bluuebunny/crossref_metadata_2025_split huggingface dataset:
Distribution of functional opioid receptors in human dorsal root ganglion neurons
Authors: Moy Jamie K. , Hartung Jane E. , Duque Melissa G. , Friedman Rob , Nagarajan Vidhya , Loeza-Alcocer Emanuel , Koerber H. Richard , Christoph Thomas , Schröder Wolfgang , Gold Michael S. 
Published: February 2020

Abstract
Preclinical evidence has highlighted the importance of the μ-opioid peptide (MOP) receptor on primary afferents for both the analgesic actions of MOP receptor agonists, as well as the development of tolerance, if not opioid-induced hyperalgesia. There is also growing interest in targeting other opioid peptide receptor subtypes (δ-opioid peptide [DOP], κ-opioid peptide [KOP], and nociceptin/orphanin-FQ opioid peptide [NOP]) on primary afferents, as alternatives to MOP receptors, which may not be associated with as many deleterious side effects. Nevertheless, results from several recent studies of human sensory neurons indicate that although there are many similarities between rodent and human sensory neurons, there may also be important differences. Thus, the purpose of this study was to assess the distribution of opioid receptor subtypes among human sensory neurons. A combination of pharmacology, patch-clamp electrophysiology, Ca2+ imaging, and single-cell semiquantitative polymerase chain reaction was used. Our results suggest that functional MOP-like receptors are present in approximately 50% of human dorsal root ganglion neurons. δ-opioid peptide-like receptors were detected in a subpopulation largely overlapping that with MOP-like receptors. Furthermore, KOP-like and NOP-like receptors are detected in a large proportion (44% and 40%, respectively) of human dorsal root ganglion neurons with KOP receptors also overlapping with MOP receptors at a high rate (83%). Our data confirm that all 4 opioid receptor subtypes are present and functional in human sensory neurons, where the overlap of DOP, KOP, and NOP receptors with MOP receptors suggests that activation of these other opioid receptor subtypes may also have analgesic efficacy.
TRPV1 antagonist BCTC inhibits pH 6.0-induced pain in human skin
Authors: Heber Stefan , Ciotu Cosmin I. , Hartner Gabriel , Gold-Binder Markus , Ninidze Nino , Gleiss Andreas , Kress Hans-Georg , Fischer Michael J.M. 
Published: February 2020

Abstract
Tissue acidosis due to ischemia occurs under several pathological conditions and is believed to contribute to pain in these circumstances. TRPV1, TRPA1, and ASICs are known to be sensitive to acidic pH. Addressing their possible role in acidosis perception, the respective antagonists BCTC, A-967079, and amiloride were injected in the volar forearm skin of 32 healthy volunteers. To investigate possible redundancies between channels, a full-factorial study design was used. Injections were performed in a prerandomized, double-blind, and balanced design. Each injection included a three-step pH protocol from pH 7.0 over pH 6.5 to pH 6.0 with a step duration of 90 seconds. Pain was reported by volunteers on a numerical scale every 10 seconds during injections. Confirming the primary hypothesis, the combination of all 3 antagonists reduced acid-induced pain at pH 6.0. Because of the full-factorial design, it could be concluded that BCTC alone, but not A-967079 or amiloride, or any combination thereof, was responsible for the observed effects, suggesting TRPV1 as primary sensor for pH 6.0-induced pain. Surprisingly, A-967079 even enhanced pain induced by pH 6.0. In cultured mouse dorsal root ganglion neurons, TPRV1 dependence of pH 6-induced calcium responses could be confirmed. Responses of hTRPV1 to acidic stimulation showed a maximum around pH6, providing an explanation for the pH-dependent inhibition by BCTC. A-967079 sensitizes pH responses is a TRPA1-responsive dorsal root ganglion neuron population, and a direct effect of A-967079 on hTRPA1 and hTRPV1 was excluded. In conclusion, inhibiting TRPV1-mediated acidosis-induced pain could be a symptomatic and potentially also a disease-modifying approach.
Combinatorial roles of mitochondria and cGMP/PKG pathway in the generation of neuronal free Zn2+ under the presence of nitric oxide
Authors: Yang De-Ming , Huang Chien-Chang , Chang Yu-Fen 
Published: February 2020

Background:
Nitric oxide (NO), which possesses both protective and toxic properties, has been observed to have a complicated biphasic character within various types of tissues, including neuronal cells. NO was also found to cause the increase of another important signaling molecular Zn2+ (termed as NZR). The molecular mechanism of NZR has been extensively investigated, but the source of Zn2+ is present of a major candidate that is yet to be answered. The NO-protein kinase G (PKG) pathway, mitochondria, and metallothioneins (MTs), are all proposed to be the individual source of NZR. However, this hypothesis remains inconclusive. In this study, we examined the function of PKG signaling cascades, the mitochondria storage, and MT-1 during NZR of living PC12 cells.

