bluuebunny/crossref_metadata_2025 huggingface dataset:
Persistent Postoperative Opioid Use
Authors: Jivraj Naheed K. , Raghavji Faizal , Bethell Jennifer , Wijeysundera Duminda N. , Ladha Karim S. , Bateman Brian T. , Neuman Mark D. , Wunsch Hannah
Published: April 2020

Background

While persistent opioid use after surgery has been the subject of a large number of studies, it is unknown how much variability in the definition of persistent use impacts the reported incidence across studies. The objective was to evaluate the incidence of persistent use estimated with different definitions using a single cohort of postoperative patients, as well as the ability of each definition to identify patients with opioid-related adverse events.

Methods

The literature was reviewed to identify observational studies that evaluated persistent opioid use among opioid-naive patients requiring surgery, and any definitions of persistent opioid use were extracted. Next, the authors performed a population-based cohort study of opioid-naive adults undergoing 1 of 18 surgical procedures from 2013 to 2017 in Ontario, Canada. The primary outcome was the incidence of persistent opioid use, defined by each extracted definition of persistent opioid use. The authors also assessed the sensitivity and specificity of each definition to identify patients with an opioid-related adverse event in the year after surgery.

Results

Twenty-nine different definitions of persistent opioid use were identified from 39 studies. Applying the different definitions to a cohort of 162,830 opioid-naive surgical patients, the incidence of persistent opioid use in the year after surgery ranged from 0.01% (n = 10) to 14.7% (n = 23,442), with a median of 0.7% (n = 1,061). Opioid-related overdose or diagnosis associated with opioid use disorder in the year of follow-up occurred in 164 patients (1 per 1,000 operations). The sensitivity of each definition to identify patients with the composite measure of opioid use disorder or opioid-related toxicity ranged from 0.01 to 0.36, while specificity ranged from 0.86 to 1.00.

Conclusions

The incidence of persistent opioid use reported after surgery varies more than 100-fold depending on the definition used. Definitions varied markedly in their sensitivity for identifying adverse opioid-related event, with low sensitivity overall across measures.

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Primary Epiphyseal Osteomyelitis (PEO) in 18 Children: A Rare Entity With Atypical Features
Authors: Shah Maulin M. , Gupta Gaurav , Makadia Akash S. , Rabbi Qaisur
Published: April 2020

Objectives:

The purpose of this study is to discuss the natural history and management of primary epiphyseal osteomyelitis (PEO), to differentiate clinico-radiologic features of PEO caused by Mycobacterium and other organisms, and to discuss their intermediate-term outcomes.

Methods:

Between 2006 and 2017, 18 patients of PEO were managed at our center. Blood investigations, x-rays, and magnetic resonance imaging of affected part were carried out. Surgical drainage of lesions was done to retrieve infective fluid and tissue for examination. Antibiotics were administered for 1 year in Mycobacterial PEO and for 6 weeks in bacterial PEO. Average follow-up of patients was 5.5 years (range, 2 to 11 y).

Results:

Boys were more commonly affected (11/18). Distal femur was the most common site involved (12/18). Eleven patients had Mycobacterium tuberculosis as the causative organism, 6 were positive for Staphylococcus aureus, and 1 for Brucella. Swelling and limp were predominant in patients with Tubercular PEO, whereas pain was more common in bacterial PEO. Nine of 11 patients with Tubercular PEO had penetration into the joint, whereas none in bacterial PEO. All patients recovered completely without residual movement restriction or growth alteration. On follow-up magnetic resonance imaging, 4 patients with Tubercular PEO had thinning of articular cartilage.

Conclusion:

High index of suspicion is required for early diagnosis of PEO. It is important to differentiate Tubercular from other bacterial PEO as it has more subtle symptoms and poor prognosis if left untreated. Aggressive surgical treatment followed by antibiotic therapy of appropriate duration is required to avoid complications related to joint destruction. To our knowledge, this is the largest reported series with longest follow-up.
Identifying the Most Appropriate ACDF Patients for an Ambulatory Surgery Center
Authors: Zuckerman Scott L. , Mummareddy Nishit , Lakomkin Nikita , Sivaganesan Ahilan , Asher Anthony , Devin Clinton J.
Published: April 2020

Study Design:

Retrospective cohort analysis of prospectively collected data.

Objectives:

Using a national cohort of patients undergoing elective anterior cervical discectomy and fusion (ACDF) in an inpatient/outpatient setting, the current objectives were to: (1) outline preoperative factors that were associated with complications, and (2) describe potentially catastrophic complications so that this data can help stratify the best suited patients for an ambulatory surgery center (ASC) compared with a hospital setting.

Summary of Background Data:

ASCs are increasingly utilized for spinal procedures and represent an enormous opportunity for cost savings. However, ASCs have come under scrutiny for profit-driven motives, lack of adequate safety measures, and inability to handle complications.

Methods:

Adults who underwent ACDF between 2008 and 2014 were identified in the National Surgical Quality Improvement Program (NSQIP) database. Inclusion criteria were: principal procedure ACDF [Current Procedural Terminology (CPT) 22551, 22552], elective, neurological/orthopedic surgeons, length of stayof 0/1 day, and being discharged home. The primary outcome was presence of any complication. The secondary outcome was occurrence of potentially catastrophic complications.

