bluuebunny/crossref_metadata_2025 huggingface dataset:
Pharmacokinetics and Pharmacodynamics of Immediate-Release Versus Extended-Release Guanfacine in Adult Daily Smokers
Authors: Verplaetse Terril L. , Roberts Walter , Moore Kelly E. , Peltier MacKenzie R. , Oberleitner Lindsay M. , McKee Sherry A.
Published: February 2019

Background

Guanfacine is Food and Drug Administration approved for hypertension and attention-deficit hyperactivity disorder and has been used off-label for migraine prophylaxis, heroin withdrawal, and more recently smoking cessation. Previous studies have shown positive effects of 3 mg/d of immediate-release (IR) guanfacine on smoking outcomes, but the dose equivalency of the IR and extended-release (ER) formulations is unknown.

Procedures

A within-subject design was used to compare the pharmacokinetics and pharmacodynamics of 3 mg/d of IR, 4 mg/d of ER, and 6 mg/d of ER guanfacine in adult daily smokers (n = 5). Plasma medication levels, vital signs, cigarettes per day, tobacco craving, and adverse events were assessed. Medication was titrated to stable dosing after each laboratory day (3 mg/d IR, then 4 mg/d ER, then 6 mg/d ER).

Results

Plasma medication levels did not differ between the 3 mg/d of IR and 4 mg/d of ER doses after 24 hours from last dose and were highest at the 6 mg/d of ER dose (3 mg/d IR: M = 3.40 ng/mL, SE = 0.34 vs 4 mg/d ER: M = 3.46 ng/mL, SE = 0.67 vs 6 mg/d ER: M = 5.92 ng/mL, SE = 1.02). All doses of guanfacine decreased heart rate and blood pressure from baseline. Absolute values of cigarettes per day (6 mg/d ER) and tobacco craving (4 and 6 mg/d ER) were lowest with the ER formulations. Treatment-emergent adverse events were subject rated as minimal to mild, except dry mouth.

Conclusions

We demonstrated similar pharmacokinetic profiles between 3 mg/d of IR guanfacine and 4 mg/d of ER guanfacine, as hypothesized. All doses of guanfacine were well tolerated.
Comparison of mycophenolate mofetil with standard treatment for autoimmune hepatitis: a meta-analysis
Authors: Yu Zhen-Jun , Zhang Lu-Lu , Huang Ting-Ting , Zhu Jian-Sheng , He Ze-Bao
Published: February 2019

Objective

To systematically evaluate the efficacy of mycophenolate mofetil (MMF) compared with the standard treatment for autoimmune hepatitis.

Methods

Medline (PubMed), Embase, and Cochrane Library databases were searched between 1966 and June 2018 for studies on prednisone and/or azathioprine/mycophenolate mofetil in autoimmune hepatitis. The keywords and descriptor terms used were ‘hepatitis’, ‘autoimmunity’, ‘prednisone’, ‘prednisolone’, ‘azathioprine’, and ‘mycophenolate mofetil’. The Z test and Cochrane Q test were used in the statistical analysis.

Results

Seven hundred and eighty-eight related articles were found; 779 studies were excluded after further review. Ultimately, seven studies (583 participants) were included. The remission rate of aminotransferase and immunoglobulin (Ig)-G levels with standard treatment was 33.33–86.67%, and the nonresponse rate was 15.15–66.67%. Although the remission rate of the aminotransferase level with prednisone and MMF was 55.17–88.89% and that of the IgG level was 61.16–88.89%, the nonresponse rate was 6.42–33.33%. Remission rates of the aminotransferase level (P<0.05, I
2=49%) and IgG level (P<0.01, I
2=0) with MMF were superior to those of standard treatment, and the nonresponse rate was lower (P<0.01, I
2=0). For those with no response to the standard treatment who were switched to MMF, the remission rates were 0, 13.33, 22.22, 25, and 34.04%. Sequential treatment with MMF was effective (P<0.01, I
2=90%).

Conclusion

Compared with the standard treatment, the combination of prednisone and MMF as a first-line treatment enables patients with autoimmune hepatitis to obtain higher remission rates of aminotransferase and IgG levels and a lower nonresponse rate. The validity and safety of long-term MMF use needs investigated further.
Treatment options for nonalcoholic fatty liver disease: a double-blinded randomized placebo-controlled trial
Authors: Anushiravani Amir , Haddadi Niloufar , Pourfarmanbar Maedeh , Mohammadkarimi Vahid
Published: February 2019

Introduction

Nonalcoholic fatty liver disease (NAFLD) is the most common liver disease worldwide and is becoming the most frequent indication of liver transplantation. Cardiovascular disease is the main cause of death in these patients. There is no Food and Drug Association-approved medication for NAFLD patients. We aimed to provide more robust evidence on the use of medications that are inexpensive and available, namely, metformin, silymarin, pioglitazone, and vitamin E, for treating NAFLD.

Materials and methods

We conducted a randomized double-blinded, placebo-controlled trial on 150 consecutive patients with NAFLD who were assigned to five groups: lifestyle plus placebo, metformin 500 mg/day, silymarin 140 mg/day, pioglithasone 15 mg/day, and vitamin E 400 IU/day, all for 3 months. Anthropometric and biochemical variables were measured at baseline and 3 months later.

