bluuebunny/crossref_metadata_2025 huggingface dataset:
Executive Function Is Associated With Off-Line Motor Learning in People With Chronic Stroke
Authors: Al-dughmi Mayis , Al-Sharman Alham , Stevens Suzanne , Siengsukon Catherine F.
Published: March 2017

Background and Purpose:

Sleep has been shown to promote off-line motor learning in individuals following stroke. Executive function ability has been shown to be a predictor of participation in rehabilitation and motor recovery following stroke. The purpose of this study was to explore the association between executive function and off-line motor learning in individuals with chronic stroke compared with healthy control participants.

Methods:

Seventeen individuals with chronic stroke (>6 months poststroke) and 9 healthy adults were included in the study. Participants underwent 3 consecutive nights of polysomnography, practiced a continuous tracking task the morning of the third day, and underwent a retention test the morning after the third night. Participants underwent testing on 4 executive function tests after the continuous tracking task retention test.

Results:

Participants with stroke showed a significant positive correlation between the off-line motor learning score and performance on the Trail-Making Test from Delis-Kaplan Executive Function System (r = 0.652; P = 0.005), while the healthy control participants did not. Regression analysis showed that the Trail-Making Test–Delis-Kaplan Executive Function System is a significant predictor of off-line motor learning (P = 0.008).

Discussion and Conclusions:

This is the first study to demonstrate that better performance on an executive function test of attention and set-shifting predicts a higher magnitude of off-line motor learning in individuals with chronic stroke. This emphasizes the need to consider attention and set-shifting abilities of individuals following stroke as these abilities are associated with motor learning. This in turn could affect learning of activities of daily living and impact functional recovery following stroke.

Video Abstract available for more insights from the authors (see Video, Supplemental Digital Content 1, http://links.lww.com/JNPT/A166).
Flexed Truncal Posture in Parkinson Disease: Measurement Reliability and Relationship With Physical and Cognitive Impairments, Mobility, and Balance
Authors: Forsyth Aimi L. , Paul Serene S. , Allen Natalie E. , Sherrington Catherine , Fung Victor S. C. , Canning Colleen G.
Published: March 2017

Background and Purpose:

Flexed truncal posture is common in people with Parkinson disease (PD); however, little is known about the mechanisms responsible or its effect on physical performance. This cross-sectional study aimed to establish the reliability of a truncal posture measurement and explore relationships between PD impairments and truncal posture, as well as truncal posture and balance and mobility.

Methods:

A total of 82 people with PD participated. Truncal posture was measured in standing as the distance between vertebra C7 and a wall. Univariate and multivariate regression analyses were performed with truncal posture and impairments, including global axial symptoms, tremor, bradykinesia, rigidity, freezing of gait (FOG), reactive stepping and executive function, as well as truncal posture with balance and mobility measures.

Results:

The truncal posture measure had excellent test-retest reliability (ICC3,1 0.79, 95% CI 0.60-0.89, P < 0.001). Global axial symptoms had the strongest association with truncal posture (adjusted R
2 = 0.08, P = 0.01), although the majority of the variance remains unexplained. Post hoc analysis revealed that several impairments were associated with truncal posture only in those who did not report FOG. Flexed truncal posture was associated with poorer performance of most balance and mobility tasks after adjustment for age, gender, disease severity, and duration (adjusted R
2 = 0.24-0.33, P < 0.001-0.03).

Discussion and Conclusions:

The C7 to wall measurement is highly reliable in people with PD. Global axial symptoms were independently associated with truncal posture. Greater flexed truncal posture was associated with poorer balance and mobility. Further studies are required to elucidate the mechanisms responsible for flexed truncal posture and the impact on activity.

Video Abstract available for more insights from the authors (see Video, Supplemental Digital Content 1, http://links.lww.com/JNPT/A164).
Self-efficacy and Walking Performance in Persons With Multiple Sclerosis
Authors: Motl Robert W. , Balto Julia M. , Ensari Ipek , Hubbard Elizabeth A.
Published: March 2017

Background and Purpose:

Impairment of walking function is a prevalent and burdensome feature of multiple sclerosis (MS), and represents a primary focus of rehabilitation research and clinical care. Research examining self-efficacy as a correlate of walking performance in MS is lacking; self-efficacy represents a theory-based, modifiable target of rehabilitation approaches for improving walking outcomes. This cross-sectional study examined the association between self-efficacy and walking performance in persons living with MS.

Methods:

The sample included 69 persons with MS who completed the Multiple Sclerosis Self-Efficacy (MSSE) Scale and Exercise Self-Efficacy (EXSE) Scale and undertook the Timed 25-Foot Walk (T25FW) and the 6-Minute Walk (6MW) tests. The data were analyzed using the Pearson product moment correlation coefficients and linear regression.

Results:

Correlation analysis indicated that function subscale scores on the MSSE correlated more strongly with T25FW (r = 0.55) than did the control subscale (r = 0.40) and EXSE (r = 0.38) scores, and both function (r = 0.67) and control (r = 0.53) subscale scores on the MSSE correlated more strongly with 6MW than did EXSE scores (r = 0.40). Linear regression analyses indicated that (1) function MSSE subscale, but not control subscale, explained significant variance in T25FW speed and 6MW distance and (2) function MSSE subscale, but not EXSE, explained significant variance in T25FW speed and 6MW distance.

