bluuebunny/crossref_metadata_2025_split huggingface dataset:
Elevated miR‐200a and miR‐141 inhibit endocrine gland‐derived vascular endothelial growth factor expression and ciliogenesis in preeclampsia
Authors: Wang Chia‐Yih , Tsai Pei‐Yin , Chen Ting‐Yu , Tsai Hui‐Ling , Kuo Pao‐Lin , Su Mei‐Tsz 
Published: April 2019

Key points
Endocrine gland‐derived vascular endothelial growth factor (EG‐VEGF) is a critical factor that facilitates trophoblast invasion in placenta.
Plasma miR‐141 and miR‐200a levels were elevated, while EG‐VEGF was decreased in peripheral blood and placenta of preeclamptic patients. Furthermore, numbers of cilia in the placenta from preeclamptic women were significantly decreased.
Elevated miR‐141 and miR‐200a inhibited the expression of EG‐VEGF, downstream extracellular signal‐regulated kinase (ERK)/matrix metalloproteinase 9 signalling and cilia formation, thus leading to defective trophoblast invasion.
The growth of the primary cilium, which transduced ERK signalling upon EG‐VEGF induction for proper trophoblast invasion, was also inhibited by miR‐141 and miR‐200a upregulation.
AbstractPreeclampsia is a severe gestational complication, and inadequate trophoblast invasion during placental development is an important pathoaetiology. Endocrine gland‐derived vascular endothelial growth factor (EG‐VEGF) is a critical factor that facilitates trophoblast invasion in placenta. By binding to the primary cilium, EG‐VEGF initiates the signalling cascade for proper embryo implantation and placental development. The miR‐200 family was predicted to target the EG‐VEGF 5′‐untranslated region, and its specific binding site was confirmed using a dual luciferase and a co‐transfection assay. In the peripheral blood and placenta of preeclamptic patients, EG‐VEGF showed significantly lower expression, whereas plasma miR‐141 and miR‐200a had higher expression compared with the controls. The biological significance of miR‐141 and miR‐200a was verified using an overexpression method in a trophoblast cell line (HTR‐8/SVneo). Elevated miR‐141 and miR‐200a inhibited the expression of EG‐VEGF, matrix metalloproteinase 9 (MMP9) and downstream extracellular signal‐regulated kinase (ERK) signalling, thus leading to defective trophoblast invasion. Additionally, the growth of the primary cilium, which transduces ERK/MMP9 signalling upon EG‐VEGF induction, was inhibited by miR‐141 and miR‐200a upregulation. Furthermore, the number of cilia in the human placenta of preeclamptic women was significantly decreased compared to normal placenta. In conclusion, the study uncovers the clinical correlations among the miR‐200 family, EG‐VEGF and the primary cilium in preeclampsia and the underlying molecular mechanisms. The results indicate that miR‐141 and miR‐200a directly targeted EG‐VEGF, suppressed primary cilia formation and inhibited trophoblast invasion. Thus, miR‐141 and miR‐200a could be explored as promising miRNA biomarkers and therapeutic targets in preeclampsia.
Differential Reduction of IP-10 and C-Reactive Protein via Aerobic Exercise or Mindfulness-Based Stress-Reduction Training in a Large Randomized Controlled Trial
Authors: Meyer Jacob D. , Hayney Mary S. , Coe Christopher L. , Ninos Cameron L. , Barrett Bruce P. 
Published: April 2019

Exercise and meditation improve health and well-being, potentially through decreasing systemic inflammation. In this study, healthy adults (N = 413) were randomized to 8 weeks of training in aerobic exercise, matched mindfulness-based stress reduction, or wait-list control. Three inflammation-related biomarkers (C-reactive protein, interleukin-6, and interferon-gamma-inducible protein-10) were assessed preintervention, directly postintervention, and 17 weeks later. Within-group analyses found that exercise participants had decreased serum interferon-gamma-inducible protein-10 postintervention and 17 weeks later, whereas C-reactive protein was lower in mindfulness-based stress-reduction participants 17 weeks postintervention only. Self-reported physical activity or amount of meditation practice did not predict biomarker changes. This study suggests that (a) training in aerobic exercise can lower interferon-gamma-inducible protein-10, a chemokine associated with interferon activity and illness, and (b) training in mindfulness meditation may have a delayed effect on C-reactive protein, an important inflammatory biomarker. The findings highlight the likelihood of multiple, distinct pathways underlying the health-promoting effects of these lifestyle interventions.
Virulence and Metabolism
Authors: Richardson Anthony R. 
Published: April 2019

