bluuebunny/crossref_metadata_2025 huggingface dataset:
Oral administration of grape seed polyphenol extract restores memory deficits in chronic cerebral hypoperfusion rats
Authors: Chen Chen , Zheng Yake , Wu Tianwen , Wu Chuanjie , Cheng Xuan
Published: December 2016

Chronic cerebral hypoperfusion (CCH) has been recognized as an important cause of both vascular dementia and Alzheimer’s disease (AD), the two most prominent neurodegenerative diseases causing memory impairment in the elderly. However, an effective therapy for CCH-induced memory impairment has not yet been established. Grape seed polyphenol extract (GSPE) has powerful antioxidant properties and protects neurons and glia during ischemic injury, but its potential use in the prevention of CCH-induced memory impairment has not yet been investigated. Here, CCH-related memory impairment was modeled in rats using permanent bilateral occlusion of the common carotid artery. A Morris water maze task was used to evaluate memory, the levels of acetylcholinesterase, choline acetyltransferase, acetylcholine were used to evaluate cholinergic function, and oxidative stress was assessed by measuring the enzyme activity of superoxide dismutase, glutathione peroxidase, malonic dialdehyde, and catalase. We found that oral administration of GSPE for 1 month can rescue memory deficits. We also found that GSPE restores cholinergic neuronal function and represses oxidative damage in the hippocampus of CCH rats. We propose that GSPE protects memory in CCH rats by reducing ischemia-induced oxidative stress and cholinergic dysfunction. These findings provide a novel application of GSPE in CCH-related memory impairments.
Skincare Bootcamp: The Evolving Role of Skincare
Authors: Rodan Katie , Fields Kathy , Majewski George , Falla Timothy
Published: December 2016

Background:

Although cosmetic procedures have a significant impact on certain aspects of aging, such as deep, wrinkling, sagging, and volume loss, they fail to address the overall quality of the skin.

Methods:

Daily skincare routines potentially can have a significant long-term impact on the overall quality of a person’s complexion.

Results:

By expanding our product knowledge, we can help our patients individualize their at-home skincare routine using effective products and ingredients designed to address their specific skin concern and support the professional care we deliver.

Conclusions:

Here, we discuss the types of products and ingredients suitable for the most common dermatologic concerns, from wrinkling to skin sensitivity, acne to sun damage.
The Unique Value of Core-only Continuing Medical Education
Authors: Lupo Mary P. , Narurkar Vic
Published: December 2016

The importance of training in minimally invasive cosmetic procedures is essential to insure safe outcomes for patients. Board certification in the appropriate specialty is one way to improve aesthetic outcomes. Meetings that consider appropriate residency training for admission can help achieve this goal.
Three-dimensional Facial Anatomy: Structure and Function as It Relates to Injectable Neuromodulators and Soft Tissue Fillers
Authors: Beer Jacob I. , Sieber David A. , Scheuer Jack F. , Greco Timothy M.
Published: December 2016

Background:

The advent of new neuromodulators and soft-tissue fillers continues to expand the nonsurgical repertoire of the core cosmetic physician.

Methods:

The authors review relevant facial anatomy as it relates to facial aging and the resultant structural changes that occur. These changes are important for the cosmetic physician to identify and understand in order to perform both safe and effective placement of neuromodulators and soft-tissue fillers. In this anatomic review, the authors review key structures that serve as landmarks for successful treatment using both neuromodulators and fillers.

Conclusions:

Knowledge of key facial anatomical structures allows the cosmetic physician to perform injection of neuromodulators and soft-tissue fillers in a reproducible manner to optimizing patient safety and results.
Technical Considerations for Filler and Neuromodulator Refinements
Authors: Montes José Raúl , Wilson Anthony J. , Chang Brian L. , Percec Ivona
Published: December 2016

Background: The toolbox for cosmetic practitioners is growing at an unprecedented rate. There are novel products every year and expanding off-label indications for neurotoxin and soft-tissue filler applications. Consequently, aesthetic physicians are increasingly challenged by the task of selecting the most appropriate products and techniques to achieve optimal patient outcomes.

Methods: We employed a PubMed literature search of facial injectables from the past 10 years (2005–2015), with emphasis on those articles embracing evidence-based medicine. We evaluated the scientific background of every product and the physicochemical properties that make each one ideal for specific indications. The 2 senior authors provide commentary regarding their clinical experience with specific technical refinements of neuromodulators and soft-tissue fillers.

Results: Neurotoxins and fillers are characterized by unique physical characteristics that distinguish each product. This results in subtle but important differences in their clinical applications. Specific indications and recommendations for the use of the various neurotoxins and soft-tissue fillers are reviewed. The discussion highlights refinements in combination treatments and product physical modifications, according to specific treatment zones.

Conclusions: The field of facial aesthetics has evolved dramatically, mostly secondary to our increased understanding of 3-dimensional structural volume restoration. Our work reviews Food and Drug Administration–approved injectables. In addition, we describe how to modify products to fulfill specific indications such as treatment of the mid face, décolletage, hands, and periorbital regions. Although we cannot directly evaluate the duration or exact physical properties of blended products, we argue that “product customization” is safe and provides natural results with excellent patient outcomes.
SCLERAL SUTURE FIXATION TECHNIQUE FOR ONE-PIECE ACRYLIC INTRAOCULAR LENS
Authors: Leung Ella H. , Mohsenin Amir , Smiddy William E.
Published: December 2016

Purpose:

To apply a previously published scleral fixation technique to secure one-piece acrylic intraocular lenses (IOLs) to the sclera.

