bluuebunny/crossref_metadata_2025_split huggingface dataset:
Extracellular annexin-A1 promotes myeloid/granulocytic differentiation of hematopoietic stem/progenitor cells via the Ca2+/MAPK signalling transduction pathway
Authors: Barbosa Christiano M. V. , Fock Ricardo Ambrósio , Hastreiter Araceli Aparecida , Reutelingsperger Cris , Perretti Mauro , Paredes-Gamero Edgar J. , Farsky Sandra H. P. 
Published: September 2019

AbstractAnnexin A1 (AnxA1) modulates neutrophil life span and bone marrow/blood cell trafficking thorough activation of formyl-peptide receptors (FPRs). Here, we investigated the effect of exogenous AnxA1 on haematopoiesis in the mouse. Treatment of C57BL/6 mice with recombinant AnxA1 (rAnxA1) reduced the granulocyte–macrophage progenitor (GMP) population in the bone marrow, enhanced the number of mature granulocytes Gr-1+Mac-1+ in the bone marrow as well as peripheral granulocytic neutrophils and increased expression of mitotic cyclin B1 on hematopoietic stem cells (HSCs)/progenitor cells (Lin−Sca-1+c-Kit+: LSK). These effects were abolished by simultaneous treatment with Boc-2, an FPR pan-antagonist. In in vitro studies, rAnxA1 reduced both HSC (LSKCD90lowFLK-2−) and GMP populations while enhancing mature cells (Gr1+Mac1+). Moreover, rAnxA1 induced LSK cell proliferation (Ki67+), increasing the percentage of cells in the S/G2/M cell cycle phases and reducing Notch-1 expression. Simultaneous treatment with WRW4, a selective FPR2 antagonist, reversed the in vitro effects elicited by rAnxA1. Treatment of LSK cells with rAnxA1 led to phosphorylation of PCLγ2, PKC, RAS, MEK, and ERK1/2 with increased expression of NFAT2. In long-term bone marrow cultures, rAnxA1 did not alter the percentage of LSK cells but enhanced the Gr-1+Mac-1+ population; treatment with a PLC (U73122), but not with a PKC (GF109203), inhibitor reduced rAnxA1-induced phosphorylation of ERK1/2 and Elk1. Therefore, we identify here rAnxA1 as an inducer of HSC/progenitor cell differentiation, favouring differentiation of the myeloid/granulocytic lineage, via Ca2+/MAPK signalling transduction pathways.
Soluble FAS ligand is not required for pancreatic islet inflammation or beta-cell destruction in non-obese diabetic mice
Authors: Trivedi Prerak M. , Fynch Stacey , Kennedy Lucy M. , Chee Jonathan , Krishnamurthy Balasubramanian , O’Reilly Lorraine A. , Strasser Andreas , Kay Thomas W. H. , Thomas Helen E. 
Published: September 2019

AbstractCD8+T cells play a central role in beta-cell destruction in type 1 diabetes. CD8+T cells use two main effector pathways to kill target cells, perforin plus granzymes and FAS ligand (FASL). We and others have established that in non-obese diabetic (NOD) mice, perforin is the dominant effector molecule by which autoreactive CD8+T cells kill beta cells. However, blocking FASL pharmacologically was shown to protect NOD mice from diabetes, indicating that FASL may have some role. FASL can engage with its receptor FAS on target cells either as membrane bound or soluble FASL. It has been shown that membrane-bound FASL is required to stimulate FAS-induced apoptosis in target cells, whereas excessive soluble FASL can induce NF-κB-dependent gene expression and inflammation. Because islet inflammation is a feature of autoimmune diabetes, we tested whether soluble FASL could be important in disease pathogenesis independent of its cell death function. We generated NOD mice deficient in soluble FASL, while maintaining expression of membrane-bound FASL due to a mutation in the FASL sequence required for cleavage by metalloproteinase. NOD mice lacking soluble FASL had normal numbers of lymphocytes in their spleen and thymus. Soluble FASL deficient NOD mice had similar islet inflammation as wild-type NOD mice and were not protected from diabetes. Our data indicate that soluble FASL is not required in development of autoimmune diabetes.
Rotavirus-Induced Neonatal Epileptic Encephalopathy—A Disease Spectrum Illustrated by Monochorionic Twins
Authors: Hopmans Esther M. , van der Heide Astrid , Chung Pui Khi , Brinkman Daniëlle , Feltkamp Mariet C.W. , van Dijk J. Gert , Steggerda Sylke J. , Niks Erik H. 
Published: September 2019