Methods:
We applied live-cell imaging in combination with pharmacological inhibitors and activators as well as in vitro Zn2+ assay to dissect the functions of the above candidates in NZR.

Results:
Two mechanisms, namely, mitochondria as the only Zn2+ source and the opening of NO–PKG-dependent mitochondrial ATP-sensitive potassium channels (mKATP) as the key to releasing NO-induced increase in mitochondrial Zn2+, were proven to be the two critical paths of NZR in neuronal-related cells.

Conclusion:
This new finding provides a reasonable explanation to previously existing and contradictory conclusions regarding the function of mitochondria/mKATP and PKG signaling on the molecular mechanism of NZR.
Thermoablative Techniques for Excessive Central Airway Collapse
Authors: de Lima Andres , Vidal Barbara , Kheir Fayez , VanderLaan Paul A. , Mallur Pavan S. , Gangadharan Sidhu P. , Majid Adnan 
Published: February 2020

Background:
Tracheobronchoplasty is the definitive treatment for patients with symptomatic excessive central airway collapse. This procedure is associated with high morbidity and mortality rates. Bronchoscopic techniques are an appealing alternative with less morbidity and the ability to apply it in nonsurgical patients. Although thermoablative methods have been proposed as treatment options to induce fibrosis of the posterior tracheobronchial wall, no studies have compared direct histologic effects of such methods. This study compared the effects of electrocautery, radiofrequency ablation, potassium titanyl phosphate laser, and argon plasma coagulation (APC) in the tracheobronchial tree in an ex vivo animal model.

Methods:
Four adult sheep cadavers were used for this study. Under flexible bronchoscopy, the posterior tracheal membrane was treated using different power settings on 4 devices. The airways were assessed for the presence of treatment-related histopathologic changes.

Results:
Histologic changes observed were that of acute thermal injury including: surface epithelium ablation, collagen fiber condensation, smooth muscle cytoplasm condensation, and chondrocyte pyknosis. No distinct histologic differences in the treated areas among different modalities and treatment effects were observed. APC at higher power settings was the only modality that produced consistent and homogenous thermal injury effects across all tissue layers with no evidence of complete erosion.

Conclusion:
Although electrocautery, radiofrequency ablation, potassium titanyl phosphate laser, and APC all induce thermal injury of the airway wall, only APC at high power settings achieves this effect without complete tissue erosion, favoring potential regeneration and fibrosis. Live animal studies are now plausible.
Is Additional Nebulized Lidocaine Helpful in Flexible Bronchoscopy?
Authors: Ho An Thi Nhat , Gandhiraj Deepthi , Jamkhana Zafar , Nayak Ravi , Patolia Setu 
Published: February 2020

Background:
Conflicting evidence of nebulized lidocaine use in bronchoscopy still exist. This study will identify whether there is any difference in various patient-related, physician-related, or procedure-related outcomes with and without lidocaine nebulization before the procedure.

Method:
The authors performed a search in 4 electronic databases, including Pubmed, Scopus, Virtual Health Library, and Google Scholar from inception to August 2019. Data on patient-reported and physician-reported outcomes, doses of sedation, and lidocaine were extracted and pooled into standardized mean difference (SMD) and mean difference (MD) using the random-effect model.

Results:
Seven randomized controlled trials with 1366 patients were included. Cough was not different between the nebulized lidocaine group and no nebulized lidocaine group (SMD, −0.12; 95% confidence interval, −0.82 to 0.59; I
2, 95%; P=0.75), so as operator’s satisfaction score, ease of the procedure, patient’s discomfort, and unwillingness to repeat the procedure. Additional nebulized lidocaine group required higher lidocaine dose (MD, 81.93; 95% confidence interval, 17.14-146.71). Studies using only local anesthesia favored the “no additional lidocaine” group in improving cough, operator’s satisfaction score, and ease of the procedure. Subgroup analysis of studies using moderate sedation showed a decrease in midazolam dose and duration of the procedure in the “additional nebulized lidocaine group.”

