bluuebunny/crossref_metadata_2025 huggingface dataset:
Characteristics of Patients Experiencing Extrapyramidal Symptoms or Other Movement Disorders Related to Dopamine Receptor Blocking Agent Therapy
Authors: Musco Shaina , Ruekert Laura , Myers Jaclyn , Anderson Dennis , Welling Michael , Cunningham Elizabeth Ann
Published: June 2019

Purpose/Background

Dopamine receptor blocking agents (DRBAs), also known as antipsychotics, are medications widely used to treat a growing number of mental health diagnoses. However, their utility is limited by the potential to cause serious adverse movement reactions. Akathisia, dystonia, parkinsonism, and tardive dyskinesia (collectively known as extrapyramidal symptoms or EPSs) are associated with reduced social and occupational functioning, negative patient attitudes toward treatment, and nonadherence to pharmacotherapy. Neuroleptic malignant syndrome is a life-threatening reaction that can result from DRBA use and cause musculoskeletal dysfunction. The aim of this study is to profile patients who have developed DRBA-related movement adverse effects and identify risk factors significantly associated with each subtype of EPSs or other movement disorders (OMDs) such as neuroleptic malignant syndrome.

Methods/Procedures

A report of all potential DRBA-related EPSs or OMDs occurrences within a large community hospital network was generated using International Classification of Diseases, Ninth Revision (ICD-9) and 10th Revision (ICD-10) billing codes. Each patient encounter was manually reviewed to confirm that a documented case of DRBA-related EPSs or OMDs had indeed occurred and subsequently determine the likely causative agent(s).

Findings/Results

The resultant cohort of 148 patients experiencing unique DRBA-related EPS or OMD events was analyzed. The average patient was female, middle-aged, and overweight. The most common DRBAs precipitating EPSs or OMDs were haloperidol and quetiapine. In the population studied, age was significantly associated with the subtype of EPSs experienced such that those patients with akathisia and dystonia tended to be younger, whereas those with tardive dyskinesia tended to be older. Body mass index (BMI) category was also negatively correlated with the incidence of dystonia. In addition, it was observed that exposure to specific DRBAs, classes, and routes of administration significantly affected the risk of developing different subtypes of EPSs or OMDs in the study population.

Implications/Conclusions

To our knowledge, this is the first study to describe an association between age and BMI with the risk of akathisia and dystonia, respectively, in patients taking DRBAs. Other trends observed with age and BMI in patients developing DRBA-related EPSs support previously reported findings. Expanding the knowledge base of individual characteristics associated with the risk of developing different subtypes of EPSs or OMDs can help providers and patients anticipate and attempt to mitigate these reactions, and may ultimately improve adherence to DRBA therapy.
Efficacy and Safety of Asenapine Versus Olanzapine in Combination With Divalproex for Acute Mania
Authors: Mahajan Vivek , Arora Manu , Tandon Vishal R. , Gillani Zahid , Praharaj Samir Kumar
Published: June 2019

Background

Atypical antipsychotics are used for the treatment of acute mania, either as monotherapy or in combination with lithium or divalproex, which have a better tolerability profile as compared with typical antipsychotics. Asenapine, a newer atypical antipsychotic, has been found to be effective for the treatment of mania, with efficacy similar to olanzapine. The objective of the study was to compare the efficacy and safety of asenapine and olanzapine when used in combination with divalproex in patients with acute mania.

Methods

One hundred twenty patients aged 18 to 55 years, diagnosed with manic episode, were randomized to receive either flexible dose of sublingual asenapine (10–20 mg/d) or tablet olanzapine (10–20 mg/d), in combination with valproate 20 mg/kg per day for a period of 6 weeks. Efficacy was measured as change in Young Mania Rating Scale and Clinical Global Impression–Bipolar using intention-to-treat analysis with last observation carried forward, and safety was measured using Udvalg for Kliniske Undersøgelser scale and Modified Simpson-Angus Extrapyramidal Side Effects Scale.

Results

There was a significant reduction in Young Mania Rating Scale and Clinical Global Impression–Bipolar scores over time in both groups, with a significantly higher reduction in the olanzapine group as shown by the group × time interaction effect. Higher weight gain, increased sleep and appetite, and tremors were seen in the olanzapine-treated patients as compared with asenapine-treated patients; however, tongue hypesthesia was seen in the asenapine group only.

Conclusions

This study found that asenapine was an effective and well-tolerated atypical antipsychotic alternative to olanzapine in combination with divalproex for the short-term management of acute mania.
Modular Prosthetic Limb Control by an Individual with Congenital Upper-Limb Amputation: A Case Report
Authors: Moran Courtney , Carroll Lydia , Yu Kristin , Stentz Lauren A. , Tsao Jack W. , Pasquina Paul , Armiger Robert
Published: June 2019

Introduction

This article presents a unique case study of an individual with congenital limb loss and long-time (>56 years) body-powered prosthesis use, who was able to control a sophisticated robotic upper-limb prosthesis using surface electromyography signals and pattern recognition (PR) algorithms. This case demonstrates that individuals with congenital limb amputation are able to learn unique strategies to intuitively control a dexterous prosthetic limb.

