bluuebunny/crossref_metadata_2025 huggingface dataset:
Associations between sleep problems and ADHD symptoms among adolescents: findings from the Shandong Adolescent Behavior and Health Cohort (SABHC)
Authors: Liu Xianchen , Liu Zhen-Zhen , Liu Bao-Peng , Sun Shi-Hua , Jia Cun-Xian
Published: December 2019

Study Objectives

Sleep problems and symptoms of attention-deficit hyperactivity disorder (ADHD) in adolescence are common. Little is known about the prospective the prospective associations between sleep and subsequent ADHD symptoms in adolescents. This study examined the prospective associations between sleep problems and subsequent ADHD symptoms in a large sample of adolescents.

Methods

Participants included 7072 adolescents from the Shandong Adolescent Behavior and Health Cohort (SABHC) study in Shandong, China. Participants were initially assessed in November–December of 2015 and were reassessed 1-year later in 2016. Sleep duration, sleep problems, and psychosocial information were collected using a structured questionnaire. ADHD symptoms were measured by the Achenbach Child Behavior Checklist-Youth Self-Report.

Results

At baseline, 7.6% participants had clinically relevant ADHD symptoms, which were highly comorbid with sleep problems including insomnia symptoms, poor sleep quality, symptoms of restless legs syndrome (RLS), frequent snoring, and short sleep duration. Of the 6531 participants without clinically relevant ADHD symptoms at baseline, 4.5% reported clinically relevant ADHD symptoms at 1-year follow-up. After adolescent and family covariates were adjusted for, insomnia (OR = 2.09, 95% CI = 1.45–3.02), RLS (OR = 1.47, 95% CI = 1.02–2.11), and frequent snoring (OR = 2.30, 95% CI = 1.36–3.90) were all significantly associated with subsequent ADHD symptoms.

Conclusion

ADHD symptoms and sleep problems are highly comorbid. Insomnia, RLS and frequent snoring appear to be significant predictors of subsequent ADHD symptoms. Our study highlights the importance of assessing and managing sleep problems for prevention and clinical treatment of ADHD symptoms in adolescence.
Measuring Regional Ethnolinguistic Diversity in Sub-Saharan Africa: Surveys vs. GIS
Authors: Gershman Boris , Rivera Diego
Published: December 2019

This paper compares two approaches to measuring subnational ethnolinguistic diversity in Sub-Saharan Africa, one based on censuses and large-scale population surveys and the other relying on the use of geographic information systems (GIS). The two approaches yield sets of regional fractionalization indices that show a moderately positive correlation, with a stronger association across rural areas. These differences matter for empirical analysis: in a common sample of regions, survey-based indices of deep-rooted diversity show a more strongly negative association with a range of development indicators relative to their highest-quality GIS-based counterparts.
Medium-Run Impacts of Management Training in Garment Clusters
Authors: Higuchi Yuki , Mhede Edwin Paul , Nam Vu Hoang , Sonobe Tetsushi
Published: December 2019

This paper investigates the impact of management training programs on garment clusters in Vietnam and Tanzania. The study found that in the medium run firms showed improvement once they had identified useful practices and adapted them to their operations. Although it takes a few years to experience a significant impact on incomes, management training can increase not just management scores but also incomes or value added.
LuxR-Type Regulator AclR1 of Azorhizobium caulinodans Regulates Cyclic di-GMP and Numerous Phenotypes in Free-Living and Symbiotic States
Authors: Liu Wei , Li Yan , Bai Xue , Wu Haiguang , Bian Lanxing , Hu Xiaoke
Published: December 2019

LuxR-type regulators play important roles in transcriptional regulation in bacteria and control various biological processes. A genome sequence analysis showed the existence of seven LuxR-type regulators in Azorhizobium caulinodans ORS571, an important nitrogen-fixing bacterium in both its free-living state and in symbiosis with its host, Sesbania rostrata. However, the functional mechanisms of these regulators remain unclear. In this study, we identified a LuxR-type regulator that contains a cheY-homologous receiver (REC) domain in its N terminus and designated it AclR1. Interestingly, phylogenetic analysis revealed that AclR1 exhibited relatively close evolutionary relationships with MalT/GerE/FixJ/NarL family proteins. Functional analysis of an aclR1 deletion mutant (ΔaclR1) in the free-living state showed that AclR1 positively regulated cell motility and flocculation but negatively regulated exopolysaccharide production, biofilm formation, and second messenger cyclic diguanylate (c-di-GMP)-related gene expression. In the symbiotic state, the ΔaclR1 mutant was defective in competitive colonization and nodulation on host plants. These results suggested that AclR1 could provide bacteria with the ability to compete effectively for symbiotic nodulation. Overall, our results show that the REC-LuxR-type regulator AclR1 regulates numerous phenotypes both in the free-living state and during host plant symbiosis.
The Management of Postsurgical Wound Complications with Plasma Rich in Growth Factors: A Preliminary Series
Authors: Anitua Eduardo , Pino Ander
Published: December 2019

BACKGROUND

Postsurgical wound complications constitute a relevant public health issue because of their frequency. There is growing evidence regarding platelet-based autologous therapies that support their use in promoting cutaneous regeneration.

OBJECTIVE

To provide preliminary data regarding the potential benefit of plasma rich in growth factors (PRGF) in the management of postsurgical wound complications.

DESIGN

Three patients suffering from poorly healing severe full-thickness wounds were treated with either one or a combination of different formulations derived from their own blood: autologous clot, fibrin membrane, injectable plasma, or topical ointment. Different treatment protocols are described, and follow-up results are reported.

