bluuebunny/crossref_metadata_2025_split huggingface dataset:
Dose-Related Concentrations of Neuroactive/Psychoactive Drugs Expected in Blood of Children and Adolescents
Authors: Fekete Stefanie , Hiemke Christoph , Gerlach Manfred 
Published: August 2019

Purpose:
Therapeutic drug monitoring is highly recommended for children and adolescents treated with neurotropic/psychotropic drugs. For interpretation of therapeutic drug monitoring results, drug concentrations (C/D) expected in a “normal” population are helpful to identify pharmacokinetic abnormalities or nonadherence. Using dose-related concentration (DRC) factors obtained from pharmacokinetic data, C/D ranges expected under steady state can be easily calculated by multiplication of DRC by the daily dose. DRC factors, however, are defined only for adults so far. Therefore, it was the aim of this study to estimate DRC factors for children and adolescents and compare them with those of adults.

Methods:
To obtain pharmacokinetic data (apparent total clearance of drugs from plasma after oral administration, elimination half-life, area under the curve, and minimum serum drug concentration) from children and adolescents treated with psychotropic drugs, a systematic review of published literature was performed, and the pharmaceutical companies that market these drugs were contacted. Available information was used for the calculation of DRC factors.

Results:
Fourteen of 26 drugs had similar DRC factors to those reported for adults; 8 and 4 had higher and lower factors, respectively. The antidepressants citalopram, clomipramine, fluvoxamine, and imipramine and the antipsychotics haloperidol and olanzapine showed higher DRC factors than those calculated for adults. The DRC factors of amphetamine and methylphenidate were higher in children (6–12 years) but not in adolescents (13–17 years). On the contrary, the antipsychotic quetiapine and the mood-stabilizing antiepileptics lamotrigine, oxcarbazepine, and topiramate showed lower DRC factors than those calculated for adults.

Conclusions:
It was concluded that concentrations of neuroactive/psychoactive drugs to be expected in blood for a given dose may differ between adults and children or adolescents, most probably owing to age-dependent differences in the elimination of these drugs.
Clearing the air: adolescent smoking trends
Authors: Solecki Susan , Adegite Enitan , Turchi Renee 
Published: August 2019

Purpose of review
The purpose of this review is to highlight the emerging smoking behaviors and varied tobacco products elevating public health concerns related to the exposure of these potentially harmful substances in the adolescent population.

Recent findings
Although adolescent smoking of traditional cigarettes has declined in the last 40 years, the inhalation of other nicotine-containing products using alternative methods and devices, such as smoking electronic cigarettes, using hookahs, vaping, and JUULing are dramatically on the rise in the adolescent population. Regardless of the novel delivery devices or methods, use of nicotine-containing products in any form is hazardous and unsafe.

Summary
If adolescent smoking trends continue at the current rate in the United States, 5.6 million of today's American youth under the age of 18 will die early from a smoking-related illness. With the emerging high-risk smoking behaviors resulting in detrimental exposure to nicotine and other harmful substances available to adolescents, pediatric healthcare providers will have an increasing responsibility to screen, to manage, and to educate patients and families to combat this imminent threat to the public health of our next generation.
The ins and outs of engineering functional tissues and organs: evaluating the in-vitro and in-situ processes
Authors: Kurniawan Nicholas A. 
Published: August 2019

Purpose of reviewFor many disorders that result in loss of organ function, the only curative treatment is organ transplantation. However, this approach is severely limited by the shortage of donor organs. Tissue engineering has emerged as an alternative solution to this issue. This review discusses the concept of tissue engineering from a technical viewpoint and summarizes the state of the art as well as the current shortcomings, with the aim of identifying the key lessons that we can learn to further advance the engineering of functional tissues and organs.Recent findingsA plethora of tissue-engineering strategies have been recently developed. Notably, these strategies put different emphases on the in-vitro and in-situ processes (i.e. preimplantation and postimplantation) that take place during tissue formation. Biophysical and biomechanical interactions between the cells and the scaffold/biomaterial play a crucial role in all steps and have started to be exploited to steer tissue regeneration.SummaryRecent works have demonstrated the need to better understand the in-vitro and in-situ processes during tissue formation, in order to regenerate complex, functional organs with desired cellular organization and tissue architecture. A concerted effort from both fundamental and tissue-specific research has the potential to accelerate progress in the field.
Back Pain in Adolescents: Characteristics, Quality of Life, and Drug Self-Management
Authors: Iacovelli Chiara , Germanotta Marco , Coraci Daniele , Mosca Rita , Vincenzi Maria Teresa , Gilardi Alessandro , Padua Luca , Aprile Irene 
Published: August 2019

