bluuebunny/crossref_metadata_2025 huggingface dataset:
Highly sensitive and multiplexed quantification of mRNA splice variants by the direct ligation of DNA probes at the exon junction and universal PCR amplification
Authors: Wang Honghong , Wang Hui , Duan Xinrui , Sun Yuanyuan , Wang Xiangdong , Li Zhengping
Published: March 2017

A highly sensitive and specific assay for detecting mRNA splice variants is developed based on ligation-dependent PCR.
Hydrodeoxygenation of isocyanates: snapshots of a magnesium-mediated CO bond cleavage
Authors: Yang Yan , Anker Mathew D. , Fang Jian , Mahon Mary F. , Maron Laurent , Weetman Catherine , Hill Michael S.
Published: March 2017

Organic isocyanates are readily converted to methyl amine products through their hydroboration with HBpin in the presence of a β-diketiminato magnesium catalyst.
Semiconducting polymer dots with bright narrow-band emission at 800 nm for biological applications
Authors: Chen Dandan , Wu I-Che , Liu Zhihe , Tang Ying , Chen Haobin , Yu Jiangbo , Wu Changfeng , Chiu Daniel T.
Published: March 2017

A semiconducting polymer with bright and narrow-band emission at 800 nm was synthesized and used for biological imaging applications.
BODIPY-containing nanoscale metal–organic frameworks as contrast agents for computed tomography
Authors: Zhang Tao , Wang Lei , Ma Chong , Wang Weiqi , Ding Jun , Liu Shi , Zhang Xuewen , Xie Zhigang
Published: March 2017

A new computed tomography (CT) imaging agent is developed based on the BODIPY-containing nanoscale metal–organic frameworks (NMOFs). The bio-safety and CT imaging of such NMOFs have been well investigated both in vitro and in vivo.
Protein kinase C β inhibits autophagy and sensitizes cervical cancer Hela cells to cisplatin
Authors: Li Na , Zhang Wei
Published: March 2017

Recently, autophagy has been indicated to play an essential role in various biological events, such as the response of cervical cancer cells to chemotherapy. However, the exact signalling mechanism that regulates autophagy during chemotherapy remains unclear. In the present study, we investigated the regulation by cisplatin on protein kinase C β (PKC β), on B-cell lymphoma 2 (Bcl-2) and on apoptosis in cervical cancer Hela cells. And then we examined the regulation by cisplatin on autophagy and the role of autophagy on the chemotherapy in Hela cells. In addition, the regulation of the PKC β on the autophagy was also investigated. Our results indicated that cisplatin promoted PKC β in Hela cells. The PKC β inhibitor reduced the cisplatin-induced apoptosis, whereas increased the cisplatin-induced autophagy in Hela cells. On the other side, the PKC β overexpression aggravated the cisplatin-induced apoptosis, whereas down-regulated the cisplatin-induced autophagy. Taken together, our study firstly recognized the involvement of PKC β in the cytotoxicity of cisplatin via inhibiting autophagy in cervical cancer cells. We propose that PKC β would sensitize cervical cancer cells to chemotherapy via reducing the chemotherapy induced autophagy in cancer cells.
The effect of cortisol in rat steatotic and non-steatotic liver transplantation from brain-dead donors
Authors: Jiménez-Castro Mónica B. , Negrete-Sánchez Elsa , Casillas-Ramírez Araní , Gulfo Jose , Álvarez-Mercado Ana I. , Cornide-Petronio María Eugenia , Gracia-Sancho Jordi , Rodés Juan , Peralta Carmen
Published: March 2017

In the present study, we examined the effects of cortisol on steatotic and non-steatotic liver grafts from brain-dead donors and characterized the underlying mechanisms involved. Non-steatotic liver grafts showed reduced cortisol and increased cortisone levels in association with up-regulation of enzymes that inactivate cortisol. Conversely, steatotic liver grafts exhibited increased cortisol and reduced cortisone levels. The enzymes involved in cortisol generation were overexpressed, and those involved in cortisol inactivation or clearance were down-regulated in steatotic liver grafts. Exogenous administration of cortisol negatively affected hepatic damage and survival rate in non-steatotic liver transplantation (LT); however, cortisol treatment up-regulated the phosphoinositide 3-kinase (PI3K)–protein kinase C (PKC) pathway, resulting in protection against the deleterious effects of brain-dead donors on damage and inflammatory response in steatotic LT as well as in increased survival of recipients. The present study highlights the differences in the role of cortisol and hepatic mechanisms that regulate cortisol levels based on the type of liver. Our findings suggest that cortisol treatment is a feasible and highly protective strategy to reduce the adverse effects of brain-dead donor livers in order to ultimately improve liver graft quality in the presence of steatosis, whereas cortisol treatment would not be recommended for non-steatotic liver grafts.
Recent Innovations in Voice Assessment Expected to Impact the Clinical Management of Voice Disorders
Authors: Van Stan Jarrad H. , Mehta Daryush D. , Hillman Robert E.
Published: March 2017

This article provides a summary of some recent innovations in voice assessment expected to have an impact in the next 5–10 years on how patients with voice disorders are clinically managed by speech-language pathologists. Specific innovations discussed are in the areas of laryngeal imaging, ambulatory voice monitoring, and “big data” analysis using machine learning to produce new metrics for vocal health. Also discussed is the potential for using voice analysis to detect and monitor other health conditions.
Assessment of positioning accuracy of vehicle trajectories for different road applications
Authors: Clausen Philipp , Gilliéron Pierre‐Yves , Perakis Harris , Gikas V. , Spyropoulou Ioanna
Published: March 2017

