bluuebunny/crossref_metadata_2025 huggingface dataset:
Prevalence of Gram-Negative Bacteria in Ventilator-Associated Pneumonia in Neonatal Intensive Care Units
Authors: Erfani Yousef , Rasti Arezoo , Janani Leila , Tanha Kiarash , Noghabi Samaneh Lotfi , Azami Seyedeh Roya , Kamali Mahboobeh
Published: June 2019

This systematic review was conducted to determine the prevalence of gram-negative bacteria in ventilator-associated pneumonia (VAP) as a potentially lethal and serious infection among mechanically ventilated neonates in neonatal intensive care units (NICUs). We searched PubMed, SCOPUS, EMBASE, and the ISI Web of Science databases as well as Google Scholar search engine up to November 20, 2017, with no restriction on language. We included studies reporting prevalence of gram-negative bacterial infection of neonatal VAP in NICUs. Risk of bias assessment using the tool developed by Hoy et al (J Clin Epidemiol. 2012; 65:934–939), and data extraction were conducted by 2 independent reviewers. A random-effects meta-analysis was used for combining the data. Of 11,072 screened references, 9 relevant studies were included in this meta-analysis. The overall pooled prevalence rate of gram-negative bacterial infections of neonates who were on mechanical ventilation for more than 48 hours was 72.0% (95% confidence interval, 0.60–0.83). Among the isolated gram-negative bacteria, Klebsiella species had the highest detection rate, with 41.0% overall pooled prevalence. When the results were merged, the VAP rate was found to be 3/1000 ventilator-days. Male sex, prolonged hospitalization stay, and cesarean delivery were statistically significant risk factors for VAP incidence in NICUs. Prevalence of gram-negative bacteria in VAP in NICUs is high, and it is mainly caused by Klebsiella species and could be affected by several factors. Further studies should be conducted on the drug resistance pattern of these bacteria. In addition, effective mechanisms for infection control should be considered to prevent these bacterial infections in VAP in NICUs.
Personality and Psychopathology in Patients With Mixed Sensory-Motor Functional Neurological Disorder (Conversion Disorder)
Authors: Søgaard Ulf , Mathiesen Birgit B. , Simonsen Erik
Published: June 2019

The purpose of this pilot study was to explore differences in the level of personality functioning, symptom severity, and personality pathology in patients with mixed sensory-motor functional neurological disorder (conversion disorder). Individuals with psychogenic nonepileptic seizures were not included. We recruited 15 patients, mean age of 33.5 years (SD, 11.4 years), 13 females and 2 males, from an outpatient clinic for psychotherapeutic treatment. We assessed the patients using the Structured Clinical Interview for DSM-4 Axis II Personality Disorders, the SCL-90-R, the Karolinska Psychodynamic Profile, and the Defense Style Questionnaire. We were able to distinguish two levels of difficulty in relation to personality functioning as distinct subgroups: 1) “neurotic” with less severe or moderate personality psychopathology and 2) “borderline” with severe personality psychopathology. Furthermore, we concluded that all patients showed severe deficits in personality functioning. The study points out the clinical relevance of identifying personality functioning as part of an assessment in the preparation of a treatment strategy.
Plasma Neutrophil Gelatinase-Associated Lipocalin Is Associated With Acute Kidney Injury and Clinical Outcomes in Neonates Undergoing Cardiopulmonary Bypass
Authors: Schroeder Luke W. , Buckley Jason R. , Stroud Robert E. , Martin Renee H. , Nadeau Elizabeth K. , Barrs Ryan , Graham Eric M.
Published: June 2019

Objectives:

Acute kidney injury is a frequent complication following neonatal cardiac surgery and is associated with significant morbidity and mortality. The objectives of this study were to determine if plasma neutrophil gelatinase-associated lipocalin levels were associated with acute kidney injury and clinical outcomes in neonates with congenital heart disease undergoing cardiopulmonary bypass.

Design:

Retrospective single-center observational study.

Setting:

A pediatric cardiac ICU within a tertiary-care academic hospital.

Patients:

Patients age less than 30 days undergoing cardiac surgery requiring cardiopulmonary bypass.

Interventions:

None.

Measurements and Main Results:

Plasma neutrophil gelatinase-associated lipocalin peaked at 12 hours postcardiopulmonary bypass and more than doubled compared with preoperative levels. Higher preoperative and 24-hour postoperative neutrophil gelatinase-associated lipocalin levels were associated with acute kidney injury (r = 0.30, r = 0.49), longer duration of mechanical ventilation (r = 0.40, r = 0.51), ICU (r = 0.32, r = 0.33) and hospital lengths of stay (r = 0.28, r = 0.32), and total hospital charges (r = 0.35, r = 0.30; all p values < 0.05).

