bluuebunny/crossref_metadata_2025 huggingface dataset:
Contrast-enhanced optical coherence tomography with picomolar sensitivity for functional in vivo imaging
Authors: Liba Orly , SoRelle Elliott D. , Sen Debasish , de la Zerda Adam
Published: March 2016

Optical Coherence Tomography (OCT) enables real-time imaging of living tissues at cell-scale resolution over millimeters in three dimensions. Despite these advantages, functional biological studies with OCT have been limited by a lack of exogenous contrast agents that can be distinguished from tissue. Here we report an approach to functional OCT imaging that implements custom algorithms to spectrally identify unique contrast agents: large gold nanorods (LGNRs). LGNRs exhibit 110-fold greater spectral signal per particle than conventional GNRs, which enables detection of individual LGNRs in water and concentrations as low as 250 pM in the circulation of living mice. This translates to ~40 particles per imaging voxel in vivo. Unlike previous implementations of OCT spectral detection, the methods described herein adaptively compensate for depth and processing artifacts on a per sample basis. Collectively, these methods enable high-quality noninvasive contrast-enhanced imaging of OCT in living subjects, including detection of tumor microvasculature at twice the depth achievable with conventional OCT. Additionally, multiplexed detection of spectrally-distinct LGNRs was demonstrated to observe discrete patterns of lymphatic drainage and identify individual lymphangions and lymphatic valve functional states. These capabilities provide a powerful platform for molecular imaging and characterization of tissue noninvasively at cellular resolution, called MOZART.
Identification of a novel interaction between corticotropin releasing hormone (Crh) and macroautophagy
Authors: Giannogonas Panagiotis , Apostolou Athanasia , Manousopoulou Antigoni , Theocharis Stamatis , Macari Sofia A. , Psarras Stelios , Garbis Spiros D. , Pothoulakis Charalabos , Karalis Katia P.
Published: March 2016

In inflammatory bowel disease (IBD), compromised restitution of the epithelial barrier contributes to disease severity. Owing to the complexity in the pathogenesis of IBD, a variety of factors have been implicated in its progress. In this study, we report a functional interaction between macroautophagy and Corticotropin Releasing Hormone (Crh) in the gut. For this purpose we used DSS colitis model on Crh −/− or wild-type (wt) with pharmacological inhibition of autophagy. We uncovered sustained basal autophagy in the gut of Crh −/− mice, which persisted over the course of DSS administration. Autophagy inhibition resulted in partial rescue of Crh −/− mice, while it increased the expression of Crh in the wt gut. Similarly, Crh deficiency was associated with sustained activation of base line autophagy. In vitro models of amino acid deprivation- and LPS-induced autophagy confirmed the in vivo findings. Our results indicate a novel role for Crh in the intestinal epithelium that involves regulation of autophagy, while suggesting the complementary action of the two pathways. These data suggest the intriguing possibility that targeting Crh stimulation in the intestine may provide a novel therapeutic approach to support the integrity of the epithelial barrier and to protect from chronic colitis.
Genome-wide Long Non-coding RNA Analysis Identified Circulating LncRNAs as Novel Non-invasive Diagnostic Biomarkers for Gynecological Disease
Authors: Wang Wen-Tao , Sun Yu-Meng , Huang Wei , He Bo , Zhao Ya-Nan , Chen Yue-Qin
Published: March 2016

Increasing evidence indicates that long non-coding RNAs (lncRNAs) play important roles in human diseases. This study aimed to investigate the tissue and serum lncRNAs that are differentially expressed between patients with endometriosis, a gynecological disease, to evaluate the potential of these lncRNAs as non-invasive markers for the disease. The differentially expressed lncRNAs as competing endogenous RNAs (ceRNAs) were also analyzed to predict their functions in disease development. Genome-wide profiling of lncRNA expression patterns revealed that many lncRNAs were abnormally expressed between sera and tissuesof the patient samples. A set of aberrant differentially expressed lncRNAs were further validated in a validation cohort of 110 serum and 24 tissue samples. Functional analysis predicted that differentially expressed lncRNAs may participate in disease development through crosstalk between the ceRNAs of miRNAs and may be involved in a range of cellular pathways including steroid or hormone responses. We also found a unique set of lncRNAs that were associated with disease severity and progression and their diagnostic values were also investigated. Our study demonstrated that lncRNAs could potentially serve as non-invasive biomarkers for the diagnosis of endometriosis and as important regulators in the progression of this disease.
Exploring regulatory networks of miR-96 in the developing inner ear
Authors: Lewis Morag A. , Buniello Annalisa , Hilton Jennifer M. , Zhu Fei , Zhang William I. , Evans Stephanie , van Dongen Stijn , Enright Anton J. , Steel Karen P.
Published: March 2016

Mutations in the microRNAMir96cause deafness in mice and humans. In the diminuendo mouse, which carries a single base pair change in the seed region of miR-96, the sensory hair cells crucial for hearing fail to develop fully and retain immature characteristics, suggesting that miR-96 is important for coordinating hair cell maturation. Our previous transcriptional analyses show that many genes are misregulated in the diminuendo inner ear and we report here further misregulated genes. We have chosen three complementary approaches to explore potential networks controlled by miR-96 using these transcriptional data. Firstly, we used regulatory interactions manually curated from the literature to construct a regulatory network incorporating our transcriptional data. Secondly, we built a protein-protein interaction network using the InnateDB database. Thirdly, gene set enrichment analysis was used to identify gene sets in which the misregulated genes are enriched. We have identified several candidates for mediating some of the expression changes caused by the diminuendo mutation, includingFos,Myc,Trp53andNr3c1, and confirmed our prediction thatFosis downregulated in diminuendo homozygotes. Understanding the pathways regulated by miR-96 could lead to potential therapeutic targets for treating hearing loss due to perturbation of any component of the network.
Biological insertion of computationally designed short transmembrane segments
Authors: Baeza-Delgado Carlos , von Heijne Gunnar , Marti-Renom Marc A. , Mingarro Ismael
Published: March 2016