Methods:

Retrospective, consecutive, noncomparative case series.

Results:

All patients (16 eyes of 15 patients) who underwent scleral fixation of 1-piece acrylic IOLs using the loop method from 2014 to 2016 were included. The mean follow-up was 8.1 months. Repositioning of dislocated 1-piece acrylic IOLs was performed in 8 eyes, a primary implantation in 5 eyes, and IOL exchange in 3 eyes. All IOLs remained well-centered postoperatively. The vision improved from an initial best-corrected visual acuity of 0.97 ± 0.74 logMAR (Snellen equivalent ≈20/190) to 0.47 ± 0.49 logMAR (≈20/60, P = 0.031) at the last follow-up. The postoperative complications were self-limited.

Conclusion:

The previously reported scleral suture fixation technique can be readily applied to one-piece acrylic IOLs.
BILATERAL SEROUS MACULAR DETACHMENT IN A PATIENT WITH NEPHROTIC SYNDROME
Authors: Bilge Ayse D. , Yaylali Sevil A. , Yavuz Sara , Simsek İlke B.
Published: December 2016

Purpose:

The purpose of this study was to report a case of a woman with nephrotic syndrome who presented with blurred vision because of bilateral serous macular detachment.

Methods:

Case report and literature review.

Results:

A 55-year-old woman with a history of essential hypertension, diabetes, and nephrotic syndrome was presented with blurred vision in both eyes. Her fluorescein angiography revealed dye leakage in the early and subretinal pooling in the late phases, and optical coherence tomography scans confirmed the presence of subretinal fluid in the subfovel area.

Conclusion:

In nephrotic syndrome cases especially with accompaniment of high blood pressure, fluid accumulation in the retina layer may occur. Serous macular detachment must be kept in mind when treating these patients.
Human Ex Vivo Artificial Anterior Chamber Model for Practice DMEK Surgery
Authors: Vasquez Perez Alfonso , Liu Christopher
Published: December 2016

Purpose:

To describe a wet lab model using human corneas for practicing all steps of Descemet membrane endothelial keratoplasty (DMEK).

Methods:

Twelve human research corneas were used for training purposes. Each DMEK surgery required 2 corneas; one for donor graft preparation and one to practice graft insertion and unfolding in a novel artificial anterior chamber model.

Results:

Six complete DMEK procedures were successfully performed. Apart from donor graft preparation and graft insertion into the anterior chamber, it was feasible to practice different and combinations of graft unfolding techniques in conditions similar to real human procedures.

Conclusions:

This wet lab model allows practicing steps of DMEK and learning significant surgical skills. Reusable instruments can be used in regular operating facilities resulting in reasonable costs.
Accuracy of Consecutive Fecal Calprotectin Measurements to Predict Relapse in Inflammatory Bowel Disease Patients Under Maintenance With Anti-TNF Therapy
Authors: Ferreiro-Iglesias Rocio , Barreiro-de Acosta Manuel , Lorenzo-Gonzalez Aurelio , Dominguez-Muñoz Juan E.
Published: December 2016

Background and Goal:

Predicting relapse in inflammatory bowel disease (IBD) patients could allow early changes in therapy. We aimed at evaluating the accuracy of consecutive fecal calprotectin (FC) measurements to predict flares in IBD patients under maintenance treatment with anti-tumor necrosis factor (TNF) drugs.

Study:

A prospective longitudinal cohort study with 16-month follow-up period was designed. IBD patients in clinical remission for at least 6 months under anti-TNF therapy were included. FC was quantified at 4-month intervals for 1 year, and patients were clinically evaluated for relapse at 2-month intervals. Diagnostic accuracy of FC for predicting relapse was evaluated by receiver-operating characteristic curve analysis.

Results:

In total, 95 of 106 included patients finalized the study and were analyzed (median age 44 y, 50.5% female, 75% with Crohn’s disease). A total of 30 patients (31.6%) had a relapse over follow-up. FC concentration was significantly higher in patients who relapsed (477 μg/g) than in patients who maintained in remission (65 μg/g) (P<0.005). The optimal cutoff to predict remission was 130 μg/g (negative predictive value of 100%), and 300 μg/g to predict relapse (positive predictive value of 78.3%).

Conclusions:

FC is a good predictor of clinical relapse and a particularly good predictor of remission over the following 4 months in patients with IBD on maintenance therapy with anti-TNF drugs. FC levels <130 μg/g is consistently associated with maintained disease remission, whereas concentrations >300 μg/g allow predicting relapse with a high probability at any time over the following 4 months.
Who Orders a Head CT?
Authors: Mazer Laura M. , Méan Marie , Tapper Elliot B.
Published: December 2016

Objective:

Traditional coagulopathic indices, including elevated international normalized ratio, do not correlate with bleeding risk in patients with cirrhosis. For this reason, head computed tomography (CT) has a low yield in cirrhotic patients with altered mental status and no trauma history. The initial diagnostic evaluation, however, is often made by nongastroenterologists influenced by the so-called “coagulopathy of cirrhosis.” We sought to examine the prevalence, impact, and malleability of this perception in an international, multispecialty cohort.

