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1.  Variety of fruit and vegetables is related to preschoolers' overall diet quality 
Preventive Medicine Reports  2016;5:112-117.
Children are encouraged to eat a specific amount of fruits and vegetables to optimize health. The purpose of this study was to assess whether consumption of a variety of fruits and vegetables, respectively, was associated with a greater diet quality among preschool-aged children. Analyses were performed using a cross-sectional, nationally representative sample of US children. Dietary intakes from 24-h dietary recalls of two-five year old children (n = 2595) in 2005–2010 NHANES were examined. Diet quality was evaluated using MyPlate equivalents and the Healthy Eating Index 2010 (HEI-2010). Variety categories were determined based on children's fruit, fruit juice, and vegetable consumption on the recalled day. Differences in diet quality were examined using t-tests. Variety of fruits and vegetables was linked to higher overall diet quality. Children who consumed whole fruit had better diet quality scores for total fruit, whole fruit, whole grains, dairy, seafood, refined grains, sodium, and empty calories (P ≤ 0.018). Significantly higher HEI-2010 scores for total fruit, whole fruit, fatty acids, sodium, and empty calories, but a lower dairy HEI-2010 score, were identified in children who drank fruit juice (P ≤ 0.038). Vegetable consumption was significantly associated with higher total vegetables, greens/beans, and empty calories, but a lower sodium score (P ≤ 0.027). Children who consumed whole fruit, fruit juice and non-starchy vegetables (P ≤ 0.017), but not white potatoes, had significantly higher total HEI-2010 scores. Reinforcing fruit and 100% fruit juice consumption may indirectly support healthier diets among children. However, underlying associations between fruit and vegetable intakes and overall diet quality should be examined further.
Highlights
•Children's variety of fruit and vegetable intake resulted in better diet quality.•Children who consumed whole fruit had better diet quality scores.•Vegetable consumption was significantly associated with higher total vegetables.•Children who consumed 100% fruit juice had higher total HEI-2010 scores.
doi:10.1016/j.pmedr.2016.12.003
PMCID: PMC5157882  PMID: 27990339
Children; Fruit; Vegetable; Diet quality; Food patterns; Dietary intakes; Healthy Eating Index; Preschool
2.  Contextual Information Drives the Reconsolidation-Dependent Updating of Retrieved Fear Memories 
Neuropsychopharmacology  2015;40(13):3044-3052.
Stored memories enter a temporary state of vulnerability following retrieval known as ‘reconsolidation', a process that can allow memories to be modified to incorporate new information. Although reconsolidation has become an attractive target for treatment of memories related to traumatic past experiences, we still do not know what new information triggers the updating of retrieved memories. Here, we used biochemical markers of synaptic plasticity in combination with a novel behavioral procedure to determine what was learned during memory reconsolidation under normal retrieval conditions. We eliminated new information during retrieval by manipulating animals' training experience and measured changes in proteasome activity and GluR2 expression in the amygdala, two established markers of fear memory lability and reconsolidation. We found that eliminating new contextual information during the retrieval of memories for predictable and unpredictable fear associations prevented changes in proteasome activity and glutamate receptor expression in the amygdala, indicating that this new information drives the reconsolidation of both predictable and unpredictable fear associations on retrieval. Consistent with this, eliminating new contextual information prior to retrieval prevented the memory-impairing effects of protein synthesis inhibitors following retrieval. These results indicate that under normal conditions, reconsolidation updates memories by incorporating new contextual information into the memory trace. Collectively, these results suggest that controlling contextual information present during retrieval may be a useful strategy for improving reconsolidation-based treatments of traumatic memories associated with anxiety disorders such as post-traumatic stress disorder.
doi:10.1038/npp.2015.161
PMCID: PMC4864640  PMID: 26062788
3.  Time to Death after Terminal Withdrawal of Mechanical Ventilation: Specific Respiratory and Physiologic Parameters May Inform Physician Predictions 
Journal of Palliative Medicine  2015;18(12):1040-1047.
Abstract
Background: Discussions about withdrawal of life-sustaining therapies often include family members of critically ill patients. These conversations should address essential components of the dying process, including expected time to death after withdrawal.
