bluuebunny/crossref_metadata_2025 huggingface dataset:
Comparative Effectiveness and Safety of Rivaroxaban in Adults With Nonvalvular Atrial Fibrillation
Authors: Aronow Wilbert S. , Shamliyan Tatyana A.
Published: November 2018

Background:

All evidence regarding benefits and harms of rivaroxaban for stroke prevention has not been appraised yet.

Study Question:

What are the comparative effectiveness and safety of rivaroxaban in adults with nonvalvular atrial fibrillation?

Data Sources:

Randomized controlled trials (RCTs), meta-analyses, and observational studies were identified in several databases in October 2018.

Study Design:

Rapid review with evidence appraisal using the Grading of Recommendations Assessment, Development and Evaluation working group approach.

Results:

Two direct RCTs (23,021 patients) suggest that rivaroxaban is noninferior to warfarin in the prevention of stroke and systemic embolism (pooled relative risk [RR] 0.73, 95% confidence interval [CI], 0.43–1.24), reduces risk of hemorrhagic stroke (RR 0.59, 95% CI, 0.38–0.92), fatal bleeding (RR 0.49, 95% CI, 0.31–0.76), and cardiac arrest (RR 0.45, 95% CI, 0.25–0.82, 2 RCTs), but increases risk of major gastrointestinal bleeding (RR 1.46, 95% CI, 1.19–1.78). In observational studies, rivaroxaban is associated with lower risk of ischemic stroke (RR 0.87, 95% CI, 0.77–0.99, 222,750 patients), acute myocardial infarction (RR 0.61, 95% CI, 0.48–0.78, 73,739 patients), and intracranial hemorrhage (RR 0.64, 95% CI, 0.45–0.92, 197,506 patients) but higher risk of gastrointestinal bleeding (RR 1.30, 95% CI, 1.19–1.42, 188,968 patients) and higher risk of mortality when compared with warfarin in European studies (RR 1.19, 103,270 patients in the UK; RR 2.02, 22,358 patients in Denmark) but lower risk of mortality in Taiwan (RR 0.58, 40,000 patients). Network meta-analyses and observational studies suggest that rivaroxaban is associated with higher risk of bleeding when compared with apixaban (RR 2.14, 72,586 patients), dabigatran (RR 1.24, 67,102 patients), and edoxaban (RR 1.32, 71,683 patients).

Conclusions:

Research on the long-term comparative effectiveness, safety, and effects on quality of life between rivaroxaban and other novel oral anticoagulants is urgently needed.
Macropolycyte in Pediatrics
Authors: Lee Anselm Chi-wai
Published: November 2018

Macropolycytes are tetraploid neutrophils produced during accelerated myelopoiesis. They have been reported in adults with pernicious anemia, sepsis, and after cytotoxic chemotherapy. Two pediatric cases are reported, one after granulocyte colony-stimulating factor treatment and the other following Kawasaki disease, respectively.
Prevalence and Risk Factors for Arterial Hypertension Development in Childhood Acute Lymphoblastic Leukemia Survivors
Authors: Ociepa Tomasz , Bartnik Magdalena , Zielezińska Karolina , Urasiński Tomasz
Published: November 2018

Background:

Childhood acute lymphoblastic leukemia (ALL) survivors are at an increased risk of cardiovascular disease including arterial hypertension (AH). The objectives of this study were to assess the prevalence of AH using 24-hour ambulatory blood pressure monitoring, explore characteristics of AH, and define risk factors for the development of AH in childhood ALL survivors.

Patients and Methods:

The study comprised 81 childhood ALL survivors (5 to 25 y of age) after a median follow-up time of 5 years. The control group consisted of 52 healthy children (5 to 17 y of age) without any known severe or chronic medical condition. Ambulatory blood pressure monitoring was performed in all patients and controls. Serum lipids were measured in all patients and controls.

Results:

ALL survivors were more likely to have AH than controls (odds ratio, 2.47; 95% confidence interval, 1.08-5.63; P=0.0315). The mean time from ALL diagnosis until diagnosis of AH was 5.1±2.97 years. Day-time diastolic SDS and day-time mean arterial pressure SDS were significantly higher in ALL cohort compared with the controls (−0.3±1.43 vs. −0.76±0.95; P=0.04 and 1.44±1.64 vs. 0.92±1.03; P=0.047). Childhood ALL survivors with AH were more likely to be systolic extreme dippers and reverse systolic/diastolic dippers compared with those with normal blood pressure (P<0.05). There was no association of AH with leukemia subtype, leukemia risk group, sex, central nervous system irradiation, and obesity.

Conclusions:

The prevalence of AH in childhood ALL survivors may be as high as 37%. We recommend regular monitoring of blood pressure in childhood ALL survivors early in the follow-up.
Increasing Syphilis Diagnoses Among Females Giving Birth in US Hospitals, 2010–2014
Authors: Aslam Maria V. , Owusu-Edusei Kwame , Kidd Sarah E. , Torrone Elizabeth A. , Dietz Patricia M.
Published: November 2018

Background

National trends in syphilis rates among females delivering newborns are not well characterized. We assessed 2010–2014 trends in syphilis diagnoses documented on discharge records and associated factors among females who have given birth in US hospitals.

Methods

We calculated quarterly trends in syphilis rates (per 100,000 deliveries) by using International Classification of Diseases, Ninth Revision, Clinical Modification codes on delivery discharge records from the National Inpatient Sample. Changes in trends were determined by using Joinpoint software. We estimated relative risks (RR) to assess the association of syphilis diagnoses with race/ethnicity, age, insurance status, household income, and census region.