Discussion and Conclusions:

We provide the first evidence of an association between self-efficacy, particularly for functioning with MS, and objective walking performance in MS. Future research to replicate and extend these results can inform rehabilitation efforts that target improvement of walking performance in persons with MS.

Digital Abstract available for more insights from the authors (see Slides, Supplemental Digital Content 1, http://links.lww.com/JNPT/A171).
Aerobic Exercise Prescription in Stroke Rehabilitation: A Web-Based Survey of US Physical Therapists
Authors: Boyne Pierce , Billinger Sandra , MacKay-Lyons Marilyn , Barney Brian , Khoury Jane , Dunning Kari
Published: March 2017

Background and Purpose:

Best practice recommendations indicate that aerobic exercise (AEX) should be incorporated into stroke rehabilitation. However, this may be challenging in clinical settings. The purpose of this study was to assess physical therapist (PT) AEX prescription for patients with stroke, including AEX utilization, barriers to AEX prescription, dosing parameters, and safety considerations.

Methods:

A cross-sectional Web-based survey study was conducted. Physical therapists with valid e-mail addresses on file with the state boards of Florida, New Jersey, Ohio, Texas, and Wyoming were eligible to participate. Survey invitations were e-mailed to all licensed PT in these states. Analysis focused on respondents who were currently involved with clinical stroke rehabilitation in common practice settings.

Results:

Results from 568 respondents were analyzed. Most respondents (88%) agreed that AEX should be incorporated into stroke rehabilitation, but 84% perceived at least one barrier. Median prescribed AEX volume varied between practice settings from 20- to 30-minute AEX sessions, 3 to 5 days per week for 2 to 8 weeks. Prescribed intensity was most commonly light or moderate; intensity was determined by the general response to AEX and patient feedback. Only 2% of respondents reported that the majority of their patients with stroke had stress tests.

Discussion and Conclusions:

Most US PTs appear to recognize the importance of AEX for persons poststroke, but clinical implementation can be challenging. Future studies and consensus are needed to clarify best practices and to develop implementation interventions to optimize AEX utilization in stroke rehabilitation.

Video Abstract availablefor more insights from the authors (see Video, Supplemental Digital Content 1, http://links.lww.com/JNPT/A167).
Influence of Cueing and an Attentional Strategy on Freezing of Gait in Parkinson Disease During Turning
Authors: Spildooren Joke , Vercruysse Sarah , Heremans Elke , Galna Brook , Verheyden Geert , Vervoort Griet , Nieuwboer Alice
Published: March 2017

Background and Purpose:

Individuals with Parkinson disease exhibit decreased axial head-pelvis rotation. Consequently, they turn more en bloc than healthy controls, which may contribute to freezing during turning. We wanted to understand the influence of auditory cueing and an attentional strategy on turning and how this related to freezing of gait (FOG).

Methods:

Fifteen participants with Parkinson disease and FOG were asked to turn 180° during baseline condition, unilateral cueing, and an attentional strategy prompting to start the turn with head rotation first. FOG occurrence, axial rotation, center of mass (COM) deviation, knee-flexion amplitude, and total turn velocity were measured using 3D motion analysis while off-medication. Normal reference values were obtained from 14 age-matched controls.

Results:

Thirty-nine FOG episodes occurred in 5 participants. FOG occurred in 52.8% of baseline trials compared with 34.6% of trials using the head-first strategy, and 3.8% of the auditory cueing trials. During the head first strategy, the initiation of head, trunk, and pelvic rotation as well as the head-pelvis separation resembled turning patterns of healthy controls, but the COM shift to the inside of the turn was exaggerated. By contrast, during cueing, turning became more en bloc, with decreased head-pelvis separation and knee-flexion amplitude.

Discussion and Conclusions:

Cueing reduced FOG but did not correct axial movement deficits. The head-first strategy improved head-pelvis dissociation but had only limited effects on FOG. These results suggest that axial and COM deviation impairments are not directly related to FOG but may rather indicate a compensatory mechanism. Cueing reinforced the en-bloc movement and might as such help prevent FOG by triggering an alternative neural mechanism for movement generation.

Video Abstract available for more insights from the authors (see Video, Supplemental Digital Content 1, http://links.lww.com/JNPT/A163).
Wild-Type Gyrase A Genotype of Neisseria gonorrhoeae Predicts In Vitro Susceptibility to Ciprofloxacin: A Systematic Review of the Literature and Meta-Analysis
Authors: Allan-Blitz Lao-Tzu , Wang Xiaoyan , Klausner Jeffrey D.
Published: March 2017

Multidrug-resistant Neisseria gonorrhoeae infections have been declared 1 of the top 3 urgent threats to public health. Approaches to combat resistance include targeted therapy with antibiotics previously thought to be ineffective, made possible by rapid molecular assays to predict susceptibility. Previous studies have associated the gyrase A (gyrA) gene of N. gonorrhoeae with in vitro resistance to ciprofloxacin. We conducted a systematic review of studies comparing N. gonorrhoeae gyrA genotype results with conventional antimicrobial susceptibility testing results. We identified 31 studies meeting inclusion criteria, among which 7 different loci for mutations in the gyrA gene were identified, from 16 countries between the years of 1996 and 2016. We then performed a meta-analysis among those studies stratifying by use of real-time polymerase chain reaction (PCR) or non–real-time PCR technique, and compared the summary receiver operating characteristic curves between the 2 PCR methods. Among studies using real-time PCR, the pooled estimate of sensitivity and specificity of gyrA genotype results for the prediction of N. gonorrhoeae susceptibility to ciprofloxacin were 98.2% (95% confidence interval [CI], 96.5–99.1%) and 98.6% (95% CI, 97.0–99.3%), respectively. The summary operating characteristic curves for studies using real-time PCR techniques were well separated from those using non–real-time PCR techniques, with only slight overlap in the CIs, suggesting that real-time PCR techniques were a more accurate approach. GyrA genotype testing is a novel approach to combating the emergence of multidrug-resistant N. gonorrhoeae and is a sensitive and specific method to predict in vitro ciprofloxacin susceptibility.
Adverse Birth Outcomes and Maternal Neisseria gonorrhoeae Infection: A Population-Based Cohort Study in Washington State
Authors: Heumann Christine L. , Quilter Laura A.S. , Eastment McKenna C. , Heffron Renee , Hawes Stephen E.
Published: March 2017

