bluuebunny/crossref_metadata_2025 huggingface dataset:
MicroRNA-29a represses osteoclast formation and protects against osteoporosis by regulating PCAF-mediated RANKL and CXCL12
Authors: Lian Wei-Shiung , Ko Jih-Yang , Chen Yu-Shan , Ke Huei-Jing , Hsieh Chin-Kuei , Kuo Chung-Wen , Wang Shao-Yu , Huang Bo-Wun , Tseng Jung-Ge , Wang Feng-Sheng
Published: September 2019

Osteoporosis deteriorates bone mass and biomechanical strength, becoming a life-threatening cause to the elderly. MicroRNA is known to regulate tissue remodeling; however, its role in the development of osteoporosis remains elusive. In this study, we uncovered that silencing miR-29a expression decreased mineralized matrix production in osteogenic cells, whereas osteoclast differentiation and pit formation were upregulated in bone marrow macrophages as co-incubated with the osteogenic cells in transwell plates. In vivo, decreased miR-29a expression occurred in ovariectomy-mediated osteoporotic skeletons. Mice overexpressing miR-29a in osteoblasts driven by osteocalcin promoter (miR-29aTg/OCN) displayed higher bone mineral density, trabecular volume and mineral acquisition than wild-type mice. The estrogen deficiency-induced loss of bone mass, trabecular morphometry, mechanical properties, mineral accretion and osteogenesis of bone marrow mesenchymal cells were compromised in miR-29aTg/OCN mice. miR-29a overexpression also attenuated the estrogen loss-mediated excessive osteoclast surface histopathology, osteoclast formation of bone marrow macrophages, receptor activator nuclear factor-κ ligand (RANKL) and C–X–C motif chemokine ligand 12 (CXCL12) expression. Treatment with miR-29a precursor improved the ovariectomy-mediated skeletal deterioration and biomechanical property loss. Mechanistically, miR-29a inhibited RANKL secretion in osteoblasts through binding to 3′-UTR of RANKL. It also suppressed the histone acetyltransferase PCAF-mediated acetylation of lysine 27 in histone 3 (H3K27ac) and decreased the H3K27ac enrichment in CXCL12 promoters. Taken together, miR-29a signaling in osteogenic cells protects bone tissue from osteoporosis through repressing osteoclast regulators RANKL and CXCL12 to reduce osteoclastogenic differentiation. Arrays of analyses shed new light on the miR-29a regulation of crosstalk between osteogenic and osteoclastogenic cells. We also highlight that increasing miR-29a function in osteoblasts is beneficial for bone anabolism to fend off estrogen deficiency-induced excessive osteoclastic resorption and osteoporosis.
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

Annexin 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

CD8+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

Rotavirus 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.
Eat your heart out: choice and handling of novel toxic prey by predatory water rats
Authors: Parrott Marissa L. , Doody J. Sean , McHenry Colin , Clulow Simon
Published: September 2019

We investigated predator–prey interactions between cane toads (Rhinella marina) and native water rats (Hydromys chrysogaster), where toads are novel prey. We show that wild water rats preferentially targeted larger toads, and consumed specific non-toxic organs only. Rats either rapidly learned these behaviours, or adapted them from hunting native frogs.
Comparison of oxidoreductive enzyme activities in three coal tar creosote-contaminated soils
Authors: Telesiński Arkadiusz , Krzyśko-Łupicka Teresa , Cybulska Krystyna , Pawłowska Barbara , Biczak Robert , Śnieg Marek , Wróbel Jacek
Published: September 2019

This study used laboratory experiments to compare the effects of coal tar creosote on the activity of oxidoreductive enzymes in sandy loam, loamy sand and sandy clay loam soils. Different amounts of coal tar creosote were added to soil samples as follows: 0 (control), 2, 10 or 50 g kg–1 dry matter. The activity of soil dehydrogenases (DHAs), o-diphenol oxidase (o-DPO), catalase (CAT), nitrate reductase (NR) and peroxidases (POX) was determined. Contamination of soil with coal tar creosote affected oxidoreductase activity. Oxidoreductive enzyme activity following soil contamination with coal tar creosote was in the following order: DHAs > CAT > NR > POX > o-DPO in loamy sand and in sandy loam; and DHAs > POX > CAT > NR > o-DPO in sandy clay loam. The index of soil oxidoreductive activity (IOx) introduced in this study confirms the negative effect of coal tar creosote on oxidoreductase activity in soil. DHAs were the most sensitive to the contamination of soil with coal tar creosote. Moreover, the greatest changes in oxidoreductase activities were observed in loamy sand. Knowledge of the mechanism underlying the effects of coal tar creosote on oxidoreductive processes may enable development of a method for the bioremediation of polycyclic aromatic hydrocarbon-contaminated soils.
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

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

Multilateral 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.