AbstractRotavirus has been associated with neonatal seizures and specific white matter magnetic resonance imaging (MRI) abnormalities. We describe monochorionic twins who not only tested positive for rotavirus with these white matter MRI abnormalities but who also showed an electroencephalogram (EEG) pattern characteristic of early infantile epileptic encephalopathy (EIEE), which has so far solely been described in epileptic encephalopathies with a poor prognosis. This report suggests that rotavirus infection must be added to the list of causes of EIEE EEG, and that the outcome then is likely more favorable. As MRI and EEG signs of rotavirus encephalopathy were present in one twin with only subtle neurologic symptoms, rotavirus may well cause insidious central nervous system complications more often. We suggest considering rotavirus infection in neonates presenting with seizures, and to add rotavirus infection to the differential diagnosis of EIEE.
Allicin Reversed the Process of Frailty in Aging Male Fischer 344 Rats With Osteoporosis
Authors: Liu Yang , You Meigui , Shen Jianwei , Xu Yaping , Li Lin , Wang Dongtao , Yang Yajun 
Published: September 2019

Abstract
The research and development of pharmaceutical intervention is insufficient for the frail older adults, especially in preclinical stage for the frail individuals with osteoporosis. Garlic exerts an antiosteoporotic effect and its vital component allicin could protect organisms against aging. The present study aimed to investigate the effect of long-term intragastric administration of allicin (low dose of 4 mg·kg−1·d−1; middle dose of 8 mg·kg−1·d−1; high dose of 16 mg·kg−1·d−1) on frailty with osteoporosis in aging male Fischer 344 rats. Frailty was assessed with a 27-item frailty index based on quantifying health-related deficits in adult male rats varied from 13 to 21 months and in control rats from 6 to 9 months. Osteoporosis was appraised by bone mineral density detected by dual-energy X-ray absorptiometry, biomechanical properties measured by a three-point bending test, and bone metabolic analysis using ELISA. Allicin could attenuate frailty index scores by reducing the accumulation of health deficits in aging male Fischer 344 rats. Meanwhile, allicin could protect against senile osteoporosis, and the underlying mechanism may involve in increasing low bone turnover through elevation of both bone formation and bone resorption, and subsequently lead to increase of bone mineral density, contributing to reversing deleterious bone biomechanical features associated with aging. The present study reveals firstly that long-term oral administration with allicin attenuated frailty with osteoporosis during the process of aging, which provides a preclinical evidence for intervention of frailty.
Collaboration Networks in Conference Diplomacy: The Case of the Nonproliferation Regime
Authors: Onderco Michal 
Published: September 2019

AbstractMultilateral conferences are the bread-and-butter of international politics. In such settings, countries may pursue their interests individually, but most of the time they prefer to act through coalitions. Such coalitions are overlapping, creating a network structure. States build and utilize networks to get agenda items pushed through or to block unfavorable ones. While sometimes they are formed on the basis of formal institutions (such as the NAM or the EU), frequently their membership is based on either ad hoc cooperation or existing informal bodies (such as the NSG, New Agenda Coalition, or Zangger Committee). The attention to such networks is, however, still in its infancy. This paper looks at how state networks within one of the most important recurring diplomatic conferences—the quinquennial NPT Review Conference—develop and transform over time. By doing so, the paper maps the existing networks and explains their transformation as an instrument of global governance.
Th2 inflammatory responses in the development of nasal polyps and chronic rhinosinusitis
Authors: Ryu Gwanghui , Kim Dae Woo 
Published: September 2019

Purpose of review
Pathogenesis of nasal polyp has been largely studied based on innate and adaptive immunity of sinonasal mucosa. So far, various factors have been identified that trigger an inflammatory response in the pathogenesis of nasal polyps. In this review, we summarized recently updated information in the understanding of mechanisms in the development of chronic rhinosinusitis with nasal polyp (CRSwNP) focusing on Th2 inflammation.