Conclusions:

Both preoperative and 24-hour postoperative plasma neutrophil gelatinase-associated lipocalin levels are associated with acute kidney injury and worse clinical outcomes in neonates undergoing cardiac surgery. Plasma neutrophil gelatinase-associated lipocalin levels may have a role in risk stratification for predicting postoperative renal dysfunction as well as providing a potential clinical trajectory in the postoperative period.
Evaluating the Practice of Repositioning Endotracheal Tubes in Neonates and Children Based on Radiographic Location*
Authors: Im Daniel D. , Ross Patrick A. , Hotz Justin , Newth Christopher J. L.
Published: June 2019

Objectives:

Chest radiographs are commonly performed in the ICU setting to confirm the position of the endotracheal tube. The purpose of this study was to evaluate the practice and accuracy of repositioning endotracheal tubes in the pediatric population based on chest radiograph.

Design:

Retrospective review of patient’s medical record and chest radiograph.

Setting:

Single-institution, academic children’s hospital.

Patients:

PICU and cardiothoracic ICU patients who had repositioning of their endotracheal tube from September 1, 2016, to September 1, 2017.

Measurements and Main Results:

Chest radiograph before and after endotracheal tube repositioning were examined measuring the distance from the endotracheal tube tip to carina. A total of 183 endotracheal tube repositionings were assessed. Twenty-nine percent of endotracheal tube repositionings resulted in a persistently malpositioned endotracheal tube, requiring another intervention. For intended endotracheal tube repositioning of ± 2.0 cm, the actual change measured compared to intended adjustment was a median of 0.7 cm (interquartile range, 0.35–1.1 cm). For intended ± 1.5 cm, the median difference was 0.4 cm (interquartile range, 0.16–0.90 cm). For intended ± 1.0 cm, the median difference was 0.5 cm (interquartile range, 0.20–0.90 cm). For intended ± 0.5 cm, the median difference was 0.3 cm (interquartile range, 0.2–0.88 cm). When the head was malpositioned the difference from intended endotracheal tube repositioning to actual was median 0.70 cm (interquartile range, 0.40–1.1 cm), this was significantly higher than when the head was in a good position

Conclusions:

When repositioning endotracheal tubes based on chest radiograph, there is a significant difference between intended and actual adjustment with great variability. Avoiding very small repositionings (± 0.5 cm) and standardizing head position prior to daily chest radiograph may reduce these errors.
A Specialized Pediatric Emergency Medicine Track Decreases Computed Tomography in Head Injured Patients
Authors: Conrad Heather B. , Hollenbach Kathryn A. , Ratnayake Kristin , Gehlbach Daniel L. , Carstairs Keri L.
Published: June 2019

Background

There is an increased emphasis on reducing exposure to ionizing radiation in pediatric patients. Guidelines from the Pediatric Emergency Care Applied Research Network help practitioners identify patients at low risk for clinically important traumatic brain injury after head injury.

Objectives

We seek to determine whether the institution of a pediatric track staffed by pediatric emergency medicine physicians (PEMs) within a community emergency department (ED) impacts the overall utilization of head computed tomography (CT) on children younger than 15 years with head injury.

Methods

We used a retrospective cohort analysis of patients under the age of 15 years presenting to a community ED in the year before and the year of institution of a pediatric emergency track. Relative risk estimates were used to determine the risk of CT use associated with nonpediatric-trained emergency providers.

Results

The community ED saw 11,094 patients and 14,639 patients younger than 15 years in fiscal years 2014–2015 and 2015–2016, respectively. In the year before PEMs, there were 312 children younger than 15 years seen for head injury; 47.09% received head CTs. After PEM coverage, there were 396 children younger than 15 years seen for head injury; 17.17% received head CTs. Pediatric patients with head injury were 2.2 times more likely to receive CTs before the institution of the pediatric track (95% confidence interval, 1.8–2.6).

Conclusion

The implementation of a pediatric emergency track demonstrated a significant decrease in CT utilization for head injury. Continued development of pediatric tracks in community EDs can lead to reduction of CTs.
The Relation Between Loss of Consciousness, Severity of Traumatic Brain Injury, and Injury of Ascending Reticular Activating System in Patients With Traumatic Brain Injury
Authors: Jang Sung Ho , Kim Oh Lyong , Kim Seong Ho , Kim Jong Bum
Published: June 2019

Objective

Loss of consciousness is an indicator of the severity of traumatic brain injury and the ascending reticular activating system has been considered as a main structure for consciousness. However, no study on the relation between loss of consciousness and ascending reticular activating system injury in traumatic brain injury has been reported. We investigated the relation between loss of consciousness, severity of traumatic brain injury, and ascending reticular activating system injury using diffusion tensor tractography.

Design

One hundred twenty patients were recruited. Three components of ascending reticular activating system, fractional anisotropy, and tract volume were measured.

Results

In lower dorsal and ventral ascending reticular activating system, fractional anisotropy and tract volume value in mild group were higher than those of moderate and severe groups, and there was no difference between moderate and severe groups. In upper ascending reticular activating system, fractional anisotropy value in mild group was higher than in moderate group, and it was higher than in moderate group than in severe group. Tract volume value in mild group was higher than in severe group. Loss of consciousness showed moderate negative correlations with tract volume value of lower dorsal ascending reticular activating system (r = −0.348), fractional anisotropy value of lower ventral ascending reticular activating system (r = −0.343), and fractional anisotropy value of upper ascending reticular activating system (r = −0.416).

