bluuebunny/crossref_metadata_2025 huggingface dataset:
Increasing the impact of randomized controlled trials: an example of a hybrid effectiveness–implementation design in psychotherapy research
Authors: Johnson Adrienne L , Ecker Anthony H , Fletcher Terri L , Hundt Natalie , Kauth Michael R , Martin Lindsey A , Curran Geoffrey M , Cully Jeffrey A
Published: November 2018

Randomized controlled trials (RCTs) are the gold standard for clinical research. However, significant delays between completion of RCTs and adoption of evidence-based practices into clinical settings remain. Engagement of stakeholders and implementation-focused outcomes to augment traditional RCTs hold the potential to increase the impact of RCT outcomes for clinical practice and more rapidly lead to the adoption of evidence-based practices in clinical settings. The purpose of this study is to discuss hybrid effectiveness–implementation designs and use a project example to highlight important methodological considerations to enhance the impact of RCTs. A hybrid effectiveness–implementation study assessed the effectiveness and implementation potential of brief cognitive behavioral therapy (bCBT) for rural Veterans. A patient-randomized trial (bCBT vs. enhanced usual care) explored the impact on depression symptoms. Implementation elements included engagement of stakeholders and a multifaceted provider training and support program to increase bCBT use by providers in Veterans Health Administration (VA) community-based outpatient clinics. Implementation outcomes included the number of providers who adopted bCBT, provider fidelity, and delivery outcomes (e.g., use of measurement-based care, treatment engagement, and completion). Hybrid designs offer opportunities to improve the alignment between research and practice, potentially improving dissemination of evidence-based interventions and reducing known delays in the translation from research to practice. Expansion of traditional RCTs through collaborative stakeholder contributions and stakeholder/consumer-informed implementation approaches is critical to improve adoption postproject. Although hybrid designs offer significant benefits related to generalizability and adoption, these approaches involve complex procedures and processes and often come at the cost of reduced internal study controls.
Activity of Demethylation Inhibitor Fungicide Metconazole on Chinese Fusarium graminearum Species Complex and Its Application in Carbendazim-Resistance Management of Fusarium Head Blight in Wheat
Authors: Duan Yabing , Tao Xian , Zhao Huahua , Xiao Xuemei , Li Meixia , Wang Jianxin , Zhou Mingguo
Published: November 2018

Fusarium graminearum species complex (FGSC), causing Fusarium head blight (FHB) of wheat, has species-specific geographical distributions in wheat-growing regions. In recent years, benzimidazole resistance of FHB pathogens has been largely widespread in China. Although the demethylation inhibitor fungicide metconazole has been used for FHB control in some countries, no information about metconazole sensitivity of Chinese FHB pathogen populations and efficacy of metconazole in FHB control in China is available. In this study, the sensitivity of FGSC to metconazole was measured with 32 carbendazim-sensitive strains and 35 carbendazim-resistant strains based on mycelial growth. The 50% effective concentration values of 67 strains were normally distributed and ranged from 0.0209 to 0.0838 μg ml−1, with a mean of 0.0481 ± 0.0134 μg ml−1. No significant difference in metconazole sensitivity was observed between carbendazim-sensitive and -resistant populations. An interactive effect of metconazole and phenamacril, a novel cyanoacrilate fungicide approved in China against Fusarium spp., in inhibiting mycelial growth showed an additive interaction at different ratios. Furthermore, field trials to evaluate the effect of metconazole and metconazole + phenamacril treatments in FHB control, deoxynivalenol (DON) production, and grain yields were performed. Compared with the fungicides carbendazim and phenamacril currently used in China, metconazole exhibits a better efficacy for FHB control, DON production, and grain yields, and dramatically reduces use dosages of chemical compounds in the field. The mixture of metconazole and phenamacril at ratios of 2:3 and 1:2 showed the greatest efficacy for FHB control, DON production, and grain yields among all the fungicide treatments but its use dosages were higher in comparison with metconazole alone. In addition, FHB control, grain yields, and DON levels were significantly correlated with each other, showing that visual disease indices can be used as an indicator of grain yields and DON contamination. Meanwhile, the frequency of carbendazim-resistant alleles in F. graminearum populations was dramatically reduced after metconazole and phenamacril alone and the mixture of metconazole and phenamacril applications, indicating that metconazole and a mixture of metconazole and phenamacril can be used for carbendazim resistance management of FHB in wheat. Overall, the findings of this study provide important data for resistance management of FHB and reducing DON contamination in wheat grains.
Determining Whether Geographic Origin and Potato Genotypes Shape the Population Structure of Phytophthora infestans in the Central Region of Colombia
Authors: Chaves Sandra Catalina , Rodríguez María Camila , Mideros María Fernanda , Lucca Florencia , Ñústez Carlos E. , Restrepo Silvia
Published: November 2018