RESULTS

Within 4 to 12 months, the treated wounds healed completely with no signs of infection, tissue necrosis, or functional impairment. No adverse events were reported.

CONCLUSION

Additional clinical trials with long-term follow-up periods and larger patient populations are needed to establish the efficacy of PRGF technology. However, these preliminary findings suggest that PRGF merits further randomized controlled studies exploring its capacity to accelerate re-epithelialization and restore functional integrity to cutaneous ulcers resulting from surgical complications.
Making Decisions in the Era of the Clinical Decision Rule: How Emergency Physicians Use Clinical Decision Rules
Authors: Chan Teresa M. , Mercuri Mathew , Turcotte Michelle , Gardiner Emily , Sherbino Jonathan , de Wit Kerstin
Published: December 2019

Purpose

Physicians are often asked to integrate clinical decision rules (CDRs) with their own cognitive processes to reach a diagnosis. Clinicians, researchers, and educators must understand these cognitive processes to evaluate and improve the diagnostic process. The authors sought to explore emergency physicians’ diagnostic processes and to examine how they integrated CDRs into their reasoning using simulated cases (with chest pain or leg pain).

Method

From August 2015 to July 2016, 16 practicing emergency physicians from 3 teaching hospitals associated with McMaster University, Ontario, Canada, were interviewed via a novel “teach aloud” protocol. Six videos of simulated patients with chest pain, breathlessness, or leg discomfort were used as prompts for the physicians to demonstrate their diagnostic thinking. Using a constructivist grounded theory analysis, 3 investigators independently reviewed the interview transcripts, meeting regularly to discuss identified themes and subthemes until sufficiency was reached.

Results

A model to describe how clinicians integrate their own decision making with CDRs was developed, showing that physicians engage in an iterative diagnostic process that repeatedly refines the differential diagnosis list. The steps in the diagnostic process were: refinement of the differential diagnosis, ordering a hierarchy of risk, the decision to test, choosing the tests, and interpreting test results. Physicians applied CDRs when they had already decided to test.

Conclusions

To date, CDRs assume a static, linear model of clinical decision making. Findings demonstrate that participants engaged in iterative and dynamic decision-making processes that changed throughout their patient encounter, contingent on multiple contextual features. Understanding these processes could inform future development of CDRs and educational strategies around these decision aids.
Transfusion of Uncrossmatched Group O Erythrocyte-containing Products Does Not Interfere with Most ABO Typings
Authors: Yazer Mark H. , Spinella Philip C. , Doyle Leilani , Kaufman Richard M. , Dunn Robyn , Hess John R. , Filho Luiz Amorim , Fontaine Magali , Gathof Birgit , Jackson Bryon , Murphy Michael F. , Pasion Jeremiah , Raval Jay S. , Rosinski Kristin , Seheult Jansen , Shih Andrew W. , Sperry Jason , Staves Julie , Tuott Erin E. , Ziman Alyssa , Triulzi Darrell J. ,   on behalf of the Biomedical Excellence for Safer Transfusion Collaborative*
Published: December 2019

Background

Group O erythrocytes and/or whole blood are used for urgent transfusions in patients of unknown blood type. This study investigated the impact of transfusing increasing numbers of uncrossmatched type O products on the recipient’s first in-hospital ABO type.

Methods

This was a retrospective cohort study. Results of the first ABO type obtained in adult, non–type O recipients (i.e., types A, B, AB) after receiving at least one unit of uncrossmatched type O erythrocyte-containing product(s) for any bleeding etiology were analyzed along with the number of uncrossmatched type O erythrocyte-containing products administered in the prehospital and/or in hospital setting before the first type and screen sample was drawn.

Results

There were 10 institutions that contributed a total of 695 patient records. Among patients who received up to 10 uncrossmatched type O erythrocyte-containing products, the median A antigen agglutination strength in A and AB individuals on forward typing (i.e., testing the recipient’s erythrocytes for A and/or B antigens) was the maximum (4+), whereas the median B antigen agglutination strength among B and AB recipients of up to 10 units was 3 to 4+. The median agglutination strength on the reverse type (i.e., testing the recipient’s plasma for corresponding anti-A and -B antibodies) was very strong, between 3 and 4+, for recipients of up to 10 units of uncrossmatched erythrocyte-containing products. Overall, the ABO type of 665 of 695 (95.7%; 95% CI, 93.9 to 97.0%) of these patients could be accurately determined on the first type and screen sample obtained after transfusion of uncrossmatched type O erythrocyte-containing products.

Conclusions

The transfusion of smaller quantities of uncrossmatched type O erythrocyte-containing products, in particular up to 10 units, does not usually interfere with determining the recipient’s ABO type. The early collection of a type and screen sample is important.

Editor’s Perspective

What We Already Know about This Topic

What This Article Tells Us That Is New
Can We Save the Implant: Rib-based Implant Removal Rates and Risk Factors Following Irrigation and Debridement (I&D) Surgery?
Authors: Lott Carina , Qiu Catherine , McNeely Lia W. , Galagedera Nirupa , Campbell Robert M. , Flynn John M. , Cahill Patrick J. , Anari Jason B.
Published: December 2019

Background:

In the event of a surgical site infection, management includes surgical debridement in an attempt to treat the infection and retain the implant; however they are often unsuccessful in this regard. Although studies have described the incidence of complications, current literature does not have sufficient evidence to provide clear recommendations regarding retention versus removal of implants. This study aims to identify predictive factors associated with the need for implant removal to decrease unnecessary attempts at implant retention.

