bluuebunny/crossref_metadata_2025 huggingface dataset:
Shift of µ-opioid Receptor Signaling in the Dorsal Reticular Nucleus Is Implicated in Morphine-induced Hyperalgesia in Male Rats
Authors: Costa Ana Rita , Sousa Marília , Wilson Steven P. , Reguenga Carlos , Teixeira-Pinto Armando , Tavares Isaura , Martins Isabel
Published: June 2020

Background

Increased descending pain facilitation accounts for opioid-induced hyperalgesia, but the underlying mechanisms remain elusive. Given the role of µ-opioid receptors in opioid-induced hyperalgesia in animals, the authors hypothesized that the dorsal reticular nucleus, a medullary pain facilitatory area, is involved in opioid-induced hyperalgesia through altered µ-opioid receptor signaling.

Methods

The authors used male Wistar rats (n = 5 to 8 per group), chronically infused with morphine, to evaluate in the dorsal reticular nucleus the expressions of the µ-opioid receptor and phosphorylated cAMP response element-binding, a downstream marker of excitatory µ-opioid receptor signaling. The authors used pharmacologic and gene-mediated approaches. Nociceptive behaviors were evaluated by the von Frey and hot-plates tests.

Results

Lidocaine fully reversed mechanical and thermal hypersensitivity induced by chronic morphine. Morphine-infusion increased µ-opioid receptor, without concomitant messenger RNA changes, and phosphorylated cAMP response element-binding levels at the dorsal reticular nucleus. µ-opioid receptor knockdown in morphine-infused animals attenuated the decrease of mechanical thresholds and heat-evoked withdrawal latencies compared with the control vector (von Frey [mean ± SD]: −17 ± 8% vs. −40 ± 9.0%; P < 0.001; hot-plate: −10 ± 5% vs. −32 ± 10%; P = 0.001). µ-opioid receptor knockdown in control animals induced the opposite (von Frey: −31 ± 8% vs. −17 ± 8%; P = 0.053; hotplate: −24 ± 6% vs. −3 ± 10%; P = 0.001). The µ-opioid receptor agonist (D-ALA2,N-ME-PHE4,GLY5-OL)-enkephalin acetate (DAMGO) decreased mechanical thresholds and did not affect heat-evoked withdrawal latencies in morphine-infused animals. In control animals, DAMGO increased both mechanical thresholds and heat-evoked withdrawal latencies. Ultra-low-dose naloxone, which prevents the excitatory signaling of the µ-opioid receptor, administered alone, attenuated mechanical and thermal hypersensitivities, and coadministered with DAMGO, restored DAMGO analgesic effects and decreased phosphorylated cAMP response element-binding levels.

Conclusions

Chronic morphine shifted µ-opioid receptor signaling from inhibitory to excitatory at the dorsal reticular nucleus, likely enhancing descending facilitation during opioid-induced hyperalgesia in the rat.

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Opioid Alternatives in Spine Surgery: A Narrative Review
Authors: Rajan Shobana , Devarajan Jagan , Krishnaney Ajit , George Arun , Rasouli Jonathan J. , Avitsian Rafi
Published: June 2020

Adequate analgesia is known to improve outcomes after spine surgery. Despite recent attention highlighting the negative effects of narcotics and their addiction potential, opioids have been the mainstay of management for providing analgesia following spine surgeries. However, side effects including hyperalgesia, tolerance, and subsequent dependence restrict the generous usage of opioids. Multimodal analgesia regimens acting through different mechanisms offer significant opioid sparing and minimize the side effects of individual drugs. Hence, they are being increasingly incorporated into enhanced recovery protocols. Multimodal analgesia includes drugs such as N-methyl-D-aspartate antagonists, nonsteroidal anti-inflammatory drugs and membrane-stabilizing agents, neuraxial opioids, local anesthetic infiltration, and fascial compartment blocks. Analgesia started before the painful stimulus, termed preemptive analgesia, facilitates subsequent pain management. Both nonsteroidal anti-inflammatory drugs and neuraxial analgesia have been conclusively shown to reduce opioid requirements after spine surgery, and there is a resurgence of interest in the use of low-dose ketamine or methadone. Neuraxial narcotics offer enhanced analgesia for a longer duration with lower dosage and side effect profiles compared with systemic opioid administration. Fascial compartment blocks are increasingly used as they provide effective analgesia with fewer adverse effects. In this narrative review, we will discuss multimodality analgesic regimens incorporating opioid-sparing adjuvants to manage pain after spine surgery.
Costs of Care for Low-Energy Extremity Gunshot Injuries are Reduced With Standardized Treatment
Authors: Nguyen Mai P. , Savakus Jonathan C. , Reich Michael S. , Golob Joseph F. , McDonald Amy A. , Como John J. , Vallier Heather A.
Published: June 2020

Objectives:

(1) To determine the overall treatment costs associated with isolated low-energy gunshot wounds (GSWs) to the extremity and (2) to estimate cost savings associated with a single-dose IV antibiotic strategy administered in the emergency room for patients with simple GSWs.

Design:

Retrospective review.

Setting:

Level I trauma center.

Patients/Participants:

Patients (N = 380) with extremity-only GSW injuries from 2010 to 2015 were retrospectively reviewed. Treatment was recorded including type and duration of antibiotics, admission, and surgical intervention.

Main Outcome Measures:

Costs were calculated including facility services in the operating room and hospital.

Results:

There were 460 GSWs in 380 patients with a mean age of 30 years old. There were 309 admissions, 273 operations performed, and 1010 days of antibiotics prescribed. The total inpatient facility cost to treat all patients was $1,701,154. Among 179 patients who could be treated by the single-dose antibiotic care pathway for simple GSWs, 132 patients (73%) received additional treatment with 108 hospital admissions, 26 debridement surgeries, and 322 days of additional oral and/or IV antibiotics. The single-dose antibiotic care pathway would have saved an average of $1436 per patient with simple GSWs in actual facility expenses.