Conclusions

Injury severity was different among the three traumatic brain injury groups in upper ascending reticular activating system but did not differ between moderate and severe groups in lower dorsal and ventral ascending reticular activating system.
Fat Grafting and the Palpable Breast Mass in Implant-Based Breast Reconstruction: Incidence and Implications
Authors: Knackstedt Rebecca W. , Gatherwright James , Ataya Dana , Duraes Eliana F. R. , Schwarz Graham S.
Published: June 2019

Background:

Fat grafting is a powerful and increasingly used technique in breast reconstruction. However, fat necrosis can lead to palpable postoperative changes that can induce anxiety and lead to unplanned diagnostic studies. The authors’ aim in this study was to evaluate the incidence, type, and timing of these unanticipated studies; the specialty of the ordering provider; and the factors that trigger the ordering process.

Methods:

A retrospective chart review was conducted for patients from 2006 to 2015 who underwent fat grafting as part of implant-based breast cancer reconstruction and had at least 1-year follow-up after fat grafting.

Results:

From 2006 to 2015, 166 patients underwent fat grafting as part of implant-based breast reconstruction. Forty-four women (26.5 percent) underwent at least one imaging procedure. Thirteen women (7.8 percent) underwent 17 biopsies. For a palpable mass, the initial imaging test most commonly ordered was ultrasound, followed by mammography/ultrasound. The percentage of patients with a diagnosis of fat necrosis on mammography, ultrasound, and biopsy was 4.2, 12.7, and 5.4 percent, respectively. Seven patients (4.2 percent) had distant metastases. Tissue diagnosis of local recurrence was never identified. Mean follow-up was 2.4 years.

Conclusions:

Fat-grafting sequelae may lead to early unplanned invasive and noninvasive procedures initiated by a variety of providers. In this study, fat grafting had no impact on local recurrence rate. As use of fat grafting grows, communication among breast cancer care providers and enhanced patient and caregiver education will be increasingly important in optimizing the multidisciplinary evaluation and monitoring of palpable breast lesions.

CLINICAL QUESTION/LEVEL OF EVIDENCE:

Therapeutic, IV.
A Quantitative Analysis of Animation Deformity in Prosthetic Breast Reconstruction
Authors: Kim John Y. S. , Qiu Cecil S. , Chiu Wen-Kuan , Feld Lauren N. , Mioton Lauren M. , Kearney Aaron , Fracol Megan
Published: June 2019

Background:

Animation deformity is characterized by implant deformity with pectoralis contraction after subpectoral implant-based breast reconstruction. Extant methods to measure and analyze animation deformity are hampered by the paucity of objective, quantitative data. The authors endeavored to supplement subjective measures with an in-depth quantitative analysis.

Methods:

Patients undergoing subpectoral implant-based breast reconstruction were followed prospectively with video analysis of animation deformity. Nipple displacement and surface area of contour deformity in resting and contracted states were quantified using imaging software. Degree of animation was compared to breast size, body mass index, division of pectoralis muscle, complications, and radiation therapy.

Results:

One hundred forty-five reconstructed breasts (88 patients) were analyzed. Mean nipple displacement was 2.12 ± 1.04 cm, mean vector of nipple displacement was 62.5 ± 20.6 degrees, and mean area of skin contour irregularity was 16.4 ± 15.41 percent. Intraoperative pectoralis division, smooth/round implants, and bilateral reconstructions were associated with greater deformity. A three-tiered grading system based on thresholds of 2-cm net nipple displacement and 25 percent skin contour irregularity placed 41.4 percent of breasts in grade 1, 35.9 percent in grade 2, and 22.8 percent in grade 3. Interrater variability testing demonstrated 89.5 percent overall agreement (kappa = 0.84).

Conclusions:

This study presents the first quantitative analysis of animation deformity in prosthetic breast reconstruction. Geometric analysis of nipple displacement vector and increasing animation with pectoralis division both implicate the inferior pectoralis myotome as a primary driver of animation deformity. A concomitant grading schema was developed to provide a standardized framework for discussing animation from patient to patient and from study to study.
Benchmarking the Outcomes of Single-Stage Augmentation Mastopexy against Primary Breast Augmentation: A Single Surgeon’s Experience of 905 Consecutive Cases
Authors: Montemurro Paolo , Cheema Mubashir , Hedén Per , Behr Björn , Wallner Christoph
Published: June 2019

Background:

Augmentation mastopexy may be a one- or two-stage procedure. Because of the opposing force vectors in augmentation and in mastopexy, some surgeons advocate a two-stage procedure. The literature appears divided on which operation has a more favorable complication profile. The purpose of this review was to benchmark the outcomes of single-stage augmentation mastopexy against those of a commonly performed aesthetic breast operation (primary breast augmentation).

Methods:

The authors reviewed electronic patient records of all consecutive female patients who underwent single-stage augmentation mastopexy and primary breast augmentation performed by the first author at our clinic between April of 2009 and May of 2017 with at least a 6-month follow-up. Data from single-stage augmentation mastopexy were benchmarked against the outcomes of primary breast augmentations performed by the same surgeon, for the same period, and at the same clinic.

