bluuebunny/crossref_metadata_2025 huggingface dataset:
Integrating Neuroscience in Criminal Law: The Dutch Situation as an Example
Authors: Noyon Lucas , van der Wolf Michiel J. F. , Mevis Paul A. M. , van Marle Hjalmar J. C.
Published: January 2019

Empirical findings demonstrate that neuroscientific expertise is increasingly prevalent in courtrooms. This suggests that both “territorial conflicts” between law and neuroscience—for example about how to conceptualize concepts like culpability—and questions regarding the integration of neuroscience and law, which both have long been present in theoretical discussions, are now finding their way to legal practice. As jurisdictions around the globe differ on multiple dimensions (e.g., on how concepts like culpability are conceptualized, embedded in legal doctrine, and how integration of neuroscience takes place within (procedural) legal frameworks) analyses on a national level are needed next to universal endeavors. In this article, the Dutch situation will be addressed. First, we will assess whether the theoretical notions underlying Dutch criminal law are compatible with the theoretical discussion between neuroscience and legal doctrine. Second, we turn to empirical evidence as to the way neuroscientific information is brought into Dutch legal practice. Finally, we will examine how (well) the current practice of forensic assessment is able to accommodate neuroscientific information. Herewith, we aim to illustrate that the manner of integration is indeed dependent on jurisdiction specific features and that the international debate would benefit from more national perspectives.
SR Ca2+ leak in skeletal muscle fibers acts as an intracellular signal to increase fatigue resistance
Authors: Ivarsson Niklas , Mattsson C. Mikael , Cheng Arthur J. , Bruton Joseph D. , Ekblom Björn , Lanner Johanna T. , Westerblad Håkan
Published: January 2019

Effective practices to improve skeletal muscle fatigue resistance are crucial for athletes as well as patients with dysfunctional muscles. To this end, it is important to identify the cellular signaling pathway that triggers mitochondrial biogenesis and thereby increases oxidative capacity and fatigue resistance in skeletal muscle fibers. Here, we test the hypothesis that the stress induced in skeletal muscle fibers by endurance exercise causes a reduction in the association of FK506-binding protein 12 (FKBP12) with ryanodine receptor 1 (RYR1). This will result in a mild Ca2+ leak from the sarcoplasmic reticulum (SR), which could trigger mitochondrial biogenesis and improved fatigue resistance. After giving mice access to an in-cage running wheel for three weeks, we observed decreased FKBP12 association to RYR1, increased baseline [Ca2+]i, and signaling associated with greater mitochondrial biogenesis in muscle, including PGC1α1. After six weeks of voluntary running, FKBP12 association is normalized, baseline [Ca2+]i returned to values below that of nonrunning controls, and signaling for increased mitochondrial biogenesis was no longer present. The adaptations toward improved endurance exercise performance that were observed with training could be mimicked by pharmacological agents that destabilize RYR1 and thereby induce a modest Ca2+ leak. We conclude that a mild RYR1 SR Ca2+ leak is a key trigger for the signaling pathway that increases muscle fatigue resistance.
GRASP depletion–mediated Golgi destruction decreases cell adhesion and migration via the reduction of α5β1 integrin
Authors: Ahat Erpan , Xiang Yi , Zhang Xiaoyan , Bekier Michael E. , Wang Yanzhuang
Published: January 2019

The Golgi apparatus is a membrane-bound organelle that serves as the center for trafficking and processing of proteins and lipids. To perform these functions, the Golgi forms a multilayer stacked structure held by GRASP55 and GRASP65 trans-oligomers and perhaps their binding partners. Depletion of GRASP proteins disrupts Golgi stack formation and impairs critical functions of the Golgi, such as accurate protein glycosylation and sorting. However, how Golgi destruction affects other cellular activities is so far unknown. Here, we report that depletion of GRASP proteins reduces cell attachment and migration. Interestingly, GRASP depletion reduces the protein level of α5β1 integrin, the major cell adhesion molecule at the surface of HeLa and MDA-MB-231 cells, due to decreased integrin protein synthesis. GRASP depletion also increases cell growth and total protein synthesis. These new findings enrich our understanding on the role of the Golgi in cell physiology and provide a potential target for treating protein-trafficking disorders.
Police Call-takers' First Substantive Question Projects the Outcome of the Call
Authors: Kent Alexandra , Antaki Charles
Published: January 2019

Police call-takers need to gather as much data as is needed, as quickly as possible, to determine whether and what action should be taken. On analysing 514 calls to a UK centre handling emergency (999) and non-emergency (101) calls, we find that the call-taker’s first substantive question already carries a diagnosis of the merits of the caller's case, and an implication of the call's likely outcome. Such questions come principally in four formats. On a gradient of increasing scepticism, these are requests for the caller's location (which are treated as indicating that police action will be taken); open-ended requests for further information (treated as neutral); and queries of the relevance of the incident or legitimacy of the caller, and reformulations of the caller's reason for calling (both projecting upcoming refusal of police action). We discuss the implications of this gradient for understanding how the call-takers manage their institutional goals. Data are in British English.
Protein fold recognition based on multi-view modeling
Authors: Yan Ke , Fang Xiaozhao , Xu Yong , Liu Bin
Published: January 2019

Motivation

Protein fold recognition has attracted increasing attention because it is critical for studies of the 3D structures of proteins and drug design. Researchers have been extensively studying this important task, and several features with high discriminative power have been proposed. However, the development of methods that efficiently combine these features to improve the predictive performance remains a challenging problem.

