bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Gram-Positive Bacterial Cell Wall
Authors: Rohde Manfred 
Published: May 2019

ABSTRACT
The chapter about the Gram-positive bacterial cell wall gives a brief historical background on the discovery of Gram-positive cell walls and their constituents and microscopic methods applied for studying the Gram-positive cell envelope. Followed by the description of the different chemical building blocks of peptidoglycan and the biosynthesis of the peptidoglycan layers and high turnover of peptidoglycan during bacterial growth. Lipoteichoic acids and wall teichoic acids are highlighted as major components of the cell wall. Characterization of capsules and the formation of extracellular vesicles by Gram-positive bacteria close the section on cell envelopes which have a high impact on bacterial pathogenesis. In addition, the specialized complex and unusual cell wall of mycobacteria is introduced thereafter. Next a short back view is given on the development of electron microscopic examinations for studying bacterial cell walls. Different electron microscopic techniques and methods applied to examine bacterial cell envelopes are discussed in the view that most of the illustrated methods should be available in a well-equipped life sciences orientated electron microscopic laboratory. In addition, newly developed and mostly well-established cryo-methods like high-pressure freezing and freeze-substitution (HPF-FS) and cryo-sections of hydrated vitrified bacteria (CEMOVIS, Cryo-electron microscopy of vitreous sections) are described. At last, modern cryo-methods like cryo-electron tomography (CET) and cryo-FIB-SEM milling (focus ion beam-scanning electron microscopy) are introduced which are available only in specialized institutions, but at present represent the best available methods and techniques to study Gram-positive cell walls under close-to-nature conditions in great detail and at high resolution.
Staphylococcus aureus
in Animals
Authors: Haag Andreas F. , Fitzgerald J. Ross , Penadés José R. 
Published: May 2019

ABSTRACT

Staphylococcus aureus
is a mammalian commensal and opportunistic pathogen that colonizes niches such as skin, nares and diverse mucosal membranes of about 20-30% of the human population.
S. aureus
can cause a wide spectrum of diseases in humans and both methicillin-sensitive and methicillin-resistant strains are common causes of nosocomial- and community-acquired infections. Despite the prevalence of literature characterising staphylococcal pathogenesis in humans,
S. aureus
is a major cause of infection and disease in a plethora of animal hosts leading to a significant impact on public health and agriculture. Infections in animals are deleterious to animal health, and animals can act as a reservoir for staphylococcal transmission to humans.

Host-switching events between humans and animals and amongst animals are frequent and have been accentuated with the domestication and/or commercialisation of specific animal species. Host-switching is typically followed by subsequent adaptation through acquisition and/or loss of mobile genetic elements such as phages, pathogenicity islands and plasmids as well as further host-specific mutations allowing it to expand into new host populations.

In this chapter, we will be giving an overview of
S. aureus
in animals, how this bacterial species was, and is, being transferred to new host species and the key elements thought to be involved in its adaptation to new ecological host niches. We will also highlight animal hosts as a reservoir for the development and transfer of antimicrobial resistance determinants.
Genetic alterations and expression of PTEN and its relationship with cancer stem cell markers to investigate pathogenesis and to evaluate prognosis in hepatocellular carcinoma
Authors: Chen Dingbao , Li Zhao , Cheng Qian , Wang Ying , Qian Lihua , Gao Jie , Zhu Ji-Ye 
Published: May 2019