Pathogen variation plays an important role in the dynamics of infectious diseases. In this study, the genetic variation of 279 Phytophthora infestans isolates was assessed using a combination of 12 microsatellite simple-sequence repeat markers. Isolates were collected from 11 different potato cultivars in 11 different geographic localities of the central region of Colombia. The objective of this study was to determine whether populations were differentiated by host genotype or geographic origin. Within a single clonal lineage, EC-1, 76 genotypes were detected. An analysis of molecular variance attributed most of the variation to differences within host genotypes rather than among the host genotypes, suggesting that host cultivars do not structure the populations of the pathogen. Furthermore, the lack of a genetic population structure according to the host cultivar was confirmed by all of the analyses, including the Bayesian clustering analysis and the minimum spanning network that used the Bruvo genetic distance, which suggested that there are no significant barriers to gene flow for P. infestans among potato cultivars. According to the geographic origin, the populations of P. infestans were also not structured, and most of the variation among the isolates was attributed to differences within localities. Only some but not all localities in the north and west of the central region of Colombia showed some genetic differentiation from the other regions. The absence of sexual reproduction of this pathogen in Colombia was also demonstrated. Important insights are discussed regarding the genetic population dynamics of the P. infestans populations of the central region of Colombia that were provided by the results. In Colombia, there is a high genetic variation within the EC-1 clonal lineage with closely related genotypes, none dominant, that coexist in a wide geographic area and on several potato cultivars.
Radiation Exposure to the Surgeon, Surgical Assistant, and Scrub Nurse During Closed Intramedullary Nailing of Long Bones—Does It Vary Depending on the Experience of the Surgeon?
Authors: Patra Sudipta K. , Shetty Ajoy P. , Jayaramaraju Dheenadhayalan , Rajasekaran Shanmuganathan
Published: November 2018

Objectives:

To assess radiation exposure (RE) to the surgical team and fluoroscopy time (FT) during closed nailing of long bone fractures performed under fluoroscopic guidance with regard to surgeon's experience.

Design:

Prospective observational study.

Setting:

Level-1 trauma center.

Participants:

Surgical team, comprising a surgeon, a surgical assistant, and a scrub nurse, for closed nailing procedures performed in 202 consecutive closed tibial and femoral diaphyseal fractures.

Intervention:

Dosimeter provided to each member of surgical team. Surgeon experience level (trainee, senior registrar, and consultant).

Main Outcome Measurements:

RE (microsieverts) to the surgical team and FT (minutes) were recorded from the dosimeter and fluoroscopic unit, respectively, and correlated with surgeon's experience.

Results:

In tibial nailing, mean RE (in µSv) per procedure to surgeon, surgical assistant, and scrub nurse was 15.2, 9.2, and 2.0 for trainees, 14.5, 8.1, and 1.6 for senior registrars, and 13.6, 7.4, and 1.5 for consultants, respectively. In femoral nailing, mean RE per procedure to surgeon, surgical assistant, and scrub nurse was 181.6, 113.6, and 37.1 for trainees, 110.1, 66.7, and 20.4 for senior registrars, and 79.9, 30.9, and 12.5 for consultants, respectively. RE to the surgeon was highest followed by surgical assistant and scrub nurse irrespective of operating surgeon's experience in both tibial and femoral nailing (P < 0.001). In tibial nailing, there was a significant difference in FT only for the stage of guide wire passage (P = 0.041), whereas in femoral nailing, total FT (P < 0.001), nail entry verification (P = 0.02), guide wire passage (P = 0.013), nail introduction (P = 0.006), and distal locking (P < 0.001) showed a significant difference.

Conclusions:

RE was maximum for operating surgeon and least for scrub nurse irrespective of operating surgeon's experience in both femoral and tibial nailing. FT and RE to the surgical team decreased with increasing experience of the surgeon in femoral nailing.

Level of Evidence:

Prognostic Level II. See Instructions for Authors for a complete description of levels of evidence.
Helicobacter pylori seroprevalence in Spain: influence of adult and childhood sociodemographic factors
Authors: Lorenzo Irene , Fernández-de-Larrea Nerea , Michel Angelika , Romero Beatriz , Lope Virginia , Bessa Xavier , Moreno Victor , Martín Vicente , Amiano Pilar , Castilla Jesús , Tardón Adonina , Dierssen-Sotos Trinidad , Peiró Rosana , Díaz-Santos Marian , Navarro Carmen , Jiménez-Moleón José J. , Butt Julia , Barricarte Aurelio , Ruiz Irune , Molina-de-la-Torre Antonio J. , Casabonne Delphine , Pérez-Gómez Beatriz , Kogevinas Manolis , del Campo Rosa , de Sanjosé Silvia , Pollán Marina , Waterboer Tim , Aragonés Nuria
Published: November 2018

Helicobacter pylori (H. pylori) chronic infection causes severe digestive diseases, including gastric cancer, and certain strains entail a higher risk. Risk factors for this infection are still not fully understood. The aim of this study was to describe the association of adult and childhood sociodemographic factors with the seroprevalence of H. pylori, and with CagA and VacA antigen-specific seropositivity among H. pylori-seropositive individuals in the Spanish adult population. Serum antibody reactivity to H. pylori proteins was evaluated using multiplex serology in 2555 population-based controls enrolled in the MCC-Spain study, a multicase–control study recruiting participants from 2008 to 2013 in different areas of Spain. H. pylori seroprevalence was defined as seropositivity against at least four bacterial proteins. Information on sociodemographics, lifestyles, and environmental exposures was collected through personal interviews. Prevalence ratios and 95% confidence intervals were estimated using Poisson regression models to assess the association of lifetime sociodemographic factors with H. pylori seroprevalence and with seropositivity for CagA and VacA. H. pylori seroprevalence was 87.2%. Seropositivity was statistically significantly higher in men, increased with age, BMI, and number of siblings, and decreased with education and socioeconomic family level at birth. Among H. pylori-seropositive individuals, seropositivity was 53.3% for CagA, 61.4% for VacA, and 38.8% for both CagA and VacA. Ever smokers had lower seroprevalence for CagA and VacA than never smokers. H. pylori seroprevalence among this Spanish adult population was high and one third of the population was seropositive for two well-known markers of gastric cancer risk: CagA and VacA. Sex, age, education, and BMI were associated with H. pylori seroprevalence.
Subacute cutaneous lupus erythematosus induced by nivolumab: two case reports and a literature review
Authors: Zitouni Nesrine B. , Arnault Jean-Philippe , Dadban Ali , Attencourt Christophe , Lok Catherine C. , Chaby Guillaume
Published: November 2018