The great majority of helical membrane proteins are inserted co-translationally into the ER membrane through a continuous ribosome-translocon channel. The efficiency of membrane insertion depends on transmembrane (TM) helix amino acid composition, the helix length and the position of the amino acids within the helix. In this work, we conducted a computational analysis of the composition and location of amino acids in transmembrane helices found in membrane proteins of known structure to obtain an extensive set of designed polypeptide segments with naturally occurring amino acid distributions. Then, using an in vitro translation system in the presence of biological membranes, we experimentally validated our predictions by analyzing its membrane integration capacity. Coupled with known strategies to control membrane protein topology, these findings may pave the way to de novo membrane protein design.
Small molecule detection by lateral flow strips via aptamer-gated silica nanoprobes
Authors: Özalp V. Cengiz , Çam Dilek , Hernandez Frank J. , Hernandez Luiza I. , Schäfer Thomas , Öktem Hüseyin A.
Published: March 2016

A fast, sensitive and ratiometric biosensor strategy for small molecule detection was developed through nanopore actuation.
Development of a biosensing system for tacrine based on nitrogen-doped graphene quantum dots and acetylcholinesterase
Authors: Benítez-Martínez S. , Caballero-Díaz E. , Valcárcel M.
Published: March 2016

The graphene quantum dot-based sensor is sensitive to reaction products resulting from acetylcholinesterase activity and it allows for the determination of tacrine acting as an enzyme inhibitor.
Proximity ligation-induced assembly of DNAzymes for simple and cost-effective colourimetric detection of proteins with high sensitivity
Authors: Wei Luming , Wang Xiaoying , Wu Dan , Li Chao , Yin Yongmei , Li Genxi
Published: March 2016

A novel colorimetric method for protein assays is firstly proposed based on proximity ligation induced assembly of Mg2+-dependent DNAzymes.
Underlying mechanisms of the synergistic role of Li2MnO3 and LiNi1/3Co1/3Mn1/3O2 in high-Mn, Li-rich oxides
Authors: Lim Jin-Myoung , Kim Duho , Park Min-Sik , Cho Maenghyo , Cho Kyeongjae
Published: March 2016

Synergistic roles of Li2MnO3 and NCM experimentally observed in high-Mn, Li-rich oxides were theoretically elucidated through the crystal field stabilisation of electronic structures, which reveals that NCM stabilises the transition metal layer of Li2MnO3.
Fluorescence staining of salicylaldehyde azine, and applications in the determination of potassium tert-butoxide
Authors: Yang Jinlai , Rui Jian , Xu Xu , Yang Yiqin , Su Jun , Xu Haijun , Wang Yunyun , Sun Nan , Wang Shifa
Published: March 2016

Salicylaldehyde azine (1), with an aggregation-induced emission (AIE) function, was synthesized from salicylaldehyde and characterized by nuclear magnetic resonance, high resolution mass spectrometry, and X-ray single crystal diffraction.
Eco-friendly fabrication of sponge-like magnetically carbonaceous fiber aerogel for high-efficiency oil–water separation
Authors: Liu Rui-Lin , Li Xing-Qiang , Liu Hui-Qin , Luo Zhi-Min , Ma Jin , Zhang Zhi-Qi , Fu Qiang
Published: March 2016

A magnetically carbonaceous fiber aerogel was for the first time fabricated by a facile approach from natural cotton and can be used as potential adsorbent without any further chemical modification for high-efficiency oil–water separation.
Nonclassical from-shell-to-core growth of hierarchically organized SAPO-11 with enhanced catalytic performance in hydroisomerization of n-heptane
Authors: Jin Dongliang , Liu Zhiting , Zheng Jingwei , Hua Weiming , Chen Jiao , Zhu Kake , Zhou Xinggui
Published: March 2016

A growth inhibitor combined tumbling crystallization to generate hierarchical SAPO-11 with enhanced isomer selectivity in hydroisomerization of n-heptane is reported.
Inhibition of Aβ(1–40) fibril formation by cyclophilins
Authors: Villmow Marten , Baumann Monika , Malesevic Miroslav , Sachs Rolf , Hause Gerd , Fändrich Marcus , Balbach Jochen , Schiene-Fischer Cordelia
Published: March 2016

Cyclophilins interact directly with the Alzheimer's disease peptide Aβ (amyloid β-peptide) and are therefore involved in the early stages of Alzheimer's disease. Aβ binding to CypD (cyclophilin D) induces dysfunction of human mitochondria. We found that both CypD and CypA suppress in vitro fibril formation of Aβ(1–40) at substoichiometric concentrations when present early in the aggregation process. The prototypic inhibitor CsA (cyclosporin A) of both cyclophilins as well as the new water-soluble MM258 derivative prevented this suppression. A SPOT peptide array approach and NMR titration experiments confirmed binding of Aβ(1–40) to the catalytic site of CypD mainly via residues Lys16–Glu22. The peptide Aβ(16–20) representing this section showed submicromolar IC50 values for the peptidyl prolyl cis–trans isomerase activity of CypD and CypA and low-micromolar KD values in ITC experiments. Chemical cross-linking and NMR-detected hydrogen–deuterium exchange experiments revealed a shift in the populations of small Aβ(1–40) oligomers towards the monomeric species, which we investigated in the present study as being the main process of prevention of Aβ fibril formation by cyclophilins.
Defining the contributions of permanent electrostatics, Pauli repulsion, and dispersion in density functional theory calculations of intermolecular interaction energies
Authors: Horn Paul R. , Mao Yuezhi , Head-Gordon Martin
Published: March 2016

