bluuebunny/crossref_metadata_2025 huggingface dataset:
Animal Models of OCD
Authors: Pittenger Christopher , Dulawa Stephanie , Thompson Summer L.
Published: October 2017

Obsessive-compulsive disorder and related conditions are characterized by demonstrable alterations in brain function, and aspects of these may, in principle, be recapitulated and studied in animals. However, the relationship between animal models and the clinical syndrome is complex. Many clinical aspects of OCD, especially those that can only be evaluated by subjective report, cannot be assessed in an animal. As a result, some discount the utility of animal modeling of OCD altogether. However, conservation of both genes and brain anatomy across mammalian species supports the opposite perspective, that key aspects of the pathophysiology of OCD and related disorders can be recapitulated in animals, and thus fruitfully studied in model systems. This introductory chapter addresses these issues, seeking to identify both the strengths and the limitations of animal studies as contributors to our understanding of OCD. This discussion provides a framework for the more specific material about particular animal models presented in this section.
Targeted Circuit Manipulations in the Modeling of OCD
Authors: Ahmari Susanne E.
Published: October 2017

Work in animal models has great potential to shed light on the neural circuit perturbations that lead to OCD-related behaviors. Circuit-specific manipulations allow testing of the causal role of the brain network abnormalities observed in clinical imaging studies, with a precision that is not possible in investigations in humans. In recent years, circuit-specific manipulations in animals using a range of technologies have confirmed that abnormalities in the cortico-striatal circuitry can produce repetitive behaviors, such as excessive grooming. This chapter summarizes these advances. Refining our understanding of the contribution of particular neural circuits to OCD-relevant behaviors can inform the development of anatomically targeted treatments, such as deep brain stimulation.
Pharmacological and Behavioral Rodent Models of OCD
Authors: Thompson Summer L. , Dulawa Stephanie C.
Published: October 2017

Obsessive-compulsive disorder (OCD) is a severe psychiatric disorder characterized by obsessions and/or compulsions. Only half of patients respond to first-line pharmacological treatments, and symptom relief is typically partial, even in responders. Gaining a better understanding of OCD etiology could lead to better treatments, and potentially to prevention. Animal models are a useful tool for studying neurobiological mechanisms underlying psychiatric phenotypes. Effective use of animal models requires identification of reliable, quantifiable features of the disorder of interest that can be measured across species. The modeled phenotypes then require assessment for predictive validity: the accuracy with which a model makes accurate predictions about the human condition. Once a model has been shown to make accurate predictions, using it to study neurobiological mechanisms is justified. The validity of spontaneous and induced rodent models of OCD is reviewed in this chapter.
Functional Neurosurgery in Severe and Treatment-Refractory OCD
Authors: Keen Erica C. , Widge Alik S. , Dougherty Darin D.
Published: October 2017

Although most patients with obsessive-compulsive disorder (OCD) attain adequate symptomatic relief with conventional first-line treatments, a meaningful fraction remain incapacitated despite numerous medication trials and intensive behavioral therapy (Garnaat et al., 2014). A subset of these patients may be candidates for surgical treatment. Stereotactic neurosurgical lesions have been used successfully since the 1960s to treat patients with especially severe, chronic, treatment-refractory OCD. This chapter briefly reviews the history of psychiatric neurosurgery and the development of the four current neurosurgical approaches to OCD. It discusses issues related to the careful selection of appropriate surgical candidates. It then reviews available outcomes data for each of the four surgical procedures. The putative mechanisms of action of these ablative neurosurgeries, in the context of our current understanding of the pathophysiology of OCD, are explored. The chapter concludes with future directions in which psychiatric neurosurgery may evolve to address current limitations and harness more fully its therapeutic potential for patients with OCD.
Clinical Features, Assessment, and Treatment of Body Dysmorphic Disorder
Authors: Zakhary Lisa , Weingarden Hilary , Sullivan Alexandra , Wilhelm Sabine
Published: October 2017

This chapter describes the clinical features of BDD and provides tools for effective assessment and diagnosis; in addition, it reviews treatments for BDD, with focus on medication and cognitive behavioral therapy. Body dysmorphic disorder (BDD) is a common and disabling disorder characterized by a preoccupation with an imagined or slight defect in appearance. Its symptomatology and treatment resemble those of OCD in some respects and it is classified in DSM-5 as an OCD-related disorder, but BDD is distinct in a number of key ways. It can lead to significant psychosocial dysfunction, poor quality of life, and suicidality. Although much is known about its clinical presentation and demographic characteristics, large gaps in treatment knowledge remain. Hopefully, research will provide answers to guide more effective treatment of this disabling illness.
Body Dysmorphic Disorder
Authors: Feusner Jamie D. , McCurdy-McKinnon Danyale
Published: October 2017

This chapter covers the latest studies addressing neurobiological and genetic/heritable factors that may contribute to body dysmorphic disorder (BDD). BDD affects approximately 2% of the population and involves perceived defects of appearance along with obsessive preoccupation and repetitive, compulsive-like behaviors. Studies of visual processing suggest that disturbances in visual perception and visuospatial information processing, characterized by heightened attention to detail and impairment in holistic and global assessment, contribute to the condition. Also reviewed are studies of brain circuitry in BDD, which implicate white matter and structural connectivity abnormalities as playing possible roles in the pathophysiology of BDD. Finally, this chapter reviews the evidence that the susceptibility for BDD may be partly heritable and that there may be shared genetic factors among the obsessive-compulsive and related disorders (of which BDD is a member) as a group.
Eating Disorder Comorbidity with OCD
Authors: Gershkovich Marina , Pascucci Olivia , Steinglass Joanna
Published: October 2017