Results

In this study, we proposed two algorithms: MV-fold and MT-fold. MV-fold is a new computational predictor based on the multi-view learning model for fold recognition. Different features of proteins were treated as different views of proteins, including the evolutionary information, secondary structure information and physicochemical properties. These different views constituted the latent space. The ε-dragging technique was employed to enlarge the margins between different protein folds, improving the predictive performance of MV-fold. Then, MV-fold was combined with two template-based methods: HHblits and HMMER. The ensemble method is called MT-fold incorporating the advantages of both discriminative methods and template-based methods. Experimental results on five widely used benchmark datasets (DD, RDD, EDD, TG and LE) showed that the proposed methods outperformed some state-of-the-art methods in this field, indicating that MV-fold and MT-fold are useful computational tools for protein fold recognition and protein homology detection and would be efficient tools for protein sequence analysis. Finally, we constructed an update and rigorous benchmark dataset based on SCOPe (version 2.07) to fairly evaluate the performance of the proposed method, and our method achieved stable performance on this new dataset. This new benchmark dataset will become a widely used benchmark dataset to fairly evaluate the performance of different methods for fold recognition.

Supplementary information

Supplementary data are available at Bioinformatics online.
Benzene metabolite hydroquinone promotes DNA homologous recombination repair via the NF-κB pathway
Authors: Yang Xuejing , Lu Yedan , He Fuhong , Hou Fenxia , Xing Caihong , Xu Peiyu , Wang Qian-Fei
Published: January 2019

Benzene, a widespread environmental pollutant, induces DNA double-strand breaks (DSBs) and DNA repair, which may further lead to oncogenic mutations, chromosomal rearrangements and leukemogenesis. However, the molecular mechanisms underlying benzene-induced DNA repair and carcinogenesis remain unclear. The human osteosarcoma cell line (U2OS/DR-GFP), which carries a GFP-based homologous recombination (HR) repair reporter, was treated with hydroquinone, one of the major benzene metabolites, to identify the potential effects of benzene on DSB HR repair. RNA-sequencing was further employed to identify the potential key pathway that contributed to benzene-initiated HR repair. We found that treatment with hydroquinone induced a significant increase in HR. NF-κB pathway, which plays a critical role in carcinogenesis in multiple tumors, was significantly activated in cells recovered from hydroquinone treatment. Furthermore, the upregulation of NF-κB by hydroquinone was also found in human hematopoietic stem and progenitor cells. Notably, the inhibition of NF-κB activity by small molecule inhibitors (QNZ and JSH-23) significantly reduced the frequency of hydroquinone-initiated HR (−1.36- and −1.77-fold, respectively, P < 0.01). Our results demonstrate an important role of NF-κB activity in promoting HR repair induced by hydroquinone. This finding sheds light on the underlying mechanisms involved in benzene-induced genomic instability and leukemogenesis and may contribute to the larger exploration of the influence of other environmental pollutants on carcinogenesis.
Dynamics in Central–Local Division of the Authority of EIA Approval in China
Authors: Ma Yun
Published: January 2019

In comparison with the dominant ‘consideration model’, the veto arrangement of environmental impact assessment (EIA) in China is a substantive regulatory feature that empowers environmental authorities to impinge on development activities. However, the anticipated efficacies thereof are compromised by the central–local division of EIA approval. The mismatch between high enforcement rates and prevalent non-compliance shows that EIA approval can be easily circumvented, especially at local levels. Recent mass, blanket devolution in a hasty manner, coupled with enthusiastic local responses in watering down EIA approval, raises serious concerns about its appropriateness and effectiveness. The tendency to deregulate by loosening environmental scrutiny and the reinvention of EIA procedures in light of project licensing processes impairs the veto effects of EIA approval. Without formal legislative empowerment in the central–local framework and individualised regulatory impact analysis, the current devolution approach is bound to endanger environmental quality and undermine the legitimacy of the veto arrangement.
Left External Carotid Artery to the Middle Cerebral Artery Bypass with Radial Artery Graft and Clip Reconstruction of a Large Middle Cerebral Artery Fusiform Aneurysm: 3-Dimensional Operative Video
Authors: Cheng Chun-Yu , Qazi Zeeshan , Sekhar Laligam N
Published: January 2019

This 16-yr-old boy presented with episodes of severe headaches, blurred vision, dizziness, and muffled hearing and was discovered to have a large fusiform aneurysm of the left middle cerebral artery (MCA), M1 segment, 20 × 12 mm in dimension. The lenticulostriate arteries were arising proximal and distal to the aneurysm, but the anterior temporal artery was arising from the aneurysm. The aneurysm culminated in the distal M1 segment, and M1 immediately branched into 3 M2 vessels, the lower one being the larger. Due to origin of the lenticulostriate arteries and the anterior temporal artery and patient's age, a bypass was preferred to a flow diversion stent.

