bluuebunny/crossref_metadata_2025 huggingface dataset:
Polymorphism in beta fibrinogen -455 g/a gene was associated with diabetic in severe ischemic stroke patients
Authors: Ritarwan Kiking , Kadri Alfansuri , Sembiring Rosita Juwita
Published: March 2018

There is a association of polymorphism in the promoter region of the beta fibrinogen gene -455 G/A with enhancement plasma fibrinogen level. Diabetes mellitus is a risk factor for early neurologic deterioration in acute ischemic stroke. The prothrombotic fibrinogen protein is frequently elevated in patients with diabetes and may be association with poorer prognosis. This study evaluated the association of beta fibrinogen gene -455 G/A promoter polymorphism on modified Ranking Scale of Ischemic Stroke patients treated with diabetic and nondiabetic group. In a Cohort study design comprises 200 consecutive patients diabetic and a nondiabetic who, three months using completed a detailed outcome stroke. Of 200 samples genotype distribution were 27.1% for GG+GA and 0% for AA with diabetic and than 4.4% for GG+GA and 0.05% diabetic patients. Fibrinogen levels were higher in diabetic than nondiabetic group patients (307.7 + 106.3 vs 278 + 84 gr/dl, p=0.002). Fibrinogen level was found to be an independent predictor for diabetic patients. On Genotype GG+GA were associated wth diabetic and nondiabetic group patients. Modified Rankin Scale on day 90 were found associated with diabetic and nondiabetic patients.

Conclusion: Elevated fibrinogen level is dose-dependently associated with 90 days outcome severity stroke with diabetic following ischemic stroke
Unconscious perception and phenomenal coherence
Authors: Quilty-Dunn Jake
Published: March 2018

It is an orthodoxy in cognitive science that perception can occur unconsciously. Recently, Hakwan Lau, Megan Peters and Ian Phillips have argued that this orthodoxy may be mistaken. They argue that many purported cases of unconscious perception fail to rule out low degrees of conscious awareness while others fail to establish genuine perception. This paper presents a case of unconscious perception that avoids these problems. It also advances a general principle of ‘phenomenal coherence’ that can insulate some forms of evidence for unconscious perception from the methodological critiques of Lau, Peters and Phillips.
Semi-supervised neighborhoods and localized patient outcome prediction
Authors: Kosel Alison E , Heagerty Patrick J
Published: March 2018

Robust statistical methods that can provide patients and their healthcare providers with individual predictions are needed to help guide informed medical decisions. Ideally an individual prediction would display the full range of possible outcomes (full predictive distribution), would be obtained with a user-specified level of precision, and would be minimally reliant on statistical model assumptions. We propose a novel method that satisfies each of these criteria via the semi-supervised creation of an axis-parallel covariate neighborhood constructed around a given point defining the patient of interest. We then provide non-parametric estimates of the outcome distribution for the subset of subjects in this neighborhood, which we refer to as a localized prediction. We implement local prediction methods using dynamic graphical methods which allow the user to vary key options such as the choice of the variables defining the neighborhood, and the size of the neighborhood.
The Effectiveness of Dry Needling and Exercise Therapy in Patients with Dizziness Caused By Cervical Myofascial Pain Syndrome; Prospective Randomized Clinical Study
Authors: Aydın Tugba , Dernek Bahar , Sentürk Ege Tülin , Karan Ayse , Aksoy Cihan
Published: March 2018

Objective

The aim of this study is to compare the effectiveness of dry needling therapy combined with exercise and exercise treatment alone for alleviating the dizziness caused by cervical myofascial pain syndrome.

Design

This was a prospective randomized clinical study that included 61 women who had dizziness and myofascial trigger points on the neck muscles. The patients were randomized into a dry needling + exercise group (N = 31) and an exercise only group (N = 30).

Results

The mean age of the patients (±SD) was 38.4 ± 8.3 years. The intragroup comparisons of the severity of neck pain, algometric measurement, number of dizziness attacks per week, severity of the dizziness, fall index, and the Dizziness Handicap Inventory were improved in both groups at the first and fourth months (P < 0.05). The intergroup comparisons of the severity of neck pain, algometric measurement, number of dizziness attacks per week, the severity of the dizziness, and the Dizziness Handicap Inventory were more improved in the dry needling + exercise group at the first or fourth month compared with their inital assessments (P < 0.05). There was no diffence in fall index scores between the groups (P > 0.05).

Conclusions

Both dry needling + exercise therapy and exercise therapy alone were effective in treating dizziness caused by cervical myofascial pain syndrome. However, dry needling + exercise treatment was superior to exercise treatment alone.
The Evidence for Laser Treatments to the Vulvo-vagina: Making Sure We Do Not Repeat Past Mistakes
Authors: Song Sophia , Budden Aaron , Short Asha , Nesbitt-Hawes Erin , Deans Rebecca , Abbott Jason
Published: March 2018

(Abstracted from Aust N Z J Obstet Gynaecol 2017; doi: 10.1111/ajo.12735)

As a result of estrogen deficiency, up to 49% of postmenopausal women will experience vulvovaginal symptoms (VVSs) such as vaginal itching, dryness, dyspareunia, and incontinence. Treatment of VVS may be nonhormonal or hormonal.
The Association Between Anticoagulation Therapy, Maternal Characteristics, and a Failed cfDNA Test Due to a Low Fetal Fraction
Authors: Burns Whitney , Koelper Nathanael , Barberio Andrea , Deagostino-Kelly Mary , Mennuti Michael , Sammel Mary D. , Dugoff Lorraine
Published: March 2018