This chapter discusses the comorbidity of eating disorders with OCD, including epidemiology, neurobiology, clinical features, and treatment. These disorders frequently cooccur. There are hints that eating disorders and OCD may share underlying neural mechanisms of illness, but these neurobiological models are preliminary. Cooccurrence of eating disorders and OCD is more common in clinical populations than community samples, highlighting the importance of assessing eating and weight history among patients with OCD. Treatment for bulimia nervosa includes psychotherapy and medication options, all with good empirical support. Treatment for anorexia nervosa emphasizes behaviorally based approaches to weight restoration treatment, with no clear evidence for medication treatments. When these illnesses occur together, treatment focused on the eating disorder yields improvement in OCD symptoms. Integrating exposure and response prevention techniques into eating disorder treatment may yield synergistic improvement in both illnesses. Future research may shed light on shared and distinct neurobiological mechanisms of these illnesses.
The Integration of New Technological Approaches in OCD Care
Authors: Feuerstein Seth
Published: October 2017

This chapter explores topics related to how technology is impacting care for patients with obsessive compulsive disorder (OCD) and providing new resources for their caregivers. It explores what has occurred and is occurring today in clinical environments with the introduction of new technologies. It goes on to describe current research into how to leverage newer technologies, and discusses what we might expect in a few years. Technology can mean many things, including new medications, novel pharmaceutical approaches such as immunotherapeutics, genetic testing to support treatment selection, and potential new diagnostic tools such as fMRI. The emphasis here is on software technology; other areas of clinically relevant technological advances are covered elsewhere in this text.
Clinical Genetics and Genomics (Oxford Desk Reference)
Authors: Firth Helen V. , Hurst Jane A.
Published: October 2017

This book on clinical genetics and genomics includes many common-sense approaches, useful standards and definitions, suggestions for appropriate testing, and excellent references. It is meant to be ‘first-line’ support. It is designed to provide a basic guide to the clinical consultation, be it in outpatients or on the ward, and is intended to be used with other data sources, web resources, and texts. Blank pages are distributed throughout the book to enable the reader to update and personalize the copy with notes from current journals, guidelines, seminars, and lectures. Medical genetics trainees, residents, and fellows should particularly find this book useful; the mature and experienced clinical geneticist should also find it useful and thoughtfully constructed.
How does the inner circle shape the policy-planning network in France?
Authors: Comet Catherine
Published: October 2017

Policy-planning organizations have undergone significant development in France over the last two decades. Interconnecting the economic, political and intellectual elites, their study merits particular attention. This paper examines the active involvement of the business community in these organizations to highlight its role in the policy-planning process. Focusing on the top 100 corporations and the top 40 policy organizations, it analyses the structure of their interlocking directorates. The cohesion of the policy-planning network significantly relies on the brokering role of a few business leaders and economists. The network discloses a core-periphery structure and a left–right polarization. The results shed light on the relative convergence among the main policy organizations and the relegation of less consensual organizations to the network periphery.
Measuring Scholastic Production by Dermatopathologists Using the H-Index: A Cross-Sectional Study
Authors: Fraga Garth R.
Published: October 2017

Academic advancement in dermatopathology requires evidence of scientific production. The H-index is a useful bibliometric for measuring scientific production because it weights both volume and impact of an individual's scholastic production. The H-index distribution among academic dermatopathologists is unknown. In this cross-sectional study of 299 dermatopathologists with academic appointments in North America, H-index, publication counts, and citation counts were retrieved from Thomas Reuters Web of Science. Analytic statistics were performed to identify best predictors of academic rank and cutoff points between academic ranks. The H-index was a superior predictor of overall academic rank than publication or citation counts. The median H-index for assistant, associate, and full professors was 4, 6, and 11, respectively. H-index cutoff scores of 8 and 10 favored associate and full professor rank, respectively. These data provide benchmarks for dermatopathologists to gauge their scientific productivity against that of their peers. Although advancement decisions will depend on a careful examination of the scope and impact of a candidate's work, assistant professors of dermatopathology with H-index scores of >7 and associate professors of dermatopathology with H-index scores of >9 may wish to consider application for promotion.
Acquisition of Somatic NRAS Mutations in Central Nervous System Melanocytes: A Predisposing Risk Factor to Primary Melanoma of the Central Nervous System, a Frequently Forgotten Pitfall in Congenital Nevi
Authors: Garrido Maria C. , Maroñas-Jiménez Lidia , Morales-Raya Carlos , Ruano Yolanda , Rodriguez-Peralto Jose L.
Published: October 2017