In energy decomposition analysis of Kohn-Sham density functional theory calculations, the so-called frozen (or pre-polarization) interaction energy contains contributions from permanent electrostatics, dispersion, and Pauli repulsion. The standard classical approach to separate them suffers from several well-known limitations. We introduce an alternative scheme that employs valid antisymmetric electronic wavefunctions throughout and is based on the identification of individual fragment contributions to the initial supersystem wavefunction as determined by an energetic optimality criterion. The density deformations identified with individual fragments upon formation of the initial supersystem wavefunction are analyzed along with the distance dependence of the new and classical terms for test cases that include the neon dimer, ammonia borane, water-Na+, water-Cl−, and the naphthalene dimer.
Impact of orifice orientation on a finite-span synthetic jet interaction with a crossflow
Authors: Van Buren Tyler , Leong Chia Min , Whalen Edward , Amitay Michael
Published: March 2016

The formation and evolution of flow structures associated with a finite-span synthetic jet issued into a zero-pressure gradient boundary layer were investigated experimentally using stereoscopic particle image velocimetry. A synthetic jet with an aspect ratio of AR = 18 was mounted on a flat plate and its interaction with a free stream, having a velocity of U∞ = 10 m/s (Reδ = 2000) at momentum coefficients of Cμ = 0.08, 0.33, and 0.75, was studied. The effect of the orifice pitch (α = 20∘–90∘) and skew (β = 0∘–90∘) angles on vortex formation as well as the global impact of the synthetic jet on the flow field was explored in detail. It was found that the orifice orientation had a significant impact on the steady and unsteady flow structures. Different orifice skew and pitch angles could result in several types of vortical structures downstream, including: no coherent vortex structure, a single (positive or negative) strong vortex, or a symmetric vortex pair. In all cases, the velocity near the wall was increased; however, cases with higher blockage (i.e., more wall-normal, transverse orifice) resulted in a strong velocity deficit in the free stream where orifices with lower pitch angles yielded in an increase in velocity throughout. The analysis is concluded with a summary of quantitative metrics that allude to flow control effectiveness.
A new characterization of geodesic spheres in the hyperbolic space
Authors: Wu Jie
Published: March 2016

This paper gives a new characterization of geodesic spheres in the hyperbolic space in terms of a “weighted” higher order mean curvature. Precisely, we show that a compact hypersurface

Σ

n
−
1

\Sigma ^{n-1}

embedded in

H

n

\mathbb {H}^n

with

V

H
k

VH_k

being constant for some

k
=
1
,
⋯
,
n
−
1

k=1,\cdots ,n-1

is a centered geodesic sphere. Here

H
k

H_k

is the

k
k

-th normalized mean curvature of

Σ
\Sigma

induced from

H

n

\mathbb {H}^n

and

V
=
cosh
⁡
r

V=\cosh r

, where

r
r

is a hyperbolic distance to a fixed point in

H

n

\mathbb {H}^n

. Moreover, this result can be generalized to a compact hypersurface

Σ
\Sigma

embedded in

H

n

\mathbb {H}^n

with the ratio

V

(

H
k

H
j

)

≡

constant

,

0
≤
j
>
k
≤
n
−
1

V\left (\frac {H_k}{H_j}\right )\equiv \mbox {constant},\;0\leq j> k\leq n-1

and

H
j

H_j

not vanishing on

Σ
\Sigma

.
Improved estimates of orange roughy biomass using an acoustic-optical system in commercial trawlnets
Authors: Ryan Tim E. , Kloser Rudy J.
Published: March 2016

Echo integration is a well-established method for estimating fish biomass, but is challenging for a low target strength (TS), deep-living fish species such as orange roughy (Hoplostethus atlanticus). A novel approach has been to utilize the infrastructure of the fishing vessel's trawlnet by attaching an acoustic-optical system (AOS) to the net's headline. Deep deployment of the AOS via the trawlnet reduces uncertainties associated with hull-mounted acoustics that include the influence of weather on data quality, low resolution due to the long range to target, large acoustic dead zone on sloping seabed, and inability to identify and differentiate other fish that co-occur with the target species. The AOS system simultaneously records acoustic data at multiple frequencies (38 and 120 kHz), species composition in video and stereo imagery, and environmental data as the net collects biological samples and/or commercial catch. All data streams were considered in a multiple-lines-of-evidence approach to give improved estimates of orange roughy biomass with low error due to species uncertainty. AOS-based biomass estimates, made over a 5-year period from 11 key spawning locations in Australia and New Zealand, showed a strong correlation (r2 = 0.97, n = 39) between frequencies (38 and 120 kHz); the 38 kHz estimates were, on average, 8% higher than 120 kHz, with a standard deviation of 20%. This similarity in estimates across frequencies improves confidence in results compared with single-frequency surveys that are potentially prone to large errors resulting from unknown (mixed) species composition and target strengths, calibration, and sound absorption uncertainties.
How Residents Develop Trust in Interns: A Multi-Institutional Mixed-Methods Study
Authors: Sheu Leslie , O’Sullivan Patricia S. , Aagaard Eva M. , Tad-y Darlene , Harrell Heather E. , Kogan Jennifer R. , Nixon James , Hollander Harry , Hauer Karen E.
Published: March 2016

Purpose

Although residents trust interns to provide patient care, little is known about how trust forms.