AimsTo investigate molecular alteration and expression of phosphatase and tensin homolog deleted on chromosome 10 (PTEN) gene in hepatocellular carcinoma (HCC), and to evaluate the correlation between PTEN and cancer stem cell (CSC) markers and the prognostic value of these markers.MethodsWe evaluated changes of PTEN and CSC markers (CD133, epithelial cell adhesion molecule (EpCAM) and CK19) in 183 resection specimens by immunohistochemistry (IHC) and detected PTEN and phosphoinositide-3-kinase catalytic-alpha (PIK3CA) gene by fluorescence in situ hybridisation (FISH) in some specimens.ResultsPTEN and CD133, EpCAM and CK19 in 183 resection specimens were studied by IHC, and PTEN and PIK3CA genes were detected by FISH. PTEN expression was reduced in 92 HCC tissues (50.3%). There were 16 HCCs with PTEN deletion (51.6%). Comparison between PTEN IHC and FISH showed that the analysis was highly concordant (54/59, 91.5%). There were 19 HCCs with PIK3CA amplification. Deletion of PTEN was positively correlated with amplification of PIK3CA. Positive expression of CD133, EpCAM and CK19 was correlated with steatosis, moderate to poor differentiation, and so on. Reduction of PTEN expression was negatively correlated with positive expression of CD133, EpCAM and CK19. Reduced expression of PTEN (p=0.028) was an independent predictor for HCC recurrence and overall survival in HCC. PTEN−/CD133+ group had shorter OS and RFS time.ConclusionsPTEN plays a key role in hepatocarcinogenesis and reduction of PTEN expression is related to increased expression of CD133, EpCAM and CK19, which is a useful tool to evaluate HCC prognosis and recurrence.
Prenatal inflammation impairs intestinal microvascular development through a TNF-dependent mechanism and predisposes newborn mice to necrotizing enterocolitis
Authors: Yan Xiaocai , Managlia Elizabeth , Tan Xiao-Di , De Plaen Isabelle G. 
Published: May 2019

Prenatal inflammation is a risk factor for necrotizing enterocolitis (NEC), and it increases intestinal injury in a rat NEC model. We previously showed that maldevelopment of the intestinal microvasculature and lack of vascular endothelial growth factor (VEGF) receptor 2 (VEGFR2) signaling play a role in experimental NEC. However, whether prenatal inflammation affects the intestinal microvasculature remains unknown. In this study, mouse dams were injected intraperitoneally with lipopolysaccharide (LPS) or saline at embryonic day 17. Neonatal intestinal microvasculature density, endothelial cell proliferation, and intestinal VEGF-A and VEGFR2 proteins were assessed in vivo. Maternal and fetal serum TNF concentrations were measured by ELISA. The impact of TNF on the neonatal intestinal microvasculature was examined in vitro and in vivo, and we determined whether prenatal LPS injection exacerbates experimental NEC via TNF. Here we found that prenatal LPS injection significantly decreased intestinal microvascular density, endothelial cell proliferation, and VEGF and VEGFR2 protein expression in neonatal mice. Prenatal LPS injection increased maternal and fetal serum levels of TNF. TNF decreased VEGFR2 protein in vitro in neonatal endothelial cells. Postnatal TNF administration in vivo decreased intestinal microvasculature density, endothelial cell proliferation, and VEGF and VEGFR2 protein expression and increased the incidence of severe NEC. These effects were ameliorated by stabilizing hypoxia-inducible factor-1α, the master regulator of VEGF. Furthermore, prenatal LPS injection significantly increased the incidence of severe NEC in our model, and the effect was dependent on endogenous TNF. Our study suggests that prenatal inflammation increases the susceptibility to NEC, downregulates intestinal VEGFR2 signaling, and affects perinatal intestinal microvascular development via a TNF mechanism. NEW & NOTEWORTHY This report provides new evidence that maternal inflammation decreases neonatal intestinal VEGF receptor 2 signaling and endothelial cell proliferation, impairs intestinal microvascular development, and predisposes neonatal mouse pups to necrotizing enterocolitis (NEC) through inflammatory cytokines such as TNF. Our data suggest that alteration of intestinal microvascular development may be a key mechanism by which premature infants exposed to prenatal inflammation are at risk for NEC and preserving the VEGF/VEGF receptor 2 signaling pathway may help prevent NEC development.
Platelet-derived growth factor receptor-α is essential for cardiac fibroblast survival
Authors: Ivey Malina J. , Kuwabara Jill T. , Riggsbee Kara L. , Tallquist Michelle D. 
Published: May 2019