Methods:

A retrospective review of early-onset scoliosis patients at a single institution treated with rib-based vertical expandable prosthetic titanium rib implants who developed infection requiring irrigation and debridement (I&D) due to wound problems including surgical site infection, skin slough, and wound dehiscence. All patients had a minimum of a 2-year follow-up. Univariate and multivariate logistic regression analyses were conducted to determine the odds of implant removal.

Results:

Fifty-nine of 181 patients (32%) required an I&D due to a wound problem. These patients underwent the initial implant procedure at a mean age of 4.6±3.8 years. In total, 29 patients ultimately underwent implant removal. Significant predictive factors for removal included total number of wound problems, total number of I&Ds, days from identification of wound problem to I&D procedure, days on antibiotics, total number of surgeries, presence of gastrostomy tube, and nonambulatory status (P<0.0001, 0.001, 0.095, 0.093, 0.082, 0.054, and 0.026, respectively). Multiple logistic regression results indicated a total number of wound problems [odds ratio (OR): 6.00, P=0.001], average days from identification of wound problem to I&D (OR: 1.03, P=0.039), and presence of a gastrostomy tube (OR: 5.7, P=0.07) as independent predictors for implant removal.

Conclusions:

Data suggests that time from the onset of signs of infection until debridement surgery inversely correlates with the ability to retain the implants. In addition, gastrostomy tube and history of previous wound infections may be predictive clinical factors for implant removal in patients with a rib-based vertical expandable prosthetic titanium rib instrumentation. Such information can be useful for clinicians in deciding on whom to attempt implant retention versus removal when a wound problem presents itself.

Level of Evidence:

Level III.
A Helpful Clue to Calciphylaxis: Subcutaneous Pseudoxanthoma Elasticum–like Changes
Authors: Chen Eric L. , Altman Igor , Braniecki Marylee
Published: December 2019

Calciphylaxis, otherwise known as calcific uremic arteriolopathy, is an aggressive disease characterized by painful, ischemic skin lesions with histologic findings of microvascular calcification involving the fat. It is most commonly seen in patients with end-stage renal disease who are on dialysis. Early diagnosis is pivotal for optimal management. However, calciphylaxis can be challenging to diagnose, as many diseases can bear a clinical resemblance to calciphylaxis. Skin biopsies are often necessitated for diagnosis, but unfortunately, one is commonly challenged with a suboptimal amount of subcutaneous fat that does not always show the classic findings of microvascular calcification. However, when calciphylaxis is clinically suspected, the microscopic detection of subcutaneous pseudoxanthoma elasticum (PXE)-like changes, although not unequivocally diagnostic of calciphylaxis, can be a helpful clue in the diagnosis. We report a case of a 49-year-old woman who was diagnosed with uremic calciphylaxis on the basis of the clinical scenario, laboratory testing, and microscopic presence of subcutaneous PXE-like changes that was highlighted with the elastic and von Kossa stains. This case demonstrates the importance of recognizing subcutaneous PXE-like changes on suboptimal skin biopsies that lack microvascular calcification, especially in those patients who are clinically suspect for calciphylaxis as to prevent delay in diagnosis and treatment.
Relationship between office isolated systolic or diastolic hypertension and white-coat hypertension across the age spectrum: a home blood pressure study
Authors: Feitosa Audes D.M. , Mota-Gomes Marco A. , Barroso Weimar S. , Miranda Roberto D. , Barbosa Eduardo C.D. , Pedrosa Rodrigo P. , Oliveira Paula C. , Feltosa Camila L.D.M. , Brandão Andréa A. , Lima-Filho José L. , Sposito Andrei C. , Coca Antonio , Nadruz Wilson
Published: December 2019

Objective:

The current study investigated the prevalence of white-coat hypertension (WCH) and white-coat uncontrolled hypertension (WUCH) throughout the age spectrum among individuals with office isolated systolic hypertension (ISH), isolated diastolic hypertension (IDH) and systolic–diastolic hypertension (SDH) who were untreated or treated with antihypertensive medications, respectively.

Methods:

We cross-sectionally evaluated 8809 untreated (42% males, 52.1 ± 16.2 years) and 9136 treated (39% males, 59.7 ± 14.5 years) individuals from two independent Brazilian populations who underwent home blood pressure monitoring. Participants were also categorized as younger (<40 years), intermediate (≥40 and <60 years) and older (≥60 years) age.

Results:

Unadjusted and adjusted analyses showed that the frequency of WCH and WUCH was significantly greater (P < 0.05) in ISH and IDH than SDH at all age groups. Logistic regression analysis adjusted for sex, BMI and studied population showed that, compared with SDH, ISH had in average 4.1, 3.1 and 1.6-fold greater risk of WCH and 3.3, 3.6 and 2.0-fold greater risk of WUCH at younger, intermediate and older ages, whereas IDH had in average 2.3, 2.6 and 2.0-fold greater risk of WCH and 3.8, 3.2 and 3.8-fold greater risk of WUCH at younger, intermediate and older ages, respectively.