(Abstracted from Prenat Diagn 2017;37:1125–1129)

Fetal cell-free DNA (cfDNA) screening has been established as a screening method for trisomies 13, 18, and 21, as well as sex chromosome aneuploidies. Despite its rapid technological advancement since becoming clinically available in 2011, some women do not receive valid results after undergoing cfDNA testing because of a low fetal fraction (FF).
Patent Foramen Ovale and Hypoxemia
Authors: Mojadidi Mohammad K. , Ruiz Juan C. , Chertoff Jason , Zaman Muhammad O. , Elgendy Islam Y. , Mahmoud Ahmed N. , Al-Ani Mohammad , Elgendy Akram Y. , Patel Nimesh K. , Shantha Ghanshyam , Tobis Jonathan M. , Meier Bernhard
Published: March 2018

Patent foramen ovale (PFO), an embryonic remnant of the fetal circulation, is present in 20–25% of adults. Although recent observational studies and clinical trials have established the link between PFO-mediated right-to-left shunting with cryptogenic stroke and migraine with aura, the role of a PFO in exacerbating hypoxemic medical conditions (ie, sleep apnea, chronic obstructive pulmonary disease, pulmonary hypertension, platypnea–orthodeoxia, pulmonary arteriovenous malformation, high-altitude pulmonary edema, and exercise desaturation) remains less understood. PFO-mediated hypoxemia occurs when deoxygenated venous blood from the right atrium enters and mixes with oxygenated arterial blood in the left atrium. Patients with an intracardiac right-to-left shunt may have profound hypoxemia out of proportion to underlying primary lung disease, even in the presence of normal right-sided pressures. The presence of right-to-left cardiac shunting can exacerbate the degree of hypoxemia in patients with underlying pulmonary disorders. In a subset of these patients, percutaneous PFO closure may result in marked improvement in dyspnea and hypoxemia. This review discusses the association between PFO-mediated right-to-left shunting with medical conditions associated with hypoxemia and explores the role of percutaneous PFO closure in alleviating the hypoxemia.
HLA-DR Expression on Monocyte Subsets in Critically Ill Children
Authors: Boeddha Navin P. , Kerklaan Dorian , Dunbar Albert , van Puffelen Esther , Nagtzaam Nicole M. A. , Vanhorebeek Ilse , Van den Berghe Greet , Hazelzet Jan A. , Joosten Koen F. , Verbruggen Sascha C. , Dik Willem A. , Driessen Gertjan J.
Published: March 2018

Background:

To longitudinally study blood monocyte subset distribution and human leukocyte antigen-DR (HLA-DR) expression on monocyte subsets in children with sepsis, post-surgery and trauma in relation to nosocomial infections and mortality.

Methods:

In 37 healthy children and 37 critically ill children (12 sepsis, 11 post-surgery, 10 trauma and 4 admitted for other reasons)—participating in a randomized controlled trial on early versus late initiation of parenteral nutrition—monocyte subset distribution and HLA-DR expression on monocyte subsets were measured by flow cytometry upon admission and on days 2, 3 and 4 of pediatric intensive care unit (PICU) stay.

Results:

Upon PICU admission, critically ill children had a higher proportion of classical monocytes (CD14++CD16−) than healthy children [PICU 95% (interquartile range [IQR] 88%–98%); controls, 87% (IQR 85%–90%), P < 0.001]. HLA-DR expression was significantly decreased within all monocyte subsets and at all time points, being most manifest on classical monocytes and in patients with sepsis. Percentage of HLA-DR expressing classical monocytes [upon PICU admission 67% (IQR 44%–88%); controls 95% (IQR 92%–98%), P < 0.001], as well as the HLA-DR mean fluorescence intensity [upon PICU admission 3219 (IQR 2650–4211); controls 6545 (IQR 5558–7647), P < 0.001], decreased during PICU stay. Patients who developed nosocomial infections (n = 13) or who died (n = 6) had lower HLA-DR expression on classical monocytes at day 2 (P = 0.002) and day 3 (P = 0.04), respectively.

Conclusions:

Monocytic HLA-DR expression decreased during PICU stay and was lower compared with controls on all examined time points, especially on classical monocytes and in children admitted for sepsis. Low HLA-DR expression on classical monocytes was associated with nosocomial infections and death.
Single Balloon–assisted Colonoscopy for Placement of Colonic Manometry Catheters
Authors: Sanghavi Rinarani M. , Centeno Ricardo Medina‐ , Barth Bradley
Published: March 2018

Objectives:

Colonic manometry is used frequently in children with long standing and difficult to manage constipation to aid in management decisions. Accurate analysis requires placement of the colonic manometry catheter in the colon without looping. This is technically difficult due to the long‐standing nature of the constipation in most patients leading to sigmoid and other colonic redundancy. Single balloon colonoscopy has been successfully used in adult in cases of difficult colonoscopy. We report the first series of single balloon–assisted colonoscopy for performing difficult colonoscopy in children and placing colonic manometry catheters.