Results:

A total of 12,169 patients underwent elective ACDF with a length of stay of 0/1 day and were discharged directly home. A total of 179 (1.47%) patients experienced a complication. Multivariate logistic regression revealed the following factors were significantly associated with a complication: Charlson Comorbidity Index (CCI) >3, history of transient ischemic attack/cerebrovascular accident, abnormal bilirubin, and operative time of >2 hours. Approximate comorbidity score cutoffs associated with <2% risk of complication were: American Society of Anesthesiologists (ASA)≤2, CCI≤2, modified frailty index (mFI) ≤0.182. A total of 51 (0.4%) patients experienced potentially catastrophic complications.

Conclusions:

The current results represent a preliminary, pilot analysis using inpatient/outpatient data in selecting appropriate patients for an ASC. The incidence of potentially catastrophic complication was 0.4%. These results should be validated in multi-institution studies to further optimize appropriate patient selection for ASCs.
Scleral fixated secondary intraocular lenses: a review of recent literature
Authors: Patel Luv G. , Starr Matthew R. , Ammar Michael J. , Yonekawa Yoshihiro
Published: April 2020

Purpose of review

A variety of techniques exist for secondary intraocular lens (IOL) implantation. Of note, scleral fixated intraocular lenses have become more popular with a variety of techniques, both with and without use of sutures. Herein, we focus on reviewing recently published studies describing the long-term outcomes of scleral fixation techniques.

Recent findings

Although initial papers describing novel techniques often report short-term outcomes, several studies have recently described intermediate and long-term outcomes for scleral fixated IOLs, albeit all being retrospective case series. Suture fixation methods with long-term follow-up, up to a minimum of 50 months, report dislocation rates between 0 and 15%. Sutureless scleral fixation techniques have increased in popularity the past several years. Although they appear to have a lower rate of IOL dislocation: several studies have reported 0% and one study 8%. The follow-up period for sutureless scleral fixation technique studies, however, is shorter with most studies reporting follow-up of less than a year. Rates of retinal detachment vary between individual studies, but are similar for both suture fixation and sutureless with the majority of studies reporting a rate between 0 and 5%. These studies show that long-term outcomes are important considerations in surgical decision-making.

Scleral fixation techniques have shown long-term durability and safety in recent retrospective studies. Comparison of techniques has been limited, and more robust studies may be required to provide stronger anatomic, functional, and comparative data.
Efficacy and toxicity comparison of nab-paclitaxel plus S-1 and nab-paclitaxel plus gemcitabine as first-line chemotherapy for metastatic pancreatic cancer
Authors: Guo Xi , Xu Yaolin , Ji Yuan , Fan Yue , Wang Dansong , Jin Dayong , Zhuang Rongyuan , Wu Lili , Lou Wenhui , Zhou Yuhong
Published: April 2020

To compare efficacy and safety of nab-paclitaxel plus gemcitabine (AG) with nab-paclitaxel plus S-1 (AS) as first-line treatment for metastatic pancreatic cancer, we conducted a retrospective analysis by reviewing medical records of 53 metastatic pancreatic cancer patients in our institution. They received either AG (nab-paclitaxel 125 mg/m2 on days 1, 8 and gemcitabine 1000 mg/m2 on days 1, 8) or AS (nab-paclitaxel 125 mg/m2 on days 1, 8 and S-1 80–120 mg on days 1–14) chemotherapy. We found that AS had higher objective response rate (36% vs 21.4%), better disease control rate (84% vs 75%), prolonged time to progression (TTP, 7.1 vs 5 months), and improved overall survival (OS, 15.3 vs 12 months) when compared with AG. In Cox proportional hazards model, sex was significantly associated with TTP (P value = .031) and metastatic sites plus treatment after progression were significantly associated with OS (P value = .028 and .01, respectively). The incidence rate of chemotherapy-related adverse events was similar in both groups. Neutropenia (50% and 60%, all grade; 21.4% and 36%, grade 3 or 4, in AG and AS group) and sensory neuropathy (21.4% and 24%, all grade; 3.6% and 4%, grade 3 or 4, in AG and AS group) were the most common hematologic and non-hematologic toxicity. Thus, we believed that AS is a reasonable and convenient alternative for patients treated with AG as first-line chemotherapy for metastatic pancreatic cancer.
Climate Change
Authors: Leddin Desmond , Macrae Finlay
Published: April 2020

The earth’s atmosphere has warmed by about 1°C compared with preindustrial temperature. This is producing changes in the earth’s climate and weather which have implications for gastrointestinal health and disease. Climate change will exacerbate current challenges with regard to provision of adequate nutrition and access to clean water. An increase in high rainfall events, flooding and droughts will be associated with an increase in enteric infections and hepatitis. Changes in habitat may result in altered distribution of gastrointestinal illness such as Vibrio cholera. Climate change will force migration between countries, and within countries, and will drive relocation from rural to urban areas, further straining sanitation and clean water provision. The infrastructure required to the delivery of gastrointestinal care is vulnerable to extreme weather events which will become more frequent. The Gastroenterology community needs to join the debate on climate change by organizing, educating, advocating, and supporting our political leaders as they face the enormous challenges posed by global warming.
Pathologist Experience and Concordance in the Diagnosis of Dysplasia in Long-standing Inflammatory Bowel Disease
Authors: Jimeno Mireya , Domingo Anna , Salas Isabel , Sánchez María R. , González Carmen , Salas Clara , Paúles María J. , Sanjuán Xavier , Carballal Sabela , Quintanilla Isabel , Molist Gemma , Cuatrecasas Miriam , Pellisé Maria
Published: April 2020