Background

Neisseria gonorrhoeae (gonorrhea) remains an important cause of reproductive and obstetric complications. There has been limited population-based research to evaluate the association between maternal gonorrhea and adverse birth outcomes.

Methods

A population-based retrospective cohort study was conducted of women with singleton pregnancies in Washington State from 2003 to 2014 using linked birth certificate and birth hospitalization discharge data. The exposed cohort consisted of women with gonorrhea diagnosed during pregnancy. The unexposed group, defined as pregnant women without gonorrhea, was selected by frequency-matching by birth year in a 4:1 ratio. Logistic regression was used to determine crude and adjusted odds ratios (OR) for the association of maternal gonorrhea and adverse birth outcomes.

Results

Women with gonorrhea during pregnancy (N = 819) were more likely to be younger, black, single, less educated, multiparous, and smokers compared with women without gonorrhea (N = 3276). Maternal gonorrhea was significantly associated with a 40% increased odds (adjusted OR, 1.4; 95% confidence interval [CI], 1.0–1.8) of low birth weight infants compared with women without gonorrhea when adjusted for marital and smoking status. Maternal gonorrhea was associated with a 60% increased odds (OR, 1.6; 95% CI, 1.3–2.0) of small for gestational age infants compared with women without gonorrhea.

Conclusions

This analysis showed that pregnant women with gonorrhea were more likely to have low birth weight infants, consistent with prior literature, and provided new evidence that maternal gonorrhea is associated with small for gestational age infants. These findings support increased public health efforts to prevent, identify, and treat gonorrhea infection during pregnancy.
The Case for Extragenital Screening of Chlamydia trachomatis and Neisseria gonorrhoeae in the College Health Setting
Authors: Drinkard Lauren N. , Huxta Rebecca A. , Halbritter Ashlee , Nguyen Giang T. , Malebranche David
Published: March 2017

Background

Although the Centers for Disease Control and Prevention does not recommend routine oropharyngeal and anorectal screening for Chlamydia trachomatis and Neisseria gonorrhoeae in the general population, they do recommend it for men who have sex with men. However, risk-based extragenital screening of men may not have been adopted at all college health centers, and existing research has not focused on the college population.

Methods

We examined health records of men at a college health center in a large urban university over 6 years to evaluate effectiveness of C. trachomatis and N. gonorrhoeae screening. We also evaluated the proportion of C. trachomatis and N. gonorrhoeae infections that would have been missed if risk-based extragenital screening were not performed. Decisions to screen at extragenital sites were based on patient-reported risk behavior.

Results

For 4093 male college students screened, 7.6% of the screening visits used extragenital screening in response to self-reported risk behaviors. The case positivity rate for C. trachomatis was 3.1% with urogenital-only screening and 3.7% with risk-prompted extragenital screening. The case positivity rate for N. gonorrhoeae was 0.7% with urogenital-only screening and 3.3% with risk-prompted extragenital screening. If the college health center had relied solely on urogenital screening rather than risk-based extragenital screening, 26.4% of C. trachomatis infections and 63.2% of N. gonorrhoeae infections would have been missed.

Conclusions

One out of four C. trachomatis infections and 2 of 3 N. gonorrhoeae infections would have been missed without extragenital screening in this analysis of college men. This study reinforces Centers for Disease Control and Prevention recommendations for risk-based extragenital screening and is the first report to focus on college men. Because guidelines exist only for men, future studies should focus on extragenital screening in college women to build evidence for another group of patients that may benefit from this practice, given the high risk in young adults.
Assessing the Performance of 3 Human Immunodeficiency Virus Incidence Risk Scores in a Cohort of Black and White Men Who Have Sex With Men in the South
Authors: Jones Jeb , Hoenigl Martin , Siegler Aaron J. , Sullivan Patrick S. , Little Susan , Rosenberg Eli
Published: March 2017

Background

Risk scores have been developed to identify men at high risk of human immunodeficiency virus (HIV) seroconversion. These scores can be used to more efficiently allocate public health prevention resources, such as pre-exposure prophylaxis. However, the published scores were developed with data sets that comprise predominantly white men who have sex with men (MSM) collected several years prior and recruited from a limited geographic area. Thus, it is unclear how well these scores perform in men of different races or ethnicities or men in different geographic regions.

Methods

We assessed the predictive ability of 3 published scores to predict HIV seroconversion in a cohort of black and white MSM in Atlanta, GA. Questionnaire data from the baseline study visit were used to derive individual scores for each participant. We assessed the discriminatory ability of each risk score to predict HIV seroconversion over 2 years of follow-up.