Recent findings
Endotype of CRSwNP presented mainly Th2-skewed inflammation, and it has been associated with refractoriness and comorbidities. Staphylococcus aureus can drive Th2 inflammation by producing enterotoxins and serine protease-like protein. Moreover, S. aureus directly affected mucosal barrier function and enhanced Th2 cytokine production by fast induction of epithelial-derived innate cytokines. Epithelial-derived innate cytokines, including TSLP, IL-25, and IL-33, promote Th2 responses via the development of innate lymphoid cells. Mast cell expresses IL-5, IL-13, and periostin, and it plays a role in the pathogenesis of nasal polyps through orchestrating eosinophil infiltration. Formation of eosinophil extracellular traps and Charcot–Leyden crystals is strongly associated with disease severity and viscous mucus plug production. Therefore, it needs to be investigated mechanistically. The role of neutrophils in Th2 inflammation has been poorly understood but appears to enhance Th2 inflammation and make it more resistant to steroid therapy.

Summary
There is growing evidence of the role of S. aureus in innate and adaptive immunity, which contribute to Th2 inflammation in CRSwNP. Innate immunity, including epithelial-derived cytokines, plays a crucial role in the development of CRSwNP by inducing various pathways and need to be investigated more as Th2-targeted biomarkers. Recently, the role of neutrophilic inflammation in Th2 inflammation has started to be studied but still remains unclear.
Anesthesia for thoracic ambulatory surgery
Authors: Raft Julien , Richebé Philippe 
Published: September 2019

Purpose of review
Ambulatory surgery plays a major role in cost-effective patient care without compromising patient safety and satisfaction. This concept improves the patient support and decreases the length of stay sometimes until ambulatory surgery. The aim of this review is to examine the current state of the art of anesthesia for thoracic ambulatory surgery.

Recent findings
Guidelines for enhanced recovery after thoracic surgery (ERATS) have recently been published. They can be safely implemented without increasing hospital readmission or mortality. Video-assisted thoracoscopy may be the best approach within a fast-track program. Anesthetic management should focus on combination of regional analgesia and general anesthesia techniques. General anesthesia should be performed with short acting agent and prevention of residual paralysis. Thoracic epidural analgesia is the gold standard technique for pain control after major thoracic surgery but not compatible with a quick hospital discharge. Thoracic paravertebral block, Serratus plane block, intercostal nerve block, and more recently erector spinae plane block have all been used with success for analgesia in thoracic surgery.

Conclusion
ERATS program may lead to improved outcomes including decreased length of stay, but it is currently too early to show the impact on thoracic ambulatory surgery that concerned selected patients for lung resection.
Pharmacological strategies in multimodal analgesia for adults scheduled for ambulatory surgery
Authors: Richebé Philippe , Brulotte Véronique , Raft Julien 
Published: September 2019

Purpose of review
The present review aims to propose pharmacological strategies to enhance current clinical practices for analgesia in ambulatory surgical settings and in the context of the opioid epidemic.

Recent findings
Each year, a high volume of patients undergoes ambulatory surgery worldwide. The multimodal analgesia proposed to ambulatory patients must provide the best analgesic effect and patient satisfaction while respecting the rules of safety for ambulatory surgery. The role of nurses, anesthesiologists, and surgeons around said surgery is to relieve suffering, achieve early mobilization and patient satisfaction, and reduce duration of stay in hospital. Currently, and particularly in North America, overprescription of opioids has reached a critical level constituting a ‘crisis’. Thus, we see the need to offer more optimal multimodal analgesia strategies to ambulatory patients.

Summary
These strategies must combine three key components when not contraindicated: regional/local analgesia, acetaminophen, and nonsteroidal anti-inflammatory drugs (NSAIDs). Adjuvants such as gabapentinoids, N-methyl-D-aspartate receptor modulators, glucocorticoids, α2-adrenergic receptor agonists, intravenous lidocaine might be added to the initial multimodal strategy, however, caution must be used regarding their side effects and risks of delaying recovery after ambulatory surgery. Weaker opioids (e.g. oxycodone, hydrocodone, tramadol) could be used rather than more powerful ones (e.g. morphine, hydromorphone, inhaled fentanyl, sufentanil). This, combined with education about postoperative weaning of opioids after surgery must be done in order to avoid long-term reliance of these drugs.
Hypertonic Saline Versus Mannitol for Traumatic Brain Injury: A Systematic Review and Meta-analysis With Trial Sequential Analysis
Authors: Schwimmbeck Franz , Voellger Benjamin , Chappell Daniel , Eberhart Leopold 
Published: September 2019

Background:
Mannitol and hypertonic saline are widely used to treat raised intracranial pressure (ICP) after traumatic brain injury (TBI), but the clinical superiority of one over the other has not been demonstrated.