Platelet-derived growth factor receptor α (PDGFRα), a receptor tyrosine kinase required for cardiac fibroblast development, is uniquely expressed by fibroblasts in the adult heart. Despite the consensus that PDGFRα is expressed in adult cardiac fibroblasts, we know little about its function when these cells are at rest. Here, we demonstrate that loss of PDGFRα in cardiac fibroblasts resulted in a rapid reduction of resident fibroblasts. Furthermore, we observe that phosphatidylinositol 3-kinase signaling was required for PDGFRα-dependent fibroblast maintenance. Interestingly, this reduced number of fibroblasts was maintained long-term, suggesting that there is no homeostatic mechanism to monitor fibroblast numbers and restore hearts to wild-type levels. Although we did not observe any systolic functional changes in hearts with depleted fibroblasts, the basement membrane and microvasculature of these hearts were perturbed. Through in vitro analyses, we showed that PDGFRα signaling inhibition resulted in an increase in fibroblast cell death, and PDGFRα stimulation led to increased levels of the cell survival factor activating transcription factor 3. Our data reveal a unique role for PDGFRα signaling in fibroblast maintenance and illustrate that a 50% loss in cardiac fibroblasts does not result in lethality.NEW & NOTEWORTHY Platelet-derived growth factor receptor α (PDGFRα) is required in developing cardiac fibroblasts, but a functional role in adult, quiescent fibroblasts has not been identified. Here, we demonstrate that PDGFRα signaling is essential for cardiac fibroblast maintenance and that there are no homeostatic mechanisms to regulate fibroblast numbers in the heart. PDGFR signaling is generally considered mitogenic in fibroblasts, but these data suggest that this receptor may direct different cellular processes depending on the cell’s maturation and activation status.
Outcomes of Patients With Severe Symptomatic Aortic Valve Stenosis After Chest Radiation: Transcatheter Versus Surgical Aortic Valve Replacement
Authors: Zhang Dongfeng , Guo Wei , Al‐Hijji Mohammed A. , El Sabbagh Abdallah , Lewis Bradley R. , Greason Kevin , Sandhu Gurpreet S. , Eleid Mackram F. , Holmes David R. , Herrmann Joerg 
Published: May 2019

Background

Patients with symptomatic severe aortic stenosis and a history of chest radiation therapy represent a complex and challenging cohort. It is unknown how transcatheter aortic valve replacement (
TAVR
) compares with surgical aortic valve replacement in this group of patients, which was the objective of this study.

Methods and Results

We retrospectively reviewed all patients with severe aortic stenosis who underwent either
TAVR
or surgical aortic valve replacement at our institution with a history of mediastinal radiation (n=55 per group). End points were echocardiographic and clinical outcomes in‐hospital, at 30 days, and at 1 year. Inverse propensity weighting analysis was used to account for intergroup baseline differences.
TAVR
patients had a higher
STS
score than surgical aortic valve replacement patients (5.1% [3.2, 7.7] versus 1.6% [0.8, 2.6],
P
<0.001) and more often (
P
<0.01 for all) a history of atrial fibrillation (45.5% versus 12.7%), chronic lung disease (47.3% versus 7.3%), peripheral arterial disease (38.2% versus 7.3%), heart failure (58.2% versus 18.2%), and pacemaker therapy (23.6% versus 1.8%). Postoperative atrial fibrillation was less frequent (1.8% versus 27.3%;
P
<0.001) and hospital stay was shorter in
TAVR
patients (4.0 [2.0, 5.0] versus 6.0 [5.0, 8.0] days;
P
<0.001). The ratio of observed‐to‐expected 30‐day mortality was lower after
TAVR
as was 30‐day mortality in inverse propensity weighting–adjusted Kaplan–Meier analyses.

Conclusions

In patients with severe aortic stenosis and a history of chest radiation therapy,
TAVR
performs better than predicted along with less adjusted 30‐day all‐cause mortality, postoperative atrial fibrillation, and shorter hospitalization compared with surgical aortic valve replacement. These data support further studies on the preferred role of
TAVR
in this unique patient population.
Lentiviral-mediated ephrin B2 gene modification of rat bone marrow mesenchymal stem cells
Authors: Zhu Min , Hua Yu , Tang Jian , Zhao Xiaoke , Zhang Ling , Zhang Yue 
Published: May 2019