Conclusions:

The overall cost associated with isolated low-energy GSWs to the extremity is high. Limiting antibiotics to a single IV dose in the emergency room can reduce treatment expenses substantially for patients with simple GSWs.

Level of Evidence:

Economic Level IV. See instructions for authors for a complete description of levels of evidence.
Inflammation Profiling of Critically Ill Coronavirus Disease 2019 Patients
Authors: Fraser Douglas D. , Cepinskas Gediminas , Slessarev Marat , Martin Claudio , Daley Mark , Miller Michael R. , O’Gorman David B. , Gill Sean E. , Patterson Eric K. , dos Santos Claudia C.
Published: June 2020

Objectives:

Coronavirus disease 2019 is caused by severe acute respiratory syndrome-coronavirus-2 infection to which there is no community immunity. Patients admitted to ICUs have high mortality, with only supportive therapies available. Our aim was to profile plasma inflammatory analytes to help understand the host response to coronavirus disease 2019.

Design:

Daily blood inflammation profiling with immunoassays.

Setting:

Tertiary care ICU and academic laboratory.

Subjects:

All patients admitted to the ICU suspected of being infected with severe acute respiratory syndrome-coronavirus-2, using standardized hospital screening methodologies, had daily blood samples collected until either testing was confirmed negative on ICU day 3 (coronavirus disease 2019 negative), or until ICU day 7 if the patient was positive (coronavirus disease 2019 positive).

Interventions:

None.

Measurements and Main Results:

Age- and sex-matched healthy controls and ICU patients that were either coronavirus disease 2019 positive or coronavirus disease 2019 negative were enrolled. Cohorts were well-balanced with the exception that coronavirus disease 2019 positive patients were more likely than coronavirus disease 2019 negative patients to suffer bilateral pneumonia. Mortality rate for coronavirus disease 2019 positive ICU patients was 40%. We measured 57 inflammatory analytes and then analyzed with both conventional statistics and machine learning. Twenty inflammatory analytes were different between coronavirus disease 2019 positive patients and healthy controls (p < 0.01). Compared with coronavirus disease 2019 negative patients, coronavirus disease 2019 positive patients had 17 elevated inflammatory analytes on one or more of their ICU days 1–3 (p < 0.01), with feature classification identifying the top six analytes between cohorts as tumor necrosis factor, granzyme B, heat shock protein 70, interleukin-18, interferon-gamma-inducible protein 10, and elastase 2. While tumor necrosis factor, granzyme B, heat shock protein 70, and interleukin-18 were elevated for all seven ICU days, interferon-gamma-inducible protein 10 transiently elevated on ICU days 2 and 3 and elastase 2 increased over ICU days 2–7. Inflammation profiling predicted coronavirus disease 2019 status with 98% accuracy, whereas elevated heat shock protein 70 was strongly associated with mortality.

Conclusions:

While many inflammatory analytes were elevated in coronavirus disease 2019 positive ICU patients, relative to healthy controls, the top six analytes distinguishing coronavirus disease 2019 positive ICU patients from coronavirus disease 2019 negative ICU patients were tumor necrosis factor, granzyme B, heat shock protein 70, interleukin-18, interferon-gamma-inducible protein 10, and elastase 2.
Lymphomatoid Papulosis With a Unique T Follicular Helper–Like Phenotype
Authors: Tran Jessica , Duvic Madeleine , Torres-Cabala Carlos A.
Published: June 2020

Lymphomatoid papulosis (LyP) is a benign skin condition that typically presents with grouped or scattered lesions on the body that self-resolve within weeks or months of onset. LyP belongs to the group of CD30-positive lymphoproliferative disorders. Several histological variants of LyP exist, and the histological features of LyP can overlap with other lymphoproliferative disorders; therefore, both histological and clinical correlations are needed for a proper diagnosis of LyP. We report an unusual case of LyP displaying a T follicular helper cell–like phenotype and histopathologically resembling the primary cutaneous CD4-positive small-sized to medium-sized T-cell lymphoproliferative disorder.
Antihyperglycemic Therapies With Expansions of US Food and Drug Administration Indications to Reduce Cardiovascular Events: Prescribing Patterns Within an Academic Medical Center
Authors: Hamid Arsalan , Vaduganathan Muthiah , Oshunbade Adebamike A. , Ayyalasomayajula Krishna K. , Kalogeropoulos Andreas P. , Lien Lillian F. , Shafi Tariq , Hall Michael E. , Butler Javed
Published: June 2020

Sodium-glucose cotransport protein-2 inhibitors (SGLT2is) and glucagon-like peptide-1 receptor agonists (GLP-1RAs) have been shown to reduce cardiovascular events in high-risk patients with type 2 diabetes mellitus (T2DM). We examined real-world use of these agents at a US academic medical center in the state of Mississippi. Prescriptions, provider specialty, and insurance status of users of SGLT2is and GLP-1RAs in patients with T2DM, and T2DM and cardiovascular disease (CVD) seen from 1st January 2013 to 30th June 2019 were obtained by electronic health records review. We identified 21,173 patients with T2DM and CVD. Overall, 306 (1.4%) and 349 (1.6%) patients received a SGLT2i and GLP-1RA, respectively. After the US Food and Drug Administration (FDA) expanded empagliflozin and liraglutide indications, a mean difference of 19.2 and 12.7 greater quarterly new prescriptions was noted, respectively, whereas no such rise in canagliflozin was observed. Primary care physicians accounted for 53.4% SGLT2i prescriptions, endocrinology for 30.3%, and cardiology for 6.0%. Primary care physicians accounted for 45.1% GLP-1RA prescriptions, endocrinology for 45.0%, and cardiology for 1.4%. Prescription patterns did not largely differ by patient insurance status. In conclusion, prescription of evidence-based therapies to improve CVD outcomes in high-risk patients with T2DM remains very low after several years of evidence generation. Low uptake was evident across insurance types. Modest increases in use were observed after regulatory expansions in labeling; however, cardiologists rarely engaged in prescription, underscoring the need for widespread implementation strategies across health care systems.
Transgender Men and the Gynecologist
Authors: MAYHEW ALLISON C. , COHEN ARIEL , GOMEZ-LOBO VERONICA
Published: June 2020