Method

Using a multi-institutional mixed-methods study design, the authors interviewed (March–September 2014) internal medicine (IM) residents in their second or third postgraduate year at a single institution to address how they develop trust in interns. Transcript analysis using grounded theory yielded a model for resident trust. Authors tested (January–March 2015) the model with residents from five IM programs using a two-section quantitative survey (38 items; 31 rated 0 = not at all to 100 = very much; 7 rated 0 = strongly disagree to 100 = strongly agree) to identify influences on how residents form trust.

Results

Qualitative analysis of 29 interviews yielded 14 themes within five previously identified factors of trust (resident, intern, relationship, task, and context). Of 478 residents, 376 (78.7%) completed the survey. Factor analysis yielded 11 factors that influence trust. Respondents rated interns’ characteristics (reliability, competence, and propensity to make errors) highest when indicating importance to trust (respective means 86.3 [standard deviation = 9.7], 76.4 [12.9], and 75.8 [20.0]). They also rated contextual factors highly as influencing trust (access to an electronic medical record, duty hours, and patient characteristics; respective means 79.8 [15.3], 73.1 [14.4], and 71.9 [20.0]).

Conclusions

Residents form trust based on primarily intern- and context-specific factors. Residents appear to consider trust in a way that prioritizes interns’ execution of essential patient care tasks safely within the complexities and constraints of the hospital environment.
Self-reported Mobility in Older Patients Predicts Early Postoperative Outcomes after Elective Noncardiac Surgery
Authors: Kim Sunghye , Marsh Anthony P. , Rustowicz Lauren , Roach Catherine , Leng Xiaoyan I. , Kritchevsky Stephen B. , Rejeski W. Jack , Groban Leanne
Published: March 2016

AbstractAbstract

Preoperative self-reported mobility, as measured by the quick, reliable, and cost-effective mobility assessment tool–short form, predicted early postoperative complications, hospital length of stay, and discharge to a nursing home in older patients scheduled for elective noncardiac surgery.

Background

Specific geriatric assessment tools may complement traditional perioperative risk stratification. The aim of this study was to evaluate whether self-reported mobility is predictive of postoperative outcomes in older patients undergoing elective noncardiac surgery.

Methods

Patients aged 69 yr or older (n = 197) underwent (1) traditional risk assessments (American Society of Anesthesiologists physical status classification and Revised Cardiac Risk Index), (2) five-point frailty evaluation, (3) self-reported mobility assessment using the Mobility Assessment Tool–short form (range, 30.21 [poor] to 69.76 [excellent]), and (4) measurements of high-sensitivity C-reactive protein. Outcomes were postoperative complications, time to discharge, and nursing home placement (NHP).

Results

In the sample of this study (mean age, 75 ± 5 yr; 51% women), 72% had intermediate- or high-risk surgery. Median time to discharge was 3 days (interquartile range, 1 to 4 days). Thirty patients (15%) developed postoperative complications, and 27 (13%) required NHP. After controlling for age, sex, body mass index, pain score, Revised Cardiac Risk Index, American Society of Anesthesiologist physical status, surgical risk, and high-sensitivity C-reactive protein, worse self-reported mobility (per 10-point decrease in Mobility Assessment Tool, which is equivalent to 1 SD) was associated with more postoperative complications (odds ratio [OR], 1.69; 95% CI, 1.05 to 2.73), later time to discharge (hazards ratio, 0.81; 95% CI, 0.68 to 0.96), and increased NHP (OR, 2.01; 95% CI, 1.13 to 3.56). By using the same model, intermediate frailty or frailty increased NHP (OR, 3.11; 95% CI, 1.02 to 9.54) but was not related to either postoperative complications or time to discharge.

Conclusions

Preoperative self-reported mobility using a novel and brief assessment may help identify elderly patients at risk for adverse postoperative events.
Neural Control of Inflammation
Authors: Steinberg Benjamin E. , Sundman Eva , Terrando Niccolo , Eriksson Lars I. , Olofsson Peder S.
Published: March 2016

AbstractAbstract

Inflammation and immunity are regulated by neural reflexes. Recent basic science research has demonstrated that a neural reflex, termed the inflammatory reflex, modulates systemic and regional inflammation in a multiplicity of clinical conditions encountered in perioperative medicine and critical care. In this review, the authors describe the anatomic and physiologic basis of the inflammatory reflex and review the evidence implicating this pathway in the modulation of sepsis, ventilator-induced lung injury, postoperative cognitive dysfunction, myocardial ischemia–reperfusion injury, and traumatic hemorrhage. The authors conclude with a discussion of how these new insights might spawn novel therapeutic strategies for the treatment of inflammatory diseases in the context of perioperative and critical care medicine.

Neural reflexes modulate systemic inflammation in clinical conditions encountered in perioperative and critical care. This review discusses how recent studies in this area are leading to new therapeutic strategies for the treatment of inflammatory diseases.
No Silver Medal for Nobel Prize Contenders
Authors: Hansson Nils , Fangerau Heiner , Tuffs Annette , Polianski Igor J.
Published: March 2016

AbstractAbstract

Taking the examples of the pioneers Carl Ludwig Schleich, Carl Koller, and Heinrich Braun, this article provides a first exploratory account of the history of anesthesiology and the Nobel Prize for physiology or medicine. Besides the files collected at the Nobel Archive in Sweden, which are presented here for the first time, this article is based on medical literature of the early 20th century. Using Nobel Prize nominations and Nobel committee reports as points of departure, the authors discuss why no anesthesia pioneer has received this coveted trophy. These documents offer a new perspective to explore and to better understand aspects of the history of anesthesiology in the first half of the 20th century.