 He underwent left frontotemporal craniotomy and orbital osteotomy, left cervical external carotid artery exposure followed by radial artery graft extraction. The Sylvian fissure was opened and intracranial ICA was exposed for proximal control. The distal M2 vessels traced back toward the aneurysm. The aneurysm was not clippable and a bypass to the larger inferior M2 branch was performed followed by aneurysm trapping. The radial artery graft bypass was placed from the left external carotid artery to the M2 segment of left MCA, followed by clip reconstruction and occlusion of the MCA aneurysm with the preservation of the anterior temporal branch and the lenticulostriate vessels. The patient had no postoperative complications. At the follow-up, one month after surgery, he was doing well, and his angiogram demonstrated patency of the bypass.

 This video shows the management of a complex fusiform M1 aneurysm with bypass and trapping.

 Informed consent was obtained from the patient prior to the surgery that included videotaping of the procedure and its distribution for educational purposes. All relevant patient identifiers have also been removed from the video and accompanying radiology slides.
Expanding the toolbox of synthetic riboswitches with guanine-dependent aptazymes
Authors: Stifel Julia , Spöring Maike , Hartig Jörg Steffen
Published: January 2019

Artificial riboswitches based on ribozymes serve as versatile tools for ligand-dependent gene expression regulation. Advantages of these so-called aptazymes are their modular architecture and the comparably little coding space they require. A variety of aptamer-ribozyme combinations were constructed in the past 20 years and the resulting aptazymes were applied in diverse contexts in prokaryotic and eukaryotic systems. Most in vivo functional aptazymes are OFF-switches, while ON-switches are more advantageous regarding potential applications in e.g. gene therapy vectors. We developed new ON-switching aptazymes in the model organism Escherichia coli and in mammalian cell culture using the intensely studied guanine-sensing xpt aptamer. Utilizing a high-throughput screening based on fluorescence-activated cell sorting in bacteria we identified up to 9.2-fold ON-switches and OFF-switches with a dynamic range up to 32.7-fold. For constructing ON-switches in HeLa cells, we used a rational design approach based on existing tetracycline-sensitive ON-switches. We discovered that communication modules responding to tetracycline are also functional in the context of guanine aptazymes, demonstrating a high degree of modularity. Here, guanine-responsive ON-switches with a four-fold dynamic range were designed. Summarizing, we introduce a series of novel guanine-dependent ribozyme switches operative in bacteria and human cell culture that significantly broaden the existing toolbox.
Phylogeny, divergence times and species delimitation of Tonicia (Polyplacophora: Chitonidae) from the eastern Pacific Ocean
Authors: Ibáñez Christian M , Eernisse Douglas J , Méndez Marco A , Valladares Moises , Sellanes Javier , Sirenko Boris I , Pardo-Gandarillas M Cecilia
Published: January 2019

The chiton genus Tonicia is composed of 12 species, 11 of which are found in the eastern Pacific, but the taxonomic status and geographical distribution of these species have long been controversial. In this study, we compare eastern Pacific Tonicia species using molecular systematics. The molecular markers cytochrome oxidase c subunit I (COI), 16S and 18S ribosomal RNA were used to estimate the phylogenetic relationships and divergence times among species. Species delimitations were inferred using a Bayesian generalized mixed Yule coalescent (bGMYC) and a Bayesian Poisson tree processes (bPTP) approach. We assigned southeastern Pacific specimens to nine recognized species based on their morphology, but these were resolved into only six species in our molecular phylogeny, suggesting that three of the recognized morpho species need to be synonymized. The bGMYC and bPTP analyses indicate the existence of six total coalescent groups interpreted as seven species in our gene tree results. Likewise, pairwise genetic distances, phylogenetic estimates and coalescent approaches support only seven lineages when considering specimens that match the nine currently recognized southeastern Pacific Tonicia species. We suggest that the colouration and morphological characters used to identify Tonicia species must be re-examined in depth.
Learning Theory and Educational Intervention: Producing Meaningful Evidence of Impact Through Layered Analysis
Authors: Cianciolo Anna T. , Regehr Glenn
Published: January 2019

Like evidence-based medicine, evidence-based education seeks to produce sound evidence of impact that can be used to intervene successfully in the future. The function of educational innovations, however, is much less well understood than the physical mechanisms of action of medical treatments. This makes production, interpretation, and use of educational impact evidence difficult. Critiques of medical education experiments highlight a need for such studies to do a better job of deepening understanding of learning in context; conclusions that “it worked” often precede scrutiny of what “it” was. The authors unpack the problem of representing educational innovation in a conceptually meaningful way. The more fundamental questions of “What is the intended intervention?” and “Did that intervention, in fact, occur?” are proposed as an alternative to the ubiquitous evaluative question of “Did it work?” The authors excavate the layers of intervention—techniques at the surface, principle in the middle, and philosophy at the core—and propose layered analysis as a way of examining an innovation’s intended function in context. The authors then use problem-based learning to illustrate how layered analysis can promote meaningful understanding of impact through specification of what was tried, under what circumstances, and what happened as a result. Layered analysis should support innovation design and evaluation by illuminating what principled adaptation of educational technique to local context could look like. It also promotes theory development by enabling more precise description of the learning conditions at work in a given implementation and how they may evolve with broader adoption.
A Seat at the Table: Strategic Engagement in Service Activities for Early-Career Faculty From Underrepresented Groups in the Academy
Authors: Carson Tiffany L. , Aguilera Adrian , Brown Susan D. , Peña Jessica , Butler Ashley , Dulin Akilah , Jonassaint Charles R. , Riley Isaretta , Vanderbom Kerri , Molina Kristine M. , Cené Crystal W.
Published: January 2019