Results

The mean age of the patients was 47.0±9.1 (range: 18–65) years and the sex distribution was 73 (48.7%) women and 77 (51.3%) men. Patients in all groups showed a significant improvement in anthropometric parameters such as waist circumference and BMI. There was no statistically significant difference in alanine transaminase and aspartate transaminase in the control group after treatment (P=0.51, 0.18, respectively); however, both liver enzymes decreased significantly in the other groups.

Discussion and conclusion

This randomized double-blinded placebo-controlled clinical trial suggested a significant benefit of silymarin, pioglitazone, and vitamin E in improving liver aminotransferases in patients with NAFLD after only 3 months, without exerting any specific side effects.
Epithelial Claudin Proteins and Their Role in Gastrointestinal Diseases
Authors: Kim David Y. , Furuta Glenn T. , Nguyen Nathalie , Inage Eisuke , Masterson Joanne C.
Published: February 2019

Our bodies are protected from the external environment by mucosal barriers that are lined by epithelial cells. The epithelium plays a critical role as a highly dynamic, selective semipermeable barrier that separates luminal contents and pathogens from the rest of the body and controlling the absorption of nutrients, fluid and solutes. A series of protein complexes including the adherens junction, desmosomes, and tight junctions function as the principal barrier in paracellular diffusion and regulators of intracellular solute, protein, and lipid transport. Tight junctions are composed of a series of proteins called occludins, junctional adhesion molecules, and claudins that reside primarily as the most apical intercellular junction. Here we will review one of these protein families, claudins, and their relevance to gastrointestinal and liver diseases.
A Noninvasive Method—Shear-Wave Elastography Compared With Transient Elastography in Evaluation of Liver Fibrosis in Patients With Chronic Hepatitis B
Authors: Xia Shujun , Ren Xinping , Ni Zhongxin , Zhan Weiwei
Published: February 2019

The aim of our study was to investigate the efficiency and feasibility of shear-wave elastography (sound touch elastography [STE], sound touch quantification [STQ]) compared with transient elastography (FibroScan) assessment in noninvasively and quantitatively identifying the degree of liver fibrosis. A total of 158 patients with chronic hepatitis B were included, and all accepted STE, STQ, and FibroScan assessments. Young's modulus (kPa) of STE, STQ, and FibroScan were evaluated, and the diagnostic performance of the 3 techniques on liver fibrosis stage was compared. The final diagnosis was based on histological findings from liver biopsy. Of all these patients, 36 patients were categorized as G/S < 2, and 122 were as G/S ≥ 2 according to Scheuer G/S scoring system. STEmean and STQmean measurements were positively correlated with liver fibrosis stage with high correlation (r = 0.852 and r = 0.803, respectively). Receiver operating characteristic analysis of STE, STQ, and FibroScan revealed that the areas under the curve of STE and STQ were markedly increased compared with that of FibroScan when differentiating early stage of liver fibrosis (S1, S2). It was concluded that shear-wave elastography (STE, STQ, and FibroScan) performs well in evaluation of liver fibrosis in patients with chronic hepatitis B, and the efficacies of STE and STQ are better than that of FibroScan.
Ultrasonography-Guided Core Needle Biopsy Did Not Reduce Diagnostic Lobectomy for Thyroid Nodules Diagnosed as Atypia of Undetermined Significance/Follicular Lesion of Undetermined Significance
Authors: Yoon Jung Hyun , Kwak Jin Young , Moon Hee Jung , Kim Eun-Kyung
Published: February 2019

In this study, we evaluated the role of ultrasonography-guided core needle biopsy (US-CNB) in deciding upon management for prior atypia of undetermined significance/follicular lesion of undetermined significance (AUS/FLUS) results. From May 2013 to June 2015, 149 thyroid nodules in 149 patients diagnosed as having AUS/FLUS were included. Of the 149 thyroid nodules, 86 (57.5%) had repeat US-guided fine needle aspiration (US-FNA) and 63 (42.3%) had US-CNB. Histopathology results were divided according to various indications for diagnostic lobectomy, and rates of diagnosis that are candidates for diagnostic lobectomy were compared. Of the 149 thyroid nodules included, 86 (57.7%) were diagnosed as benign, 27 (18.1%) as malignancy, and 36 (24.2%) as inconclusive. Repeat US-FNA had significantly higher rates of inconclusive diagnosis compared with US-CNB, 33.7% to 11.1% (P = 0.003). Nodules with US-CNB had significantly higher rates of surgery or follow-up, whereas those with US-FNA had higher rates of repeated biopsy (P < 0.001). Rates of cytopathologic candidates for diagnostic lobectomy did not show significant differences between repeat US-FNA and US-CNB for any of the indications (all P > 0.05). Based on this, we concluded that US-CNB has higher diagnostic rates than did repeat US-FNA, but it does not provide superior guidance over repeat US-FNA in deciding upon diagnostic lobectomy for thyroid nodules with prior AUS/FLUS cytology results.
Risk Threshold Algorithm for Thyroid Nodule Management Demonstrates Increased Specificity and Diagnostic Accuracy as Compared With American College of Radiology Thyroid Imaging, Reporting and Data System; Society of Radiologists in Ultrasound; and American Thyroid Association Management Guidelines
Authors: Clark Toshimasa James , McKinney Kristin , Jensen Alexandria , Patel Nayana U.
Published: February 2019