Conclusion:

ISH and IDH were associated with higher prevalence of WCH and WUCH than SDH across all age spectrum. In addition, treated and untreated ISH individuals with age less than 60 years and treated IDH individuals of all ages had the highest risk of having WCH phenotypes.
Long-Term Survival, Posttraumatic Stress, and Quality of Life post Extracorporeal Membrane Oxygenation
Authors: Harley Olivia , Reynolds Claire , Nair Priya , Buscher Hergen
Published: December 2019

The past years has seen a surge in usage of extracorporeal membrane oxygenation (ECMO). Little is known about long-term survival, posttraumatic stress, and quality of life (QoL). A single-centre retrospective cohort study on consecutive patients supported with ECMO between 2012 and 2016. Survivors completed a QoL questionnaire (Short-Form 36 [SF-36]) and the posttraumatic stress disorder (PTSD) Civilian Version (PCL-C). Two-hundred forty-one patients (age 52 years, 158 males) received ECMO. One hundred fifty-one patients (62.7%) survived to discharge, of these 129 (85%) were alive at a median follow-up of 31.8 months. Median survival was 56.6 months. Seventy-six (58.9%) returned a completed survey. The ECMO cohort experienced a decrease in QoL in all domains which was significantly associated with a high risk for PTSD with 30.8% in the highest PTSD risk bracket. Renal replacement therapy and duration of ECMO were significantly associated with increased mortality but not with QoL. The diagnoses of primary graft dysfunction or respiratory failure were independently associated with better long-term survival, but there was no difference in QoL between different underlying conditions. Despite good long-term survival rates, reduced QoL and PTSD were frequently observed. These findings reaffirm the need for long-term follow-up and rehabilitation in this population.
Achieving Osmotic Stability in the Context of Critical Illness and Acute Kidney Injury During Continuous Renal Replacement Therapy
Authors: Fang Diana , Chabrier-Rosello Jorge O. , McMahon Blaithin A. , Fülöp Tibor , Achanti Anand
Published: December 2019

The concept of osmotic stability during renal replacement therapy has received limited attention thus far. We report an illustrative case of a previously healthy 22 year old male presenting after prolonged ventricular fibrillation with 75 minutes of resuscitative efforts before regaining spontaneous perfusing rhythm. Central nervous system protecting hypothermia protocol and veno-arterious (VA) extracorporeal membrane oxygenator (ECMO) therapy were initiated at hospital admission due to refractory hypoxemia. Cardiovascular imaging procedures described global hypokinesis. Due to the combination of anuria, mixed acidosis and hemodynamic instability, we started continuous renal replacement therapy (CRRT) in continuous veno-venous hemodiafiltration functionality with added hypertonic saline solution (HTS) protocol, calculated to stabilize his serum sodium between 148 and 150 mEq/L. Serum osmolality also ranged between 321 and 317 mOsm/kg thereafter. Course was complicated by an acute right leg ischemia distal to VA ECMO cannula placement, requiring salvage therapy with cryoamputation. Vasoactive medication requirement and hemodynamics improved after the addition of intravenous (IV) hydrocortisone. Brain magnetic resonance imaging (MRI) 22 days post-arrest showed signals of limited hypoxic injury. He left the hospital in stable condition with limited neurologic sequelae. Therefore, the use of HTS during CRRT is a viable way to address potential or manifest cerebral edema and reduce the degree of cerebral injury.
Updates on current evidence for biologics in chronic rhinosinusitis
Authors: Nasta Melina S. , Chatzinakis Vasileios A. , Georgalas Christos C.
Published: December 2019

Purpose of review

The purpose of this review is to present the most important recent developments concerning biologics as a therapeutic option for chronic rhinosinusitis (CRS).

Recent findings

mAb anti-IL-4 receptor α (Dupilumab) was recently approved by Food and Drug Administration (FDA) for patients with CRSwNP and four other biologics are under investigation, with promising preliminary results.

CRS is a disease associated with a significant symptom burden and high-indirect costs. Despite recent advances in combined approaches, persistent symptoms or recurrences are not uncommon. Monoclonal antibodies, used mainly to treat asthma, have recently been shown to have a positive impact on controlling the symptoms of CRS and reducing the need for endoscopic sinus surgery. Dupilumab, mepolizumab, reslizumab, benralizumab and omalizumab are discussed and their mechanism of action, risk and current evidence on efficacy are presented. Preliminary studies show encouraging results with relatively few side effects. Once the high cost of such therapies is addressed, they could prove an important adjuvant therapy for patients with CRS. Large-scale clinical trials designed to evaluate them are called for.
Indications for Eustachian tube dilation
Authors: Siow Jin-Keat , Tan Jian-Li
Published: December 2019

Purpose of review

Eustachian tube dilation is a controversial surgical procedure because the intended problem for which it is meant to address, obstructive Eustachian tube dysfunction, is a clinical diagnosis without a reliable diagnostic tool to test.

In the past 10 years, balloon dilation Eustachian tuboplasty (BDET) has been the most commonly performed Eustachian tube dilation procedure. The present review seeks to identify the patients who may benefit from this procedure and thus propose the indications.

Recent findings

Two randomized controlled trials for BDET published in the past 2 years showed statistically significant improvement in terms of symptomatic relief based on the ETDQ-7 scores and conversion of abnormal tympanograms (type B and type C) to normal tympanograms (type A).