Results

The predictive ability of each score was low among all MSM and lower among black men compared to white men. Each score had lower sensitivity to predict seroconversion among black MSM compared to white MSM and low area under the curve values for the receiver operating characteristic curve indicating poor discriminatory ability.

Conclusions

Reliance on the currently available risk scores will result in misclassification of high proportions of MSM, especially black MSM, in terms of HIV risk, leading to missed opportunities for HIV prevention services.
Can Social Network Analysis Help Address the High Rates of Bacterial Sexually Transmitted Infections in Saskatchewan?
Authors: Trecker Molly A. , Dillon Jo-Anne R. , Lloyd Kathy , Hennink Maurice , Jolly Ann , Waldner Cheryl
Published: March 2017

Background

Saskatchewan has one of the highest rates of gonorrhea among the Canadian provinces—more than double the national rate. In light of these high rates, and the growing threat of untreatable infections, improved understanding of gonorrhea transmission dynamics in the province and evaluation of the current system and tools for disease control are important.

Methods

We extracted data from a cross-sectional sample of laboratory-confirmed gonorrhea cases between 2003 and 2012 from the notifiable disease files of the Regina Qu'Appelle Health Region. The database was stratified by calendar year, and social network analysis combined with statistical modeling was used to identify associations between measures of connection within the network and the odds of repeat gonorrhea and risk of coinfection with chlamydia at the time of diagnosis.

Results

Networks were highly fragmented. Younger age and component size were positively associated with being coinfected with chlamydia. Being coinfected, reporting sex trade involvement, and component size were all positively associated with repeat infection.

Conclusions

This is the first study to apply social network analysis to gonorrhea transmission in Saskatchewan and contributes important information about the relationship of network connections to gonorrhea/chlamydia coinfection and repeat gonorrhea. This study also suggests several areas for change of systems-related factors that could greatly increase understanding of social networks and enhance the potential for bacterial sexually transmitted infection control in Saskatchewan.
Cardiotoxic (Arrhythmogenic) Effects of 1,1-Difluoroethane Due to Electrolyte Imbalance and Cardiomyocyte Damage
Authors: Joshi Kaushal , Barletta Michael , Wurpel John
Published: March 2017

Inhalant abuse is the intentional inhalation of chemical vapors to attain euphoric effects. Many common household products are abused by inhalation and one is 1,1-difluoroethane (DFE), which is a halogenated hydrocarbon used in refrigeration, dust-off spray, and airbrush painting. Although many human DFE abuse cases have been studied, the etiology and mechanism of sudden death is still unknown. In this study, an animal model was used to simulate the human conditions of DFE inhalation abuse that results in sudden death.

Current research targets mechanistic studies involving electrolyte changes and cardiomyocyte damage after DFE administration in vivo. To investigate these changes, Sprague Dawley rats (N = 6) were exposed to 30 seconds of 20 L/min of DFE in multiple doses. Isoflurane acted as a control. Two additional groups, epinephrine and epinephrine + DFE, were included to simulate the clinical condition of DFE abuse. Plasma sodium, potassium, calcium, and magnesium levels were measured, followed by lactate dehydrogenase, creatine kinase, and cardiac troponin I levels. In addition, oxidative stress markers were also evaluated in all animal groups. Electrolyte levels showed a significant rise in plasma potassium and magnesium levels for the treated groups. In addition, lactate dehydrogenase, creatine kinase, and cardiac troponin I levels in DFE and epinephrine + DFE administered rats were significantly elevated as compared with control. Some oxidative stress makers were also elevated significantly in treatment groups. Furthermore, histopathological analysis showed hyperemia/congestion in treated rats.

These results support cardiotoxic effects indicating that DFE results in fatal arrhythmias, and the study can be important during clinical cases involving inhalant abuse.
Forensic Image Analyses of Skin and Underlying Muscles as a Tool for Postmortem Interval Delimitation
Authors: El-Nahass El-Shaymaa , Moselhy Walaa A. , Hassan Nour El-Houda Y.
Published: March 2017

One of the biggest challenges for forensic pathologists is to diagnose the postmortem interval (PMI) delimitation; therefore, the aim of this study was to use a routine histopathologic examination and quantitative analysis to obtain an accurate diagnosis of PMI. The current study was done by using 24 adult male albino rats divided into 8 groups based on the scarification schedule (0, 8, 16, 24, 32, 40, 48, and 72 hours PMI). Skin specimens were collected and subjected to a routine histopathologic processing. Examination of hematoxylin-eosin–stained sections from the skin, its appendages and underlying muscles were carried out. Morphometric analysis of epidermal nuclear chromatin intensities and area percentages, reticular dermis integrated density, and sebaceous gland nuclei areas and chromatin condensation was done. Progressive histopathologic changes could be detected in epidermis, dermis, hypodermis, underlying muscles including nerve endings, and red blood cells in relation to hours PMI. Significant difference was found in epidermal nuclear chromatin intensities at different-hours PMI (atP< 0.001). The highest intensity was detected 40 hours PMI. Quantitative analysis of measurements of dermal collagen area percentages revealed a high significant difference between 0 hours PMI and 24 to 72 hours PMI (P< 0.001). As the PMI increases, sebaceous gland nuclei and nuclear chromatin condensation showed a dramatic decrease. Significant differences of sebaceous gland nuclei areas between 0 hours and different-hours PMI (P< 0.001) were obtained. A combination between routine histopathologic examination and quantitative and morphometric analysis of the skin could be used to evaluate the time of death in different-hours PMI.
Evaluation of a Novel and Standardized Technique for Subcutaneous Upper Limb Dissection
Authors: Hoggard Sam , Wilson Charles A.
Published: March 2017