Results:

One hundred four single-stage augmentation mastopexies and 801 primary breast augmentations were performed during this period, with mean follow-up of 15.4 months and 14.0 months, respectively. Augmentation mastopexy patients were significantly more likely to be older, have a higher body mass index, have more children, and were significantly less likely to use oral contraceptives. There was no statistically significant difference in overall complication rate between the two groups.

Conclusions:

The authors’ experience suggests that single-stage augmentation mastopexy has outcomes comparable to those of primary breast augmentation. Smokers were more likely to undergo reoperation because of postoperative complication (seroma), but the rate of implant exchange was not different.

CLINICAL QUESTION/LEVEL OF EVIDENCE:

Therapeutic, III.
Can Early ‘Shallow’ Needle-knife Papillotomy be the First Choice in ERCP?
Authors: Kalayci Mustafa U. , Altintas Tansu
Published: June 2019

Purpose:

Needle-knife sphincterotomy, known as ‘precut’ is recommended as the second option in the case of difficult cannulation due to its potential higher complication (bleeding and perforation) rates. The aim of this study was to present our experience on early shallow needle-knife papillotomy (eSNKP) as the first-line choice independently of standard technique with or without difficult cannulation.

Materials and Methods:

A total of 70 patients underwent therapeutic endoscopic retrograde cholangiopancreatography. A standard eSNKP and guidewire cannulation technique was routinely preferred as a first-line intervention. Deep biliary cannulation rate and timing were recorded, as well as intraoperative and postoperative complication rates.

Results:

Successful deep biliary cannulation was performed in 66 (94.3%) patients during the first procedure. In 4 patients (5.7%), the procedure was terminated due to failed cannulation and repeated successfully after 72 hours. Minor complications were observed in 3 (4.3%) patients. No mortality was seen.

Conclusion:

eSNKP is a safe, time-saving, and effective technique as the first-line of endoscopic retrograde cholangiopancreatography for common bile duct cannulation.
Neuropsychological Test Performance and MRI Markers of Dementia Risk
Authors: Walter Stefan , Dufouil Carole , Gross Alden L. , Jones Richard N. , Mungas Dan , Filshtein Teresa J. , Manly Jennifer J. , Arpawong Thalida E. , Glymour M. Maria
Published: June 2019

Background:

To use neuropsychological assessments for studying the underlying disease processes contributing to dementia, it is crucial that they correspond to magnetic resonance imaging (MRI)-based measures of dementia, regardless of educational level.

Methods:

French 3-City Dijon MRI study cohort members (n=1782) with assessments of white matter lesion volume (WMLV), hippocampal volume (HCV), and cerebrospinal fluid volume (CSFV), and 6 waves of neuropsychological assessments over 11 years, including Mini-Mental State Examination (MMSE), plus 5 other tests combined using a Z-score or item-response theory (IRT-cognition) comprised the study cohort. We evaluated, testing interactions, whether education modified associations of MRI markers with intercept or rate of change of MMSE, Z-score composite, or IRT-cognition.

Results:

In linear models, education modified the associations of WMLV and CSFV with MMSE and CSFV and Z-score composite. In mixed models, education modified the associations of WMLV and CSFV with level of MMSE and the association of HCV with slope of MMSE. Education also modified the association with CSFV and slope of Z-score composite decline. There was no evidence that education modified associations between MRI measures and level or slope of IRT-cognition.

Conclusions:

Longitudinal analysis of correctly scaled neuropsychological assessments may provide unbiased proxies for MRI-based measures of dementia risk.
Thermal performance of scleractinian corals along a latitudinal gradient on the Great Barrier Reef
Authors: Jurriaans S. , Hoogenboom M. O.
Published: June 2019

Species have evolved different mechanisms to cope with spatial and temporal temperature variability. Species with broad geographical distributions may be thermal generalists that perform well across a broad range of temperatures, or they might contain subpopulations of locally adapted thermal specialists. We quantified the variation in thermal performance of two coral species,
Porites cylindrica
and
Acropora
spp., along a latitudinal gradient over which temperature varies by approximately 6°C. Photosynthesis rates, respiration rates, maximum quantum yield and maximum electron transport rates were measured on coral fragments exposed to an acute temperature increase and decrease up to 5°C above and below the local average temperature. Results showed geographical variation in the performance curves of both species at holobiont and symbiont level, but this did not lead to an alignment of the optimal temperature for performance with the average temperature of the local environment, suggesting suboptimal coral performance of these coral populations in summer. Furthermore, symbiont thermal performance generally had an optimum closer to the average environmental temperature than holobiont performance, suggesting that symbionts have a higher capacity for acclimatization than the coral host, and can aid the coral host when temperatures are unfavourable.