Global navigation satellite systems (GNSS) has become a kind of positioning standard due to the high penetration rate of this technology on mass market intelligent transportation systems (ITS) applications. However, this positioning technique remains a real challenge for very demanding ITS services which require continuity and a specific accuracy of the data. This study reports on a practical and methodological approach for the evaluation of the GNSS and multi‐sensors positioning and attitude of vehicles in real life conditions. Test scenarios have been set up with several positioning sensors mounted on a vehicle for the collection of raw data on different road sections. The measurement of a high quality reference trajectory with an accuracy of several centimetres allows to estimate position accuracy under different environmental conditions. The authors will show in detail the results and identify some typical situations (e.g. sub‐urban environment) where the quality of positioning parameters is reduced to several metres instead of dm and may impact the level of ITS services, e.g. road user charging or safety applications. This study results from the methodology developed in the satellite positioning performance assessment for road applications COST Action on the performance assessment of positioning terminals for ITS.
Properties and physical interpretation of the dynamic interactions between voltage source converters and grid: electrical oscillation and its stability control
Authors: Zhang Chen , Cai Xu , Li Zheng , Rygg Atle , Molinas Marta
Published: March 2017

Voltage source converters (VSCs) play an important role in the power conversion of renewable power generation (RPG) systems. Conventional power systems are considerably affected by power electronic devices in systems with a high percentage of RPG. Various abnormal interactions in the form of oscillations between VSCs and grid have been reported, whereas the mechanism at the core is still lacking understanding. In this study, the properties of interactions between the VSC and grid are investigated, and through an analytical model the mechanisms of electrical oscillations are revealed. First, a simple resistance–inductance–capacitance (RLC) equivalent to the small‐signal model of VSC–grid system was derived based on the knowledge of virtual passive element effects of VSC. Then, an intrinsic oscillatory point in the RLC circuit was identified, the damping characteristics of the current controller and phase‐locked‐loop (PLL) at this point were analysed. Subsequently, a critical stability criterion for the determination of PLL bandwidth that may trigger oscillations was established. For the improvement of the overall damping, a VSC stabiliser was proposed. Finally, the mechanism analysis and analytical criteria were verified by time‐domain simulations in PSCAD/EMTDC.
Design of electrode configuration for in vitro experiments of epiretinal electrical stimulation of retinal ganglion cells
Authors: Biswas Satarupa , Das Soumen , Mahadevappa Manjunatha
Published: March 2017

Progress in epiretinal prostheses needs attention towards the electrode tissue interface. A simulation study prior to biological evaluation can give an assessment of the spatial distribution of electrical and thermal parameters throughout the retinal tissue. The aim was to configure an electrode array that can elicit focal response in the tissue keeping charge density and heat produced within safety limits to avoid tissue damage. The AC/DC module and bioheat module of COMSOL Multiphysics 4.4 were used to numerically model the electrode tissue interface with different electrode size ranging from 10 to 500µm and configurations that are the best suit for in vitro experimental applications. Parameters like electric field, current density, potential, heat flux and temperature were evaluated. Electrodes having diameters 50–200µm produce steady and reproducible results with charge density and heat produced within safe limits. The configuration with a centre stimulating and surrounding alternating ground and recording electrodes arranged hexagonally could produce a focal response. The design of a multielectrode array is proposed which acts as a stimulator as well as a sensor for neural responses from isolated animal retina.
Pflegepersonalbesetzung: Deutschland hinkt international hinterher
Authors: Doelfs Guntram
Published: March 2017

Viele Pflegekräfte in deutschen Kliniken arbeiten wegen zu hoher Arbeitsbelastung am Limit. Seit Jahren läuft deshalb eine erbitterte Debatte um eine gesetzlich vorgegebene Personalquote für den Pflegedienst. Dabei zeigen laut einer neuen Studie internationale Beispiele, dass gesetzlich verbindliche Personalschlüssel für Pflegekräfte die Arbeitsüberlastung verringern und die Qualität der Pflege verbessern können.
Ernährungsberatung: Von wegen „nicht erlösrelevant“
Authors: Gaede Kirsten
Published: March 2017

Rund 20 bis 60 Prozent aller Patient sind – je nach Definition der Mangelernährung – bei ihrer Aufnahme ins Krankenhaus kachektisch. Trotzdem spielt die Ernährung im Klinikbetrieb kaum eine Rolle. Das Unternehmen Medilog möchte dies mit einem speziellen Angebot für Krankenhäuser ändern.
Qualitätsberichte: Ungeliebt und unverstanden
Authors: Rössing Sabine
Published: March 2017

Die Qualitätsberichte der Krankenhäuser sind zu sperrigen Konvoluten verkommen. Mit einer Korrektur seiner Vorgaben lässt der G-BA sich Zeit.
Hygienische Trinkwasserversorgung: Wasser ist wichtig
Authors: Thalmayr Maria
Published: March 2017

Um Hygieneprobleme in Trinkwasserinstallationen von vornherein zu vermeiden, wird sich die Bauphilosophie des Gesundheitswesens in mancherlei Hinsicht ändern müssen. Vor allem aber muss das Thema Trinkwasserversorgung endlich die Wichtigkeit erfahren, die es tatsächlich hat – schon bei der Planung.
Where are they?
Authors: Livio Mario , Silk Joseph
Published: March 2017