Objectives: The study objective was to aid physician communication about the dying process by identifying predictors of time to death after terminal withdrawal of mechanical ventilation.
Methods: We conducted an observational analysis from a single-center, before–after evaluation of an intervention to improve palliative care. We studied 330 patients who died after terminal withdrawal of mechanical ventilation. Predictors included patient demographics, laboratory, respiratory, and physiologic variables, and medication use.
Results: The median time to death for the entire cohort was 0.58 hours (interquartile range (IQR) 0.22–2.25 hours) after withdrawal of mechanical ventilation. Using Cox regression, independent predictors of shorter time to death included higher positive end-expiratory pressure (per 1 cm H2O hazard ratio [HR], 1.07; 95% CI 1.04–1.11); higher static pressure (per 1 cm H2O HR, 1.03; 95% CI 1.01–1.04); extubation prior to death (HR, 1.41; 95% CI 1.06–1.86); and presence of diabetes (HR, 1.75; 95% CI 1.25–2.44). Higher noninvasive mean arterial pressure predicted longer time to death (per 1 mmHg HR, 0.98; 95% CI 0.97–0.99).
Conclusions: Comorbid illness and key respiratory and physiologic parameters may inform physician predictions of time to death after withdrawal of mechanical ventilation. An understanding of the predictors of time to death may facilitate discussions with family members of dying patients and improve communication about end-of-life care.
doi:10.1089/jpm.2015.0115
PMCID: PMC4677508  PMID: 26555010
4.  Genomic Investigations of Evolutionary Dynamics and Epistasis in Microbial Evolution Experiments 
Microbial evolution experiments enable us to watch adaptation in real time, and to quantify the repeatability and predictability of evolution by comparing identical replicate populations. Further, we can resurrect ancestral types to examine changes over evolutionary time. Until recently, experimental evolution has been limited to measuring phenotypic changes, or to tracking a few genetic markers over time. However, recent advances in sequencing technology now make it possible to extensively sequence clones or whole-population samples from microbial evolution experiments. Here, we review recent work exploiting these techniques to understand the genomic basis of evolutionary change in experimental systems. We first focus on studies that analyze the dynamics of genome evolution in microbial systems. We then survey work that uses observations of sequence evolution to infer aspects of the underlying fitness landscape, concentrating on the epistatic interactions between mutations and the constraints these interactions impose on adaptation.
doi:10.1016/j.gde.2015.08.008
PMCID: PMC4710057  PMID: 26370471
5.  Gastrostomy with peritoneal collar versus percutaneous endoscopic gastrostomy  
Journal of Medicine and Life  2016;9(4):408-412.
Aim. The present study aimed to perform a medico-surgical comparative analysis of the 2 most widely used techniques: gastrostomy with peritoneal collar versus percutaneous endoscopic gastrostomy, based on the vast clinical experience in an Upper Digestive Surgery Clinic.
Materials and method. A retrospective study was carried out between January 2010 and January 2015 on the patients admitted for a surgical solution for feeding. The indications, preoperative preparation, surgical techniques, and postoperative outcomes were analyzed.
Results. Out of the 94 cases admitted for a surgical solution for feeding, 67 underwent gastrostomy with peritoneal collar (GPC) and in 27 cases percutaneous endoscopic gastrostomy (PEG) was performed. The indications for GPC were benign or malign causes of dysphagia, the most frequent being malign tumors of tongue, pharynx and larynx (47.76%), advanced inoperable esophageal or eso-cardiac cancers (26,86%), post-caustic esophageal stenosis (10.44%). PEG was performed in patients with functional difficulties of swallowing: sequelae of cerebral vascular accidents (44.44%), low Glasgow Coma Scale Score (29.62%) of different etiologies, Parkinson disease (18.51%) advanced dementia (7.4%), early nasopharyngeal cancer (2 cases). The intraoperatory and postoperatory complications were few and of minor importance in both techniques, but PEG allowed an immediate retake of alimentation (vs. at least 48 hours wait in GPC), with less gastric stasis, biliary reflux and aspiration related respiratory problems.
Conclusions. Both techniques are easy and safe to perform, but an appropriate selection is required according to the cause of the swallowing difficulty. In cases with permeable digestive tube, PEG may be an excellent minimally invasive solution, but the costs and availability of the PEG kit and prehydrolyzed nutritive solution, as well as the co-existence of an upper digestive endoscopy service were limitations that had to be taken into account.