Surveillance colonoscopies focused to detect dysplasia are recommended to prevent colorectal cancer in patients with long-standing colonic inflammatory bowel disease (IBD). To date, histologic diagnosis and gradation of IBD-related dysplasia has been challenged by a high variability among pathologists. We aimed to analyze the observer characteristics that are correlated with concordance deviations in this diagnosis. Eight pathologists evaluated a set of 125 endoscopic biopsy samples with a representative distribution of nondysplastic and dysplastic lesions from long-standing IBD patients. Two rounds of diagnosis were carried out during a period of 18 months. The κ test was applied to analyze concordance. Pathologists were grouped on the basis of their experience. A subanalysis was performed by eliminating the highly prevalent nondysplastic samples, as well as an analysis after observers’ grouping. Overall interobserver agreement was good (κ=0.73), with an even higher pairwise value (κ=0.86) as well as the intraobserver agreement values (best κ=0.85). After eliminating the highly prevalent nondysplastic samples, the interobserver agreement was still moderate to good (best overall κ=0.50; best paired κ=0.72). Notable differences were seen between the pathologists with a high-volume and low-volume practice (best overall κ=0.61 and 0.41, respectively). The agreement in the diagnosis of dysplasia in IBD endoscopic biopsies may have been undervalued over time. This is the first study evaluating pathologists’ diagnostic robustness in this field. The results suggest that examining a large volume of samples is the key factor to increase the consistency in the diagnosis and gradation of IBD-related dysplasia.
GLILD Revisited
Authors: Larsen Brandon T. , Smith Maxwell L. , Tazelaar Henry D. , Yi Eunhee S. , Ryu Jay H. , Churg Andrew
Published: April 2020

Common variable immunodeficiency (CVID) and selective immunoglobulin A deficiency (IgAD) often cause chronic lung disease, but the pulmonary pathologic features of these systemic diseases are poorly recognized by pathologists. It has been claimed that CVID cases show a characteristic combination of noncaseating granulomas-lymphoid proliferations termed granulomatous-lymphocytic interstitial lung disease (GLILD). We present 34 surgical lung biopsy cases of CVID and 4 of IgAD. Noncaseating granulomas were seen in 23/34 (68%) CVID and 2/4 (50%) IgAD cases. A statistically identical pattern of benign lymphoid proliferation was found in CVID and IgAD whether or not granulomas were present. Organizing pneumonia, sometimes considered a part of GLILD, was seen in 25/34 (74%) CVID and 2/4 (50%) IgAD cases and did not correlate with the presence of granulomas. On follow-up, 3 CVID patients died (only 1 of pulmonary disease), while 21 others are alive at 1 to 300 months with no difference by presence or absence of granulomas. Three IgAD patients with follow-up are alive. We conclude that CVID and IgAD are indistinguishable in surgical lung biopsies and a subset of both show patterns that would qualify as GLILD, while other cases lack granulomas but have identical patterns of lymphoid infiltration and organizing pneumonia. We suggest that GLILD is neither a specific nor a useful entity, and biopsies from CVID and IgAD patients should be diagnosed simply by microscopic pattern(s) observed. The prognosis of CVID with lymphoid infiltrates with or without granulomas in this series was good, contrary to claims in the literature about GLILD.
Nonprofit Hospitals' Response to the Opioid Epidemic in Urban Communities: A Content Analysis of Hospitals' Community Health Needs Assessments and Implementation Strategies
Authors: Singh Simone , Kiessling Karalyn , Rhodes Jordan
Published: April 2020

Context:

Addressing the opioid epidemic requires a coordinated community response; yet, the role that nonprofit hospitals play in these efforts has not been systematically examined.

Objective:

To explore hospital-initiated strategies to address opioid use in urban communities most affected by the opioid epidemic.

Design:

We conducted content analysis of publicly available community health needs assessments (CHNAs) and accompanying implementation strategies of 140 nonprofit hospitals. We employed a qualitative approach using open coding methods to explore the extent to which hospitals identified opioid use as a community health need and engaged in interventions to address opioid use in their communities. We also conducted bivariate analysis to compare organizational and community characteristics of hospitals that did and did not engage in strategies to address opioid use.

Setting:

One hundred forty nonprofit hospitals in urban areas with high opioid death rates across 25 states.

Results:

Almost 70% of CHNAs identified opioid use as a community health need, and 63% of implementation strategies included at least 1 hospital-initiated activity to address this need. More than 90% of these implementation strategies involved providing additional capacity for and access to treatment. Bivariate analysis showed that hospitals that engaged in activities to address opioid use did not differ meaningfully from hospitals that did not engage in such activities, with 2 exceptions. Hospitals that relied on consultants to prepare the CHNA were more likely to engage in activities to address opioid use as were hospitals located in Medicaid expansion states.

Conclusions:

Nonprofit hospitals are taking action to address the opioid epidemic in their communities, most commonly by providing additional treatment capacity for patients with opioid use. While an important contribution, hospitals need incentives to develop a more comprehensive response to the opioid epidemic that extends beyond medical care to include the social and economic determinants of this crisis.
Proper Disposal of Prescription Opioids in Southwest Virginia: Assessment of Patient, Physician, and Medical Student Beliefs and Practices
Authors: Bouzaher Malek H. , Miller Thomas K.
Published: April 2020

Context:

Southwestern Virginia demonstrates the highest regional mortality rate from prescription opioid overdoses. Nationally, 65% of patients misusing opioid medications received them from friends and family, underscoring the need for effective disposal of unused narcotics.

Objectives:

(1) To understand patient, provider, and medical student beliefs and misconceptions regarding proper methods of opioid disposal; (2) to characterize discrepancies that exist between patient self-reported habits and medical student/provider perceptions of opioid usage, disposal, and diversion.