Nivolumab is widely used to treat several late-stage malignancies such as melanoma and non-small-cell lung cancer by inhibiting the interaction between the programmed cell death protein-1 and its ligand. By stimulating an antitumor immune response, it also leads to immune adverse events. Here. we report two cases of subacute cutaneous lupus erythematosus (SCLE) induced by nivolumab. Case 1: a 72-year-old woman with a stage IV melanoma. Two months after nivolumab discontinuation because of autoimmune hepatitis, the patient was in complete remission and pruritic nummular erythematous plaques appeared on the back and arms. Case 2: a 43-year-old man put under nivolumab for a metastatic non-small-cell lung cancer. After two cycles, an annular erythematous eruption appeared on the hands, arms, and chest. The hypothesis of SCLE was confirmed by biopsies showing lymphoid perivascular inflammatory infiltrates, with scarce C3 deposits along the basal layer of the epidermis in patient 2. Both patients tested positive for antinuclear antibodies and anti-SSA antibodies. Lesions were regressive under topical corticosteroids and hydroxychloroquine for the first patient and oral prednisone for the second patient. No systemic involvement was observed. The occurrence of SCLE 2 months after nivolumab discontinuation is evidence that the drug effect is prolonged because of the maintenance of programmed cell death protein-1 reception saturation for months. A causal relationship between SCLE and nivolumab is suggested by (i) the occurrence of SCLE after at least two cycles, (ii) the regression of lesions following treatment with corticosteroids and hydroxychloroquine, and (iii) the fact that it appeared after remission in our first patient.
Incidence rate and risk factors for suicide death in patients with skin malignant melanoma: a Surveillance, Epidemiology, and End Results analysis
Authors: Yang Jin , Chen Siying , Li Yuanjie , Wang Bin , Xin Xiaojing , Xue Xia , Pan Zhenyu , Lyu Jun
Published: November 2018

The purpose of this study was to use the Surveillance, Epidemiology, and End Results database to identify the incidence rate and risk factors for suicide death in patients with skin malignant melanoma (MM) in the USA. We screened cases of skin MM in the SEER database. The balance of covariates between the two groups was examined by the
χ

2-test and Fisher’s exact test. Logistic regression was used to identify independent risk factors for committing suicide. A propensity 1: 2 matched analysis was applied to minimize the risk of bias. In total, 103 500 patients with skin MM were included in the study, of whom 623 had died of suicide. The rate of suicide death did not differ significantly between different time intervals. In logistic regression before propensity score matching, age, being divorced, separated, or widowed, receiving radiation or chemotherapy, and the elapsed time since diagnosis were independently associated with an increased rate of suicide death. Only age (P  <  0.001) and being in the first year after a diagnosis (P  <  0.001) significantly increased the risk of suicide death after propensity score matching. In addition, after the propensity score matching, age was a risk factor for localized, regional, and unstaged, and being the first year after a diagnosis was only a risk factor for regional. It is important to identify and treat people at risk of suicide as early as possible. These results can help clinicians to understand suicidal patients and provide them with appropriate support.
New procognitive enhancers acting at the histamine H3 and AMPA receptors reverse natural forgetting in mice: comparisons with donepezil and memantine in the object recognition task
Authors: Louis Caroline , Llopis Karine , Danober Laurence , Panayi Fany , Lestage Pierre , Beracochea Daniel
Published: November 2018

This study evaluated the procognitive effects of S 38093 (a new inverse agonist of the histaminergic H3 receptor) and S 47445 (a new α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid) in 2–3-month-old Swiss mice as compared with donepezil and memantine, two main reference compounds in the treatment of Alzheimer’s disease. The object recognition task allows the study of natural forgetting and is classically used in assessing drug effects on memory. Here, we show that mice exhibit significant object recognition at short (15 min) but not long (24 h) retention intervals separating the familiarization and recognition phases. S 47445 (1.0, 3.0, and 10.0 mg/kg) and S 38093 (0.3, 1.0, and 3.0 mg/kg), both administered postoperatively, 1 h before familiarization and recognition sessions, rescued memory at the long retention interval; their memory-enhancing effects were as powerful as those obtained with donepezil or memantine (1.0 and 3.0 mg/kg for both compounds). Thus, S 38093 and S 47445, detected as positive controls in the object recognition task, are promising compounds for the treatment of amnesic syndromes.
IMMUNE RECOVERY UVEITIS-LIKE SYNDROME MIMICKING RECURRENT T-CELL LYMPHOMA AFTER AUTOLOGOUS BONE MARROW TRANSPLANT
Authors: Lavine Jeremy A. , Singh Arun D. , Baynes Kimberly , Srivastava Sunil K.
Published: November 2018

Purpose:

To report the multimodal imaging findings of immune recovery uveitis mimicking recurrent T-cell lymphoma after autologous bone marrow transplant therapy.