Design:

An electronic survey was distributed to internal medicine, surgery, emergency medicine, and gastroenterology physicians. Respondents were presented with a cirrhotic patient with hepatic encephalopathy, no history of trauma, and a nonfocal neurological examination. Respondents rated likelihood to order head CT at presentation, after obtaining labs [international normalized ratio (INR) 2.4 and platelets 59×103/μL], and finally after reading the results of a study demonstrating the low yield of head CT in this setting.

Results:

In total, 1286 physicians from 6 countries, 84% from the United States. Of these, 62% were from internal medicine, 25% from emergency medicine, 8% from gastroenterology, and 5% from surgery. Totally, 47% of respondents were attending physicians. At each timepoint, emergency physicians were more likely, and gastroenterologists less likely, to scan than all other specialties (P<0.0001). Evidence on the low yield of head CT reduced likelihood to scan for all specialties. Qualitative analysis of open-ended comments confirmed that concern for “coagulopathy of cirrhosis” motivated CT orders.

Conclusions:

Perceptions regarding the coagulopathy of cirrhosis, which vary across specialties, impact clinical decision-making. Exposure to clinical evidence has the potential to change practice patterns.
Hepatic Issues and Complications Associated With Inflammatory Bowel Disease
Authors: Saubermann Lawrence J. , Deneau Mark , Falcone Richard A. , Murray Karen F. , Ali Sabina , Kohli Rohit , Ekong Udeme D. , Valentino Pamela L. , Grossman Andrew B. , Rand Elizabeth B. , Jonas Maureen M. , Saeed Shehzad A. , Kamath Binita M.
Published: December 2016

Hepatobiliary disorders are common in patients with inflammatory bowel disease (IBD), and persistent abnormal liver function tests are found in approximately 20% to 30% of individuals with IBD. In most cases, the cause of these elevations will fall into 1 of 3 main categories. They can be as a result of extraintestinal manifestations of the disease process, related to medication toxicity, or the result of an underlying primary hepatic disorder unrelated to IBD. This latter possibility is beyond the scope of this review article, but does need to be considered in anyone with elevated liver function tests. This review is provided as a clinical summary of some of the major hepatic issues that may occur in patients with IBD.
Psychopharmacotherapy in Pregnancy and Breastfeeding
Authors: Vitale Salvatore Giovanni , Laganà Antonio Simone , Muscatello Maria Rosaria Anna , La Rosa Valentina Lucia , Currò Veronica , Pandolfo Gianluca , Zoccali Rocco Antonio , Bruno Antonio
Published: December 2016

Importance

Fifteen percent to 20% of pregnant women suffer from mental disorders, and 86% of them are not treated due to potential teratogenic risks for the fetus. Several drugs seem to be safe during pregnancy but knowledge regarding risks of antenatal exposure to drugs is still limited.

Objective

The aim of this article is to provide a review of literature, data, and a clinical guideline concerning the treatment and management of mental disorders during pregnancy and lactation.

Evidence Acquisition

Bibliographical research was carried out using Medline and Pubmed (from 2005 until 2015) and articles, books and Websites were consulted.

Results

Regarding antidepressants, only paroxetine seems to lead to an increased risk of malformations, whereas fluoxetine, fluvoxamine, sertraline, citalopram, escitalopram and venlafaxine do not appear to increase this risk. The use of duloxetine is associated with an increased risk of miscarriage during pregnancy but not with an increased risk of adverse events, such as birth defects. There is no clear evidence of malformation risk associated with the use of antipsychotics, whereas a risk associated with pregnancy and newborn outcome has been detected. All mood stabilizers are associated with risks of birth defects and perinatal complications.

Conclusions and Relevance

Taking psychoactive drugs is possible during pregnancy, but it is important to consider various effects of the drugs. Future research should focus on prospective and longitudinal studies with an adequate evaluation of confounding variables. This should be followed by long-term studies to obtain accurate measures of child development.

Target Audience

Obstetricians and gynecologists, family physicians

Learning Objectives

After completing this activity, the learner should be better able to identify the main categories of psychiatric drugs used during pregnancy and breastfeeding, discuss side effects for the mother and the newborn associated with these drugs, and use the most appropriate drug according to different clinical situations.
Developing a Clinical Protocol for Habitual Physical Activity Monitoring in Youth With Cerebral Palsy
Authors: Nicholson Kristen , Weaver Aaron , George Ameeka , Hulbert Robert , Church Chris , Lennon Nancy
Published: December 2016

Purpose:

The StepWatch (SW) has been used to monitor physical activity (PA) in youth with cerebral palsy; however, there is no standard collection protocol. The goal was to develop such a protocol.

Methods:

Data were examined from patients who wore the SW for 8 to 14 days. The Spearman-Brown prediction formula determined the minimum number of days for reliable PA. Weekdays were compared to weekends and 10- and 60-second collection intervals were examined.

Results:

The PA data were collected from 98 youth with cerebral palsy. Results showed 3 days would provide reliable representation of PA, participants took significantly more steps during school days compared with weekends, and there were no differences between collection intervals.