Conclusion:
Additional administration of nebulized lidocaine increased the total dose of lidocaine used and did not improve cough symptoms, operator-satisfaction score, ease of the procedure, and willingness to repeat the procedure. Subgroup analysis of studies using moderate sedation showed a decrease in midazolam use and in procedure duration but the clinical significance of these findings is uncertain.
Strategies for prediction of drug-resistant pathogens and empiric antibiotic selection in community-acquired pneumonia
Authors: Gil Ryan , Webb Brandon J. 
Published: February 2020

Purpose of review
Although most patients with community-acquired pneumonia (CAP) are appropriately treated with narrow-spectrum antibiotics, predicting which patients require coverage of drug-resistant pathogens (DRP) remains a challenge. The 2019 American Thoracic Society/Infectious Diseases Society of America CAP guidelines endorse using locally validated prediction models for DRP. Here we review risk factors for DRP and provide a summary of available risk prediction models.

Recent findings
Both inadequate initial empiric spectrum as well as unnecessary broad-spectrum antibiotic use are associated with poor outcomes in CAP. Multiple prediction models for DRP-based patient-level risk factors have been published, with some variation in included predictor variables and test performance characteristics. Seven models have been robustly externally validated, and implementation data have been published for two of these models. All models demonstrated better performance than the healthcare-associated pneumonia criteria, with most favoring sensitivity over specificity. We also report validation of the novel, risk factor-based treatment algorithm proposed in the American Thoracic Society/Infectious Diseases Society of America guidelines which strongly favors specificity over sensitivity, especially in nonsevere pneumonia.

Summary
Using patient-level risk factors to guide the decision whether to prescribe broad-spectrum antibiotics is a rational approach to treatment. Several viable candidate prediction models are available. Hospitals should evaluate the local performance of existing scores before implementing in routine clinical practice.
MicroRNAs: future biomarkers and targets of therapy in asthma?
Authors: Specjalski Krzysztof , Niedoszytko Marek 
Published: February 2020

Purpose of review
MicroRNAs (miRNAs) are small noncoding RNA molecules that are considered one of the fundamental regulatory mechanisms of gene expression. They are involved in many biologic processes, such as signal transduction, cell proliferation and differentiation, apoptosis and stress responses. The purpose of this review is to present recent knowledge about the role of miRNAs in asthma and outline possible applications of miRNAs.

Recent findings
A core set of miRNAs involved in asthma includes downregulated let-7 family, miR-193b, miR-375 as well as upregulated miR-21, miR-223, miR-146a, miR-142-5p, miR-142-3p, miR-146b and miR-155. Recently it has been shown that most of the involved miRNAs increase secretion of Th2 cytokines, decrease secretion of Th1 cytokines, promote differentiation of T cells towards Th2 or play a role in hyperplasia and hypertrophy of bronchial smooth muscle cells. The profiles of miRNAs correlate with clinical characteristics, including lung function, phenotype and severity of asthma.

Summary
Recent publications confirmed crucial regulatory role of miRNAs in the pathomechanism of asthma. Some single miRNAs or their sets hold the promise for their use as asthma biomarkers facilitating diagnosis or prediction of treatment outcomes. They are also possible target of future therapies. The studies in this field are lacking though.
Current opinion in otolaryngology and head and neck surgery: clival chordoma and its management
Authors: Snyderman Carl H. , Gardner Paul A. 
Published: February 2020

Purpose of review
Chordomas of the clival region are challenging tumors to treat due to their location and infiltrative behavior. The primary goal of treatment remains a gross total resection (GTR). Advances in surgical techniques, especially the adoption of endoscopic endonasal techniques, provide improved rates of surgical resection while minimizing secondary surgical morbidities.

Recent findings
Advances in the management of clival chordomas include further development of endoscopic endonasal approaches to the clivus and petroclival region, enhanced understanding of the biologic behavior of chordomas and prognostic value of molecular markers, and increased experience with newer radiation therapy modalities such as proton beam therapy.