Congenital melanocytic nevi (CMN) are benign melanocytic proliferations that are usually present at birth. A somatic mosaicism for an NRAS point mutation is responsible for the several phenotypic abnormalities that may be associated with congenital nevi. We report the case of a 7-year-old boy with a proliferative nodule (PN) arising in a Giant CMN completely excised and with several visceral and intraspinal melanoma metastases with no evidence of primary cutaneous melanoma. The careful analysis of the clinical, morphologic, and molecular features allowed the distinction of between the benign PN (BPN) and the melanoma. The BPN showed a characteristic comparative genomic hybridization pattern with gains or losses of whole chromosomes, whereas the melanoma displayed gains or losses involving complex partial chromosomal copy number gains or losses. Leptomeningeal melanocytes are more susceptible to transformation by oncogenic NRAS than cutaneous melanocytes, and central nervous system melanomas are more common than cutaneous melanomas in the setting of CMN. Thus, it has been recommended to characterize the congenital disease in patients with 2 CMN at birth, independently of size and site, with a single magnetic resonance imaging screening younger than the age of 1 year.
Ameliorative Effect of Epigallocatechin Gallate on Cardiac Hypertrophy and Fibrosis in Aged Rats
Authors: Muhammed Ibrahim , Sankar Suruthi , Govindaraj Sakthivel
Published: October 2017

The objective of the present study is to evaluate the effect of epigallocatechin gallate (EGCG) on aging-mediated cardiac hypertrophy, fibrosis, and apoptosis. The Wistar albino rats were divided into 4 groups (n = 18). Group I: young (3 months), group II: aged (24–26 months), group III: aged + EGCG (200 mg/kg for 30 days), and group IV: young + EGCG. At the end of 30 days, EGCG administration to the aged animals showed significant (P < 0.001) reduction of low-density lipoprotein, very low-density lipoprotein, triglyceride, total cholesterol with concomitant increase of high-density lipoprotein (P < 0.001) when compared with aged rats. Increased (P < 0.001) heart volume, weight with concomitant increase of left ventricular wall thickness, and reduced ventricular cavity were observed in aged rats supplemented with EGCG compared with aged animals. Histology and histomorphometry study of aged animals treated with EGCG showed marked increases in the diameter and volume of cardiomyocytes with concomitant reduction of numerical density when compared with aged animals. Reduced reactive oxygen species (P < 0.001) production with association of increased antioxidant defense system (P < 0.001) in aged hearts supplemented with EGCG when compared with aged animals. TUNEL staining and fibrosis showed a marked increase in apoptotic cell death (P < 0.001) and collagen deposition (P < 0.001) in aged animals treated with EGCG when compared with aged animals. Aged animals treated with EGCG showed a marked increase in protein expression of TGFβ, TNFα, and nuclear factor kappa B (NF-κB) and significant (P < 0.001) alteration in the gene expression of TGFβ, TNFα, NF-κB, α-SMA, and Nrf2 when compared with aged animals. Taken together, it is evident that EGCG may potentially inhibit aging-induced cardiac hypertrophy, fibrosis, and apoptosis, thereby preserving cardiac function. The proposed mechanism would be inhibition of reactive oxygen species–dependent activation of TGFβ1, TNFα, and NF-κB signaling pathway. Hence, the present study suggests that EGCG can be useful to fight against aging-induced cardiac hypertrophy, fibrosis, and apoptosis.
The Idea of Beauty and Its Biases: Critical Notes on the Aesthetics of Plastic Surgery
Authors: Di Stefano Nicola
Published: October 2017

Two biases affect the idea of beauty often embodied in aesthetic surgery. The first one is that the living body is the sum of different parts; the second one claims that beauty results from the sum of beautiful elements. Taken together, these 2 biases explain most of the aesthetic surgery procedures, in which a localized improvement is supposed to impact on the whole body image. In this article, I put into question these 2 problematic assumptions, showing that Western and Eastern aesthetics, on one side, and philosophical reflections, on the other side, support a different conception of beauty. In particular, an alternative idea that opens to authenticity and imperfection and focuses on the living body rather than on the mere anatomical surface is proposed here as a more adequate concept of beauty for aesthetic surgery.
Direct-to-Implant versus Two-Stage Tissue Expander/Implant Reconstruction: 2-Year Risks and Patient-Reported Outcomes from a Prospective, Multicenter Study
Authors: Srinivasa Dhivya R. , Garvey Patrick B. , Qi Ji , Hamill Jennifer B. , Kim Hyungjin M. , Pusic Andrea L. , Kronowitz Steven J. , Wilkins Edwin G. , Butler Charles E. , Clemens Mark W.
Published: October 2017

Background:

Direct-to-implant breast reconstruction offers time-saving advantages over two-stage techniques. However, use of direct-to-implant reconstruction remains limited, in part, because of concerns over complication rates.
1,2
The authors’ aim was to compare 2-year complications and patient-reported outcomes for direct-to-implant versus tissue expander/implant reconstruction.

Methods:

Patients undergoing immediate direct-to-implant or tissue expander/implant reconstruction were enrolled in the Mastectomy Reconstruction Outcomes Consortium, an 11-center prospective cohort study. Complications and patient-reported outcomes (using the BREAST-Q questionnaire) were evaluated. Outcomes were compared using mixed-effects regression models, adjusting for demographic and clinical characteristics.

Results:

Of 1427 patients, 99 underwent direct-to-implant reconstruction and 1328 underwent tissue expander/implant reconstruction. Two years after reconstruction and controlling for covariates, direct-to-implant and tissue expander/implant reconstruction patients did not show statistically significant differences in any complications, including infection. Multivariable analyses found no significant differences between the two groups in patient-reported outcomes, with the exception of sexual well-being, where direct-to-implant patients fared better than the tissue expander/implant cohort (p = 0.047).