Conclusions:

We recommend setting the SW for 7 days at 10-second collection rate. Data should be analyzed if at least 3 days of data are present. Weekdays and weekend days should be noted, and both included when possible.
Gamification in Physical Therapy: More Than Using Games
Authors: Janssen Joep , Verschuren Olaf , Renger Willem Jan , Ermers Jose , Ketelaar Marjolijn , van Ee Raymond
Published: December 2016

The implementation of computer games in physical therapy is motivated by characteristics such as attractiveness, motivation, and engagement, but these do not guarantee the intended therapeutic effect of the interventions. Yet, these characteristics are important variables in physical therapy interventions because they involve reward-related dopaminergic systems in the brain that are known to facilitate learning through long-term potentiation of neural connections. In this perspective we propose a way to apply game design approaches to therapy development by “designing” therapy sessions in such a way as to trigger physical and cognitive behavioral patterns required for treatment and neurological recovery. We also advocate that improving game knowledge among therapists and improving communication between therapists and game designers may lead to a novel avenue in designing applied games with specific therapeutic input, thereby making gamification in therapy a realistic and promising future that may optimize clinical practice.
Importance of Initiating a “Tummy Time” Intervention Early in Infants With Down Syndrome
Authors: Wentz Erin E.
Published: December 2016

Purpose:

This study compared differences in motor development in infants with Down syndrome beginning a tummy time intervention before 11 weeks of age and after 11 weeks of age.

Methods:

Nineteen infants with Down syndrome participated in tummy time until they could independently transition in and out of sitting. Motor development was assessed monthly using the Bayley III Motor Scales and compared between the groups.

Results:

A difference in motor development between early and late groups is apparent 1, 2, and 3 months following intervention initiation. Conclusion: Early implemented tummy time was effective in reducing motor delay in young infants with Down syndrome and is a prudent first step in intervention.
Effects of Combined Exercise Training on Functional Performance in Children With Cerebral Palsy: A Randomized-Controlled Study
Authors: Peungsuwan Punnee , Parasin Pattamavadee , Siritaratiwat Wantana , Prasertnu Jilada , Yamauchi Junichiro
Published: December 2016

Purpose:

The purpose of this study was to investigate the effects of combined exercise training on functional performance in participants with cerebral palsy.

Methods:

Fifteen participants with spastic cerebral palsy were randomly allocated into either exercise or control groups. Participants in the exercise group participated in a combined strength and endurance training program for 70 minutes per day, 3 days per week, for 8 weeks, whereas those in the control group did not participate in an exercise program. Study participants in both groups continued with their regular physical therapy during the study.

Results:

After the 8-week training, a 6-minute walk, 30-second sit-to-stand, 10-m walk, and Functional Reach Tests, participants in the exercise group had significant improvement over their baseline values and were significantly higher than those in the control group.

Conclusions:

Combined exercise training improved walking ability, functional lower limb strength, and balance in participants with cerebral palsy.
Physical Therapy Dosing: Frequency and Type of Intervention in Pediatric Postacute Hospital Care
Authors: Dumas Helene M. , Fragala-Pinkham Maria A. , Rosen Elaine L. , Folmar Eric
Published: December 2016

Purpose:

To examine differences in physical therapy dosing frequency recommendations based on children's characteristics and to describe types of intervention recommended at postacute hospital admission.

Methods:

Demographic and clinical information, recommended physical therapy intervention frequency, and intervention types were collected for all admissions from April 1, 2015, to March 1, 2016. Differences across 2 groups, children with recommendations for “less” (≤3x/wk) or “more” (≥4x/wk) frequent therapy, were examined. Types of interventions recommended were described and the measure of association between frequency and type was determined.

Results:

Older children, those with higher admission functional scores, and children with less dependence on medical technology were recommended for “more.” Therapeutic exercise was the most common intervention recommended. Greater physical therapy frequency was associated with Functional Training and Motor Function Training.

Conclusion:

Children's age, functional level, and technology dependence influence dosing recommendations. Interventions focused on function are associated with greater physical therapy frequency.
A Cytokine Pattern That Differentiates Preseroconversion From Postseroconversion Phases of Primary HIV Infection
Authors: Pastor Lucia , Parker Erica , Carrillo Jorge , Urrea Victor , Fuente-Soro Laura , Respeito Durval , Jairoce Chenjerai , Mandomando Inacio , Blanco Julià , Naniche Denise
Published: December 2016

Background:

During acute HIV infection, HIV actively replicates but seroconversion has not yet occurred. Primary HIV infection (PHI) is characterized by a transient nonspecific febrile illness, a massive inflammatory response, and the progressive appearance of anti-HIV-specific antibodies. In this study, we have identified patterns of inflammatory biomarkers associated with the innate immunological reaction before completion of a full humoral response.

Methods:

A symptom-based screening was used to identify acute HIV infection in the Manhiça District Hospital in Mozambique. Plasma levels of biomarkers were determined by Luminex and enzyme-linked immunosorbent assay. Anti-HIV antibodies were analyzed by flow cytometry and Western blot. Statistical analyses used random forest and logistic regression models.