Based on the review of the evidence available so far, the proposed indication for Eustachian tube dilation using BDET is for a patient with ALL of the following: aural fullness greater than 12 weeks; type B or C tympanogram; ETDQ-7 mean score more than 2; and failed medical management including Valsalva maneuver and either 4 weeks of nasal steroids or 1 week of oral steroids.
Severe Abdominal Manifestations in Juvenile Dermatomyositis
Authors: Besnard Caroline , Gitiaux Cyril , Girard Muriel , Galmiche‐Rolland Louise , Talbotec Cécile , Quartier Pierre , Bodemer Christine , Berteloot Laureline , Bader‐Meunier Brigitte
Published: December 2019

Juvenile dermatomyositis (JDM) is a rare and heterogeneous pediatric‐onset idiopathic inflammatory myopathy. Gastrointestinal (GI) involvement occurs in 22% to 37% of JDM patients but has only been described in case reports. In this retrospective, single‐center, observational study, we aimed to assess the causes and management of severe GI manifestations in JDM patients. We studied a cohort of 9 patients among 110 JDM patients followed during the study period (8.3%). The GI complications were related to JDM in most cases (17/19), with digestive tract involvement (n = 10), acute pancreatitis (n = 4), and hepatitis (n = 3). Three patients died from refractory JDM 2.9 years (2–3.6) after the JDM diagnosis. We highlight the need to consider pancreatitis as a main diagnostic factor in JDM patients with severe GI manifestations and the requirement of early aggressive treatment for these patients.
Understanding Nurse Perception of Leader Empathy
Authors: Stuart Wilma Powell , Moore Bridget , Sims Brook M.
Published: December 2019

Patient perception of caregiver empathy has been studied internationally for decades. Although leadership empathy has been described as having a critical influence on staff retention, this subject is less evident in the literature. This article described a study undertaken to gain a baseline understanding of nurses' perceptions of leader empathy from those they identify as their managers. A baseline for nurses' perception of leader empathy has been established that may be used to benchmark future interventions to assess and improve nurses' perception of their leaders' empathy in the work setting.
Possibility of Deep Learning in Medical Imaging Focusing Improvement of Computed Tomography Image Quality
Authors: Nakamura Yuko , Higaki Toru , Tatsugami Fuminari , Honda Yukiko , Narita Keigo , Akagi Motonori , Awai Kazuo
Published: December 2019

Deep learning (DL), part of a broader family of machine learning methods, is based on learning data representations rather than task-specific algorithms. Deep learning can be used to improve the image quality of clinical scans with image noise reduction. We review the ability of DL to reduce the image noise, present the advantages and disadvantages of computed tomography image reconstruction, and examine the potential value of new DL-based computed tomography image reconstruction.
Online psychosocial interventions for posttreatment cancer survivors: an international evidence review and update
Authors: Skrabal Ross Xiomara , Gunn Kate M. , Olver Ian , Willems Roy A. , Lechner Lilian , Mesters Ilse , Bolman Catherine A.W.
Published: December 2019

Purpose of review

The present review describes recent research on online psychosocial interventions for posttreatment cancer survivors from January 2018 to June 2019.

Recent findings

Twenty-three studies were included in the review (the majority included were feasibility studies and only five randomized controlled trials had large samples). Websites were the most common platforms for intervention delivery (9/23) and cognitive behavioral therapy was the most frequently used therapeutic approach (11/23). Three interventions based on this framework and delivered via websites or combined website-telehealth platforms showed to be effective in improving psychosocial issues (fear of cancer recurrence, insomnia, sleep quality, and prospective memory failures) in posttreatment cancer survivors. Web-based self-compassion writing was also found to be effective in addressing body image distress and body appreciation in breast cancer survivors. Feasibility studies mostly showed online interventions to be plausible and acceptable to cancer survivors. A good representation of online interventions for young adult cancer survivors (30%) was found.

Online interventions show promise in addressing the psychosocial needs of cancer survivors. Despite new online interventions being found to be feasible and acceptable and some showing promise in addressing important psychosocial issues in cancer survivors posttreatment, more rigorous studies are required to inform supportive care for this population.
A short period of dark-adaptation is sufficient to generate light-induced photoreceptor degeneration in pigmented zebrafish
Authors: Khan Amanda S. , Friemel Taylor D. , Grillo Stephanie L. , Stella Salvatore L.
Published: December 2019

Light-induced retinal degeneration (LIRD) models are used to recapitulate the pathologies of retinal diseases that affect photoreceptors. Current LIRD models use a dark-adaptation period of 7–14 days followed by high-intensity light exposure. The purpose of this study was to determine whether photoreceptor damage and death would occur in pigmented zebrafish using a short period of dark-adaptation. Zebrafish were dark-adapted for 24 h and then exposed to constant high-intensity light for 48 h. Immunohistochemical analysis was performed on vertical retinal sections to assess damage and apoptosis. Photoreceptors exhibited structural damage, apoptosis, and cell loss after 24 and 48 h of light exposure as previously reported in studies using 7–14 day dark-adaption. Also, photoreceptors lost following light damage were regenerated after 28 days. These results suggest that a short period of dark-adaptation is sufficient for a LIRD model in pigmented zebrafish.
Involvement of 5-HT2A, 5-HT2B and 5-HT2C receptors in mediating the ventrolateral orbital cortex-induced antiallodynia in a rat model of neuropathic pain
Authors: Xu Wen-Jin , Wang Yu-Ying , Zhao Yan , Jia Hong , Tang Jing-Shi , Huo Fu-Quan , Liu Hua
Published: December 2019