Using nominations and Nobel committee reports from the archive of the Nobel committee in Sweden as points of departure, the authors discuss why no anesthesia pioneers have received the Nobel Prize for physiology or medicine.
Treatment dilemma in multiple metatarsal fractures: when to operate?
Authors: Mahan Susan T. , Lierhaus Anneliese M. , Spencer Samantha A. , Kasser James R.
Published: March 2016

Fractures of multiple metatarsals in the pediatric population are uncommon; however, indications for surgical treatment have not been delineated. The aim of this study was to review multiple metatarsal fractures to help refine surgical indications. A total of 98 patients had multiple metatarsal fractures; displacement greater than 10% shaft width (displaced) was encountered in 33 (34.0%) patients. Fifteen patients had displacement of more than 75% shaft width of one metatarsal. Patients older than 14 years of age were more likely to have surgery for their injury (52.6%) than those younger than 14 years of age (3.7%) (P<0.0001). Younger patients and those with less than 75% displacement should be considered for nonoperative care. Levels of Evidence: Level IV.
Fixation of Displaced Medial Epicondyle Fractures in Adolescents
Authors: Pace Gregory I. , Hennrikus William L.
Published: March 2016

Background:

Open reduction and internal fixation of displaced medial epicondyle fracture dislocations in adolescents is recommended for incarceration of the epicondyle in the joint and for athletes who need a stable elbow for their sport. A screw placed across the epicondyle into the medial column avoiding the olecranon fossa is a common fixation method. One author has recommended adding a metal washer to the screw fixation because of the perceived risk of epicondyle fragmentation or penetration when using a screw alone. The purpose of this study was to determine whether the use of a screw and washer for the fixation of pediatric medial epicondyle fractures results in less fragmentation of the epicondyle at the time of surgery and more complaints of hardware prominence leading to a second surgery to remove a deep implant.

Methods:

A retrospective review was performed of patients treated surgically for displaced medial epicondyle fracture dislocations between 2008 and 2014.

Results:

Sixteen patients with a total of 17 fracture dislocations were included in the study. The average follow-up was 11.5 months. Twelve fractures were treated with a screw and washer and 5 fractures were treated with a screw alone. All fractures healed. No fracture treated with a screw alone resulted in fragmentation or penetration of the epicondyle fragment. Seven of 12 patients treated with a screw and washer requested deep metal removal due to prominence and irritation at the medial epicondyle. No patient treated with a screw alone requested metal removal (58% vs. 0%; P=0.04).

Conclusions:

One author suggested that adding a washer to the screw for fixation of medial epicondyle fractures improved the ability to safely compress the fragment. However, the results of the present study report no case of fragmentation or penetration of the epicondyle when a washer was not used. In addition, the use of a screw and washer significantly increased the likelihood of a second surgery for removal of prominent hardware.

Level of Evidence:

Level IV.
Breast Ultrasound: Indications and Findings
Authors: GUNDRY KATHLEEN R.
Published: March 2016

Breast ultrasound is a widely used adjuvant to mammography for the detection of breast cancer. This chapter will review some of the basic ultrasound technical factors and techniques, describe findings on ultrasound with an emphasis on the Breast Imaging Reporting and Data System terminology, and present the indications for breast ultrasound. New innovations in breast ultrasound, such as elastography, ultrasound contrast, 3-dimensional, and automated whole-breast ultrasound, will be reviewed. Ultrasound-guided breast procedures are also presented.
Epidemiology and Prognosis of Primary Periocular Sweat Gland Carcinomas
Authors: Baker Meredith S. , Yin Vivian T. , Ivan Doina , Allen Richard C. , Carter Keith D. , Esmaeli Bita , Shriver Erin M.
Published: March 2016

Purpose:

To characterize the clinical presentation, management, and outcomes of patients with sweat gland carcinoma of the periocular region. To review the pathologic classification scheme, compare the clinical behavior between subtypes, and discuss treatment recommendations for periocular sweat gland carcinomas.

Methods:

Retrospective study from 2 tertiary centers, which are part of the American Society of Ophthalmic Plastic and Reconstructive Surgery Oncology Database.

Results:

Twenty-two patients, of whom 13 (59%) were female, were included in the study. The median age was 69 years. The median follow-up time was 23 months. Twenty (91%) patients had lesions that were slow growing and were present for several months to years before diagnosis. Presentation was varied, and pathology included mucinous carcinoma (7; 32%), microcystic adnexal carcinoma (4; 18%), endocrine mucin-producing sweat gland carcinoma (4; 18%), eccrine carcinoma (2; 9%), apocrine carcinoma (2; 9%), poorly differential adnexal carcinoma (2; 9%), and hidroadenocarcinoma (1; 5%). Microcystic adnexal carcinoma tended to present with the largest tumor dimension (range: 25–32 mm) and mucinous carcinoma the smallest (range: 5–13 mm). Treatments included Mohs micrographic excision in 10 patients (45.5%), wide local excision in 10 patients (45.5%), and orbital exenteration in 2 patients (9%). No lesions ≤T2b (by AJCC 7th edition classification for eyelid carcinomas) had local recurrence or nodal metastasis. No patients had distant metastasis.

Conclusions:

Sweat gland carcinomas tend to grow slowly and be present for several months to years before diagnosis. Overall, microcystic adnexal carcinoma subtype showed more aggressive clinical behavior than mucinous subtypes. Eyelid carcinomas AJCC category T2b or less were associated with better outcomes.
A Prospective, Comparative Study of the Pain of Local Anesthesia Using 2% Lidocaine, 2% Lidocaine With Epinephrine, and 2% Lidocaine With Epinephrine–Bupivicaine Mixture for Eyelid Surgery
Authors: Han Jung-woo , Nah Seung Kwan , Lee Sang Yeul , Kim Chang Yeom , Yoon Jin Sook , Jang Sun Young
Published: March 2016

Purpose:

A mixture of 2% lidocaine with epinephrine and bupivacaine was developed to achieve the fast-onset anesthetic effect of lidocaine and the long-lasting effect of bupivacaine. The authors compared pain scores between 2% lidocaine, 2% lidocaine with epinephrine, and 2% lidocaine with epinephrine–bupivicaine mixture during local anesthesia for eyelid surgeries.