PMCID: PMC5141402  PMID: 27928446
dysphagia; swallowing difficulties; surgical solution for feeding; percutaneous endoscopic gastrostomy
6.  Safety profile of lamotrigine in overdose 
Background:
Lamotrigine is an anticonvulsant as well as a mood stabilizer. Apart from its established use in the treatment of epilepsy, there has been an expansion of its use in the treatment of mental disorders. Patients with epilepsy as well as those with mental disorders are at increased risk of deliberate drug overdoses. An evidence base for the safety profile of lamotrigine in overdose is an essential tool for prescribers. The objective of this study was to carry out a narrative synthesis of the existing evidence for the safety profile of lamotrigine in overdose.
Methods:
A systematic search was conducted of EMBASE (1974 to December 2015), MEDLINE (1946 to December 2015), PsycINFO (1806 to December 2015) and CINAHL (1981 to December 2015) databases. Studies were included in which there was a deliberate or accidental single drug overdose of lamotrigine, with its toxic effects described. Studies that did not involve an overdose were excluded. A narrative synthesis of the described toxic effects was carried out.
Results:
Out of 562 articles identified, 26 studies were included, mainly in the form of case reports and series. The most commonly described toxic effects of lamotrigine were on the central nervous system, specifically seizures, movement disorders and reduced consciousness. Other toxic effects included QTc interval and QRS complex prolongations, hypersensitivity reactions, serotonin syndrome as well as rhabdomyolysis possibly due to seizures and/or agitation. Deaths were recorded in two studies, with cardiovascular and neurological toxic effects described.
Conclusions:
Even though lamotrigine has been reported to be well tolerated, there is a risk of toxic effects which can be life threatening in overdose. This needs to be borne in mind when prescribing to patients at an increased risk of deliberate drug overdose.
doi:10.1177/2045125316656707
PMCID: PMC5167082  PMID: 28008350
death; lamotrigine; overdose; safety; toxicity
7.  Coastal leatherback turtles reveal conservation hotspot 
Scientific Reports  2016;6:37851.
Previous studies have shown that the world’s largest reptile – the leatherback turtle Dermochelys coriacea – conducts flexible foraging migrations that can cover thousands of kilometres between nesting sites and distant foraging areas. The vast distances that may be travelled by migrating leatherback turtles have greatly complicated conservation efforts for this species worldwide. However, we demonstrate, using a combination of satellite telemetry and stable isotope analysis, that approximately half of the nesting leatherbacks from an important rookery in South Africa do not migrate to distant foraging areas, but rather, forage in the coastal waters of the nearby Mozambique Channel. Moreover, this coastal cohort appears to remain resident year-round in shallow waters (<50 m depth) in a relatively fixed area. Stable isotope analyses further indicate that the Mozambique Channel also hosts large numbers of loggerhead turtles Caretta caretta. The rare presence of a resident coastal aggregation of leatherback turtles not only presents a unique opportunity for conservation, but alongside the presence of loggerhead turtles and other endangered marine megafauna in the Mozambique Channel, highlights the importance of this area as a marine biodiversity hotspot.
doi:10.1038/srep37851
PMCID: PMC5122952  PMID: 27886262
8.  Hippocampal Plasticity During the Progression of Alzheimer’s disease 
Neuroscience  2015;309:51-67.
Neuroplasticity involves molecular changes in central nervous system (CNS) synaptic structure and function throughout life. The concept of neural organization allows for synaptic remodeling as a compensatory mechanism to the early pathobiology of Alzheimer’s disease (AD) in an attempt to maintain brain function and cognition during the onset of dementia. The hippocampus, a crucial component of the medial temporal lobe memory circuit, is affected early in AD and displays synaptic and intraneuronal molecular remodeling against a pathological background of extracellular amyloid-beta (Aβ) deposition and intracellular neurofibrillary tangle (NFT) formation in the early stages of AD. Here we discuss human clinical pathological findings supporting the concept that the hippocampus is capable of neural plasticity during mild cognitive impairment (MCI), a prodromal stage of AD and early stage AD.