The search for extraterrestrial life is increasingly informed by our knowledge of exoplanets. Within three decades, we may know whether extrasolar life is rare.
Evaluation of SmartFlare probe applicability for verification of RNAs in early equine conceptuses, equine dermal fibroblast cells and trophoblastic vesicles
Authors: Budik S. , Tschulenk W. , Kummer S. , Walter I. , Aurich C.
Published: March 2017

Live cell RNA imaging has become an important tool for studying RNA localisation, dynamics and regulation in cultured cells. Limited information is available using these methods in more complex biological systems, such as conceptuses at different developmental stages. So far most of the approaches rely on microinjection of synthetic constructs into oocytes during or before fertilisation. Recently, a new generation of RNA-specific probes has been developed, the so named SmartFlare probes (Merck Millipore). These consist of a central 15-nm gold particle with target-specific DNAs immobilised on its surface. Because of their central gold particle, SmartFlare probes are detectable by transmission electron microscopy. The aim of the present study was to investigate the uptake and distribution of SmartFlare probes in equine conceptuses at developmental stages suitable for embryo transfer (Days 6–10), equine trophoblast vesicles and equine dermal fibroblast cell cultures, and to determine whether differences among these cell types and structures exist. Probe uptake was followed by transmission electron microscopy and fluorescence microscopy. Although the embryonic zona pellucida did not reduce uptake of the probe, the acellular capsule fully inhibited probe internalisation. Nanogold particles were taken up by endocytosis by all cell types examined in a similar manner with regard to time and intracellular migration. They were processed in endosomal compartments and accumulated within lysosomal structures after longer incubation times. In conclusion, the SmartFlare probe is applicable in equine conceptuses, but its use is limited to the developmental stages before the formation of the embryonic capsule.
Life-history characteristics of the yakka skink, Egernia rugosa, indicate long-term social structure
Authors: Peck Stephen , Gardner Michael G. , Seddon Jennifer M. , Baxter Greg
Published: March 2017

One lineage of squamates, the Egernia group, has received particular study due to stable aggregations identified in many of the species. Egernia rugosa is a large, terrestrial, viviparous skink and has been reported living communally. To investigate whether this species lives in social aggregations, we examined life-history characteristics in one population within the Mulga Lands bioregion of south-west Queensland. We found this skink used both active and inactive rabbit burrows. Parturition occurred in January/February and took several days to complete, with a mean litter size of 2.4 and a mean snout–vent length (SVL) of 84.5 mm. Six subadult age cohorts were identified. Juveniles took at least five years to reach sexual maturity and lizards had a life expectancy of >12 years. Lizards were found clustered in aggregations of up to 21 individuals (mean = 7.21) of multiple ages. An average of 50% (range = 31–67%) of all individuals within each of the age cohorts were located at their original location for two or more seasons. Dispersal was recorded for older subadult lizards. These characteristics support the hypothesis that E. rugosa aggregations comprise long-term family units; however, genetic analysis would be needed to confirm kin-based associations.
Permeation of macromolecules into the renal glomerular basement membrane and capture by the tubules
Authors: Lawrence Marlon G. , Altenburg Michael K. , Sanford Ryan , Willett Julian D. , Bleasdale Benjamin , Ballou Byron , Wilder Jennifer , Li Feng , Miner Jeffrey H. , Berg Ulla B. , Smithies Oliver
Published: March 2017

Significance

Human kidneys contain ∼2 x 10
6
glomeruli that produce ∼180 L per day of primary filtrate. Downstream tubules reabsorb most of the water, salt, and desirable low-molecular weight substances, leaving 1 to 2 L per day of urine containing undesirable waste products. Currently, most investigators think that the primary filtrate is low in protein because fluid exiting the glomerulus passes through slits spanned by a diaphragm that acts as a low-porosity molecular sieve. Our experiments challenge this view; they show that size-dependent permeation into the glomerular basement membrane and into a gel-like coat that covers the slits, together with saturable tubular reabsorption, determines which macromolecules reach the urine. The slit diaphragm is essential for capillary structure but may not directly determine glomerular size selectivity.
Disaster management curricula: strategy to create doctors with disaster resilience in Aceh, Indonesia
Authors: Wahyuniati N , Maulana R , Ichsan I
Published: March 2017

Faculty of Medicine of Syiah Kuala University has one special block called Disaster Management block (the last block on the curricula) on Competency-Based Curriculum of Medical Sciences with the Problem-Based Learning method. This block has four credits, allocated seven weeks learning period including one week for evaluation. The placement of disaster management block in the 7th semester (last semester) aims to allow students to implement more easily the complete basic and clinical medical knowledge and then have it integrated with the management capabilities during adisaster. This article evaluates two components: 1) Disaster management module, by comparing the content of modules used in three different academic years, the academic year 2013/2014, 2014/2015 and 2015/2016, 2) The final grade, by comparing the final grade of disaster management block in 4 years (comparing students class of 2008, 2009, 2010 and 2011). The results revealed that on every academic year there were additions and strengthening of the material to ensure that students achieve a complete learning experience, and there was a slight increase in student’s grades where the number of students who receive grades A has increased while the number of students who receive grades E decreased.
An analytic method for bounding 𝜓(𝑥)
Authors: Büthe Jan
Published: March 2017

In this paper we present an analytic algorithm which calculates almost sharp bounds for the normalized remainder term

(
t
−
ψ
(
t
)
)

/

t

(t-\psi (t))/\sqrt t

for

t
≤
x

t\leq x

in expected run time

O
(

x

1

/

2
+
ε

)