Methods:

Retrospective chart review was performed to identify patients undergoing the procedure. All patients had prior preparation with nasogastric golytely.

Results:

Using the single balloon technique, 36 patients underwent placement of the colonic manometry catheter (ages ranging from 3 to 16 years, weights 12 to 95 kg). Catheter placement was successful in all cases with procedure times of 20 to 105 minutes. No major complications were noted.

Conclusions:

This is the first reported series of using single balloon–assisted colonoscopy to perform difficult colonoscopy in children and place colonic manometry catheters. It may have other therapeutic implications in children such as removal of polyps or placement of similar catheters.
The Health Care Transition of Youth With Liver Disease Into the Adult Health System
Authors: Vajro Pietro , Fischler Björn , Burra Patrizia , Debray Dominique , Dezsofi Antal , Guercio Nuzio Salvatore , Hadzic Nedim , Hierro Loreto , Jahnel Joerg , Lamireau Thierry , McKiernan Patrick , McLin Valerie , Nobili Valerio , Socha Piotr , Smets Francoise , Baumann Ulli , Verkade Henkjan J.
Published: March 2018

Background:

Medical advances have dramatically improved the long‐term prognosis of children and adolescents with once‐fatal hepatobiliary diseases. However, there is no generally accepted optimal pathway of care for the transition from paediatric care to the adult health system.

Aim:

The purpose of this position paper is to propose a transition process for young people with paediatric onset hepatobiliary diseases from child‐centred to adult‐centred healthcare services.

Methods:

Seventeen ESPGHAN/EASL physicians from 13 countries (Austria, Belgium, France, Germany, Hungary, Italy, the Netherlands, Norway, Poland, Spain, Sweden, Switzerland, and United Kingdom) formulated and answered questions after examining the currently published literature on transition from childhood to adulthood. PubMed and Google Scholar were systematically searched between 1980 and January 2018. Quality of evidence was assessed by the Grading of Recommendation Assessment, Development and Evaluation (GRADE) system. Expert opinions were used to support recommendations whenever the evidence was graded weak. All authors voted on each recommendation, using the nominal voting technique.

Results:

We reviewed the literature regarding the optimal timing for the initiation of the transition process and the transfer of the patient to adult services, principal documents, transition multi‐professional team components, main barriers, and goals of the general transition process. A transition plan based on available evidence was agreed focusing on the individual young people's readiness and on coordinated teamwork, with transition monitoring continuing until the first year of adult services.

We further agreed on selected features of transitioning processes inherent to the most frequent paediatric‐onset hepatobiliary diseases. The discussion highlights specific clinical issues that will probably present to adult gastrointestinal specialists and that should be considered, according to published evidence, in the long‐term tracking of patients.

Conclusions:

Transfer of medical care of individuals with paediatric onset hepatobiliary chronic diseases to adult facilities is a complex task requiring multiple involvements of patients and both paediatric and adult care providers.
The Use and Safety of a Novel Haemostatic Spray in the Endoscopic Management of Acute Nonvariceal Upper Gastrointestinal Bleeding in Children
Authors: Thomson Mike , Urs Arun , Narula Priya , Rao Prithviraj , Belsha Dalia
Published: March 2018

Aims and Background:

Advanced endohaemostatic technique performance and experience is extremely variable in distribution amongst paediatric endoscopists. Haemostatic spray (Hemospray), a novel endohaemostatic topically applied powder has the advantage of extreme ease of use and; hence may lower the threshold of competency required by the endoscopist thereby potentially reducing mortality. The aim of the study is to prospectively evaluate the efficacy and the safety of haemostatic spray in paediatric patients with acute upper gastrointestinal bleeding (AUGIB).

Methods:

Prospective enrolment of children with AUGIB (Group 1) occurred, either as primary therapy or as an adjunct to standard endohaemostatic therapeutic techniques. Patients were assessed for likely need for endohaemostatic intervention of >8 of 24 of the paediatric Sheffield AUGIB score.

A follow‐up endoscopy occurred in those deemed to have clinical need pre‐discharge. For comparison, another group (Group 2) of patients, who received conventional endohaemostatic treatment in the preceding 36 months, were reviewed.

Results:

A total of 20 applications of Hemospray occurred in 17 patients (8 boys, median (range) age: 6.5 years (2 days to 17.75 years) and a total of 29 patients were enrolled in Group 2 (16 boys, median [range] age: 5.1 [0.25–17.0]). All patients tolerated haemostatic spray applications with no adverse events. The haemostatic spray group achieved 100% initial haemostasis with 18% rebleeding rate, although only a 6% failure rate after re‐application. In the conventional group, similar 100% initial haemostasis was achieved with 24% rebleeding rate and 7% failure rate necessitating surgical interventions.

Conclusions:

This paediatric series suggests that monotherapy with haemostatic spray is as effective as conventional approaches in the management of AUGIB.
The Treatment of Post-hysterectomy Vaginal Vault Prolapse: A Systematic Review and Meta-analysis
Authors: Coolen Anne-Lotte W. M. , Bui Bich Ngoc , Dietz Viviane , Wang Rui , van Montfoort Aafke P. A. , Mol Ben Willem J. , Roovers Jan-Paul W. R. , Bongers Marlies Y.
Published: March 2018

(Abstracted from Int Urogynecol J 2017;28:1767–1783)

Although treatment of posthysterectomy vaginal vault prolapse (VVP) has been investigated in several randomized clinical trials, the best treatment remains controversial. There has been no prior systematic overview comparing VVP treatments.
Pain Management for First-Trimester Uterine Aspiration
Authors: Moayedi Ghazaleh , Tschann Mary
Published: March 2018

Importance

First-trimester uterine aspiration can easily be performed in the office setting if adequate pain management for the patient is achieved. It is important for clinicians to understand evidence-based approaches for pain control to ensure a safe and efficient procedure.