doi:10.1016/j.neuroscience.2015.03.006
PMCID: PMC4567973  PMID: 25772787
9.  A bioreactor system for in vitro tendon differentiation and tendon tissue engineering 
There is significant clinical demand for functional tendon grafts in human and veterinary medicine. Tissue engineering techniques combining cells, scaffolds and environmental stimuli may circumvent the shortcomings of traditional transplantation processes. In this study, the influence of cyclic mechanical stimulation on graft maturation and cellular phenotype was assessed in an equine model. Decellularized tendon scaffolds from four equine sources were seeded with syngeneic bone marrow-derived mesenchymal stem cells and subjected to 0%, 3% or 5% strain at 0.33Hz for up to one hour daily for 11 days. Cells cultured at 3% strain integrated deep into their scaffolds, altered extracellular matrix composition, adopted tendon-like gene expression profiles, and increased construct elastic modulus and ultimate tensile strength to native levels. This bioreactor protocol is therefore suitable for cultivating replacement tendon material or as an in vitro model for studying differentiation of stem cells toward tendon.
doi:10.1002/jor.22848
PMCID: PMC5098427  PMID: 25664422
tendon; tissue engineering; bioreactor; extracellular matrix; mesenchymal stem cell
10.  rs4771122 predicts multiple measures of long-term weight loss after bariatric surgery 
Obesity surgery  2015;25(11):2225-2229.
We examined the association of 34 single nucleotide polymorphisms with weight loss up to 9.5 years after Roux-en-Y surgery. Participants were enrollees in the NUgene biobank with stored DNA and linked electronic health records. Ninety-five self-identified white participants underwent surgery and had follow-up weights obtained between 1 and 9.5 years after surgery. SNP rs4771122 was the variant most significantly associated with long term weight loss after surgery in a repeated linear mixed model (p = .004) of long-term weight loss. In this model, each additional copy of the minor allele was associated with nearly 5 percent greater percentage weight loss. This same SNP was also nominally significantly (p < .05) associated with weight loss trajectories, weight loss nadir, and weight loss 2 years after surgery.
doi:10.1007/s11695-015-1872-7
PMCID: PMC4598314  PMID: 26337695
Bariatric Surgery; Repeated Measures; Predictors; Long Term Weight Loss; Roux-en-Y gastric bypass; SNP; Obesity GWAS
11.  Covert and Overt Hepatic Encephalopathy: Diagnosis and Management 
Hepatic encephalopathy (HE) is part of a spectrum of neurocognitive changes in cirrhosis. HE is divided into two broad categories based on severity, covert (CHE) and overt (CHE). CHE has a significant impact on a patient’s quality of life, driving performances, and has recently been associated with increased hospitalizations and death. Likewise, OHE is associated with increased rates of hospitalizations and mortality, and poor quality of life. Given its significant burden on patients, care takers, and the health care system, it’s imperative for early diagnosis and management. In addition, a focus should also be directed on patient and family member education on the disease progression and adherence to medications. Treatment strategies include the use of non-absorbable disaccharides, antibiotics (i.e. rifaximin), and potentially probiotics. Other therapies currently under further investigation include: L-ornithine-L-aspartate, ornithine phenylacetate, glycerol phenylbutyrate, molecular adsorbent recirculating system, and albumin infusion.
doi:10.1016/j.cgh.2015.06.039
PMCID: PMC4618040  PMID: 26164219
Cirrhosis; Covert Hepatic Encephalopathy; Overt Hepatic Encephalopathy; Hepatic Encephalopathy; Ammonia; lactulose; Rifaximin
12.  Shopping for Direct-to-Consumer Screening: Buyers and Clinicians Beware 
Journal of General Internal Medicine  2015;30(10):1400-1401.
doi:10.1007/s11606-015-3313-7
PMCID: PMC4579228  PMID: 25855482
13.  Impact of Rotation Correction after Brace Treatment on Prognosis in Adolescent Idiopathic Scoliosis 
Asian Spine Journal  2016;10(5):893-900.
Study Design
Level 4 retrospective review.
Purpose
Brace treatment is the standard nonoperative treatment for adolescent idiopathic scoliosis (AIS). Rotation correction is also important, because AIS involves a rotation deformity. The purpose of this study was to evaluate the impact of rotation correction after Osaka Medical College (OMC) brace treatment on clinical outcomes in AIS.