Conclusions:

This prospective, multi-institutional study showed no statistically significant differences between direct-to-implant and tissue expander/implant reconstruction, in either complication rates or most patient-reported outcomes at 2 years postoperatively. Direct-to-implant reconstruction appears to be a viable alternative to expander/implant reconstruction. This analysis provides new evidence on which to base reconstructive decisions.

CLINICAL QUESTION/LEVEL OF EVIDENCE:

Therapeutic, II.
Do Bacteria and Biofilm Play a Role in Double-Capsule Formation around Macrotextured Implants?
Authors: Danino M. Alain , Nizard Nathanaël , Paek Laurence S. , Govshievich Alexander , Giot Jean-Phillipe
Published: October 2017

Background:

The double capsule is a complication mostly described in aggressive macrotextured implants. Mechanical shear stress applied onto an immature periprosthetic capsule has been linked to their formation. The authors aim to demonstrate the role of bacterial phenotype and biofilm in the development of the double capsule.

Methods:

Seven double capsules formed at the interface of macrotextured breast expander implants were studied using scanning electron microscopy. Two samples for each surface of the inner capsule layer (the prosthesis interface and the intercapsular space) were analyzed for bacteria cell size, bacterial density, and biofilm deposition.

Results:

Although all routine bacterial cultures were negative, the prosthesis interface had both higher bacteria load and biofilm deposition compared with the intercapsular space (Mann-Whitney U test, p = 0.004 and p = 0.008, respectively). Moreover, bacteria cell sizes were significantly smaller at the prosthesis interface in six of seven samples. Comparison of bacteria density and biofilm dispersion showed an increase of biofilm extracellular matrix deposition over 2000 cells/mm2 (linear regression, p = 0.0025). These results indicate a common trend among bacteria species.

Conclusions:

Bacterial expression between the different surfaces of the double capsule displays significant differences; bacteria at the prosthesis interface are mostly in a biofilm state, whereas they demonstrate a planktonic phenotype at the intercapsular space. When a sufficient amount of bacteria are present at a specific location, quorum sensing may trigger a biofilm phenotypic switch in planktonic bacteria cells. Biofilm formation may alter capsule formation through immune response, thereby weakening capsule strength and facilitating extracellular matrix delamination and double-capsule formation.

CLINICAL QUESTION/LEVEL OF EVIDENCE:

Therapeutic, V.
Impact of an Event Reporting System on Resident Complication Reporting in Plastic Surgery Training: Addressing an ACGME and Plastic Surgery Milestone Project Core Competency
Authors: Parikh Rajiv P. , Snyder-Warwick Alison , Naidoo Sybill , Skolnick Gary B. , Patel Kamlesh B.
Published: October 2017

Background:

The Accreditation Council for Graduate Medical Education and Plastic Surgery Milestone Project has identified practice-based learning and improvement, which involves systematically analyzing current practices and implementing changes, as a core competency in residency education. In surgical care, complication reporting is an essential component of practice-based learning and improvement as complications are analyzed in morbidity and mortality conference for quality improvement. Unfortunately, current methods for capturing a comprehensive profile of complications may significantly underestimate the true occurrence of complications. Therefore, the objectives of this study are to evaluate an intervention for complication reporting and compare this to current practice, in a plastic surgery training program.

Methods:

This is a preintervention and postintervention study evaluating resident reporting of complications on a plastic surgery service. The intervention was an online event reporting system developed by department leadership and patient safety experts. The cohorts consisted of all patients undergoing surgery during two separate 3-month blocks bridged by an implementation period. A trained reviewer recorded complications, and this served as the reference standard. Fisher’s exact test was used for binary comparisons.

Results:

There were 32 complications detected in 219 patients from June to August of 2015 and 35 complications in 202 patients from October to December of 2015. The proportion of complications reported in the preintervention group was nine of 32 (28.1 percent). After the intervention, this significantly increased to 32 of 35 (91.4 percent) (p < 0.001).

Conclusion:

An intervention using an event reporting system, supported by departmental leadership, led to significant improvements in complication reporting by plastic surgery residents.
Lymphatic Territories (Lymphosomes) in the Rat: An Anatomical Study for Future Lymphatic Research
Authors: Suami Hiroo , Scaglioni Mario F.
Published: October 2017

Background:

Understanding the precise anatomy in experimental animals is crucial for correct design of research projects. Rats are commonly used for scientific research in plastic surgery because of their availability in academic institutions, moderate cost, and sizable vessels for microsurgical procedures. In past publications about rat anatomy, lymphatic mapping has been limited and incomplete. The aim of this study was to comprehensively map the superficial lymphatic system in the rat.

Methods:

Twenty-seven Sprague-Dawley rats were used for this study. Indocyanine green fluorescence lymphography was used to identify the lymphatic vessels and lymph nodes. Under general anaesthesia, indocyanine green was injected intradermally at multiple spots along the dorsal and medial midlines, front and hind paws, ears, and tail. The course of the lymphatic vessels was traced on the skin with a marker pen and photographed. The superficial lymphatic vessels in each rat were sketched on a graphic template and all of the templates were superimposed using graphics software to define the relationship between the lymphatic vessel and sentinel node.