Many academic institutions strive to promote more diverse and inclusive campuses for faculty, staff, and students. As part of this effort, these institutions seek to include individuals from historically underrepresented groups (URGs)—such as women, people from racial/ethnic minority populations, persons with disabilities—on committees and in other service activities. However, given the low number of faculty members from URGs at many institutions, these faculty members tend to receive more requests to provide service to the institution or department (e.g., serving on committees, mentoring) than their counterparts from majority groups. Faculty members from URGs, especially early-career faculty, thus risk becoming overburdened with providing service at the expense of working on other scholarly activities required for promotion and tenure (i.e., conducting research, publishing). Although many scholars and others have written about this “minority tax” and its implications for early-career faculty from underrepresented racial/ethnic minority groups, fewer have published about how this tax extends beyond racial/ethnic minorities to women and persons with disabilities. Further, the literature provides scant practical advice on how to avoid overburdening early-career faculty from URGs. Here, a group of multidisciplinary early- and mid-career faculty members from URGs seek to provide their peers from URGs with practical strategies for both evaluating the appropriateness of service requests and declining those that are not a good fit. The authors also provide institutional leaders with actionable recommendations to prevent early-career faculty from URGs from becoming overburdened with service.
Concomitant Anterior Cruciate Ligament Reconstruction and Temporary Hemiepiphysiodesis in the Skeletally Immature: A Combined Technique
Authors: O’Brien Adam O. , Stokes Julia , Bompadre Viviana , Schmale Gregory A.
Published: January 2019

Background:

Young athletes with an anterior cruciate ligament (ACL) disruption and limb malalignment pose a treatment dilemma. Little has been published regarding limb malalignment in this population. Our aim is to review the results of combined treatment of an ACL deficient knee and genu valgum in skeletally immature patients.

Methods:

A retrospective review of skeletally immature patients who underwent transphyseal ACL reconstruction and concomitant hemiepiphysiodesis between 2004 and 2015 by 1 surgeon at a single institution was performed. Included patients had at least a year of growth remaining and were followed to skeletal maturity. Patients with a diagnosis of a connective tissue disorder were excluded. Knee stability, rate of retear, the rate of mechanical axis correction, and time to full correction were determined.

Results:

Ninety skeletally immature patients underwent transphyseal ACL reconstruction, 8 of which met inclusion criteria. Mean time to correction of the valgus deformity was 13 months (0.4 degree/mo). No patient required additional surgeries for malalignment. All patients had improvement in knee stability. One patient had a retear of their ACL reconstruction, for a failure rate of 13%. Preoperative mechanical lateral distal femoral angle and mechanical axis deviation corrected to near-neutral alignment for all treated limbs and were significantly different (P=0.001) than those measured preoperatively.

Conclusions:

Promising results were seen for simultaneous correction of genu valgum and transphyseal ACL reconstruction. Treatment of both pathologies in a concomitant surgery can be considered in the appropriate population, with expected results comparable to each procedure in isolation.

Level of Evidence:

Level IV—case series.
Olecranon Fractures in Pediatric Patients With Osteogenesis Imperfecta
Authors: Tayne Samantha , Smith Peter A.
Published: January 2019

Background:

Osteogenesis imperfecta (OI) is a hereditary disorder characterized by an abnormality of the quality or quantity of type I collagen, leading to bone fragility. Fractures in children with OI may result from minor trauma and have atypical patterns. Previous studies have found a strong relationship between olecranon fractures and OI in pediatric populations, but the characteristics of olecranon fractures within the OI patient population have not been fully described.

Methods:

We reviewed the records of 358 children with a diagnosis of OI. Of those, 29 had at least 1 olecranon fracture. We collected general information relating to the patient’s diagnosis of OI including OI type, fracture history, mobility, and bisphosphonate treatment. Information regarding the fracture, treatment, and the occurrence of bilateral fractures were recorded, as well as weight, height, and axial bone mineral density z-score from the time of the fracture.

Results:

Within our OI population of 358 patients, we found an incidence of olecranon fracture of 8.1% (29 patients). The olecranon fractures occurred predominantly in the type I population (27 of 29). Within the population of patients specifically with OI type I (200 patients) the incidence is 13.5%, with 6% of OI type I patients sustaining bilateral olecranon fractures. The percentage of children with one olecranon fracture subsequently sustaining another on the contralateral side was 41.4%. The mean time to the second fracture was 5 months. The mean age at the time of the first olecranon fracture was 11.9 years old. The average axial bone mineral density z-score was −2.5 for primary fractures. All 12 patients who suffered a contralateral olecranon fracture had OI type I.

Conclusions:

Olecranon fractures in the OI population occur most commonly in patients with type I OI and during early adolescence, a period of rapid growth. There is a high rate of bilateral olecranon fractures, with the contralateral fracture occurring quickly after the primary fracture. Further studies may elucidate risk factors to determine which patients are most likely to fracture the contralateral side and therefore drive treatment and potentially prevention.