Objectives
Back pain is one of the major problems for the public health system in the western world. The purposes of this study were to assess back pain in a large cohort of adolescents; to evaluate the prevalence, intensity, and features; and obtain information about drug management of this symptom.

Methods
One thousand four hundred seventy-one healthy students aged 14 to 19 years were enrolled in the study. The subjects underwent a face-to-face interview using an ad hoc questionnaire, the Numeric Rating Scale, the Neuropathic Pain Symptom Inventory, and the Short-Form 36 questionnaire.

Results
Sixty-eight percent of adolescents reported moderate to severe pain, with a higher prevalence of moderate/severe pain in female. The intensity of pain was higher (P < 0.001) in females than in men. A correlation was found between pain and quality of life. Considering the adolescents with severe pain, 21.6% requested a doctor's opinion, and 18% used analgesics (63.2% of them without a doctor's prescription), with a frequency of about 2 times per month.

Conclusions
We found that the prevalence of back pain in adolescents is very high, with the consequences on quality of life, and it becomes frequently a self-managed symptom. This should encourage research on the causes of pain in order to limit the risk factors underlying the pain development and obtain a good prevention strategy.
Business Leaders' Attitudes About Value of Employee and Community Health
Authors: Heffernan Megan , Meit Michael , Powers Molly , Castrucci Brian C. , Sellers Katie 
Published: August 2019

Objective:
This study uses qualitative methodology to describe a range of business leaders' attitudes about health.

Methods:
Five Chambers of Commerce executives and 10 business leaders shared their opinions on the value they place on health in their business and the larger community.

Results:
Employee health was highlighted as a top priority among business leaders. The importance of business investment in community health more broadly was not discussed as frequently among business leaders. While attitudes may vary across industries and company sizes, many business executives recognized the direct role health plays in their business productivity and revenue. Compared with employee health, community health was not as salient to these business leaders; however, they do recognize the link between community health and economic development.

Conclusions:
Increasing business leaders' engagement in improving community health may require additional education and resources. Further research is needed to gather representative data on business leaders' attitudes about health.
Lessons Learned From Breast Implant Registries
Authors: Wurzer Paul , Hundeshagen Gabriel , Cambiaso-Daniel Janos , Fischer Sebastian , Hoflehner Helmut , Spendel Stephan , Lumenta David B. , Kamolz Lars P. , Kneser Ulrich , Hirche Christoph 
Published: August 2019

Objective
Over several decades, numerous national and international registries on breast implants went online, aiming to collect prospective data to provide increased safety for patients and surgeons. We performed a review of all published data on breast implant registries to assess availability and quality of data and determine its usefulness and impact.

Materials and Methods
PubMed, Ovid, and Web of Science were searched to identify all articles containing breast implant registries in English language. The review was registered at PROSPERO (CRD42016041255) and performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. There was no limitation by publication date.

Results
Eight hundred ninety-five articles were identified; after removal of duplicates, 536 abstracts were screened on breast implant registries in plastic and reconstructive surgery. Unrelated articles, non-English articles, and not breast implant–related studies were excluded. Twenty breast implant registry–related articles met the inclusion criteria; 7 articles contained actual data on breast implants. Compared with international trends, only a minimal percentage of performed surgical breast augmentations is documented in registries, and the overall data quality and availability were low.