Design:

Descriptive, cross-sectional, observational study.

Setting:

Large, nonprofit health care organization and allopathic medical school in Southwestern Virginia.

Participants:

All ambulatory patients 18 years or older presenting for elective consultation at health system orthopedics department; all institutionally employed physicians with active system e-mail addresses; and all current students at the associated medical school.

Main Outcomes/Measures:

Patients: The number who had received information regarding proper methods of opioid disposal, intended disposal method, methods of disposal considered appropriate, comfort level with opioid disposal, and demographic data. Physicians and Medical Students: The number who had received instruction regarding proper methods of opioid disposal, acceptable means of opioid disposal, most appropriate disposal method, disposal method most likely to be employed by patients, practice profile/prescribing data, and medical school year.

Results:

In total, 64% of patients (n = 255/750) had never received instruction from a physician regarding opioid disposal; 56% of physicians (n = 212/732) and 78% (n = 80/171) of medical students indicated that they never received formal instruction regarding methods of disposal. The majority of physicians believed that their patients are most likely to use in-home methods of disposal or store prescription medications for future use; 61% of patients indicated a preference for accessible disposal facilities.

Conclusions:

The discrepancy between patient and physician responses highlights a lack of communication regarding disposal of unused opioid medications and is a target for future intervention.
Early Evidence of an Opioid Education Campaign: A Case Study of Rhode Island
Authors: Rath Jessica M. , Hair Elizabeth C. , Barton Alexis A. , Kreslake Jennifer M. , Geraci John , Palmerini Maureen , Coderre Tom , Vallone Donna M.
Published: April 2020

Context:

The opioid crisis poses a significant burden at a national level, and certain states have seen particularly high rates of misuse, addiction, and overdose. In 2017, Rhode Island reported opioid-related deaths nearly twice the national average.

Objective:

To test message efficacy and evaluate the effectiveness of campaign messaging to shift attitudes/beliefs related to opioid misuse in Rhode Island.

Design:

In phase 1, near-final versions of 6 advertisements were shown to a sample of the target audience via an online survey portal to assess responses to the messages (N = 1210). Phase 2 of the study employed a pre/posttest design whereby 2 cross-sectional surveys were conducted, first prior to the campaign launch (N = 456) and another survey 6 months later in Rhode Island (N = 433).

Setting:

Phase 1 was conducted online using a nationally representative panel, and phase 2 included a convenience sample of participants in Rhode Island recruited to undergo an online survey.

Participants:

Eighteen- to 29-year-old members of a nationally representative online panel (phase 1) and 15- to 34-year-olds living in the state of Rhode Island during data collection periods.

Main Outcome Measure(s):

Empathy and destigmatization (“someone like me could become addicted...” and “those who are dependent on prescription opioids are victims”) and perceived risk of developing dependence on opioids.

Results:

In both phases, there was an increase in empathy (“someone”) (phase 1: pretest [31%], posttest [42%; z = 5.5, P < .0001] and phase 2 [34% baseline vs 41% follow-up; z = 2.0, P = .04]) and destigmatization (“victims”) (phase 1: pretest [54%], posttest [58%; z = 2.2, P = .01] and phase 2 [46% baseline vs 54% follow-up; z = 2.2, P = .03]). There was also an increase in perceived risk: phase 1 (pretest [65%], posttest [75%; z = 5.4, P < .0001]) and phase 2 (66% baseline vs 74% follow-up; z = 2.5, P = .01).

Conclusions:

This study demonstrated the potential efficacy of a media campaign to shift young adults' opioid-related attitudes.
A Three-part Quality Improvement Initiative to Increase Patient Satisfaction and Reduce Appointment Time
Authors: Manohar Sujal , McLeod Crystal
Published: April 2020

Introduction:

PediPlace, a busy pediatric not-for-profit clinic in Lewisville, Tex., struggles with prolonged patient wait times. This quality improvement (QI) project aimed to reduce appointment lengths and improve the patient experience.

Methods:

PediPlace introduced 3 interventions: improved patient tracking to measure timing on the electronic health record interface, elimination of script repetition between medical assistants and providers, and patient art kits.

Results:

From over 2,000 surveys indicated that patients were more satisfied; the percentage of negative survey comments decreased from 20% in 2017 and 2018 to under 10% in 2019. The overall rating of the clinic rose from 3.8 to 4.75 (on a scale of 1–5) after QI interventions as well. The number of patients not checked out declined from 49 errors in October–December 2018 to 25 errors in January–March 2019, indicating that this part of the initiative was initially successful. However, subsequent months experienced higher error rates. Analysis of over 20,000 appointments from June 2018 to July 2019 showed that appointment length did not change after interventions.

Conclusions:

There was no difference in appointment lengths between Hispanic/Latino patients and other patients, and an encouraging finding that suggests PediPlace providers are effective bilingual communicators. Furthermore, anecdotal evidence indicated that the art kits were positively received. The interventions appeared to improve the patient experience but did not impact appointment length. PediPlace plans to continue QI initiatives in the future.
Brief Report: Relationship Between Nonalcoholic Fatty Liver Disease and Cardiovascular Disease in Persons With HIV
Authors: Kaplan Alyson , Simon Tracey G. , Henson Jacqueline B. , Wang Thomas , Zheng Hui , Osganian Stephanie A. , Rosenblatt Russell , Lake Jordan , Corey Kathleen E.
Published: April 2020

Background:

Nonalcoholic fatty liver disease (NAFLD) and HIV are independently associated with cardiovascular disease (CVD). However, the factors associated with NAFLD in persons living with HIV (PWH) and whether CVD is more frequent in PWH with NAFLD are currently unknown.