Level of Evidence:

Level IV—retrospective cohort study.
Histological Features of Flagellate Erythema
Authors: Ching Daniel , Wood Benjamin A. , Tiwari Shevya , Chan Jonathan , Harvey Nathan T.
Published: January 2019

Flagellate erythema is a distinctive eruption characterized by “whip-like” linear or curvilinear streaks and plaques, occurring mainly on the trunk. It has classically been described in 2 disparate clinical settings: chemotherapy with bleomycin and ingestion of mushrooms (most commonly Shiitake mushrooms). Most of the literature comprises single case reports, often with minimal histological description of rather nonspecific features. We describe in detail the histological features of 3 cases of flagellate erythema (2 related to bleomycin therapy and one related to ingestion of mushrooms) and review the findings described in the literature to define the spectrum of histological changes encountered in this eruption. Our 3 cases showed mild epidermal changes, with spongiosis and variable interface inflammation. All 3 showed a relatively prominent dermal lymphohistiocytic infiltrate, with features suggestive of a lymphocytic vasculopathy extending to at least the mid-reticular dermis. Eosinophils were a prominent component of the inflammatory infiltrate in 2 cases. Our review of the literature identified a total of 45 publications, representing reports of 46 patients, containing histological information. As well as bleomycin- and mushroom-related cases, similar eruptions have been reported in the context of connective tissue disease and other drugs. Although cases related to connective tissue disease show features of the underlying condition, cases secondary to drugs or mushrooms predominantly show features compatible with common patterns of exanthematous/morbilliform drug reaction. In particular, subtle spongiosis and/or interface dermatitis combined with a dermal lymphocytic infiltrate that includes increased numbers of eosinophils is a common finding. Features of a lymphocytic vasculopathy may be seen in a subset of these cases.
Development of a Brief Screen for Symptoms of Posttraumatic Stress Disorder in Young Children: The Young Child PTSD Screen
Authors: Scheeringa Michael S.
Published: January 2019

Objective:

The ability to reliably detect posttraumatic stress disorder (PTSD) symptoms that require treatment in young children through screening efforts is a critical step toward providing appropriate treatment. The developmental differences in this age group compared to older youths pose challenges for accurate detection. A brief age-appropriate screen has not yet been quantitatively validated. This study aimed to address that gap by creating a rapid and brief screen based on empirical data that focused on sensitivity and face validity for children aged 3 to 6 years.

Methods:

A trauma-exposed group (N = 284) and a non-trauma-exposed group (N = 46), aged 3 to 6 years, were assessed using a semistructured diagnostic interview with their primary caregivers.

Results:

One hundred twenty combinations of items were evaluated for sensitivity, specificity, positive predictive value, negative predictive value, associations with functional impairment, and frequency of false positives. Many combinations of items performed well on these psychometrics, and the final selection of a 6-item screener was influenced by considerations of face validity so that the screen would best reflect the unique symptoms of PTSD.

Conclusion:

The screener proposed is a promising tool that will benefit from additional research to examine its psychometric properties as a stand-alone PTSD screen. Future research ought to include test–retest reliability and replication of these findings in other samples and settings. Eventual uses of a brief screen for PTSD in young children include screening during primary care visits and large-scale screening efforts following disasters, for which cost and time need to be considered.
Evaluating the Accuracy of Hemorrhoids: Comparison Among Specialties and Symptoms
Authors: Idrees Jay J. , Clapp McKenzie , Brady Justin T. , Stein Sharon L. , Reynolds Harry L. , Steinhagen Emily
Published: January 2019

BACKGROUND:

A large proportion of patients with anorectal complaints are referred to colorectal surgeons with the label of hemorrhoids.

OBJECTIVE:

The purpose of this study was to review presenting symptoms and frequency of accurate diagnosis, as well as to analyze determinants of misdiagnosis to guide educational endeavors.

DESIGN:

This was a retrospective study.

SETTINGS:

The study was conducted at a tertiary care academic center.

PATIENTS:

The charts of patients referred to a colorectal clinic with the diagnosis of hemorrhoids from January 1, 2012, to January 1, 2017, were reviewed.

MAIN OUTCOME MEASURES:

The accuracy of the referring provider’s diagnosis of hemorrhoids was measured.

RESULTS:

Review of charts identified 476 patients with the referral diagnosis of hemorrhoids. The most common presenting symptoms were bleeding (63%; n = 302), pain (48%; n = 228), and protrusion (39%; n = 185). Anal examination (ie, external inspection and/or digital internal examination) was documented in only 48%. The hemorrhoid diagnostic accuracy was 65% (n = 311). Among patients with incorrect hemorrhoid diagnoses (35%; n = 169), actual diagnosis was anal fissure (34%), skin tag (27%), and hypertrophied papilla (6%). One rectal and 2 anal carcinomas were found (0.63%). Compared with general practitioners, gastroenterologists had 86% higher odds of correct diagnosis (OR = 1.86 (95% CI, 1.10–3.10); p = 0.02), whereas the gynecologists had 68% lower odds of correct diagnosis at the time of referral (OR = 0.32 (95% CI, 0.10–0.80); p = 0.02). On multivariable analysis, referring specialty was not predictive of accurate diagnosis. Patients presenting with protrusion had 73% higher odds of accurate diagnosis (OR = 1.7 (95% CI, 1.1–2.7); p = 0.02), whereas patients presenting with pain (OR = 1.6 (95% CI, 1.1–2.5); p = 0.03) or pruritus (OR = 2.5 (95% CI, 1.2–5.0); p = 0.008) were more likely to be misdiagnosed.