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.

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.
Word Identification With Temporally Interleaved Competing Sounds by Younger and Older Adult Listeners
Authors: Helfer Karen S. , Poissant Sarah F. , Merchant Gabrielle R.
Published: September 2019

Objectives:

The purpose of this experiment was to contribute to our understanding of the nature of age-related changes in competing speech perception using a temporally interleaved task.

Design:

Younger and older adults (n = 16/group) participated in this study. The target was a five-word sentence. The masker was one of the following: another five-word sentence; five brief samples of modulated noise; or five brief samples of environmental sounds. The stimuli were presented in a temporally interleaved manner, where the target and masker alternated in time, always beginning with the target. Word order was manipulated in the target (and in the masker during trials with interleaved words) to compare performance when the five words in each stream did versus did not create a syntactically correct sentence. Talker voice consistency also was examined by contrasting performance when each word in the target was spoken by the same talker or by different talkers; a similar manipulation was used for the masker when it consisted of words. Participants were instructed to repeat back the target words and ignore the intervening words or sounds. Participants also completed a subset of tests from the NIH Cognitive Toolbox.

Results:

Performance on this interleaved task was significantly associated with listener age and with a metric of cognitive flexibility, but it was not related to the degree of high-frequency hearing loss. Younger adults’ performance on this task was better than that of older adults, especially for words located toward the end of the sentence. Both groups of participants were able to take advantage of correct word order in the target, and both were negatively affected, to a modest extent, when the masker words were in correct syntactic order. The two groups did not differ in how phonetic similarity between target and masker words influenced performance, and interleaved environmental sounds or noise had only a minimal effect for all listeners. The most robust difference between listener groups was found for the use of voice consistency: older adults, as compared with younger adults, were less able to take advantage of a consistent target talker within a trial.

Conclusions:

Younger adults outperformed older adults when masker words were interleaved with target words. Results suggest that this difference was unlikely to be related to energetic masking and/or peripheral hearing loss. Rather, age-related changes in cognitive flexibility and problems encoding voice information appeared to underlie group differences. These results support the contention that, in real-life competing speech situations that produce both energetic and informational masking, older adults’ problems are due to both peripheral and nonperipheral changes.
Deep Learning in Automated Region Proposal and Diagnosis of Chronic Otitis Media Based on Computed Tomography
Authors: Wang Yan-Mei , Li Yike , Cheng Yu-Shu , He Zi-Yu , Yang Juan-Mei , Xu Jiang-Hong , Chi Zhang-Cai , Chi Fang-Lu , Ren Dong-Dong
Published: September 2019

Objectives:

The purpose of this study was to develop a deep-learning framework for the diagnosis of chronic otitis media (COM) based on temporal bone computed tomography (CT) scans.

Design:

A total of 562 COM patients with 672 temporal bone CT scans of both ears were included. The final dataset consisted of 1147 ears, and each of them was assigned with a ground truth label from one of the 3 conditions: normal, chronic suppurative otitis media, and cholesteatoma. A random selection of 85% dataset (n = 975) was used for training and validation. The framework contained two deep-learning networks with distinct functions: a region proposal network for extracting regions of interest from 2-dimensional CT slices; and a classification network for diagnosis of COM based on the extracted regions. The performance of this framework was evaluated on the remaining 15% dataset (n = 172) and compared with that of 6 clinical experts who read the same CT images only. The panel included 2 otologists, 3 otolaryngologists, and 1 radiologist.

Results:

The area under the receiver operating characteristic curve of the artificial intelligence model in classifying COM versus normal was 0.92, with sensitivity (83.3%) and specificity (91.4%) exceeding the averages of clinical experts (81.1% and 88.8%, respectively). In a 3-class classification task, this network had higher overall accuracy (76.7% versus 73.8%), higher recall rates in identifying chronic suppurative otitis media (75% versus 70%) and cholesteatoma (76% versus 53%) cases, and superior consistency in duplicated cases (100% versus 81%) compared with clinical experts.