Objective

This article reviews the literature regarding pharmacologic and nonpharmacologic pain control options for first-trimester abortion performed in the clinical setting. Preoperative, procedural, and postoperative pain control are all reviewed.

Evidence Acquisition

Authors searched the online database PubMed for relevant published literature through January 2018. To identify possible publications for review, the key word “abortion” was paired with the following key words: “pain,” “pain-control,” “pain management,” “aspiration,” “paracervical block,” “sedation, “non-pharmacologic,” and “post-operative.”

Results

Optimizing pain control for first-trimester uterine aspiration may involve interventions before, during, and after the surgery. Evidence shows patients benefit from premedication with nonsteroidal anti-inflammatory drugs, a defined paracervical block technique, and an option to use one of several nonpharmacologic interventions.

Conclusions and Relevance

Pain management for first-trimester uterine aspiration should be individualized for optimal patient satisfaction. Evidence supports multiple approaches to support this individualization. Targeted interventions before, during, and after the procedure should be offered to improve procedure experience and satisfaction.

Target Audience

Obstetricians and gynecologists, family physicians.

Learning Objectives

After completing this activity, the learner should be better able to identify at least 3 evidence-based pharmacologic pain interventions for first-trimester uterine aspiration, interpret evidence for nonpharmacologic pain management interventions for first-trimester uterine aspiration, analyze the gaps in knowledge for current pain management options, and compare predictors of pain for uterine aspiration.
A Forensic Approach to Sotos Syndrome
Authors: Byard Roger W.
Published: March 2018

Sotos syndrome is a childhood overgrowth condition that is caused by deletions or mutations in the NSD1 gene located on chromosome 5q35. The syndrome is associated with a wide variety of features that may result in sudden death. The aim of this report was to investigate the spectrum of potential findings in cases presenting to autopsy. A 4-month-old girl with Sotos syndrome was found dead after being put down to sleep. Her death was due to complex cardiac disease that included surgically repaired atrial and ventricular septal defects and valve abnormalities, with cardiomegaly. If the features of Sotos syndrome are identified de novo at autopsy, genetic investigations are warranted, although the recurrence risk is low. The involvement of a clinical geneticist may assist in evaluating cases, and postmortem imaging studies may provide useful information.
Sudden and Unexpected Death During Sexual Activity, Due to a Glial Cyst of the Pineal Gland
Authors: Barranco Rosario , Lo Pinto Sara , Cuccì Maria , Caputo Fiorella , Fossati Francesca , Fraternali Orcioni Giulio , Ventura Francesco
Published: March 2018

Cysts of the pineal gland are benign lesions. Often asymptomatic, in the majority of cases they are discovered incidentally during brain magnetic resonance imaging or autopsy. Sporadically, however, they may cause such symptoms as chronic headache, loss of consciousness, corticospinal and sensory impairment, and, in some cases, even sudden death. A 45-year-old woman, in apparently good health, collapsed and died suddenly, after reaching orgasm while engaged in sexual intercourse. According to the circumstantial account of her relatives, the woman suffered from severe headaches, which were exacerbated by certain types of physical strain, such as sexual activity. Postmortem examination revealed no external injuries or internal diseases except for a cystic lesion of the pineal gland. Microscopically, the wall of the cyst consisted of a layer of glial tissue surrounded by an area of pineal elements. A complete forensic approach concluded that the cause of death was fatal cardiorespiratory failure resulting from midbrain compression due to a nonneoplastic pineal gland cyst, exacerbated by sexual activity. In this case, the intracranial pressure increase, secondary to Valsalva maneuver during climax, may further aggravate compression on the brainstem, thus concurring to determine the death.
The impact of paediatric antimicrobial stewardship programmes on patient outcomes
Authors: Patel Sanjay V. , Vergnano Stefania
Published: March 2018

Purpose of review

Although there has been an unprecedented global effort to reduce the spread of antimicrobial resistance, little emphasis has been placed on children. This review aims to evaluate the impact of paediatric antimicrobial stewardship programmes as well as providing a practical approach for effectively implementing them in community-based settings and in hospitals.

Recent findings

Although rates of serious bacterial infection are low in children, the rates of antimicrobial use and resistance are comparable with adults. Different strategies are required to implement antimicrobial stewardship in community-based settings compared to in hospitals. Nationally coordinated, whole-system approaches have achieved long-term, sustainable reductions in antimicrobial prescribing, as well as reductions in resistance rates at population level, with no evidence of an increase in rate of serious infection or bacterial complications.