Materials and Methods

After completing four training sessions using a virtual integration environment, a single subject participated in 12 in-laboratory clinical training sessions using the modular prosthetic limb (MPL)—a novel multiple–degree-of-freedom dexterous upper-limb prosthesis prototype. Baseline assessments were made with her body-powered prosthesis, as well as a two-site direct-control myoelectric Bebionic she had recently received. Functional assessments with the MPL were conducted during sessions 6 and 12. Outcome measures included timed box and blocks (BB) test, Assessment of Capacity for Myoelectric Control (ACMC), Jebsen-Taylor Hand Function Test (JTHFT), Trinity Amputation and Prosthesis Experience Scale, Upper Extremity Functional Scale (UEFS), and NASA Task Load Index.

Results

The subject was able to control two independent wrist degrees of freedom and up to three independent hand grasps of the MPL, using an array of surface electrodes. Improvements in the BB and ACMC were observed, although the total time to complete the JTHFT stayed relatively the same from weeks 6 to 12, using the MPL. While her enpoint perceived funcitonal ability with the MPL was 58% compared with 83% with her personal myoelectric prosthesis (12 hours of use vs 4–5 weeks of use as denoted on the UEFS); the subject reported short length of training, a long-term body-powered prosthetic user with congenital limb loss was able to demonstrate objective improvements in control of a dexterous prosthetic hand over a 12-week period of in-laboratory training, achieving intuitive independent control of a variety of simultaneous individual wrist motions and grasp patterns using PR.

Conclusions

This case demonstrates that even individuals with congenital amputation may be considered as candidates for upper-limb PR-controlled myoelectric prosthetic devices using surface electrodes.
Infant skin care: updates and recommendations
Authors: Johnson Eleanor , Hunt Raegan
Published: June 2019

Purpose of review

Neonatal skin acclimates rapidly to dry, aerobic conditions at birth and skin function gradually matures throughout infancy. Gentle skin care practices support the ongoing development and function of newborn skin. This article reviews research updates and current skin care recommendations for full-term infants, premature infants, and infants born with severe cutaneous manifestations of genetic skin disorders.

Recent findings

Although safe early bathing of full-term infants with environmental controls is possible, delaying the first newborn bath for 12–24 h of life offers benefits of increased parental bonding and breastfeeding success. Swaddled bathing every 4 days is an effective bathing strategy for premature neonates. Among infants with a family history of atopic dermatitis, regular application of bland skin moisturizers reduces their risk of developing the disease. For newborns with erosive or blistering genetic skin conditions, use of specialized wound dressings and emollients promotes wound healing and helps limit skin damage. Environmental control with humidified incubators helps prevent life-threatening hypernatremic dehydration among babies born with collodion membranes; however, affected infants can tolerate breaks outside of the humidifier to promote parent–infant bonding.

This article reviews infant skin care recommendations relevant to pediatric practice. Research to further optimize newborn skin care is ongoing, particularly, for the special populations of premature neonates and infants born with severe skin disease.
Minced Skin Grafting for Promoting Wound Healing and Improving Donor-Site Appearance after Split-Thickness Skin Grafting: A Prospective Half-Side Comparative Trial
Authors: Miyanaga Toru , Kishibe Miyuki , Yamashita Masanobu , Kaneko Takayoshi , Kinoshita Fumiya , Shimada Kenichi
Published: June 2019

Background:

Minced skin grafting is a procedure that involves mincing of the harvested skin and grafting it back onto the wounds. The authors aimed to investigate whether minced skin grafting reduces the healing time and improves the sequential postoperative appearance of donor sites.

Methods:

A single-center, two-treatment, half-side comparative study was performed. The split-thickness skin remaining after grafting was minced until pasty. The small pasty graft mass was uniformly spread on half of the entire donor site. Minced skin grafting was not performed on the other side. The data from 30 patients were used for analysis.

Results:

The average time to complete healing of the donor sites in the minced skin grafting and control groups was 9.4 ± 2.5 and 12.4 ± 3.6 days, respectively. The difference in the healing time between the two groups was statistically significant (p < 0.001). Three blinded surgeons used a scale to grade photographs according to the degree of conspicuous donor sites in comparison with the normal skin around the donor sites. All observers reported that the differences in donor-site appearance between the minced skin grafting and control groups were statistically significant at postoperative months 1 and 2, and two observers reported that the differences in donor-site appearance were significant at months 4, 6, and 12. The differences in the number of patients with donor-site dyspigmentation between the minced skin grafting and control groups at 12 months were statistically significant (p < 0.05).

Conclusion:

This prospective half-side comparative trial demonstrates that minced skin grafting promotes wound healing and improves donor-site appearance after split-thickness skin grafting.

CLINICAL QUESTION/LEVEL OF EVIDENCE:

Therapeutic, II.
Prediction of Number of Casts and Need of Tenotomy Using Pirani Score in the Management of Clubfoot
Authors: Ayehualem Sileshi , Asmare Yared , Abrha Mueez , Muche Abebe
Published: June 2019

Background:

Clubfoot also called as congenital tailpipes equinovarus is a complex ankle and foot deformity characterized by forefoot adduction and supination, midfoot cavus and hindfoot varus and equinus. It is estimated that more than 100,000 babies are born each year worldwide with clubfoot, and 80% are seen in developing nations. Different scoring systems are used for grading the severity of deformity or monitoring the natural history of clubfoot. The Pirani scoring system is now routinely used in most clubfoot clinics, including Cure Ethiopia, Children's Hospital.

Methods:

A facility based retrospective study was conducted on 278 idiopathic club feet successfully treated by the Ponseti method and scored by Pirani system between September 2013/14 to September 2017/2018. Age at presentation, number of casts required, need for percutaneous Achilles tenotomy, casting effects were recorded.