Conclusions:

This article presented a deep-learning framework that automatically extracted the region of interest from two-dimensional temporal bone CT slices and made diagnosis of COM. The performance of this model was comparable and, in some cases, superior to that of clinical experts. These results implied a promising prospect for clinical application of artificial intelligence in the diagnosis of COM based on CT images.
Association Between Saccule and Semicircular Canal Impairments and Cognitive Performance Among Vestibular Patients
Authors: Pineault Kevin , Pearson Deryck , Wei Eric , Kamil Rebecca , Klatt Brooke , Agrawal Yuri
Published: September 2019

Objectives:

Growing evidence suggests that vestibular function impacts higher-order cognitive ability such as visuospatial processing and executive functioning. Despite evidence demonstrating vestibular functional impairment impacting cognitive performance, it is unknown whether cognitive ability is differentially affected according to the type of vestibular impairment (semicircular canal [SCC] versus saccule) among patients with diagnosed vestibular disease.

Design:

Fifty-four patients who presented to an academic neurotologic clinic were recruited into the study. All patients received a specific vestibular diagnosis. Forty-one patients had saccule function measured with the cervical vestibular-evoked myogenic potential, and 43 had SCC function measured using caloric irrigation. Cognitive tests were administered to assess cognitive performance among patients. One hundred twenty-five matched controls were recruited from the Baltimore Longitudinal Study of Aging to compare cognitive performance in patients relative to age-matched healthy controls.

Results:

Using multivariate linear regression analyses, patients with bilaterally absent cervical vestibular-evoked myogenic potential responses (i.e., bilateral saccular impairments) were found to take longer in completing the Trail-Making test (β = 25.7 sec, 95% confidence interval = 0.3 to 51.6) and to make significantly more errors on the Benton Visual Retention test part-C (β = 4.5 errors, 95% confidence interval [CI] = 1.2 to 7.8). Patients with bilateral SCC impairment were found to make significantly more errors on the Benton Visual Retention test part-C (β = 9.8 errors, 95% CI = 0.2 to 19.4). From case–control analysis, for each SD difference in Trail-Making test part-B time, there was a corresponding 142% increase in odds of having vestibular impairment (odds ratio = 2.42, 95% CI = 1.44 to 4.07).

Conclusions:

These data suggest that bilateral saccule and SCC vestibular impairments may significantly affect various domains of cognitive performance. Notably, the cognitive performance in patients in this study was significantly poorer relative to age-matched healthy adults. Cognitive assessment may be considered in patients with saccule and SCC impairments, and cognitive deficits in vestibular patients may represent an important target for intervention.
Cochlear Implant Use Remains Consistent Over Time in Children With Single-Sided Deafness
Authors: Ganek Hillary V. , Cushing Sharon L. , Papsin Blake C. , Gordon Karen A.
Published: September 2019

Objectives:

To measure the acceptance of a cochlear implant by children with single-sided deafness (SSD) using datalogging technology in the cochlear implant processor.

Design:

Datalogs from follow-up clinical audiology appointments for 23 children with SSD were extracted from their cochlear implant processors ranging from 1 to 8 visits (M = 3.74, SD = 1.79). The number of hours the cochlear implant was in use per day, the number of times the coil disconnected from the internal device, and the percentage of daily cochlear implant use in different auditory environments were collected from the datalogs. Linear mixed-effects regressions were used to analyze the relationship between age, hearing experience, cochlear implant use, and coil-offs per day. Nonlinear regressions were conducted to evaluate cochlear implant use in different environments.

Results:

Children with SSD wore their cochlear implants for 6.22 (SD = 2.81; range = 0.0004 to 14.74) hours per day on average. No significant change in cochlear implant use was seen as the children grew older or gained more hearing experience. As hearing experience increased, the number of coil-offs per day was reduced. Preschoolers spent more time in “music” and “speech” and less time in “noise” and “quiet” than older and younger children while older children spent more time in “speech-in-noise.”

Conclusions:

Children with SSD consistently wear their cochlear implants. However, the auditory environments to which they are exposed vary over time. Regular cochlear implant use by this population suggests that it does not detract from a normal-hearing ear and that children with SSD appreciate access to bilateral input.
Overgrowth of the Femur After Internal Fixation in Children With Femoral Shaft Fracture—A Multicenter Study
Authors: Park Kyeong-Hyeon , Park Byoung Kyu , Oh Chang-Wug , Kim Dae-Wook , Park Hoon , Park Kun-Bo
Published: September 2019

Objectives:

To evaluate overgrowth after internal fixation for pediatric femur fracture and to identify any factors related with overgrowth in terms of fracture type and fixation method.

Design:

Retrospective comparative study.

Setting:

Multicenter, children's hospital and general hospital.

Patients/Participants:

Eighty-seven children between 4 and 10 years of age were included. Length-stable fracture was noted in 49 children, and length-unstable fracture was found in 38 children.