We studied diagnostic performance of an algorithm guiding thyroid nodule management using a malignancy risk model as compared with extant management guidelines. Single-institution, retrospective study was performed with sequential cases from pathology registry from 2012 to 2015. Seventy-eight patients were enrolled, with benign and malignant groups defined by aspiration results. Risk Threshold Algorithm determined management based off of a logistic regression model and a risk threshold. American College of Radiology Thyroid Imaging, Reporting and Data System (ACR TI-RADS), Society of Radiologists in Ultrasound (SRU), and American Thyroid Association (ATA) guidelines were used in comparison. Sensitivity, specificity, positive/negative predictive values, receiver operating characteristic (ROC) values were derived, with significance assessed via McNemar and permutation tests. Forty-four benign nodules and 40 papillary thyroid carcinomas were included. Risk Threshold Algorithm area under the ROC curve was 0.80 versus 0.59 (ACR TI-RADS), 0.49 (SRU), and 0.44 (ATA); all areas under the ROC curve differences were statistically significant. Risk Threshold Algorithm demonstrates sensitivity, specificity, positive predictive value, and negative predictive values of 63%, 91%, 86%, and 73% at the risk threshold maximizing diagnostic performance, compared with 85%, 39%, 56%, and 74% (ACR TI-RADS); 85%, 18%, 50%, and 57% (SRU); and 89%, 11%, 50%, and 83% (ATA). Sensitivity and specificity were significantly different between all groups except SRU versus TI-RADS. The Risk Threshold Algorithm, based on a malignancy risk model, demonstrates increased overall diagnostic accuracy as compared with ACR TI-RADS, SRU, and ATA management guidelines. Through eliminating unnecessary biopsy, patient anxiety, and morbidity can be reduced.
The Ultrasound Anatomy of Nerves in the Interscalene Groove
Authors: Verdecchia Nicole M. , Ibinson James W. , Orebaugh Steven L.
Published: February 2019

In the interscalene groove, nerve structures are in close proximity and may not be visible as separate structures, increasing the risk of insertion of the needle tip within the epineurium. We evaluated whether experienced regional anesthesiologists can distinguish between nerve elements lying in close proximity on ultrasound images.

Brachial plexus elements from 4 nonpreserved cadavers were arranged in a water bath. Ultrasound images of the nerve roots and trunks were taken. Regional anesthesiologists and residents were asked whether they could distinguish the nerves as 2 separate structures and if they could identify a pair of nerve roots versus a single trunk.

Attending anesthesiologists reported the ability to discriminate 2 nerve structures when a 2-mm space was arranged between them in 54% of images; however, when in direct contact, this recognition was significantly lower. The residents reported a higher ability to discriminate the 2 nerves in all scenarios. In addition, the attending anesthesiologists successfully identified paired nerve roots versus nerve trunks in 70% of the images, significantly higher than chance (P = 0.01), whereas the fraction of correct resident responses was not significantly different from guessing.

When nerves were placed in close proximity, experienced regional anesthesiologists had difficulty identifying them as separate structures and were incorrect nearly one-third of the time in discriminating 2 closely positioned roots versus a nerve trunk. This underscores the importance of cautious needle insertion into the interscalene groove, where nerve elements are often juxtaposed one to another.
Multimodality Imaging of Congenital Variants in the Gallbladder
Authors: Whittle Carolina , Skoknic Velimir , Maldonado Ignacio , Schiappacasse Giancarlo , Pose Georgette
Published: February 2019

Congenital variants of the gallbladder development are infrequent and sometimes represent an asymptomatic imaging finding. In this case series, we want to present multimodality imaging findings that permit the diagnosis. Ultrasound, multidetector computed tomography, and magnetic resonance images are included.

The proper recognition of these infrequent congenital benign entities avoids unnecessary complementary examinations and misdiagnosis. Although ultrasound represents the most commonly used initial diagnostic tool, the increased use of magnetic resonance imaging and the wide use of multidetector computed tomography make it crucial to know how these entities are seen.

A retrospective review of cases of congenital variants of gallbladder through different imaging modalities was performed in our computer archives. Representative images were selected. Agenesis, hypoplasia, septated, duplicated, intrahepatic, and left-sided gallbladder are described.

Better understanding and recognition of congenital anomalies in gallbladder images will avoid misdiagnosis.
Shear-Wave Elastography in the Characterization of Pleural Effusions
Authors: Ozgokce Mesut , Durmaz Fatma , Yavuz Alpaslan , Üney İbrahim , Yildiz Hanifi , Arslan Harun , Dundar Ilyas , Havan Nuri , Ogul Hayri
Published: February 2019

The aim of the study was to investigate the efficacy of shear-wave elastography (SWE) in the differentiation of transudative and exudative pleural effusions. This monocentric study comprised 60 cases (17 transudative, 43 exudative).Transthoracic SWE was performed in 60 cases for whom to use thoracentesis for the pleural fluid analysis was planned. The mean SWE values of each patient were recorded, and the correlation between the biochemical analysis results of pleural fluid after thoracentesis and SWE findings was evaluated. The effusion SWE values and biochemical analysis results were compared. Of the 60 patients who participated in this study, 32 (53.4) were male and 28 (46.6%) were female. The mean ± SD age was 59 ± 17.09 years (range = 21–89 years). Simultaneous serum biochemical analysis was performed for the patients with PE. The mean ± SD shear-wave velocity value of the transudative fluid was calculated 2.29 ± 0.41 (1.6–2.94), whereas the mean ± SD shear-wave velocity value of the exudative pleural fluid was calculated as 3.29 ± 0.63 (2.01–4.88) (P < 0.001). The receiver operating characteristic analysis showed that sensitivity and specificity were found as 91% and 76.5%, respectively, when the cutoff value was selected as 2.52 m/s in the differentiation of the transudative and exudative effusions.