Recently, greater attention has been paid to the care of gender dysphoric and gender incongruent individuals. Gynecologists may be called upon to care for individuals who were assigned female at birth throughout or following social, medical, or surgical gender transition. Thus, gynecologists need to be aware of language regarding sex and gender, treatment typically used for the care of gender dysphoric or incongruent individuals, and aspects of well gynecologic care necessary for these individuals. This review highlights these aspects of care for transgender males to aid the general gynecologist in the care and treatment of these individuals.
QUANTITATIVE TOPOGRAPHIC CURVATURE MAPS OF THE POSTERIOR EYE UTILIZING OPTICAL COHERENCE TOMOGRAPHY
Authors: McNabb Ryan P. , Liu Alice S. , Gospe Sidney M. , El-Dairi Mays , Meekins Landon C. , James Charlene , Vann Robin R. , Izatt Joseph A. , Kuo Anthony N.
Published: June 2020

Purpose:

Deformations of the retina such as staphylomas in myopia or scleral flattening in high intracranial pressure can be challenging to quantify with en face imaging. We describe an optical coherence tomography-based method for the generation of quantitative posterior eye topography maps in normal and pathologic eyes.

Methods:

Using “whole eye” optical coherence tomography, we corrected for subjects' optical distortions to generate spatially accurate posterior eye optical coherence tomography volumes and created local curvature (K

M
, mm−1) topography maps for each consented subject. We imaged nine subjects, three normal, two with myopic degeneration, and four with papilledema including one that was imaged longitudinally.

Results:

Normal subjects mean temporal K

M
was 0.0923 mm−1, nasal K

M
was 0.0927 mm−1, and K

M
local variability was 0.0162 mm−1. In myopic degeneration, subjects K

M
local variability was higher at 0.0836 mm−1. In papilledema subjects nasal K

M
was flatter compared with temporal K

M
(0.0709 vs. 0.0885 mm−1). Mean intrasession K

M
repeatability for all subjects was 0.0036 mm−1.

Conclusion:

We have developed an optical coherence tomography based method for quantitative posterior eye topography that offers the ability to analyze local curvature with micron scale resolution and offers the potential to help clinicians and researchers characterize subtle, local retinal deformations earlier in patients and follow their development over time.
Aerosol generation through phacoemulsification
Authors: Lee Hanbin , Naveed Hasan , Ashena Zahra , Nanavaty Mayank A.
Published: June 2020

Purpose:

To evaluate whether phacoemulsification is an aerosol-generating procedure in an ex vivo experimental model.

Setting:

Sussex Eye Hospital, Brighton, United Kingdom.

Design:

Experimental study.

Methods:

In this ex vivo study on 15 porcine eyes, an optical particle counter was used to measure particles of 10 µm and less using the cumulative mode based on the 6 in-built channel sizes. The 2 parts of the study were to: (1) assess the efficacy of the particle counter in the theater environment where there are dynamic changes in temperature and humidity; and (2) to measure aerosol generation with 3 phacoemulsification settings: (i) continuous power with 80% longitudinal (5 eyes); (ii) continuous power with 100% torsional (5 eyes); and (iii) continuous power with 80% longitudinal with application of hydroxypropyl methylcellulose (HPMC) on the ocular surface (5 eyes). Five measurements were taken prephacoemulsification and 5 during phacoemulsification per eye therefore totaling 75 measurements.

Results:

Maximum aerosols were captured when the counter faced the aerosol source. There was no significant difference in aerosol generation of all sizes during each phacoemulsification setting with torsional, longitudinal, and longitudinal with HPMC (P > .01). Combining data of all 3 phacoemulsification settings (150 measurements from 15 eyes), there was no significant difference comparing prephacoemulsification and during phacoemulsification for aerosols of 5 µm or less (1455 vs 1363.85, P = .60), more than 5 to 10 μm (1.5 vs 1.03, P = .43), and of 10 µm or less (1209 vs 1131.55, P = .60).

Conclusions:

Phacoemulsification did not generate aerosols of 10 μm or less with continuous power using 80% longitudinal, 100% torsional, and 80% longitudinal setting with HPMC on the surface.
The era of artificial intelligence–based individualized telemedicine is coming
Authors: Jheng Ying-Chun , Kao Chung-Lan , Yarmishyn Aliaksandr A. , Chou Yu-Bai , Hsu Chih-Chien , Lin Tai-Chi , Hu Hou-Kai , Ho Ta-Kai , Chen Po-Yin , Kao Zih-Kai , Chen Shih-Jen , Hwang De-Kuang
Published: June 2020

Artificial intelligence (AI), Internet of Things (IoT), and telemedicine are deeply involved in our daily life and have also been extensively applied in the medical field, especially in ophthalmology. Clinical ophthalmologists are required to perform a vast array of image exams and analyze images containing complicated information, which allows them to diagnose the disease type and grade, make a decision on remedy, and predict treatment outcomes. AI has a great potential to assist ophthalmologists in their daily routine of image analysis and relieve their work burden. However, in spite of these prospects, the application of AI may also be controversial and associated with several legal, ethical, and sociological concerns. In spite of these issues, AI has indeed become an irresistible trend and is widely used by medical specialists in their daily routines in what we can call now, the era of AI. This review will encompass those issues and focus on recent research on the AI application in ophthalmology and telemedicine.
Assessment of Gastric Emptying Times Between Pediatrics and Adults With Cyclic Vomiting Syndrome
Authors: Kamal Afrin , Sarvepalli Shashank , Selvakumar Praveen , Lopez Rocio , Radhakrishnan Kadakkal , Gabbard Scott
Published: June 2020