Conclusions
Only a fraction of performed breast augmentations is documented properly in a registry. Currently, there are no published data based on a clinical quality registry. Sustained funding and reliable administrative governmental structures remain crucial to establish an adequate clinical quality registry for breast implants as currently launched in Australia to analyze outcomes and risk factors for an increased patient safety.
Antithrombin III Contributes to the Protective Effects of Fresh Frozen Plasma Following Hemorrhagic Shock by Preventing Syndecan-1 Shedding and Endothelial Barrier Disruption
Authors: Lopez Ernesto , Peng Zhanglong , Kozar Rosemary A. , Cao Yanna , Ko Tien C. , Wade Charles E. , Cardenas Jessica C. 
Published: August 2019

ABSTRACT

Background:
Endothelial dysfunction during hemorrhagic shock (HS) is associated with loss of cell-associated syndecan-1 (Sdc1) and hyperpermeability. Fresh frozen plasma (FFP) preserves Sdc1 and reduces permeability following HS, although the key mediators remain unknown. Antithrombin III (ATIII) is a plasma protein with potent anti-inflammatory and endothelial protective activity. We hypothesized that the protective effects of FFP on endothelial Sdc1 and permeability are mediated, in part, through ATIII.

Methods:
ATIII and Sdc1 were measured in severely injured patients upon admission (N = 125) and hospital day 3 (N = 90) for correlation analysis. In vitro effects of ATIII on human lung microvascular endothelial cells (HLMVECs) were determined by pretreating cells with vehicle, FFP, ATIII-deficient FFP, or purified ATIII followed by TNFα stimulation. Sdc1 expression was measured by immunostaining and permeability by electrical impedance. To determine the role of ATIII in vivo, male mice were subjected to a fixed pressure exsanguination model of HS, followed by resuscitation with FFP, ATIII-deficient FFP, or ATIII-deficient FFP with ATIII repletion. Lung Sdc1 expression was assessed by immunostaining.

Results:
Pearson correlation analysis showed a significant negative correlation between plasma levels of Sdc1 and ATIII (R = −0.62; P < 0.0001) in injured patients on hospital day 3. Also, in vitro, FFP and ATIII prevented TNFα-induced permeability (P < 0.05 vs TNFα) in HLMVECs. ATIII-deficient FFP had no effect; however, ATIII restoration reestablished its protective effects in a dose-dependent manner. Similarly, FFP and ATIII prevented TNFα-induced Sdc1 shedding in HLMVECs; however, ATIII-deficient FFP did not. In mice, Sdc1 expression was increased following FFP resuscitation (1.7 ± 0.5, P < 0.01) vs. HS alone (1.0 ± 0.3); however, no improvement was seen following ATIII-deficient FFP treatment (1.3 ± 0.4, P = 0.3). ATIII restoration improved Sdc1 expression (1.5 ± 0.9, P < 0.05) similar to that of FFP resuscitation.

Conclusions:
ATIII plays a role in FFP-mediated protection of endothelial Sdc1 expression and barrier function, making it a potential therapeutic target to mitigate HS-induced endothelial dysfunction. Further studies are needed to elucidate the mechanisms by which ATIII protects the endothelium.
Predictive survival factors of the traumatically injured on venovenous extracorporeal membrane oxygenation: A Bayesian model
Authors: Huang James E. , Holland Seth R. , Patrick Joshua , Piper Lydia C. , Sams Valerie G. 
Published: August 2019

BACKGROUND
Venovenous extracorporeal membrane oxygenation (ECMO) has had encouraging evidence suggesting efficacy and acceptable safety in trauma patients with refractory respiratory failure. Given the obstacles of accruing adequate quality prospective data for a resource-intensive modality, it is unclear what is indicative of survival to discharge. We investigate pre-ECMO characteristics (age, Injury Severity Score [ISS], time from admission to cannulation, P:F ratio) in trauma patients to determine correlation with survival.

METHODS
To address these challenges, we use Bayesian inference and patients from a level I trauma center and Extracorporeal Life Support Organization–designated Gold Center of Excellence (N = 12), published literature, and Markov chain Monte Carlo simulation to determine if there is strong predictive probability regarding survival to discharge.