Shear-wave elastography may help in the differentiation of transudative and exudative of the pleural effusions.
The Clinical Value of New Scoring System of Cervical Lymph Node
Authors: Shen Haolin , Lv Guorong , Ke Linfang , Li Ling , Zheng Chunnuan , Yang Shuping
Published: February 2019

To distinguish malignant cervical lymphadenopathy, we established a new scoring system based on ultrasound features. Two hundred sixty-three patients with cervical lymphadenopathy received ultrasonic examination and underwent ultrasound-guided core needle biopsy or fine needle aspiration. The scoring system was proposed by multivariate logistic regression analysis and compared with Liao scoring system (0.06 × age + 4.76 × shortest-to-longest axis ratio + 2.15 × internal echo + 1.80 × vascular pattern). A new scoring system model, 1.346 × margin + 1.339 × hilum + 2.411 × calcification + 2.619 × vascular pattern + 0.837 × shortest-to-longest axis ratio, was generated. Lymph nodes were regarded as malignancy when the score was ≥2.4. Compared with the Liao scoring system, the new scoring system had larger area under the curve (0.86 versus 0.76,P= 0.036), specificity (86.7% versus 75.0%,P= 0.001), accuracy (87.1% versus 80.6%,P= 0.007), and positive predictive value (89.0% versus 80.0%,P= 0.043). Sensitivity (87.4% versus 85.3%,P= 0.647) and negative predictive value (85.0% versus 81.0%,P= 0.395) did not differ. We concluded that the new scoring system is more reliable and can play an important role in the differential diagnosis of cervical lymph nodes.
The Role of the US Surgeon in Global Care
Authors: Corlew Daniel Scott
Published: February 2019

There is a great mismatch between surgeon workforce capacity in the US and other high income countries (HICs) and that in low and lower middle income countries (LMICs). Many surgeons in HICs are willing to try to be of assistance in LMICs. It is not intuitive, though, exactly how such assistance is best delivered. Similarly, the body of literature describing what is known about the needs in LMICs may not be in the usual cadre of journals and sources accessed by many practicing surgeons. Consequently, many surgeons who are capable and willing to help in LMICs are often not sure how their abilities might be best used.

This essay presents a very brief overview of what is known about those needs, then presents some commentary on how the practicing surgeon in the US and other HICs may be best utilized, with particular attention to the short term trip model. Deployment in the short term trip model is often the most practical and available means of making this effort for HIC surgeons. This model has come under significant criticism in recent years, often for good reason, but it is argued that details of the implementation of that model can determine its applicability to developmental needs. Given the practicality of short term deployments for HIC surgeons, it behooves Ministries of Health and NGOs to examine how trips of this nature can be incorporated into the overall bigger picture of surgical development.

This essay aims to help the perspective of the HIC surgeon as s/he seeks to contribute to the development of surgical access and quality for the approximately five billion people in the world who do not have adequate access to surgical care.
Distal Finger Reconstruction by Bilateral Lateral Hallux Osteo-onychocutaneous Free Flap
Authors: Wang Zengtao , Sun Wenhai , Lineaweaver William C. , Hao Liwen , Qiu Shenqiang , Zhang Lishan , Chen Chao , Chiu Yung-Cheng , Yilihamu Yilizati , Zhang Feng
Published: February 2019

Objective

In this report, we present our experience on the use of bilateral lateral hallux osteo-onychocutaneous free flaps for reconstruction of distal finger and the aesthetic and functional results of this technique in a series of cases.

Patients and Methods

From February 2005 to May 2015, 7 patients underwent finger reconstruction distal to the distal interphalangeal joint using the bilateral lateral hallux osteo-onychocutaneous free flaps. The mean age was 29.3 years (range, 24–33 years). The lateral hallux osteo-onychocutaneous flaps were harvested from bilateral donor sites. The size of each flap was designed based on the size of half distal finger defect. The lateral hallux osteo-onychocutaneous free flaps from both donor sites were combined to reconstruct the distal finger. More than 50% of hallux nail was preserved in each of donor sites, which was covered with a local flap.

Results

All flaps used for reconstruction survived without complications after surgery. The average length of follow-up was 93.4 months (range, 16–163 months). All reconstructed distal fingers showed good aesthetic appearance, except one that underwent a secondary debulking procedure. The average total active motion of the finger was 215.7 degrees (range, 200–230 degrees). Neither pain nor numbness sensation in the reconstructed fingers was complained by the patients. The donor site morbidity was minimal. All patients had pain-free and good function outcome in both feet.

Conclusions

The use of the bilateral lateral hallux osteo-onychocutaneous free flaps may provide an option for distal finger reconstruction with satisfactory function and anesthetic outcomes with minimal hallux donor site morbidity.
Practice Site Contributions to the Overall Growth of a Burn Care Network
Authors: Mullins Fred , Lineaweaver William C.
Published: February 2019