Methods:

This was a double-blind, randomized, prospective, comparative study. In total, 120 consecutive patients (43 males, 77 females, mean age = 47.2 ± 21.2) who underwent bilateral eyelid surgery under subcutaneous anesthesia were asked to report pain scores for each eye during the first injection of anesthesia. Each patient was randomly assigned to receive 1 of the 3 anesthetic agents in 1 eyelid, and 1 of the remaining 2 agents in the other.

Results:

The pH values of the 2% lidocaine, 2% lidocaine with epinephrine, and 2% lidocaine with epinephrine–bupivicaine mixture were 6.23 ± 0.21, 4.21 ± 0.37, and 3.87 ± 0.19, respectively. The pain scores of each were 4.3 ± 1.8, 5.1 ± 1.8, and 5.7 ± 1.9, respectively. The 2% lidocaine with epinephrine produced a statistically significantly higher pain score than 2% lidocaine (p = 0.044, generalized estimating equation method). The mixture also showed a significantly higher pain score than 2% lidocaine (p = 0.003, generalized estimating equation method).

Conclusions:

Epinephrine seemed to increase subjective pain scores. Compared with 2% lidocaine with epinephrine, 2% lidocaine with epinephrine–bupivicaine mixture was not significantly different in terms of subjective symptoms or pH.
A Comparison of Life Stress and Depressive Symptoms in Pregnant Taiwanese and Immigrant Women
Authors: Tsao Ying , Creedy Debra K. , Gamble Jenny
Published: March 2016

Background:

An increasing number of women from other countries, mostly Mainland China and Southeast Asia, are marrying Taiwanese husbands and settling in Taiwan. Immigration, marriage abroad, and pregnancy may be stressful and adversely affect maternal health. Relatively little research has compared the life stress and depressive symptoms of pregnant women of different ethnic groups living in nonmetropolitan areas in Taiwan.

Purpose:

This study investigates the levels of life stress and depressive symptoms in pregnant Taiwanese women and Vietnamese “foreign brides” currently living in southern Taiwan.

Methods:

Eligible women in their last trimester of pregnancy who attended their local antenatal clinic were recruited for the study. Participants completed standardized measures, including the Difficult Life Circumstances Scale, Social Support APGAR Scale, and Edinburgh Postnatal Depression Scale.

Results:

Two hundred thirty-six Taiwanese women and 44 Vietnamese women participated. Major life difficulties for both groups of women were related to their marital relationship, housing, or health problems. Taiwanese participants reported perceiving financial strain more often than their Vietnamese peers, whereas Vietnamese participants reported perceiving greater concerns regarding their children’s development and about recent physical abuse than their Taiwanese peers. Furthermore, the Vietnamese participants reported less social support and higher rates of antenatal depression than Taiwanese participants.

Conclusions/Implications for Practice:

Clinical nurses and midwives should be sensitive to the particular difficulties and insufficient social support faced by pregnant women from different backgrounds in Taiwan. Women from foreign countries or those under unique challenging circumstances may face a particular risk of adverse outcomes. Identifying stresses informs the development of effective nursing interventions and support activities for new mothers and their families.
Correlation Between Fractional Exhaled Nitric Oxide Levels and Efficacy of Inhaled Corticosteroids in Children With Bronchial Asthma
Authors: Gao Si-Ju , Ge Yun-Peng , Zhang Chun-Juan
Published: March 2016

To investigate correlation between fractional exhaled nitric oxide (FeNO) levels and efficacy of inhaled corticosteroids in children with bronchial asthma. Between October 2013 and December 2014, 133 cases of children with bronchial asthma were randomly divided into the glucocorticoid group (n = 67; inhaled with Seretide/Pulmicort) and the nonglucocorticoid group (n = 66; inhaled with short-acting β2 receptor agonist if needed); and alternatively 72 cases of healthy children were regarded as the control group. FeNO, forced expiratory volume in 1 second to predicted value, forced expiratory volume in 1 second/forced vital capacity, induced sputum eosinophils (EOS)%, and total serum immunoglobulin (Ig) E and serum EOS% were detected and childhood asthma control test (C-ACT) scale was investigated pretreatment and 3 and 6 months posttreatment, respectively. FeNO levels, induced sputum EOS%, total serum IgE, and serum EOS% were significantly lower, whereas forced expiratory volume in 1 second to predicted value, forced expiratory volume in 1 second/forced vital capacity, and C-ACT scores were obviously improved in the glucocorticoid group 6 months posttreatment compared with those of pretreatment (all P < 0.05). FeNO levels, induced sputum EOS%, and total serum IgE were significantly lower, whereas C-ACT scores were significantly higher in the glucocorticoid group compared with those of the nonglucocorticoid group (all P < 0.05). In the glucocorticoid group, induced sputum EOS% and total serum IgE showed significantly positive correlations with FeNO levels (r = 0.73, P < 0.01; r = 0.56, P < 0.01), whereas C-ACT scores were negatively correlated with FeNO levels (r = −0.67, P < 0.01). FeNO levels might be correlated with efficacy of inhaled corticosteroids in children with bronchial asthma.
An Immunohistochemical Algorithm for Ovarian Carcinoma Typing
Authors: Köbel Martin , Rahimi Kurosh , Rambau Peter F. , Naugler Christopher , Le Page Cécile , Meunier Liliane , de Ladurantaye Manon , Lee Sandra , Leung Samuel , Goode Ellen L. , Ramus Susan J. , Carlson Joseph W. , Li Xiaodong , Ewanowich Carol A. , Kelemen Linda E. , Vanderhyden Barbara , Provencher Diane , Huntsman David , Lee Cheng-Han , Gilks C. Blake , Mes Masson Anne-Marie
Published: March 2016