Background & Aims:

Cyclic vomiting syndrome (CVS) is characterized by episodes of nausea and vomiting separated by symptom-free intervals. Rome IV guidelines have now distinguished CVS from other disorders such as cannabinoid hyperemesis. The pathogenesis of CVS, however, is poorly understood. Limited data exist on gastric emptying (GE) in patients with CVS. Therefore, the authors aim to measure the GE profile in pediatrics and adults with CVS.

Materials and Methods:

Patients with the diagnosis of CVS (per NASPGHAN and Rome IV) between December 1998 and March 2017 who underwent gastric emptying study (GES) and without documented cannabis use were included. Clinical features including demographics, medication use, and comorbidities were also recorded. Frequency of rapid, normal, and delayed emptying was reported, and multinomial univariate logistic regression was used to identify factors associated with each type of emptying.

Key Results:

Sixty-seven subjects were included (50.7% female individuals, pediatrics n=15, adults n=52). At 2-hour retention, 40% of pediatric patients met criteria for rapid, 33.3% for normal, and 26.7% for delayed GE. In adults, 50% met criteria for rapid, 46.2% for normal, and 3.8% for delayed GE. For every 5-year increase in age, odds of rapid emptying on GES increased.

Conclusions:

(1) GE is predominantly rapid at 2 hours in pediatrics and adults with CVS. (2) Rapid GE seems to increase with age. (3) Current guidelines do not recommend GE in the initial management, however, further studies may play a role to help differentiate CVS from other functional gastric disorders.
Dual tracer 68Ga-DOTATOC and 18F-FDG PET/computed tomography radiomics in pancreatic neuroendocrine neoplasms: an endearing tool for preoperative risk assessment
Authors: Mapelli Paola , Partelli Stefano , Salgarello Matteo , Doraku Joniada , Pasetto Stefano , Rancoita Paola M.V. , Muffatti Francesca , Bettinardi Valentino , Presotto Luca , Andreasi Valentina , Gianolli Luigi , Picchio Maria , Falconi Massimo
Published: June 2020

Aim

To explore the potentiality of radiomics analysis, performed on 68Ga-DOTATOC and fluorine-18-fluorodeoxyglucose (18F-FDG) PET/computed tomography (CT) images, in predicting tumour aggressiveness and outcome in patients candidate to surgery for pancreatic neuroendocrine neoplasms (PanNENs).

Patients and methods

Retrospective study including 61 patients who underwent 68Ga-DOTATOC and 18F-FDG PET/CT before surgery for PanNEN. Semiquantitative variables [SUVmax and somatostatin receptor density (SRD) for 68Ga-DOTATOC PET; SUVmax and MTV for 18F-FDG PET] and texture features [intensity variability, size zone variability (SZV), zone percentage, entropy; homogeneity, dissimilarity and coefficient of variation (Co-V)] have been analysed to evaluate their possible role in predicting tumour characteristics. Principal component analysis (PCA) was firstly performed and then multiple regression analyses were performed by using the extracted principal components.

Results

Regarding 68Ga-DOTATOC PET, SZV, entropy, intensity variability and SRD were predictive for tumour dimension. Regarding 18F-FDG PET, intensity variability, SZV, homogeneity, SUVmax and MTV were predictive for tumour dimension. Four principal components were extracted from PCA: PC1 correlated with all 18F-FDG variables, while PC2, PC3 and PC4 with 68Ga-DOTATOC variables. PC1 was the only significantly predicting angioinvasion (P = 0.0222); PC4 was the only one significantly predicting lymph nodal involvement (P = 0.0151). All principal components except PC4 significantly predicted tumour dimension (P  <0.0001 for PC1, P = 0.0016 for PC2 and P < 0.0001 for PC3). Co-V from 68Ga-DOTATOC PET/CT was predictive of the outcome.

Conclusion

Specific texture features derived from preoperative 68Ga-DOTATOC and 18F-FDG PET/CT could noninvasively predict specific tumour characteristics and patients’ outcome, delineating the potential role of dual tracer technique and texture analysis in the risk assessment of patients with PanNENs.
Cerebral Hemodynamic Profile in Ischemic and Hemorrhagic Brain Injury Acquired During Pediatric Extracorporeal Membrane Oxygenation
Authors: Tian Fenghua , Farhat Abdelaziz , Morriss Michael C , Tweed Jefferson , Li Xilong , Huet Beverley , Thiagarajan Ravi R. , Raman Lakshmi
Published: June 2020

Objectives:

To describe the cerebral hemodynamic profiles associated with ischemic and hemorrhagic brain injury during neonatal and pediatric extracorporeal membrane oxygenation.

Design:

A retrospective cohort study.

Setting:

Tertiary PICU.

Patients:

Forty-seven neonatal and pediatric patients (0–15 yr of age) placed on extracorporeal membrane oxygenation from January 2014 to December 2018.