Summary
Improved surgical techniques enhance our ability to achieve a GTR while minimizing morbidity of surgery. Molecular markers may allow stratification of patients into prognostic groups and help direct further therapy. A combination of surgery with GTR and proton beam or intensity modulated radiotherapy currently offers the best potential for cure. Therapy with new immune system modulators is promising but is reserved for clinical trials.
Evaluating the Necessity of Capsulectomy in Cases of Textured Breast Implant Replacement
Authors: Swanson Eric 
Published: February 2020

Background
Capsulectomy has traditionally been recommended as a treatment for capsular contracture after breast augmentation. With the advent of breast implant–associated anaplastic large-cell lymphoma (BIA-ALCL), and the Food and Drug Administration's decision to ban Biocell textured devices, this operation has taken on new importance. This review was undertaken to better inform clinical recommendations for women with textured devices.

Methods
An electronic search was performed using PubMed to identify all the available literature on the subject of capsulectomy and open capsulotomy (the alternative treatment).

Results
Fifty-seven articles on this topic were identified. Capsulectomy was widely recommended for treatment of capsular contracture, although many authors recommended leaving thin capsular tissue behind in the absence of symptoms. En bloc resection was recommended only for women with a diagnosis of BIA-ALCL. No information supported a prophylactic role for capsulectomy in asymptomatic women with textured breast implants who are concerned regarding their future risk of BIA-ALCL. Routine pathologic examination in asymptomatic patients was not supported.

Discussion
Capsulectomy adds substantially to the surgical risk, discomfort, recovery time, and expense. Implant removal or replacement without a simultaneous capsulectomy is atraumatic and poses negligible risk.

Conclusions
Capsulectomy introduces additional morbidity and is not mandatory for asymptomatic patients. Implant removal or exchange for smooth implants without a capsulectomy may be an acceptable choice for many women who do not demonstrate capsular pathology. However, any symptoms or surgical findings suggesting pathology warrant a capsulectomy. En bloc resections are reserved for patients diagnosed with BIA-ALCL.
Acute respiratory distress syndrome in the forward environment. Retrospective analysis of acute respiratory distress syndrome cases among French Army war casualties
Authors: Schmitt Johan , Boutonnet Mathieu , Goutorbe Philippe , Raynaud Laurent , Carfantan Cyril , Luft Antoine , Pasquier Pierre , Meaudre Eric , Bordes Julien 
Published: February 2020

BACKGROUND
According to the Joint Theater Trauma Registry, 26% to 33% of war casualties develop acute respiratory distress syndrome (ARDS), with high mortality. Here, we aimed to describe ARDS incidence and severity among patients evacuated from war zones and admitted to French intensive care units (ICUs).

METHODS
We performed an observational retrospective multicentric review of all patients evacuated from war zones and admitted to French ICUs between 2003 and 2018. Our analysis included all medical and trauma patients developing ARDS according to the Berlin definition. We evaluated ARDS incidence, and determined ARDS severity from arterial blood gas analysis. Analyzed parameters included invasive ventilation duration, ARDS treatments, ICU stay length, and 30-day and 90-day mortalities.

RESULTS
Among 141 included patients (84% military; median age, 30 years), 57 (42%) developed ARDS. Acute respiratory distress syndrome was mild in 13 (22%) patients, moderate in 24 (42%) patients, and severe in 20 (36%) patients. Evacuation occurred in less than 26 hours for 32 war casualties, 17 non–war-related trauma patients, and 8 medical patients. Among severe trauma patients, median Injury Severity Score was 34, and Abbreviated Injury Scale thorax was 3. Upon French ICU admission, median partial pressure of oxygen in arterial blood/inspirated fraction of oxygen ratio was 241 [144–296]. Administered ARDS treatments included intubation (98%, n = 56), protective ventilation (87%, n = 49), neuromuscular blockade (76%, n = 43), prone position (16%, n = 9), inhaled nitric oxide (10%, n = 6), almitrine (7%, n = 7), and extracorporeal life support (4%, n = 2). Median duration of invasive ventilation was 13 days, ICU stay was 18 days, 30-day mortality was 14%, and 90-day mortality was 21%.

CONCLUSION
Acute respiratory distress syndrome was frequent and severe among French patients evacuated from war theaters. Improved treatment capacities are needed in the forward environment—for example, a specialized US team can provide extracorporeal life support for highly hypoxemic war casualties.