O(x^{1/2+\varepsilon })

for every

ε
>
0

\varepsilon >0

. The method has been implemented and used to calculate such bounds for

t
≤

10

19

t\leq 10^{19}

. In particular, these imply that

l
i
(
x
)
−
π
(
x
)

li(x)-\pi (x)

is positive for

2
≤
x
≤

10

19

2\leq x\leq 10^{19}

.
AQUA-DUCT: a ligands tracking tool
Authors: Magdziarz Tomasz , Mitusińska Karolina , Gołdowska Sandra , Płuciennik Alicja , Stolarczyk Michał , Ługowska Magdalena , Góra Artur
Published: March 2017

Motivation

The identification and tracking of molecules which enter active site cavity requires screening the positions of thousands of single molecules along several thousand molecular dynamic steps. To fill the existing gap between tools searching for tunnels and pathways and advanced tools employed for accelerated water flux investigations, we have developed AQUA-DUCT.

Results

AQUA-DUCT is an easy-to-use tool that facilitates analysis of the behaviour of molecules that penetrate any selected region in a protein. It can be used for any type of molecules, e.g. water, oxygen, carbon dioxide, organic solvents, ions.

Availability and Implementation

Linux, Windows, macOS, OpenBSD, http://www.aquaduct.pl.

Supplementary information

Supplementary data are available at Bioinformatics online.
Cost effectiveness of cascade testing for familial hypercholesterolaemia, based on data from familial hypercholesterolaemia services in the UK
Authors: Kerr Marion , Pears Robert , Miedzybrodzka Zofia , Haralambos Kate , Cather Moyra , Watson Melanie , Humphries Steve E.
Published: March 2017

Aims

Familial hypercholesterolaemia (FH) is a vastly under-diagnosed genetic disorder, associated with early development of coronary heart disease and premature mortality which can be substantially reduced by effective treatment. Patents have recently expired on high-intensity statins, reducing FH treatment costs. We build a model using UK data to estimate the cost effectiveness of DNA testing of relatives of those with monogenic FH.

Methods and Results

A Markov model was used to estimate the cost effectiveness of cascade testing, using data from UK cascade services. The estimated incremental cost effectiveness ratio (ICER) was £5806 and the net marginal lifetime cost per relative tested was £2781. More than 80% of lifetime costs were diagnosis-related and incurred in the 1st year. In UK services, 23% of 6396 index cases were mutation-positive. For each mutation-positive index case, 1.33 relatives were tested, resulting overall in a rate of 0.31 tested relatives per tested index case. If the number of relatives tested per tested index case rose to 3.2 (projected by National Institute for Health and Care Excellence in 2008) the ICER would reduce to £2280 and lifetime costs to £1092.

Conclusion

Cascade testing of relatives of those with suspected FH is highly cost effective. The current Europe-wide high levels of undiagnosed FH, and associated morbidity and mortality, mean adoption of cascade services should yield substantial quality of life and survival gains.
Minimally Invasive Transforaminal Lumbar Interbody Fusion: Meta-analysis of the Fusion Rates. What is the Optimal Graft Material?
Authors: Parajón Avelino , Alimi Marjan , Navarro-Ramirez Rodrigo , Christos Paul , Torres-Campa Jose M , Moriguchi Yu , Lang Gernot , Härtl Roger
Published: March 2017

BACKGROUND

Minimally invasive transforaminal lumbar interbody fusion (MIS-TLIF) is an increasingly popular procedure with several potential advantages over traditional open TLIF.

OBJECTIVE

The current study aimed to compare fusion rates of different graft materials used in MIS-TLIF, via meta-analysis of the published literature.

METHODS

A Medline search was performed and a database was created including patient's type of graft, clinical outcome, fusion rate, fusion assessment modality, and duration of follow-up. Meta-analysis of the fusion rate was performed using StatsDirect software (StatsDirect Ltd, Cheshire, United Kingdom).

RESULTS

A total of 1533 patients from 40 series were included. Fusion rates were high, ranging from 91.8% to 99%. The imaging modalities used to assess fusion were computed tomography scans (30%) and X-rays (70%). Comparison of all recombinant human bone morphogenetic protein (rhBMP) series with all non-rhBMP series showed fusion rates of 96.6% and 92.5%, respectively. The lowest fusion rate was seen with isolated use of autologous local bone (91.8%). The highest fusion rate was observed with combination of autologous local bone with bone extender and rhBMP (99.1%). The highest fusion rate without the use of BMP was seen with autologous local bone + bone extender (93.1%). The reported complication rate ranged from 0% to 35.71%. Clinical improvement was observed in all studies.

CONCLUSION

Fusion rates are generally high with MIS-TLIF regardless of the graft material used. Given the potential complications of iliac bone harvesting and rhBMP, use of other bone graft options for MIS-TLIF is reasonable. The highest fusion rate without the use of rhBMP was seen with autologous local bone plus bone extender (93.1%).
Streptobacillus moniliformis Bacteremia in a Pet Shop Employee: Case Report and Literature Review
Authors: Suzuki Kiyozumi , Hirai Yuji , Morita Fujiko , Nakamura Ayako , Uehara Yuki , Naito Toshio
Published: March 2017

A 39-year-old pet shop employee who sustained a bite from one of his store’s rats developed fever and arthritis. Streptobacillus moniliformis was cultured from the patient’s blood, confirming a diagnosis of rat-bite fever. Treatment with standard antibiotics was successful. Although rat-bite fever is commonly considered a zoonosis transmitted by wild or laboratory rats, our case emphasizes that it may be transmitted by pet animals as well.
Pulmonary Histoplasma Infection After Allogeneic Hematopoietic Stem Cell Transplantation: Case Report and Review of the Literature
Authors: Natarajan Mukil , Swierzbinski Matthew J. , Maxwell Sandra , Zelazny Adrian M. , Fahle Gary A. , Quezado Martha , Barrett John , Battiwalla Minoo , Lionakis Michail S.
Published: March 2017