Beginning in 2009, The Joseph M. Still Burn Center in Augusta, Georgia began to develop additional practice sites. By 2018, 6 burn centers had been established and the practice network had been organized as the Burn and Reconstructive Centers of America.Between 2015 and 2017, the entire network had 2 consecutive years of increasing burn admissions of +21% and +20%. The proportion of burn admissions managed by the additional sites grew from 37% to 47% during the same period. All practice sites, including the Augusta center, demonstrated sustained net growth of burn admissions.These data show that this practice development plan has achieved substantial growth in burn admissions throughout the practice, with the newly developed sites contributing disproportionately to overall network practice growth. These findings also suggest that the development of new sites could affect burn center accessibility and utilization for burn patients in these areas.
CCR5-Positive Inflammatory Monocytes are Crucial for Control of Sepsis
Authors: Castanheira Fernanda Vargas e Silva , de Lima Kalil Alves , Cebinelli Guilherme Cesar Martelossi , Sônego Fabiane , Kanashiro Alexandre , Colon David-Fernando , Borges Vanessa , Czaikoski Paula Giselle , Mota José Mauricio , Cunha Thiago Mattar , Alves-Filho José Carlos , Liew Foo Y. , Cunha Fernando Queiroz
Published: February 2019

Neutrophils and inflammatory monocytes control sepsis by migration to the site of infection via their chemokine receptors. CCR5 is a chemokine receptor that is not expressed on neutrophils and inflammatory monocytes under homeostatic conditions. However, it has been demonstrated that CCR5 can become expressed on these cells during different models of inflammation. In the present study, we investigated if CCR5 is also expressed on neutrophil and inflammatory monocytes during sepsis, exerting an important role in the migration of these cells to the infectious focus. Using cecal ligation and puncture model to induce polymicrobial sepsis, we demonstrated that the expression of CCR5 is induced on CD11b+Ly6G−Ly6Chigh inflammatory monocytes, but not on neutrophils (CD11b+Ly6G+Ly6C−). Furthermore, CCR5 plays an important role for the migration of the inflammatory monocytes to infection focus during sepsis. CCR5-expressing inflammatory monocytes migrate from the bone marrow to the circulation and then into the site of infection, where they phagocytize and kill the bacteria. Consequently, CCR5−/− mice showed increased systemic inflammatory response and mortality compared to wild-type mice. These data therefore demonstrate a hitherto unrecognized protective role of CCR5 in sepsis.
Autoimmune glial fibrillary acidic protein astrocytopathy
Authors: Kunchok Amy , Zekeridou Anastasia , McKeon Andrew
Published: February 2019

Purpose of review

To describe a recently characterized autoimmune, inflammatory central nervous system (CNS) disorder known as autoimmune glial fibrillary acidic protein (GFAP) astrocytopathy.

Recent findings

Affected patients present with symptoms of one or more of meningitis (headache and neck ache), encephalitis (delirium, tremor, seizures, or psychiatric symptoms), and myelitis (sensory symptoms and weakness). Optic disc papillitis (blurred vision) is common. CNS inflammation is evident in characteristic T1 postgadolinium enhancement of GFAP-enriched CNS regions, and lymphocytic cerebrospinal fluid (CSF) white cell count elevation. CSF is more reliable than serum for GFAP-immunoglobulin G (IgG) testing. Ovarian teratoma commonly coexists, particularly among patients with accompanying N-methyl-D-aspartate receptor or aquaporin-4 autoimmunity. Parainfectious autoimmunity is suspected in some other patients, though the culprit organism is rarely verified. Pathophysiologic relevance of T cells is underscored by neuropathology and cases of dysregulated T-cell function (HIV or checkpoint inhibitor cancer therapy). Corticosteroid-responsiveness is a hallmark of the disease. Relapses occur in approximately 20% of patients, necessitating transition to a steroid-sparing drug. Reported outcomes vary, though in the authors’ experience, early and sustained intervention usually portends recovery.

Autoimmune GFAP astrocytopathy is a treatable autoimmune CNS disease diagnosable by GFAP-IgG testing in CSF. This disease presents opportunities to explore novel mechanisms of CNS autoimmunity and inflammation.
Aripiprazole-Induced Hoarseness: A Case Report
Authors: Işik Ümit , Çam Ray Perihan
Published: February 2019

Objectives

Aripiprazole is an atypical antipsychotic drug that is commonly used in children and adolescents.

Methods

The most common adverse effects of aripiprazole include fatigue, nausea, increased appetite, headache, sedation, and somnolence.

Results

To our knowledge, there are no data regarding aripiprazole-induced hoarseness in the existing literature.

Conclusions

We present a case of a preschool boy with attention-deficit/hyperactivity disorder and oppositional defiant disorder who displayed hoarseness after aripiprazole therapy.
Diagnostic challenges in supraventricular tachycardia: anticipating value of natriuretic peptides
Authors: Yetkin Ertan
Published: February 2019

It is important not to overlook supraventricular tachycardia (SVT) in patients complaining of palpitation or tachycardia-related symptoms but with normal ECG and heart rate in emergency department or outpatient clinics. The severity and presentation of symptoms is highly variable and depends on features including heart rate, duration of tachycardia, underlying heart disease, and individual patient perception. Early measurement of natriuretic peptides in patients presenting with palpitation and/or tachycardia-related symptoms would guide the clinician to rule out tachycardia and/or SVT. High levels of natriuretic peptides within 30 min of postattack period would certainly increase the likelihood of SVT.
Is diabetes mellitus equivalent to atherosclerotic cardiovascular disease from a healthcare cost perspective? Insights from the Medical Expenditure Panel Survey: 2010–2013
Authors: Feldman David I. , Valero-Elizondo Javier , Salami Joseph A. , Rana Jamal S. , Ogunmoroti Oluseye , Okunrintemi Victor , Osondu Chukwuemeka U. , Spatz Erica S. , Virani Salim S. , Blankstein Ron , Blaha Michael J. , Veledar Emir , Nasir Khurram
Published: February 2019