Results:

A total of 287 clinical folders of children were retrieved (424 feet). The mean (±SD) number of casts required for correction of the deformity was 5.54 ± 1.63. The number of cast required for correction is significantly, and positively correlated with initial severity of Pirani score (r = 0.62 for right foot; r = 0.675 for left foot). There is a significant difference on the overall initial Pirani score between tenotomy and non- tenotomy group (P value < 0.001).

Conclusion:

The study revealed that severity of initial Pirani score can be used to estimate the number of Ponseti cast required for correction of clubfoot deformity and the need for tenotomy. Besides, the number of Ponseti cast required may not be affected by age of a child at the commencement of treatment.
Transcranioplasty Ultrasound Through a Sonolucent Cranial Implant Made of Polymethyl Methacrylate: Phantom Study Comparing Ultrasound, Computed Tomography, and Magnetic Resonance Imaging
Authors: Belzberg Micah , Shalom Netanel Ben , Lu Angela , Yuhanna Edward , Manbachi Amir , Tekes Aylin , Huang Judy , Brem Henry , Gordon Chad
Published: June 2019

Background:

Current methods of transcranial diagnostic ultrasound imaging are limited by the skull's acoustic properties. Craniotomy, craniectomy, and cranioplasty procedures present opportunities to circumvent these limitations by substituting autologous bone with synthetic cranial implants composed of sonolucent biomaterials.

Objective:

This study examined the potential to image the brain using transcranioplasty ultrasound (TCU) through a sonolucent cranial implant.

Materials and Methods:

A validated adult brain phantom was imaged using computed tomography (CT), magnetic resonance imaging (MRI), and ultrasound without an implant. Next, for experimental comparison, TCU was performed through a sonolucent implant composed of clear polymethyl methacrylate.

Results:

All imaging modalities successfully revealed elements of the brain phantom, including the bilateral ventricular system, the falx cerebri, and a deep hyperdense mass representing a brain tumor or hematoma. In addition, ultrasound images were captured which closely resembled axial images obtained with both CT and MRI.

Conclusion:

The results obtained in this first-ever, preclinical, phantom study suggest TCU is now a viable immediate and long-term diagnostic imaging modality deserving of further clinical investigation.
The Utility of Endoscope-Assisted Rigid Bronchoscopy in Pediatric Airway Foreign Body Removals
Authors: Ozdemir Suleyman , Surmelioglu Ozgur , Tarkan Ozgur , Tuncer Ulku , Kiroglu Mete , Dagkiran Muhammed
Published: June 2019

Introduction:

Aspiration of foreign bodies is an emergency condition in children and may result in death, especially in children under 3 years of age. Therefore, diagnosis and treatment must be made rapidly.

Objective:

This study sought to summarize our experience with endoscope-assisted rigid bronchoscopy (RB) in the diagnosis and treatment of pediatric tracheobronchial foreign body emergencies to reduce complications and mortality.

Methods:

This was a retrospective cross-sectional study. The medical records of 337 children diagnosed with clinically suspected airway foreign body aspiration in the pediatric emergency department were analyzed retrospectively. The patients were divided into 2 groups with endoscopy used during RB in group 1 whereas group 2 was RB only. The surgeons who performed the bronchoscopies completed a survey on the advantages/disadvantages of these 2 procedures.

Results:

All of the patients had a positive history of suspected foreign body aspiration and foreign bodies were identified in 77.1% of the patients during RB. There were 161 (47.8%) patients in group 1 and 176 (52.2%) patients in group 2. In group 2, 5 patients showed transient hypoxia, and 6 patients had an episode of transient bleeding during the operations. These numbers were 3 and 3, respectively, in group 1. One patient in group 2 suffered cardiac arrest and died during surgery. The authors did not see any long-term complications after these operations and the authors did not find any statistically significant differences between the groups for complication rates.

Conclusion:

The RB is the gold standard procedure for removal of pediatric airway foreign bodies. The survey used in this study and our extensive experience have shown that the distal bronchi and foreign bodies can be visualized more effectively when using a rigid endoscope during RB, especially in children under the age of 3 years. In order to improve the safety of the surgical procedure, the authors propose that endoscope-assisted RB should be used in emergencies concerning foreign bodies in the airways of children.
Role of Autologous Fat Injection in Neglected Patients With Anterior Plagiocephaly
Authors: Kalantar-Hormozi Abdoljalil , Abbaszadeh-Kasbi Ali , Kalantar-Hormozi Hadis , Hosseinizadegan Fatemeh , Davai Nazanin Rita
Published: June 2019

Anterior plagiocephaly is a type of non-syndromic craniosynostosis requiring surgery. In this study, the authors have presented 15 neglected patients with anterior plagiocephaly. Two of patients had moderate plagiocephaly whereas others had mild plagiocephaly. A total of 38 procedures (fat injections) were performed on these patients. Following procedures, 2 of patients were under corrected, 2 of who were over corrected, and others were adequate corrected. One of the patients developed fat necrosis. None of them showed persistent over correction. Authors believe that autologous fat transplantation is a safe and effective method, in patients with anterior plagiocephaly who have not been operated, to improve patients’ appearance and, subsequently, their self-esteem as well as their social function.
A National Comparison of Operative Outcomes of New and Experienced Surgeons
Authors: Kelz Rachel R. , Sellers Morgan M. , Niknam Bijan A. , Sharpe James E. , Rosenbaum Paul R. , Hill Alexander S. , Zhou Hong , Hochman Lauren L. , Bilimoria Karl Y. , Itani Kamal , Romano Patrick S. , Silber Jeffrey H.
Published: June 2019

Objective:

To determine whether outcomes achieved by new surgeons are attributable to inexperience or to differences in the context in which care is delivered and patient complexity.

