteins suitable for imaging in rice, we screened twelve whose spectral profiles spanned most of the visible spectrum. This identified five proteins, mTurquoise2, mClover3, mNeonGreen, mKOκ and tdTomato that are robustly expressed and visible in mesophyll cells of stably transformed plants. Using microparticle bombardment, we show that mTurquoise2 and mNeonGreen can be used for simultaneous multicolour imaging of different sub-cellular compartments. Overall, we conclude that mTurquoise2, mClover3, mNeonGreen, mKOκ and tdTomato are suitable for high resolution live imaging of rice leaves, both after transient and stable transformation. Along with the rapid microparticle bombardment method, which allows transient transformation of major cell types in the leaf blade, these fluorescent reporters should greatly facilitate the analysis of gene expression and cell biology in rice.

One sentence summary

We report five fluorescent reporters suitable for functional analysis in rice leaves.
Inhibition of jasmonate-mediated plant defences by the fungal metabolite higginsianin B
Authors: Dallery Jean-Félix , Zimmer Marlene , Halder Vivek , Suliman Mohamed , Pigné Sandrine , Le Goff Géraldine , Gianniou Despoina D. , Trougakos Ioannis P. , Ouazzani Jamal , Gasperini Debora , O’Connell Richard J.
Published: May 2019

Infection of Arabidopsis thaliana by the ascomycete fungus Colletotrichum higginsianum is characterised by an early symptomless biotrophic phase followed by a destructive necrotrophic phase. The fungal genome contains 77 secondary metabolism-related biosynthetic gene clusters (BGCs), and their expression during the infection process is tightly regulated. Deleting CclA, a chromatin regulator involved in repression of some BGCs through H3K4 trimethylation, allowed overproduction of 3 families of terpenoids and isolation of 12 different molecules. These natural products were tested in combination with methyl jasmonate (MeJA), an elicitor of jasmonate responses, for their capacity to alter defence gene induction in Arabidopsis. Higginsianin B inhibited MeJA-triggered expression of the defence reporter VSP1p:GUS, suggesting it may block bioactive JA-Ile synthesis or signalling in planta. Using the JA-Ile sensor Jas9-VENUS, we found that higginsianin B, but not three other structurally-related molecules, suppressed JA-Ile signalling by preventing degradation of JAZ proteins, the repressors of JA responses. Higginsianin B likely blocks the 26S proteasome-dependent degradation of JAZ proteins because it inhibited chymotrypsin- and caspase-like protease activities. The inhibition of target degradation by higginsianin B also extended to auxin signalling, as higginsianin B treatment reduced IAA-dependent expression of DR5p:GUS. Overall, our data indicate that specific fungal secondary metabolites can act similarly to protein effectors to subvert plant immune and developmental responses.

Highlight

A diterpene secondary metabolite produced by a fungal pathogen suppresses plant jasmonate defense signalling by preventing the proteasomal degradation of JAZ repressor proteins.
Fingerprints of high-dimensional coexistence in complex ecosystems
Authors: Barbier Matthieu , de Mazancourt Claire , Loreau Michel , Bunin Guy
Published: May 2019

The coexistence of many competing species is a long-standing puzzle in ecology. Classic niche theory explains coexistence by trade-offs between a few essential species traits. Here we study an unexplored frontier of this theory: we assume that coexistence is intrinsically high-dimensional, arising from many traits and trade-offs at once. Species interactions then appear almost random, but their disorder hides a diffuse statistical structure: competitors that become successful start by subtly favoring each other, and partitioning their impacts on other species. We validate our quantitative predictions using data from grassland biodiversity experiments. We conclude that a high biodiversity can be attained through a pattern of collective organization that cannot be understood at the species level, but exhibits the fingerprint of high-dimensional interactions.
Polygenic risk score of alcohol consumption predicts alcohol-related morbidity and all-cause mortality
Authors: Kiiskinen Tuomo , Mars Nina J. , Palviainen Teemu , Koskela Jukka , Ripatti Pietari , Rämö Joel T. , Ruotsalainen Sanni ,   FinnGen, GSCAN Consortium, Palotie Aarno , Madden Pamela A.F. , Rose Richard J. , Kaprio Jaakko , Salomaa Veikko , Mäkelä Pia , Havulinna Aki S. , Ripatti Samuli
Published: May 2019

Objective

To develop a highly polygenic risk score (PRS) for alcohol consumption and study whether it predicts alcohol-related morbidity and all-cause mortality.