ABSTRACT

Staphylococcus aureus
is clearly the most pathogenic member of the
Staphylococcaceae
. This is in large part due to the acquisition of an impressive arsenal of virulence factors that are coordinately regulated by a series of dedicated transcription factors. What is becoming more and more appreciated in the field is the influence of the metabolic state of
S. aureus
on the activity of these virulence regulators and their roles in modulating metabolic gene expression. Here I highlight recent advances in
S. aureus
metabolism as it pertains to virulence. Specifically, mechanisms of nutrient acquisition are outlined including carbohydrate and non-carbohydrate carbon/energy sources as well as micronutrient (Fe, Mn, Zn and S) acquisition. Additionally, energy producing strategies (respiration versus fermentation) are discussed and put in the context of pathogenesis. Finally, transcriptional regulators that coordinate metabolic gene expression are outlined, particularly those that affect the activities of major virulence factor regulators. This chapter essentially connects many recent observations that link the metabolism of
S. aureus
to its overall pathogenesis and hints that the mere presence of a plethora of virulence factors may not entirely explain the extraordinary pathogenic potential of
S. aureus
.
Mechanical thrombectomy in nonagenarians with acute ischemic stroke
Authors: Meyer Lukas , Alexandrou Maria , Leischner Hannes , Flottmann Fabian , Deb-Chatterji Milani , Abdullayev Nuran , Maus Volker , Politi Maria , Roth Christian , Kastrup Andreas , Thomalla Goetz , Mpotsaris Anastasios , Fiehler Jens , Papanagiotou Panagiotis 
Published: April 2019

BackgroundMechanical thrombectomy (MT) is a safe and effective therapy for ischemic stroke. Nevertheless, very elderly patients aged ≥90 years were either excluded or under-represented in previous trials. It remains uncertain whether MT is warranted for this population or whether there should be an upper age limit.MethodsWe retrospectively reviewed 79 patients with stroke aged ≥90 years from three neurointerventional centers who underwent MT between 2013 and 2017. Good functional outcome was defined as modified Rankin scale (mRS) ≤2 and assessed at 90-day follow-up. Successful recanalization was graded by Thrombolysis in Cerebral Infarction Scale (TICI) ≥2 b. Feasibility and safety assessments included unsuccessful recanalization attempts (TICI 0), time from groin puncture to recanalization, symptomatic intracranial hemorrhage (sICH), mortality, and intervention-related serious adverse events.ResultsOnly occlusions within the anterior circulation were included. Median time from groin puncture to recanalization was 39 min (IQR 25–57 min). The rate of successful recanalization (TICI ≥2 b) was 69.6% (55/79). Good functional outcome (mRS ≤2) at 90 days was observed in 16% (12/75) of patients. In-hospital mortality was 29.1% (23/79) and increased significantly at 90 days (46.7%, 35/75; p<0.001). sICH occurred in 5.1% (4/79) of patients. No independent predictor for good functional outcome (mRS ≤2) at 90 days was identified through logistic regression analysis.ConclusionMT in nonagenarians leads to high mortality rates and less frequently good functional outcome compared with younger patient cohorts in previous large randomized trials. However, MT appears to be safe and beneficial for a certain number of very elderly patients and therefore should generally not be withheld from nonagenarians.
Carnitine Is Associated With Atherosclerotic Risk and Myocardial Infarction in HIV‐Infected Adults
Authors: Sinha Arjun , Ma Yifei , Scherzer Rebecca , Rahalkar Smruti , Neilan Brendan D. , Crane Heidi , Drozd Daniel , Martin Jeffrey , Deeks Steven G. , Hunt Peter , Hsue Priscilla Y. 
Published: April 2019

Background

People living with
HIV
(
PLWH
) have an increased risk of myocardial infarction (
MI
). Changes in the gut microbiota that occur with chronic
HIV
infection could play a role in
HIV
‐associated atherosclerosis. Choline, carnitine, betaine, and trimethylamine N‐oxide are small molecules that are, in part, metabolized or produced by the gut microbiome. We hypothesized that these metabolites would be associated with carotid artery intima‐media thickness and
MI
in
PLWH
.