Background:

Although prior studies suggest that new surgeon outcomes are worse than those of experienced surgeons, factors that underlie these phenomena are poorly understood.

Methods:

A nationwide observational tapered matching study of outcomes of Medicare patients treated by new and experienced surgeons in 1221 US hospitals (2009–2013). The primary outcome studied is 30-day mortality. Secondary outcomes were examined.

Results:

In total, 694,165 patients treated by 8503 experienced surgeons were matched to 68,036 patients treated by 2119 new surgeons working in the same hospitals. New surgeons’ patients were older (25.8% aged ≥85 vs 16.3%,P<0.0001) with more emergency admissions (53.9% vs 25.8%,P<0.0001) than experienced surgeons’ patients. Patients of new surgeons had a significantly higher baseline 30-day mortality rate compared with patients of experienced surgeons (6.2% vs 4.5%,P<0.0001;OR 1.42 (1.33, 1.52)). The difference remained significant after matching the types of operations performed (6.2% vs 5.1%, P<0.0001; OR 1.24 (1.16, 1.32)) and after further matching on a combination of operation type and emergency admission status (6.2% vs 5.6%, P=0.0007; OR 1.12 (1.05, 1.19)). After matching on operation type, emergency admission status, and patient complexity, the difference between new and experienced surgeons’ patients’ 30-day mortality became indistinguishable (6.2% vs 5.9%,P=0.2391;OR 1.06 (0.97, 1.16)).

Conclusions:

Among Medicare beneficiaries, the majority of the differences in outcomes between new and experienced surgeons are related to the context in which care is delivered and patient complexity rather than new surgeon inexperience.
Sciatic and Femoral Nerve Resection During Extended Radical Surgery for Advanced Pelvic Tumours
Authors: Brown Kilian G. M. , Solomon Michael J. , Lau Yee Chen , Steffens Daniel , Austin Kirk K. S. , Lee Peter J.
Published: June 2019

Objective:

To report survival, functional, and quality-of-life (QoL) outcomes after extended radical resection for advanced pelvic tumors with en bloc sciatic or femoral nerve resection.

Background:

Advanced pelvic tumors involving the sciatic or femoral nerve have traditionally been considered inoperable. Small studies have suggested acceptable functional outcomes can be achieved after pelvic exenteration with en bloc sciatic nerve resection.

Method:

Consecutive patients who underwent extended radical pelvic surgery with en bloc resection of the sciatic or femoral nerves at a single center were included.

Results:

Of 713 radical pelvic resections, 68 patients (9.5%) had en bloc sciatic or femoral nerve resection. Complete sciatic, partial sciatic, and complete femoral nerve resection was performed in 26 (38%), 38 (56%), and 4 patients (6%), respectively. Overall and major postoperative complication rates were 63% and 40%, respectively. R0 resection was achieved in 65% of patients, which translated to 55% and 76% overall and local recurrence-free 5-year survival in those with colorectal cancer. Twenty-two (96%) and 25 (92%) patients could mobilize independently after complete and partial sciatic nerve resection, respectively. Physical QoL was significantly lower at 6 months after surgery compared with baseline (P = 0.041), but returned to baseline at 12 months (P = 0.163). There was no difference in mental or overall QoL at 6 or 12 months compared with baseline.

Conclusion:

En bloc sciatic and femoral nerve resection can be performed during extended radical pelvic resections with morbidity and survival outcomes comparable with existing exenteration literature, including in patients with recurrent rectal cancer. Physical QoL may be impaired after surgery, but returns to baseline by 12 months.
Accuracy of Detecting Residual Disease After Neoadjuvant Chemoradiotherapy for Esophageal Cancer
Authors: Eyck Ben M. , Onstenk Barbera D. , Noordman Bo J. , Nieboer Daan , Spaander Manon C. W. , Valkema Roelf , Lagarde Sjoerd M. , Wijnhoven Bas P. L. , van Lanschot J. Jan B.
Published: June 2019

Objective:

The aim of this study was to perform a meta-analysis on the accuracy of endoscopic biopsies, EUS, and 18F-FDG PET(-CT) for detecting residual disease after neoadjuvant chemoradiotherapy (nCRT) for esophageal cancer.

Summary of Background Data:

After nCRT, one-third of patients have a pathologically complete response in the resection specimen. Before an active surveillance strategy could be offered to these patients, clinically complete responders should be accurately identified.

Methods:

Embase, Medline, Cochrane, and Web-of-Science were searched until February 2018 for studies on accuracy of endoscopic biopsies, EUS, or PET(-CT) for detecting locoregional residual disease after nCRT for squamous cell- or adenocarcinoma. Pooled sensitivities and specificities were calculated using random-effect meta-analyses.