Methods:
According to the PRISMA statement, this meta-analysis reports on randomized controlled trials investigating hypertonic saline compared with mannitol in the treatment of elevated ICP following TBI. The protocol for the literature searches (Medline, Embase, Central databases), quality assessment, endpoints (mortality, favorable outcome, brain perfusion parameters), and statistical analysis plan (including a trial sequential analysis) were prospectively specified and registered on the PROSPERO database (CRD42017057112).

Results:
A total of 12 randomized controlled trials with 464 patients were eligible for inclusion in this analysis. Although there was a nonsignificant trend in favor of hypertonic saline, there were no significant differences in mortality between the 2 treatments (relative risk [RR]: 0.69, 95% confidence interval [CI]: 0.45, 1.04; P=0.08). There were also no significant differences in favorable neurological outcome between hypertonic saline (HS) and mannitol (RR: 1.28, 95% CI: 0.86, 1.90; P=0.23). There was no difference in ICP at 30 to 60 minutes after treatment (mean difference [MD]: −0.19 mm Hg, 95% CI: −0.54, 0.17; P=0.30), whereas ICP was significantly lower after HS compared with mannitol at 90 to 120 minutes (MD: −2.33 mm Hg, 95% CI: −3.17, −1.50; P<0.00001). Cerebral perfusion pressure was higher between 30 to 60 and 90 to 120 minutes after treatment with HS compared with after treatment with mannitol (MD: 5.48 mm Hg, 95% CI: 4.84, 6.12; P<0.00001 and 9.08 mm Hg, 95% CI: 7.54, 10.62; P<0.00001, respectively). Trial sequential analysis showed that the number of cases was insufficient to produce reliable statements on long-term outcomes.

Conclusion:
There are indications that HS might be superior to mannitol in the treatment of TBI-related raised ICP. However, there are insufficient data to reach a definitive conclusion, and further studies are warranted.
An Ethnography of Parents' Perceptions of Patient Safety in the Neonatal Intensive Care Unit
Authors: Ottosen Madelene J. , Engebretson Joan , Etchegaray Jason , Arnold Cody , Thomas Eric J. 
Published: September 2019

Background:
Parents of neonates are integral components of patient safety in the neonatal intensive care unit (NICU), yet their views are often not considered. By understanding how parents perceive patient safety in the NICU, clinicians can identify appropriate parent-centered strategies to involve them in promoting safe care for their infants.

Purpose:
To determine how parents of neonates conceptualize patient safety in the NICU.

Methods:
We conducted qualitative interviews with 22 English-speaking parents of neonates from the NICU and observations of various parent interactions within the NICU over several months. Data were analyzed using thematic content analysis. Findings were critically reviewed through peer debriefing.

Findings:
Parents perceived safe care through their observations of clinicians being present, intentional, and respectful when adhering to safety practices, interacting with their infant, and communicating with parents in the NICU. They described partnering with clinicians to promote safe care for their infants and factors impacting that partnership. We cultivated a conceptual model highlighting how parent-clinician partnerships can be a core element to promoting NICU patient safety.

Implications for Practice:
Parents' observations of clinician behavior affect their perceptions of safe care for their infants. Assessing what parents observe can be essential to building a partnership of trust between clinicians and parents and promoting safer care in the NICU.

Implications for Research:
Uncertainty remains about how to measure parent perceptions of safe care, the level at which the clinician-parent partnership affects patient safety, and whether parents' presence and involvement with their infants in the NICU improve patient safety.
Mothers' Experiences in the NICU Before Family-Centered Care and in NICUs Where It Is the Standard of Care
Authors: Neu Madalynn , Klawetter Susanne , Greenfield Jennifer C. , Roybal Kristi , Scott Jessica L. , Hwang Sunah S. 
Published: September 2019