Methods:

From the Partners HealthCare Research Patient Data Registry, we identified PWH with and without NAFLD between 2010 and 2017. NAFLD was defined using validated histological or radiographic criteria. CVD was defined by an ICD-9 diagnosis of coronary artery disease, myocardial infarction, coronary revascularization, peripheral vascular disease, heart failure, transient ischemic attack, or stroke and was confirmed by clinician review. Multivariable logistic regression was performed to examine the relationship between NAFLD and CVD.

Results:

Compared with PWH without NAFLD (n = 135), PWH with NAFLD (n = 97) had higher body mass index and more frequently had hypertension, obstructive sleep apnea, diabetes mellitus, dyslipidemia, coronary artery disease, and CVD (P < 0.01 for all). PWH with NAFLD were also more likely to have CD4+ T-cell counts (CD4) <200 cells/mm3. In multivariable models, the presence of NAFLD was significantly associated with CVD (adjusted odds ratio 3.08, 95% confidence interval: 1.37 to 6.94) and CD4 <200 cells/mm3 (adjusted odds ratio 4.49, 95% confidence interval: 1.74 to 11.55).

Conclusion:

In PWH, CVD was independently associated with prevalent NAFLD after controlling for traditional CVD risk factors. NAFLD was also associated with CD4 <200 cells/mm3, suggesting that immune dysfunction may be related to NAFLD. Both CVD and low CD4+ count as risk factors for NAFLD require prospective evaluation.
Simulation-Based Examination of Arterial Line Insertion Method Reveals Interdisciplinary Practice Differences
Authors: Golden Antoinette , Alaska Yasser , Levinson Andrew T. , Davignon Kristopher R. , Lueckel Stephanie N. , Lynch Kenneth A. , Jay Gregory , Kobayashi Leo
Published: April 2020

Introduction

Arterial cannulation is frequently performed on intensive care unit (ICU) and operating room patients; a 1% complication rate has been reported. Investigators applied simulation to study clinical providers' arterial catheter (AC) insertion performance and to assess for interdisciplinary and intradisciplinary variation that may contribute to complications.

Methods

Anesthesia, medical critical care, and surgical critical care providers with AC insertion experience were enrolled at 2 academic hospitals. Each subject completed a simulated AC insertion on an in situ task trainer. Using a Delphi-derived checklist that incorporated published recommendations, expert opinion, and institutional requirements, 2 investigators completed offline video reviews to compare subjects' technical performance.

Results

Ten anesthesia, 11 medical ICU (MICU, 1 excluded), and 10 surgical ICU (SICU) subjects with significant between-group differences in training level and AC insertion experience were enrolled for 2 years. Differences in procedural planning, equipment preparation, and patient preparation steps did not attain significance across groups except for anesthesia participants using only ad hoc AC kits, and MICU and SICU subjects preferentially using commercial kits (P < 0.001). Time-outs were completed by 1 anesthesia subject, 5 MICU subjects, and 4 SICU subjects (P = 0.29, NS). For proceduralist preparation steps, fewer anesthesiology subjects donned gowns (P < 0.001). Only MICU subjects used ultrasound guidance (P = 0.0053), and only MICU (100%) and SICU (100%) subjects sutured ACs in place. Overall observance of sterile technique was similar across groups at 70% to 100% (P = 0.32).

Conclusions

Simulated AC insertions revealed procedural performance variability that may derive from individual provider differences, discipline-based practice parameters, and setting-specific cultural factors.
Guideline-based Chinese herbal medicine treatment plus standard care for severe coronavirus disease 2019 (G-CHAMPS): evidence from China
Authors: Ye Yong-an
Published: April 2020

Objectives

To assess outcomes in patients who have severe coronavirus disease 2019 (COVID-19) and were treated with either China guideline based Chinese herbal medicines (CHMs) plus standard care or standard care alone.

Design

A pilot randomized controlled trial.

Setting

Hubei Provincial Hospital of Integrated Chinese and Western Medicine, Wuhan, China

Patients

A total of 42 adults with severe COVID-19.

Interventions

Participants in the CHM plus standard care group received CHM and standard care, and the control group received standard care alone.

Measurements and Main Results

The primary outcome was the change in the disease severity category of COVID-19 after treatment at 7 days. Among 42 participants who were randomized (mean [SD] age 60.43 years [12.69 years]; 21 [50%] were aged ≥ 65 years; and 35 [83%] women, 42 (100%) had data available for the primary outcome. For the primary outcome, one patient from each group died during treatment; the odds of a shift towards death was lower in the CHM plus group than the standard care alone group (common OR 0.59, 95% CI 0.148 to 2.352 P=.454). Three (2 from the CHM plus group and 1 from the standard care alone group) patients progressed from severe to critical illness. After treatment, mild, moderate, and severe COVID-19 disease accounted for 18% (5) vs 14% (2), 71% (20) vs 64% (9), and 0% (0) vs 7% (1) of the patients treated with CHM plus standard care vs. standard care alone.