It is often necessary to dissect the subcutaneous tissues to confirm or exclude the presence of cutaneous bruising. We undertook a literature search that demonstrated that there is currently no standardized technique for subcutaneous dissection, and the specific incisions and dissections used probably vary between individual pathologists. It is our experience that dissections wider than the area of cutaneous bruising visible externally often reveal bruises not identified on external inspection. We propose a standardized technique for subcutaneous dissection of the upper limb that allows direct inspection of the subcutaneous tissues of the forearm and dorsum of the hand. We have evaluated this technique by comparing the number of bruises detected on external inspection with the number of bruises verified by subcutaneous dissection. Our study has shown a significant increase in the detection of bruises on subcutaneous dissection when compared with external inspection alone. One hundred sixteen forensic autopsies in which the technique was performed were included in our series. We recorded bruises seen on external examination alone and compared the number with additional bruises that were discovered on dissecting the upper limbs. In 49 cases (42%), the technique uncovered additional bruises that were missed on external examination alone.
Ectopic Pelvic Fibroid in a Woman With Uterine Agenesis and Mayer-Rokitansky-Küster-Hauser Syndrome
Authors: Amaratunga Thelina , Kirkpatrick Iain , Yan Yi , Karlicki Fern
Published: March 2017

Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome is a rare disorder characterized by aplasia or hypoplasia of the uterus and vagina due to arrest in the development of the müllerian ducts. Women with this syndrome have the normal 46 XX karyotype, normal female secondary sex characteristics, and primary amenorrhea. Only a few cases have been described in the literature where a fibroid develops from a rudimentary, nonfunctioning uterus in patients with MRKH syndrome. In even rarer instances, a fibroid can develop in patients with a congenitally absent uterus.

Here, we present the first reported case of an ectopic fibroid in association with congenital absence of a uterus found by ultrasound in a 66-year-old white female patient with MRKH syndrome and unilateral renal agenesis.
Long-term Follow-up of MEN1 Patients Who Do Not Have Initial Surgery for Small ≤2 cm Nonfunctioning Pancreatic Neuroendocrine Tumors, an AFCE and GTE Study
Authors: Triponez Frederic , Sadowski Samira M. , Pattou François , Cardot-Bauters Catherine , Mirallié Eric , Le Bras Maëlle , Sebag Frédéric , Niccoli Patricia , Deguelte Sophie , Cadiot Guillaume , Poncet Gilles , Lifante Jean-Christophe , Borson-Chazot Françoise , Chaffanjon Philippe , Chabre Olivier , Menegaux Fabrice , Baudin Eric , Ruszniewski Philippe , Du Boullay Hélène , Goudet Pierre
Published: March 2017

Objective:

To report long-term follow-up of patients with multiple endocrine neoplasia type 1 (MEN1) and nonfunctioning pancreatic neuroendocrine tumors (NF-PET).

Background:

Pancreaticoduodenal tumors occur in almost all patients with MEN1 and are a major cause of death. The natural history and clinical outcome are poorly defined, and management is still controversial for small NF-PET.

Methods:

Clinical outcome and tumor progression were analyzed in 46 patients with MEN1 with 2 cm or smaller NF-PET who did not have surgery at the time of initial diagnosis. Survival data were analyzed using the Kaplan-Meier method.

Results:

Forty-six patients with MEN1 were followed prospectively for 10.7 ± 4.2 (mean ± standard deviation) years. One patient was lost to follow-up and 1 died from a cause unrelated to MEN1. Twenty-eight patients had stable disease and 16 showed significant progression of pancreaticoduodenal involvement, indicated by increase in size or number of tumors, development of a hypersecretion syndrome, need for surgery (7 patients), and death from metastatic NF-PET (1 patient). The mean event-free survival was 13.9 ± 1.1 years after NF-PET diagnosis. At last follow-up, none of the living patients who had undergone surgery or follow-up had evidence of metastases on imaging studies.

Conclusions:

Our study shows that conservative management for patients with MEN1 with NF-PET of 2 cm or smaller is associated with a low risk of disease-specific mortality. The decision to recommend surgery to prevent tumor spread should be balanced with operative mortality and morbidity, and patients should be informed about the risk-benefit ratio of conservative versus aggressive management when the NF-PET represents an intermediate risk.
Coronary Artery Bypass Graft Surgery and Dementia Risk in the Cardiovascular Health Study
Authors: Kuźma Elżbieta , Airdrie Jac , Littlejohns Thomas J. , Lourida Ilianna , Thompson-Coon Jo , Lang Iain A. , Scrobotovici Monica , Thacker Evan L. , Fitzpatrick Annette , Kuller Lewis H. , Lopez Oscar L. , Longstreth William T. , Ukoumunne Obioha C. , Llewellyn David J.
Published: March 2017

Introduction:

The association between history of coronary artery bypass graft surgery (CABG) and dementia risk remains unclear.

Methods:

We conducted a prospective cohort analysis using data on 3155 elderly adults free from prevalent dementia from the US population-based Cardiovascular Health Study (CHS) with adjudicated incident all-cause dementia, Alzheimer disease (AD), vascular dementia (VaD), and mixed dementia.