Overview of Literature
Brace treatment has a significant effect on the progression of AIS. However, few reports have examined rotation correction after brace treatment.
Methods
A total of 46 patients who wore the OMC brace were retrospectively reviewed. The curve magnitude was determined according to the Cobb method, and the rotation angle of the apical vertebrae was measured by the modified Nash-Moe method. Based on the difference in the rotation angle before and after the initial brace treatment, patients were divided into two groups. Group A (n=33) was defined as no change or improvement of the rotation angle; group B (n=13) was defined as deterioration of the rotation angle. If the patients had curve or rotation progression of 5° or more at skeletal maturity, or had undergone surgery, the treatment was considered a failure.
Results
Differences of rotation angle between before and after the initial brace treatment were 2°±2° in group A and –3°±2° in group B (p<0.001). The rates of treatment failure were 42% in group A and 77% in group B (p<0.05). This study included 25 patients with Lenke type 1 (54%). Group A (24%) with Lenke type 1 also had a significantly better success rate of brace treatment than group B (75%) (p<0.05).
Conclusions
Insufficient rotation correction increased brace treatment failure. Better rotation correction resulted in a higher success rate of brace treatment in patients with Lenke type 1.
doi:10.4184/asj.2016.10.5.893
PMCID: PMC5081324  PMID: 27790317
Adolescent idiopathic scoliosis; Brace treatment; Rotation correction; Brace treatment failure; Clinical outcome
14.  How Stable are Temperaments in the Clinical Setting: A Pilot Study 
Background
An essential point in evaluating the utility of measuring temperaments is the stability of the instrument used especially in the presence of mental disorders. One of the most commonly used instruments in the clinical setting is the Temperament Evaluation of Memphis, Pisa, Paris and San Diego Auto-questionnaire (TEMPS-A). To our knowledge, the TEMPS-A’s stability in an outpatient adult clinical setting has not been evaluated.
Objective:
To assess the stability of the effect of temperament, time and clinical intervention.
Methods:
A sample of 89 adult outpatients was assessed at baseline and follow-up on their TEMPS-A scores. Diagnoses of mental disorders were reached through clinical interviews, and the severity of the conditions was clinically assessed at baseline and follow-up on a Likert scale. Changes in scores were examined in terms of z-scores, and possible predictors of the change in scores were assessed.
Results:
Eighty-nine percent of all subjects’ temperaments scores did not change or changed less than one z-score, and specifically: 84.2% in the case of depressive, 89.9% for cyclothymic, 92.1% for hyperthymic, 92.2% for irritable, and 86.5% for anxious temperaments. For all of the five temperaments, age, gender, time difference between baseline and follow up, number of diagnoses, and percent improvement were not significantly associated with the change in temperament scores.
Limitations:
Well-established severity measures would add to the validity of any future findings.
Conclusion:
Shifts in temperament scores between baseline and follow-up were minor, thus proving the stability of temperaments and the TEMPS-A scale in a clinical setting.
doi:10.2174/1745017901612010059
PMCID: PMC5054501  PMID: 27733865
Anxious; Cyclothymic; Dysthymic; Hyperthymic; Irritable; Temps A
15.  Role of spleen elastography in patients with chronic liver diseases 
World Journal of Gastroenterology  2016;22(35):7857-7867.
The development of liver cirrhosis and portal hypertension (PH), one of its major complications, are structural and functional alterations of the liver, occurring in many patients with chronic liver diseases (CLD). Actually the progressive deposition of hepatic fibrosis has a key role in the prognosis of CLD patients. The subsequent development of PH leads to its major complications, such as ascites, hepatic encephalopathy, variceal bleeding and decompensation. Liver biopsy is still considered the reference standard for the assessment of hepatic fibrosis, whereas the measurement of hepatic vein pressure gradient is the standard to ascertain the presence of PH and upper endoscopy is the method of choice to detect the presence of oesophageal varices. However, several non-invasive tests, including elastographic techniques, are currently used to evaluate the severity of liver disease and predict its prognosis. More recently, the measurement of the spleen stiffness has become particularly attractive to assess, considering the relevant role accomplished by the spleen in splanchnic circulation in the course of liver cirrhosis and in the PH. Moreover, spleen stiffness as compared with liver stiffness better represents the dynamic changes occurring in the advanced stages of cirrhosis and shows higher diagnostic performance in detecting esophageal varices. The aim of this review is to provide an exhaustive overview of the actual role of spleen stiffness measurement as assessed by several elastographic techniques in evaluating both liver disease severity and the development of cirrhosis complications, such as PH and to highlight its potential and possible limitations.