Measurements and Main Results:

Continuous monitoring of mean arterial pressure and cerebral tissue oxygen saturation was conducted through entire extracorporeal membrane oxygenation run. Wavelet analysis was performed to assess changes in cerebral autoregulation and to derive pressure-dependent autoregulation curves based on the mean arterial pressure and cerebral tissue oxygen saturation data. Patients were classified into three brain injury groups: no-injury, ischemic injury, and hemorrhagic injury based on neuroimaging results. No-injury patients (n = 23) had minimal variability in the autoregulation curve over a broad range of blood pressure. Ischemic injury (n = 16) was more common than hemorrhagic injury (n = 8), and the former was associated with increased mortality and morbidity. Ischemic group showed significant abnormalities in cerebral autoregulation in the lower blood pressure range, suggesting pressure-dependent cerebral perfusion. Hemorrhagic group had highest average blood pressure as well as the lowest cerebral tissue oxygenation saturation, suggesting elevated cerebral vascular resistance. Mean heparin dose during extracorporeal membrane oxygenation was lower in both ischemic and hemorrhagic groups compared with the no-injury group.

Conclusions:

This study outlines distinct differences in underlying cerebral hemodynamics associated with ischemic and hemorrhagic brain injury acquired during extracorporeal membrane oxygenation. Real-time monitoring of cerebral hemodynamics in patients acquiring brain injury during extracorporeal membrane oxygenation can help optimize their management.
Malaria in HIV-infected patients in a nonendemic setting
Authors: Lam Elina , Hites Maya , Cantinieaux Brigitte , Van Laethem Yves , De Wit Stéphane , Martin Charlotte
Published: June 2020

Background:

The impact of HIV infection on malaria is unclear in nonendemic areas. In endemic territories, HIV has been reported to be a risk factor for higher morbidity. Nowadays, as HIV-infected patients travel more, it is important to assess the impact of HIV at the individual level on imported malaria.

Material and methods:

This retrospective case–control study collected data on HIV-infected patients diagnosed with malaria (2000–2017) and matched them with two controls based on age, sex and ethnicity. Clinical and biological parameters were collected and compared.

Results:

We identified 47 cases and matched them with 94 controls. Comparing each of the WHO 2014 severity criteria, hyperparasitemia above 10% (P = 0.006; 12.8 versus 1.1%), icterus (P = 0.042; 14.9 versus 4.3%), acute renal failure (P = 0.022; 25.5 versus 9.6%) and bacteraemia (P = 0.014; 6.4 versus 0%) were significantly more present in HIV-infected patients with a trend to more cerebral malaria (12.8 versus 6.4%). HIV- infected patients were hospitalized more frequently and for longer periods. We observed a higher number of severity criteria when CD4+ T-cell count was lower, especially below 200 cells/μl. The difference in occurrence of severe malaria disappeared when patients with CD4+ T-cell count more than 500 cells/μl and undetectable viral load (n = 9) were compared with controls. De-novo HIV diagnosis was made during the malaria episode in 17% of cases.

Conclusion:

HIV infection has an impact on the imported malaria profile, although it is unclear whether well controlled HIV-infected patients have a higher risk of severe malaria. HIV-infected patients should be particularly targeted for pretravel advice.
Choosing Daily Labs Wisely in the Hospital: A Novel Tool for Assessing Laboratory Testing Appropriateness
Authors: Murphy Caleb J. , Duran Alisa M. , Diem Susan J. , Bowman Peterson Jill M.
Published: June 2020

Background:

The Minnesota Lab Appropriateness (MLAB) criteria were developed for assessing appropriateness of complete blood counts (CBCs) and serum electrolyte panels (SEPs) ordered for adult inpatients.

Methods:

Two independent raters used the MLAB criteria to rate appropriateness of labs ordered during 50 hospitalizations through retrospective medical record review.

Results:

Evaluation of 208 CBCs and 253 SEPs on a 2-category scale (appropriate/inappropriate) resulted in an inappropriate lab rate of 24% and 25% for CBCs and SEPs, respectively. Using a 3-category Likert scale that included an “equivocal” rating to allow for clinical uncertainty, 17% of CBCs and 20% of SEPs were considered inappropriate. Interrater reliability was “substantial” using the dichotomous scale for both CBCs and SEPs. Using the 3-category Likert scale, reliability was “substantial” for CBCs and “moderate” for SEPs.

Conclusion:

The MLAB criteria identified inappropriate labs at a rate consistent with published figures, with good interrater reliability.
Uncommon Childhood Unilateral Cervical Giant Thymic Cyst
Authors: Aydin Ahmet Halit , Çakli Hamdi , Canaz Funda , Uzun Tankut
Published: June 2020

Cervical thymic cysts are rare and present in the first decade of life. They constitute 0.3% to 1% of congenital neck masses. Thymic tissue foci, which exist between the mandible and the mediastinum, can be found at the descent of the thymic primordium. Thymic cysts should be considered in pediatric patients who present with cervical neck masses. The diagnosis of thymic cysts can only be made by histopathologic examinations. In recent years, the number of reports of thymic cyst cases have increased, one possible cause being the heightened awareness of thymic cysts among pathologists.
Epidemiology and Pattern of Oral and Maxillofacial Trauma
Authors: Wusiman Patiguli , Maimaitituerxun Buhailiqiguli , Guli  , Saimaiti Adilijiang , Moming Adili
Published: June 2020

Purpose:

Maxillofacial trauma represents a serious public health problem and their epidemiology is extremely variable.

The objective of the present study was to analyze and discuss the epidemiological characteristics of 2492 patients with oral and maxillofacial trauma over a 5-year period.

Patients and Methods:

This retrospective study was conducted at different hospitals of Xinjiang from 2012 to 2016. Data were collected for the cause of injury, age and gender distribution, frequency and type of injury, localization and frequency of soft tissue injuries, dentoalveolar trauma, facial bone fractures, presence of associated injuries, nerve injury, different treatment protocols. All the data were analyzed using statistical analysis that is chi squared test.

Statistical analyses performed included descriptive analysis, chi square test, and logistic regression analyses.