This article is part of the theme issue ‘Physiological diversity, biodiversity patterns and global climate change: testing key hypotheses involving temperature and oxygen’.
Linking thermal adaptation and life-history theory explains latitudinal patterns of voltinism
Authors: Kong Jacinta D. , Hoffmann Ary A. , Kearney Michael R.
Published: June 2019

Insect life cycles are adapted to a seasonal climate by expressing alternative voltinism phenotypes—the number of generations in a year. Variation in voltinism phenotypes along latitudinal gradients may be generated by developmental traits at critical life stages, such as eggs. Both voltinism and egg development are thermally determined traits, yet independently derived models of voltinism and thermal adaptation refer to the evolution of dormancy and thermal sensitivity of development rate, respectively, as independent influences on life history. To reconcile these models and test their respective predictions, we characterized patterns of voltinism and thermal response of egg development rate along a latitudinal temperature gradient using the matchstick grasshopper genus
Warramaba
. We found remarkably strong variation in voltinism patterns, as well as corresponding egg dormancy patterns and thermal responses of egg development. Our results show that the switch in voltinism along the latitudinal gradient was explained by the combined predictions of the evolution of voltinism and of thermal adaptation. We suggest that latitudinal patterns in thermal responses and corresponding life histories need to consider the evolution of thermal response curves within the context of seasonal temperature cycles rather than based solely on optimality and trade-offs in performance.

This article is part of the theme issue ‘Physiological diversity, biodiversity patterns and global climate change: testing key hypotheses involving temperature and oxygen’.
Thermal performance across levels of biological organization
Authors: Rezende Enrico L. , Bozinovic Francisco
Published: June 2019

Thermal performance curves are widely used to describe how ambient temperature impacts different attributes of ectothermic organisms, from protein function to life-history traits, and to predict the potential effects of global warming on ecological systems. Nonetheless, from an analytical standpoint, they remain primarily heuristic and few attempts have been made to develop a formal framework to characterize these curves and disentangle which factors contribute to their variation. Here we employ a nonlinear regression approach to assess if they vary systematically in shape depending on the performance proxy of choice. We compare curves at contrasting levels of organization, namely photosynthetic rates in plants (n= 43), running speeds in lizards (n= 51) and intrinsic rates of population increase in insects (n= 47), and show with discriminant analyses that differences lie in a single dimension accounting for 99.1% of the variation, resulting in 75.8% of classification accuracy. Differences revolve primarily around the thermal range for elevated performance (greater than or equal to 50% of maximum performance), which is broader for photosynthetic rates (median of 26.4°C), intermediate for running speeds (19.5°C) and narrower for intrinsic rates of increase (12.5°C). We contend, confounding taxonomic factors aside, that these differences reflect contrasting levels of biological organization, and hypothesize that the thermal range for elevated performance should decrease at higher organization levels. In this scenario, instantaneous or short-term measures of performance may grossly overestimate the thermal safety margins for population growth and reproduction. Taken together, our analyses suggest that descriptors of the curve are highly correlated and respond in tandem, potentially resulting in systematic variation in shape across organization levels. Future studies should take into consideration this potential bias, address if it constitutes a general pattern and, if so, explain why and how it emerges.

This article is part of the theme issue ‘Physiological diversity, biodiversity patterns and global climate change: testing key hypotheses involving temperature and oxygen’.
Scaling of thermal tolerance with body mass and genome size in ectotherms: a comparison between water- and air-breathers
Authors: Leiva Félix P. , Calosi Piero , Verberk Wilco C. E. P.
Published: June 2019

Global warming appears to favour smaller-bodied organisms, but whether larger species are also more vulnerable to thermal extremes, as suggested for past mass-extinction events, is still an open question. Here, we tested whether interspecific differences in thermal tolerance (heat and cold) of ectotherm organisms are linked to differences in their body mass and genome size (as a proxy for cell size). Since the vulnerability of larger, aquatic taxa to warming has been attributed to the oxygen limitation hypothesis, we also assessed how body mass and genome size modulate thermal tolerance in species with contrasting breathing modes, habitats and life stages. A database with the upper (CTmax) and lower (CTmin) critical thermal limits and their methodological aspects was assembled comprising more than 500 species of ectotherms. Our results demonstrate that thermal tolerance in ectotherms is dependent on body mass and genome size and these relationships became especially evident in prolonged experimental trials where energy efficiency gains importance. During long-term trials, CTmax was impaired in larger-bodied water-breathers, consistent with a role for oxygen limitation. Variation in CTmin was mostly explained by the combined effects of body mass and genome size and it was enhanced in larger-celled, air-breathing species during long-term trials, consistent with a role for depolarization of cell membranes. Our results also highlight the importance of accounting for phylogeny and exposure duration. Especially when considering long-term trials, the observed effects on thermal limits are more in line with the warming-induced reduction in body mass observed during long-term rearing experiments.

This article is part of the theme issue ‘Physiological diversity, biodiversity patterns and global climate change: testing key hypotheses involving temperature and oxygen’.
Two-component systems regulate ABC transporters in antimicrobial peptide production, immunity and resistance
Authors: Ahmad Ashfaq , Majaz Sidra , Nouroz Faisal
Published: June 2019

Bacteria offer resistance to a broad range of antibiotics by activating their export channels of ATP-binding cassette transporters. These transporters perform a central role in vital processes of self-immunity, antibiotic transport and resistance. The majority of ATP-binding cassette transporters are capable of detecting the presence of antibiotics in an external vicinity and are tightly regulated by two-component systems. The presence of an extracellular loop and an adjacent location of both the transporter and two-component system offers serious assistance to induce a quick and specific response against antibiotics. Both systems have demonstrated their ability of sensing such agents, however, the exact mechanism is not yet fully established. This review highlighted the three key functions of antibiotic resistance, transport and self-immunity of ATP-binding cassette transporters and an adjacent two-component regulatory system.
Phenome-wide search for pleiotropic loci highlights key genes and molecular pathways for human complex traits
Authors: Shikov Anton E. , Predeus Alexander V. , Barbitoff Yury A.
Published: June 2019