doi:10.3748/wjg.v22.i35.7857
PMCID: PMC5028802  PMID: 27672283
Cirrhosis; Spleen stiffness; Elastography; Portal hypertension; Transient elastography
16.  Revealing humans’ sensorimotor functions with electrical cortical stimulation 
Direct electrical stimulation (DES) of the human brain has been used by neurosurgeons for almost a century. Although this procedure serves only clinical purposes, it generates data that have a great scientific interest. Had DES not been employed, our comprehension of the organization of the sensorimotor systems involved in movement execution, language production, the emergence of action intentionality or the subjective feeling of movement awareness would have been greatly undermined. This does not mean, of course, that DES is a gold standard devoid of limitations and that other approaches are not of primary importance, including electrophysiology, modelling, neuroimaging or psychophysics in patients and healthy subjects. Rather, this indicates that the contribution of DES cannot be restricted, in humans, to the ubiquitous concepts of homunculus and somatotopy. DES is a fundamental tool in our attempt to understand the human brain because it represents a unique method for mapping sensorimotor pathways and interfering with the functioning of localized neural populations during the performance of well-defined behavioural tasks.
doi:10.1098/rstb.2014.0207
PMCID: PMC4528819  PMID: 26240422
electrical stimulation; sensorimotor maps; somatotopy; homunculus; language; human
18.  Effect of femoral canal shape on mechanical stress distribution and adaptive bone remodelling around a cementless tapered-wedge stem 
Bone & Joint Research  2016;5(9):362-369.
Objectives
In total hip arthroplasty (THA), the cementless, tapered-wedge stem design contributes to achieving initial stability and providing optimal load transfer in the proximal femur. However, loading conditions on the femur following THA are also influenced by femoral structure. Therefore, we determined the effects of tapered-wedge stems on the load distribution of the femur using subject-specific finite element models of femurs with various canal shapes.
Patients and Methods
We studied 20 femurs, including seven champagne flute-type femurs, five stovepipe-type femurs, and eight intermediate-type femurs, in patients who had undergone cementless THA using the Accolade TMZF stem at our institution. Subject–specific finite element (FE) models of pre- and post-operative femurs with stems were constructed and used to perform FE analyses (FEAs) to simulate single-leg stance. FEA predictions were compared with changes in bone mineral density (BMD) measured for each patient during the first post-operative year.
Results
Stovepipe models implanted with large-size stems had significantly lower equivalent stress on the proximal-medial area of the femur compared with champagne-flute and intermediate models, with a significant loss of BMD in the corresponding area at one year post-operatively.
Conclusions
The stovepipe femurs required a large-size stem to obtain an optimal fit of the stem. The FEA result and post-operative BMD change of the femur suggest that the combination of a large-size Accolade TMZF stem and stovepipe femur may be associated with proximal stress shielding.
Cite this article: M. Oba, Y. Inaba, N. Kobayashi, H. Ike, T. Tezuka, T. Saito. Effect of femoral canal shape on mechanical stress distribution and adaptive bone remodelling around a cementless tapered-wedge stem. Bone Joint Res 2016;5:362–369. DOI: 10.1302/2046-3758.59.2000525.
doi:10.1302/2046-3758.59.2000525
PMCID: PMC5017138  PMID: 27601435
Tapered-wedge stem; Finite element analysis; Total hip arthroplasty; Adaptive bone remodelling
19.  Human Cytochrome P450 2W1 Is Not Expressed in Adrenal Cortex and Is Only Rarely Expressed in Adrenocortical Carcinomas 
PLoS ONE  2016;11(9):e0162379.