Results

Overall, estimated syphilis rates decreased during 2010–2012 at 1.0% per quarter (P < 0.001) and increased afterward at 1.8% (P < 0.001). The syphilis rate increase was statistically significant across all sociodemographic groups and all US regions, with substantial increases identified among whites (35.2% per quarter; P < 0.001) and Medicaid recipients (15.1%; P < 0.001). In 2014, the risk of syphilis diagnosis was greater among blacks (RR, 13.02; 95% confidence interval [CI], 9.46–17.92) or Hispanics (RR, 4.53; 95% CI, 3.19–6.42), compared with whites; Medicaid recipients (RR, 4.63; 95% CI, 3.38–6.33) or uninsured persons (RR, 2.84; 95% CI, 1.74–4.63), compared with privately insured patients; females with the lowest household income (RR, 5.32; 95% CI, 3.55–7.97), compared with the highest income; and females in the South (RR, 2.42; 95% CI, 1.66–3.53), compared with the West.

Conclusions

Increasing syphilis rates among pregnant females of all backgrounds reinforce the importance of prenatal screening and treatment.
Three-Dimensional Printing Technology Combined With Postmortem Computed Tomography Angiography as New Form of Forensic Evidence
Authors: Wang Zhuoqun , Wan Lei , Shao Yu , Zou Donghua , Liu Ningguo , Chen Yijiu
Published: November 2018

Postmortem computed tomography (PMCT) and PMCT angiography are increasingly used in forensic practice. However, their application in court is still limited because they need professional equipment or software to be displayed. In this article, the authors introduce 3-dimensional (3D) printing technology as a new approach to provide evidence in court. A 67-year-old woman suffered from severe sick sinus syndrome, and she was fitted with a ventricular demand inhibited pacemaker. The operation failed as the doctor accidentally perforated her heart with an electrode wire. Her heart stopped beating, and she died after the operation. Targeted PMCT with pulmonary artery angiography was performed after the body was dissected, and a model of the heart was reconstructed using 3D printing technology, with different colored materials. The results confirmed by the autopsy suggested that the victim had died of cardiac rupture. The apex close to the right margin of the heart showed a tiny cleft where the contrast agent was flowing out. The heart model was an effective way to interpret this medical injury. This 3D printing technology, combined with PMCT angiography, provides a convenient, efficient tool for identifying the cause of death. It could become a powerful form of court evidence in the future.
Tumor Budding and Cell Nest Size Are Highly Prognostic in Laryngeal and Hypopharyngeal Squamous Cell Carcinoma
Authors: Boxberg Melanie , Kuhn Peer-Hendrik , Reiser Marianne , Erb Anna , Steiger Katja , Pickhard Anja , Straßen Ulrich , Koob Isabelle , Kolk Andreas , Warth Arne , Jesinghaus Moritz , Weichert Wilko
Published: November 2018

Squamous cell carcinoma (SCC) is the most common cancer of the head and neck region including—among others—laryngeal (LSCC) and hypopharyngeal (HSCC) subsites. LSCC/HSCC are heterogenous diseases with respect to patient outcome. Currently, tumor stage–based patient stratification is essential to predict prognosis and thus selection of the appropriate treatment modalities. In contrast, the prognostic impact of the current HSCC/LSCC grading system according to the WHO classification is limited. Recently, a novel grading system based on tumor budding activity (BA) and cell nest size (CNS) has been introduced for SCC in different anatomic regions of the upper aerodigestive tract. To test and transvalidate this grading scheme in LSCC and HSCC, we retrospectively correlated BA, CNS, and additional histomorphologic parameters with clinicopathologic data of 157 treatment-naive patients. In doing so, we demonstrate that a 3-tiered novel grading system (well-differentiated [nG1], intermediately [nG2], and poorly differentiated [nG3]) based on a sum score for BA and CNS is highly and independently prognostic for patient survival in LSCC/HSCC, strongly outperforming the current WHO grading scheme with a hazard ratio for disease-specific survival of 6.6 for nG2 and 13.4 for nG3 cases (P<0.001). This finding contributes to a growing body of evidence that a CNS and BA-based pan-entity grading system in SCC might be useful and seems to capture differences in underlying SCC biology crucial for survival.
Displaced Cartilage Within Lymph Node Parenchyma Is a Novel Biopsy Site Change in Resected Mediastinal Lymph Nodes Following EBUS-TBNA
Authors: Doxtader Erika E. , Pijuan Lara , Lepe Marcos , Alex Deepu , Canepa Mariana , Deeken Amy H. , Gibier Jean-Baptiste , Jain Deepali , Janaki Nafiseh , Jelinek Alexis , Kumar Sunil , Labiano Tania , L’Imperio Vincenzo , Michael Claire , Pagni Fabio , Panizo Angel , Quintana Liza M. , Roy-Chowdhuri Sinchita , Sanchez-Font Albert , Skipper Daniel C. , Spruill Laura S. , Torous Vanda , Wu Roseann I. , Sauter Jennifer L. , Mukhopadhyay Sanjay
Published: November 2018