Results:

Indocyanine green fluorescence lymphography was able to demonstrate the superficial lymphatic vessels in the rat. Six groups of regional lymph node/s were identified and lymphatic pathways to those nodes delineated. The authors’ lymphosome concept was successfully applied to the rat, with six lymphosomes identified.

Conclusions:

The authors succeeded in performing superficial lymphatic mapping in the rat. The authors’ anatomical findings can provide further information about the lymphatic system in the normal state and promote understanding of pathologic changes generated by surgical manipulation for future studies.
Impact of Patient Subtype and Surgical Variables on Abdominoplasty Outcomes: A 12-Year Massachusetts General Hospital Experience
Authors: Seth Akhil K. , Lin Alex M. , Austen William G. , Gilman Robert H. , Gallico Gregory G. , Colwell Amy S.
Published: October 2017

Background:

The traditional abdominoplasty is one of the most common surgical procedures performed. This study evaluates the impact of different surgical techniques and clinical patient factors on abdominoplasty outcomes.

Methods:

A retrospective review of consecutive patients undergoing abdominoplasty was performed.

Results:

Seven hundred seventy-nine patients with a mean age of 43.7 years and a body mass index of 27 kg/m2 underwent abdominoplasty. The majority were women (92.9 percent), and massive weight loss was present in 34.8 percent. Abdominoplasty techniques included traditional (59.4 percent), belt lipectomy (17.9 percent), fleur-de-lis (16.4 percent), umbilical float (9.2 percent), and mini-abdominoplasty (2.8 percent). Half of the study population [n = 384 (49.3 percent)] had concurrent surgical procedures. Total complications (23.0 percent) consisted primarily of wound- and scar-related complications (15.3 percent). Approximately 60 percent of patients received heparin chemoprophylaxis, with overall thromboembolic and hematoma rates less than 1 percent. Univariate analysis revealed that massive weight loss (p = 0.04), fleur-de-lis (p = 0.03) or belt lipectomy (p = 0.05) techniques, and concurrent medial thigh lift (p < 0.001) all significantly increased complications. Previous scars, amount of weight loss, operative time, liposuction, and other concurrent procedures did not affect total complications. Male sex (OR, 1.96; p = 0.04), fleur-de-lis technique (OR, 1.71; p = 0.04), and medial thigh lift (OR, 3.3; p < 0.001) were independent risk factors for total postoperative complications.

Conclusion:

This study demonstrates that abdominoplasty alone or in combination with liposuction and aesthetic breast surgery can be performed safely, with an acceptable complication profile.

CLINICAL QUESTION/LEVEL OF EVIDENCE:

Risk, III.
Eyelid Reconstruction
Authors: Chang Edward I. , Esmaeli Bita , Butler Charles E.
Published: October 2017

Learning Objectives:

After reading this article, the participant should be able to: 1. Describe eyelid anatomy and demonstrate full understanding of the critical structures and basic principles of eyelid reconstruction. 2. Evaluate individual defects, analyze the missing components, and formulate a reconstructive algorithm. 3. Anticipate potential complications and design effective strategies to manage and treat common complications following eyelid reconstruction.

Defects of the eyelid can result from trauma, burns, or resection of cutaneous malignancies. Repair of eyelid defects presents unique challenges to reconstructive surgeons. A fundamental understanding of eyelid anatomy and familiarity with the myriad of options for reconstruction are critical for achieving optimal outcomes. Under ideal circumstances, the aims of reconstruction should be to restore form and function and to replace “like with like.”
Reducing and Sustaining Duplicate Medical Record Creation by Usability Testing and System Redesign
Authors: Khunlertkit Adjhaporn , Dorissaint Leonard , Chen Allen , Paine Lori , Pronovost Peter J.
Published: October 2017

Objectives

Duplicate medical record creation is a common and consequential health care systems error often caused by poor search system usability and inappropriate user training.

Methods

We conducted two phases of scenario-based usability testing with patient registrars working in areas at risk of generating duplicate medical records. Phase 1 evaluated the existing search system, which led to system redesigns. Phase 2 tested the redesigned system to mitigate potential errors before health system-wide implementation. To evaluate system effectiveness, we compared the monthly potential duplicate medical record rates for preimplementation and postimplementation months.

Results

The existing system could not effectively handle a misspelling, which led to failed search and duplicate medical record creation. Using the existing system, 96% of registrars found commonly spelled patient names whereas only 69% successfully found complicated names. Registrars lacked knowledge and usage of a phonetic matching function to assist in misspelling. The new system consistently captured the correct patient regardless of misspelling, but search returned more potential matches, resulting in, on average, 4 seconds longer to select common names. Potential monthly duplicate medical record rate reduced by 38%, from 4% to 2.3% after implementation of the new system, and has sustained at an average of 2.5% for 2 years.