Histoplasmosis causes a wide spectrum of clinical illness, including disseminated infection in the immunocompromised. We report a case of pulmonary histoplasmosis in an allogeneic stem cell transplant recipient and review the literature on this topic. Histoplasmosis in this patient population is uncommon, but it is associated with poor outcome.
Expanding Local Cancer Clinical Trial Options: Analysis of the Economic Impact of the Midwest Cancer Alliance in Kansas
Authors: Gafford J. Atlee , Gurley-Calvez Tami , Krebill Hope , Lai Sue Min , Christiadi  , Doolittle Gary C.
Published: March 2017

Purpose

Patients benefit from receiving cancer treatment closer to home when possible and at high-volume regional centers when specialized care is required. The purpose of this analysis was to estimate the economic impact of retaining more patients in-state for cancer clinical trials and care, which might offset some of the costs of establishing broader cancer trial and treatment networks.

Method

Kansas Cancer Registry data were used to estimate the number of patients retained in-state for cancer care following the expansion of local cancer clinical trial options through the Midwest Cancer Alliance based at the University of Kansas Medical Center. The 2014 economic impact of this enhanced local clinical trial network was estimated in four parts: Medical spending was estimated on the basis of National Cancer Institute cost-of-care estimates. Household travel cost savings were estimated as the difference between in-state and out-of-state travel costs. Trial-related grant income was calculated from administrative records. Indirect and induced economic benefits to the state were estimated using an economic impact model.

Results

The authors estimated that the enhanced local cancer clinical trial network resulted in approximately $6.9 million in additional economic activity in the state in 2014, or $362,000 per patient retained in-state. This estimate includes $3.6 million in direct spending and $3.3 million in indirect economic activity. The enhanced trial network also resulted in 45 additional jobs.

Conclusions

Retaining patients in-state for cancer care and clinical trial participation allows patients to remain closer to home for care and enhances the state economy.
Graduates’ Perceptions of Learning Affordances in Longitudinal Integrated Clerkships: A Dual-Institution, Mixed-Methods Study
Authors: Latessa Robyn A. , Swendiman Robert A. , Parlier Anna Beth , Galvin Shelley L. , Hirsh David A.
Published: March 2017

Purpose

The authors explored affordances that contribute to participants’ successful learning in longitudinal integrated clerkships (LICs).

Method

This dual-institutional, mixed-methods study included electronic surveys and semistructured interviews of LIC graduates who completed their core clinical (third) year of medical school. These LIC graduates took part in LICs at Harvard Medical School from 2004 to 2013 and the University of North Carolina School of Medicine–Asheville campus from 2009 to 2013. The survey questions asked LIC graduates to rate components of LICs that they perceived as contributing to successful learning. A research assistant interviewed a subset of study participants about their learning experiences. The authors analyzed aggregate data quantitatively and performed a qualitative content analysis on interview data.

Results

The graduates reported multiple affordances that they perceive contributed to successful learning in their LIC. The most reported components included continuity and relationships with preceptors, patients, place, and peers, along with integration of and flexibility within the curriculum.

Conclusions

As LIC models grow in size and number, and their structures and processes evolve, learners’ perceptions of affordances may guide curriculum planning. Further research is needed to investigate to what degree and by what means these affordances support learning in LICs and other models of clinical education.
Nebulization of Antiinfective Agents in Invasively Mechanically Ventilated Adults
Authors: Solé-Lleonart Candela , Rouby Jean-Jacques , Blot Stijn , Poulakou Garyfallia , Chastre Jean , Palmer Lucy B. , Bassetti Matteo , Luyt Charles-Edouard , Pereira Jose M. , Riera Jordi , Felton Tim , Dhanani Jayesh , Welte Tobias , Garcia-Alamino Jose M. , Roberts Jason A. , Rello Jordi
Published: March 2017

Background

Nebulization of antiinfective agents is a common but unstandardized practice in critically ill patients.

Methods

A systematic review of 1,435 studies was performed in adults receiving invasive mechanical ventilation. Two different administration strategies (adjunctive and substitute) were considered clinically relevant. Inclusion was restricted to studies using jet, ultrasonic, and vibrating-mesh nebulizers. Studies involving children, colonized-but-not-infected adults, and cystic fibrosis patients were excluded.

Results

Five of the 11 studies included had a small sample size (fewer than 50 patients), and only 6 were randomized. Diversity of case-mix, dosage, and devices are sources of bias. Only a few patients had severe hypoxemia. Aminoglycosides and colistin were the most common antibiotics, being safe regarding nephrotoxicity and neurotoxicity, but increased respiratory complications in 9% (95% CI, 0.01 to 0.18; I2 = 52%), particularly when administered to hypoxemic patients. For tracheobronchitis, a significant decrease in emergence of resistance was evidenced (risk ratio, 0.18; 95% CI, 0.05 to 0.64; I2 = 0%). Similar findings were observed in pneumonia by susceptible pathogens, without improvement in mortality or ventilation duration. In pneumonia caused by resistant pathogens, higher clinical resolution (odds ratio, 1.96; 95% CI, 1.30 to 2.96; I2 = 0%) was evidenced. These findings were not consistently evidenced in the assessment of efficacy against pneumonia caused by susceptible pathogens.