Results:

Forty-four studies were included for meta-analyses. For detecting residual disease at the primary tumor site, 12 studies evaluated endoscopic biopsies, 11 qualitative EUS, 14 qualitative PET, 8 quantitative PET using maximum standardized uptake value (SUVmax), and 7 quantitative PET using percentage reduction of SUVmax (%ΔSUVmax). Pooled sensitivities and specificities were 33% and 95% for endoscopic biopsies, 96% and 8% for qualitative EUS, 74% and 52% for qualitative PET, 69% and 72% for PET-SUVmax, and 73% and 63% for PET-%ΔSUVmax. For detecting residual nodal disease, 11 studies evaluated qualitative EUS with a pooled sensitivity and specificity of 68% and 57%, respectively. In subgroup analyses, sensitivity of PET-%ΔSUVmax and EUS for nodal disease was higher in squamous cell carcinoma than adenocarcinoma.

Conclusions:

Current literature suggests insufficient accuracy of endoscopic biopsies, EUS, and 18F-FDG PET(-CT) as single modalities for detecting residual disease after nCRT for esophageal cancer.
Survival Following Liver Transplantation for Patients With Nonresectable Liver-only Colorectal Metastases
Authors: Dueland Svein , Syversveen Trygve , Solheim Jon Magnus , Solberg Steinar , Grut Harald , Bjørnbeth Bjørn Atle , Hagness Morten , Line Pål-Dag
Published: June 2019

Objective:

To determine overall survival and disease-free survival in selected patients with nonresectable liver-only colorectal cancer receiving liver transplantation.

Background:

Patients with nonresectable colorectal cancer receiving palliative chemotherapy has a 5-year overall survival of about 10%. Liver transplantation provided an overall survival of 60% in a previous study (SECA-I). Risk factors for death were carcinoembryonic antigen (CEA) >80 μg/L, progressive disease on chemotherapy, size of largest lesion>5.5 cm, and less than 2 years from resection of the primary tumor to transplantation.

Methods:

In this prospective (SECA-II) study, we included colorectal cancer patients with nonresectable liver-only metastases determined by computed tomography (CT)/magnetic resonance imaging/positron emission tomography scans and at least 10% response to chemotherapy. Time from diagnosis to liver transplant was required to be more than 1 year.

Results:

At a median follow-up of 36 months, Kaplan-Meier overall survival at 1, 3, and 5 years were 100%, 83%, and 83%, respectively. Disease-free survival at 1, 2, and 3 years were 53%, 44%, and 35%, respectively. Overall survival from time of relapse at 1, 2, and 4 years were 100%, 73%, and 73%, respectively. Recurrence was mainly slow growing pulmonary metastases amenable to curative resection. Fong Clinical Risk Score of 1 to 2 at the time of diagnosis resulted in longer disease-free survival than score 3 to 4 (P = 0.044). Patients included in the present study had significantly better prognostic factors than the previous SECA-I study.

Conclusion:

Liver transplantation provides the longest overall survival reported in colorectal cancer patient with nonresectable liver metastases. Improved selection criteria give patients with nonresectable colorectal liver metastases a 5-year overall survival comparable to other indications for liver transplantation.
Preoperative Ultrasound Assessment of Regional Lymph Nodes in Melanoma Patients Does not Provide Reliable Nodal Staging
Authors: Thompson John F. , Haydu Lauren E. , Uren Roger F. , Andtbacka Robert H. , Zager Jonathan S. , Beitsch Peter D. , Agnese Doreen M. , Mozzillo Nicola , Testori Alessandro , Bowles Tawnya L. , Hoekstra Harald J. , Kelley Mark C. , Sussman Jeffrey , Schneebaum Schlomo , Smithers B. Mark , McKinnon Gregory , Hsueh Eddy , Jacobs Lisa , Schultz Erwin , Reintgen Douglas , Kane John M. , Friedman Erica B. , Wang Hejing , Van Kreuningen Lisa , Schiller Vicki , Elashoff David A. , Elashoff Robert , Cochran Alistair J. , Stern Stacey , Faries Mark B.
Published: June 2019

Objective:

To assess whether preoperative ultrasound (US) assessment of regional lymph nodes in patients who present with primary cutaneous melanoma provides accurate staging.

Background:

It has been suggested that preoperative US could avoid the need for sentinel node (SN) biopsy, but in most single-institution reports, the sensitivity of preoperative US has been low.

Methods:

Preoperative US data and SNB results were analyzed for patients enrolled at 20 centers participating in the screening phase of the second Multicenter Selective Lymphadenectomy Trial. Excised SNs were histopathologically assessed and considered positive if any melanoma was seen.

Results:

SNs were identified and removed from 2859 patients who had preoperative US evaluation. Among those patients, 548 had SN metastases. US was positive (abnormal) in 87 patients (3.0%). Among SN-positive patients, 39 (7.1%) had an abnormal US. When analyzed by lymph node basin, 3302 basins were evaluated, and 38 were true positive (1.2%). By basin, the sensitivity of US was 6.6% (95% confidence interval: 4.6–8.7) and the specificity 98.0% (95% CI: 97.5–98.5). Median cross-sectional area of all SN metastases was 0.13 mm2; in US true-positive nodes, it was 6.8 mm2. US sensitivity increased with increasing Breslow thickness of the primary melanoma (0% for ≤1 mm thickness, 11.9% for >4 mm thickness). US sensitivity was not significantly greater with higher trial center volume or with pre-US lymphoscintigraphy.

