bluuebunny/crossref_metadata_2025 huggingface dataset:
General practitioners’ considerations of and experiences with multimorbidity patients: A qualitative study
Authors: Ørtenblad Lisbeth , Nissen Nina Konstantin
Published: November 2019

Introduction

General practitioners’ management of multimorbid patients is mostly described as a burden, although it is also indicated that fundamental characteristics of general practice are well-suited to accommodate appropriate management of multimorbidity. However, little is known about actual practices among general practitioners. This study explores general practitioners’ management of their multimorbid patients.

Methods

A qualitative methodological design using participant observation and interviews. Interpretive description was used as the analytical framework. The study took place in a provincial town in Denmark. Three general practices with a total of 12 general practitioners participated.

Results

‘Multimorbidity’ as general terminology does not reflect the practice of the general practitioners. Their approach is based on the functional capacity of individual patients. The heterogeneity of the group was classified into three categories determining the general practitioners’ approach: the well-functioning patients, the surprising patients and the fragile patients. Three core characteristics were identified as pivotal for the general practitioners’ approach: holistic view of the patient’s situation, patient-centred focus and coordinator and facilitator. These are fundamental characteristics of general practice, but become especially significant because they accommodate the complexity and heterogeneity of multimorbid patients.

Discussion

This study expands the subject field by exploring the general practitioners’ actual practices, thereby providing new perspectives into features that support appropriate management of multimorbid patients. General practitioners balance administrative and clinical regulations in their considerations of accommodating the heterogeneity and complexity of multimorbid patients. This suggests that better possibilities must be provided to realize the fundamental characteristics of general practice to support their management of multimorbid patients.
Correlating Psychological Comorbidities and Outcomes After Spine Surgery
Authors: Jackson Keith L. , Rumley Jacob , Griffith Matthew , Agochukwu Uzondu , DeVine John
Published: November 2019

Study Design:

Literature review.

Objective:

The aim of this literature review is to examine the effects of psychological disorders on postoperative complications, surgical outcomes, and long-term narcotic use. We also hope to detail the value of preoperative identification and treatment of these pathologies.

Methods:

A series of systematic reviews of the relevant literature examining the effects of psychological disorders and spine surgery was conducted using PubMed and Cochrane databases.

Results:

Combined, the database queries yielded 2275 articles for consideration. After applying screening criteria, 96 articles were selected for inclusion. Patients with underlying psychological disease have higher rates of delirium, readmission, longer hospital stays, and higher rates of nonroutine discharge following spine surgery. They also have higher rates of chronic postoperative narcotic use and may experience worse surgical outcomes. Because of these defined issues, researchers have developed multiple screening tools to help identify patients with psychological disorders preoperatively for potential treatment. Treatment of these disorders prior to surgery may significantly improve surgical outcomes.

Conclusion:

Patients with psychological disorders represent a unique population with respect to their higher rates of spinal pain complaints, postoperative complications, and worsened functional outcomes. However, proper identification and treatment of these conditions prior to surgery may significantly improve many outcome measures in this population. Future investigations in this field should attempt to develop and validate current strategies to identify and treat individuals with psychological disorders before surgery to further improve outcomes.
Risk Factors Associated With Femoral Ring Allograft Breakage in ALIF
Authors: Philipp Travis , Radoslovich Stephanie S. , Yoo Jung U.
Published: November 2019

Study design:

This is a retrospective chart review.

Objectives:

To identify the incidence of, and variables correlated with, femoral ring allograft (FRA) fracture following anterior lumbar interbody fusion (ALIF).

Methods:

All patients who underwent ALIF using FRAs at an academic institution over 10 years were included. Postoperative radiographs were reviewed by both the primary and senior authors; fracture and no-fracture groups were created for comparison. Patient and surgical characteristics were extracted from electronic medical records. Frequency data comparisons were performed using contingency table analysis; comparisons of means were analyzed for continuous variables. A multivariate linear regression model was developed using screw use, graft height <12 mm, index level, and weight as variables.

Results:

A total of 76 FRAs in 59 patients were identified, 13 (17%) of which fractured. Age, sex, smoking status, use of buttress screws, weight, index level, and presence of spondylolisthesis were not correlated with incidence of fracture ( P > .05). There was a significant correlation between the height of FRA and incidence of fracture; 2% (1/52) of grafts ≥12 mm and 50% (12/24) of grafts <12 mm fractured ( P < .0001). Using ordinary least-squares regression, this result was independent of patient weight, use of screws, and index level. Of 10 patients, 9 did not require revision surgery to achieve fusion.

Conclusions:

Graft height was the only variable correlated with incidence of FRA fracture. Graft height <12 mm is an independent risk factor for FRA fracture in patients undergoing ALIF, and their use should be avoided in ALIF procedures.
Thoracolumbar Fracture Dislocations Without Spinal Cord Injury: Classification and Principles of Management
Authors: Kanna Rishi Mugesh , Raja Dilip Chand , Shetty Ajoy P. , Rajasekaran Shanmuganathan
Published: November 2019

Study Design:

Retrospective cohort study.