LIMITATIONS:

This is a retrospective study. Not all of the charts contained all data points. The number of patients may limit the power of the study to detect some differences.

CONCLUSIONS:

A variety of anorectal complaints are diagnosed as hemorrhoids by providers who have initial contact with the patients. Educational programs directed toward improving physician knowledge can potentially improve diagnostic accuracy and earlier initiation of appropriate care. Presenting symptoms other than protrusion lead to higher rate of misdiagnosis by a referring physician. See Video Abstract at http://links.lww.com/DCR/A847.
Accurate Nipple Areolar Positioning in Nipple-sparing Mastectomy Reconstruction
Authors: Mayer Alexander P. , Goodreau Adam M. , Blanchet Nadia P.
Published: January 2019

Nipple-sparing mastectomy continues to grow in popularity as oncologic indications for preserving the nipple areolar complex have become less stringent and more patients with genetic predispositions to breast cancer seek aesthetically superior prophylactic mastectomy reconstructions. Nonetheless, nipple malposition remains a common and disturbing complication. This article proposes several anatomic variations that predispose to nipple malposition and a strategy to avoid it through a reliable, easily reproducible method of preoperative marking and intraoperative stabilization.
Optimizing Outcomes in Nipple-sparing Mastectomy: Mastectomy Flap Thickness Is Not One Size Fits All
Authors: Frey Jordan D. , Salibian Ara A. , Choi Mihye , Karp Nolan S.
Published: January 2019

Nipple-sparing mastectomy (NSM) places greater stress on the breast-skin envelope compared with traditional mastectomy techniques. Precise mastectomy flap dissection is critical to optimize breast skin flap thickness and minimize complication risk. This study evaluated patient-specific factors associated with mastectomy flap quality to improve technical success in NSM. Ideal NSM flap thickness was determined for all NSMs from 2006 to 2016 with available preoperative breast magnetic resonance imaging (MRIs). Demographic, operative variables, and flap thickness were compared for NSMs as stratified by body mass index (BMI) and mastectomy weight. Of the 1,037 NSMs, 420 cases (40.5%; 243 patients) had MRI data available, which included 379 (36.5%) preoperative breast MRIs. Average BMI was 24.08 kg/m2, whereas average mastectomy weight was 442.28 g. NSMs were classified according to BMI <25 kg/m2, 25–30 kg/m2, and >30 kg/m2. Average ideal overall NSM flap thicknesses in these groups were 10.43, 12.54, and 14.91 mm, respectively. Each incremental increase in average overall NSM flap thickness per BMI category was statistically significant (P < 0.0001; P < 0.0001; P = 0.0002). NSMs were also classified into mastectomy weight categories: <400 g, 400–799 g, and ≥800 g. Average overall NSM flap thicknesses in these groups were 9.97, 12.21, and 14.50 mm, respectively. Each incremental increase in average overall NSM flap thickness per mastectomy weight category was similarly statistically significant (P < 0.0001; P < 0.0001; P < 0.0001). NSM flap thickness and quality is related to BMI and breast size. Characterizing these anatomic variations preoperatively will help surgeons optimize mastectomy flap dissections and minimize ischemic complications in breast reconstruction after NSM.
RATES OF EXUDATIVE RECURRENCE FOR EYES WITH INACTIVATED WET AGE-RELATED MACULAR DEGENERATION ON 12-WEEK INTERVAL DOSING WITH BEVACIZUMAB THERAPY
Authors: Hwang Richard Y. , Santos Daniella , Oliver Scott C. N.
Published: January 2019

Purpose:

To determine the recurrence rate of exudative age-related macular degeneration (wet AMD) in patients on 12-week dosing interval anti–vascular endothelial growth factor (anti-VEGF) bevacizumab therapy.

Methods:

A retrospective chart review was performed on wet AMD patients treated with anti-VEGF therapy using a “treat-and-extend” methodology at one physician's practice site over 2 years (2012–2014). Charts were evaluated for visual acuity, anti-VEGF agent used, treatment interval, duration of treatment, trials off of anti-VEGF therapy, evidence of exudation, and wet AMD recurrence characteristics.

Results:

Three hundred and twenty-one wet AMD patients were treated. Fifty-seven eyes were without active exudation by clinical examination or optical coherence tomography (OCT) and were maintained on repeating 12-week interval suppressive anti-VEGF therapy. Sixteen percent (8/49) showed exudation recurrence with an average 10% cumulative recurrence rate per year for eyes on bevacizumab. Eight eyes without active exudation were discontinued off of bevacizumab therapy. Sixty-three percent (5/8) demonstrated recurrence on average 4 months after stopping therapy.