Biopsy site changes in mediastinal lymph nodes (LNs) attributable to prior endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) have not been studied in a systematic manner. Twenty-four contributors from 14 institutions in 5 countries collaborated via social media (Twitter) to retrospectively review consecutive cases of resected mediastinal LNs from patients with prior EBUS-TBNA. Resected LNs were reexamined by submitting pathologists for changes attributable to EBUS-TBNA. Patients who received neoadjuvant therapy were excluded. Cases with suspected biopsy site changes underwent central review by 5 pathologists. A total of 297 mediastinal LN resection specimens from 297 patients (183 male/114 female, mean age: 65 y, range: 23 to 87) were reviewed. Biopsy site changes were most common in station 7 (10 cases) followed by 11R, 4R, and 10R, and were found in 34/297 (11.4%) cases, including displacement of tiny cartilage fragments into LN parenchyma in 26, intranodal or perinodal scars in 7, and hemosiderin in 1. Cartilage fragments ranged from 0.26 to 1.03 mm in length and 0.18 to 0.62 mm in width. The mean interval between EBUS-TBNA and LN resection was 38 days (range: 10 to 112) in cases with biopsy site changes. A control group of 40 cases without prior EBUS-TBNA, including 193 mediastinal LN stations, showed no evidence of biopsy site changes. Biopsy site changes are identified in a subset of resected mediastinal LNs previously sampled by EBUS-TBNA. The location of the abnormalities, temporal association with prior EBUS-TBNA, and the absence of such findings in cases without prior EBUS-TBNA support the contention that they are caused by EBUS-TBNA.
Mismatch in Spouses' Anger-Coping Response Styles and Risk of Early Mortality: A 32-Year Follow-Up Study
Authors: Bourassa Kyle J. , Sbarra David A. , Ruiz John M. , Karciroti Niko , Harburg Ernest
Published: November 2018

Objective

Research in psychosomatic medicine includes a long history of studying how responses to anger-provoking situations are associated with health. In the context of a marriage, spouses may differ in their anger-coping response style. Where one person may express anger in response to unfair, aggressive interpersonal interactions, his/her partner may instead suppress anger. Discordant response styles within couples may lead to increased relational conflict, which, in turn, may undermine long-term health. The current study sought to examine the association between spouses' anger-coping response styles and mortality status 32 years later.

Methods

The present study used data from a subsample of married couples (N = 192) drawn from the Life Change Event Study to create an actor-partner interdependence model.

Results

Neither husbands' nor wives' response styles predicted their own or their partners' mortality. Wives' anger-coping response style, however, significantly moderated the association of husbands' response style on mortality risk 32 years later, β = −0.18, −0.35 to −0.01, p = .039. Similarly, husbands' response style significantly moderated the association of wives' response style and their later mortality, β = −0.24, −0.38 to −0.10, p < .001. These effects were such that the greater the mismatch between spouses' anger-coping response style, the greater the risk of early death.

Conclusions

For a three-decade follow-up, husbands and wives were at greater risk of early death when their anger-coping response styles differed. Degree of mismatch between spouses' response styles may be an important long-term predictor of spouses' early mortality risk.
Patient Experiences With Handling of Analgesic Transdermal Patches and Challenges in Correct Drug Administration: A Pilot Study on Patient Education
Authors: Lampert Anette , Kessler Jens , Washington-Dorando Phoebe , Bardenheuer Hubert J. , Bocek Eknes Emilia M. , Krisam Johannes , Haefeli Walter E. , Seidling Hanna M.
Published: November 2018

Background

Although problems during transdermal patch administration are primarily caused by insufficient knowledge, patient education programs are lacking. We compared patient education by a clinical pharmacist on knowledge on correct patch administration with routine counseling during patient-physician consultation in a pilot study.

Methods

After baseline assessment of knowledge and difficulties with patch administration, patients in the outpatient pain clinic of Heidelberg University Hospital were allocated to intervention (n = 12) or control group (n = 11). In both groups, identical information leaflets on transdermal patch use were dispensed. Intervention patients additionally received verbal counseling on correct patch administration by a clinical pharmacist. After 4 weeks, patients were called for a follow-up assessment on knowledge and perspective on administration difficulties.

Results

Patients reported several difficulties with transdermal patch administration, such as local skin reaction, difficulties with opening the packaging, and poor adhesion. Although patient education increased the ratio of correct answers in the intervention group twice as much than in the control group, overall knowledge was comparable between groups after education (P = 0.602).

Conclusions

Patients encountered numerous problems with transdermal patch administration although on long-term use. Patient education can improve knowledge on correct patch administration. However, the pilot study demonstrated the need for further efforts to improve ease of use of transdermal patch, such as patch adhesion.
Impact Analysis of the Routine Use of Dual-Energy Computed Tomography for Characterization of Incidental Renal Lesions
Authors: Wortman Jeremy R. , Shyu Jeffrey Y. , Fulwadhva Urvi P. , Sodickson Aaron D.
Published: November 2018

Objective

The aim of this study was to quantify the prevalence of incidental, indeterminate renal lesions on routine contrast-enhanced abdominal computed tomography (CT) and the proportion of such lesions that could be exonerated by dual-energy CT (DECT) postprocessing as benign hyperdense cysts.

Methods

The reports for 2729 consecutive contrast-enhanced DECT scans in the emergency department setting were reviewed for the mention of any renal lesion. For scans with a reported lesion, images were reviewed to assess for the presence of an indeterminate lesion that could not be definitively characterized as benign. All indeterminate lesions were reviewed with DECT postprocessing by 2 radiologists to assess for enhancement and other imaging characteristics and characterized by readers as benign or not definitively benign. Agreement between readers was assessed statistically, and disagreement was resolved by consensus.