Methods:

A 71-year-old man presented with posterior uveitis 6 weeks after chemotherapy and autologous bone marrow transplant for angioimmunoblastic T-cell lymphoma. Multimodal imaging included fluorescein angiography, fundus autofluorescence, and optical coherence tomography. Diagnostic testing included ocular polymerase chain reaction and diagnostic vitrectomy.

Results:

Clinical examination demonstrated vitritis and perivascular deep retinal whitening. Imaging of the retinal whitening showed late hyperfluorescence on fluorescein angiography, hyperautofluorescence on fundus autofluorescence, and ellipsoid zone loss on optical coherence tomography without infiltrative lesions. Testing was negative for syphilis, herpes simplex virus, varicella-zoster virus, and cytomegalovirus. After no clinical improvement with valacyclovir and intravitreal foscarnet treatment, diagnostic vitrectomy was performed. Bacterial and fungal cultures were negative, and herpes simplex virus, varicella-zoster virus, and cytomegalovirus were not detected by polymerase chain reaction. Cytopathology showed mature small nonneoplastic lymphocytes, macrophages, and monocytes. Flow cytometry demonstrated a reactive T-cell population. The patient demonstrated clinical improvement over time with spontaneous resolution of all retinal findings.

Conclusion:

This case most likely represents immune recovery uveitis-like syndrome. Diagnostic vitrectomy is highly valuable when the differential includes inflammatory, infectious, and neoplastic processes.
CONVERSION OF FOCAL CHOROIDAL EXCAVATION WITH THE ONSET OF CENTRAL SEROUS CHORIORETINOPATHY: REPORT OF 2 CASES AND REVIEW OF THE LITERATURE
Authors: Docherty Gavin , Sidiqi Ahmad , Martens Rosanna , Akil Handan , Navajas Eduardo V.
Published: November 2018

Purpose:

To describe two cases of focal choroidal excavation (FCE) conversion in patients with central serous chorioretinopathy.

Methods:

Case report and literature review of cases of FCE conversion.

Results:

A 35-year-old asymptomatic pregnant patient was found to have conforming FCE on spectral domain optical coherence tomography of the right eye during hydroxychloroquine screening. Three months later, she presented with decreased vision in the right eye and subretinal fluid in both eyes secondary to central serous chorioretinopathy. Spectral domain optical coherence tomography revealed that her FCE had changed to nonconforming type. A 40-year-old male patient was found to have nonconforming FCE and subretinal fluid in his right eye on spectral domain optical coherence tomography. On follow-up, spectral domain optical coherence tomography demonstrated resolution of subretinal fluid and conversion of nonconforming FCE to conforming type. Literature review showed that most cases of FCE remain stable over time. Conversion from nonconforming FCE to conforming type has been described after photodynamic therapy or anti–vascular endothelial growth factor therapy. Conversion from conforming to nonconforming type has been described in 2 cases that developed subretinal fluid in the setting of acute central serous chorioretinopathy.

Conclusion:

Our cases and literature review suggest that nonconforming FCE is the result of persistent subretinal fluid. Further studies are necessary to determine whether symptomatic nonconforming SRF needs treatment to reduce subretinal fluid.
Using Group-based Trajectory Models and Propensity Score Weighting to Detect Heterogeneous Treatment Effects
Authors: Winn Aaron N. , Fergestrom Nicole M. , Neuner Joan M.
Published: November 2018

Background:

We extend an interrupted time series study design to identify heterogenous treatment effects using group-based trajectory models (GBTMs) to identify groups before a new policy and then examine if the effects of the policy has consistent impacts across groups using propensity score weighting to balance individuals within trajectory groups who are and are not exposed to the policy change. We explore this by examining how adherence to endocrine therapy (ET) for women with breast cancer was impacted by reducing copayments for medications by the introduction of generic ETs among women who do not receive a subsidy (the “treatment” group) to those that do receive a subsidy and are not exposed to any changes in copayments (the “control” group).

Methods:

We examined monthly adherence to ET using the proportion of days covered for women diagnosed with breast cancer between 2008 and 2009 using SEER-Medicare data. To account for baseline trends, we characterize adherence for 1 year before generic approval of ET using GBTMs, within each groups we generate inverse probability treatment weights of not receiving a subsidy. We compared adherence after generic entry within each GBTM using a modified Poisson model.

Results:

GBTMs for adherence in the 1-year pregeneric identified 6 groups. When comparing patients who did and did not receive a subsidy we found no overall effect of generic introduction. However, 1 of the 6 identified adherence groups postgeneric adherence increased [the “consistently low” (risk ratio=1.91; 95% confidence interval=1.34–2.72)].