Diabetes mellitus (DM) and atherosclerotic cardiovascular disease (ASCVD) both increase the risk for a major adverse cardiac event, and are therefore considered priority conditions clinically. Although guidelines encourage clinicians to treat them similarly, many researchers do not consider DM an ASCVD risk-equivalent. However, from a healthcare system standpoint it is more important to determine whether DM is an economic burden equivalent to ASCVD. Using data from the Household Component of the 2010–2013 Medical Expenditure Panel Survey, we determined that the diagnosis of DM yields significantly lower healthcare expenditures and resource utilization when compared with ASCVD. In fact, the healthcare cost associated with DM alone is almost $1000 less than ASCVD. That being said, the cost and resource utilization was highest among those individuals diagnosed with ASCVD+DM, underscoring the importance of primary and secondary prevention to help detect individuals early and initiate proper lifestyle and aggressive therapeutic managements.
Development of clinical trials to extend healthy lifespan
Authors: Justice Jamie N. , Niedernhofer Laura , Robbins Paul D. , Aroda Vanita R. , Espeland Mark A. , Kritchevsky Stephen B. , Kuchel George A. , Barzilai Nir
Published: February 2019

Significant progress in defining the biology of aging, particularly in animal models, supports the geroscience hypothesis, which posits that by therapeutically targeting biological aging, the onset of multiple age-related diseases can be delayed ‘en suite’. Geroscience investigators are preparing to test this hypothesis in humans for the first time. In this review, we describe development of large-scale clinical trials designed to determine whether multiple age-related health conditions can be simultaneously alleviated with interventions targeting the underlying biology of aging. We describe the rationale and collaborative, consensus building approach used to design the first aging outcome trial called Targeting Aging with Metformin. Through this case study, we outline features that could be more broadly extended to other geroscience-guided clinical trials, including a process for selecting biochemical and molecular markers of biologic age and we provide a perspective on the potential impact of clinical trials targeting aging.
Hox genes mediate the escalation of sexually antagonistic traits in water striders
Authors: Crumière Antonin Jean Johan , Khila Abderrahman
Published: February 2019

Sexual conflict occurs when traits favoured in one sex impose fitness costs on the other sex. In the case of sexual conflict over mating rate, the sexes often undergo antagonistic coevolution and escalation of traits that enhance females' resistance to superfluous mating and traits that increase males' persistence. How this escalation in sexually antagonistic traits is established during ontogeny remains unclear. In the water strider
Rhagovelia antilleana,
male persistence traits consist of sex combs on the forelegs and multiple rows of spines and a thick femur in the rear legs. Female resistance traits consist of a prominent spike-like projection of the pronotum. RNAi knockdown against the Hox gene
Sex Combs Reduced
resulted in the reduction in both the sex comb in males and the pronotum projection in females. RNAi against the Hox gene
Ultrabithorax
resulted in the complete loss or reduction of all persistence traits in male rear legs. These results demonstrate that Hox genes can be involved in intra- and inter-locus sexual conflict and mediate escalation of sexually antagonistic traits.
High levels of functional divergence in toxicity towards prey among the venoms of individual pigmy rattlesnakes
Authors: Smiley-Walters Sarah A. , Farrell Terence M. , Gibbs H. Lisle
Published: February 2019

Venom is a complex molecular phenotype that shows high levels of variation in expressed proteins between individuals within and between populations. However, the functional significance of this variation in terms of toxicity towards prey is largely unknown. Here, we assessed the relative toxicity of venom from individual pygmy rattlesnakes (
Sistrurus miliarius
) on brown anoles (
Anolis sagrei
) using a novel assay involving tests of fixed doses of venom from individual snakes on individual lizards. We found high levels of functional variation between individual venoms within populations with individual differences (nested within population) explaining 3.6 times more variation in toxicity than population differences. Our results suggest a previously unappreciated adaptive significance to within-population variation in venom. They argue that selective mechanisms that maintain variation within populations may be of equal or greater importance to divergent selection leading to local adaption between populations as evolutionary explanations of venom variation within species.
Black soldier fly larvae feed by forming a fountain around food
Authors: Shishkov Olga , Hu Michael , Johnson Christopher , Hu David L.
Published: February 2019

The black soldier fly is a non-pest insect of interest to the sustainability community due to the high eating rates of its edible larvae. When found on carcases or piles of rotting fruit, this larva often outcompetes other species of scavengers for food. In this combined experimental and theoretical study, we elucidate the mechanism by which groups of black soldier fly larvae can eat so quickly. We use time-lapse videography and particle image velocimetry to investigate feeding by black soldier fly larvae. Individually, larvae eat in 5 min bursts, for 44% of the time, they are near food. This results in their forming roadblocks around the food, reducing the rate that food is consumed. To overcome these limitations, larvae push each other away from the food source, resulting in the formation of a fountain of larvae. Larvae crawl towards the food from below, feed and then are expelled on the top layer. This self-propagating flow pushes away potential roadblocks, thereby increasing eating rate. We present mathematical models for the rate of eating, incorporating flow rates measured from our experiments.
The role of adhesion in contact mechanics
Authors: Ciavarella M. , Joe J. , Papangelo A. , Barber J. R.
Published: February 2019