Results

Two thousand seven hundred twenty-nine scans were performed in 2406 unique patients; a renal lesion was reported in 805 unique patient scans (33.4%). Review of these 805 scans led to discovery of 137 indeterminate lesions in 125 scans (5.2% of patients). Of the 137 lesions, 70 (51.1%) were classified as benign hyperdense cysts by readers, with the remaining 67 lesions classified as not definitively benign (43 solid masses, 9 Bosniak IIF cysts, 8 Bosniak III cysts, 7 Bosniak IV cysts).

Conclusions

Incidental indeterminate renal lesions are common on routine contrast-enhanced CT. More than half of these lesions could potentially be exonerated with DECT as benign Bosniak II cysts, which could avert the need for further workup in 2.8% of patients undergoing routine abdominal CT.
Family-Centered Care During Constraint-Induced Therapy After Chronic Stroke: A Feasibility Study
Authors: Blanton Sarah , Scheibe Deborah Cussen , Rutledge Ashley Holmes , Regan Bridget , O’Sullivan Colleen Schwartz , Clark Patricia C.
Published: November 2018

Purpose

This feasibility study evaluated a theory-based intervention (CARE-CITE) designed to engage carepartners (CPs) in supporting stroke survivor upper extremity rehabilitation.

Design

The study was a one-group design with pre- and posttest and 1 month follow-up (N = 7 dyads).

Methods

Feasibility was determined by participant retention, CP and stroke survivor intervention adherence, and CP acceptability of the intervention (exit interview). Measures of CP depressive symptoms, fatigue, and family conflict around stroke recovery and stroke survivor upper extremity function are reported. Data were analyzed using descriptive statistics.

Findings

All participants completed the study and adhered to the intervention, and CPs found CARE-CITE helpful. Descriptively, better scores were observed for CP's mental health, family conflict, stroke survivor confidence, and upper extremity tasks performed.

Conclusion

These results provide initial evidence that CARE-CITE is feasible after chronic stroke and that CPs and stroke survivors may benefit from family-centered care.

Clinical Relevance

Improving CP skills in supporting rehabilitation activities may improve stroke survivor upper extremity function.
Lateral Toe Pulp Flap Used in Reconstruction of Distal Dorsal Toe Defect
Authors: Cheng Li-Fu , Lee Jiunn-Tat , Wu Meng-Si
Published: November 2018

Background

When the distal dorsal part of the great toe is injured, especially with exposure of a tendon, bone, or joint, applying a free or local flap is difficult because of the lack of locally available tissue for reconstruction. Management of the distal dorsal part of a great toe soft tissue defect can be challenging for plastic surgeons.

Patient and Method

An 18-year-old woman presented with an injury to the dorsal aspect of her right great toe caused by a cobra bite. After fasciotomy, the wound showed exposure of the extensor hallucis longus tendon. After demarcation and infection control, the wound was reconstructed using a lateral toe pulp flap of approximately 3.5 × 1.0 cm2. The flap was transposed to the defect, and the donor site was closed primarily. Toe pulp flaps are mainly used to reconstruct finger pulp defects and are useful because they provide a glabrous skin flap suitable for resurfacing fingertip injuries. A lateral toe pulp flap uses a homodigital adjacent skin flap, which is transposed to cover the soft tissue defect. Using a quick and straightforward procedure, we designed this flap to reconstruct a distal dorsal defect of the great toe, with minimal morbidity at the donor site.

Results

The flap initially showed mild congestion but survived completely.

Conclusions

Applying a lateral toe pulp flap is a quick, simple, and reliable 1-stage procedure. It may be an effective option in reconstructing distal dorsal defects of the great toe.
Suppression of Oxygen Radicals Protects Diabetic Endothelium Damage and Tissue Perfusion in a Streptozotocin-Induced Diabetes Rodent Model
Authors: Chen Rong-Fu , Chang Chih-Hau , Wang Chun-Ting , Kuo Yur-Ren
Published: November 2018

Background

Oxygen free radicals play a central role in diabetic angiopathy. This study investigated whether suppression of oxygen radicals could decrease endothelial damage and increase peripheral tissue circulation in a diabetic rodent model.

Methods

Sprague-Dawley rats were treated using streptozotocin to induce diabetes. The experiments were performed 4 weeks after diabetes induction: group 1: control, consisted of normal rats; group 2: diabetes, did not receive treatment; groups III (SOD10) and IV (SOD50): diabetes, received polyethylene glycol–conjugated superoxide dismutase (SOD), an antioxidant, 10 and 50 U/kg per day intraperitoneally for 4 weeks. Each subgroup consisted of 10 rats. Oxygen radicals in blood mononuclear cells were detected by flow cytometry. The blood lipid peroxidation byproduct malondialdehyde was measured. Tissue perfusion of hind limb was examined by laser Doppler. The expressions of oxygen radicals, as demonstrated by 8-hydroxyguanosine (8-OG), and constitutive endothelial nitric oxide synthase in distal femoral vessels were examined by immunohistochemical staining.

Results

Oxygen radicals, as demonstrated by H2O2 with 2′,7′-dichlorofluorescin diacetate–conjugated expression, were significantly increased in diabetic rats. However, the SOD treatment groups significantly suppressed the H2O2 reaction. Diabetic-induced high malondialdehyde levels were significantly suppressed in the SOD50 group. The topical tissue blood perfusion was significantly increased as detected by laser Doppler in SOD10 and SOD50 groups, as compared with that in diabetes without treatment group (P < 0.05). The expression of 8-OG was markedly increased in the diabetic endothelium and subintima compared with that in normal vessels. Polyethylene glycol–conjugated SOD significantly suppressed 8-OG expression and protected endothelial nitric oxide synthase expression.