Antimicrobial stewardship programmes in neonates and children have unique characteristics and issues. There is currently no consensus on how to measure consumption of antimicrobials in neonates and children. This is a research priority. Benchmarking and clinical networks in neonates and paediatrics are important to share practice and drive best use of antimicrobials.
Simultaneous Implant Placement in a Mandibular Defect Reconstructed With a Free Fibula Graft and Fabrication of a Fixed Metal Porcelain Prosthesis
Authors: Kökat Ali M. , Erçöçen Ali R. , Karayazgan-Saraçoğlu Banu
Published: March 2018

This clinical report presents the multidisciplinary treatment approach for a 23-year-old male patient who underwent a total mandibular reconstruction due to trauma in the past and experienced postoperative complications. For his retreatment, exposed fixation plate was removed and infected bone was debrided and then a free fibula graft augmentation with simultaneous implant placement procedure was performed. After an osseointegration period of 6 months, a screw-retained porcelain fused to metal fixed prosthesis was fabricated and delivered.
An Unusual Case of Headache: Isolated Fungus Ball in Concha Bullosa
Authors: Bulut Fuat , Kazikdas Kadir Cagdas
Published: March 2018

A concha bullosa forms when the middle turbinate becomes pneumatized, which is a common anatomic variation; however, fungus ball in concha bullosa is rather rare. An otherwise healthy 52-year-old man presented to our ear, nose and throat clinic with the complaints of midfacial pressure headache and malodorous postnasal drip. Computed tomography of the paranasal sinuses demonstrated a polypoid hyperdense lesion with slight microcalcifications in the right nasal cavity, accompanied with a complicated fluid collection in the right frontoethmoideal recess seen as hypodensity in contrast to this hyperdensity. The histopathological examination reported a fungal infection. We present an extremely rare case of isolated fungal mass in the right middle concha detected in an early stage without any evidence of fungal infection of the other paranasal sinuses and discuss the importance of reevaluation of the computed tomography scans in suspicion of a fungal sinusitis.
Endoscopic Transsphenoidal Surgery for an Adult Patient With Giant Exophytic Chiasmatic/Hypothalamic Glioma
Authors: Wang Jing , Jia Jianwu , Hou Zhaoyuan , Yuan Xunhui , Sun Gaoling , Niu Jianyi , Li Zhiping
Published: March 2018

Optic pathway hypothalamic gliomas are intrinsic low-grade gliomas involving the optic nerve, chiasm, optic tract, and hypothalamus. The rarity of these tumors and their unpredictable course make assessment and standardization of treatment modalities difficult. Tumor debulking via various transcranial approaches was considered to be effective at controlling tumor growth, but with high rates of severe surgery-related complications. In the present case, endoscopic transsphenoidal surgery was initiated to debulk the exophytic chiasmatic/hypothalamic glioma with good preservation of hypothalamic and endocrine functions. The authors suggest transsphenoidal surgery with tumor debulking could be an effective and safe treatment for patients with chiasmatic/hypothalamic gliomas.
RAD51 paralogs regulate double strand break repair pathway choice by limiting Ku complex retention
Authors: Mejías-Navarro Fernando , Gómez-Cabello Daniel , Huertas Pablo
Published: March 2018

RAD51 paralogs are a group of conserved proteins in eukaryotes that are involved in the repair of DNA breaks at several levels. On one hand, they help the strand invasion step catalyzed by RAD51. Also, they play late roles in Holliday Junction metabolism. Here we uncover a new role of the RAD51 paralogs at an earlier event in the repair of broken chromosomes. All five RAD51 paralogs affect the balance between double strand break repair pathways. Specifically, they favor homology-mediated repair over non-homologous end-joining. Such role is independent of RAD51 or the checkpoint activity of these proteins. Moreover, it defines a novel control point of double strand break repair independent and subsequent to DNA-end resection initiation.

Mechanistically, RAD51 paralogs limit the retention of Ku80 at the sites of DNA breaks. Thus, our data extend the role of this family of proteins to the earliest event of double strand break repair.
A novel mouse model ofCampylobacter jejunienteropathy and diarrhea
Authors: Giallourou N , Medlock GL , Bolick DT , Medeiros PHQS , Ledwaba SE , Kolling GL , Tung K , Guerry P , Swann JR , Guerrant RL
Published: March 2018

Campylobacterinfections are among the leading bacterial causes of diarrhea and of ‘environmental enteropathy’ (EE) and growth failure worldwide. However, the lack of an inexpensive small animal model of enteric disease withCampylobacterhas been a major limitation for understanding its pathogenesis, interventions or vaccine development. We describe a robust standard mouse model that can exhibit reproducible bloody diarrhea or growth failure, depending on the zinc or protein deficient diet and on antibiotic alteration of normal microbiota prior to infection. Zinc deficiency and the use of antibiotics create a niche forCampylobacterinfection to establish by narrowing the metabolic flexibility of these mice for pathogen clearance and by promoting intestinal and systemic inflammation. Several biomarkers and intestinal pathology in this model also mimic those seen in human disease. This model provides a novel tool to testing specific hypotheses regarding disease pathogenesis as well as vaccine development that is currently in progress.