Conclusions:

This study describes a new approach to identify heterogenous effects when using an interrupted time series research design.
Palliative Care in Adolescents and Young Adults With Cancer—Why Do Adolescents Need Special Attention?
Authors: Pinkerton Ross , Donovan Leigh , Herbert Anthony
Published: November 2018

Meeting shortfalls in the provision of care to adolescents and young adults with cancer has focused largely on improving outcomes and psychosocial support. A significant percentage of adolescents and young adults with cancer will die of disease because of initial poor prognosis conditions or disease relapse. In adults, progress has been made in the concept of an integrated cancer/palliative care service. In pediatric oncology, the application of this philosophy of care has lagged behind somewhat. In the case of adolescents, particularly those with advanced cancer, the palliative care needs, in a broader sense than only end-of-life care, are often not adequately met, irrespective of whether treatment is delivered in a pediatric or adult cancer service. There are a number of age-specific aspects to palliative and supportive care for adolescents. Complex interactions between clinicians, parents, and patients potentially limit the young person's ability to influence care planning. The wide variation in real or perceived competency at this age, the developmental challenges in relation to behavior, communication, and coping strategy all require particular professional expertise that is not always available.
Characterizing chronic pain in late adolescence and early adulthood: prescription opioids, marijuana use, obesity, and predictors for greater pain interference
Authors: Anastas Tracy , Colpitts Kelsey , Ziadni Maisa , Darnall Beth D. , Wilson Anna C.
Published: November 2018

Introduction:

Chronic pain in late adolescence and young adults is understudied and poorly characterized.

Objectives:

We sought to characterize key variables that may impact pain interference in late adolescents and young adults with chronic pain, including prescription opioid use, marijuana use, psychological symptoms, and obesity.

Methods:

Retrospective, cross-sectional medical chart review for patients aged 17 to 23 years (N = 283; 61% Females) seeking care at a tertiary care pain clinic. Data on pain characteristics, health behaviors, and mental health distress were examined, in addition to self-reported pain intensity and interference.

Results:

Overlapping pain conditions were common in this young adult sample (mean ≥ 2 pain conditions). Back pain was the most commonly cited pain condition, and the majority of pain was of unknown etiology. Results revealed high rates for current opioid prescription, overweight or obese status, and mental health problems. Those using prescription opioids were more likely to endorse tobacco use and had greater pain interference. Importantly, the presence of mental health distress and opioid use were predictive of higher levels of pain-related interference.

Conclusion:

Treatment-seeking adolescents and young adults with chronic pain evidence complex care needs that include pain and mental comorbidities, as well as risky health behaviors. Pain and mental health distress were associated with poorer physical health, opioid prescription and marijuana use, and pain-related interference. Findings underscore the need for additional research on pain, treatment patterns, and health behaviors and their impact on developmental trajectories, as well as the need to develop and apply effective early interventions in this at-risk population.
Neonatal Teratoma: Craniofacial Treatment
Authors: Oommen John , Mohammed Hafiz , Ayyappan Kutty Shanker , Mammen Abraham , Kalathingal Kader , Vellani Thamunni Chandrabose , Sivadasan Anand , Nair Santhy
Published: November 2018

Teratomas are rare congenital neoplasms. Head and neck locations of the tumor are uncommon with combined intracranial and extracranial extensions being even more rare. The authors present a case of teratoma involving the temporal, buccal, maxillary, orbital and extending to the intracranial regions, which was successfully managed by surgical resection.
Karapandzic Flap: A Useful Option for Reconstruction of Lower Lip
Authors: Sane Vikrant Dilip , Rathi Pallavi , Narla Bhawana , Khandelwal Saurabh , Pathan Wasim
Published: November 2018

Lip carcinoma is a common cancer of the head and neck region and it more commonly affects the lower lip (>90%). Out of all the carcinomas affecting the lower lip, squamous cell carcinoma accounts for 95% of the patients. Reconstruction of lower lip is a challenging task, as it requires taking into consideration the restoration of function as well as aesthetics. In this study, a patient for whom successful reconstruction of lower lip defect was done using the Karapandzic flap was presented.
Suturing a Vomer Flap to the Hard Palate Through a Hole When the Nasal Lining is Not Available
Authors: Hwang Kun , Kim Hyung Mook
Published: November 2018

The nasal lining by suturing a vomer flap onto the bony ridge of the cleft through a hole was repaired.

A 16-month-old girl had an incomplete bilateral posterior cleft palate. While incising the periosteum and elevating the nasal mucosa from the cleft edge of the right side, the mucosa was sheared and a buttonhole was made, and as a result, the nasal lining could not be coapted. A vomer flap to close the nasal lining was applied. On the left side, the nasal mucosa from the cleft margin was sutured to the vomer flap. On the right side, where no nasal lining was available, 2 holes were drilled 5 mm lateral to each bony cleft margin, and the vomer flap was sutured to the palate with 4-0 vicryl through the holes. The elevated bilateral mucoperiosteal flaps were brought together to the midline and sutured to the anterior triangular flap in a V-Y pushback fashion.