LEVEL OF EVIDENCE
Prognostic and epidemiological study, level III.
The dose-dependent relationship between blood transfusions and infections after trauma: A population-based study
Authors: Nederpelt Charlie J. , El Hechi Majed , Parks Jonathan , Fawley Jason , Mendoza April E. , Saillant Noelle , King David R. , Fagenholz Peter J. , Velmahos George C. , Kaafarani Haytham M.A. 
Published: February 2020

OBJECTIVE
The relationship between total transfusion volume and infection in the trauma patient remains unclear, especially at lower volumes of transfusion. We sought to quantify the cumulative, independent impact of transfusion within 24 hours of admission on the risk of infection in trauma patients.

METHODS
Using the Trauma Quality Improvement Program 2013 to 2016 database, we included all patients who received blood transfusions in the first 4 hours. Patients who were transferred or had incomplete/wrongly coded information on transfusion volume were excluded. Patients were divided into 20 cohorts based on the total blood product volume transfused in the first 24 hours. A composite infection variable (INF) was created, including surgical site infection, ventilator-associated pneumonia, urinary tract infection, central line associated blood stream infection, and sepsis. Univariate and stepwise multivariable logistic regression analyses were performed to study the relationship between blood transfusion and INF, controlling for demographics (e.g., age, sex), comorbidities (e.g., cirrhosis, diabetes, steroid use), severity of injury (e.g., vital signs on arrival, mechanism, Injury Severity Score), and operative and angiographic interventions.

RESULTS
Of 1,002,595 patients, 37,568 were included. The mean age was 42 ± 18.6 years, 74.6% were males, 68% had blunt trauma, and median Injury Severity Score was 25 [17–34]. Adjusting for all available confounders, odds of INF increased incrementally from 1.00 (reference, 0–2 units) to 1.23 (95% confidence interval, 1.11–1.37) for 4 units transfused to 4.89 (95% confidence interval, 2.72–8.80) for 40 units transfused. Each additional unit increased the odds of INF by 7.6%.

CONCLUSION
Transfusion of the bleeding trauma patient was associated with a dose-dependent increased risk of infectious complications. Trauma surgeons and anesthesiologists should resuscitate the trauma patient until prompt hemorrhage control while avoiding overtransfusion.

LEVEL OF EVIDENCE
Retrospective cohort study, Therapeutic IV.
A comparison of adolescent penetrating trauma patients managed at pediatric versus adult trauma centers in a mature trauma system
Authors: Rogers Frederick B. , Horst Michael A. , Morgan Madison E. , Vernon Tawnya M. , Gaines Barbara A. , Rogers Amelia T. , Gross Brian W. , Cook Alan D. , Bradburn Eric H. 
Published: February 2020

BACKGROUND
While there is little debate that pediatric trauma centers (PTC) are uniquely equipped to manage pediatric trauma patients, the extent to which adolescents benefit from treatment there remains controversial. We sought to elucidate differences in management approach and outcome between PTC and adult trauma centers (ATC) for the adolescent penetrating trauma population. We hypothesized that improved mortality would be observed at ATC for this subset of patients.

METHODS
Adolescent patients (age, 15–18 years), presenting to Pennsylvania-accredited trauma centers between 2003 and 2017 with penetrating injury, were queried from the Pennsylvania Trauma Outcome Study database. Dead on arrival, transfer patients, and those admitted to a Level III or Level IV trauma center were excluded from analysis. Patient length of stay, number of complications, surgical intervention, and mortality were compared between ATC and PTC. Multilevel mixed effects logistic regression models with trauma center as the clustering variable were used to assess the impact of center type (ATC/PTC) on management approach and mortality adjusted for appropriate covariates.

RESULTS
A total of 2,630 adolescent patients met inclusion criteria (PTC: n = 428 [16.3%]; ATC: n = 2,202 [83.7%]). Pediatric trauma centers had a lower adjusted odds of mortality (adjusted odds ratio [AOR], 0.35; 95% confidence interval [CI], 0.17–0.74; p = 0.006) and a lower adjusted odds of surgery (AOR, 0.67; 95% CI, 0.0.48–0.93; p = 0.016) than their ATC counterparts. There were no differences in complication rates (AOR, 0.94; 95% CI, 0.57–1.55; p = 0.793) or length of stay longer than 4 days (AOR, 0.95; 95% CI, 0.61–1.48; p = 0.812) between the PTCs and ATCs. There were also differences in penetrating injury type between PTC and ATC.

CONCLUSION
The adolescent penetrating trauma patient population treated at PTC had less surgery performed with improved mortality compared with ATC.

LEVEL OF EVIDENCE
Therapeutic, Level IV.