Adhesive (e.g. van der Waals) forces were not generally taken into account in contact mechanics until 1971, when Johnson, Kendall and Roberts (JKR) generalized Hertz’ solution for an elastic sphere using an energetic argument which we now recognize to be analogous to that used in linear elastic fracture mechanics. A significant result is that the load–displacement relation exhibits instabilities in which approaching bodies ‘jump in’ to contact, whereas separated bodies ‘jump out’ at a tensile ‘pull-off force’. The JKR approach has since been widely used in other geometries, but at small length scales or for stiffer materials it is found to be less accurate. In conformal contact problems, other instabilities can occur, characterized by the development of regular patterns of regions of large and small traction. All these instabilities result in differences between loading and unloading curves and consequent hysteretic energy losses. Adhesive contact mechanics has become increasingly important in recent years with the focus on soft materials (which generally permit larger areas of the interacting surfaces to come within the range of adhesive forces), nano-devices and the analysis of bio-systems. Applications are found in nature, such as insect attachment forces, in nano-manufacturing, and more generally in industrial systems involving rubber or polymer contacts. In this paper, we review the strengths and limitations of various methods for analysing contact problems involving adhesive tractions, with particular reference to the effect of the inevitable roughness of the contacting surfaces.
On uncorrelated inter-monomer Förster energy transfer in Fenna–Matthews–Olson complexes
Authors: Kell Adam , Khmelnitskiy Anton Yu. , Reinot Tonu , Jankowiak Ryszard
Published: February 2019

The Fenna–Matthews–Olson (FMO) light-harvesting antenna protein of green sulfur bacteria is a long-studied pigment–protein complex which funnels energy from the chlorosome to the reaction centre where photochemistry takes place. The structure of the FMO protein from
Chlorobaculum tepidum
is known as a homotrimeric complex containing eight bacteriochlorophyll
a
per monomer. Owing to this structure FMO has strong intra-monomer and weak inter-monomer electronic coupling constants. While long-lived (sub-picosecond) coherences within a monomer have been a prevalent topic of study over the past decade, various experimental evidence supports the presence of subsequent inter-monomer energy transfer on a picosecond time scale. The latter has been neglected by most authors in recent years by considering only sub-picosecond time scales or assuming that the inter-monomer coupling between low-energy states is too weak to warrant consideration of the entire trimer. However, Förster theory predicts that energy transfer of the order of picoseconds is possible even for very weak (less than 5 cm
–1
) electronic coupling between chromophores. This work reviews experimental data (with a focus on emission and hole-burned spectra) and simulations of exciton dynamics which demonstrate inter-monomer energy transfer. It is shown that the lowest energy 825 nm absorbance band cannot be properly described by a single excitonic state. The energy transfer through FMO is modelled by generalized Förster theory using a non-Markovian, reduced density matrix approach to describe the electronic structure. The disorder-averaged inter-monomer transfer time across the 825 nm band is about 27 ps. While only isolated FMO proteins are presented, the presence of inter-monomer energy transfer in the context of the overall photosystem is also briefly discussed.
Anniversary address Friday 30 November 2018
Authors: Ramakrishnan Venki
Published: February 2019

I want to start by congratulating my former colleague Greg Winter on his Nobel Prize, as well as the winners of this year's Medals and Awards. It is also with great sadness that I note that Aaron Klug, who was president from 1995 to 2000, died 10 days ago.
Ecological feedback on diffusion dynamics
Authors: Park Hye Jin , Gokhale Chaitanya S.
Published: February 2019

Spatial patterns are ubiquitous across different scales of organization in ecological systems. Animal coat pattern, spatial organization of insect colonies and vegetation in arid areas are prominent examples from such diverse ecologies. Typically, pattern formation has been described by reaction–diffusion equations, which consider individuals dispersing between subpopulations of a global pool. This framework applied to public goods game nicely showed the endurance of populations via diffusion and generation of spatial patterns. However, how the spatial characteristics, such as diffusion, are related to the eco-evolutionary process as well as the nature of the feedback from evolution to ecology and vice versa, has been so far neglected. We present a thorough analysis of the ecologically driven evolutionary dynamics in a spatially extended version of ecological public goods games. Furthermore, we show how these evolutionary dynamics feed back into shaping the ecology, thus together determining the fate of the system.
Resilience or robustness: identifying topological vulnerabilities in rail networks
Authors: Pagani Alessio , Mosquera Guillem , Alturki Aseel , Johnson Samuel , Jarvis Stephen , Wilson Alan , Guo Weisi , Varga Liz
Published: February 2019

Many critical infrastructure systems have network structures and are under stress. Despite their national importance, the complexity of large-scale transport networks means that we do not fully understand their vulnerabilities to cascade failures. The research conducted through this paper examines the interdependent rail networks in Greater London and surrounding commuter area. We focus on the morning commuter hours, where the system is under the most demand stress. There is increasing evidence that the topological shape of the network plays an important role in dynamic cascades. Here, we examine whether the different topological measures of resilience (stability) or robustness (failure) are more appropriate for understanding poor railway performance. The results show that resilience, not robustness, has a strong correlation with the consumer experience statistics. Our results are a way of describing the complexity of cascade dynamics on networks without the involvement of detailed agent-based models, showing that cascade effects are more responsible for poor performance than failures. The network science analysis hints at pathways towards making the network structure more resilient by reducing feedback loops.
When a male perceives a female: the effect of waxy components on the body surface on decision-making in the invasive pest weevil
Authors: Isa Mutsumi , Kumano Norikuni , Tatsuta Haruki
Published: February 2019