Results:

Of 3116 rapid test seronegative or indeterminate individuals, 85 (2.7%) had positive plasma HIV viral load and were enrolled as PHI, of which n = 45 (52.9%), n = 8 (9.4%), n = 12 (14.1%), and n = 20 (23.5%) were classified as Fiebig I-III, IV, V, and VI stages, respectively, by Western blot. Comparison of individuals at early (Fiebig I-IV) and late (Fiebig V-VI) immune stages identified significant differences in the expression level of plasma B-cell activating factor , monocyte chemotactic protein-1, sCD163, and monokine induced by interferon (IFN-γ). This cytokine signature classified patients in the preseroconversion phase with a sensitivity of 92.5% and a specificity of 81.2%

Conclusions:

Identification of a cytokine signature specific for the preseroconversion stage of PHI may help to understand the earliest HIV pathogenic events and identify new potential targets for immunotherapy aimed at modulating the cytokine response to HIV infection.
Ultrasound-Guided Needle Biopsy of Neck Lymph Nodes in Patients With Suspected Lung Cancer
Authors: Duguay Sean , Wagner Jason M. , Zheng Wei , Ling Johnny , Zhao Lichao C. , Allen Karen S. , North Justin C. , Deb Subrato J.
Published: December 2016

Background

The purpose of this study is to determine the ability of ultrasound guided needle biopsy of a neck lymph node to provide adequate tissue for complete pathologic evaluation of suspected metastatic lung cancer, including molecular testing for epidermal growth factor receptor gene mutations by pyrosequencing and anaplastic lymphoma kinase gene rearrangement by fluorescence in situ hybridization.

Methods

Institutional review board approval was obtained and the requirement for informed consent was waived. All ultrasound guided neck biopsies performed July 1, 2011, to June 30, 2015, were retrospectively reviewed, and all biopsies performed for suspected lung cancer metastatic to supraclavicular and cervical lymph nodes were included.

Results

Forty patients with suspected lung cancer underwent ultrasound-guided needle biopsy of an abnormal appearing neck lymph node identified on preprocedure computed tomography or positron emission tomography/computed tomography. Thirty-seven patients were subsequently diagnosed with lung cancer and 3 were diagnosed with lymphoma. A definitive pathologic diagnosis was rendered in 95% of neck node biopsies (38/40; 95% confidence interval, 84%–99%). Of the 36 specimens diagnostic for lung cancer, 16 were considered for further molecular testing and the specimen was adequate for molecular testing in 15 (94%; 73%–100%) cases. Therefore, the neck node biopsy specimens were adequate for complete pathologic workup in 93% (37/40; 81%–98%). No complications related to the biopsies were observed.

Conclusions

In patients presenting with suspected lung cancer and suspicious neck lymph nodes, ultrasound-guided needle biopsy frequently provides adequate tissue for complete pathologic evaluation and eliminates the need for more invasive procedures.
The complexity of atrial fibrillation newly diagnosed after ischemic stroke and transient ischemic attack: advances and uncertainties
Authors: Cerasuolo Joshua O. , Cipriano Lauren E. , Sposato Luciano A.
Published: December 2016

Purpose of review

Atrial fibrillation is being increasingly diagnosed after ischemic stroke and transient ischemic attack (TIA). Patient characteristics, frequency and duration of paroxysms, and the risk of recurrent ischemic stroke associated with atrial fibrillation detected after stroke and TIA (AFDAS) may differ from atrial fibrillation already known before stroke occurrence. We aim to summarize major recent advances in the field, in the context of prior evidence, and to identify areas of uncertainty to be addressed in future research.

Recent findings

Half of all atrial fibrillations in ischemic stroke and TIA patients are AFDAS, and most of them are asymptomatic. Over 50% of AFDAS paroxysms last less than 30 s. The rapid initiation of cardiac monitoring and its duration are crucial for its timely and effective detection. AFDAS comprises a heterogeneous mix of atrial fibrillation, possibly including cardiogenic and neurogenic types, and a mix of both. Over 25 single markers and at least 10 scores have been proposed as predictors of AFDAS. However, there are considerable inconsistencies across studies. The role of AFDAS burden and its associated risk of stroke recurrence have not yet been investigated.

AFDAS may differ from atrial fibrillation known before stroke in several clinical dimensions, which are important for optimal patient care strategies. Many questions remain unanswered. Neurogenic and cardiogenic AFDAS need to be characterized, as it may be possible to avoid some neurogenic cases by initiating timely preventive treatments. AFDAS burden may differ in ischemic stroke and TIA patients, with distinctive diagnostic and treatment implications. The prognosis of AFDAS and its risk of recurrent stroke are still unknown; therefore, it is uncertain whether AFDAS patients should be treated with oral anticoagulants.
Preliminary Predictors of Initial Attendance, Symptom Burden, and Motor Subtype in a US Functional Neurological Disorders Clinic Population
Authors: Perez David L. , Young Sigrid S. , King Julie N. , Guarino Anthony J. , Dworetzky Barbara A. , Flaherty Alice , Chemali Zeina , Caplan David , Dickerson Bradford C.
Published: December 2016

Background and Objective:

Although many patients present with functional neurological symptoms (FNS), few US clinics offer specialized FNS care, and data on clinic attendees remain limited. We determined predictors of initial attendance, symptom burden, and FNS subtype in the first patients referred to our Functional Neurological Disorders Clinic for suspected FNS.