Intervention:

Thirty-six children were treated by minimal invasive plate osteosynthesis (MIPO), and elastic stable intramedullary nail fixation (ESIN) was used in 51 children.

Main Outcome Measurements:

The degree of overgrowth after internal fixation compared to fracture type, fracture site, and surgical method. Multivariable logistic regression analysis was conducted to identify factors related with overgrowth.

Results:

The average overgrowth of the femur was 10.5 ± 7.3 mm. There was no patient who required correction for final leg length discrepancy (>2 cm). There was no significant difference in overgrowth between ESIN (9.9 ± 7.2 mm) and MIPO (11.2 ± 7.6 mm) (P = 0.417). Overgrowth was similar among length-unstable fractures (12.3 ± 7.4 mm) and length-stable fractures (9.2 ± 7.0 mm), although it was statistically greater in length-unstable fractures (P = 0.048). In the MIPO group, length-unstable fractures were associated with an increased log odds of 6.873 for overgrowth of the femur (P = 0.042).

Conclusions:

Femur overgrowth after internal fixation seems to not be a clinically significant problem, regardless of whether that be for length-stable or length-unstable fractures and whether they were treated by MIPO or ESIN. Length-unstable fracture may be a risk factor for overgrowth in children. However, the difference is very small, and the postoperative overgrowth would likely not be a significant factor in deciding the surgical plan.

Level of Evidence:

Therapeutic Level III. See Instructions for authors for a complete description of levels of evidence.
VEPTR Treatment of Early Onset Scoliosis in Children Without Rib Abnormalities: Long-term Results of a Prospective, Multicenter Study
Authors: El-Hawary Ron , Morash Kevin , Kadhim Muayad , Vitale Michael , Smith John , Samdani Amer , Flynn John
Published: September 2019

Background:

In 2007, this prospective study on vertical expandable prosthetic titanium rib (VEPTR) treatment of early onset scoliosis in children without rib abnormalities was initiated. Two-year follow-up results have previously been reported. This study examines whether, at 5-year follow-up, VEPTR continues to control scoliosis and allow spinal growth.

Methods:

A prospective, multicenter, observational cohort design was used. Patients underwent traditional VEPTR implantation ≥5 years before analysis. Preimplantation and last available images were compared, regardless of whether VEPTR remained in vivo. Additional analysis was performed if VEPTR was in vivo ≥5 years.

Results:

This study included 59 patients (mean age at VEPTR implantation, 6.1±2.4 y; mean follow-up, 6.9±1.4 y). Currently, 24 patients still have VEPTR, whereas 24 have converted (13 fusions, 6 MCGR, 3 growing rods, 1 hybrid, and 1 Shilla). Three have had VEPTR explanted, 6 are unknown, and 2 have deceased. On last available imaging (n=59; mean follow-up, 4.8±1.9 y), scoliosis improved from 71.8±18.0 degrees preoperatively to 60.9±20.3 degrees (P<0.001) and T1- T12 height increased (15.8±3.2 to 19.3±3.8 cm, P<0.001). T1-S1 height also increased (24.8±4.4 to 31.2±5.3 cm, P<0.001), representing 119% age-matched growth. Composite improvement of scoliosis, T1-T12, and T1-S1 height was achieved in 79% of patients. A subset of 29 patients with VEPTR was analyzed at most recent follow-up ≥5 years while VEPTR remained in vivo (24 patients with VEPTR above, and 5 who later converted to other devices). Mean age at implantation was 5.0±2.2 years, with a mean VEPTR treatment duration of 6.2±1.1 years. Scoliosis improved from preoperatively (69.3±14.5 to 61.6±16.1 degrees, P=0.006), with mild recurrence from postoperative to 5 years. T1-T12 height increased (15.0±3.3 to 18.7±3.3 cm, P<0.001) and T1-S1 height increased (23.7±4.5 to 30.1±4.6 cm, P<0.001), representing 83% age-matched growth. Composite improvement was achieved in 83% of patients. Instrumented sagittal length also increased during this period (21.8±4.2 to 30.3±5.1 cm, P<0.001).

Conclusion:

At a 5-year follow-up, VEPTR continues to control scoliosis and allow spinal growth.

Level of Evidence:

Level II—prospective cohort, therapeutic study.
Is Initial Posterior Atlantoaxial Fixation and Fusion Applying Bilateral C1–2 Transarticular Screws and C1 Laminar Hooks Reliable for Acute Pediatric Atlantoaxial Instability?
Authors: Guo Xiang , Han Zhao , Chen Qunxiang , Yang Jun , Chen Fei , Guo Qunfeng , Lin Peida , Ni Bin
Published: September 2019

Study Design.