Insects use various semiochemicals for sexual communication and mate recognition; these can therefore be used to govern the behaviours of harmful pest species, and several candidate chemicals have been explored for this purpose. For the West Indian sweet potato weevil,
Euscepes postfasciatus
, which is one of the most serious pests of sweet potato, no effective capture techniques, such as sex pheromone lures, exist. Toward exploring promising procedures for monitoring these weevils, we assessed the effect of secretions on the body surface on the recognition of congeners and on courtship behaviour in the weevils. Our study clearly demonstrated that weevils responded to extracts from the body surface, and the behaviour adopted by the weevils varied significantly depending on the condition of the extracts. Furthermore, we found a significantly prolonged retention time for males on glass beads covered with extracts of females based on survival analysis. These findings are, as far as we are aware, the first to show the effect of lipid components of the body surface on decision-making in these economically important pest weevils.
Climbing adaptations, locomotory disparity and ecological convergence in ancient stem ‘kangaroos’
Authors: Den Boer Wendy , Campione Nicolás E. , Kear Benjamin P.
Published: February 2019

Living kangaroos, wallabies and rat-kangaroos (Macropodoidea) constitute the most ecologically diverse radiation of Australasian marsupials. Indeed, even their hallmark bipedal hopping gait has been variously modified for bounding, walking and climbing. However, the origins of this locomotory adaptability are uncertain because skeletons of the most ancient macropodoids are exceptionally rare. Some of the stratigraphically oldest fossils have been attributed to Balbaridae—a clade of potentially quadrupedal stem macropodoids that became extinct during the late Miocene. Here we undertake the first assessment of balbarid locomotion using two-dimensional geometric morphometrics and a correlative multivariate analysis of linear measurements. We selected the astragalus and pedal digit IV ungual as proxies for primary gait because these elements are preserved in the only articulated balbarid skeleton, as well as some unusual early Miocene balbarid-like remains that resemble the bones of modern tree-kangaroos. Our results show that these fossils manifest character states indicative of contrasting locomotory capabilities. Furthermore, predictive modelling reveals similarities with extant macropodoids that employ either bipedal saltation and/or climbing. We interpret this as evidence for archetypal gait versatility, which probably integrated higher-speed hopping with slower-speed quadrupedal progression and varying degrees of scansoriality as independent specializations for life in forest and woodland settings.
Bioimmobilization of lead by
Bacillus subtilis
X3 biomass isolated from lead mine soil under promotion of multiple adsorption mechanisms
Authors: Qiao Weichuan , Zhang Yunhao , Xia Hao , Luo Yang , Liu Si , Wang Shiyu , Wang Weihan
Published: February 2019

In this study, a lead-resistant bacterium,
Bacillus subtilis
X3, was used to prepare a lead bioadsorbent for immobilization and removal of lead in lead solution. The lead shot precipitate was analysed by scanning electron microscopy combined with energy dispersive X-ray fluorescence microscopy, Fourier transform infrared spectroscopy, X-ray diffraction and X-ray photoelectron spectroscopy. The adsorbed lead was mainly mineralized to form Pb
5
(PO
4
)
3
OH, Pb
10
(PO
4
)
6
(OH)
2
and Pb
5
(PO
4
)
3
Cl; however, other mechanisms that can also promote the mineralization of lead should not be ignored. For example, Na
+
and Ca
2+
on the cell wall surface were exchanged with Pb
2+
in solution, which confirmed that the ion-exchange process occurred before mineralization. Moreover, adsorption bridging caused by extracellular polymeric substances also accelerated the further aggregation of lead, and the biomass was encapsulated by lead gradually. Hydroxyl, carbonyl, carboxyl and amine groups were not observed in lead mineral crystals, but the complexation between lead and these groups still benefited the mineralization of lead. The valence of Pb(II) was not changed after mineralization, which indicated that the biosorption process was not a redox reaction. Finally, biosorption occurred on the outer surface of the cell, but its specific surface area was relatively small, limiting the amount and efficiency of biosorption.
Diving behaviour of Cuvier's beaked whales (Ziphius cavirostris) off Cape Hatteras, North Carolina
Authors: Shearer Jeanne M. , Quick Nicola J. , Cioffi William R. , Baird Robin W. , Webster Daniel L. , Foley Heather J. , Swaim Zachary T. , Waples Danielle M. , Bell Joel T. , Read Andrew J.
Published: February 2019

Cuvier's beaked whales exhibit exceptionally long and deep foraging dives. The species is little studied due to their deep-water, offshore distribution and limited time spent at the surface. We used LIMPET satellite tags to study the diving behaviour of Cuvier's beaked whales off Cape Hatteras, North Carolina from 2014 to 2016. We deployed 11 tags, recording 3242 h of behaviour data, encompassing 5926 dives. Dive types were highly bimodal; deep dives (greater than 800 m,n= 1408) had a median depth of 1456 m and median duration of 58.9 min; shallow dives (50–800 m,n= 4518) were to median depths of 280 m with a median duration of 18.7 min. Most surface intervals were very short (median 2.2 min), but all animals occasionally performed extended surface intervals. We found no diel differences in dive depth or the percentage of time spent deep diving, but whales spent significantly more time near the surface at night. Other populations of this species exhibit similar dive patterns, but with regional differences in depth, duration and inter-dive intervals. Satellite-linked tags allow for the collection of long periods of dive records, including the occurrence of anomalous behaviours, bringing new insights into the lives of these deep divers.