Conclusions

Performance of randomized trials evaluating the impact of nebulized antibiotics with more homogeneous populations, standardized drug delivery, predetermined clinical efficacy, and safety outcomes is urgently required. Infections by resistant pathogens might potentially have higher benefit from nebulized antiinfective agents. Nebulization, without concomitant systemic administration of the drug, may reduce nephrotoxicity but may also be associated with higher risk of respiratory complications.
A Prospective Study of Chronic Pain after Thoracic Surgery
Authors: Bayman Emine Ozgur , Parekh Kalpaj R. , Keech John , Selte Atakan , Brennan Timothy J.
Published: March 2017

Background

The goal of this study was to detect the predictors of chronic pain at 6 months after thoracic surgery from a comprehensive evaluation of demographic, psychosocial, and surgical factors.

Methods

Thoracic surgery patients were enrolled 1 week before surgery and followed up 6 months postsurgery in this prospective, observational study. Comprehensive psychosocial measurements were assessed before surgery. The presence and severity of pain were assessed at 3 and 6 months after surgery. One hundred seven patients were assessed during the first 3 days after surgery, and 99 (30 thoracotomy and 69 video-assisted thoracoscopic surgery, thoracoscopy) patients completed the 6-month follow-up. Patients with versus without chronic pain related to thoracic surgery at 6 months were compared.

Results

Both incidence (P = 0.37) and severity (P = 0.97) of surgery-related chronic pain at 6 months were similar after thoracotomy (33%; 95% CI, 17 to 53%; 3.3 ± 2.1) and thoracoscopy (25%; 95% CI, 15 to 36%; 3.3 ± 1.7). Both frequentist and Bayesian multivariate models revealed that the severity of acute pain (numerical rating scale, 0 to 10) is the measure associated with chronic pain related to thoracic surgery. Psychosocial factors and quantitative sensory testing were not predictive.

Conclusions

There was no difference in the incidence and severity of chronic pain at 6 months in patients undergoing thoracotomy versus thoracoscopy. Unlike other postsurgical pain conditions, none of the preoperative psychosocial measurements were associated with chronic pain after thoracic surgery.
MicroRNA-182-5p Regulates Nerve Injury–induced Nociceptive Hypersensitivity by Targeting Ephrin Type-b Receptor 1
Authors: Zhou Xuelong , Zhang Chenjing , Zhang Congjuan , Peng Yunan , Wang Yin , Xu Hongjiao
Published: March 2017

Background

The authors and others have previously shown that the up-regulation of spinal ephrin type-b receptor 1 plays an essential role in the pathologic process of nerve injury–induced nociceptive hypersensitivity, but the regulatory mechanism remains unclear.

Methods

Radiant heat and von Frey filaments were applied to assess nociceptive behaviors. Real-time quantitative polymerase chain reaction, Western blotting, fluorescence in situ hybridization, immunofluorescence, immunohistochemistry, dual-luciferase reporter gene assays, recombinant lentivirus, and small interfering RNA were used to characterize the likely mechanisms.

Results

Periphery nerve injury induced by chronic constriction injury of the sciatic nerve significantly reduced spinal microRNA-182-5p (miR-182-5p) expression levels, which were inversely correlated with spinal ephrin type-b receptor 1 expression (R
2 = 0.90; P < 0.05; n = 8). The overexpression of miR-182-5p in the spinal cord prevented and reversed the nociceptive behaviors induced by sciatic nerve injury, accompanied by a decreased expression of spinal ephrin type-b receptor 1 (recombinant lentiviruses containing pre-microRNA-182: 1.91 ± 0.34 vs. 1.24 ± 0.31, n = 4; miR-182-5p mimic: 2.90 ± 0.48 vs. 1.51 ± 0.25, n = 4). In contrast, the down-regulation of spinal miR-182-5p facilitated the nociceptive behaviors induced by sciatic nerve injury and increased the expression of spinal ephrin type-b receptor 1 (1.0 ± 0.26 vs. 1.74 ± 0.31, n = 4). Moreover, the down-regulation of miR-182-5p and up-regulation of ephrin type-b receptor 1 caused by sciatic nerve injury were mediated by the N-methyl-d-aspartate receptor.

Conclusions

Collectively, our findings reveal that the spinal ephrin type-b receptor 1 is regulated by miR-182-5p in nerve injury–induced nociceptive hypersensitivity.
Recent developments in the management of germ cell tumors
Authors: Msaouel Pavlos , Bilen Mehmet A. , Zhang Miao , Campbell Matthew , Wang Jennifer , Tu Shi-Ming
Published: March 2017

Purpose of review

In the present review, we summarize the recent developments in the management of germ cell tumors (GCTs).

Recent findings

Treatment-related acute and late-onset toxicity remains a key challenge in the management of GCTs. Recent data show that patients with large retroperitoneal lymph node metastases are at increased risk of venous thromboembolism and may benefit from prophylactic anticoagulation. Predictive models have been developed to identify patients with residual retroperitoneal lymph node masses who are more likely to benefit from surgical resection. However, their clinical use remains hampered by relatively low accuracy. There are currently multiple conventional-dose chemotherapy (CDCT) options for salvage therapy in patients with refractory or recurrent disease. In addition, more efficacious high-dose chemotherapy (HDCT) regimens continue to be developed. The role of salvage CDCT versus HDCT is currently being prospectively investigated.