Conclusions

For the first time, the G-CHAMPS trial provided valuable information for the national guideline-based CHM treatment for hospitalized patients with severe COVID-19. CHM effects in COVID-19 may be clinically important and warrant further consideration and studies.
Lectin-like Intestinal Defensin Inhibits 2019-nCoV Spike binding to ACE2
Authors: Wang Cheng , Wang Shaobo , Li Daixi , Zhao Xia , Han Songling , Wang Tao , Zhao Gaomei , Chen Yin , Chen Fang , Zhao Jianqi , Wang Liting , Sun Wei , Huang Yi , Su Yongping , Wei Dongqing , Zhao Jinghong , Wang Junping
Published: April 2020

The burgeoning epidemic caused by novel coronavirus 2019 (2019-nCoV) is currently a global concern. Angiotensin-converting enzyme-2 (ACE2) is a receptor of 2019-nCoV spike 1 protein (S1) and mediates viral entry into host cells. Despite the abundance of ACE2 in small intestine, few digestive symptoms are observed in patients infected by 2019-nCoV. Herein, we investigated the interactions between ACE2 and human defensins (HDs) specifically secreted by intestinal Paneth cells. The lectin-like HD5, rather than HD6, bound ACE2 with a high affinity of 39.3 nM and weakened the subsequent recruitment of 2019-nCoV S1. The cloak of HD5 on the ligand-binding domain of ACE2 was confirmed by molecular dynamic simulation. A remarkable dose-dependent preventive effect of HD5 on 2019-nCoV S1 binding to intestinal epithelial cells was further evidenced byin vitroexperiments. Our findings unmasked the innate defense function of lectin-like intestinal defensin against 2019-nCoV, which may provide new insights into the prevention and treatment of 2019-nCoV infection.
A new mutant mouse model lacking mitochondrial-associated CB1receptor
Authors: Pagano Zottola Antonio C. , Soria-Gomez Edgar , Bonilla-del-Río Itziar , Muguruza Carolina , Terral Geoffrey , Robin Laurie M. , da Cruz José F. Oliveira , Redon Bastien , Lesté-Lasserre Thierry , Tolentino-Cortes Tarson , Puente Nagore , Barreda-Gómez Gabriel , Chaouloff Francis , Callado Luis F. , Grandes Pedro , Marsicano Giovanni , Bellocchio Luigi
Published: April 2020

The idea that the effects of drugs largely depend on subcellular target location is emerging as a novel predictive factor of their beneficial or adverse outcomes. G protein-coupled type-1 cannabinoid receptors (CB1) are regulators of several brain functions as well as the main targets of cannabinoid-based medicines.

Besides their classical location at plasma membranes, CB1receptors are present at different locations within cells, including in association to mitochondrial membranes (mtCB1). Here we report the generation and characterization of a mutant mouse line, which lack mtCB1receptors.
Epitope-based chimeric peptide vaccine design against S, M and E proteins of SARS-CoV-2 etiologic agent of global pandemic COVID-19: anin silicoapproach
Authors: Rahman M. Shaminur , Hoque M. Nazmul , Islam M. Rafiul , Akter Salma , Rubayet-Ul-Alam A. S. M. , Siddique Mohammad Anwar , Saha Otun , Rahaman Md. Mizanur , Sultana Munawar , Hossain M. Anwar
Published: April 2020

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the cause of the ongoing pandemic of coronavirus disease 2019 (COVID-19), a public health emergency of international concern declared by the World Health Organization (WHO). An immuno-informatics approach along with comparative genomic was applied to design a multi-epitope-based peptide vaccine against SARS-CoV-2 combining the antigenic epitopes of the S, M and E proteins. The tertiary structure was predicted, refined and validated using advanced bioinformatics tools. The candidate vaccine showed an average of ≥ 90.0% world population coverage for different ethnic groups. Molecular docking of the chimeric vaccine peptide with the immune receptors (TLR3 and TLR4) predicted efficient binding. Immune simulation predicted significant primary immune response with increased IgM and secondary immune response with high levels of both IgG1 and IgG2. It also increased the proliferation of T-helper cells and cytotoxic T-cells along with the increased INF-γ and IL-2 cytokines. The codon optimization and mRNA secondary structure prediction revealed the chimera is suitable for high-level expression and cloning. Overall, the constructed recombinant chimeric vaccine candidate demonstrated significant potential and can be considered for clinical validation to fight against this global threat, COVID-19.
Burst-dependent synaptic plasticity can coordinate learning in hierarchical circuits
Authors: Payeur Alexandre , Guerguiev Jordan , Zenke Friedemann , Richards Blake A. , Naud Richard
Published: April 2020

Synaptic plasticity is believed to be a key physiological mechanism for learning. It is well-established that it depends on pre and postsynaptic activity. However, models that rely solely on pre and postsynaptic activity for synaptic changes have, to date, not been able to account for learning complex tasks that demand credit assignment in hierarchical networks. Here, we show that if synaptic plasticity is regulated by high-frequency bursts of spikes, then neurons higher in a hierarchical circuit can coordinate the plasticity of lower-level connections. Using simulations and mathematical analyses, we demonstrate that, when paired with short-term synaptic dynamics, regenerative activity in the apical dendrites, and synaptic plasticity in feedback pathways, a burst-dependent learning rule can solve challenging tasks that require deep network architectures. Our results demonstrate that well-known properties of dendrites, synapses, and synaptic plasticity are sufficient to enable sophisticated learning in hierarchical circuits.
Divergent microbiota of echinoid eggs separated by the Isthmus of Panama
Authors: Carrier Tyler J. , Lessios Harilaos A. , Reitzel Adam M.
Published: April 2020