A retrospective case series study with at least 10 years of follow-up data.

Objective.

To validate the reliability of bilateral C1–2 transarticular screws and C1 laminar hooks and a bone autograft for acute pediatric atlantoaxial instability.

Summary of Background Data.

The reliability of initial posterior atlantoaxial fusion in pediatric patients is still controversial. To date, however, only a few published articles with short-term follow-up data are available to help spinal surgeons understand the effects of posterior atlantoaxial fusion in the skeletally immature spine.

Methods.

Five pediatric patients with acute atlantoaxial instability underwent atlantoaxial fusion using the above technique over a 3-year period. During a minimum 10-year follow-up period, not only outcomes and complications were investigated, but the vertical growth of the constructed spine in relation to the growth of the entire cervical spine, overall cervical spinal alignment, and adjacent-segment instability were evaluated.

Results.

The clinical follow-up indicated solid fusion and complete clinical relief from symptoms. No neural or vascular impairment was observed. The radiological evaluation showed that all patients had growth within the fusion construct reaching a mean 35.4% of the entire cervical spine. There were no radiological indicators of subaxial instability, even when cervical sagittal alignments became straight with a mean C2–7 angle of 6.4°.

Conclusion.

The results showed that initial posterior atlantoaxial fusion accomplished with bilateral C1–2 transarticular screws, C1 laminar hooks fixation, and bony autograft is a reliable surgical technique for treating acute pediatric atlantoaxial instability without negative effects on vertical growth at the fused level or the stability of the subaxial spine.

Level of Evidence: 3
Independent Association Between Type of Intraoperative Blood Transfusion and Postoperative Delirium After Complex Spinal Fusion for Adult Deformity Correction
Authors: Elsamadicy Aladine A. , Adil Syed M. , Charalambous Lefko , Drysdale Nicolas , Koo Andrew B. , Lee Megan , Kundishora Adam J. , Camara-Quintana Joaquin , Kolb Luis , Laurans Maxwell , Abbed Khalid , Karikari Isaac O.
Published: September 2019

Study Design.

Retrospective cohort study.

Objective.

To determine whether type of intraoperative blood transfusion used is associated with increased incidence of postoperative delirium after complex spine fusion involving five levels or greater.

Summary of Background Data.

Postoperative delirium after spine surgery has been associated with age, cognitive status, and several comorbidities. Intraoperative allogenic blood transfusions have previously been linked to greater complication risks and length of hospital stay. However, whether type of intraoperative blood transfusion used increases the risk for postoperative delirium after complex spinal fusion remains relatively unknown.

Methods.

The medical records of 130 adult (≥18 years old) spine deformity patients undergoing elective, primary complex spinal fusion (more than or equal to five levels) for deformity correction at a major academic institution from 2010 to 2015 were reviewed. We identified 104 patients who encountered an intraoperative blood transfusion. Of the 104, 15 (11.5%) had Allogenic-only, 23 (17.7%) had Autologous-only, and 66 (50.8%) had Combined transfusions. The primary outcome investigated was the rate of postoperative delirium.

Results.

There were significant differences in estimated blood loss (Combined: 2155.5 ± 1900.7 mL vs. Autologous: 1396.5 ± 790.0 mL vs. Allogenic: 1071.3 ± 577.8 mL vs. None: 506.9 ± 427.3 mL, P < 0.0001) and amount transfused (Combined: 1739.7 ± 1127.6 mL vs. Autologous: 465.7 ± 289.7 mL vs. Allogenic: 986.9 ± 512.9 mL, P < 0.0001). The Allogenic cohort had a significantly higher proportion of patients experiencing delirium (Combined: 7.6% vs. Autologous: 17.4% vs. Allogenic: 46.7% vs. None: 11.5%, P = 0.002). In multivariate nominal-logistic regression analysis, Allogenic (odds ratio [OR]: 24.81, 95% confidence interval [CI] [3.930, 156.702], P = 0.0002) and Autologous (OR: 6.43, 95% CI [1.156, 35.772], P = 0.0335) transfusions were independently associated with postoperative delirium.

Conclusion.

Our study suggests that there may be an independent association between intraoperative autologous and allogenic blood transfusions and postoperative delirium after complex spinal fusion. Further studies are necessary to identify the physiological effect of blood transfusions to better overall patient care and reduce healthcare expenditures.

Level of Evidence: 3