Conclusions

Suppression of oxygen radicals, particularly with the higher dosage of polyethylene glycol–conjugated SOD at 50 U/kg per day, could have a positive effect to protect against endothelial damage and enhance peripheral perfusion in diabetes.
The Effectiveness of an International Cleft Mission Model in Asia
Authors: Mao Shih-Hsuan , Ajiwe Tochi , Wang Rebecca , Wong Fen-Hwa , Chou Pang-Yun , Lo Lun-Jou
Published: November 2018

Background

Cleft lip/palate is a congenital craniofacial anomaly affecting patients physically and psychosocially and has contributed to the global burden of surgical disease, especially in underprivileged areas. For 20 years, Noordhoff Craniofacial Foundation (NCF) and the Chang Gung Craniofacial Center (CGCFC) have carried out missions to these areas. Rather than implementing short-term missions that lack proper follow-up care, the team has provided an effective, long-term, and multidisciplinary approach for the treatment of patients with cleft lip/palate. In this study, we evaluate the sustainability and effectiveness of the cleft mission model implemented by NCF and CGCFC.

Methods

Data from the years 1998–2017 were retrieved from the NCF database. All local centers were evaluated by a 3-stage categorization, levels 1 to 3, based on 4 criteria: (1) capacity to carry out independent missions, (2) diversity of cleft-care professionals, (3) diversity of surgical service offered, and (4) collaboration with local hospitals. Support and training of personnel were provided based on deficiency in these criteria. Noordhoff Craniofacial Foundation made close collaborations and partnerships with several organizations that shared its mission for comprehensive cleft care in developing countries.

Results

In all, 19 partner cleft teams in 9 different countries were established. In coordination with these teams, NCF and CGCFC have treated 1846 patients across 78 mission trips. To date, 158 personnel from 19 different countries have been successfully trained to provide cleft care in local centers. Most partner cleft teams centers have progressively reached category level 3, including those in the Philippines, Cambodia, and Mongolia.

Conclusions

In order to establish and maintain sustainable cleft care in developing regions, commitment and compassion toward those who lack essential resources are necessary. Noordhoff Craniofacial Foundation and CGCFC have achieved a successful and practicable model through seeding medical personnel in order to provide effective and sustainable cleft care to the regions in need.
Costochondral Grafting for Nasal Airway Reconstruction in an Infant With Frontonasal Dysplasia
Authors: Fujisawa Kou , Watanabe Shoji , Kato Motoi , Utsunomiya Hiroki , Watanabe Azusa
Published: November 2018

Frontonasal dysplasia (FND) is a congenital malformation of the central portion of the face, including the eyes, nose, and forehead. Owing to its rarity and wide spectrum of phenotypes, the optimal timing and technique of surgery remain controversial. Here, we report a case of a patient with FND, who presented with respiratory distress. The deformed nostrils were so small that the patient could not normally breathe through the nose immediately after birth. Rhinoplasty using a costochondral graft was performed at 16 months of age. After surgery, the nostrils enlarged and the appearance of the nose improved. Although congenital nasal deformity is frequently corrected during adolescence, surgery at an early stage can be considered when important issues are noted, such as inability to breathe through the nose.
Hemorrhage Attenuates Neutrophil Recruitment in Response to Secondary Respiratory Infection by Pseudomonas Aeruginosa
Authors: Lee Kayla , Cohen Joshua T. , Wilson Zachary S. , Zhao Runping , Lomas-Neira Joanne , Chung Chun-Shiang , Chen Yaping , Jamieson Amanda M. , Ayala Alfred , Lefort Craig T.
Published: November 2018

Neutrophil recruitment into the lung airspaces plays an important role in the containment and clearance of bacteria. Hemorrhagic shock, a complication of traumatic injury, induces immune dysfunction that compromises host defense and frequently leads to secondary infection. The objective of the current study was to determine whether prior hemorrhage impacts neutrophil recruitment in response to secondary Pseudomonas aeruginosa. Experiments were performed using a mouse model (C57BL/6) of respiratory infection by P. aeruginosa (strain PA103, 3 × 105 colony-forming units [CFUs]) that is delivered by intratracheal inhalation 24 h after hypovolemic hemorrhagic shock (fixed mean arterial blood pressure at 35 mmHg for 90 min, Ringer's lactate infused as fluid resuscitation). By postmortem flow cytometry analyses of bronchoalveolar lavage fluid, we observe that prior hemorrhage attenuates the entry of neutrophils into the lung airspaces in response to P. aeruginosa. The reduction in neutrophil recruitment occurs in an amplified inflammatory environment, with elevated lung tissue levels of interleukin 6 and C-X-C motif ligand 1 in mice receiving hemorrhage prior to infection. As compared to either insult alone, outcome to sequential hemorrhage and respiratory infection includes enhanced mortality. The effect of prior hemorrhage on clearance of P. aeruginosa, as determined by quantifying bacterial CFUs in lung tissue, was not statistically significant at 24 h postinfection, but our data suggest that further inquiry may be needed to fully understand the potential impact of hemorrhagic shock on this process. These results suggest that changes in neutrophil recruitment may contribute to the immune dysfunction following hemorrhagic shock that renders the host susceptible to severe respiratory infection.
Dexmedetomidine Attenuates Acute Lung Injury Induced by Heatstroke and Improve Outcome
Authors: Geng Yan , Li Ru , He Si-Xiao , Yang Huo-Hong , Deng Qiao-ting , Shao Xiang-yang , Wu Ying-song , Xu Wei-wen , Ma Qiang
Published: November 2018

Introduction:

Dexmedetomidine (DEX) has been demonstrated to inhibit inflammatory response and protect against multiorgan injury in various scenarios. The objectives of the present study were to ascertain whether DEX is able to attenuate acute lung injury (ALI) under heatstroke (HS), and to explore the underlying mechanism.