Results:

In the CHS, the hazard ratio (HR) for all-cause dementia was 1.93 [95% confidence interval (CI), 1.36-2.74] for those with CABG history compared with those with no CABG history after adjustment for potential confounders. Similar HRs were observed for AD (HR=1.71; 95% CI, 0.98-2.98), VaD (HR=1.42; 95% CI, 0.56-3.65), and mixed dementia (HR=2.73; 95% CI, 1.55-4.80). The same pattern of results was observed when these CHS findings were pooled with a prior prospective study, the pooled HRs were 1.96 (95% CI, 1.42-2.69) for all-cause dementia, 1.71 (95% CI, 1.04-2.79) for AD and 2.20 (95% CI, 0.78-6.19) for VaD.

Discussion:

Our results suggest CABG history is associated with long-term dementia risk. Further investigation is warranted to examine the causal mechanisms which may explain this relationship or whether the association reflects differences in coronary artery disease severity.
Dexmedetomidine Combined With Intravenous Anesthetics in Electroconvulsive Therapy
Authors: Li Xiang , Tan Fang , Cheng Nan , Guo Na , Zhong Zhi-Yong , Hei Zi-Qing , Zhu Qian-Qian , Zhou Shao-Li
Published: March 2017

Objective

The aim of this study was to investigate how the combined use of dexmedetomidine with intravenous anesthetics influences seizure duration and circulatory dynamics in electroconvulsive therapy (ECT).

Methods

A literature search was performed to identify studies that evaluated the effect of dexmedetomidine on motor- or electroencephalogram (EEG)–based seizure durations and maximum mean arterial pressure (MAP) and heart rate (HR) after ECT. Moreover, recovery time and post-ECT agitation were evaluated.

Results

Six studies enrolling 166 patients in 706 ECT sessions were included. There was no significant difference in motor or EEG seizure duration between dexmedetomidine and nondexmedetomidine groups [motor: 6 studies; mean difference (MD), 1.62; 95% confidence interval (CI), −2.24 to 5.49; P = 0.41; EEG: 3 studies; MD, 2.34; 95% CI, −6.03 to 10.71; P = 0.58]. Both maximum MAP and HR after ECT were significantly reduced in the dexmedetomidine group (MAP: 6 studies; MD, −4.83; 95% CI, −8.43 to −1.22; P = 0.009; HR: 6 studies; MD, −6.68; 95% CI, −10.74 to −2.62; P = 0.001). Moreover, the addition of dexmedetomidine did not significantly prolong recovery time when the reduced-dose propofol was used (4 studies; MD, 63.27; 95% CI, −15.41 to 141.96; P = 0.12).

Conclusions

The use of dexmedetomidine in ECT did not interfere with motor and EEG seizure durations but could reduce maximum MAP and HR after ECT. Besides, the addition of dexmedetomidine in ECT did not prolong recovery time when reduced-dose propofol was used. It might be worthwhile for patients to receive dexmedetomidine before the induction of anesthesia in ECT.
Key Issues Review: Evolution on rugged adaptive landscapes
Authors: Obolski Uri , Ram Yoav , Hadany Lilach
Published: March 2017

Adaptive landscapes represent a mapping between genotype and fitness. Rugged adaptive landscapes contain two or moreadaptive peaks:allele combinations that differ in two or more genes and confer higher fitness than intermediate combinations. How would a population evolve on such rugged landscapes? Evolutionary biologists have struggled with this question since it was first introduced in the 1930’s by Sewall Wright.

Discoveries in the fields of genetics and biochemistry inspired various mathematical models of adaptive landscapes. The development of landscape models led to numerous theoretical studies analyzing evolution on rugged landscapes under different biological conditions. The large body of theoretical work suggests that adaptive landscapes are major determinants of the progress and outcome of evolutionary processes.

Recent technological advances in molecular biology and microbiology allow experimenters to measure adaptive values of large sets of allele combinations and constructempirical adaptive landscapesfor the first time. Such empirical landscapes have already been generated in bacteria, yeast, viruses, and fungi, and are contributing to new insights about evolution on adaptive landscapes.

In this Key Issues Review we will: (i) introduce the concept of adaptive landscapes; (ii) review the major theoretical studies of evolution on rugged landscapes; (iii) review some of the recently obtained empirical adaptive landscapes; (iv) discuss recent mathematical and statistical analyses motivated by empirical adaptive landscapes, as well as provide the reader with source code and instructions to implement simulations of adaptive landscapes; and (v) discuss possible future directions for this exciting field.
Activity of Sulfa Drugs and Their Combinations against Stationary PhaseB. burgdorferiin vitro
Authors: Feng Jie , Zhang Shuo , Shi Wanliang , Zhang Ying
Published: March 2017