Conclusions

Usability testing was an effective method to reveal problems and aid system redesign to deliver a more user friendly system, hence reducing the potential for medical record duplication. Greater standards for usability would ensure that these improvements can be realized before rather than after exposing patients to risks.
Effective Prostate-Specific Membrane Antigen–Based 18F-DCFPyL–Guided Cryoablation of a Single Positive Site in a Patient Believed to Be More Metastatic on 11C-Choline PET/CT
Authors: Cornelis Francois H. , Durack Jeremy C. , Morris Michael J. , Scher Howard I. , Solomon Stephen B.
Published: October 2017

PET/CT-guided interventions using specific radiotracers are promising for detecting avid lesions not well visualized with other imaging methods. A 72-year-old man who initially presented with prostate cancer Gleason 5 + 4 (prostate-specific antigen [PSA] = 7.9 ng/mL) underwent radical prostatectomy and node dissection. Three years after radiation, a rising PSA was observed over 6 months with PSA level reaching 1.08 ng/mL. He was evaluated with prostate-specific membrane antigen–based (PSMA) 18F-DCFPyL PET/CT, conventional CT, 18F-FDG PET/CT, and 11C-choline PET/CT. The PSMA 18F-DCFPyL PET/CT successfully targeted oligometastatic prostate cancer, whereas the other imaging studies were not correct in assessing disease extent.
Unusual Uptake of 131I in a Cutaneous Benign Fibrous Histiocytoma in a Patient With Thyroid Cancer
Authors: Zhou Huijun , Yan Jiaqi , Huang Rui , Li Lin
Published: October 2017

A 52-year-old man with papillary thyroid cancer underwent total thyroidectomy and subsequent 131I remnant ablation. The postablation whole-body radioiodine scanning showed an unexpected focus on the upper right arm. SPECT/CT found that the abnormal focus of radioactivity was from body surface. Histopathology confirmed the diagnosis of benign fibrous histiocytoma.
Potential Use of 18F-THK5351 PET to Identify Wallerian Degeneration of the Pyramidal Tract Caused by Cerebral Infarction
Authors: Ishibashi Kenji , Kameyama Masashi , Tago Tetsuro , Toyohara Jun , Ishii Kenji
Published: October 2017

A 41-year-old man underwent 18F-THK5351 PET 2 years after a right middle cerebral artery infarction. 18F-THK5351 PET imaging revealed intense radioligand uptake along the ipsilateral pyramidal tract from the corona radiata to the medulla; intense uptake changed from the right side to the left side with descending axial sections at the level of the pyramidal decussation. 18F-THK5351 reportedly binds to monoamine oxidase B, which is highly expressed in astrocytes, suggesting that 18F-THK5351 concentrates in the lesion where gliosis occurs. Hence, in this case, 18F-THK5351 uptake may represent Wallerian degeneration accompanied with gliosis in the ipsilateral pyramidal tract.
Imaging Characteristics of Chemotherapy Related Adult-Onset Still Disease
Authors: Lu Yang , Chasen Beth A. , Macapinlac Homer A.
Published: October 2017

A 60-year-old man with lymphoma completed chemotherapy on October 21, 2016, with complete remission. He then received rituximab maintenance therapy. Since March 2017, he has had progressive fatigue, myalgias, rash, weight loss, diarrhea, and recurrent low-grade fever. Subsequent bone marrow biopsy and FDG PET/CT demonstrated no active lymphoma. An 111In–white blood cell scan showed abnormal tracer uptake on 20-hour postinjection, but not on 3-hour postinjection images, including innumerable skeleton muscle foci, multiple cutaneous foci, and persistent diffuse increased uptake in the lungs. Diagnosis of adult-onset Still disease was made accordingly. The patient's cytopenia was deemed a chemotherapy-related adverse effect.
Small Bowel Metastasis From Hepatocellular Carcinoma Detected by 18F-FDG PET/CT But Not by 11C-Acetate PET/CT
Authors: Yoo Su Woong , Kim Dong-Yeon , Lee Changho , Min Jung-Joon , Kwon Seong Young
Published: October 2017

Gastrointestinal tract is rarely a metastatic site of hepatocellular carcinoma (HCC). We present a 43-year-old woman with small bowel metastasis from HCC in which metastasis was detected using 18F-FDG PET/CT. However, the site of metastasis showed no significant uptake on 11C-acetate PET/CT. 11C-acetate PET/CT has a limited value in HCC patients with suspected extrahepatic metastasis, compared with 18F-FDG PET/CT.
Effect of Prosthetic Rehabilitation on Nutritional Status in Older Adults
Authors: Tanasić Ivan , Radaković Tijana , Tihaček-Šojić Ljiljana , Milić-Lemić Aleksandra
Published: October 2017

This study aimed to assess the effectiveness of various combinations of the implant-supported overdentures and removable partial dentures on nutritional status in a randomized sample of 150 older adults. The body mass index (BMI) and the Mini Nutritional Assessment (MNA) were recorded before and after prosthetic rehabilitation. There was statistically significant improvement in the MNA and BMI, measured before prosthetic rehabilitation, and after 6 and 12 months (P < .001). The prosthetic rehabilitation of patients 65 years and older, using implant-supported overdentures and removable partial dentures, improved BMI and MNA scores used in the assessment of nutritional status.
Vitamin D in Household Food Supplies of Homebound Older Adults Receiving Home-Delivered Meals
Authors: Lashway Nancy F. , Hallman William K. , Byrd-Bredbenner Carol , Cuite Cara L. , McWilliams Rita M. , Netterville Linda , Robson Mark G.
Published: October 2017