Conclusion:

In the MSLT-II screening phase population, SN tumor volume was usually too small to be reliably detected by US. For accurate nodal staging to guide the management of melanoma patients, US is not an effective substitute for SN biopsy.
Resolvin D1 Attenuates the Organ Injury Associated With Experimental Hemorrhagic Shock
Authors: Sordi Regina , Chiazza Fausto , Collotta Debora , Migliaretti Giuseppe , Colas Romain A. , Vulliamy Paul , Brohi Karim , Dalli Jesmond , Collino Massimo , Thiemermann Christoph
Published: June 2019

Objective:

To evaluate the potential changes in the plasma levels of resolvin D1 (RvD1) in patients with trauma and hemorrhage. Having found that trauma results in a profound reduction in plasma RvD1 in patients, we have then investigated the effects of RvD1 on the organ injury and dysfunction associated with hemorrhagic shock (HS) in the rat.

Background:

HS is a common cause of death in trauma due to excessive systemic inflammation and multiple organ failure. RvD1 is a member of the resolvin family of pro-resolution mediators.

Methods:

Blood samples were drawn from critically injured patients (n = 27, ACITII-prospective observational cohort study) within 2 hours of injury for targeted liquid chromatography tandem mass spectrometry. HS rats (removal of blood to reduce arterial pressure to 30 ± 2 mm Hg, 90 minutes, followed by resuscitation) were treated with RvD1 (0.3 or 1 μg/kg intravenous (i.v.)) or vehicle (n = 7). Parameters of organ injury and dysfunction were determined.

Results:

Plasma levels of RvD1 (mg/dL) were reduced in patients with trauma+HS (0.17 ± 0.08) when compared with healthy volunteers (0.76 ± 0.25) and trauma patients (0.62 ± 0.20). In rats with HS, RvD1 attenuated the kidney dysfunction, liver injury, and tissue ischemia. RvD1 also reduced activation of the nuclear factor (NF)-κB pathway and reduced the expression of pro-inflammatory proteins such as inducible nitric oxide synthase, tumor necrosis factor-α, interleukin-1β, and interleukin-6.

Conclusion:

Plasma RvD1 is reduced in patients with trauma-HS. In rats with HS, administration of synthetic RvD1 on resuscitation attenuated the multiple organ failure associated with HS by a mechanism that involves inhibition of the activation of NF-κB.
GBA1-associated parkinsonism: new insights and therapeutic opportunities
Authors: Ryan Emory , Seehra Gurpreet , Sharma Pankaj , Sidransky Ellen
Published: June 2019

Purpose of review

GBA1 mutations, which result in the lysosomal disorder Gaucher disease, are the most common known genetic risk factor for Parkinson disease and Dementia with Lewy Bodies (DLB). The pathogenesis of this association is not fully understood, but further elucidation of this link could lead to new therapeutic options.

Recent findings

The characteristic clinical phenotype of GBA1-PD resembles sporadic Parkinson disease, but with an earlier onset and more severe course. Many different GBA1 mutations increase the risk of Parkinson disease, some primarily detected in specific populations. Glucocerebrosidase deficiency appears to be associated with increased α-synuclein aggregation and accumulation, mitochondrial dysfunction because of impaired autophagy, and increased endoplasmic reticulum stress.

As our understanding of GBA1-associated Parkinson disease increases, new treatment opportunities emerge. MicroRNA profiles are providing examples of both up-regulated and down-regulated proteins related to GBA1 and may provide new therapeutic targets. Chaperone therapy, directed at either misfolded glucocerebrosidase or α-synuclein aggregation, is currently under development and there are several early clinical trials ongoing. Substrate reduction therapy, aimed at lowering the accumulation of metabolic by-products, especially glucosylsphingosine, is also being explored. Basic science insights from the rare disorder Gaucher disease are serving to catapult drug discovery for parkinsonism.
Improved forecasts of influenza-associated hospitalization rates with Google Search Trends
Authors: Kandula Sasikiran , Pei Sen , Shaman Jeffrey
Published: June 2019

Reliable forecasts of influenza-associated hospitalizations during seasonal outbreaks can help health systems better prepare for patient surges. Within the USA, public health surveillance systems collect and distribute near real-time weekly hospitalization rates, a key observational metric that makes real-time forecast of this outcome possible. In this paper, we describe a method to forecast hospitalization rates using a population level transmission model in combination with a data assimilation technique. Using this method, we generated retrospective forecasts of hospitalization rates for five age groups and the overall population during five seasons in the USA and quantified forecast accuracy for both near-term and seasonal targets. Additionally, we describe methods to correct for under-reporting of hospitalization rates (backcast) and to estimate hospitalization rates from publicly available online search trends data (nowcast). Forecasts based on surveillance rates alone were reasonably accurate in predicting peak hospitalization rates (within ± 25% of the actual peak rate, three weeks before peak). The error in predicting rates one to four weeks ahead, remained constant for the duration of the seasons, even during periods of increased influenza incidence. An improvement in forecast quality across all age groups, seasons and targets was observed when backcasts and nowcasts supplemented surveillance data. These results suggest that the model-inference framework can provide reasonably accurate real-time forecasts of influenza hospitalizations; backcasts and nowcasts offer a way to improve system tolerance to observational errors.
Brian Cox and the new enlightenment
Authors: Skouen Tina
Published: June 2019