Over recent decades, genome-wide association studies (GWAS) have dramatically changed the understanding of human genetics. A recent genetic data release by UK Biobank has allowed many researchers worldwide to have comprehensive look into the genetic architecture of thousands of human phenotypes. In this study, we developed a novel statistical framework to assess phenome-wide significance and genetic pleiotropy across the human phenome based on GWAS summary statistics. We demonstrate widespread sharing of genetic architecture components between distinct groups of traits. Apart from known multiple associations inside the MHC locus, we discover high degree of pleiotropy for genes involved in immune system function, apoptosis, hemostasis cascades, as well as lipid and xenobiotic metabolism. We find several notable examples of novel pleiotropic loci (e.g., the MIR2113 microRNA broadly associated with cognition), and provide several possible mechanisms for these association signals. Our results allow for a functional phenome-wide look into the shared components of genetic architecture of human complex traits, and highlight crucial genes and pathways for their development.
TWIST1 homodimers and heterodimers orchestrate lineage-specific differentiation
Authors: Fan Xiaochen , Waardenberg Ashley J. , Demuth Madeleine , Osteil Pierre , Sun Jane , Loebel David A.F. , Graham Mark , Tam Patrick P.L. , Fossat Nicolas
Published: June 2019

The extensive array of bHLH transcription factors and their combinations as dimers underpin the diversity of molecular function required for cell type specification during embryogenesis. The bHLH factor TWIST1 plays pleiotropic roles during development. However, which combinations of TWIST1 dimers are involved and what impact each dimer imposes on the gene regulation network controlled by TWIST1 remain elusive. In this work, proteomic profiling of human-TWIST1 expressing cell lines and transcriptome analysis of mouse cranial mesenchyme have revealed that TWIST1 homodimer and heterodimers with TCF3, TCF4 and TCF12 E-proteins are the predominant dimer combinations. Dimers formation or their balance are altered by disease-causing mutations in TWIST1 helix domains, which may account for the defective differentiation of the craniofacial mesenchyme observed in patients. Functional analyses of the loss and gain of TWIST1-E-protein dimer activity have revealed previously unappreciated roles in guiding lineage differentiation of embryonic stem cells: TWIST1-E-protein heterodimers activate the differentiation of mesoderm and neural crest cells which is accompanied by epithelial-to-mesenchymal transition, while TWIST1 homodimers maintain the stem cells in a progenitor state and block entry to the endoderm lineage.
SS-31 Reverses Mitochondrial Fragmentation in Fibroblasts from Patients with DCMA, a Mitochondrial Cardiomyopathy
Authors: Machiraju Pranav , Wang Xuemei , Sabouny Rasha , Huang Joshua , Zhao Tian , Iqbal Fatima , King Melissa , Prasher Dimple , Lodha Arijit , Ravandi Amir , Argiropoulos Bob , Sinasac David , Khan Aneal , Shutt Timothy , Greenway Steven C.
Published: June 2019

Objectives

We used patient dermal fibroblasts to characterize the mitochondrial abnormalities associated with the dilated cardiomyopathy with ataxia syndrome (DCMA) and to study the effect of the mitochondrially-targeted peptide SS-31 as a potential novel therapeutic.

Background

DCMA is an understudied autosomal recessive disorder thought to be related to Barth syndrome but caused by mutations in DNAJC19, a protein of unknown function localized to the mitochondria. The clinical disease is characterized by 3-methylglutaconic aciduria, dilated cardiomyopathy, abnormal neurological development and other heterogeneous features. Until recently no effective therapies had been identified and affected patients frequently died in early childhood from intractable heart failure.

Methods

Dermal fibroblasts from four pediatric patients with DCMA were used to establish parameters of mitochondrial dysfunction. Mitochondrial structure, reactive oxygen species (ROS) production, cardiolipin composition and gene expression were evaluated.

Results

Immunocytochemistry with semi-automated quantification of mitochondrial structural metrics and transmission electron microscopy demonstrated mitochondria to be highly fragmented in DCMA fibroblasts compared to healthy control cells. Live-cell imaging demonstrated significantly increased ROS production in patient cells. These structural and functional abnormalities were reversed by treating DCMA fibroblasts with SS-31, a synthetic peptide that localizes to the inner mitochondrial membrane. Levels of cardiolipin were not significantly different between control and DCMA cells and were unaffected by SS-31 treatment.