Relationships between animals and their associated microbiota is dependent on the evolutionary history of the host and on the environment. The majority of studies tend to focus on one of these factors and rarely consider how both determine the community composition of the associated bacteria. One “natural experiment” to test how evolutionary history, shared environments, and the interaction between these factors drive community composition is to compare geminate species pairs. Echinoids separated by the Isthmus of Panama are suitable for this comparison due to the known evolutionary history and differences in oceanographic characteristics of the Caribbean Sea and Pacific Ocean. By comparing the egg-associated microbiota for theEchinometraandDiademageminate species pairs, we show that both pairs of geminate species associate with distinct bacterial communities in patterns consistent with phylosymbiosis, and that the interaction between the evolutionary history of the host and the environment best explain differences in these communities. Moreover, we find that particular microbial taxa differed considerably between, but not within, oceans and that the microbiota of the two CaribbeanEchinometraspecies were dominated by the phototrophic Oxyphotobacteria.
Nutritional inter-dependencies and a carbazole-dioxygenase are key elements of a bacterial consortium relying on aSphingomonasfor the degradation of the fungicide thiabendazole
Authors: Sotirios Vasileiadis , Chiara Perruchon , Benjamin Scheer , Lorenz Adrian , Nicole Steinbach , Marco Trevisan , Patricia Plaza-Bolaños , Ana Agüera , Antonis Chatzinotas , Dimitrios Karpouzas G
Published: April 2020

Background

Thiabendazole (TBZ), is a benzimidazole fungicide and anthelminthic whose high persistence and toxicity pose a serious environmental threat. In our quest for environmental mitigation we previously isolated the first TBZ-degrading bacterial consortium and provided preliminary evidence for its composition and the degrading role of aSphingomonas. Here, we employed a multi-omic approach combined with DNA-stable isotope probing (SIP) to determine the genetic make-up of the key consortium members, to disentangle nutritional and metabolic interdependencies, to identify the transformation pathway of TBZ and to understand the genetic network driving its transformation.

Results

Time-series SIP in combination with amplicon sequencing analysis verified the key role ofSphingomonasin TBZ degradation by assimilating over 80% of the13C-labelled phenyl moiety of TBZ. Non-target mass spectroscopy (MS) analysis showed the accumulation of thiazole-4-carboxamidine as a single dead-end transformation product and no phenyl-containing derivative, in line with the phenyl moiety assimilation in the SIP analysis. Time series metagenomic analysis of the consortium supplemented with TBZ or succinate led to the assembly of 18 metagenome-assembled genomes (MAGs) with >80% completeness, six (Sphingomonas3X21F,γ-Proteobacterium34A,Bradyrhizobiaceae9B andHydrogenophaga19A, 13A, and 23F) being dominant. Meta-transcriptomic and -proteomic analysis suggested thatSphingomonasmobilize a carbazole dioxygenase (car) operon during the initial cleavage of TBZ to thiazole-4-carboxamidine and catechol, the latter is further transformed by enzymes encoded in a catecholortho-cleavage (cat) operon; both operons being up-regulated during TBZ degradation. Computational docking analysis of the terminal oxygenase component ofcar, CarAa, showed high affinity to TBZ, comparable to carbazole, reinforcing its high potency for TBZ transformation. These results suggest no interactions between consortium members in TBZ transformation, performed solely bySphingomonas. In contrast, gene expression network analysis revealed strong interactions betweenSphingomonasMAG 3X12F andHydrogenophagaMAG 23F, withHydrogenophagaactivating its cobalamin biosynthetic pathway andSphingomonasits cobalamin salvage pathway along TBZ degradation.

Conclusions

Our findings suggest interactions between consortium members which align with the “black queen hypothesis”:Sphingomonasdetoxifies TBZ, releasing consortium members by a toxicant; in return for this,Hydrogenophaga23F provides cobalamin to the auxotrophicSphingomonas.
AutoRELACS: Automated Generation And Analysis Of Ultra-parallel ChIP-seq
Authors: Arrigoni L. , Ferrari F. , Weller J. , Bella C. , Bönisch U. , Manke T.
Published: April 2020

Chromatin immunoprecipitation followed by sequencing (ChIP-seq) is a method used to profile protein-DNA interactions genome-wide. RELACS (Restriction Enzyme-based Labeling of Chromatinin Situ) is a recently developed ChIP-seq protocol that deploys a chromatin barcoding strategy to enable standardized and high-throughput generation of ChIP-seq data. The manual implementation of RELACS is constrained by human processivity in both data generation and data analysis. To overcome these limitations, we have developed AutoRELACS, an automated implementation of the RELACS protocol using the liquid handler Biomek i7 workstation. We match the unprecedented processivity in data generation allowed by AutoRELACS with the automated computation pipelines offered by snakePipes. In doing so, we build a continuous workflow that streamlines epigenetic profiling, from sample collection to biological interpretation. Here, we show that AutoRELACS successfully automates chromatin barcode integration, and is able to generate high-quality ChIP-seq data comparable with the standards of the manual protocol, also for limited amounts of biological samples.
Canonical and noncanonical features of the mouse visual cortical hierarchy
Authors: D’Souza Rinaldo D. , Wang Quanxin , Ji Weiqing , Meier Andrew M. , Kennedy Henry , Knoblauch Kenneth , Burkhalter Andreas
Published: April 2020