Objective To determine the effect of the upregulation or knockdown of the ephrinB2 ( Efnb2) gene and the effect of EphB4/EphrinB2 signalling in rat bone marrow mesenchymal stem cells (BMSCs). Methods Rat BMSCs were infected with lentivirus vectors carrying EphrinB2 and shRNA-EphrinB2. EphrinB2 mRNA and protein levels were quantified. At 28 days of culture with neuronal cell-conditioned differentiation medium, levels of microtubule-associated protein 2 (MAP2), CD133 and nestin were detected in EphrinB2/BMSCs and shEphrinB2/BMSCs using quantitative polymerase chain reaction and immunofluorescence. The ability of these cells to migrate was evaluated using a transwell assay. Results BMSCs were successfully isolated as indicated by their CD90+ CD29+ CD34– CD45– phenotype. Three days after ephrinB2 transduction, BMSC cell bodies began to shrink and differentiate into neuron-like cells. At 28 days, levels of MAP2, CD133 and nestin, as well as the number of migratory cells, were higher in lenti-EphrinB2-BMSCs than in the two control groups. The shEphrinB2/BMSCs had reduced levels of MAP2, CD133 and nestin; and a lower rate of cell migration. Similarly, increased levels of Grb4 andp21-activated kinase in the EphB4/EphrinB2 reverse signalling pathway were observed by Western blot. Conclusions LV-EphrinB2 can be efficiently transduced into BMSCs, which then differentiate into neuron-like cells.
Neutrophil-to-lymphocyte ratio predicts hematoma growth in intracerebral hemorrhage
Authors: Wang Zhigang , Gong Qingyong , Guo Cheng , Luo Yong , Chen Lvan 
Published: May 2019

Objective Early hematoma growth is a major determinant of early neurological deterioration and poor clinical outcome in patients with spontaneous intracerebral hemorrhage (ICH). Inflammation plays a major role in the pathophysiology of ICH. This study aimed to evaluate the potential of the neutrophil-to-lymphocyte ratio (NLR) for predicting early hematoma growth after ICH. Methods A retrospective review was performed of patients with acute spontaneous ICH who were admitted to the Stroke Center of the First People’s Hospital of Jingmen between January 2014 and January 2017. The NLR was computed from admission blood work. Brain computed tomography scans were performed at admission and repeated within 24 hours. Hematoma growth was defined as absolute growth >6 mL or relative growth >33%. Results A total of 123 patients were included and early hematoma growth occurred in 30 (24%) patients. Multivariate analysis showed that the NLR (odds ratio, 1.22; 95% confidence interval, 1.09–1.38) was independently associated with early hematoma growth. The best predictive cut-off of the NLR for early hematoma growth was 6.49 (sensitivity, 50%; specificity, 69%). Conclusions A high NLR is independently predictive of early hematoma growth and may aid in risk stratification of patients with ICH on admission.
Lateral Posterior Tibial Slope in Male and Female Athletes Sustaining Contact Versus Noncontact Anterior Cruciate Ligament Tears: A Prospective Study
Authors: DePhillipo Nicholas N. , Zeigler Connor G. , Dekker Travis J. , Grantham W. Jeffrey , Aman Zachary S. , Kennedy Mitchell I. , LaPrade Robert F. 
Published: May 2019

Background: Lateral posterior tibial slope (PTS) has been identified as a risk factor for primary anterior cruciate ligament (ACL) tears. Purpose/Hypothesis: The purpose was to prospectively determine if there was a difference in lateral PTS between male and female athletes sustaining contact ACL tears as compared with a group of sex-, age-, and activity-matched athletes who sustained noncontact ACL tears. It was hypothesized that there would be no difference in degree of lateral PTS between contact and noncontact mechanisms among patients sustaining primary ACL tears in sports. Study Design: Cohort study; Level of evidence, 3. Methods: Data from patients who underwent primary ACL reconstruction without posterior cruciate ligament injury between 2016 and 2018 by a single surgeon were prospectively analyzed. Measurements of lateral PTS were performed on magnetic resonance imaging. Mean values of lateral PTS were compared between the ACL tear groups. Additionally, a group of patients with intact knee ligaments were matched to patients with ACL tears to serve as controls. Results: A total of 245 patients had complete primary ACL tears during the inclusion period. Of these, 56 (23%) reported a contact mechanism of injury at the time of ACL tear, and 56 patients who sustained noncontact ACL tears were matched to the contact ACL tear group. There were no significant differences in sex ( P≥ .999), age ( P = .990), or body mass index ( P = .450) between the patient groups. The mean lateral PTS was 9.1°± 2.9° for the ACL contact and 9.9°± 3.0° for the ACL noncontact group ( P = .180). There was a significant difference in mean lateral PTS between the ACL tear groups (noncontact and contact: 9.5°± 3.0°) and matched control group (5.6°± 1.9°, P = .0001). Conclusion: The lateral PTS was significantly increased among patients with contact and noncontact ACL tears as compared with controls. However, there were no differences in lateral PTS between patients who sustained contact and noncontact ACL tears. Lateral PTS measured on magnetic resonance imaging does not appear to be predictive of the mechanism of injury type among patients who sustain a contact or noncontact primary ACL tear.
Effect of Delayed Primary Anterior Cruciate Ligament Reconstruction on Medial Compartment Cartilage and Meniscal Health
Authors: Everhart Joshua S. , Kirven J. Caid , Abouljoud Moneer M. , DiBartola Alex C. , Kaeding Christopher C. , Flanigan David C. 
Published: May 2019