This method could be used to cover the nasal lining when nasal mucosa is not available.
Trans-Oral Robotic Surgery of Submandibular Gland Removal With Preservation of Sublingual Gland and Wharton's Duct
Authors: Lin Xiaozhen , Liang Limin , Shao Xiaojun , Han Xiaodong
Published: November 2018

In surgical removal of a submandibular gland, trans-cervical approach has esthetic problem and existing trans-oral approaches are extensively invasive. The authors have used trans-oral robotic surgery to remove the submandibular gland with preservation of the sublingual gland and the Wharton's duct, and hereby report the case and discuss our preliminary experiences.
Pattern Recognition Receptor-reactivity Screening of Liver Transplant Patients
Authors: Sosa Rebecca A. , Rossetti Maura , Naini Bita V. , Groysberg Victoria M. , Kaldas Fady M. , Busuttil Ronald W. , Chang Yu-Ling , Gjertson David W. , Kupiec-Weglinski Jerzy W. , Reed Elaine F.
Published: November 2018

Objective and Background:

Pattern recognition receptors (PRRs) on immune and parenchymal cells can detect danger-associated molecular patterns (DAMPs) released from cells damaged during ischemia-reperfusion injury (IRI), in heart attack or stroke settings, but also as an unavoidable consequence of solid organ transplantation. Despite IRI being a significant clinical problem across all solid organ transplants, there are limited therapeutics and patient-specific diagnostics currently available.

Methods:

We screened portal blood samples obtained from 67 human liver transplant recipients both pre- [portal vein (PV) sample] and post-(liver flush; LF) reperfusion for their ability to activate a panel of PRRs, and analyzed this reactivity in relation to biopsy-proven IRI.

Results:

PV samples from IRI+ orthotopic liver transplantation (OLT) patients (n = 35) decreased activation of hTLR4- and hTLR9-transfected cells, whereas PV from IRI− patients (n = 32) primarily increased hTLR7 and hNOD2 activation. LF samples from OLT-IRI patients significantly increased activation of hTLR4 and hTLR9 over IRI− LF. In addition, the change from baseline reactivity to hTLR4/9/NOD2 was significantly higher in IRI+ than IRI− OLT patients.

Conclusions:

These results demonstrate that TLR4/7/9 and NOD2 are involved in either promoting or attenuating hepatic IRI, and suggest a diagnostic screening of portal blood for reactivity to these PRRs might prove useful for prediction and/or therapeutic intervention in OLT patients before transplantation.
The Biology of ‘Risk-On’. Decreasing Inflammatory and Stress Responses on a London Trading Floor
Authors: Xie N. Z. , Page L. , Granger D. A. , Coates J. M.
Published: November 2018

Human physiological arousal is highly sensitive to information and uncertainty. Little is known, however, about how to measure information in natural settings, nor about which physiological systems respond to it. Financial market prices, and their volatility, present a convenient measure of informational load. Here we report on a study into the physiological response of traders in the City of London during a period of extreme, but declining, volatility. We sampled salivary cortisol, the main stress hormone, and the pro-inflammatory cytokines, IL-1β, IL-6, IL-8, and TNF-α three times a day for two weeks. We found that average daily cortisol levels tracked closely an index of equity and bond volatility, as did levels of IL-1β. Within-day cortisol and IL-1β levels also tracked one hour lagged volatility. Interestingly, the cascade of endocrine and immunological changes was initiated by IL-1β, the first responder of the stress and inflammatory responses. Our results have implications for finance because chronic stress and the immune response known as ‘sickness behaviour’ could have powerful effects on risk-taking and market stability.
Analysis of structural variants in four African Cichlids highlights an association with developmental and immune related genes
Authors: Penso-Dolfin Luca , Man Angela , Haerty Wilfried , Palma Federica Di
Published: November 2018

African Lakes Cichlids are one of the most impressive example of adaptive radiation. Independently in Lake Victoria, Tanganyika, and Malawi, several hundreds of species arose within the last 10 million to 100,000 years. Whereas most analyses in Cichlids focused on nucleotide substitutions across species to investigate the genetic bases of this explosive radiation, to date, no study has investigated the contribution of structural variants (SVs) to speciation events (through a reduction of gene flow) and adaptation to different ecological niches. Here, we annotate and characterize the repertoires and evolutionary potential of different SV classes (deletion, duplication, inversion, insertions and translocations) in five Cichlid species (Haplochromis burtoni, Metriaclima zebra, Neolamprologus brichardi, Pundamilia nyererei and Oreochromis niloticus). We investigate the patterns of gain/loss across the phylogeny for each SV type enabling the identification of both lineage specific events and a set of conserved SVs, common to all four species in the radiation. Both deletion and inversion events show a significant overlap with SINE elements, while inversions additionally show a limited, but significant association with DNA transposons. Inverted regions are enriched for genes regulating behaviour, or involved in skeletal and visual system development. We also find that duplicated regions show enrichment for genes associated with “antigen processing and presentation” (GO:0019882) and other immune related categories. Altogether, we provide the first, comprehensive overview of rearrangement evolution in East African Cichlids, and some initial insights into their possible contribution to adaptation.
A genetically encoded probe for imaging HA-tagged protein translation, localization, and dynamics in living cells and animals
Authors: Zhao Ning , Kamijo Kouta , Fox Philip D. , Oda Haruka , Morisaki Tatsuya , Sato Yuko , Kimura Hiroshi , Stasevich Timothy J.
Published: November 2018

To expand the toolbox of imaging in living cells, we have engineered a new single chain variable fragment (scFv) that binds the classic linear HA epitope with high affinity and specificityin vivo. The resulting probe, which we call the HA frankenbody, is capable of lighting up in multiple colors HA-tagged nuclear, cytoplasmic, and membrane proteins in diverse living cell types. The HA frankenbody also enables state-of-the-art single-molecule experiments, which we demonstrate by tracking single mRNA translation dynamics in living U2OS cells and neurons. In combination with the SunTag, we track two mRNA species simultaneously to demonstrate comparative single-molecule studies of translation can now be done with genetically encoded tools alone. Finally, we use the HA frankenbody to precisely quantify the expression of HA tagged proteins in developing zebrafish embryos. The versatility of the HA frankenbody makes it a powerful new tool for imaging protein dynamicsin vivo.