Conclusions

Our results demonstrate the abnormal mitochondrial structure and function in fibroblasts from patients with DCMA and suggest that SS-31 may represent a potential therapy for this devastating disease.
How to build a fast and highly sensitive sound detector that remains robust to temperature shifts
Authors: Chen Minghui , von Gersdorff Henrique
Published: June 2019

Frogs must have sharp hearing abilities during the warm summer months to successfully find mating partners. This study aims to understand how frog hair cell ribbon-type synapses preserve both sensitivity and temporal precision during temperature changes. We performedin vitropatch-clamp recordings of hair cells and their afferent fibers in bullfrog amphibian papillae under room (23-25°C) and high (30-33°C) temperature. Afferent fibers exhibited a wide heterogeneity in membrane input resistance (Rin) from 100 MΩ to 1000 MΩ, which may contribute to variations in spike threshold and firing frequency. At higher temperatures, most fibers increased their frequency of action potential firing due to an increase in spontaneous EPSC frequencies. Hair cell resting membrane potential (Vrest) remained surprisingly stable during temperature increases, although both inward Ca2+current and outward K+current increased in amplitude. This increase in Ca2+current may explain the higher spontaneous EPSC frequencies. The larger “leak currents” at Vrestlowered Rinand produced higher electrical resonant frequencies. However, lower Rinshould decrease sensitivity to sound detection via smaller receptor potentials. Using membrane capacitance measurements, we suggest that hair cells can partially compensate for this reduced sensitivity by increasing exocytosis efficiency and the size of the readily releasable pool of synaptic vesicles. Furthermore, paired recordings of hair cells and their afferent fibers showed that synaptic delays become shorter and multivesicular release becomes more synchronous at higher temperatures, which should improve temporal precision. Altogether, our results explain many previousin vivoobservations on the temperature dependence of spikes in auditory nerves.

Significance Statement

The vertebrate inner ear detects and transmits auditory information over a broad dynamic range of sound frequency and intensity. It achieves remarkable sensitivity to soft sounds and precise frequency selectivity. How does the ear of cold-blooded vertebrates maintain its performance level as temperature changes? More specifically, how does the hair cell to afferent fiber synapse in bullfrog amphibian papilla adjust to a wide range of physiological temperatures without losing its sensitivity and temporal fidelity to sound signals? This study usesin vitroexperiments to reveal the biophysical mechanisms that explain many observations made fromin vivoauditory nerve fiber recordings. We find that higher temperature facilitates vesicle exocytosis and electrical tuning to higher sound frequencies, which benefits sensitivity and selectivity.
Untargeted metabolite analysis of Ocimum leaves shows species specific variations
Authors: Shree Manu , Nanda Ranjan K , Masakapalli Shyam K
Published: June 2019

Tulsi (Ocimum species), the queen of herbs is a common ingredient in beverages with perceived health benefits. Recently published Ocimum genome highlighted the presence of several genes that contributes to important phytochemicals but a comprehensive metabolite profiling to study the water soluble metabolites of Ocimum is lacking. In this study, untargeted metabolic profiling of hot water extract of fresh and air dried leaves of O. basilicum, O. sanctum and O. kilimandscharicum species employing gas chromatography and mass spectrometry (GC-MS) was attempted. Analysis of hot water extracts of Ocimum leaves will provide details of molecules consumed and species specific differences, if any. Several metabolic features including amino acids (glycine, serine glutamate), organic and other acids (succinic acid, fumaric acid, 4-amino butanoic acid), sugars and their derivatives (glucose, sucrose, mannitol, fructose) and secondary metabolites (shikimic acid, quinic acid, catechol, gamma amino butyric acid, eugenol) were identified. Multivariate statistical analysis of GC-MS data indicated several species specific metabolic similarities and differences. Based on variable importance parameter score of >1, it was observed that in case of air dried extracts, glucose, fumaric acid, and D-mannitol displayed as important variables for species specific variation. Whereas in case of fresh leaves extracts, the variation was prominent due to xylose, D-allose and an unknown metabolic feature detected at 24 min (metabolite@24 with highest m/z 75). Phytochemical phenotype of Ocimum leaves not only shows species specific variations but these may partly explain their difference in taste and health benefits from their use as hot beverages.
Easy Kinetics: a novel enzyme kinetic characterization software
Authors: Morabito Gabriele
Published: June 2019

Here will be presented the software Easy Kinetics, a publicly available graphical interface that allows rapid evaluation of the main kinetics parameters in an enzyme catalyzed reaction. In contrast to other similar commercial software using algorithms based on non-linear regression models to reach these results, Easy Kinetics is based on a completely different original algorithm, requiring in input the spectrophotometric measurements of ΔAbs/min taken twice at only two different substrate concentrations. The results generated show however a significant concordance with those ones obtained with the most common commercial software used for enzyme kinetics characterization, GraphPad Prism 8©, suggesting that Easy Kinetics can be used for routine tests in enzyme kinetics as an alternative valid software.
The succession pattern of bacterial diversity in compost using pig manure mixed with wood chips analyzed by 16S rRNA gene analysis
Authors: Li Zhengfeng , Yang Yan , Xia Yuzhen , Wu Tao , Zhu Jie , Wang Zhaobao , Yang Jianming
Published: June 2019