The present study examined the roles of 5-HT2A, 5-HT2B and 5-HT2C receptor subtypes in mediating the ventrolateral orbital cortex (VLO)-induced antiallodynia in a rat model of neuropathic pain induced by spared nerve injury (SNI). Change of mechanical paw withdrawal threshold (PWT) was measured using von-Frey filaments. Microinjection of preferential or selective 5-HT2A/C, 5-HT2B and 5-HT2C receptor agonists, (±)-1-(2,5-Dimethoxy-4-iodophenyl)-2-aminopropane hydrochloride (DOI), α-methyl-5-(2-thienylmethoxy)-1H-Indole-3-ethanamine hydrochloride (BW723C86) and 1-(3-Chlorophenyl)-piperazine hydrochloride (m-CPP) into the VLO significantly depressed allodynia induced by SNI, and the inhibitory effect of DOI was blocked or attenuated by selective 5-HT2A/C receptor antagonists ketanserin (+)-tartrate salt (ketanserin) and 5-HT2A receptor antagonist R-(+)-alpha-(2,3-dimethoxyphenyl)-1-[2-(4-fluorophenylethyl)]-4-piperidinemethanol (M100907); the effects of BW723C86 and m-CPP were antagonized by 5-HT2B receptor antagonists N-(1-Methyl-1H-5-indolyl)-N′-(3-methyl-5-isothiazolyl)urea (SB204741) and 5-HT2C receptor antagonist RS102221 hydrochloride hydrate (RS-102221), respectively. These results suggest that 5-HT2A, 5-HT2B, 5-HT2C receptor subtypes are involved in mediating the VLO-induced antiallodynia in the neuropathic pain state.
Intracellular quality control of mitochondrial DNA: evidence and limitations
Authors: Knorre Dmitry A.
Published: December 2019

Eukaryotic cells can harbour mitochondria with markedly different transmembrane potentials. Intracellular mitochondrial quality-control mechanisms (e.g. mitophagy) rely on this intracellular variation to distinguish functional and damaged (depolarized) mitochondria. Given that intracellular mitochondrial DNA (mtDNA) genetic variation can induce mitochondrial heterogeneity, mitophagy could remove deleterious mtDNA variants in cells. However, the reliance of mitophagy on the mitochondrial transmembrane potential suggests that mtDNAs with deleterious mutations in ATP synthase can evade the control. This evasion is possible because inhibition of ATP synthase can increase the mitochondrial transmembrane potential. Moreover, the linkage of the mtDNA genotype to individual mitochondrial performance is expected to be weak owing to intracellular mitochondrial intercomplementation. Nonetheless, I reason that intracellular mtDNA quality control is possible and crucial at the zygote stage of the life cycle. Indeed, species with biparental mtDNA inheritance or frequent ‘leakage’ of paternal mtDNA can be vulnerable to invasion of selfish mtDNAs at the stage of gamete fusion. Here, I critically review recent findings on intracellular mtDNA quality control by mitophagy and discuss other mechanisms by which the nuclear genome can affect the competition of mtDNA variants in the cell.

This article is part of the theme issue ‘Linking the mitochondrial genotype to phenotype: a complex endeavour’.
Linking paternally inherited mtDNA variants and sperm performance
Authors: Bettinazzi Stefano , Nadarajah Sugahendni , Dalpé Andréanne , Milani Liliana , Blier Pierre U. , Breton Sophie
Published: December 2019

Providing robust links between mitochondrial genotype and phenotype is of major importance given that mitochondrial DNA (mtDNA) variants can affect reproductive success. Because of the strict maternal inheritance (SMI) of mitochondria in animals, haplotypes that negatively affect male fertility can become fixed in populations. This phenomenon is known as ‘mother's curse’. Doubly uniparental inheritance (DUI) of mitochondria is a stable exception in bivalves, which entails two mtDNA lineages that evolve independently and are transmitted separately through oocytes and sperm. This makes the DUI mitochondrial lineages subject to different sex-specific selective sieves during mtDNA evolution, thus DUI is a unique model to evaluate how direct selection on sperm mitochondria could contribute to male reproductive fitness. In this study, we tested the impact of mtDNA variants on sperm performance and bioenergetics in DUI and SMI species. Analyses also involved measures of sperm performance following inhibition of main energy pathways and sperm response to oocyte presence. Compared to SMI, DUI sperm exhibited (i) low speed and linearity, (ii) a strict OXPHOS-dependent strategy of energy production, and (iii) a partial metabolic shift towards fermentation following egg detection. Discussion embraces the adaptive value of mtDNA variation and suggests a link between male-energetic adaptation, fertilization success and paternal mitochondria preservation.

This article is part of the theme issue ‘Linking the mitochondrial genotype to phenotype: a complex endeavour’.
Sex-specific effects of mitochondrial haplotype on metabolic rate inDrosophila melanogastersupport predictions of the Mother's Curse hypothesis
Authors: Nagarajan-Radha Venkatesh , Aitkenhead Ian , Clancy David J. , Chown Steven L. , Dowling Damian K.
Published: December 2019