Background:The time required to develop a secondary cartilage or meniscal injury in the medial compartment after anterior cruciate ligament (ACL) injury is not well understood.Purpose:To determine the association between time delay until ACL reconstruction and the presence of medial compartment Outerbridge grade 3 or 4 chondral injury or medial meniscal tear requiring treatment.Study Design:Cohort study; Level of evidence, 3.Methods:A total of 609 patients underwent primary ACL reconstruction at a single institution at a median 46 days between injury and surgery (61.4% male; mean age, 26.5 years [SD, 11.1]). Chondral status was graded according to Outerbridge criteria at the time of surgery. Multivariate regression analysis was used to assess the relationship between time delay until surgery and medial compartment chondral injury or meniscal injury requiring treatment. Adjustment was performed as needed for patient demographics, sporting activity, and prior knee injuries. Time until surgery had a nonlinear association with medial compartment health and was more effectively described in discrete intervals rather than as a continuous variable. The optimal time intervals to predict medial compartment health were determined by comparison of Bayes information criterion values between fully adjusted regression models.Results:After controlling for relevant confounders, delay of surgery >8 weeks had an increased likelihood of a medial meniscal tear requiring partial meniscectomy (adjusted odds ratio [aOR], 2.30; 95% CI, 1.04-5.12; P = .04) and a decreased likelihood of a meniscal tear requiring repair (aOR, 0.50; 95% CI, 0.32-0.76; P = .001). Delay of surgery >5 months had an increased likelihood of a medial Outerbridge grade ≥3 chondral defect (aOR, 3.11; 95% CI, 1.64-5.87; P = .001) or a grade 4 defect (aOR, 3.84; 95% CI, 1.75-8.45; P = .001).Conclusion:From the time of ACL injury, risk of an irreparable medial meniscal tear found at the time of ACL reconstruction is significantly increased by 8 weeks, and risk of high-grade medial chondral damage is increased by 5 months.
Practice Patterns in the Treatment of Patients With Severe Alcohol Withdrawal: A Multidisciplinary, Cross-Sectional Survey
Authors: Buell Danielle , Filewod Niall , Ailon Jonathan , Burns Karen E. A. 
Published: May 2019

Purpose: To characterize physicians’ stated practices in the treatment of patients with severe acute alcohol withdrawal syndrome (sAAWS) and to use intravenous (IV) phenobarbital as an adjuvant treatment for sAAWS. Methods: A multidisciplinary, cross-sectional, self-administered survey at 2 large academic centers specializing in inner-city healthcare. Results: We analyzed 105 of 195 questionnaires (53.8% response rate). On average, clinicians managed 32 cases of AAWS over a 6-month period, of which 7 (21.9%) were severe. Haloperidol (Haldol; 40 [39%]), clonidine (Catapres; 31 [30%]), phenobarbital (Luminal, Tedral; 29 [27%]) and propofol (Diprivan; 29 [28%]) were the most commonly used adjuvant medications for sAAWS. Sixty-three (60%) of respondents did not use phenobarbital in practice. Of phenobarbital users, 23 (55%) respondents used it early in patients who were refractory to symptom-triggered benzodiazepine treatment. Others waited until patients experienced seizures (5 [10%]) or required intensive care unit admission (8 [18%]). Respondents who used phenobarbital preferred to use the IV versus oral form (66% vs 29%, P < .001). Most respondents, however, were unfamiliar with the pharmacokinetics, side effects, contraindications, and evidence supporting phenobarbital use for sAAWS. Although many respondents (64 [61%]) expressed discomfort using phenobarbital, 87 (83%) expressed comfort or neutrality with enrolling patients in a trial to evaluate IV phenobarbital in sAAWS. Conclusions: Considerable stated practice variation exists in how clinicians treat patients with sAAWS. Our findings support conduct of a pilot trial to evaluate IV phenobarbital as an adjuvant treatment to symptom-triggered benzodiazepines for sAAWS and have informed trial design.