There are 5 major histotypes of ovarian carcinomas. Diagnostic typing criteria have evolved over time, and past cohorts may be misclassified by current standards. Our objective was to reclassify the recently assembled Canadian Ovarian Experimental Unified Resource and the Alberta Ovarian Tumor Type cohorts using immunohistochemical (IHC) biomarkers and to develop an IHC algorithm for ovarian carcinoma histotyping. A total of 1626 ovarian carcinoma samples from the Canadian Ovarian Experimental Unified Resource and the Alberta Ovarian Tumor Type were subjected to a reclassification by comparing the original with the predicted histotype. Histotype prediction was derived from a nominal logistic regression modeling using a previously reclassified cohort (N=784) with the binary input of 8 IHC markers. Cases with discordant original or predicted histotypes were subjected to arbitration. After reclassification, 1762 cases from all cohorts were subjected to prediction models (χ2Automatic Interaction Detection, recursive partitioning, and nominal logistic regression) with a variable IHC marker input. The histologic type was confirmed in 1521/1626 (93.5%) cases of the Canadian Ovarian Experimental Unified Resource and the Alberta Ovarian Tumor Type cohorts. The highest misclassification occurred in the endometrioid type, where most of the changes involved reclassification from endometrioid to high-grade serous carcinoma, which was additionally supported by mutational data and outcome. Using the reclassified histotype as the endpoint, a 4-marker prediction model correctly classified 88%, a 6-marker 91%, and an 8-marker 93% of the 1762 cases. This study provides statistically validated, inexpensive IHC algorithms, which have versatile applications in research, clinical practice, and clinical trials.
Characteristics of Age-Discordant Partnerships Associated With HIV Risk Among Young South African Women (HPTN 068)
Authors: Ritchwood Tiarney D. , Hughes James P. , Jennings Larissa , MacPhail Catherine , Williamson Brian , Selin Amanda , Kahn Kathleen , Gómez-Olivé F. Xavier , Pettifor Audrey
Published: March 2016

Objective:

Sexual liaisons between older men and younger women have been linked to greater risk of HIV acquisition. This study aims to (1) identify psychosocial and behavioral factors associated with age-discordant (partner ≥5 years) versus age-concordant partnerships (−1< partner <5) and (2) examine the association between partner age discordance and young South African women's sexual behavior.

Methods:

We used generalized estimating equations to analyze responses from 656 sexually experienced women (aged 13–20 years) from rural Mpumalanga province.

Results:

Partner age discordance was associated with greater odds of reporting both more frequent sex [adjusted odd ratio (aOR) = 1.77; 95% confidence interval (CI): 1.20 to 2.60] and having a partner with concurrent partnerships (aOR = 1.77; 95% CI: 1.22 to 2.57). Age-discordant partnerships were associated with greater odds of casual partnerships (aOR = 1.50; 95% CI: 1.06 to 2.13), having a partner with concurrent partnerships (aOR = 1.71; 95% CI: 1.19 to 2.46), and more frequent intercourse (ie, having sex at least 2 or 3 times per month) (aOR = 2.04; 95% CI: 1.39 to 3.00). They were associated with lower odds of reporting condom use at last sex (aOR = 0.70; 95% CI: 0.50 to 0.98) and always using condoms (aOR = 0.53; 95% CI: 0.32 to 0.88) in age-discordant partnerships.

Conclusions:

Our findings suggest that a history of age-discordant partnerships, and to a lesser extent having an age-discordant partner, is linked to HIV risk among young South African women; however, the link between partner age discordance and HIV risk may be more strongly related to the characteristics of age-discordant partnerships than to the characteristics of young women who form such partnerships.
The Effect of Timing of Initiation of Antiretroviral Therapy on Loss to Follow-up in HIV–Tuberculosis Coinfected Patients in South Africa: An Open-Label, Randomized, Controlled Trial
Authors: Yende-Zuma Nonhlanhla , Naidoo Kogieleum
Published: March 2016

Objective:

To evaluate the effect of early integrated, late-integrated, and delayed antiretroviral therapy (ART) initiation during tuberculosis (TB) treatment on the incidence rates of loss to follow-up (LTFU) and to evaluate the effect of ART initiation on LTFU rates within trial arms in patients coinfected with TB and HIV.

Methods:

A substudy within a 3-armed, open label, randomized, controlled trial. Patients were randomized to initiate ART either early or late during TB treatment or after the TB treatment completion. We reported the incidence and predictors of LTFU from TB treatment initiation during the 24 months of follow-up. LTFU was defined as having missed 4 consecutive monthly visits with the inability to make contact.

Results:

Of the 642 patients randomized, a total of 96 (15.0%) were LTFU at a median of 6.0 [interquartile range (IQR), 1.1–11.3] months after TB treatment initiation. Incidence rates of LTFU were 7.5 per 100 person-years (PY) [95% confidence interval (CI): 4.9 to 11], 10.9 per 100 PY (95% CI: 7.6 to 15.1), and 11.0 per 100 PY (95% CI: 7.6 to 15.4) in the early integrated, late-integrated, and delayed treatment arms (P = 0.313). Incidence rate of LTFU before and after ART initiation was 31.7 per 100 PY (95% CI: 11.6 to 69.0) vs. 6.1 per 100 PY (95% CI: 3.7 to 9.4); incidence rate ratio (IRR) was 5.2 (95% CI: 2.1 to 13.0; P < 0.001) in the early integrated arm; 31.9 per 100 PY (95% CI: 20.4 to 47.5) vs. 4.7 per 10 PY (95% CI: 2.4 to 8.2) and IRR was 6.8 (95% CI: 3.4 to 13.6; P < 0.0001) in the late-integrated arm; and 21.9 per 100 PY (95% CI: 14.6 to 31.5) vs. 2.8 per 100 PY (95% CI: 0.9 to 6.6) and IRR was 7.7 (95% CI: 3.0 to 19.9; P < 0.0001) in the sequential arm.