Evolutionary theory proposes that maternal inheritance of mitochondria will facilitate the accumulation of mitochondrial DNA (mtDNA) mutations that are harmful to males but benign or beneficial to females. Furthermore, mtDNA haplotypes sampled from across a given species distribution are expected to differ in the number and identity of these ‘male-harming’ mutations they accumulate. Consequently, it is predicted that the genetic variation which delineates distinct mtDNA haplotypes of a given species should confer larger phenotypic effects on males than females (reflecting mtDNA mutations that are male-harming, but female-benign), or sexually antagonistic effects (reflecting mutations that are male-harming, but female-benefitting). These predictions have received support from recent work examining mitochondrial haplotypic effects on adult life-history traits inDrosophila melanogaster. Here, we explore whether similar signatures of male-bias or sexual antagonism extend to a key physiological trait—metabolic rate. We measured the effects of mitochondrial haplotypes on the amount of carbon dioxide produced by individual flies, controlling for mass and activity, across 13 strains ofD. melanogasterthat differed only in their mtDNA haplotype. The effects of mtDNA haplotype on metabolic rate were larger in males than females. Furthermore, we observed a negative intersexual correlation across the haplotypes for metabolic rate. Finally, we uncovered a male-specific negative correlation, across haplotypes, between metabolic rate and longevity. These results are consistent with the hypothesis that maternal mitochondrial inheritance has led to the accumulation of a sex-specific genetic load within the mitochondrial genome, which affects metabolic rate and that may have consequences for the evolution of sex differences in life history.

This article is part of the theme issue ‘Linking the mitochondrial genotype to phenotype: a complex endeavour’.
Convergent patterns of evolution of mitochondrial oxidative phosphorylation (OXPHOS) genes in electric fishes
Authors: Elbassiouny Ahmed A. , Lovejoy Nathan R. , Chang Belinda S. W.
Published: December 2019

The ability to generate and detect electric fields has evolved in several groups of fishes as a means of communication, navigation and, occasionally, predation. The energetic burden required can account for up to 20% of electric fishes' daily energy expenditure. Despite this, molecular adaptations that enable electric fishes to meet the metabolic demands of bioelectrogenesis remain unknown. Here, we investigate the molecular evolution of the mitochondrial oxidative phosphorylation (OXPHOS) complexes in the two most diverse clades of weakly electric fishes—South American Gymnotiformes and African Mormyroidea, using codon-based likelihood approaches. Our analyses reveal that although mitochondrial OXPHOS genes are generally subject to strong purifying selection, this constraint is significantly reduced in electric compared to non-electric fishes, particularly for complexes IV and V. Moreover, analyses of concatenated mitochondrial genes show strong evidence for positive selection in complex I genes on the two branches associated with the independent evolutionary origins of electrogenesis. These results suggest that adaptive evolution of proton translocation in the OXPHOS cellular machinery may be associated with the evolution of bioelectrogenesis. Overall, we find striking evidence for remarkably similar effects of electrogenesis on the molecular evolution of mitochondrial OXPHOS genes in two independently derived clades of electrogenic fishes.

This article is part of the theme issue ‘Linking the mitochondrial genotype to phenotype: a complex endeavour’.
Mitonuclear conflict and cooperation govern the integration of genotypes, phenotypes and environments
Authors: Rand David M. , Mossman Jim A.
Published: December 2019

The mitonuclear genome is the most successful co-evolved mutualism in the history of life on Earth. The cross-talk between the mitochondrial and nuclear genomes has been shaped by conflict and cooperation for more than 1.5 billion years, yet this system has adapted to countless genomic reorganizations by each partner, and done so under changing environments that have placed dramatic biochemical and physiological pressures on evolving lineages. From putative anaerobic origins, mitochondria emerged as the defining aerobic organelle. During this transition, the two genomes resolved rules for sex determination and transmission that made uniparental inheritance the dominant, but not a universal pattern. Mitochondria are much more than energy-producing organelles and play crucial roles in nutrient and stress signalling that can alter how nuclear genes are expressed as phenotypes. All of these interactions are examples of genotype-by-environment (GxE) interactions, gene-by-gene (GxG) interactions (epistasis) or more generally context-dependent effects on the link between genotype and phenotype. We provide evidence from our own studies inDrosophila, and from those of other systems, that mitonuclear interactions—either conflicting or cooperative—are common features of GxE and GxG. We argue that mitonuclear interactions are an important model for how to better understand the pervasive context-dependent effects underlying the architecture of complex phenotypes. Future research in this area should focus on the quantitative genetic concept of effect size to place mitochondrial links to phenotype in a proper context.

This article is part of the theme issue ‘Linking the mitochondrial genotype to phenotype: a complex endeavour’.
Temperature-gradient incubation isolates multiple competitive species from a single environmental sample
Authors: Houghton Karen M. , Stewart Lucy C.
Published: December 2019

High-throughput sequencing has allowed culture-independent investigation into a wide variety of microbiomes, but sequencing studies still require axenic culture experiments to determine ecological roles, confirm functional predictions and identify useful compounds and pathways. We have developed a new method for culturing and isolating multiple microbial species with overlapping ecological niches from a single environmental sample, using temperature-gradient incubation. This method was more effective than standard serial dilution-to-extinction at isolating methanotrophic bacteria. It also highlighted discrepancies between culture-dependent and -independent techniques; 16S rRNA gene amplicon sequencing of the same sample did not accurately reflect cultivatable strains using this method. We propose that temperature-gradient incubation could be used to separate out and study previously ‘unculturable’ strains, which co-exist in both natural and artificial environments.
PI-Plat: A high-resolution image-based 3D reconstruction method to estimate growth dynamics of rice inflorescence traits
Authors: Sandhu Jaspreet , Zhu Feiyu , Paul Puneet , Gao Tian , Dhatt Balpreet K. , Ge Yufeng , Staswick Paul , Yu Hongfeng , Walia Harkamal
Published: December 2019

Background

Recent advances in image-based plant phenotyping have improved our capability to study vegetative stage growth dynamics. However, more complex agronomic traits such as inflorescence architecture (IA), which predominantly contributes to grain crop yield are more challenging to quantify and hence are relatively less explored. Previous efforts to estimate inflorescence-related traits using image-based phenotyping have been limited to destructive end-point measurements. Development of non-destructive inflorescence phenotyping platforms could accelerate the discovery of the phenotypic variation with respect to inflorescence dynamics and mapping of the underlying genes regulating critical yield components.