Background:Family-centered care (FCC) in neonatal intensive care units (NICUs) was initiated in 1992 to promote a respectful response to individual family needs and support parental participation in care and decision-making for their infants. Although benefits of FCC have been reported, changes in the maternal experience in the NICU are unknown.Purpose:The purpose of this study was to compare mothers' experiences in NICUs where FCC is the standard of care and to compare these with the experiences of mothers 2 decades ago.Methods:In this qualitative descriptive design, mothers of infants born under 32 weeks postconceptional age were asked to describe their experiences with their infant's birth and hospitalization. Open-ended probing questions clarified maternal responses. Saturation was reached after 14 interviews. Iterative coding and thematic grouping was used for analysis.Results:Common themes that emerged were: (1) visiting; (2) general caregiving; (3) holding; (4) feeding; and (5) maternal ideas for improvement. Findings indicated important improvements in privacy, mother–nurse relationship, ease of visiting, and maternal knowledge and participation in infant caregiving.Implications for Practice:Mothers suggested improvements such as additional comforts in private rooms, areas in the NICU where they can meet other mothers, and early information on back-transport. Better recognition and response for mothers without adequate social support would provide much needed emotional assistance.Implications for Research:Future research addressing benefits of webcams, wireless monitors, back-transport, maternity leave, and accommodations for extended visiting for siblings would address other needs mentioned by mothers.
The Beneficence of Cuddle Therapy in Hyperekplexia
Authors: Seale Jamie , Murphy Jennifer , Mantle Ashley , Chan Belinda 
Published: September 2019

Background:
Benevolent injustice occurs when well-intentioned treatment efforts produce an outcome that limits the potential of a patient. The unintended harm can result in significant moral distress for the family and the healthcare team.

Clinical Findings:
We discussed an ethical dilemma regarding a neonate who had suspected seizure and hypoxic–ischemic encephalopathy after home birth delivery. The healthcare team experienced moral distress about the mother's desire to not use anti-seizure medications and instead trial other interventions such as cuddling. Subsequently, clinical analysis ruled out a seizure disorder. Genetic studies on this neonate confirmed hereditary hyperekplexia, which presented as exaggerated Moro reflex and apnea that mimicked seizure.

Intervention:
We discussed how applying any one of the 4 basic ethical principles of autonomy, beneficence, nonmaleficence, or justice could counteract benevolent injustice and moral distress.

Outcomes:
Discussions with the patient's mother and nurse allowed the team to overcome their reluctance to try the mother's treatment recommendations. This resulted in adopting the seemingly counterintuitive intervention of cuddling that turned out to be effective for this neonate with hereditary hyperekplexia.

Practice Recommendations:
The moral distress associated with benevolent injustice should be identified early to minimize long-term consequences to the patient, family, and healthcare team. Healthcare teams should learn to apply ethical principles when discussing patient care concerns in an unbiased manner. Guided ethical discussions allow us to be more efficient in providing family-centered care that aligns with the patient's best interest.
Neural Modulation Transmission Is a Marker for Speech Perception in Noise in Cochlear Implant Users
Authors: Gransier Robin , Luke Robert , van Wieringen Astrid , Wouters Jan 
Published: September 2019

Objectives:
Cochlear implants (CIs) restore functional hearing in persons with a severe hearing impairment. Despite being one of the most successful bionic prosthesis, performance with CI (in particular speech understanding in noise) varies considerably across its users. The ability of the auditory pathway to encode temporal envelope modulations (TEMs) and the effect of degenerative processes associated with hearing loss on TEM encoding is assumed to be one of the reasons underlying the large intersubject differences in CI performance. The objective of the present study was to investigate how TEM encoding of the stimulated neural ensembles of human CI recipients is related to speech perception in noise (SPIN).

Design:
We used electroencephalography as a noninvasive electrophysiological measure to assess TEM encoding in the auditory pathway of CI users by means of the 40-Hz electrically evoked auditory steady state response (EASSR). Nine CI users with a wide range of SPIN outcome were included in the present study. TEM encoding was assessed for each stimulation electrode of each subject and new metrics; the CI neural modulation transmission difference (CIMTD) and the CI neural modulation transmission index (CIMTI) were developed to quantify the amount of variability in TEM encoding across the stimulated neural ensembles of the CI electrode array.

Results:
EASSR patterns varied across the CI electrode array and subjects. We found a strong correlation (r = 0.89, p = 0.001) between the SPIN outcomes and the variability in EASSR amplitudes across the array as assessed with CIMTD/CIMTI.

Conclusions:
The results of the present study show that the 40-Hz EASSR can be used to objectively assess the neural encoding of TEMs in human CI recipients. Overall reduced or largely variable TEM encoding of the neural ensembles across the electrode array, as quantified with the CIMTD/CIMTI, is highly correlated with speech perception in noise outcome with a CI.