Methods:

Male C57BL/6 mice were exposed to ambient temperature of 39.5 ± 0.2°C until core temperature reach 43°C. DEX or 0.9% saline was injected i.p. immediately. At the end of the experiment, bronchoalveolar lavage fluid (BALF) and lung tissue were harvested.

Results:

HS induce ALI and pulmonary dysfunction, while DEX treatment could significantly inhibit lung injury and improve respiratory dysfunction under HS. The overall effect was beneficial and improved the 72 h cumulative survival rate of mice with HS. Furthermore, HS significantly elevated the levels of cytokines in BALF, as well as increased the activity of toll-like receptor 4 (TLR4)/MyD88/nuclear factor-κB (NFκB) signaling pathway in lung tissue, while DEX treatment could inhibit such effects. Finally, DEX could upregulate the expression of caveolin 1 downregulated by HS, which may contribute to the inhibition of TLR4/MyD88/NFκB signaling pathway.

Discussion:

In conclusion, the present results indicated that DEX may protect against lung inflammatory response and injury under HS via TLR4/MyD88/NFκB signaling pathway, and caveolin-1 may participate in the effects.
The Effect of Catheterization on Susceptibility of Uropathogens After Pelvic Reconstructive Surgery
Authors: Baird Rachael C. , Romich Ellen , Holthaus Emily , Barber Matthew D. , Ferrando Cecile A.
Published: November 2018

Objective

The aim of this study was to determine whether bacterial uropathogens from positive urine cultures and uropathogen antibiotic susceptibility differ between catheterized (C) and noncatheterized (NC) patients after pelvic reconstructive surgery.

Methods

This is a retrospective cohort study of patients with a positive urine culture within 1 year of pelvic reconstructive surgery. Patients were categorized as having an indwelling catheter placed for urinary retention or voiding dysfunction within 48 hours of specimen collection versus no catheter. Microbiology reports provided uropathogens and antibiotic susceptibility for each culture. Student t test, χ2, and logistic regression were used to compare rates of non–Escherichia coli uropathogens and susceptibility to first-line antibiotics between C and NC groups.

Results

A total of 427 positive urine cultures from 317 unique patients were identified. Positive urine cultures from C patients were less likely to contain E. coli (47.1% NC vs 29.2% C; P = 0.0009), with enterococcus being the most common non–E. coli uropathogen. The odds of non–E. coli uropathogens increased with age (adjusted odds ratio, 4.25; 95% confidence interval, 1.95–9.28; P = 0.0003 for the oldest patients). Cultures from C patients were more likely to have a uropathogen not susceptible to sulfamethoxazole/trimethoprim (20.5% NC vs 32.1% C; P = 0.03), nitrofurantoin (19.2% NC vs 34.6% C; P = 0.002), and cefazolin (18.1% NC vs 49.4% C; P < 0.0001).

Conclusions

After pelvic reconstructive surgery, patients with a positive urine culture who have undergone catheterization within 48 hours of specimen collection are more likely to have non–E. coli uropathogens, with 1 in 3 cultures being not susceptible to common first-line antibiotics. This highlights the importance of performing susceptibility testing rather than treating empirically after pelvic reconstructive surgery.
Management of penetrating intraperitoneal colon injuries: A meta-analysis and practice management guideline from the Eastern Association for the Surgery of Trauma
Authors: Cullinane Daniel C. , Jawa Randeep S. , Como John J. , Moore Ashlee E. , Morris David S. , Cheriyan Jerry , Guillamondegui Oscar D. , Goldberg Stephanie R. , Petrey Laura , Schaefer Gregory P. , Khwaja Kosar A. , Rowell Susan E. , Barbosa Ronald R. , Bass Gary A. , Kasotakis George , Robinson Bryce R.H.
Published: November 2018

BACKGROUND

The management of penetrating colon injuries in civilians has evolved over the last four decades. The objectives of this meta-analysis are to evaluate the current treatment regimens available for penetrating colon injuries and assess the role of anastomosis in damage control surgery to develop a practice management guideline for surgeons.

METHODS

Using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) methodology, a subcommittee of the Practice Management Guidelines section of EAST conducted a systematic review using MEDLINE and EMBASE articles from 1980 through 2017. We developed three relevant problem, intervention, comparison, and outcome (PICO) questions regarding penetrating colon injuries. Outcomes of interest included mortality and infectious abdominal complications.

RESULTS

Thirty-seven studies were identified for analysis, of which 16 met criteria for quantitative meta-analysis and included 705 patients considered low-risk in six prospective randomized studies. Seven hundred thirty-eight patients in 10 studies undergoing damage control laparotomy and repair or resection and anastomosis (R&A) were included in a separate meta-analysis. Meta-analysis of high-risk patients undergoing repair or R&A was not feasible due to inadequate data.