Methods:

We reviewed the charts of 62 consecutive patients (46 women, 16 men). Regression analyses investigated predictors of keeping the first scheduled clinic appointment. For the 49 patients who did keep that appointment, regression analyses examined neuropsychiatric factors associated with symptom burden and motor FNS subtypes.

Results:

The odds of not keeping the first appointment were 10.4 times greater for patients referred from the emergency department than from other sources. The patients who kept their appointment reported a symptom burden that was significantly associated with a past FNS-related emergency department visit and a diagnosis of another medically unexplained somatic syndrome. The number of FNS findings on neurological examination also correlated with a history of an FNS-related emergency department visit. Patients with psychogenic non-epileptic seizures reported cognitive complaints and prior psychiatric hospitalizations significantly more often than did patients with other FNS. One fourth of all patients had two or more motor FNS.

Conclusions:

In our FNS cohort, patients were less likely to keep an initial clinic appointment if they were referred from the emergency department than from other sources. Patients with psychogenic non-epileptic seizures were more likely to report cognitive symptoms and past psychiatric hospitalizations than patients with other FNS.
Short Follow-up Bias Confounds Estimates of the “Typical” Clinical Course of Susac Syndrome
Authors: Vodopivec Ivana , Prasad Sashank
Published: December 2016

Background:

To evaluate the validity of the prevailing concept that Susac syndrome (SS), a rare microvasculopathy of the brain, retina, and inner ear, is a self-limiting disease.

Methods:

We performed a literature search to identify all cases of SS reported between 1973 and October 2015. If available, we determined their demographics, duration of follow-up, and the clinical course that was labeled as monocyclic or polycyclic. We attempted to determine the number of relapses and the relapse rate in patients with polycyclic disease.

Results:

Our literature search yielded 185 relevant publications reporting 405 cases of SS. The duration of follow-up could be determined in 247/405 cases, with a range 0.5–312 months. The mean was 41 months but the distribution was skewed, with a median of 24 months. Defining the clinical course as monocyclic or polycyclic was possible in 102 patients who were followed for greater than 24 months; 53 were identified as having a polycyclic course. Patients labeled polycyclic were followed longer than those labeled monocyclic (median 62 vs 42 months, P < 0.001). The number or frequency of attacks per patient could not be determined.

Conclusions:

The follow-up of published cases of SS is short, creating an inherent bias toward the impression that the disease is self-limiting. Our findings suggest that stratification of SS into monocyclic, polycyclic, and chronic continuous courses may oversimplify the phenotype of SS; instead, the possibility of a relapsing-remitting course must be considered in all patients with this disorder.
Reversible Charles Bonnet Syndrome After Oculoplastic Procedures
Authors: Beaulieu Robert A. , Tamboli Diana A. , Armstrong Blair K. , Hogan R. Nick , Mancini Ronald
Published: December 2016

Individuals with Charles Bonnet syndrome (CBS) typically have severe visual loss and experience visual hallucinations yet have no psychiatric disease. Visual impairment often is due to end-stage glaucoma or macular degeneration. We report 3 cases of CBS in patients who underwent an oculoplastic surgical procedure. One patient experienced binocular visual distortion due to excessive topical ophthalmic ointment, and 2 patients experienced monocular visual impairment from patching. Visual hallucinations resolved once vision returned to baseline. We highlight the possibility of transient CBS in postoperative patients who have temporary iatrogenic vision impairment in one or both eyes.
Creating a universal SNP and small indel variant caller with deep neural networks
Authors: Poplin Ryan , Chang Pi-Chuan , Alexander David , Schwartz Scott , Colthurst Thomas , Ku Alexander , Newburger Dan , Dijamco Jojo , Nguyen Nam , Afshar Pegah T. , Gross Sam S. , Dorfman Lizzie , McLean Cory Y. , DePristo Mark A.
Published: December 2016

Next-generation sequencing (NGS) is a rapidly evolving set of technologies that can be used to determine the sequence of an individual’s genome1by calling genetic variants present in an individual using billions of short, errorful sequence reads2. Despite more than a decade of effort and thousands of dedicated researchers, the hand-crafted and parameterized statistical models used for variant calling still produce thousands of errors and missed variants in each genome3,4. Here we show that a deep convolutional neural network5can call genetic variation in aligned next-generation sequencing read data by learning statistical relationships (likelihoods) between images of read pileups around putative variant sites and ground-truth genotype calls. This approach, called DeepVariant, outperforms existing tools, even winning the “highest performance” award for SNPs in a FDA-administered variant calling challenge. The learned model generalizes across genome builds and even to other mammalian species, allowing non-human sequencing projects to benefit from the wealth of human ground truth data. We further show that, unlike existing tools which perform well on only a specific technology, DeepVariant can learn to call variants in a variety of sequencing technologies and experimental designs, from deep whole genomes from 10X Genomics to Ion Ampliseq exomes. DeepVariant represents a significant step from expert-driven statistical modeling towards more automatic deep learning approaches for developing software to interpret biological instrumentation data.
Ancient recombination events between human herpes simplex viruses
Authors: Burrel Sonia , Boutolleau David , Ryu Diane , Agut Henri , Merkel Kevin , Leendertz Fabian H. , Calvignac-Spencer Sébastien
Published: December 2016