Neocortical circuit computations underlying active vision are performed by a distributed network of reciprocally connected, functionally specialized areas. Mouse visual cortex is a dense, hierarchically organized network, comprising subnetworks that form preferentially interconnected processing streams. To determine the detailed layout of the mouse visual hierarchy, laminar patterns formed by interareal axonal projections, originating in each of ten visual areas were analyzed. Reciprocally connected pairs of areas, and shared targets of pairs of source areas, exhibited structural features consistent with a hierarchical organization. Beta regression analyses, which estimated a continuous measure of hierarchical distance, indicated that the network comprises multiple hierarchies embedded within overlapping processing levels. Single unit recordings showed that within each processing stream, receptive field sizes typically increased with increasing hierarchical level; however, ventral stream areas showed overall larger receptive field diameters. Together, the results reveal canonical and noncanonical hierarchical network motifs in mouse visual cortex.
Minimal structural elements required for midline repulsive signaling and regulation ofDrosophilaRobo1
Authors: Brown Haley E. , Evans Timothy A.
Published: April 2020

The Roundabout (Robo) family of axon guidance receptors has a conserved ectodomain arrangement of five immunoglobulin-like (Ig) domains plus three fibronectin (Fn) repeats. Based on the strong evolutionary conservation of this domain structure among Robo receptors, as well asin vitrostructural and domain-domain interaction studies of Robo family members, this ectodomain arrangement is predicted to be important for Robo receptor signaling in response to Slit ligands. Here, we define the minimal ectodomain structure required for Slit binding and midline repulsive signalingin vivobyDrosophilaRobo1. We find that the majority of the Robo1 ectodomain is dispensable for both Slit binding and repulsive signaling. We show that a significant level of midline repulsive signaling activity is retained when all Robo1 ectodomain elements apart from Ig1 are deleted, and that the combination of Ig1 plus one additional ectodomain element (Ig2, Ig5, or Fn3) is sufficient to restore midline repulsion to wild type levels. Further, we find that deleting four out of five Robo1 Ig domains (ΔIg2-5) does not affect negative regulation of Robo1 by Commissureless (Comm) or Robo2, while variants lacking all three fibronectin repeats (ΔFn1-3 and ΔIg2-Fn3) are insensitive to regulation by both Comm and Robo2, signifying a novel regulatory role for Robo1’s Fn repeats. Our results provide anin vivoperspective on the importance of the conserved 5+3 ectodomain structure of Robo receptors, and suggest that specific biochemical properties and/or ectodomain structural conformations observedin vitrofor domains other than Ig1 may have limited significance forin vivosignaling in the context of midline repulsion.
Sequence analysis of SARS-CoV-2 genome reveals features important for vaccine design
Authors: Kames Jacob , Holcomb David D. , Kimchi Ofer , DiCuccio Michael , Hamasaki-Katagiri Nobuko , Wang Tony , Komar Anton A. , Alexaki Aikaterini , Kimchi-Sarfaty Chava
Published: April 2020

As the SARS-CoV-2 pandemic is rapidly progressing, the need for the development of an effective vaccine is critical. A promising approach for vaccine development is to generate, through codon pair deoptimization, an attenuated virus. This approach carries the advantage that it only requires limited knowledge specific to the virus in question, other than its genome sequence. Therefore, it is well suited for emerging viruses for which we may not have extensive data. We performed comprehensivein silicoanalyses of several features of SARS-CoV-2 genomic sequence (e.g., codon usage, codon pair usage, dinucleotide/junction dinucleotide usage, RNA structure around the frameshift region) in comparison with other members of the coronaviridae family of viruses, the overall human genome, and the transcriptome of specific human tissues such as lung, which are primarily targeted by the virus. Our analysis identified the spike (S) and nucleocapsid (N) proteins as promising targets for deoptimization and suggests a roadmap for SARS-CoV-2 vaccine development, which can be generalizable to other viruses.
rapidPop: Rapid population assessments of wildlife using camera trap data in R Shiny Applications
Authors: Tabak Michael A. , Lewis Jesse S. , Schlichting Peter E , Snow Nathan P. , VerCauteren Kurt C. , Miller Ryan S.
Published: April 2020

rapidPopis a new R package for implementing occupancy models for Rapid Population Assessments (RPAs) with data from camera traps. RPAs are designed to provide quick assessments of a density index so that users can identify relative changes in density associated with changes in conditions (Schlichtinget al., 2020). For example, users may want to assess if there was a change in density after an effort to cull an invasive species.rapidPopprovides a Shiny Application for running occupancy models with the option to include the effect of parameters on occupancy (e.g., before or after a culling operation).
Root xylem in three woody angiosperm species is not more vulnerable to embolism than stem xylem
Authors: Wu Min , Zhang Ya , Oya Thais , Marcati Carmen Regina , Pereira Luciano , Jansen Steven
Published: April 2020

Aims

Since plants are compartmentalised organisms, failure of their hydraulic transport system could differ between organs. We test here whether xylem tissue of stems and roots differ in their drought-induced embolism resistance, and whether intact roots are equally resistant to embolism than root segments.

Methods

Embolism resistance of stem and root xylem was measured based on the pneumatic technique forAcer campestre,A. pseudoplatanusandCorylus avellana, comparing also intact roots and root segments ofC. avellana. Moreover, we compared anatomical features such as interconduit pit membrane between roots and stems.

Results

We found a higher embolism resistance for roots than stems, although a significant difference was only found forA. pseudoplatanus.Interconduit pit membrane thickness was similar for both organs of the twoAcerspecies, but pit membranes were thicker in roots than stems ofC. avellana. Also, embolism resistance of an intact root network was similar to thick root segments forC. avellana.

Conclusion

Our observations show that root xylem is not more vulnerable to embolism than stem xylem, although more species need to be studied to test if this finding can be generalised. We also demonstrated that the pneumatic method can be applied to non-terminal plant samples.