Food sources of vitamin D become increasingly important as the ability of older adults to activate vitamin D produced from sun exposure declines. Household food supplies of homebound older adults receiving home-delivered meals contained modest amounts of vitamin D with key sources being milk, fish and shellfish, eggs and egg substitutes, ready-to-eat cereals, and spreads. To improve access to this nutrient, an economical adjunct to home-delivered meals programs is providing an additional meal consisting of vitamin D–fortified milk and ready-to-eat cereal, pouches of tuna or salmon and vitamin D–fortified juice, and/or vitamin D supplements. Improving vitamin D status could help ameliorate cognitive decline, falls, and skeletal strength and decrease institutionalization of older adults and health care costs.
Conservation of specificity in two low-specificity protein
Authors: Wheeler Lucas C. , Anderson Jeremy A. , Morrison Anneliese J. , Wong Caitlyn E. , Harms Michael J.
Published: October 2017

S100 proteins bind linear peptide regions of target proteins and modulate their activity. The peptide binding interface, however, has remarkably low specificity and can interact with many target peptides. It is not clear if the interface discriminates targets in a biological context, or whether biological specificity is achieved exclusively through external factors such as subcellular localization. To discriminate these possibilities, we used an evolutionary biochemical approach to trace the evolution of paralogs S100A5 and S100A6. We first used isothermal titration calorimetry to study the binding of a collection of peptides with diverse sequence, hydrophobicity, and charge to human S100A5 and S100A6. These proteins bound distinct, but overlapping, sets of peptide targets. We then studied the peptide binding properties of S100A5 and S100A6 orthologs sampled from across five representative amniote species. We found that the pattern of binding specificity was conserved along all lineages, for the last 320 million years, despite the low specificity of each protein. We next used Ancestral Sequence Reconstruction to determine the binding specificity of the last common ancestor of the paralogs. We found the ancestor bound the whole set of peptides bound by modern S100A5 and S100A6 proteins, suggesting that paralog specificity evolved by subfunctionalization. To rule out the possibility that specificity is conserved because it is difficult to modify, we identified a single historical mutation that, when reverted in human S100A5, gave it the ability to bind an S100A6-specific peptide. These results indicate that there are strong evolutionary constraints on peptide binding specificity, and that, despite being able to bind a large number of targets, the specificity of S100 peptide interfaces is indeed important for the biology of these proteins.
Computational discovery of tissue morphology biomarkers in very long-term survivors with pancreatic ductal adenocarcinoma
Authors: Sarnecki Jacob S. , Wood Laura D. , Wolfgang Christopher L. , Hruban Ralph H. , Maitra Anirban , Wirtz Denis , Wu Pei-Hsun
Published: October 2017

Pancreatic ductal adenocarcinoma (PDAC) is one of the deadliest forms of cancer, with an average 5-year survival rate of only 8%. Within PDAC patients, however, there is a small subset of patients who survive >10 years. Deciphering underlying reasons behind prolonged survival could potentially provide new opportunities to treat PDAC; however, no genomic, transcriptomic, proteomic, or clinical signatures have been found to robustly separate this subset of patients. Digital pathology, in combination with machine learning, provides an opportunity to computationally search for tissue morphology patterns associated with disease outcomes. Here, we developed a computational framework to analyze whole-slide images (WSI) of PDAC patient tissue and identify tissue-morphology signatures for very long term surviving patients. Our results indicate that less tissue morphology heterogeneity is significantly linked to better patient survival and that the extra-tumoral space encodes prognostic information for survival. Based on information from morphological heterogeneity in the tumor and its adjacent area, we established a machine learning model with an AUC of 0.94. Our analysis workflow highlighted a quantitative visual-based tissue phenotype analysis that also allows direct interaction with pathology. This study demonstrates a pathway to accelerate the discovery of undetermined tissue morphology associated with pathogenesis states and prognosis and diagnosis of patients by utilizing new computational approaches.
Modulation of theNeisseria gonorrhoeaedrug efflux conduit MtrE
Authors: Tamburrino Giulia , Llabrés Salomé , Vickery Owen N. , Pitt Samantha J. , Zachariae Ulrich
Published: October 2017

Widespread antibiotic resistance, especially of Gram-negative bacteria, has become a severe concern for human health. Tripartite efflux pumps are one of the major contributors to resistance in Gram-negative pathogens, by efficiently expelling a broad spectrum of antibiotics from the organism. InNeisseria gonorrhoeae, one of the first bacteria for which pan-resistance has been reported, the most expressed efflux complex is MtrCDE. Here we present the electrophysiological characterisation of the outer membrane component MtrE and the membrane fusion protein MtrC, obtained by a combination of planar lipid bilayer recordings andin silicotechniques. Ourin vitroresults show that MtrE can be regulated by periplasmic binding events and that the interaction between MtrE and MtrC is sufficient to stabilize this complex in an open state. In contrast to other efflux conduits, the open complex only displays a slight preference for cations. The maximum conductance we obtain in thein vitrorecordings is comparable to that seen in our computational electrophysiology simulations conducted on the MtrE crystal structure, indicating that this state may reflect a physiologically relevant open conformation of MtrE. Our results suggest that the MtrC/E binding interface is an important modulator of MtrE function, which could potentially be targeted by new efflux inhibitors.
Image-based methods for phenotyping growth dynamics and fitness components inArabidopsis thaliana
Authors: Vasseur François , Wang George , Bresson Justine , Schwab Rebecca , Weigel Detlef
Published: October 2017

Background

The model speciesArabidopsis thalianahas extensive resources to investigate intraspecific trait variability and the genetic bases of ecologically relevant traits. However, the cost of equipment and software required for high-throughput phenotyping is often a bottleneck for large-scale studies, such as mutant screening or quantitative genetics analyses. Simple tools are needed for the measurement of fitness-related traits, like relative growth rate and fruit production, without investment in expensive infrastructures. Here, we describe methods that enable the estimation of biomass accumulation and fruit number from the analysis of rosette and inflorescence images taken with a regular camera.