Herpes simplex viruses 1 and 2 (HSV-1 and HSV-2) are seen as close relatives but also unambiguously considered as evolutionary independent units. Here, we sequenced the genomes of 18 HSV-2 isolates characterized by divergent UL30 gene sequences to further elucidate the evolutionary history of this virus. Surprisingly, genome-wide recombination analyses showed that all HSV-2 genomes sequenced to date comprise HSV-1 fragments. Using phylogenomic analyses, we could also show that two main HSV-2 lineages exist. One lineage is mostly restricted to sub-Saharan Africa while the other has reached a global distribution. Interestingly, only the worldwide lineage is characterized by ancient recombination events with HSV-1. Our findings highlight the complexity of HSV-2 evolution, a virus of likely zoonotic origin which later recombined with its human-adapted relative. They also suggest that co-infections with HSV-1 and 2 may have genomic and potentially functional consequences and should therefore be monitored more closely.
Cortical excitability controls the strength of mental imagery
Authors: Keogh Rebecca , Bergmann Johanna , Pearson Joel
Published: December 2016

Mental imagery provides an essential simulation tool for remembering the past and planning the future, with its strength affecting both cognition and mental health. Research suggests that neural activity spanning prefrontal, parietal, temporal, and visual areas supports the generation of mental images. Exactly how this network controls the strength of visual imagery remains unknown. Here, brain imaging and transcranial magnetic phosphene data show that lower resting activity and excitability levels in early visual cortex (V1-V3) predict stronger sensory imagery. Electrically decreasing visual cortex excitability using tDCS increases imagery strength, demonstrating a causative role of visual cortex excitability in controlling visual imagery. These data suggest a neurophysiological mechanism of cortical excitability involved in controlling the strength of mental images.
Universal expressions of population change by the Price equation: natural selection, information, and maximum entropy production
Authors: Frank Steven A.
Published: December 2016

The Price equation shows the unity between the fundamental expressions of change in biology, in information and entropy descriptions of populations, and in aspects of thermodynamics. The Price equation partitions the change in the average value of a metric between two populations. A population may be composed of organisms or particles or any members of a set to which we can assign probabilities. A metric may be biological fitness or physical energy or the output of an arbitrarily complicated function that assigns quantitative values to members of the population. The first part of the Price equation describes how directly applied forces change the probabilities assigned to members of the population when holding constant the metrical values of the members—a fixed metrical frame of reference. The second part describes how the metrical values change, altering the metrical frame of reference. In canonical examples, the direct forces balance the changing metrical frame of reference, leaving the average or total metrical values unchanged. In biology, relative reproductive success (fitness) remains invariant as a simple consequence of the conservation of total probability. In physics, systems often conserve total energy. Nonconservative metrics can be described by starting with conserved metrics, and then studying how coordinate transformations between conserved and nonconserved metrics alter the geometry of the dynamics and the aggregate values of populations. From this abstract perspective, key results from different subjects appear more simply as universal geometric principles for the dynamics of populations subject to the constraints of particular conserved quantitiesa.
A global co-expression network approach for connecting genes to specialized metabolic pathways in plants
Authors: Wisecaver Jennifer H. , Borowsky Alexander T. , Tzin Vered , Jander Georg , Kliebenstein Daniel J. , Rokas Antonis
Published: December 2016

Plants produce a tremendous diversity of specialized metabolites (SMs) to interact with and manage their environment. A major challenge hindering efforts to tap this seemingly boundless source of pharmacopeia is the identification of SM pathways and their constituent genes. Given the well-established observation that the genes comprising a SM pathway are co-regulated in response to specific environmental conditions, we hypothesized that genes from a given SM pathway would form tight associations (modules) with each other in gene co-expression networks, facilitating their identification. To evaluate this hypothesis, we used 10 global co-expression datasets—each a meta-analysis of hundreds to thousands of expression experiments—across eight plant model organisms to identify hundreds of modules of co-expressed genes for each species. In support of our hypothesis, 15.3-52.6% of modules contained two or more known SM biosynthetic genes (e.g., cytochrome P450s, terpene synthases, and chalcone synthases), and module genes were enriched in SM functions (e.g., glucoside and flavonoid biosynthesis). Moreover, modules recovered many experimentally validated SM pathways in these plants, including all six known to form biosynthetic gene clusters (BGCs). In contrast, genes predicted based on physical proximity on a chromosome to form plant BGCs were no more co-expressed than the null distribution for neighboring genes. These results not only suggest that most predicted plant BGCs do not represent genuine SM pathways but also argue that BGCs are unlikely to be a hallmark of plant specialized metabolism. We submit that global gene co-expression is a rich, but largely untapped, data source for discovering the genetic basis and architecture of plant natural products, which can be applied even without knowledge of the genome sequence.
Localizing hidden regularities with known temporal structure in the EEG evoked response data
Authors: Kuznetsova Aleksandra , Krugliakova Elena , Ossadtchi Alexei
Published: December 2016