Results:

A total of 2492 maxillofacial trauma patients were seen in 1981 patients with a male to female ratio of 3.88:1. The age group 21 to 30 years accounted for the largest subgroup in both sexes. The most common etiology of the trauma was traffic accident, accounted for 41.8%. The mandible (31.97%) was the most common site of fracture followed by the zygoma (25.3%). The common type associated injuries was limb injury (27.5%), it was followed by brain (24.5%) and eye (21.4%) injuries. The common nerve injury was the facial nerve injury, accounting for 62.9%.

Conclusion:

The incidence of oral and maxillofacial trauma is related to gender, age, and the cause of trauma. Young adults are the most likely group (P < 0.05). Maxillofacial trauma is often associated with limb, craniocerebral, and eye injuries. Traffic accident is the main cause of maxillofacial injury (P < 0.5).
The Effect of Probiotic Supplementation on Glycemic Control in Women With Gestational Diabetes Mellitus
Authors: Koczarski Molly
Published: June 2020

Benefits of probiotic supplementation for symptoms associated with gestational diabetes are limited. The purpose of this review was to investigate the effects of probiotic supplementation on glycemic control in women with gestational diabetes mellitus (GDM). A systematic search for randomized controlled trials (RCTs) reporting probiotic supplementation in GDM patients (2000 through 2019) yielded 65 articles. Eight RCTs met the criteria for inclusion. Probiotics decreased fasting plasma glucose and serum insulin levels. Significant effects were found on insulin resistance, insulin sensitivity, and lipid profiles. Probiotic supplementation may improve glycemic control, insulin resistance, and lipid profiles; more research is needed.
Motor Cortex Function in APOE4 Carriers and Noncarriers
Authors: Yasen Alia L. , Eick Geeta N. , Sterner Kirstin N. , Christie Anita D.
Published: June 2020

Purpose:

The ε4 allele of the apolipoprotein-E gene has been associated with disease activity including Alzheimer disease, multiple sclerosis, and cardiovascular disease. Individuals who possess the ε4 variant of this gene (ε4 carriers) also demonstrate higher levels of cognitive impairment and lower motor scores compared with noncarriers. The purpose of this study was to establish whether there is a difference in motor cortex function between apoε4 carriers and noncarriers. We hypothesized that carriers would have lower levels of excitability and excitatory transmitter (glutamate) and similar levels of intracortical inhibition and inhibitory neurotransmitter (gamma-aminobutyric acid) than noncarriers.

Methods:

Fifty-two participants provided saliva samples to determine apoε4 carrier status. Measures of motor cortex excitability and inhibition were obtained using transcranial magnetic stimulation, and measures of glutamate and gamma-aminobutyric acid concentrations were obtained using proton magnetic resonance spectroscopy.

Results:

No significant differences in transcranial magnetic stimulation (P ≥ 0.19) or proton magnetic resonance spectroscopy measures (P ≥ 0.90) were found between carriers and noncarriers.

Conclusions:

The results from this study suggest that motor cortex function, as assessed by transcranial magnetic stimulation measures of excitability and inhibition, and MRS measures of excitatory and inhibitory neurotransmitter are similar in those who possess an apoε4 allele and those who do not.
Identification of a PGXPP degron motif in dishevelled and structural basis for its binding to the E3 ligase KLHL12
Authors: Chen Zhuoyao , Wasney Gregory A. , Picaud Sarah , Filippakopoulos Panagis , Vedadi Masoud , D'Angiolella Vincenzo , Bullock Alex N.
Published: June 2020

Wnt signalling is dependent on dishevelled proteins (DVL1-3), which assemble an intracellular Wnt signalosome at the plasma membrane. The levels of DVL1-3 are regulated by multiple Cullin-RING E3 ligases that mediate their ubiquitination and degradation. The BTB-Kelch protein KLHL12 was the first E3 ubiquitin ligase to be identified for DVL1-3, but the molecular mechanisms determining its substrate interactions have remained unknown. Here, we mapped the interaction of DVL1-3 to a ‘PGXPP' motif that is conserved in other known partners and substrates of KLHL12, including PLEKHA4, PEF1, SEC31 and DRD4. To determine the binding mechanism, we solved a 2.4 Å crystal structure of the Kelch domain of KLHL12 in complex with a DVL1 peptide that bound with low micromolar affinity. The DVL1 substrate adopted a U-shaped turn conformation that enabled hydrophobic interactions with all six blades of the Kelch domain β-propeller. In cells, the mutation or deletion of this motif reduced the binding and ubiquitination of DVL1 and increased its stability confirming this sequence as a degron motif for KLHL12 recruitment. These results define the molecular mechanisms determining DVL regulation by KLHL12 and establish the KLHL12 Kelch domain as a new protein interaction module for a novel proline-rich motif.
Thrombotic microvascular injury is not mediated by thrombotic microangiopathy despite systemic complement activation in Covid-19 patients
Authors: De Voeght Adrien , Calmes Doriane , Beck Floran , Sylvestre Jean-Baptiste , Delvenne Philippe , Peters Pierre , Vertenoeil Gaelle , Baron Frédéric , Layios Nathalie , Canivet Jean-Luc
Published: June 2020

Hypoxemia and coagulopathy are common in severe symptomatic patients of coronavirus disease 2019 (COVID-19). Histological evidence shows implication of complement activation and lung injury. We research sign of complement activation and presence of thrombotic microangiopathy in 8 severe patients. Six of them presented moderate elevation of final pathway of complement – sC5b-9 (median value : 350 ng/mL [IQR : 300,5 - 514,95 ng/mL]). Two patients have been autopsied and presence of thrombotic microvascular injury have been found. Interestingly, none the 8 patients had signs of mechanical hemolytic anemia (median value of hemoglobin : 10,5 gr/dL[IQR : 8,1 - 11,9], median value of haptoglobuline 4,49 [IQR 3,55-4,66], none of the patients has schistocyte) and thrombocytopenia (median value: 348000/mL [IQR : 266 000 - 401 000). Finally, all 8 patients had elevated d-dimer (median value : 2226 µgr/l [IQR : 1493 – 2362]) and soluble fibrin monomer complex (median value : 8.5 mg/mL, IQR[<6 – 10.6]). In summary, this study show moderate activation of complement and coagulation with presence of thrombotic microvascular injury in patients with severe COVID-19 without evidence of systemic thrombotic microangiopathy.