Conclusion:

The findings in this study suggest that if a patient can be extended to 12-week interval bevacizumab therapy, there is on average a 10% chance of recurrence with each successive year. If anti-VEGF therapy is discontinued in these patients, there is an increased chance of recurrence by 4 months.
A multicenter randomized controlled trial on the efficacy of intradiscal methylene blue injection for chronic discogenic low back pain: the IMBI study
Authors: Kallewaard Jan Willem , Wintraecken Veerle M. , Geurts José W. , Willems Paul C. , van Santbrink Henk , Terwiel Chris T.M. , van Kleef Maarten , van Kuijk Sander M.J.
Published: January 2019

A study published in PAIN in 2010 showed remarkable effects of intradiscal methylene blue (MB) injections compared with placebo on pain intensity in patients with chronic discogenic low back pain (CD-LBP). Both groups received lidocaine hydrochloride injections for pain associated with the procedure. We replicated the design of the previously published study and performed a multicenter, double-blind, randomized, placebo-controlled trial to assess whether the extraordinary effects of MB on pain intensity could be confirmed. The primary outcomes were treatment success defined as at least 30% reduction in pain intensity and the Patients' Global Impression of Change 6 months after the intervention. We included 84 patients with CD-LBP of which 14 (35%) in the MB plus lidocaine group showed treatment success compared with 11 (26.8%) in the control group who received placebo plus lidocaine (P = 0.426). Twenty-seven percent of all participants treated with MB stated that their overall health improved much or very much (Patients' Global Impression of Change), vs 25.6% in the placebo group (P = 0.958). We were unable to confirm that intradiscal MB injections are better capable of significantly reducing pain in patients with CD-LBP 6 months after treatment compared with placebo. We observed that over one-quarter of patients receiving only lidocaine injections reported treatment success, which is in contrast with the previously published study. Our results do not support the recommendation of using intradiscal MB injections for patients with CD-LBP.
An investigation of the effect of experimental pain on logical reasoning
Authors: Attridge Nina , Keogh Edmund , Eccleston Christopher
Published: January 2019

Pain disrupts attention to prioritise avoidance of harm and promote analgesic behaviour. This could in turn have negative effects on higher-level cognitions, which rely on attention. In the current article, we examined the effect of thermal pain induction on 3 measures of reasoning: the Cognitive Reflection Test, Belief Bias Syllogisms task, and Conditional Inference task. In experiment 1, the thermal pain was set at each participant's pain threshold. In experiment 2, it was set to a minimum of 44°C or 7/10 on a visual analogue scale (whichever was higher). In experiment 3, performance was compared in no pain, low-intensity pain, and high-intensity pain conditions. We predicted that the experience of pain would reduce correct responding on the reasoning tasks. However, this was not supported in any of the 3 studies. We discuss possible interpretations of our failure to reject the null hypothesis and the importance of publishing null results.
Cannabis effects on lipoproteins
Authors: Lazarte Julieta , Hegele Robert A.
Published: January 2019

Purpose of review

The endocannabinoid system affects several physiological functions. A family of endocannabinoid receptors is susceptible to cannabis constituents. Cannabis is widely used in our society and following its recent legalization in Canada, we focus on how exposure to cannabis and pharmacologic cannabinoid receptor type 1 (CB1) inhibition affect lipoprotein levels.

Recent findings

Several groups have reported that exposure to cannabis does not increase weight despite the marked increase in caloric intake. In observational studies, the effect of smoked cannabis exposure on plasma lipids is variable. Some studies in specific patient populations with longer exposure to cannabis seemed to identify slightly more favorable lipoprotein profiles in the exposed group. Several larger controlled clinical trials using orally administered rimonabant, a CB1 receptor antagonist, have consistently shown relative improvements in weight and plasma levels of triglyceride and high-density lipoprotein cholesterol among patients receiving the treatment.

The widely variable findings on the relationship of cannabis in various forms with plasma lipids preclude any definitive conclusions. Cannabis has complex effects on the cardiovascular system and its effects on lipid profile must be considered in this overall context. Further properly controlled research is required to better understand this topic.
Current status of familial hypercholesterolemia in Chinese populations
Authors: Tomlinson Brian , Hu Miao , Chow Elaine
Published: January 2019

Purpose of review

Heterozygous familial hypercholesterolemia often went unrecognized in China when population cholesterol levels were low, but rapid economic development has changed the situation. This review will discuss the current position of awareness, diagnosis, and management of familial hypercholesterolemia in Chinese populations.

Recent findings

The phenotype of familial hypercholesterolemia in China and other Chinese populations has become similar to that in Western countries, although it may still be somewhat less severe. The prevalence in Chinese populations is also similar to that in other countries and it has been found in up to 7% of Chinese patients with premature coronary heart disease. Most of the mutations are in the low-density lipoprotein receptor gene but the pattern of mutations differs from that in Whites. Chinese patients may be more responsive to statins than Whites but patients with familial hypercholesterolemia are often undertreated.

Increasing population cholesterol levels have changed the phenotype of familial hypercholesterolemia in China and Chinese patients now resemble those in Western countries. International initiatives are facilitating increased awareness and identification of cases and more effective management of the condition.
The role of carbapenem-resistant pathogens in cSSTI and how to manage them
Authors: Del Giacomo Paola , Losito Angela Raffaella , Tumbarello Mario
Published: January 2019

Purpose of review

Skin and soft tissue infections (SSTIs) with a wide spectrum of disease severity ranging from uncomplicated to potentially lethal are still a leading cause of morbidity and mortality. The burden of carbapenem-resistant gram-negative bacteria (CR-GNB) in SSTIs is increasing. Luckily, the armamentarium of drugs available is recently expanding as well. The present review looks at data on the role CR-GNB in SSTIs and on the old and new drugs available for the treatment of carbapenem-resistant Enterobacteriaceae (CRE), Pseudomonas, and Acinetobacter.