One-sentence summary

A genetically encodable intracellular single-chain variable fragment that selectively binds the HA epitope (YPYDVPDYA) with high affinity in living cells and organisms can be used to quantify HA-tagged protein translation, localization, and dynamics.
EEG-based detection of the locus of auditory attention with convolutional neural networks
Authors: Vandecappelle Servaas , Deckers Lucas , Das Neetha , Ansari Amir Hossein , Bertrand Alexander , Francart Tom
Published: November 2018

In a multi-speaker scenario, the human auditory system is able to attend to one particular speaker of interest and ignore the others. It has been demonstrated that it is possible to use electroencephalography (EEG) signals to infer to which speaker someone is attending by relating the neural activity to the speech signals. However, classifying auditory attention within a short time interval remains the main challenge. We present a convolutional neural network-based approach to extract the locus of auditory attention (left/right) without knowledge of the speech envelopes. Our results show that it is possible to decode the locus of attention within 1 to 2 s, with a median accuracy of around 81%. These results are promising for neuro-steered noise suppression in hearing aids, in particular in scenarios where per-speaker envelopes are unavailable.
Life history and dispersal timing evolve in response to metapopulation connectedness
Authors: Masier Stefano , Bonte Dries
Published: November 2018

Dispersal evolution impacts the fluxes of individuals and hence, connectivity in metapopulations. Connectivity is therefore decoupled from the structural connectedness of the patches within the spatial network. Because of demographic feedbacks, local selection can additionally steer the evolution of other life history traits. We investigated how different levels of connectedness affect dispersal and life history evolution by varying the interpatch distance in replicated experimental metapopulations of the two-spotted spider. We implemented a shuffling treatment to separate local- and metapopulation-level selection.

With lower metapopulation connectedness, an increased starvation resistance and delayed dispersal evolved. Intrinsic growth rates evolved at the local level by transgenerational plasticity or epigenetic processes. Changes in patch connectedness thus induce the genetic and non-genetic evolution of dispersal costs and demographic traits at both the local and metapopulation level. These trait changes are anticipated to impact metapopulations eco-evolutionary dynamics, and hence, the persistence and performance of spatially structured populations.
Fgf3 is crucial for the generation of monoaminergic cerebrospinal fluid contacting cells in zebrafish
Authors: Reuter Isabel , Jäckels Jana , Kneitz Susanne , Kuper Jochen , Lesch Klaus-Peter , Lillesaar Christina
Published: November 2018

In most vertebrates, including zebrafish, the hypothalamic serotonergic cerebrospinal fluid-contacting (CSF-c) cells constitute a prominent population. In contrast to the hindbrain serotonergic neurons, little is known about the development and function of these cells. Here, we identify Fibroblast growth factor (Fgf)3 as the main Fgf ligand controlling the ontogeny of serotonergic CSF-c cells. We show thatfgf3positively regulates the number of serotonergic CSF-c cells, as well as a subset of dopaminergic and neuroendocrine cells in the posterior hypothalamus. Further, expression of the ETS-domain transcription factoretv5bis downregulated afterfgf3impairment. Previous findings identifiedetv5bas critical for the proliferation of serotonergic progenitors in the hypothalamus, and therefore we now suggest that Fgf3 acts viaetv5bduring early development to ultimately control the number of mature serotonergic CSF-c cells. Moreover, our analysis of the developing hypothalamic transcriptome shows that the expression offgf3is upregulated uponfgf3loss-of-function, suggesting activation of a self-compensatory mechanism. Together, these results highlight Fgf3 in a novel context as part of a signalling pathway of critical importance for hypothalamic development.

Summary statement

This study highlights Fgf3 in a novel context where it is being part of a signalling pathway of critical importance for development of hypothalamic monoaminergic cells in zebrafish.
Folic acid, but not folate, regulates different stages of neurogenesis in the ventral hippocampus of adult female rats
Authors: Qiu Wansu , Gobinath Aarthi R. , Wen Yanhua , Austin Jehannine , Galea Liisa A.M.
Published: November 2018