This paper studies the Royal Society's public rhetoric of science by analysing Brian Cox, whose rise to science prominence corresponded with his period as a Royal Society University Research Fellow from 2005 to 2013. The first study, to my knowledge, to address this major figure in popular science, the paper analyses his goals and methods in light of the ‘new Enlightenment’ that was advocated by the Society's then President, Paul Nurse, in 2012. Like the founders of this national science academy in the 1660s, Nurse hailed Francis Bacon as a lodestar when it comes to inspiring awe and respect of rationality and of what science can do both in Britain and globally. Appointed as the Society's first Professor for Public Engagement in Science in 2015, Cox has worked to achieve the Society's goals of creating enthusiasm and ‘demonstrating the value of science to everyone’. He has also been instrumental in recruiting more young people to pursue a career in science. Through rhetorical analysis of a lecture video and other online material, the paper identifies some key features in his style of performance, especially regarding his methods of producing awe and wonder.
A compactness measure of sustainable building forms
Authors: D’Amico Bernardino , Pomponi Francesco
Published: June 2019

Global population growth and urbanization necessitate countless more buildings in this century, causing an unprecedented increase in energy consumption, greenhouse gas emissions, waste generation and resource use. It is imperative to achieve maximal efficiency in buildings quickly. The building envelope is a key element to address environmental concerns, as it is responsible for thermal transfers to the outdoors, causing energy demand and carbon emissions. It also requires cladding, thus consuming a significant amount of finite resources. This paper investigates the relationship between surface area and indoor space to unravel the sustainability of building forms. Firstly, we demonstrate what the optimal form is. Secondly, as a single definite form is of little use in practice, we develop a scale-independent metric to measure the degree of optimality of building forms and show its practical use. This newly developed metric can significantly help in early design stages, by quantifying how much a building form deviates from optimality and identifying the domain of alternative geometries to bring us closer to it. This compactness measure also represents a theoretical basis for further research, to explore how optimality changes when additional parameters are factored in. It therefore contributes to both theory and practice to support global efforts towards sustainable built environments.
Aggression and discrimination among closely versus distantly related species of
Drosophila
Authors: Gupta Tarun , Howe Sarah E. , Zorman Marlo L. , Lockwood Brent L.
Published: June 2019

Fighting between different species is widespread in the animal kingdom, yet this phenomenon has been relatively understudied in the field of aggression research. Particularly lacking are studies that test the effect of genetic distance, or relatedness, on aggressive behaviour between species. Here we characterized male–male aggression within and between species of fruit flies across the
Drosophila
phylogeny. We show that male
Drosophila
discriminate between conspecifics and heterospecifics and show a bias for the target of aggression that depends on the genetic relatedness of opponent males. Specifically, males of closely related species treated conspecifics and heterospecifics equally, whereas males of distantly related species were overwhelmingly aggressive towards conspecifics. To our knowledge, this is the first study to quantify aggression between
Drosophila
species and to establish a behavioural bias for aggression against conspecifics versus heterospecifics. Our results suggest that future study of heterospecific aggression behaviour in
Drosophila
is warranted to investigate the degree to which these trends in aggression among species extend to broader behavioural, ecological and evolutionary contexts.
Functional characterization of three flavonoid glycosyltransferases from
Andrographis paniculata
Authors: Li Yuan , Li Xin-Lin , Lai Chang-Jiang-Sheng , Wang Rui-Shan , Kang Li-Ping , Ma Ting , Zhao Zhen-Hua , Gao Wei , Huang Lu-Qi
Published: June 2019

Andrographis paniculata
is an important traditional medicinal herb in South and Southeast Asian countries with diverse pharmacological activities that contains various flavonoids and flavonoid glycosides. Glycosylation can transform aglycones into more stable, biologically active and structurally diverse glycosides. Here, we report three glycosyltransferases from the leaves of
A. paniculata
(ApUFGTs) that presented wide substrate spectra for flavonoid glycosylation and exhibited multi-site glycosylation on the substrate molecules. They acted on the 7-OH position of the A ring and were able to glycosylate several other different types of compounds. The biochemical properties and phylogenetic analysis of these glycosyltransferases were also investigated. This study provides a basis for further research on the cloning of genes involved in glycosylation from
A. paniculata
and offers opportunities for enhancing flavonoid glycoside production in heterologous hosts. These enzymes are expected to become effective tools for drug discovery and for the biosynthesis of derivatives via flavonoid glycosylation.
Do restrained eaters show increased BMI, food craving and disinhibited eating? A comparison of the Restraint Scale and the Restrained Eating scale of the Dutch Eating Behaviour Questionnaire
Authors: Adams Rachel C. , Chambers Christopher D. , Lawrence Natalia S.
Published: June 2019

Despite being used interchangeably, different measures of restrained eating have been associated with different dietary behaviours. These differences have impeded replicability across the restraint literature and have made it difficult for researchers to interpret results and use the most appropriate measure for their research. Across a total sample of 1731 participants, this study compared the Restraint Scale (RS), and its subscales, to the Dutch Eating Behaviour Questionnaire (DEBQ) across several traits related to overeating. The aim was to explore potential differences between these two questionnaires so that we could help to identify the most suitable measure as a prescreening tool for eating-related interventions. Results revealed that although the two measures are highly correlated with one another (
r
s
=
0.73–0.79), the RS was more strongly associated with external (
r
s = −0.07 to 0.11 versus −0.18 to −0.01) and disinhibited eating (
r
s
=
0.46 versus 0.31), food craving (
r
s
=
0.12–0.27 versus 0.02–0.13 and 0.22 versus −0.06) and body mass index (
r
s
=
0.25–0.34 versus −0.13 to 0.15). The results suggest that, compared to the DEBQ, the RS is a more appropriate measure for identifying individuals who struggle the most to control their food intake.
Reduced diversity and stability of coral-associated bacterial communities and suppressed immune function precedes disease onset in corals
Authors: Pollock F. Joseph , Lamb Joleah B. , van de Water Jeroen A. J. M. , Smith Hillary A. , Schaffelke Britta , Willis Bette L. , Bourne David G.
Published: June 2019