Recent findings

The most recent information concern the availability of new antibiotics that, even if no specific clinical trials on complicated SSTIs (cSSTIs) have been performed, may play a role in clinical practice also for the treatment of cSSTIs caused by CR-GNB. Ceftolozane-tazobactam has been found to be a good option for CR Pseudomonas infections including SSTIs. Ceftazidime-avibactam is approved for several indications, including aerobic GNB infections with limited treatment options. Meropenem–vaborbactam therapy has been associated with decreased mortality in infections caused by CRE. Eravacycline has the potential to become useful for the treatment of CR Acinetobacter for which the treatment options are limited.

In the carbapenem resistance era, the physicians goal should be to stratify patients according to risk factors for CR-GNB causing SSTIs in order to minimize inappropriate initial therapies. Some recently approved drugs seem destined to become the backbone of target therapy in patients with severe infections caused by susceptible CR-GNB strains. Prompt diagnosis of cSSTIs is crucial and, when feasible, surgical debridement as source control is essential as well.
Insecticide resistance genes affect
Culex quinquefasciatus
vector competence for West Nile virus
Authors: Atyame Célestine M. , Alout Haoues , Mousson Laurence , Vazeille Marie , Diallo Mawlouth , Weill Mylène , Failloux Anna-Bella
Published: January 2019

Insecticide resistance has been reported to impact the interactions between mosquitoes and the pathogens they transmit. However, the effect on vector competence for arboviruses still remained to be investigated. We examined the influence of two insecticide resistance mechanisms on vector competence of the mosquito
Culex quinquefasciatus
for two arboviruses, Rift Valley Fever virus (RVFV) and West Nile virus (WNV). Three
Cx. quinquefasciatus
lines sharing a common genetic background were used: two insecticide-resistant lines, one homozygous for amplification of the

Ester
2

locus (SA2), the other homozygous for the acetylcholinesterase
ace-1 G119S
mutation (SR) and the insecticide-susceptible reference line Slab. Statistical analyses revealed no significant effect of insecticide-resistant mechanisms on vector competence for RVFV. However, both insecticide resistance mechanisms significantly influenced the outcome of WNV infections by increasing the dissemination of WNV in the mosquito body, therefore leading to an increase in transmission efficiency by resistant mosquitoes. These results showed that insecticide resistance mechanisms enhanced vector competence for WNV and may have a significant impact on transmission dynamics of arboviruses. Our findings highlight the importance of understanding the impacts of insecticide resistance on the vectorial capacity parameters to assess the overall consequence on transmission.
Real-time Detection of Driver’s Movement Intention in Response to Traffic Lights
Authors: Khaliliardali Zahra , Chavarriaga Ricardo , Zhang Huaijian , Gheorghe Lucian A. , Perdikis Serafeim , Millán José del R.
Published: January 2019

Movements are preceded by certain brain states that can be captured through various neuroimaging techniques. Brain-Computer Interfaces can be designed to detect the movement intention brain state during driving, which could be beneficial in improving the interaction between a smart car and its driver, by providing assistance in-line with the driver’s intention. In this paper, we present an Electroencephalogram based decoder of such brain states preceding movements performed in response to traffic lights in two experiments: in a car simulator and a real car. The results of both experiments (N=10: car simulator, N=8: real car) confirm the presence of anticipatory Slow Cortical Potentials in response to traffic lights for accelerating and braking actions. Single-trial classification performance exhibits an Area Under the Curve (AUC) of 0.71±0.14 for accelerating and 0.75±0.13 for braking. The AUC for the real car experiment are 0.63±0.07 and 0.64±0.13 for accelerating and braking respectively. Moreover, we evaluated the performance of real-time decoding of the intention to brake during online experiments only in the car simulator, yielding an average accuracy of 0.64±0.1. This paper confirm the existence of the anticipatory slow cortical potentials and the feasibility of single-trial detection these potentials in driving scenarios.
Dynamic Change of Electrostatic Field in TMEM16F Permeation Pathway Shifts Its Ion Selectivity
Authors: Ye Wenlei , Han Tina W. , He Mu , Jan Yuh Nung , Jan Lily Y.
Published: January 2019

TMEM16F is activated by elevated intracellular Ca2+, and functions both as a small-conductance ion channel permeable to Ca2+ and as a phospholipid scramblase. It is important to hold this positive feedback in check to prevent prolonged Ca2+-overloading in cells. We hypothesize that TMEM16F shifts its ion selectivity so that it is more permeable to Cl− than cations at high intracellular Ca2+ concentration. We tested this hypothesis with the Q559K mutant that shows no current rundown in excised patch with prolonged Ca2+ elevation. Recorded in NaCl−based solution, the channel shifted its ion selectivity from Na+-selective to Cl−-selective when intracellular Ca2+ was increased. The ion selectivity switch did not correlate with changes of channel open state. Rather, it was indicative of an alteration of electrostatic field in the permeation pathway. Shifting ion-selectivity synergistically by intracellular divalent ions and membrane potential could work as a built-in mechanism that allows TMEM16F to brake the positive feedback.