CONCLUSIONS

In adult civilian patients sustaining penetrating colon injury without signs of shock, significant hemorrhage, severe contamination, or delay to surgical intervention we recommend that colon repair or R&A be performed rather than routine colostomy. In adult high-risk civilian trauma patients sustaining penetrating colon injury, we conditionally recommend that colon repair or R&A be performed rather than routine colostomy. In adult civilian trauma patients sustaining penetrating colon injury who had damage control laparotomy, we conditionally recommend that routine colostomy not be performed; instead, definitive repair or delayed R&A or anastomosis at initial operation should be performed rather than routine colostomy.

LEVEL OF EVIDENCE

Systematic review/meta-analysis, level III.
The adaptive shaping of social behavioural phenotypes during adolescence
Authors: Sachser Norbert , Hennessy Michael B. , Kaiser Sylvia
Published: November 2018

Developmental behavioural plasticity is a process by which organisms can alter development of their behavioural phenotype to be better adapted to the environment encountered later in life. This ‘shaping’ process depends on the presence of reliable cues by which predictions can be made. It is now established that cues detected by the mother can be used (primarily via hormones prenatally and maternal behaviour in the early postnatal stage) to shape the behavioural phenotype of her offspring. However, it is becoming increasingly clear that adolescence is another period in which conditions are well-suited for such shaping to occur. We review here how mammalian social behaviour may be shaped in adolescence. We identify limited extant examples, briefly discuss underlying mechanisms, and provide evidence that observed changes are indeed adaptive. We contend that while plasticity diminishes with age, the shaping of the behavioural phenotype in adolescence offers several advantages, including that adolescence is closer to the onset of mating than are earlier phases of life; that unlike earlier phases, information is obtained directly from the environment rather than mediated by the mother; and unlike later in adulthood, there is substantial underlying neural plasticity associated with development to support behavioural change. We also consider conditions that favour the occurrence of social behaviour plasticity during adolescence, including a high degree of sociality and a prolonged developmental period and the implication of these conditions for the occurrence of sex differences in the shaping process.
EuMoBot: replicating euglenoid movement in a soft robot
Authors: Digumarti Krishna Manaswi , Conn Andrew T. , Rossiter Jonathan
Published: November 2018

Swimming is employed as a form of locomotion by many organisms in nature across a wide range of scales. Varied strategies of shape change are employed to achieve fluidic propulsion at different scales due to changes in hydrodynamics. In the case of microorganisms, the small mass, low Reynolds number and dominance of viscous forces in the medium, requires a change in shape that is non-invariant under time reversal to achieve movement. The
Euglena
family of unicellular flagellates evolved a characteristic type of locomotion called euglenoid movement to overcome this challenge, wherein the body undergoes a giant change in shape. It is believed that these large deformations enable the organism to move through viscous fluids and tiny spaces. The ability to drastically change the shape of the body is particularly attractive in robots designed to move through constrained spaces and cluttered environments such as through the human body for invasive medical procedures or through collapsed rubble in search of survivors. Inspired by the euglenoids, we present the design of EuMoBot, a multi-segment soft robot that replicates large body deformations to achieve locomotion. Two robots have been fabricated at different sizes operating with a constant internal volume, which exploit hyperelasticity of fluid-filled elastomeric chambers to replicate the motion of euglenoids. The smaller robot moves at a speed of

body lengths per cycle (20 mm min
−1
or 2.2 cycles min
−1
) while the larger one attains a speed of

body lengths per cycle (4.5 mm min
−1
or 0.4 cycles min
−1
). We show the potential for biomimetic soft robots employing shape change to both replicate biological motion and act as a tool for studying it. In addition, we present a quantitative method based on elliptic Fourier descriptors to characterize and compare the shape of the robot with that of its biological counterpart. Our results show a similarity in shape of 85% and indicate that this method can be applied to understand the evolution of shape in other nonlinear, dynamic soft robots where a model for the shape does not exist.
Measuring bilayer surface energy and curvature in asymmetric droplet interface bilayers
Authors: Barlow Nathan E. , Kusumaatmaja Halim , Salehi-Reyhani Ali , Brooks Nick , Barter Laura M. C. , Flemming Anthony J. , Ces Oscar
Published: November 2018

For the past decade, droplet interface bilayers (DIBs) have had an increased prevalence in biomolecular and biophysical literature. However, much of the underlying physics of these platforms is poorly characterized. To further our understanding of these structures, lipid membrane tension on DIB membranes is measured by analysing the equilibrium shape of asymmetric DIBs. To this end, the morphology of DIBs is explored for the first time using confocal laser scanning fluorescence microscopy. The experimental results confirm that, in accordance with theory, the bilayer interface of a volume-asymmetric DIB is curved towards the smaller droplet and a lipid-asymmetric DIB is curved towards the droplet with the higher monolayer surface tension. Moreover, the DIB shape can be exploited to measure complex bilayer surface energies. In this study, the bilayer surface energy of DIBs composed of lipid mixtures of phosphatidylgylcerol (PG) and phosphatidylcholine are shown to increase linearly with PG concentrations up to 25%. The assumption that DIB bilayer area can be geometrically approximated as a spherical cap base is also tested, and it is discovered that the bilayer curvature is negligible for most practical symmetric or asymmetric DIB systems with respect to bilayer area.
Resolving the complex Bordetella pertussis genome using barcoded nanopore sequencing
Authors: Ring Natalie , Abrahams Jonathan S. , Jain Miten , Olsen Hugh , Preston Andrew , Bagby Stefan
Published: November 2018