Results

The major objective of this study is to evaluate post-fertilization development and growth dynamics of inflorescence at high spatial and temporal resolution in rice. For this, we developed the Panicle Imaging Platform (PI-Plat) to comprehend multi-dimensional features of IA in a non-destructive manner. We used 11 rice genotypes to capture multi-view images of primary panicle on weekly basis after the fertilization. These images were used to reconstruct a 3D point cloud of the panicle, which enabled us to extract digital traits such as voxel count and color intensity. We found that the voxel count of developing panicles is positively correlated with seed number and weight at maturity. The voxel count from developing panicles projected overall volumes that increased during the grain filling phase, wherein quantification of color intensity estimated the rate of panicle maturation. Our 3D based phenotyping solution showed superior performance compared to conventional 2D based approaches.

Conclusions

For harnessing the potential of the existing genetic resources, we need a comprehensive understanding of the genotype-to-phenotype relationship. Relatively low-cost sequencing platforms have facilitated high-throughput genotyping, while phenotyping, especially for complex traits, has posed major challenges for crop improvement. PI-Plat offers a low cost and high-resolution platform to phenotype inflorescence-related traits using 3D reconstruction-based approach. Further, the non-destructive nature of the platform facilitates analyses of the same panicle at multiple developmental time points, which can be utilized to explore the genetic variation for dynamic inflorescence traits in cereals.
Reprogrammed Pteropus Bat Stem Cells Present Distinct Immune Signature and are Highly Permissive for Henipaviruses
Authors: Aurine Noémie , Baquerre Camille , Gaudino Maria , Jean Christian , Dumont Claire , Rival-Gervier Sylvie , Kress Clémence , Horvat Branka , Pain Bertrand
Published: December 2019

Bats are unique among mammals due to the ability of powered flight and exceptional longevity. They are also asymptomatic hosts for numerous viruses, including recently emerged zoonotic Henipaviruses Nipah and Hendra, which are highly pathogenic for humans and other mammals. Better understanding of how bats control viral infection requires development of relevant permissive cellular experimental models. By applying a somatic reprogramming protocol to Pteropus bat primary cells, using a novel combination of ESRRB, CDX2, and c-MYC transcription factors, we generated bat reprogrammed cells exhibiting stem cell-like characteristics and a neural stem cell-like molecular signature. These cells present a unique interferon-stimulated transcriptomic signature and both produce and respond to interferon type-I, highlighting differences between stem cells from bats and other mammals. In contrast to primary bat cells, these reprogrammed cells are highly susceptible to infection by Henipavirus, thereby enabling isolation of new bat viruses, study of virus-bat interactions, and better understanding of bat biology.

Summary sentence

Somatic reprogramming provides new bat stem cells with unique immune properties and original viral permissivness
Adenita: Interactive 3D modeling and visualization of DNA Nanostructures
Authors: de Llano Elisa , Miao Haichao , Ahmadi Yasaman , Wilson Amanda J. , Beeby Morgan , Viola Ivan , Barisic Ivan
Published: December 2019

We present Adenita, a novel software tool for the design of DNA nanostructures in a user-friendly integrated environment for molecular modeling. Adenita is capable of handling large DNA origami structures, re-use them as building blocks of new designs and provide on demand feedback, thus overcoming effectively some of the limitations of existing tools. Additionally, it integrates all major established approaches to DNA nanostructure design (DNA origami, wireframe nanostructures and DNA tiles) and allows to combine them. We show-case Adenita by re-using a large nanorod designed with Cadnano [1] to create a new nanostructure through user interactions that employ different editors to modify the original nanorod.
Elucidating the competition between heterotrophic denitrification and DNRA using the resource-ratio theory
Authors: Jia Mingsheng , Winkler Mari K.H. , Volcke Eveline I.P.
Published: December 2019

Denitrification and dissimilatory nitrate reduction to ammonium (DNRA) are two microbial processes competing for nitrate and organic carbon (COD). Their competition has great implications for nitrogen loss, conservation, and greenhouse gas emissions. Nevertheless, a comprehensive and mechanistic understanding of the governing factors for this competition is still lacking. We applied the resource-ratio theory and verified it with competition experiments of denitrification and DNRA reported in the literature. Based on this theory, we revealed how COD/N ratio, influent resource concentrations, dilution rate, and stoichiometric and kinetic parameters individually and collectively define the boundaries for different competition outcomes in continuous cultures. The influent COD/N ratio alone did not drive competition outcome as the boundary COD/N ratio for different competition outcomes changed significantly with influent resource concentrations. The stoichiometry of the two processes was determinative for the boundaries, whereas the affinity for the resources (Ks), maximum specific growth rate (μmax) of the two species and the dilution rate had significant impacts as well but mainly at low influent resource concentrations (e.g., <100 μM nitrate). The proposed approach allows for a more comprehensive understanding of the parameters controlling microbial selection and explains apparently conflicting experimental results. The results from this model also provide testable hypotheses and tools for understanding and managing the fate of nitrate in ecosystems and for other species that compete for two resources.