Methods and Results

Carotid artery intima‐media thickness was measured at baseline and at a median interval of 4 years in 162
PLWH
from the
SCOPE
(Study of the Consequences of the Protease Inhibitor Era) cohort in San Francisco,
CA
. Separately, 105
PLWH
(36 cases with type I adjudicated
MI
and 69 controls without
MI
) were selected from the Center for AIDS Research Network of Integrated Clinical Systems, a multicenter clinic‐based cohort. Controls were matched by demographics,
CD
4 cell count, and duration of viral suppression. In the
SCOPE
cohort, higher carnitine levels had a significant association with presence of carotid plaque and greater baseline and progression of mean carotid artery intima‐media thickness after adjusting for traditional cardiovascular disease risk factors. In the treated and suppressed subgroup, these associations with carnitine remained significant after adjustment for cardiovascular disease risk factors. In the Center for AIDS Research Network of Integrated Clinical Systems cohort, the risk of
MI
was significantly increased in subjects with carnitine levels in the highest quartile after adjustment for cardiovascular disease risk factors.

Conclusions

In
PLWH
, including the treated and suppressed subgroup, carnitine is independently associated with carotid artery intima‐media thickness, carotid plaque, and
MI
in 2 separate cohorts. These results emphasize the potential role of gut microbiota in
HIV
‐associated atherosclerosis and
MI
, especially in relation to carnitine metabolism.
Impact of minimal invasive extracorporeal circulation on the need of red blood cell transfusion
Authors: Ellam Sten , Pitkänen Otto , Lahtinen Pasi , Musialowicz Tadeusz , Hippeläinen Mikko , Hartikainen Juha , Halonen Jari 
Published: April 2019

Objective: Minimal invasive extracorporeal circulation may decrease the need of packed red blood cell transfusions and reduce hemodilution during cardiopulmonary bypass. However, more data are needed on the effects of minimal invasive extracorporeal circulation in more complex cardiac procedures. We compared minimal invasive extracorporeal circulation and conventional extracorporeal circulation methods of cardiopulmonary bypass. Methods: A total of 424 patients in the minimal invasive extracorporeal circulation group and 844 patients in the conventional extracorporeal circulation group undergoing coronary artery bypass grafting and more complex cardiac surgery were evaluated. Age, sex, type of surgery, and duration of perfusion were used as matching criteria. Hemoglobin <80 g/L was used as red blood cell transfusion trigger. The primary endpoint was the use of red blood cells during the day of operation and the five postoperative days. Secondary endpoints were hemodilution (hemoglobin drop after the onset of perfusion) and postoperative bleeding from the chest tubes during the first 12 hours after the operation. Results: Red blood cell transfusions were needed less often in the minimal invasive extracorporeal circulation group compared to the conventional extracorporeal circulation group (26.4% vs. 33.4%, p = 0.011, odds ratio 0.72, 95% confidence interval 0.55-0.93), especially in coronary artery bypass grafting subgroup (21.3% vs. 35.1%, p < 0.001, odds ratio 0.50, 95% confidence interval 0.35-0.73). Hemoglobin drop after onset of perfusion was also lower in the minimal invasive extracorporeal circulation group than in the conventional extracorporeal circulation group (24.2 ± 8.5% vs. 32.6 ± 12.6%, p < 0.001). Postoperative bleeding from the chest tube did not differ between the groups (p = 0.808). Conclusion: Minimal invasive extracorporeal circulation reduced the need of red blood cell transfusions and hemoglobin drop when compared to the conventional extracorporeal circulation group. This may have implications when choosing the perfusion method in cardiac surgery.
Distinctive features of positive anti-cell antibody tests (indirect immunofluorescence on HEp-2 cells) in patients with non-autoimmune diseases
Authors: Agustinelli R A , Rodrigues S H , Mariz H A , Prado M S , Andrade L E C 
Published: April 2019