In this paper we describe a novel data driven spatial filtering technique that can be applied to the ERP analysis in order to find statistically significant hidden differential activations in the EEG data. The technique is based on the known morphological characteristics of the response. Underlying optimization problem is formulated as a generalized Rayleigh quotient maximization problem. We supply our tech-nique with a relevant randomization-based statistical test to assess the significance of the discovered phenomenon. Furthermore, we describe an application of the proposed method to the EEG data acquired in the study devoted to the analysis of the auditory neuroplasticity. We show how the mismatch negativity component, a tiny and short-lasting negative response that hallmarks the novel stimuli activating primary error-detection mechanisms, can be detected after filtration.
First record of double-edged sword effect of caterpillar-induced plant volatiles in nature
Authors: El-Sayed Ashraf M. , Suckling David M.
Published: December 2016

Plants release volatiles in response to caterpillar feeding that attract natural enemies of the herbivores, a tri-trophic interaction which has been considered an indirect plant defence against herbivores. The caterpillar-induced plant volatiles have been reported to repel or attract conspecific adult herbivores. Apple seedlings infested withPandemis pyrusanalarvae uniquely release five compounds (benzyl alcohol, benzyl nitrile, phenylacetaldehyde, indole, and (E)-nerolidol). These compounds and other known caterpillar-induced plant volatiles were tested to investigate the response of both herbivores and natural enemies. In field tests, binary blends of benzyl nitrile and acetic acid or 2-phenylethanol and acetic acid attracted a large number of conspecific male and female adult moths. On the other hand, a ternary blend of benzyl nitrile, 2-phenylethanol and acetic acid attracted the largest numbers of the general predator, the common green lacewing,Chrysoperla carnea.This study provides the first record of caterpillar-induced plant volatile attraction to conspecific adult herbivores as well as predators under natural conditions.
HICL table can manipulate all proteins in human complete proteome
Authors: Xie Zhenhua
Published: December 2016

Background

The data of human complete proteome in the databases of Universal Protein Resource (UniProt) or National Center for Biotechnology Information(NCBI) were disorderly organized and hardly handled by an ordinary biologist.

Results

The HICL table enable an ordinary biologist efficiently to handle the human complete proteome with 67911 entries, to get an overview on the distribution of the physicochemical features of all proteins in the human complete proteome, to perceive the details of the distribution patterns of the physicochemical features in some protein family members and protein variants, to find some particular proteins.

Moreover, two discoveries were made via the HICL table: (1) The amino aicds(Asp,Glu) have symmetrical trend of the distributions versus pI, but the amino aicds(Arg, Lys) have local asymmetrical trend of the distributions versus pI in human complete proteome. (2) Protein sequence, besides amino acid properties, can in theory influence the modal distribution of protein isoelectric points.

Conclusion

I has created the HICL table as a robust tool for orderly managing 67911 proteins in human complete proteome by their physicochemical features, the names and sequences. Any proteins with the particular physicochemical features can be screened out from the human complete proteome via the HICL table. In addition, the unbalanced distribution of the amino aicds(Arg, Lys) in high pI proteins of human complete proteome and the effect of protein sequence on modal distribution of protein isoelectric points have been discovered through the HICL table.
Machine-learning annotation of human splicing branchpoints
Authors: Signal Bethany , Gloss Brian S , Dinger Marcel E , Mercer Timothy R
Published: December 2016

Background

The branchpoint element is required for the first lariat-forming reaction in splicing. However due to difficulty in experimentally mapping at a genome-wide scale, current catalogues are incomplete.

Results

We have developed a machine-learning algorithm trained with empirical human branchpoint annotations to identify branchpoint elements from primary genome sequence alone. Using this approach, we can accurately locate branchpoints elements in 85% of introns in current gene annotations. Consistent with branchpoints as basal genetic elements, we find our annotation is unbiased towards gene type and expression levels. A major fraction of introns was found to encode multiple branchpoints raising the prospect that mutational redundancy is encoded in key genes. We also confirmed all deleterious branchpoint mutations annotated in clinical variant databases, and further identified thousands of clinical and common genetic variants with similar predicted effects.

Conclusions

We propose the broad annotation of branchpoints constitutes a valuable resource for further investigations into the genetic encoding of splicing patterns, and interpreting the impact of common- and disease-causing human genetic variation on gene splicing.
Magnitude and mechanism of siderophore-mediated competition in bacterial interactions
Authors: Schiessl Konstanze T. , Janssen Elisabeth M.-L. , Kraemer Stephan M. , McNeill Kristopher , Ackermann Martin
Published: December 2016

Whether microbial interactions are predominantly cooperative or competitive is a central question in microbial ecology, and determines the composition and stability of microbial communities. The secretion of iron chelators called siderophores is a model system for cooperative interactions, even though these chelators can also mediate competition by depriving competitors of iron. Using a genetically engineered experimental system based on thePseudomonas aeruginosasiderophore pyochelin, we found that secreting siderophores to inhibit a competitor can lead to higher benefits than secreting siderophores to make iron available. Based on thermodynamic modeling, we propose that competitive inhibition by siderophores is efficient in kinetically controlled saturated systems, where dissolution of precipitated iron phases is slow. Under these conditions, met in many natural environments, secreted siderophores temporarily reduce the concentration of available iron and can thus induce growth inhibition in a competing strain, even at high iron concentrations. These findings give insight into the function of siderophores: In addition to its cooperative nature, siderophore secretion could also be a widespread mechanism for mediating competitive interactions. Our functional investigation reveals a complexity in microbial interaction networks that would remain hidden when focusing on genomic information alone.