Folate is an important regulator of hippocampal neurogenesis, and in utero spinal cord development. Both high levels of folic acid and low levels of folate can be harmful to health, as low levels of folate have been linked to several diseases while high folic acid supplements can mask a vitamin B12 deficiency. Depressed patients exhibit folate deficiencies, lower levels of hippocampal neurogenesis, elevated levels of homocysteine, and elevated levels of the stress hormone, cortisol, which may be inter-related. Here, we are interested in whether different doses of natural folate or synthetic folic acid diets can influence neurogenesis in the hippocampus, levels of plasma homocysteine, and serum corticosterone in adult female rats. Adult female Sprague-Dawley rats underwent dietary interventions for 29 days. Animals were randomly assigned to six different dietary groups: folate deficient + succinylsulfathiazole (SST), low 5-methyltetrahydrofolate (5-MTHF), low 5-MTHF + (SST), high 5-MTHF + SST, low folic acid, and high folic acid. SST was added to a subset of the 5-MTHF diets to eliminate folic acid production in the gut. Before and after dietary treatment, blood samples were collected for corticosterone and homocysteine analysis, and brain tissue was collected for neurogenesis analysis. High folic acid and low 5-MTHF without SST increased the number of immature neurons (doublecortin-expressing cells) within the ventral hippocampus compared to folate deficient controls. Low 5-MTHF without SST significantly increased the number of immature neurons compared to low and high 5-MTHF + SST, indicating that SST interfered with elevations in neurogenesis. Low folic acid and high 5-MTHF+SST reduced plasma homocysteine levels compared to controls, but there was no significant effect of diet on serum corticosterone levels. Low folic acid and high 5-MTHF+SST reduced the number of mature new neurons in the ventral hippocampus (BrdU/NeuN-positive cells) compared to folate deficient controls. Overall, folic acid dose-dependently influenced neurogenesis, with low levels decreasing but high levels increasing, neurogenesis in the ventral hippocampus, suggesting this region, which is important for regulating stress, is particularly sensitive to folic acid in diets. Furthermore, the addition of SST negated the effects of 5-MTHF to increase neurogenesis in the ventral hippocampus.
Two linked loci under mutation-selection balance and Muller’s ratchet
Authors: Khudyakova Ksenia A. , Neretina Tatiana Yu. , Kondrashov Alexey S.
Published: November 2018

We report the complete analysis of a deterministic model of deleterious mutations and negative selection against them at two haploid loci without recombination. As long as mutation is a weaker force than selection, mutant alleles remain rare at the only stable equilibrium, and otherwise, a variety of dynamics are possible. If the mutation-free genotype is absent, generally the only stable equilibrium is the one that corresponds to fixation of the mutant allele at the locus where it is less deleterious. This result suggests that fixation of a deleterious allele that follows a click of the Muller’s ratchet is governed by natural selection, instead of random drift.
Wheel-running exercise before and during gestation against acute and sensitized cocaine psychomotor-activation in offspring
Authors: Lespine Louis-Ferdinand , Plenevaux Alain , Tirelli Ezio
Published: November 2018

While animal research has consistently reported preventive effects of exercise against drug abuse vulnerability, little is known about the influence of the developmental stage during which exercise is displayed on addictive drugs responsiveness. This study aimed to determine whether prenatal exercise could attenuate acute cocaine reactivity and psychomotor sensitization in youth offspring. We used a split-plot factorial design where C57BL/6J females were randomly assigned into sedentary or exercised (wheel-running) conditions before and during gestation, the wheels being removed on gestational day 18. Offspring were weaned, gendered and individually housed on 24-28 days old. At 38-42 days old, they were tested for their acute psychomotor responsiveness to 8 mg/kg cocaine and their initiation of sensitization over 8 additional once-daily administrations, the long-term expression of sensitization occurring 30 days later. Adolescent females born from exercised mothers were much less responsive to the acute psychomotor-stimulating effect of cocaine than those born from sedentary mothers (d = 0.75, p = .02), whereas there was no evidence for such a difference in males (d = 0.34, p = .17). However, we did not find sizeable attenuating effects of prenatal exercise on the initiation and the long-term expression of the psychomotor-activating effect of cocaine, in either sex (Cohen’s ds varying from −0.23 to 0.39). These results suggest that prenatal exercise may induce initial protection against cocaine responsiveness in youth females, a finding that warrants further research.
Iodine-enhanced micro-CT imaging of soft tissue on the example of peripheral nerve regeneration
Authors: Heimel Patrick , Swiadek Nicole Victoria , Slezak Paul , Kerbl Markus , Schneider Cornelia , Nürnberger Sylvia , Redl Heinz , Teuschl Andreas Herbert , Hercher David
Published: November 2018

Microcomputed tomography (μCT) is widely used for the study of mineralized tissues but a similar use for soft tissues is hindered by their low X-ray attenuation. This limitation can be overcome by the recent development of different staining techniques. Staining with Lugol’s solution, a mixture of one part iodine and two parts potassium iodide in water, stands out among these techniques for its low complexity and cost. Currently, Lugol staining is mostly used for anatomical examination of tissues. In the present study we seek to optimize the quality and reproducibility of the staining for ex vivo visualization of soft tissues in the context of a peripheral nerve regeneration model in the rat.

We show that the staining result not only depends on the concentration of the staining solution, but also on the amount of stain in relation to the tissue volume and composition, necessitating careful adaptation of the staining protocol to the respective specimen tissue. This optimization can be simplified by a stepwise staining which we show to yield a similar result compared to staining in a single step. Lugol staining solution results in concentration dependent tissue shrinkage which can be minimized but not eliminated. We compared the shrinkage of tendon, nerve, skeletal muscle, heart, brain and kidney with six iterations of Lugol staining.

60 ml of 0.3% Lugol’s solution per cm3 of tissue for 24h yielded good results on the example of a peripheral nerve regeneration model and we were able to show that the regenerating nerve inside a silk fibroin tube can be visualized in 3D using this staining technique. This information helps in deciding the region of interest for histological imaging and provides a 3D context to histological findings. Correlating both imaging modalities has the potential to improve the understanding of the regenerative process.