Lyme disease is a most common vector borne disease in the US. Although the majority of Lyme patients can be cured with the standard 2-4 week antibiotic treatment, at least 10-20% of patients continue to suffer from prolonged post-treatment Lyme disease syndrome (PTLDS). While the cause for this is unclear, one possibility is that persisting organisms are not killed by current Lyme antibiotics. In our previous studies, we screened an FDA drug library and an NCI compound library onB. burgdorferiand found some drug hits including sulfa drugs as having good activity againstB. burgdorferistationary phase cells. In this study, we evaluated the relative activity of three commonly used sulfa drugs sulfamethoxazole (Smx), dapsone (Dps), sulfachlorpyridazine (Scp), and also trimethoprim (Tmp), and assessed their combinations with the commonly prescribed Lyme antibiotics for activities againstB. burgdorferistationary phase cells. Using the same molarity concentration, dapsone, sulfachlorpyridazine and trimethoprim showed very similar activity against stationary phaseB. burgdorferienriched in persisters, however, sulfamethoxazole was the least active drug among the three sulfa drugs tested. Interestingly, contrary to other bacterial systems, Tmp did not show synergy in drug combinations with the three sulfa drugs at their clinically relevant serum concentrations againstB. burgdorferi. We found that sulfa drugs combined with other antibiotics were more active than their respective single drugs and that four-drug combinations were more active than three-drug combinations. Four drug combinations dapsone+minocycline+cefuroxime+azithromycin and dapsone+minocycline+cefuroxime+rifampin showed best activity against stationary phaseB. burgdorferiin these sulfa drug combinations. However, these 4-sulfa drug containing combinations still had considerably less activity againstB. burgdorferistationary phase cells than the daptomycin+cefuroxime+doxycycline used as a positive control which completely eradicatedB. burgdorferistationary phase cells. Future studies are needed to evaluate and optimize the sulfa drug combinationsin vitroand also in animal models.
Socio-environmental and measurement factors drive spatial variation in influenza-like illness
Authors: Lee Elizabeth C. , Arab Ali , Goldlust Sandra , Viboud Cécile , Bansal Shweta
Published: March 2017

The mechanisms hypothesized to drive spatial heterogeneity in reported influenza activity include: environmental factors, contact patterns, population age structure, and socioeconomic factors linked to healthcare access and quality of life. Harnessing the large volume and high specificity of diagnosis codes in medical claims data for influenza seasons from 2002-2009, we estimate the importance of socio-environmental determinants and measurement-related factors on observed variation in influenza-like illness (ILI) across United States counties. We found that South Atlantic states tended to have higher ILI seasonal intensity, and a combination of transmission, environmental, influenza subtype, socioeconomic and measurement factors explained the variation in seasonal intensity across our study period. Moreover, our models suggest that sentinel surveillance systems should have fixed report locations across years for the most robust inference and prediction, and high volumes of data can offset measurement biases in opportunistic data samples.
Assessing the distribution and determinants of vaccine underutilization in the United States
Authors: Goldlust Sandra , Lee Elizabeth C. , Haran Murali , Rohani Pejman , Bansal Shweta
Published: March 2017

Despite advances in sanitation and immunization, vaccine-preventable diseases remain a significant cause of morbidity and mortality worldwide. In high-income countries such as the United States, coverage rates for vaccination against childhood infections remains high. However, the phenomenon of vaccine hesitancy makes maintenance of herd immunity difficult, impeding global disease eradication efforts. Reaching the ‘last mile’ will require early detection of vaccine hesitancy (driven by philosophical or religious choices), identifying pockets of susceptibility due to underimmunization (driven by vaccine unavailability, costs ineligibility), determining the factors associated with the behavior and developing targeted strategies to ameliorate the concerns. Towards this goal, we harness high-resolution medical claims data to geographically localize vaccine refusal and underimmunization (collectively, ‘underutilization’) in the United States and identify the socio-economic determinants of the behaviors. Our study represents the first large-scale effort for vaccination behavior surveillance and has the potential to aid in the development of targeted public health strategies for optimizing vaccine uptake.
Genetic characterization of the Zika virus epidemic in the US Virgin Islands
Authors: Black Allison , Potter Barney , Dudas Gytis , Feldstein Leora , Grubaugh Nathan D , Andersen Kristian G , Ellis Brett R , Ellis Esther M , Bedford Trevor
Published: March 2017

Here we release draft genome sequences of Zika virus (ZIKV) that were sequenced from PCR-positive diagnostic specimens collected by the United States Virgin Islands Department of Health (USVI DoH) as part of their ongoing response to the ZIKV outbreak. We will use these sequences to conduct a genomic epidemiological study of ZIKV transmission in the USVI. We are releasing these genomes in the hope that they are useful for those individuals involved in the public health response to ZIKV and to other groups working to understand Zika virus transmission and evolution.
DHX15 regulates CMTR1-dependent gene expression and cell proliferation
Authors: Inesta-Vaquera Francisco , Galloway Alison , Chandler Laurel , Rojas-Fernandez Alejandro , Chaugule Viduth K. , Weidlich Simone , Peggie Mark , Cowling Victoria H
Published: March 2017

CMTR1 contributes to mRNA cap formation by methylating the O-2 position of the 1sttranscribed nucleotide ribose. mRNA cap O-2 methylation has roles in mRNA translation and self-RNA tolerance in innate immunity, however its role in cell physiology is unclear. We report that CMTR1 is recruited to Serine-5 phosphorylated RNA Pol II CTD, facilitating cotranscriptional methylation. We isolated CMTR1 in a complex with DHX15, an RNA helicase functioning in splicing and ribosome biogenesis, and characterised it as a regulator of CMTR1. When bound to DHX15, CMTR1 activity is repressed and prevented from binding to RNA pol II, thus constraining 1stnucleotide methylation to a co-transcriptional event. Conversely CMTR1 activates DHX15 helicase activity and influences its nuclear localisation, which is likely to impact on several nuclear functions. The impact of the CMTR1-DHX15 interaction is complex and will depend on the relative expression of these enzymes and their interactors, and the cellular dependency on different RNA processing pathways. In HCC1806 cells, the DHX15-CMTR1 interaction controls ribosome loading of a subset of mRNAs and impacts on cell proliferation.
Non-linear disease tolerance curves reveal distinct components of host responses to viral infection
Authors: Gupta Vanika , Vale Pedro F.
Published: March 2017