Key points

Severe covid-19 patients show moderate elevation of final activation of complement

No sign of Thrombotic microangiopathy is found in severe covid-19 patients
What association do political interventions, environmental and health variables have with the number of Covid-19 cases and deaths? A linear modeling approach
Authors: Walach Harald , Hockertz Stefan
Published: June 2020

Background and Question

It is unclear which variables contribute to the variance in corona-virus disease (Covid-19) related deaths and Corono-virus2 (Cov2) cases. We wanted to see which contribution public health variables make in addition to health systems, health, and population variables to explain Covid-19 cases and deaths

Method

We modelled the relationship of various predictors (health systems variables, population and population health indicators) together with variables indicating public health measures (school closures, border closures, country lockdown) in 40 European and other countries, using Generalized Linear Models and minimized information criteria to select the best fitting and most parsimonious models.

Results

We fitted two models with log-linearly linked variables on gamma-distributed outome variables (CoV2 cases and Covid-19 related deaths, standardized on population). CoV2-cases were best predicted by number of tests (b = 2*10−7, p =.00005), life-expectancy in a country (b = 0.19, p < .000001), and border closure (b = −0.93, p = .001). Population standardized deaths were best predicted by time, the virus had been in the country (b = 0.02, p = .02), life expectancy (b = 0.2, p = .000005), smoking (b = −0.08, p = .00001), and school closures (b = 2.54, p = .0001). Model fit statistics and model adequacy were good (model 1: Chi2/DF = 0.43; model 2: Chi2/DF = 0.88).

Discussion and Interpretation

Only few variables were good predictors. Of the public health variables only border closure had the potential of preventing cases and none were predictors for preventing deaths. School closures, likely as a proxy for social distancing in severely ill patients, was associated with increased deaths.

Conclusion

The pandemic seems to run its autonomous course and only border closure has the potential to prevent cases. None of them contributes to preventing deaths.
A systematic review and meta-analysis reveals long and dispersive incubation period of COVID-19
Authors: Wei Yongyue , Wei Liangmin , Liu Yihan , Huang Lihong , Shen Sipeng , Zhang Ruyang , Chen Jiajin , Zhao Yang , Shen Hongbing , Chen Feng
Published: June 2020

Background

The incubation period of SARS-CoV-2 remains uncertain, which has important implications for estimating transmission potential, forecasting epidemic trends, and decision-making in prevention and control.

Purpose

To estimate the central tendency and dispersion for incubation period of COVID-19 and, in turn, assess the effect of a certain length of quarantine for close contacts in active monitoring.

Data Sources

PubMed, Embase, medRxiv, bioRxiv, and arXiv, searched up to April 26, 2020

Study Selection

COVID-19 studies that described either individual-level incubation period data or summarized statistics for central tendency and dispersion measures of incubation period were recruited.

Data Extraction

From each recruited study, either individual-level incubation period data or summarized statistics for central tendency and dispersion measures were extracted, as well as population characteristics including sample size, average age, and male proportion.

Data Synthesis

Fifty-six studies encompassing 4 095 cases were included in this meta-analysis. The estimated median incubation period for general transmissions was 5.8 days [95% confidence interval (95%CI), 5.3 to 6.2 d]. Median and dispersion were higher for SARS-CoV-2 incubation compared to other viral respiratory infections. Furthermore, about 20 in 10 000 contacts in active monitoring would develop symptoms after 14 days, or below 1 in 10 000 for young-age infections or asymptomatic transmissions.

Limitation

Small sample sizes for subgroups; some data were possibly used repeatedly in different studies; limited studies for outside mainland China; non-negligible intra-study heterogeneity.

Conclusion

The long, dispersive incubation period of SARS-CoV-2 contributes to the global spread of COVID-19. Yet, a 14-day quarantine period is sufficient to trace and identify symptomatic infections, which while could be justified according to a better understanding of the crucial parameters.
Draft genome sequence of the pulse crop blackgram [Vigna mungo(L.) Hepper] reveals potential R-genes
Authors: Souframanien J , Raizada Avi , Dhanasekar Punniyamoorthy , Suprasanna Penna
Published: June 2020

Blackgram [Vigna mungo(L.) Hepper] (2n = 2x = 22), an important Asiatic legume crop, is a major source of dietary protein for the predominantly vegetarian population. Here we construct a draft genome sequence of blackgram, for the first time, by employing hybrid genome assembly with Illumina reads and third generation Oxford Nanopore sequencing technology. The finalde novowhole genome of blackgram is ~ 475 Mb (82 % of the genome) and has maximum scaffold length of 6.3 Mb with scaffold N50 of1.42 Mb. Genome analysis identified 18655 genes with mean coding sequence length of 970bp. Around 96.7 % of predicted genes were annotated. Nearly half of the assembled sequence is composed of repetitive elements with retrotransposons as major (47.3% of genome) transposable elements, whereas, DNA transposons made up only 2.29% of the genome. A total of 166014 SSRs, including 65180 compound SSRs, were identified and primer pairs for 34816 SSRs were designed. Out of the 18665 proteins, 678 proteins showed presence of R-gene related domains. KIN class was found in majority of the proteins (372) followed by RLK (79) and N (79). The genome sequence of blackgram will facilitate identification of agronomically important genes and accelerate the genetic improvement of blackgram.
Health and Economic Costs of Early, Delayed and No Suppression of COVID-19: The Case of Australia
Authors: Kompas Tom , Grafton R. Quentin , Che Tuong Nhu , Chu Long , Camac James
Published: June 2020