Author Summary

Campylobacter jejunihas been identified as one of the leading causes of enteropathy and diarrhea. In developing countries, these repeated enteric infections often result in growth deficits and cognitive impairment. There is a lack of small animal models ofCampylobacterinfection. This is a major hurdle in understanding the pathogenesis ofCampylobacterinfection in order to lead to therapeutic treatments and vaccines. We have developed a highly reproducible mouse model ofCampylobacterinfection that has clinical outcomes that match those of malnourished children. We hope that these insights intoCampylobactersusceptibility will lead to the development of treatments against this major cause of diarrheal illness.
Recombinant expression of Proteorhodopsin and biofilm regulators in Escherichia coli for nanoparticle binding and removal in a wastewater treatment model
Authors: Yang Justin , Wei Yvonne , Yeh Catherine , Liou Florence , Chen William , Lu Dylan , Chen Christine , Pei Justin , Lee Candice , Chen Emily , Lin Ashley , Imbrogulio Paul , Chang Katie , Hu Andrew , Kao Jesse , Chen Kelly , Tei Audrey , Yang Chansie , Hsu Katherine , Hsia Laurent , Wallace Oscar , Hau Abby , Liu Allen , Huang William , Chang Stephanie , Chang Catherine , Tsai Leona , Wang Avery , Lee Chang Sun , Wang Alvin , Shah Moksha , Yim Leon , Tsao Sean , Chiang Teresa , Clapper Jude C.
Published: March 2018

The small size of nanoparticles is both an advantage and a problem. Their high surface-area-to-volume ratio enables novel medical, industrial, and commercial applications. However, their small size also allows them to evade conventional filtration during water treatment, posing health risks to humans, plants, and aquatic life. This project aims to remove nanoparticles during wastewater treatment using genetically modified Escherichia coli in two ways: 1) binding citrate-capped nanoparticles with the membrane protein Proteorhodopsin, and 2) trapping nanoparticles using Escherichia coli biofilm produced by overexpressing two regulators: OmpR234 and CsgD. We demonstrate experimentally that Escherichia coli expressing Proteorhodopsin binds to 60 nm citrate-capped silver nanoparticles. We also successfully upregulate biofilm production and show that Escherichia coli biofilms are able to trap 30 nm gold particles. Finally, both Proteorhodopsin and biofilm approaches are able to bind and remove nanoparticles in simulated wastewater treatment tanks. We envision integrating our trapping system in both rural and urban wastewater treatment plants to efficiently capture all nanoparticles before treated water is released into the environment.

Financial Disclosure

This work was funded by the Taipei American School. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Competing Interests

The authors have declared that no competing interests exist.

Ethics Statement

N/A

Data Availability

Yes – all data are fully available without restriction. Sequences for the plasmids used in this study are available through the Registry of Standard Biological Parts. Links to raw data are included in Supplementary Information.
A Metagenomic Meta-Analysis Reveals Functional Signatures of Health and Disease in the Human Gut Microbiome
Authors: Armour Courtney , Nayfach Stephen , Pollard Katherine , Sharpton Thomas
Published: March 2018

While recent research indicates that human health depends, in part, upon the symbiotic relationship between gut microbes and their host, the specific interactions between host and microbe that define health are poorly resolved. Metagenomic clinical studies clarify this definition by revealing gut microbial taxa and functions that stratify healthy and diseased individuals. However, the typical single-disease focus of microbiome studies limits insight into which microbiome features robustly associate with health, indicate general deviations from health, or predict specific diseases. Additionally, the focus on taxonomy may limit our understanding of how the microbiome relates to health given observations that different taxonomic members can fulfill similar functional roles. To improve our understanding of the association between the gut microbiome and health, we integrated about 2,000 gut metagenomes obtained from eight clinical studies in a statistical meta-analysis. We identify characteristics of the gut microbiome that associate generally with disease, including functional alpha-diversity, beta-diversity, and beta-dispersion. Moreover, we resolve microbiome modules that stratify diseased individuals from controls in a manner independent of study-specific effects. Many of the differentially abundant functions overlap multiple diseases suggesting a role in host health, while others are specific to a single disease and may associate with disease-specific etiologies. Our results clarify potential microbiome-mediated mechanisms of disease and reveal features of the microbiome that may be useful for the development of microbiome-based diagnostics. Ultimately, our study clarifies the definition of a healthy microbiome and how perturbations to it associate with disease.
Genomic analysis ofAcinetobacter baumanniiprophages reveals remarkable diversity and suggests profound impact on bacterial virulence and fitness
Authors: Costa Ana Rita , Monteiro Rodrigo , Azeredo Joana
Published: March 2018

The recent nomination by the World Health Organization ofAcinetobacter baumanniias the number one priority pathogen for the development of new antibiotics is a direct consequence of its fast evolution of pathogenicity, and in particular of multidrug resistance. While the development of new antibiotics is critical, understanding the mechanisms behind the crescent bacterial pathogenicity is equally relevant. Often, resistance and other bacterial virulence elements are contained on highly mobile pieces of DNA that can easily spread to other bacteria. Prophages are one of the mediators of this form of gene transfer, and have been frequently found in bacterial genomes, often offering advantageous features to the host. Here we question the contribution of prophages for the evolution ofA. baumanniipathogenicity. We found prophages to be notably diverse and widely disseminated inA. baumanniigenomes. Also remarkably,A. baumanniiprophages encode for multiple putative virulence factors that may be implicated in the bacterium’s capacity to colonize host niches, evade the host immune system, subsist in unfavorable environments, and tolerate antibiotics. Overall our results point towards a significant contribution of prophages for the dissemination and evolution of pathogenicity inA. baumannii, and highlight their clinical relevance.
SISS-Geo: Leveraging Citizen Science to Monitor Wildlife Health Risks in Brazil
Authors: Chame Marcia , Barbosa Helio J. C. , Gadelha Luiz M. R. , Augusto Douglas A. , Krempser Eduardo , Abdalla Livia
Published: March 2018