Human cytochome P450 2W1 (CYP2W1) enzyme is expressed in fetal colon and in colon tumors. The level of expression is higher in colon metastases than in the parent tumors and the enzyme is a possible drug target for treatment of colorectal cancer, as demonstrated in mouse xenograft studies. A previous study published in this journal reported that CYP2W1 is highly expressed in normal and transformed adrenal tissue. However, adrenal expression of CYP2W1 protein was not seen in previous studies in our research group. To clarify this inconsistency, we have used qRT-PCR and Western blotting with CYP2W1-specific antibodies to probe a panel of 27 adrenocortical carcinomas and 35 normal adrenal cortex samples. CYP2W1 mRNA expression is seen in all samples. However, significant CYP2W1 protein expression was found in only one tumor sample (a testosterone-producing adrenocortical carcinoma) and not in any normal tissue. Differences in the specificity of the CYP2W1 antibodies used in the two studies may explain the apparent discrepancy. We conclude that normal adrenal tissue lacks P450 2W1 enzyme expression; also, adrenocortical carcinomas generally do not express the enzyme. This information thus underline the colon cancer specificity of CYP2W1 enzyme expression and has implications for the development of anti-colon cancer therapies based on CYP2W1 as a drug target, since 2W1-dependent bioactivation of prodrugs for CYP2W1 will not take place in normal adrenal tissue or other non-transformed tissues.
doi:10.1371/journal.pone.0162379
PMCID: PMC5012573  PMID: 27598485
20.  Concurrent Mucosal Melanoma and Angiofibroma of the Nose 
Malignant melanoma rarely develops in the paranasal sinuses, and generally has a poor prognosis. However, mucosal melanoma can masquerade both clinically and histopathologically as a benign lesion, rendering accurate early diagnosis difficult. On the other hand, angiofibroma, a benign tumor, is more easily diagnosed than a mucosal melanoma, because the former exhibits specific histopathological features. No cases of concurrent angiofibroma and mucosal melanoma have been reported to date. We describe such a case below.
doi:10.21053/ceo.2015.01333
PMCID: PMC4996105  PMID: 27095516
Melanoma; Angiofibroma; Nasal cavity
21.  A Theoretical Basis for Entropy-Scaling Effects in Human Mobility Patterns 
PLoS ONE  2016;11(8):e0161630.
Characterizing how people move through space has been an important component of many disciplines. With the advent of automated data collection through GPS and other location sensing systems, researchers have the opportunity to examine human mobility at spatio-temporal resolution heretofore impossible. However, the copious and complex data collected through these logging systems can be difficult for humans to fully exploit, leading many researchers to propose novel metrics for encapsulating movement patterns in succinct and useful ways. A particularly salient proposed metric is the mobility entropy rate of the string representing the sequence of locations visited by an individual. However, mobility entropy rate is not scale invariant: entropy rate calculations based on measurements of the same trajectory at varying spatial or temporal granularity do not yield the same value, limiting the utility of mobility entropy rate as a metric by confounding inter-experimental comparisons. In this paper, we derive a scaling relationship for mobility entropy rate of non-repeating straight line paths from the definition of Lempel-Ziv compression. We show that the resulting formulation predicts the scaling behavior of simulated mobility traces, and provides an upper bound on mobility entropy rate under certain assumptions. We further show that this formulation has a maximum value for a particular sampling rate, implying that optimal sampling rates for particular movement patterns exist.
doi:10.1371/journal.pone.0161630
PMCID: PMC5003381  PMID: 27571423
22.  Ureteral metastasis from prostate cancer 
BMJ Case Reports  2014;2014:bcr2014206736.
A 59-year-old man had an elevated prostate-specific antigen (PSA) concentration (439 ng/mL) in December 2008. We diagnosed prostatic adenocarcinoma by prostate needle biopsy. CT and MRI showed a prostatic tumour with bone and lymph node metastases. Combined androgen blockade therapy reduced the PSA level temporarily. After the PSA level gradually started to increase again and reached 27.27 ng/mL in October 2010, the patient was diagnosed with castration-resistant prostate cancer and treated with docetaxel chemotherapy. Radiological examination detected left hydronephrosis and a tumour in the left lower ureter in March 2011. Retrograde pyelography and urine cytology of class 3 from the left ureter indicated that the ureteral mass was a urothelial carcinoma. A left nephroureterectomy was performed. After the operation, the pathological examination showed a metastatic prostate carcinoma, accompanied by a decrease in the serum PSA level from 59.56 to 45.33 ng/mL.
doi:10.1136/bcr-2014-206736
PMCID: PMC4154035  PMID: 25168825
23.  Metavinculin tunes the flexibility and the architecture of vinculin induced bundles of actin filaments 
Journal of molecular biology  2015;427(17):2782-2798.