Design

Biobank-based prospective cohort study

Setting

FinnGen Study (Finland)

Participants

96,499 genotyped participants from the nationwide prospective FinnGen study and 36,499 participants from prospective cohorts (Health 2000, FINRISK, Twin Cohort) with detailed baseline data and up to 25 years of follow-up time.

Main outcome measures

Incident alcohol-related morbidity and alcohol-related or all-cause mortality, based on hospitalizations, outpatient specialist care, drug purchases, and death reports.

Results

In 96,499 FinnGen participants there were in total 4,785 first-observed incident alcohol-related health events. The PRS of alcohol consumption was associated with alcohol-related morbidity and the risk estimate (hazard ratio, HR) between the highest and lowest quintiles of the PRS was 1.67 [ 95 % confidence interval: 1.52-1.84], p=3.2*10−27). In 28,639 participants with comprehensive baseline data from prospective Health 2000 and FINRISK cohorts, 911 incident first alcohol-related events were observed. When adjusted for self-reported alcohol consumption, education, marital status, and gamma-glutamyl transferase blood levels, the risk estimate between the highest and lowest quintiles of the PRS was 1.58 (CI=[1.26-1.99], p=8.2*10−5). The PRS was also associated with all-cause mortality with a risk estimate of 1.33 between the highest and lowest quintiles (CI=[1.2-1.47], p=4.5e-08) in the adjusted model. In all 39,695 participants with self-reported alcohol consumption available, a 1 SD increase in the PRS was associated with 11.2 g (=0.93 drinks) higher weekly alcohol consumption (β=11.2 [9.85-12.58 g], p = 2.3*10−58).

Conclusions

The PRS for alcohol consumption associates for both alcohol-related morbidity and all-cause mortality. These findings underline the importance of heritable factors in alcohol-related behavior and the related health burden. The results highlight how measured genetic risk for an important behavioral risk factor can be used to predict related health outcomes.
IPSC-derived neuronal cultures expressing the Alzheimer’s disease associated rare TREM2 R47H variant enables the construction of an Aβ-induced gene regulatory network
Authors: Martins Soraia , Müller-Schiffmann Andreas , Bohndorf Martina , Wruck Wasco , Sleegers Kristel , Van Broeckhoven Christine , Korth Carsten , Adjaye James
Published: May 2019

Recently, genes associated with immune response and inflammation have been identified as genetic risk factors for late-onset Alzheimer’s disease (LOAD). One of them is the rare p.Arg47His (R47H) variant within triggering receptor expressed on myeloid cells 2 (TREM2), which has been shown to increase the risk for developing AD 2-3-fold. Here, we report the generation and characterization of a model of LOAD using lymphoblast-derived iPSCs from patients harbouring the R47H mutation in TREM2 (AD TREM2 iPSCs), as well as from control individuals without dementia (CON iPSCs). iPSCs efficiently differentiate into mature neuronal cultures and comparative global transcriptome analysis identified a distinct gene expression profile in AD TREM2 neuronal cultures. Furthermore, manipulation of the iPSC-derived functional neuronal cultures with an Aβ-S8C dimer highlighted metabolic pathways, phagosome and immune response as the most perturbed pathways in AD TREM2 neuronal cultures. Through the construction of an Aβ-induced gene regulatory network, we were able to identify an Aβ signature linked to protein processing in the endoplasmic reticulum (ER) which emphasised ER-stress, as a potential causal role in LOAD. Overall, this study has shown that our AD-iPSC based model can be used for in-depth studies to better understand the molecular mechanisms underlying the etiology of LOAD and provides new opportunities for screening of potential therapeutic targets.