The ability to tolerate infection is a key component of host defence and offers potential novel therapeutic approaches for infectious diseases. To yield successful targets for therapeutic intervention, it is important that the analytical tools employed to measure disease tolerance are able to capture distinct host responses to infection. Here, we show that commonly used methods that estimate tolerance as a linear relationship may be inadequate, and that more flexible, non-linear estimates of this relationship may reveal variation in distinct components of host defence. To illustrate this, we measured the survival ofDrosophila melanogastercarrying either a functional or non-functional regulator of the JAK-STAT immune pathway (G9a) when challenged with a range of concentrations of Drosophila C Virus (DCV). While classical linear model analyses indicated thatG9aaffected tolerance only in females, a more powerful non-linear logistic model showed thatG9amediates viral tolerance to different extents in both sexes. This analysis also revealed thatG9aacts by changing the sensitivity to increasing pathogen burdens, but does not reduce the ultimate severity of infection. These results indicate that fitting non-linear models to host health-pathogen burden relationships may offer better and more detailed estimates of disease tolerance.
The Genetic History of Northern Europe
Authors: Mittnik Alissa , Wang Chuan-Chao , Pfrengle Saskia , Daubaras Mantas , Zariņa Gunita , Hallgren Fredrik , Allmäe Raili , Khartanovich Valery , Moiseyev Vyacheslav , Furtwängler Anja , Andrades Valtueña Aida , Feldman Michal , Economou Christos , Oinonen Markku , Vasks Andrejs , Tõrv Mari , Balanovsky Oleg , Reich David , Jankauskas Rimantas , Haak Wolfgang , Schiffels Stephan , Krause Johannes
Published: March 2017

Recent ancient DNA studies have revealed that the genetic history of modern Europeans was shaped by a series of migration and admixture events between deeply diverged groups. While these events are well described in Central and Southern Europe, genetic evidence from Northern Europe surrounding the Baltic Sea is still sparse. Here we report genome-wide DNA data from 24 ancient North Europeans ranging from ~7,500 to 200 calBCE spanning the transition from a hunter-gatherer to an agricultural lifestyle, as well as the adoption of bronze metallurgy. We show that Scandinavia was settled after the retreat of the glacial ice sheets from a southern and a northern route, and that the first Scandinavian Neolithic farmers derive their ancestry from Anatolia 1000 years earlier than previously demonstrated. The range of Western European Mesolithic hunter-gatherers extended to the east of the Baltic Sea, where these populations persisted without gene-flow from Central European farmers until around 2,900 calBCE when the arrival of steppe pastoralists introduced a major shift in economy and established wide-reaching networks of contact within the Corded Ware Complex.
Despite reproductive interference, the net outcome of reproductive interactions among spider mite species is not necessarily costly
Authors: Clemente Salomé H. , Santos Inês , Ponce Rita , Rodrigues Leonor R. , Varela Susana A. M. , Magalhães Sara
Published: March 2017

This preprint has been reviewed and recommended by Peer Community in Evolutionary Biology (http://dx.doi.org/10.24072/pci.evolbiol.100025). Reproductive interference is considered a strong ecological force, potentially leading to species exclusion. This supposes that the net effect of reproductive interactions is strongly negative for one of the species involved. Testing this requires a comprehensive analysis of interspecific reproductive interactions, accounting for the order and timing of mating events, and for their effects on either fertility or fecundity. To this aim, we measured reproductive interactions between a focal species,Tetranychus urticae, and an invasive (T.evansi) and a resident (T. ludeni) species, varying the mating sequence and interval, and measuring the effect of such crosses on fecundity and offspring sex ratio (a measure of fertility, as these species are haplodiploid). We found that mating with heterospecifics affected fecundity and sex ratio negatively, but also positively, depending on the species involved, and on the order and timing of mating events. Overall, the net effect of reproductive interactions was weak despite strong effects of particular events. In natural situations, the outcome of reproductive interactions will thus hinge upon the frequency of each event.
Contractility, Differential Tension and Membrane Removal direct zebrafish Epiboly Biomechanics
Authors: Marsal Maria , Martin-Blanco Enrique
Published: March 2017

Precise tissue remodeling during development is essential for shaping embryos and for optimal organ function. Epiboly is an early gastrulation event by which the blastoderm expands around the yolk to engulf it. Three different layers are involved, an epithelial layer (the enveloping layer, EVL), the embryo proper, constituted by the deep cells (DCs), and the yolk cell. Although teleost epiboly has been studied for many years, a clear understanding of its mechanics was still missing. Here we present new information on the cellular, molecular and mechanical elements involved in epiboly that, together with some other recent data and upon comparison with previous biomechanical models, lets conclude that the expansion of the epithelia is passive and driven by cortical contraction and membrane removal in the adjacent layer, the External Yolk Syncytial Layer (E-YSL). The isotropic actomyosin contraction of the E-YSL generates an anisotropic stress pattern and a directional net movement as a result of the differences in the deformation response of two opposites adjacent domains (the EVL and the Yolk Cytoplasmic Layer - YCL). Contractility is accompanied by the local formation of membrane folds and the membrane removal by Rab5ab dependent macropinocytosis. The increase in area of the epithelia during the expansion is achieved by cell-shape changes (flattening) responding to spherical geometrical cues. The counterbalance between the geometry of the embryo and forces dissipation is therefore essential for epiboly global coordination.