RESULTS
Bayesian inference probabilities expressed as odds ratios with 95% credible intervals (CrIs) were as follows: age (e
βage = 0.981; CrI, 0.976–0.985), ISS (e
βISS = 0.996; CrI, 0.980–1.012), P:F ratio (e
βpf = 1.000; CrI, 0.996–1.003), and time from admission to ECMO (e
βtime = 0.988; CrI, 0.974–1.004). Bayes factors (BF) were as follows: BFage = 3.151, BFISS = 3.564 × 1013, BFpf = 0.463, and BFtime = 913.758.

CONCLUSION
Age was the only pre-ECMO factor that demonstrated the most certain effect on hospital mortality for trauma patients placed on venovenous ECMO. The ISS and time to ECMO initiation had some appreciable impact on survival although less certain than age; P:F ratio likely had none. However, the pre-ECMO factors that were found to have any impact on mortality were relatively diminutive. More studies are necessary to update prior distributions and enhance accuracy.

LEVEL OF EVIDENCE
Prognostic, Level IV.
Disproportionally low funding for trauma research by the National Institutes of Health: A call for a National Institute of Trauma
Authors: Glass Nina E. , Riccardi Julia , Farber Nicole I. , Bonne Stephanie L. , Livingston David H. 
Published: August 2019

BACKGROUND
Trauma is a major cause of death and disability in all ages. Previous reviews have suggested that National Institutes of Health (NIH) funding for trauma is not commensurate with its burden of disease, but a detailed analysis has been lacking. We postulated that NIH spending on trauma research was lower than previously thought and was distributed widely, preventing a comprehensive research strategy that could decrease trauma morbidity and mortality.

METHODS
The NIH Research Portfolio Online Reporting Tool was initially screened using a search of over 20 terms including “trauma,” “injury,” “shock,” “MVC,” and excluding clearly unrelated conditions, for example, “cancer.” The details of all grants that screened positive underwent manual review to identify true trauma-related grants. An expert panel was used to adjudicate any ambiguity.

RESULTS
In FY2016, NIH awarded 50,137 grants, of which 6,401 (13%) were captured by our initial screen. Following review, 1,888 (28%) were identified as trauma-related; 3.7% of all NIH grants. These grants (US $720 million) represent only 2.9% of the NIH extramural budget. In addition, the grants were funded and administered by 24 of the institutes and centers across the NIH ranging from 0.01% (National Cancer Institute) to 11% (National Institute of Neurological Disorders and Stroke and National Institute of Arthritis and Musculoskeletal and Skin Diseases) of their extramural portfolios.

CONCLUSION
Given the extreme burden of trauma-related disability and years of life lost, this review of extramural NIH funding definitively demonstrates that trauma is severely underfunded. The lack of a dedicated home for trauma research at NIH leads to a diffusion of grants across many institutes and makes it impossible to direct a focused and effective national research endeavor to improve outcomes. These data demonstrate the need for a National Institute of Trauma at the NIH to help set an agenda to reach the national goal of Zero Preventable Deaths.
Location, location, location: Utilizing Needs-Based Assessment of Trauma Systems-2 in trauma system planning
Authors: Dooley Jennings H. , Ozdenerol Esra , Sharpe John P. , Magnotti Louis J. , Croce Martin A. , Fischer Peter E. 
Published: August 2019

BACKGROUND
In 2015, the American College of Surgeons Committee on Trauma introduced the Needs-Based Assessment of Trauma Systems (NBATS) tool to quantify the optimal number of trauma centers for a region. While useful, more focus was required on injury population, distribution, and transportation systems. Therefore, NBATS-2 was developed utilizing advanced geographical modeling. The purpose of this study was to evaluate NBATS-2 in a large regional trauma system.