The well-being of wildlife health involves many challenges, such as monitoring the movement of pathogens; expanding health surveillance beyond humans; collecting data and extracting information to identify and predict risks; integrating specialists from different areas to handle data, species and distinct social and environmental contexts; and, the commitment to bringing relevant information to society. In Brazil, there is still the difficulty of building a mechanism that is not impaired by its large territorial extension and its poorly integrated sectoral policies. The Brazilian Wildlife Health Information System, SISS-Geo, is a platform for collaborative monitoring that intends to overcome the challenges in wildlife health. It aims integration and participation of various segments of society, encompassing: the registration of occurrences by citizen scientists; the reliable diagnosis of pathogens from the laboratory and expert networks; and computational and mathematical challenges in analytical and predictive systems, knowledge extraction, data integration and visualization, and geographic information systems. It has been successfully applied to support decision-making on recent wildlife health events, such as a Yellow Fever epizooty.
Mitotic progression, arrest, exit or death is determined by centromere integrity and independent of de novo transcription
Authors: Novais-Cruz Marco , Abad Maria Alba , van Ijcken Wilfred F.J. , Galjart Niels , Jeyaprakash A. Arockia , Maiato Helder , Ferrás Cristina
Published: March 2018

Recent studies have challenged the prevailing dogma that transcription is repressed during mitosis. Transcription was also proposed to sustain the spindle assembly checkpoint (SAC) for several hours in response to unattached kinetochores. Here we used live-cell imaging of human cells in culture, combined with RNA-seq and qPCR, to investigate the requirement for de novo transcription during mitosis. Under conditions of persistently unattached kinetochores, transcription inhibition with actinomycin D, or treatment with other DNA-intercalating drugs, delocalized the chromosomal passenger complex (CPC) protein Aurora B from centromeres, compromising SAC robustness and cell fate. However, we were unable to detect significant changes in transcript levels. Moreover, inhibition of transcription independently of DNA intercalation had no effect on SAC response, mitotic progression, exit or death. Mechanistically, we show that DNA intercalating agents reduce the interaction of the CPC with nucleosomes. Thus, the capacity of human cells to progress, sustain, exit or die in mitosis relies on centromere integrity, rather than de novo transcription.
Rhizosphere bacterial community composition depends on plant diversity legacy in soil and plant species identity
Authors: Schmid Marc W. , Hahl Terhi , van Moorsel Sofia J. , Wagg Cameron , De Deyn Gerlinde B. , Schmid Bernhard
Published: March 2018

Soil microbes are known to be involved in a number of essential ecosystem processes such as nutrient cycling, plant productivity and the maintenance of plant species diversity. However, how plant species diversity and identity affect soil microbial diversity and community composition is largely unknown. We tested whether, over the course of 11 years, distinct soil bacterial communities developed under plant monocultures and mixtures, and if over this timeframe plants with a monoculture or mixture history changed in the microbial communities they associated with. For eight species, we grew offspring of plants that had been grown for 11 years in the same monocultures or mixtures (monoculture- or mixture-type plants) in pots inoculated with microbes extracted from the monoculture and mixture soils. After five months of growth in the glasshouse, we collected rhizosphere soil from each plant and used 16S-rRNA gene sequencing to determine the community composition and diversity of the bacterial communities. Microbial community structure in the plant rhizosphere was primarily determined by soil legacy (monoculture vs. mixture soil) and by plant species identity, but not by plant legacy (monoculture- vs. mixture-type plants). In seven out of the eight plant species bacterial abundance was larger when inoculated with microbes from mixture soil. We conclude that plant diversity can strongly affect belowground community composition and diversity, feeding back to the assemblage of rhizosphere microbial communities in newly establishing plants. Thereby our work demonstrates that concerns for plant biodiversity loss are also concerns for soil biodiversity loss.
Efficiently inferring the demographic history of many populations with allele count data
Authors: Kamm John A. , Terhorst Jonathan , Durbin Richard , Song Yun S.
Published: March 2018

The sample frequency spectrum (SFS), or histogram of allele counts, is an important summary statistic in evolutionary biology, and is often used to infer the history of population size changes, migrations, and other demographic events affecting a set of populations. The expected multipopulation SFS under a given demographic model can be efficiently computed when the populations in the model are related by a tree, scaling to hundreds of populations. Admixture, back-migration, and introgression are common natural processes that violate the assumption of a tree-like population history, however, and until now the expected SFS could be computed for only a handful of populations when the demographic history is not a tree. In this article, we present a new method for efficiently computing the expected SFS and linear functionals of it, for demographies described by general directed acyclic graphs. This method can scale to more populations than previously possible for complex demographic histories including admixture. We apply our method to an 8-population SFS to estimate the timing and strength of a proposed “basal Eurasian” admixture event in human history. We implement and release our method in a new open-source software packagemomi2.
DNA metabarcoding from sample fixative as a quick and voucher preserving biodiversity assessment method
Authors: Alida Zizka Vera Marie , Leese Florian , Peinert Bianca , Geiger Matthias Felix
Published: March 2018