Results

We developed two models to predict plant dry mass and fruit number from the parameters extracted with the analysis of rosette and inflorescence images. Predictive models were trained by sacrificing growing individuals for dry mass estimation, and manually measuring a fraction of individuals for fruit number at maturity. Using a cross-validation approach, we showed that quantitative parameters extracted from image analysis predicts more 90% of both plant dry mass and fruit number. When used on 451 natural accessions, the method allowed modelling growth dynamics, including relative growth rate, throughout the life cycle of various ecotypes. Estimated growth-related traits had high heritability (0.65 <H2< 0.93), as well as estimated fruit number (H2= 0.68). In addition, we validated the method for estimating fruit number withrev5, a mutant with increased flower abortion.

Conclusions

The method we propose here is based on the automated computerization of plant images with ImageJ, and subsequent statistical modelling in R. It allows plant biologists to measure growth dynamics and fruit number in hundreds of individuals with simple computing steps that can be repeated and adjusted to a wide range of laboratory conditions. It is thus a flexible toolkit for the measurement of fitness-related traits in large plant populations.
Early Detection of Apathetic Phenotypes in Huntington’s Disease Knock-in Mice Using Open Source Tools
Authors: Minnig Shawn , Bragg Robert M. , Tiwana Hardeep S. , Solem Wes T. , Hovander William S. , Vik Eva-Mari S. , Hamilton Madeline , Legg Samuel R. W. , Shuttleworth Dominic D. , Coffey Sydney R. , Cantle Jeffrey P. , Carroll Jeffrey B.
Published: October 2017

Apathy is one of the most prevalent and progressive psychiatric symptom in Huntington’s disease (HD) patients. However, preclinical work in HD mouse models tend to focus on molecular and motor, rather than affective, phenotypes. Measuring behavior in mice often produces noisy data and requires large cohorts to detect phenotypic rescue with appropriate power. The operant equipment necessary for measuring affective phenotypes is typically expensive, proprietary to commercial entities, and bulky which can render adequately sized mouse cohorts as cost-prohibitive. Thus, we describe here a home-built open-source alternative to commercial hardware that is reliable, scalable, and reproducible. Using off-the-shelf hardware, we adapted and built several of the rodent operant buckets (ROBucket) designed to test HttQ111/+ mice for attention deficits in fixed ratio (FR) and progressive ratio (PR) tasks. We find that, despite normal performance in reward attainment in the FR task, HttQ111/+ mice exhibit reduced PR performance at 9-11 months of age, suggesting motivational deficits. We replicated this in two independent cohorts, which demonstrates the reliability and utility of both the apathetic phenotype, and these ROBuckets, for preclinical HD studies.
Neuronal CCL2 expression drives inflammatory monocyte infiltration into the brain during acute virus infection
Authors: Howe Charles L , LaFrance-Corey Reghann G. , Goddery Emma N , Mirchia Kanish
Published: October 2017

Background

Viral encephalitis is a dangerous compromise between the need to robustly clear pathogen from the brain and the need to protect neurons from bystander injury. Theiler's murine encephalomyelitis virus (TMEV) infection of C57Bl/6 mice is a model of viral encephalitis in which the compromise results in hippocampal damage and permanent neurological sequelae. We previously identified brain infiltrating inflammatory monocytes as the primary driver of this hippocampal pathology, but the mechanisms involved in recruiting these cells to the brain were unclear.

Methods

Chemokine expression levels in the hippocampus were assessed by microarray, ELISA, RT-PCR, and immunofluorescence. Monocyte infiltration during acute TMEV infection was measured by flow cytometry. CCL2 levels were manipulated by immunodepletion and by specific removal from neurons in mice generated by crossing a line expressing the Cre recombinase behind the synapsin promoter to animals with floxed CCL2.

Results

Inoculation of the brain with TMEV induced hippocampal production of the proinflammatory chemokine CCL2 that peaked at 6 hours postinfection, whereas inoculation with UV-inactivated TMEV did not elicit this response. Immunofluorescence revealed that hippocampal neurons expressed high levels of CCL2 at this timepoint. Genetic deletion of CCR2 and systemic immunodepletion of CCL2 abrogated or blunted the infiltration of inflammatory monocytes into the brain during acute infection. Specific genetic deletion of CCL2 from neurons reduced serum and hippocampal CCL2 levels and inhibited inflammatory monocyte infiltration into the brain.

Conclusions

We conclude that intracranial inoculation with infectious TMEV rapidly induces the expression of CCL2 in neurons, and this cellular source is necessary for CCR2-dependent infiltration of inflammatory monocytes into the brain during the most acute stage of encephalitis. These findings highlight a unique role for neuronal production of chemokines in the initiation of leukocytic infiltration into the infected central nervous system.