Disease is an emerging threat to coral reef ecosystems worldwide, highlighting the need to understand how environmental conditions interact with coral immune function and associated microbial communities to affect holobiont health. Increased coral disease incidence on reefs adjacent to permanently moored platforms on Australia's Great Barrier Reef provided a unique case study to investigate environment–host–microbe interactions
in situ
. Here, we evaluate coral-associated bacterial community (16S rRNA amplicon sequencing), immune function (protein-based prophenoloxidase-activating system), and water quality parameters before, during and after a disease event. Over the course of the study, 31% of tagged colonies adjacent to platforms developed signs of white syndrome (WS), while all control colonies on a platform-free reef remained visually healthy. Corals adjacent to platforms experienced significant reductions in coral immune function. Additionally, the corals at platform sites that remained visually healthy throughout the study had reduced bacterial diversity compared to healthy colonies at the platform-free site. Interestingly, prior to the observation of macroscopic disease, corals that would develop WS had reduced bacterial diversity and significantly greater community heterogeneity between colonies compared to healthy corals at the same location. These results suggest that activities associated with offshore marine infrastructure impacts coral immunocompetence and associated bacterial community, which affects the susceptibility of corals to disease.
Contrasting characteristic behaviours among common laboratory mouse strains
Authors: Sultana Razia , Ogundele Olalekan M. , Lee Charles C.
Published: June 2019

Mice are widely used to model wide-ranging human neurological disorders, from development to degenerative pathophysiology. Behavioural and molecular characteristics of these mouse models are influenced by the genetic background of each strain. Among the most commonly used strains, the inbred C57BL/6J, BALB/c, CBA and 129SvEv lines and the CD1 outbred line are particularly predominant. Despite their prevalence, comparative performance of these strains on many standard behavioural tests commonly used to assess neurological conditions remains diffusely and indirectly accessible in the literature. Given that independent studies may be conducted with mice of differing genetic backgrounds, any variation in characteristic behavioural responses of specific strains should be delineated in order to properly interpret results among studies. Thus, in the present study, we aimed to characterize these commonly used mice strains through several standard behavioural tests. Here, we found that animals from different genetic background strains exhibited varying behavioural patterns when assessed for sociability/novelty, memory function, and negative behaviours like despair and stress calls. These results suggest that genetic variation among strains may be responsible—in part—for strain-specific behavioural phenotypes and potential predisposition to some neurological disorders.
Trophic structure modulates community rescue following acidification
Authors: Bell Graham , Fugère Vincent , Barrett Rowan , Beisner Beatrix , Cristescu Melania , Fussmann Gregor , Shapiro Jesse , Gonzalez Andrew
Published: June 2019

Community rescue occurs when a community that experiences lethal stress persists only through the spread of rare types, either genotypes or species, resistant to the stress. Rescue interacts with trophic structure because physical stress experienced by a focal assemblage within the community may also be experienced by its predators and prey. In general, trophic structure will facilitate rescue only when a stress has a less severe effect on a focal assemblage than on its predators. In other circumstances, when stress affects prey or has only a weak effect on predators, trophic structure is likely to hamper rescue. We exposed a community of phytoplankton and zooplankton derived from a natural lake to acidification in outdoor mesocosms large enough to support trophically complex communities. Rescue of the phytoplankton from severe acidification was facilitated by prior exposure to sublethal stress, confirming previous results from microcosm experiments. Even communities that have previously been less highly stressed were eventually rescued, however, because their zooplankton predators were more sensitive to acidification and became extinct. Our experiment shows how community rescue following severe stress is modulated by the differential effect of the stress relative to trophic level.
Long-term experimental evolution reveals purifying selection on piRNA-mediated control of transposable element expression
Authors: Bergthorsson Ulfar , Sheeba Caroline J. , Konrad Anke , Belicard Tony , Beltran Toni , Katju Vaishali , Sarkies Peter
Published: June 2019

Transposable elements (TEs) are an almost universal constituent of eukaryotic genomes. In animals, Piwi-interacting small RNAs (piRNAs) and repressive chromatin often play crucial roles in preventing TE transcription and thus restricting TE activity. Nevertheless, TE content varies widely across eukaryotes and the dynamics of TE activity and TE silencing across evolutionary time is poorly understood. Here we used experimentally evolved populations ofC. elegansto study the dynamics of TE expression over 400 generations. The experimental populations were evolved at three different population sizes to manipulate the efficiency of natural selection versus genetic drift. We demonstrate increased TE expression relative to the ancestral population, with the largest increases occurring in the smallest populations. We show that the transcriptional activation of TEs within active regions of the genome is associated with failure of piRNA-mediated silencing, whilst desilenced TEs in repressed chromatin domains retain small RNAs. Additionally, we find that the sequence context of the surrounding region influences the propensity of TEs to lose silencing through failure of small RNA-mediated silencing. Together, our results show that natural selection inC. elegansis responsible for maintaining low levels of TE expression, and provide new insights into the epigenomic features responsible.