Vinculin is an abundant protein found at cell-cell and cell-extracellular matrix junctions. In muscles, a longer splice-isoform of vinculin, metavinculin, is also expressed. The metavinculin-specific insert is part of the C-terminal tail domain, the actin-binding site of both isoforms. Mutations in the metavinculin-specific insert are linked to heart disease such as dilated cardiomyopathies. Vinculin tail domain (VT) both binds and bundles actin filaments. Metavinculin tail domain (MVT) binds actin filaments in a similar orientation but does not bundle filaments. Recently, MVT was reported to sever actin filaments. In this work, we asked how MVT influences F-actin alone or in combination with VT. Cosedimentation and limited proteolysis experiments indicated a similar actin binding affinity and mode for both VT and MVT. In real time TIRF microscopy experiments MVT’s severing activity was negligible. Instead, we found that MVT binding caused a two-fold reduction in F-actin’s bending persistence length and increased susceptibility to breakage. Perhaps MVT allows the load of muscle contraction to act as a signal to reorganize actin filaments. Using mutagenesis and site-directed labeling with fluorescence probes, we determined that MVT alters actin interprotomer contacts and dynamics, which presumably reflect the observed changes in bending persistence length. Finally, we found that MVT decreases the density and thickness of actin filament bundles generated by VT. Altogether, our data suggest that MVT alters actin filament flexibility and tunes filament organization in the presence of VT. Both of these activities are potentially important for muscle cell function.
doi:10.1016/j.jmb.2015.07.005
PMCID: PMC4540644  PMID: 26168869
24.  The OVLT initiates the fall in arterial pressure evoked by high dose lipopolysaccharide: Evidence that dichotomous, dose-related mechanisms mediate endotoxic hypotension 
Journal of neuroimmunology  2015;285:94-100.
This study tested the hypothesis that lipopolysaccharide (LPS) lowers arterial pressure through two different mechanisms depending on the dose. Previously, we found that a low hypotensive dose of LPS (1 mg/kg) lowers arterial pressure by activating vagus nerve afferents. Here we report that hypotension evoked by high dose LPS (15 mg/kg) can be prevented by injecting lidocaine into the OVLT but not by vagotomy or inactivation of the NTS. The hypotension produced by both LPS doses was correlated with elevated extracellular norepinephrine concentrations in the POA and prevented by blocking alpha-adrenergic receptors. Thus, initiation of endotoxic hypotension is dose-related, mechanistically.
doi:10.1016/j.jneuroim.2015.05.023
PMCID: PMC4511856  PMID: 26198924
Endotoxin; lipopolysaccharide; septic shock; OVLT; preoptic area
25.  A high-throughput imaging-based mapping platform for the systematic identification of gene positioning factors 
Cell  2015;162(4):911-923.
Summary
Genomes are non-randomly arranged in the 3D space of the cell nucleus. Here we have developed HIPMap, a high-precision, high-throughput, automated fluorescent in situ hybridization imaging pipeline, for mapping of the spatial location of genome regions at large scale. High-throughput imaging position mapping (HIPMap) enabled an unbiased siRNA screen for factors involved in genome organization in human cells. We identify 50 cellular factors required for proper positioning of a set of functionally diverse genomic loci. Positioning factors include chromatin remodelers, histone modifiers and nuclear envelope and pore proteins. Components of the replication and post-replication chromatin re-assembly machinery are prominently represented amongst positioning factors and timely progression of cells through replication, but not mitosis, is required for correct gene positioning. Our results establish a method for the large scale mapping of genome locations and have led to the identification of a compendium of cellular factors involved in spatial genome organization.
Graphical Abstract
doi:10.1016/j.cell.2015.07.035
PMCID: PMC4538709  PMID: 26276637

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