Finally, intratumoral heterogeneity is a common finding in cancer and an obvious observation in GCTs. Despite intratumoral heterogeneity, recent studies on nonseminomatous GCT have identified distinct histological subgroups and a potentially lethal clinical phenotype. Importantly, comprehensive molecular profiling so far has not elucidated the biologic basis or the clinical underpinnings of intratumoral heterogeneity in GCTs.

Remaining challenges to be addressed include minimizing therapeutic toxicity and improving outcomes in patients with refractory/recurrent GCTs or malignant transformation of teratomas.
Clinical Characteristics of Arteriovenous Malformations of the Head and Neck
Authors: Kim Jae Bong , Lee Jeong Woo , Choi Kang Young , Yang Jung Dug , Cho Byung Chae , Lee Seok-Jong , Kim Yong-Sun , Lee Jong Min , Huh Seung , Chung Ho Yun
Published: March 2017

BACKGROUND

Arteriovenous malformation (AVM) of the head and neck regions show low incidence; hence, studies regarding the causative factors of onset, diagnostic criteria, clinical aspects, treatment methods, and outcomes remain lacking.

OBJECTIVE

To share the diagnostic and treatment experiences at the center and to understand the treatments' effect through a retrospective analysis of cases in the past 15 years.

MATERIALS AND METHODS

The authors included 60 patients with AVM in the head and neck area between January 1999 and September 2014 to investigate diagnostic methods, distributions and locations of lesions, clinical stage, and treatment methods by retrospective evaluation.

RESULTS

In all, 3.7% were diagnosed with AVMs of the head and neck. No sex-related differences were observed, and the mean age at diagnosis was 27.6 ± 14.24 years. The left (26 patients, 43%) and V2 sections (33 patients, 55%) of the head and neck were the most frequent locations. Stage II (28 patients, 47%) had the largest distribution. Forty-four patients (73%) showed improvement after sclerotherapy, embolization, and surgical resection.

CONCLUSION

The diagnosis and treatment of AVMs should be approached on a case-by-case basis by gathering opinions from specialists in each department using medical history, physical examination, and imaging results.
Autonomic Nervous System Function After a Skin-to-Skin Contact Intervention in Infants With Congenital Heart Disease
Authors: Harrison Tondi M. , Brown Roger
Published: March 2017

Background:

Infants with complex congenital heart disease (CCHD) demonstrate impaired autonomic nervous system (ANS) regulation, which may contribute to commonly observed impairments in feeding, growth, and development. Close mother-infant physical contact improves ANS function in other high-risk infant populations.

Objective:

Our purposes were to examine feasibility of a 2-week daily skin-to-skin contact (SSC) intervention and to describe change in ANS function in response to the intervention.

Methods:

Feasibility was assessed by recruitment and retention rates, safety, and acceptability. Autonomic nervous system function was measured with linear and nonlinear measures of heart rate variability (HRV) during a feeding before the 14-day SSC intervention and 3 times during a 4-week follow-up.

Results:

Recruitment rate was 72%; retention rate was 55.5%. Mothers were universally positive about SSC. Ten mothers and infants completed a daily mean of 77.05 minutes of SSC during the 14-day intervention with no adverse events. Baseline high-frequency HRV, reactivity to challenge, and recovery after challenge improved during the 6-week study. Nonlinear measures demonstrated abnormally high sympathetic activity, especially after feeding, in most infants.

Conclusions:

Skin-to-skin contact is feasible in infants with CCHD. Linear measures of HRV suggested improvements in ANS function with this intervention. This article is one of the first to describe nonlinear HRV measures in infants with CCHD. Additional research is needed to identify variations in linear and nonlinear effects based on specific cardiac conditions and with varying intervention doses and timing. This low-cost, low-risk intervention has the potential to improve outcomes in infants with CCHD.
Technological Complexity
Authors: Clancy Thomas R.
Published: March 2017

As systems evolve over time, their natural tendency is to become increasingly more complex. Studies in the field of complex systems have generated new perspectives on the application of management strategies in health systems. Much of this research appears as a natural extension of the cross-disciplinary field of systems theory. This article focuses on why technological complexity is increasing and strategies nurse administrators can use to successfully implement change in the face of it.
Recurrent SRF-RELA Fusions Define a Novel Subset of Cellular Myofibroma/Myopericytoma
Authors: Antonescu Cristina R. , Sung Yun-Shao , Zhang Lei , Agaram Narasimhan P. , Fletcher Christopher D.
Published: March 2017

Cellular myofibroblastic tumors other than desmoid-type fibromatosis are often diagnostically challenging due to their relative rarity, lack of known genetic abnormalities, and expression of muscle markers which may be confused with sarcomas with myogenic differentiation. In this study we investigate the molecular alterations of a group of cellular myofibroblastic lesions with in the myofibroma and myopericytoma spectrum for better subclassification. Two index cases were studied by paired-end RNA sequencing for potential fusion gene discovery. One chest wall soft tissue tumor in a 3-month-old girl case showed a SRF-C3orf62 fusion, while the other, a forearm lesion in an 8-year-old girl, showed a SRF-RELA fusion. Further screening of 42 cellular examples of myofibroma/myopericytoma by fluorescence in situ hybridization identified additional 8 cases with recurrent SRF gene rearrangements, 6 of them showing identical SRF-RELA fusions. The cohort was composed of 7 females and 3 males, with a wide age range of 3 months to 63 years (mean=17). All tumors showed a densely packed growth of oval to spindle cells with fibrillary eosinophilic cytoplasm, arranged either in intersecting fascicles or with a distinct nested pattern around a rich vascular network. Despite the dense cellularity and variable mitotic activity none of the lesions displayed nuclear pleomorphism or necrosis. All tumors showed coexpression for SMA and desmin, in most cases with a strong and diffuse pattern of staining, while myogenin was consistently negative. No distant metastases were seen in the few cases with follow-up information. A control group of 34 well-characterized myofibroblastic and perivascular tumors, including 10 typical myofibromas and 3 myopericytomas, were also investigated for SRF gene abnormalities by fluorescence in situ hybridization and were negative. In summary, we report a subset of cellular variants of myofibroma and myopericytoma showing a smooth muscle-like immunophenotype and harboring recurrent SRF-RELA gene fusions, which mimic sarcomas with myogenic differentiation.
Cytology Preparations of Formalin Fixative Aid Detection of Giardia in Duodenal Biopsy Samples
Authors: Panarelli Nicole C. , Gobara Nariman , Hoda Rana S. , Chaump Michael , Jessurun Jose , Yantiss Rhonda K.
Published: March 2017