Objective The objective of this study was to determine whether characteristics of positive results in the indirect immunofluorescence assay on HEp-2 cells for anti-cell antibodies (HEp-2 IFA) differ between patients with non-autoimmune diseases (NADs) and patients with systemic autoimmune rheumatic diseases (SARDs). Methods Cross-sectional observational study comparing HEp-2 IFA test results in three groups: (a) 558 NAD patients comprising four subgroups (cancer ( n = 95), infectious diseases ( n = 148), psychiatric diseases ( n = 163), common non-infectious chronic diseases ( n = 152)); (b) 194 SARD patients; (c) 1217 healthy individuals (HIs). Sera were tested at 1:80 dilution and diluted to the end titer. Slides were analyzed by two independent blinded examiners. Results A positive HEp-2 IFA test occurred in 102 (18.3%) NAD patients, 170 (87.6%) SARD patients and 150 (12.3%) HIs. The four NAD subgroups did not differ regarding HEp-2 IFA frequency, titer or pattern. HEp-2 IFA titer was higher in NAD patients than in HIs and both had lower titer than SARD patients. Nuclear dense fine speckled pattern was more frequent in NAD patients and HIs than in SARD patients ( p < 0.001). Nuclear homogeneous and nuclear coarse speckled patterns were more frequent in SARD patients than in the other groups ( p < 0.001). The nuclear fine speckled pattern was prevalent in all three groups, but presented a gradient in titer across them; HIs and NAD patients had low and intermediary titers, which were significantly lower than in SARD patients ( p < 0.001). Conclusion Positive HEp-2 IFA frequency, pattern and titer present differential features in NAD and SARD patients, and this attribute adds value to the test in the diagnosis of SARDs.
Diet and lupus: what do the patients think?
Authors: Robinson G A , Mcdonnell T , Wincup C , Martin-Gutierrez L , Wilton J , Kalea A Z , Ciurtin C , Pineda-Torra I , Jury E C 
Published: April 2019

Objectives Cardiovascular disease is the leading cause of mortality in patients with systemic lupus erythematosus. Therefore, using diet to control blood lipid levels and modify cardiovascular disease risk could be a promising therapeutic strategy to control disease symptoms. The primary objective of this study was to learn about systemic lupus erythematosus patient experiences with diet, including their opinion on considering diet as a therapeutic option. The secondary objective was to obtain this information in a cost- and time-effective manner. Methods A lay summary and a 15-question diet-based online survey were publicly available for 3 weeks. Social media was used to promote the survey through relevant charities, hospitals and research groups. Results A total of 300 responses were received, 284 from patients with systemic lupus erythematosus. Patients reported that there was a lack of clinical counselling regarding diet, with only 24% stating their doctor had spoken to them about diet. Despite this, 100% of patients stated they would change their diet if they knew it would help their symptoms and 83% would take part in a future diet-based clinical trial. Text analysis of patient research suggestions identified a particular interest in using diet to treat fatigue and manage disease flares. Conclusions This project successfully gathered patient information regarding diet and systemic lupus erythematosus over a short timeframe using an anonymous social media platform. The survey provided evidence that patients support further research and potential diet intervention studies investigating the effect of diet on the symptoms of systemic lupus erythematosus.
Creating Pathways to Personal Resilience Through Classroom Simulations
Authors: Walker Lorin , Luechtefeld Ray , Long Walker Jo Anne 
Published: April 2019