We compare the health and economic costs of early (actual), delayed and no suppression of COVID-19 infections in 2020 in Australia. Using a fit-for-purpose compartment model that we fitted from recorded data, a value of a statistical life year (VSLY) and an age-adjusted value of statistical life (A-VSL), we find: (1) the economic costs of no suppression are multiples more than for early suppression; (2) VSLY welfare losses of fatalities equivalent to GDP losses mean that for early suppression to not to be the preferred strategy requires that Australians prefer more than 12,500–30,000 deaths to the economy costs of early suppression, depending on the fatality rate; and (3) early rather than delayed suppression imposes much lower economy and health costs. We conclude that in high-income countries, like Australia, a ‘go early, go hard’ strategy to suppress COVID-19 results in the lowest estimated public health and economy costs.
The role of pre-existing chronic disease in cardiac complications from SARS-CoV-2 infection: A systematic review and meta-analysis
Authors: Sinclair Jane E. , Zhu Yanshan , Xu Gang , Ma Wei , Shi Haiyan , Ma Kun-Long , Cao Chun-Feng , Kong Ling-Xi , Wan Ke-Qiang , Liao Juan , Wang Hai-Qiang , Arentz Matt , Redd Meredith , Gallo Linda A. , Short Kirsty R.
Published: June 2020

Importance

SARS-CoV-2 is associated with multiple direct and indirect effects to the heart. It is not yet well defined whether patient groups at increased risk of severe respiratory disease due to SARS-CoV-2 infection also experience a heightened incidence of cardiac complications.

Objective

We sought to analyse the role of pre-existing chronic disease (chronic respiratory illness, cardiovascular disease (CVD), hypertension and diabetes mellitus) in the development of cardiac complications from SARS-CoV-2.

Data Sources

We retrospectively investigated published (including pre-prints), publicly released, de-identified, data made available between Dec 1, 2019, and May 11, 2020. Information was accessed from PubMed, Embase, medRxiv and SSRN.

Study Selection

379 full-text articles were reviewed and 321 excluded for lack of original research, irrelevance to outcome, inappropriate cohort, or small patient numbers (case reports of <10 patients). Data were extracted from two studies and the remaining 56 contacted to request appropriate data, to which three responded with data contributions. A final of five studies were included.

Data Extraction and Synthesis

This systematic review was conducted based on PRISMA and MOOSE statements. Included studies were critically appraised using Newcastle Ottawa Quality Assessment Scale (NOS). Data were extracted independently by multiple observers. A fixed-effects model was selected for the meta-analysis based on relatively low heterogeneity between the studies (I2<50%).

Main Outcome and Measures

Cardiac complications were determined via blood levels of cardiac biomarkers above the 99thpercentile of the upper reference limit, abnormalities in electrocardiography, and/or abnormalities in echocardiography.

Results

SARS-CoV-2-infected patients who developed cardiac complications were, on average, 10 years older than those that did not. Pooled analyses showed the development of cardiac complications from SARS-CoV-2 was significantly increased in patients with underlying chronic respiratory illness (OR 2.88[1.45,5.71]), CVD (OR 5.12[3.09,8.48]), hypertension (OR 4.37[2.99,6.39]) and diabetes mellitus (OR 2.61[1.67,4.09]).

Conclusions and Relevance

Older age and pre-existing chronic respiratory illness, CVD, hypertension, and diabetes mellitus may represent prognostic factors for the development of additional cardiac complications in COVID-19, highlighting the need for a multidisciplinary approach to chronic disease patient management and providing justification for a larger scale observational study.
Dragon III- Phase II Randomized Controlled Trial: Neoadjuvant FLOT versus SOX for Patients with Locally Advanced Gastric Cancer
Authors: Sah Birendra Kumar , Zhang Benyan , Zhang Huan , Li Jian , Yuan Fei , Ma Tao , Shi Min , Xu Wei , Zhu Zhenglun , Liu Wentao , Yan Chao , Li Chen , Liu Bingya , Yan Min , Zhu Zhenggang
Published: June 2020

Background

Neoadjuvant chemotherapy with docetaxel, oxaliplatin, fluorouracil, and leucovorin (the FLOT regimen) has shown promising results in terms of pathological response and survival rate. However, tegafur gimeracil oteracil potassium capsule (S-1) plus oxaliplatin (the SOX regimen) is a more favorable chemotherapy regimen in Eastern countries. We conducted this study to evaluate the safety and efficacy of both regimens and to explore a suitable regimen for gastric cancer patients.

Methods

Patients with locally advanced gastric cancer (LAGC) were 1:1 randomly assigned to receive either 4 cycles of the FLOT regimen or 3 cycles of the SOX regimen before curative gastrectomy. The primary endpoint was the comparison of complete or subtotal tumor regression grading (TRG1a+ TRG1b) in the primary tumor.

Results

Altogether, 74 patients were enrolled between August 2018 and March 2020. There was no significant difference in pretreatment clinicopathological parameters between the FLOT group and the SOX group (p>0.05). There was no significant difference in adverse effects or postoperative morbidity and mortality between the two groups (p>0.05). Similarly, there was no significant difference in the proportion of tumor regression grading between the FLOT group and the SOX group (p>0.05). In the ITT population, complete or subtotal TRG was 20.0% in the FLOT group versus 32.4% in the SOX group (p>0.05).

Conclusion

Our study demonstrates that the FLOT and SOX regimens are similarly effective for locally advanced gastric cancer patients in terms of clinical downstaging and pathological response. A large-scale phase III randomized controlled trial is necessary to validate this result.