Giardiasis is the most common intestinal parasitic infection in the United States. The organism elicits no, or minimal, inflammatory changes in duodenal biopsy samples, so it can be easily overlooked. We performed this study to determine whether Giardia could be isolated from the formalin fixative of biopsy samples, and to evaluate the value of fluid analysis in the assessment for potential infection. We prospectively evaluated duodenal biopsy samples from 92 patients with a clinical suspicion of giardiasis or symptoms compatible with that diagnosis (ie, diarrhea, bloating, or abdominal pain) Biopsy samples were routinely processed and stained with hematoxylin and eosin. Histologic diagnoses included giardiasis (5 cases, 4%), normal findings (64 cases, 70%), peptic injury/active duodenitis (12 cases, 13%), and intraepithelial lymphocytosis with villous blunting (10 cases, 12%). Fifteen cases (13%) showed detached degenerated epithelial cells or mucus droplets in the intervillous space that resembled Giardia. Cytology slides were prepared from formalin in the biopsy container using the standard Cytospin protocol and reviewed by a cytopathologist blinded to the biopsy findings. Cytologic evaluation revealed Giardia spp. in all 5 biopsy-proven cases, and identified an additional case that was not detected by biopsy analysis. Organisms were significantly more numerous (mean: 400 trophozoites; range, 120 to 810) and showed better morphologic features in cytology preparations compared with tissue sections (mean: 129 trophozoites; range, 37 to 253 organisms; P=0.05). Our findings suggest that cytology preparations from formalin fixative can resolve diagnostically challenging cases and even enhance Giardia detection in some cases.
Multiple Organ Dysfunction Syndrome: A Challenge for the Pediatric Critical Care Community
Authors: Tamburro Robert F. , Jenkins Tammara L.
Published: March 2017

The multiple organ dysfunction syndrome is highly prevalent among critically ill children both at the time of their admission and throughout their PICU stay. It is associated with a wide variety of clinical conditions and diagnoses. In addition to its prevalence, it is closely associated with mortality, and the risk of death seems to increase as the number of failing organs increases. Thus, preventing the progression or development of organ failure holds promise as a method to improve outcomes for a wide range of critically ill children. However, despite being first described 4 decades ago, much remains to be learned about this syndrome including its triggering events, pathophysiology, and genetic predispositions. In addition, a better understanding of the influence of age and development on its occurrence and severity is needed as neonates and infants seem to be differentially afflicted. In an attempt to begin to address these issues, the Pediatric Trauma and Critical Illness Branch of the Eunice Kennedy Shriver National Institute of Child Health and Human Development convened experts in the field at a 2-day workshop to discuss this syndrome, identify key knowledge gaps, and consider potential opportunities for future research.
Epidemiology and Outcomes of Pediatric Multiple Organ Dysfunction Syndrome
Authors: Watson R. Scott , Crow Sheri S. , Hartman Mary E. , Lacroix Jacques , Odetola Folafoluwa O.
Published: March 2017

Objective:

To summarize the epidemiology and outcomes of children with multiple organ dysfunction syndrome as part of the Eunice Kennedy Shriver National Institute of Child Health and Human Development multiple organ dysfunction syndrome workshop (March 26–27, 2015).

Data Sources:

Literature review, research data, and expert opinion.

Study Selection:

Not applicable.

Data Extraction:

Moderated by an experienced expert from the field, issues relevant to the epidemiology and outcomes of children with multiple organ dysfunction syndrome were presented, discussed, and debated with a focus on identifying knowledge gaps and research priorities.

Data Synthesis:

Summary of presentations and discussion supported and supplemented by the relevant literature.

Conclusions:

A full understanding the epidemiology and outcome of multiple organ dysfunction syndrome in children is limited by inconsistent definitions and populations studied. Nonetheless, pediatric multiple organ dysfunction syndrome is common among PICU patients, occurring in up to 57% depending on the population studied; sepsis remains its leading cause. Pediatric multiple organ dysfunction syndrome leads to considerable short-term morbidity and mortality. Long-term outcomes of multiple organ dysfunction syndrome in children have not been well studied; however, studies of adults and children with other critical illnesses suggest that the risk of long-term adverse sequelae is high. Characterization of the long-term outcomes of pediatric multiple organ dysfunction syndrome is crucial to identify opportunities for improved treatment and recovery strategies that will improve the quality of life of critically ill children and their families. The workshop identified important knowledge gaps and research priorities intended to promote the development of standard definitions and the identification of modifiable factors related to its occurrence and outcome.