The genome of Bordetella pertussis is complex, with high G+C content and many repeats, each longer than 1000 bp. Long-read sequencing offers the opportunity to produce single-contig B. pertussis assemblies using sequencing reads which are longer than the repetitive sections, with the potential to reveal genomic features which were previously unobservable in multi-contig assemblies produced by short-read sequencing alone. We used an R9.4 MinION flow cell and barcoding to sequence five B. pertussis strains in a single sequencing run. We then trialled combinations of the many nanopore user community-built long-read analysis tools to establish the current optimal assembly pipeline for B. pertussis genome sequences. This pipeline produced closed genome sequences for four strains, allowing visualization of inter-strain genomic rearrangement. Read mapping to the Tohama I reference genome suggests that the remaining strain contains an ultra-long duplicated region (almost 200 kbp), which was not resolved by our pipeline; further investigation also revealed that a second strain that was seemingly resolved by our pipeline may contain an even longer duplication, albeit in a small subset of cells. We have therefore demonstrated the ability to resolve the structure of several B. pertussis strains per single barcoded nanopore flow cell, but the genomes with highest complexity (e.g. very large duplicated regions) remain only partially resolved using the standard library preparation and will require an alternative library preparation method. For full strain characterization, we recommend hybrid assembly of long and short reads together; for comparison of genome arrangement, assembly using long reads alone is sufficient.
Meeting the challenges of high-dimensional data analysis in immunology
Authors: Palit Subarna , Theis Fabian J. , Zielinski Christina E.
Published: November 2018

Recent advances in cytometry have radically altered the fate of single-cell proteomics by allowing a more accurate understanding of complex biological systems. Mass cytometry (CyTOF) provides simultaneous single-cell measurements that are crucial to understand cellular heterogeneity and identify novel cellular subsets. High-dimensional CyTOF data were traditionally analyzed by gating on bivariate dot plots, which are not only laborious given the quadratic increase of complexity with dimension but are also biased through manual gating. This review aims to discuss the impact of new analysis techniques for in-depths insights into the dynamics of immune regulation obtained from static snapshot data and to provide tools to immunologists to address the high dimensionality of their single-cell data.
Hi-C yields chromosome-length scaffolds for a legume genome, Trifolium subterraneum
Authors: Dudchenko Olga , Pham Melanie , Lui Christopher , Batra Sanjit S. , Hoeger Marie , Nyquist Sarah K. , Durand Neva C. , Shamim Muhammad S. , Machol Ido , Erskine William , Aiden Erez Lieberman , Kaur Parwinder
Published: November 2018

We present a chromosome-length assembly of the genome of subterranean clover, Trifolium subterraneum, a key Australian pasture legume. Specifically, in situ Hi-C data (48X) was used to correct misjoins and anchor, order, and orient scaffolds in a previously published genome assembly (TSUd_r1.1; scaffold N50: 287kb). This resulted in an improved genome assembly (TrSub3; scaffold N50: 56Mb) containing eight chromosome-length scaffolds that span 95% of the sequenced bases in the input assembly.
CRISPR-Cas12a-assisted PCR tagging of mammalian genes
Authors: Fueller Julia , Herbst Konrad , Meurer Matthias , Gubicza Krisztina , Kurtulmus Bahtiyar , Knopf Julia D. , Kirrmaier Daniel , Buchmuller Benjamin C. , Pereira Gislene , Lemberg Marius K. , Knop Michael
Published: November 2018

Here we describe a time-efficient strategy for endogenous C-terminal gene tagging in mammalian tissue culture cells. An online platform is used to design two long gene-specific oligonucleotides for PCR with generic template cassettes to create linear dsDNA donors, termed PCR cassettes. PCR cassettes encode the tag (e.g. GFP), a Cas12a CRISPR RNA for cleavage of the target locus and short homology arms for directed integration via homologous recombination. The integrated tag is coupled to a generic terminator shielding the tagged gene from the co-inserted auxiliary sequences. Co-transfection of PCR cassettes with a Cas12a-encoding plasmid leads to robust endogenous expression of tagged genes, with tagging efficiency of up to 20% without selection, and up to 60% when selection markers are used. We used target-enrichment sequencing to investigate all potential sources of artefacts. Our work outlines a quick strategy particularly suitable for exploratory studies using endogenous expression of fluorescent protein tagged genes
Neural Signatures of Prediction Errors in a Decision-Making Task Are Modulated by Action Execution Failures
Authors: McDougle Samuel D. , Butcher Peter A. , Parvin Darius , Mushtaq Fasial , Niv Yael , Ivry Richard B. , Taylor Jordan A.
Published: November 2018

Decisions must be implemented through actions, and actions are prone to error. As such, when an expected outcome is not obtained, an individual should not only be sensitive to whether the choice itself was suboptimal, but also whether the action required to indicate that choice was executed successfully. The intelligent assignment of credit to action execution versus action selection has clear ecological utility for the learner. To explore this scenario, we used a modified version of a classic reinforcement learning task in which feedback indicated if negative prediction errors were, or were not, associated with execution errors. Using fMRI, we asked if prediction error computations in the human striatum, a key substrate in reinforcement learning and decision making, are modulated when a failure in action execution results in the negative outcome. Participants were more tolerant of non-rewarded outcomes when these resulted from execution errors versus when execution was successful but the reward was withheld. Consistent with this behavior, a model-driven analysis of neural activity revealed an attenuation of the signal associated with negative reward prediction error in the striatum following execution failures. These results converge with other lines of evidence suggesting that prediction errors in the mesostriatal dopamine system integrate high-level information during the evaluation of instantaneous reward outcomes.