Metabarcoding is a powerful tool for biodiversity assessment and has become increasingly popular in recent years. Although its reliability and applicability have been proven in numerous scientific studies, metabarcoding still suffers from some drawbacks. One is the usually mandatory destruction of specimens before DNA extraction, which is problematic because it does not allow a later taxonomic evaluation of the results. Additionally, metabarcoding often implements a time-consuming step, where specimens need to be separated from substrate or sorted in different size classes. A non-destructive protocol, excluding any sorting step, where the extraction of DNA is conducted from a samples fixative (ethanol) could serve as an alternative. We test an innovative protocol, where the sample preserving ethanol is filtered and DNA extracted from the filter for subsequent DNA metabarcoding. We first tested the general functionality of this approach on 15 mock communities comprising one individual of eight different macroinvertebrate taxa each and tried to increase DNA yield through different treatments (ultrasonic irradiation, shaking, freezing). Application of the method was successful for most of the samples and taxa, but showed weaknesses in detecting mollusc taxa. In a second step, the community composition detected in DNA from ethanol was compared to conventional bulk sample metabarcoding of complex environmental samples. We found that especially taxa with pronounced exoskeleton or shells (Coleoptera, Isopoda) and small taxa (Trombidiformes) were underrepresented in ethanol samples regarding taxa diversity and read numbers. However, read numbers of Diptera (mainly chironomids) and Haplotaxida were higher in ethanol derived DNA samples, which might indicate the detection of stomach content, which would be an additional advantage of this approach. Concerning EPT (Ephemeroptera, Plecoptera, Trichoptera) taxa which are decisive for the determination of ecological statuses, both methods had 46 OTUs in common with 4 unique to the ethanol samples and 10 to the bulk samples. Results indicate that fixative-based metabarcoding is a non-destructive, time-saving alternative for biodiversity assessments focussing on taxa used for ecological status determination. For a comprehensive picture on total biodiversity, the method might however not be sufficient and conventional bulk sample metabarcoding should be applied.
Non-productive Binding Modes as a Prominent Feature of Aβ1-40Fiber Elongation: Insights from Molecular Dynamics Simulation
Authors: Kar Rajiv K , Brender Jeffrey R , Ghosh Anirban , Bhunia Anirban
Published: March 2018

Amyloid formation has been implicated in a number of neurodegenerative diseases. The elongation of amyloid fibers is thermodynamically strongly favorable but kinetic traps exist where the incoming monomer binds in an incompatible conformation that blocks further elongation. Unfortunately, this process is difficult to follow experimentally at the atomic level. It is also too complex to simulate in full detail and thus so far has been explored either through coarse-grained simulations, which may miss many important interactions, or full atomic simulations in which the incoming peptide is constrained to be near the ideal fiber geometry. Here we use an alternate approach starting from a docked complex in which the monomer is from an experimental NMR structure of one of the major conformations in the unbound ensemble, a largely unstructured peptide with the central hydrophobic region in a 310helix. A 1000 ns full atomic simulation in explicit solvent shows the formation of a metastable intermediate by sequential, concerted movements of both the fiber and monomer. A Markov state model shows the unfolded monomer is trapped at the end of the fiber in a set of interconverting anti-parallel β-hairpin conformations. The simulation here may serve as a model for the binding of other non-β-sheet conformations to amyloid fibers.
Complex haplotypes of metabolizingGSTM1gene deletion harbors signatures of a selective sweep in East Asian populations
Authors: Saitou M. , Satta Y. , Gokcumen O.
Published: March 2018

The deletion of the metabolizing Glutathione S-transferase Mu 1 (GSTM1) gene was previously associated with multiple cancers, metabolic and autoimmune disorders, as well as drug response. It is unusually common, with allele frequency reaching up to 75% in some human populations. Such high allele frequency of a derived allele with apparent impact on an otherwise conserved gene is a rare phenomenon. To investigate the evolutionary history of this locus, we analyzed 310 genomes using population genetics tools. Our analysis revealed a surprising lack of linkage disequilibrium between the deletion and the flanking single nucleotide variants in this locus, indicating gene conversion events. Tests that measure extended homozygosity and rapid change in allele frequency identified signatures of an incomplete soft-sweep in the locus. Using empirical approaches, we identified theTanukihaplogroup, which carries theGSTM1deletion and is found in approximately 70% of East Asian chromosomes. This haplogroup has rapidly increased its frequency in East Asian populations, contributing to a high population differentiation among continental human populations. We showed that extended homozygosity and population differentiation for this haplogroup is incompatible with simulated neutral expectations in East Asian populations. In parallel, we revealed that theTanukihaplogroup is significantly associated with the expression levels of otherGSTMgenes. Collectively, our results suggest that theTanukihaplogroup has likely undergone a soft sweep in East Asia with multiple functional consequences. Our study provides the necessary framework for further studies to elucidate the evolutionary reasons that maintain disease-susceptibility variants in theGSTM1locus.

Lay summary

Here, we describe the evolutionary forces that shape the variation in a genomic region, which has been associated with bladder cancer, metabolic and autoimmune disorders and response to different drugs. Our results reveal a new genetic type common in Asian populations that may have important evolutionary and biomedical implications.