Conclusion:

LTFU rates were not significantly different between the 3 trials arms. However, ART initiation within each trial arm resulted in a significant reduction in LTFU rates among TB patients.
Cervicovaginal and Rectal Fluid as a Surrogate Marker of Antiretroviral Tissue Concentration: Implications for Clinical Trial Design
Authors: Cottrell Mackenzie L. , Prince Heather M. A. , Allmon Andrew , Mollan Katie R. , Hudgens Michael G. , Sykes Craig , White Nicole , Malone Stephanie , Dellon Evan S. , Madanick Ryan D. , Shaheen Nicholas J. , Patterson Kristine B. , Kashuba Angela D. M.
Published: March 2016

Background:

Quantifying tissue drug concentrations can yield important information during drug development, but complicates pharmacokinetic study design. Mucosal fluids collected by direct aspiration (cervicovaginal fluid; CVF) or swab (rectal fluid; RF) might be used as tissue concentration surrogates, but these relationships are not well characterized.

Methods:

Forty-nine healthy women, given a single oral dose of tenofovir, maraviroc, emtricitabine, or raltegravir at 50%–200% of the treatment dose, provided 13 plasma, 12 CVF, 12 RF and one cervical, vaginal and rectal tissue biopsy over 48 hours. Relationships between these paired samples were characterized by linear and multiple linear regression. Adjusted r2 values were used to select the final predictive models.

Results:

CVF exposure increased linearly with dose for all antiretrovirals (r2 ≥ 0.23, P ≤ 0.02) except raltegravir (r2 = 0.08, P = 0.19). In RF, only emtricitabine increased linearly with dose (r2 = 0.27, P = 0.01). For all antiretrovirals, CVF and RF concentrations significantly correlated with mucosal tissue concentrations (female genital tract r2 ≥ 0.37, rectal tissue r2 ≥ 0.50, P ≤ 0.001). In the final multivariate models, plasma and fluid concentrations were both associated with FGT concentrations for all antiretrovirals (r2 ≥ 0.81, P < 0.001). The same was noted for rectal tissue (r2 ≥ 0.58, P < 0.001) except for tenofovir, for which RF alone was predictive of tissue concentration (r2 = 0.91, P < 0.001).

Conclusions:

Mucosal fluids were positively correlated with tissue concentrations and including plasma concentrations improved the regression models in most cases. Dose linearity in CVF, but not RF, suggests a saturation process in lower gastrointestinal tract tissue. These findings suggest that mucosal fluid and plasma concentrations may be used for qualitative inference of tissue concentrations for these antiretrovirals.
Gene Transfer to the Outflow Tract
Authors: Dang Yalong , Loewen Ralitsa , Parikh Hardik , Roy Pritha , Loewen Nils
Published: March 2016

Elevated intraocular pressure is the primary cause of open angle glaucoma. Outflow resistance exists within the trabecular meshwork but also at the level of Schlemm′s canal and further downstream within the outflow system. Viral vectors allow to take advantage of naturally evolved, highly efficient mechanisms of gene transfer, a process that is termed transduction. They can be produced at biosafety level 2 in the lab using protocols that have evolved considerably over the last 15 to 20 years. Applied by an intracameral bolus, vectors follow conventional as well as uveoscleral outflow pathways. They may affect other structures in the anterior chamber depending on their transduction kinetics which can vary among species when using the same vector. Not all vectors can express long-term, a desirable feature to address the chronicity of glaucoma. Vectors that integrate into the genome of the target cell can achieve transgene function for the life of the transduced cell but are mutagenic by definition. The most prominent long-term expressing vector systems are based on lentiviruses that are derived from HIV, FIV, or EIAV. Safety considerations make non-primate lentiviral vector systems easier to work with as they are not derived from human pathogens. Non-integrating vectors are subject to degradation and attritional dilution during cell division. Lentiviral vectors have to integrate in order to express while adeno-associated viral vectors (AAV) often persist as intracellular concatemers but may also integrate. Adeno- and herpes viral vectors do not integrate and earlier generation systems might be relatively immunogenic. Nonviral methods of gene transfer are termed transfection with few restrictions of transgene size and type but often a much less efficient gene transfer that is also short-lived. Traditional gene transfer delivers exons while some vectors (lentiviral, herpes and adenoviral) allow transfer of entire genes that include introns. Recent insights have highlighted the role of non-coding RNA, most prominently, siRNA, miRNA and lncRNA. SiRNA is highly specific, miRNA is less specific, while lncRNA uses highly complex mechanisms that involve secondary structures and intergenic, intronic, overlapping, antisense, and bidirectional location. Several promising preclinical studies have targeted the RhoA or the prostaglandin pathway or modified the extracellular matrix. TGF-β and glaucoma myocilin mutants have been transduced to elevate the intraocular pressure in glaucoma models. Cell based therapies have started to show first promise. Past approaches have focused on the trabecular meshwork and the inner wall of Schlemm′s canal while new strategies are concerned with modification of outflow tract elements that are downstream of the trabecular meshwork.