Background. College or university classroom simulations have the potential to create valuable educational outcomes that are difficult to achieve by other means. Personal resilience is one outcome that has achieved significant attention in the literature. Personal resilience is the ability to bounce back, learn from, and move forward after adverse experiences. Aim. This study posits that student personal resilience will increase following participation in university undergraduate management courses that use simulations that are grounded in a proposed teleological process model that includes six causal relationships. Method. Eighty-four students participated in either a Capstone strategy course using the Capsim simulation or a semester-long classroom as organization open simulation called XB that involved student management of all course aspects. The Connor-Davidson Resilience Scale (CD-RISC 10) survey instrument was used to measure personal resilience at both the beginning and end of each course. Results. In several cases, student personal resilience was significantly increased after courses utilizing simulations involving specific features. Conclusions. Participation in these kinds of experiences (with faculty support) may significantly increase levels of personal resilience among students. Recommendations. Simulations with the specified causal attributes might be used to foster student outcomes such as personal resilience, which typically are not a part of traditional course objectives.
Impact of Sagittal Talar Inclination on Total Ankle Replacement Failure
Authors: Le Vu , Escudero Mario , Symes Michael , Salat Peter , Wing Kevin , Younger Alastair , Penner Murray , Veljkovic Andrea 
Published: April 2019

Background: Restoration of ankle alignment is important in total ankle arthroplasty (TAA), but sagittal alignment of the talar component is less studied than coronal sagittal. Little has been published on the importance of sagittal talar alignment in TAA. The radiographic talar component inclination was hypothesized to be predictive of TAA survival, subsidence, and functional outcomes. Methods: A retrospective review of the Vancouver End-Stage Ankle Arthritis Database was performed on all TAAs at a single center over 11 years utilizing 1 of 2 implants. Talar component inclination (TCI) angles were measured and standard descriptive statistics were completed with a survival analysis. Inter- and intraobserver reliability were determined. Postoperative TCI angles were analyzed against several definitions of TAA survival and patient-reported outcome measures from the database. A total of 109 TAAs satisfied inclusion and exclusion criteria. Results: A postoperative talar component inclination angle greater than 22 degrees was associated with talar component anterior subsidence, defined as a change in that angle of 5 degrees or more between postoperative and last available radiographs. This was still significant after adjusting for confounders: age, gender, body mass index, and presence of inflammatory arthritis. All measured angles had good inter- and intraobserver reliability. Conclusion: Surgeons should avoid dorsiflexing the talar prosthesis during TAA, which hypothetically diminishes the ankle critical dorsiflexion range. This may cause anterior talar undercoverage in terminal dorsiflexion and may edge load the talar prosthesis, predisposing to anterior subsidence. Elevated TCI was a simple and reliable radiographic measurement to predict long-term TAA outcome due to predictable anterior subsidence of the talar prosthesis. Level of Evidence: Level III, retrospective comparative series.
Delirium in patients with ischaemic and haemorrhagic stroke: findings from a scoping review
Authors: Mansutti Irene , Saiani Luisa , Palese Alvisa 
Published: April 2019

Background:Delirium is a complex syndrome characterised by disturbances in attention and awareness, associated with alterations in cognitive functions, which can emerge in a time frame of hours or days and tend to fluctuate in severity over time. Delirium is a clinical manifestation of the brain’s vulnerability and diminished resilience to insult. Stroke patients are particularly vulnerable to delirium episodes.Aims:The aim of this study was to map: (a) studies focused on ischaemic or haemorrhagic post-stroke delirium; (b) factors that have been investigated as being possibly associated with post-stroke delirium; and (c) outcomes that have been studied to date.Methods:A scoping review was performed. Medline, CINAHL, Cochrane Database of Systematic Reviews, PsycINFO and Scopus databases were searched. Eligible studies were those: (a) exploring any variable regarding delirium in patients with stroke; (b) involving adults; (c) as primary studies; (d) written in English; and (e) published before April 2017.Results:To date 25 studies have been published, mainly prospective or cohort studies. The most commonly studied predisposing factors have been the older age, gender, aetiology of the stroke and its location, and the presence of previous cognitive decline/dementia. The most studied precipitating factors to date have been pneumonia, urinary tract infections and symptoms of neglect. Functional dependence, length of inhospital stays, post-stroke cognitive impairments or dementia, short and long-term mortality have been the most studied post-stroke delirium outcomes.Conclusions:Studies across different clinical settings, also at the international level, including more female patients and a wider range of ages should be designed in order to improve the evidence available to develop specific clinical guidelines. Standardised frameworks of research addressing the great variability of methods and measures used in the field should be established at the international level by clinicians and researchers’ experts in the field.