The pig manure mixed with wood chips and formed compost by means of fermentation. We found that the protease activity, organic matter content and ammonium nitrogen concentration were higher in the early stage of composting. Meanwhile, the urease activity was highest in the high temperature period. The carbon to nitrogen ratio of the compost decreased continuously with fermentation. The dynamic change in the composition of bacterial overtime in the compost of a 180 kg piles were explored using microbial diversity analysis. The results showed that the microbial species increased with the compost fermentation. At the early stage of composting, the phyla of Firmicutes and Actinomycetes were dominant. The microbes in the high temperature period were mainly composed of Firmicutes and Proteobacteria while the proportion ofBacteroideswas increased during the cooling period. In the compost of maturity stage, the proportion ofChloroflexiincreased, becoming dominant species with other microorganisms includingFirmicutes, Proteobacteria, Bacteroides, Chloroflexibut notActinomycetes. Bacteria involved in lignocellulose degradation, such as those of theThermobifida, Cellvibrio, Mycobacterium, StreptomycesandRhodococcus, were concentrated in the maturity stages of composting. Through correlation analysis, the environmental factors including organic matter, ammonium nitrogen and temperature were consistent with the succession of microbial includingRhodocyclaceae, Anaerolineaceae, Thiopseudomonas, SinibacillusandTepidimicrobium. The change of urease activity and carbon to nitrogen ratio corresponded to microbial communities, mainly containingAnaerolineaceae, Rhodocyclaceae, Luteimoas, Bacillaceae, Corynebacterium, Bacillus, Anaerococcus, Lactobacillus, Ignatzschineria, andBacillaceae.
Can Cynodon dactylon be used to suppress invasive weeds? The effects of density-dependent on the growth and development of Tagetes minuta and Gutenbergia cordifolia
Authors: Ngondya Issakwisa B. , Treydte Anna C. , Ndakidemi Patrick A. , Munishi Linus K.
Published: June 2019

Plant-Plant competitive interactions have been reported to be among the forces that shape plant community structure. We studied the effects of varying the density of Cynodon dactylon on the growth and development of the invasive plant species Tagetes minuta and Gutenbergia cordifolia in pot and field plot experiments following a completely randomized design. Increasing densities of C. dactylon strongly reduced T. minuta and G. cordifolia growth and development, leaf total chlorophyll and increased leaf anthocyanin of both invasive species. These detrimental effects may have contributed to poorer T. minuta and G. cordifolia performance under C. dactylon densities of more than 8 individuals per pot/plot compared to those in pots/plots without C. dactylon. This study suggests that C. dactylon can be successfully used to manage the two invasive plants, thus, improving forage production and biomass in affected rangelands.
Fronto-parietal contributions to episodic retrieval—evidence from neurodegenerative disorders
Authors: Ramanan Siddharth , Strikwerda-Brown Cherie , Mothakunnel Annu , Hodges John R. , Piguet Olivier , Irish Muireann
Published: June 2019

Converging evidence suggests a critical role for the parietal cortices in episodic memory retrieval. Here, we examined episodic memory performance in Corticobasal Syndrome (CBS), a rare neurodegenerative disorder presenting with early parietal atrophy in the context of variable medial temporal lobe damage. Forty-four CBS patients were contrasted with 29 typical Alzheimer's disease (AD), 29 healthy Controls, and 20 progressive supranuclear palsy patients presenting with brainstem atrophy as a disease control group. Participants completed standardized assessments of verbal episodic memory (learning, delayed recall, and recognition), and underwent structural and diffusion-weighted MRI. Selective delayed recall deficits were evident in the CBS group relative to Controls, at an intermediate level to the stark amnesia displayed by AD, and Control-level performance noted in progressive supranuclear palsy. Considerable variability within the CBS group on delayed recall performance led to the identification of memory-spared (N = 19) and memory-impaired (N = 25) subgroups. Whereas CBS-Spared showed no significant memory deficits, the CBS-Impaired subgroup were indistinguishable from typical AD across all episodic memory measures. Whole-brain voxel-based morphometry analyses implicated fronto-parietal and medial temporal regions in delayed recall performance in both the CBS-Impaired and AD groups. Furthermore, diffusion tensor imaging analyses revealed correlations between delayed recall performance and altered structural connectivity between fronto-parietal and frontotemporal regions in the CBS-Impaired group. Our findings underscore the importance of a distributed brain network including frontal, medial temporal, and parietal brain regions in supporting the capacity for successful episodic memory retrieval.
Scenes facilitate associative memory and integration
Authors: Robin Jessica , Olsen Rosanna K.
Published: June 2019

How do we form mental links between related items? Forming associations between representations is a key feature of episodic memory and provides the foundation for learning and guiding behavior. Theories suggest that spatial context plays a supportive role in episodic memory, providing a scaffold on which to form associations, but this has mostly been tested in the context of autobiographical memory. We examined the memory boosting effect of spatial stimuli in memory using an associative inference paradigm combined with eye-tracking. Across two experiments, we found that memory was better for associations that included scenes, even indirectly, compared to objects and faces. Eye-tracking measures indicated that these effects may be partly mediated by greater fixations to scenes compared to objects, but did not explain the differences between scenes and faces. These results suggest that scenes facilitate associative memory and integration across memories, demonstrating evidence in support of theories of scenes as a spatial scaffold for episodic memory. A shared spatial context may promote learning and could potentially be leveraged to improve learning and memory in educational settings or for memory-impaired populations.