METHODS
Data from all injured patients from 2016 to 2017 with an Injury Severity Score greater than 15 was collected from the trauma registry of the existing (legacy) center. Injury location and demographics were analyzed by zip code. A regional map was built using US census data to include hospital and population demographic data by zip code. Spatial modeling was conducted using ArcGIS to estimate an area within a 45-minute drive to a trauma center.

RESULTS
A total of 1,795 severely injured patients were identified across 54 counties in the tri-state region. Forty-eight percent of the population and 58% of the injuries were within a 45-minute drive of the legacy trauma center. With the addition of another urban center, injured and total population coverage increased by only 1% while decreasing the volume to the existing center by 40%. However, the addition of two rural trauma centers increased coverage significantly to 62% of the population and 71% of the injured (p < 0.001). The volume of the legacy center was decreased by 25%, but the self-pay rate increased by 16%.

CONCLUSION
The geospatial modeling of NBATS-2 adds a new dimension to trauma system planning. This study demonstrates how geospatial modeling applied in a practical tool can be incorporated into trauma system planning at the local level and used to assess changes in population and injury coverage within a region, as well as potential volume and financial implications to a current system.

LEVEL OF EVIDENCE
Care management/economic, level V.
Comparison of the causes of death and wounding patterns in urban firearm-related violence and civilian public mass shooting events
Authors: Maghami Sam , Hendrix Cheralyn , Matecki Mary , Mahendran Karthika , Amdur Richard , Mitchell Roger , Diaz Francisco , Estroff Jordan , Smith E. Reed , Shapiro Geoff , Sarani Babak 
Published: August 2019

BACKGROUND
There are no reports comparing wounding pattern in urban and public mass shooting events (CPMS). Because CPMS receive greater media coverage, there is a connation that the nature of wounding is more grave than daily urban gun violence. We hypothesize that the mechanism of death following urban gunshot wounds (GSWs) is the same as has been reported following CPMS.

METHODS
Autopsy reports of all firearm-related deaths in Washington, DC were reviewed from January 1, 2016, to December 31, 2017. Demographic data, firearm type, number and anatomic location of GSWs, and organ(s) injured were abstracted. The organ injury resulting in death was noted. The results were compared with a previously published study of 19 CPMS events involving 213 victims.

RESULTS
One hundred eighty-six urban autopsy reports were reviewed. There were 171 (92%) homicides and 13 (7%) suicides. Handguns were implicated in 180 (97%) events. One hundred eight (59%) gunshots were to the chest/upper back, 85 (46%) to the head, 77 (42%) to an extremity, and 71 (38%) to the abdomen/lower back. The leading mechanisms of death in both urban firearm violence and CPMS were injury to the brain, lung parenchyma, and heart. Fatal brain injury was more common in CPMS events as compared with urban events involving a handgun.

CONCLUSION
There is little difference in wounding pattern between urban and CPMS firearm events. Based on the organs injured, rapid point of wounding care and transport to a trauma center remain the best options for mitigating death following all GSW events.

LEVEL OF EVIDENCE
Epidemiological, level IV.
Repertoire of morphable proteins in an organism
Authors: Izumi Keisuke , Saho Eitaro , Kutomi Ayuka , Tomoike Fumiaki , Okada Tetsuji 
Published: August 2019

AbstractAll living organisms have evolved to contain a set of proteins with variable physical and chemical properties. Efforts in the field of structural biology have contributed to uncovering the shape and the variability of each component. A set of experimental coordinates for a given protein can be used to define the “morphness/unmorphness”. Here we show the results of global analysis of more than a thousand E. coli proteins, demonstrating that it would be a comprehensive method of understanding the evolved repertoire in an organism. By collecting “UnMorphness Factor” (UMF) determined for each of the proteins, the lowest and the highest boundaries of the experimentally observable structural variation are understood. The distribution of UMFs obtained for an organism is expected to represent how rigid and flexible components are balanced. The present analysis extends to evaluate the growing data from single particle cryo-electron microscopy, providing valuable information on effective interpretation to structural changes of proteins and the supramolecular complexes. The data and the method presented here also conform to FAIR data principles, having potential significance to advance the field of structural and molecular cell biology.