Objectives:

Thoracic and lumbar fracture dislocations (TLFD) are high-velocity injuries and frequently result in gross neurological deficit. Very rarely, such patients present with intact neurology. Pathomechanics of injury, radiological assessment, surgical techniques, and principles of fixation in such challenging situations have not been described previously.

Methods:

Retrospective review of 36 patients of TLFD without cord injury was performed for demographics, clinical and radiological data, and management. The injuries were classified based on the direction of translation into 4 types: coronal translation (type 1), sagittal translation (type 2), combined translation—antero (type 3a), and combined translation—retro (type 3b). The injuries were managed by meticulous unilateral exposure and temporary fixation, decompression, gradual reduction of dislocation, and long segment fixation.

Results:

In 36 patients, the injuries were classified as type 1 (n = 9), type 2 (n = 10), type 3a (n = 14), and type 3b (n = 3). Imaging/intraoperative observation showed varying degrees of disintegrity of disc, facet joints, and posterior ligamentous complex in the 4 different injury types. Patients with the different injury types also needed individualistic surgical approaches to aid safe reduction of dislocation. Neurological assessment was performed using American Spinal Injury Association score (ASIA), and 16 patients had minimal neurological deficits (ASIA-D) and all were type 3 injury. The mean anteroposterior and lateral translation were corrected from 8.3 ± 3.4 to 1.7 ± 1.3 mm, and 4.7 ± 4.8 to 0.7 ± 0.8 mm respectively.

Conclusion:

This is the largest case series of TLFD without cord injury. Knowledge of the different injury types and principles of safe surgical reduction of the dislocation are important for the treating surgeon to ensure successful outcomes.
Validation of claims data to identify death among aged persons utilizing enrollment data from health insurance unions
Authors:   on behalf of BiDAME (Big Data Analysis of Medical care for the Elderly in Kyoto), Sakai M. , Ohtera S. , Iwao T. , Neff Y. , Kato G. , Takahashi Y. , Nakayama T.
Published: November 2019

The identification of death is critical for epidemiological research. Despite recent developments in health insurance claims databases, the quality of death information in claims is not guaranteed because health insurance claims are collected primarily for reimbursement. We aimed to examine the usefulness and limitations of death information in claims data and to examine methods for improving the quality of death information for aged persons.

We used health insurance claims data and enrollment data (as the gold standard) from September 2012 through August 2015 for nondependent persons aged 65–74 years enrolled in Japanese workplace health insurance. Overall, 3,710,538 insured persons were registered in the database during the study period. We analyzed 45,441 eligible persons. Inpatient and outpatient deaths were identified from the discharge/disease status in the claims, with sensitivities of 94.3% and 47.4%, specificities of 98.5% and 99.9%, and PPVs of 96.3% and 95.7%, respectively, using enrollment data as the gold standard. For outpatients, death defined as a combination of disease status and charge data for terminal care still indicated low sensitivity (54.7%).

The validity of death information in inpatient claims was high, suggesting its potential usefulness for identifying death. However, given the low sensitivity for outpatient deaths, the use of death information obtained solely from records in outpatient claims is not recommended.
Ameliorating potency of Chenopodium album Linn. and vitamin C against mercuric chloride-induced oxidative stress in testes of Sprague Dawley rats
Authors: Jahan Sarwat , Azad Tayyaba , Ayub Amina , Ullah Asad , Afsar Tayyaba , Almajwal Ali , Razak Suhail
Published: November 2019

Background

Mercury has been documented as an industrial risk that posed a serious danger to human health. Mercury exposure results in oxidative stress that may lead to the pathogenesis of male reproductive dysfunction. The present study investigated the ameliorating potential of Chenopodium album L. and vitamin C against mercuric chloride-induced oxidative deterioration of reproductive functions in adult male rats.

Methods

Group 1 (control) received saline. Group 2 received Mercury (0.15 mg/kg b.w, i.p) dissolved in distilled water. Groups 3 and 4 were given oral gavage of vitamin C (200 mg/kg b.w) and the ethanolic extract of C. album (200 mg/kg b.w) respectively, along with Mercury (0.15 mg/kg b.w, i.p). Group 5 was treated only with C. album (200 mg/kg b.w). After 30 days of the treatment, the rats were dissected and their testicular tissue and the cauda epididymis were used for biochemical analysis while blood plasma was used for protein determination.

Results

The applied dose-treatment of Mercury-induced oxidative stress in the testis and cauda epididymis tissues of the rats was apparent by a noteworthy decrease in total protein, CAT, SOD, POD, and GST values while there was increase in ROS and TBARS levels. Furthermore, Mercury decreases daily sperm production and enhanced sperm DNA damage as noticeable by an increase in the head and tail length of comets and decrease in intact DNA. There was no significant effect on the body weight and the weight of the reproductive tissues. Treatment with C. album significantly ameliorated the total protein, ROS, and TBARS content. Similarly, the level of CAT, SOD, POD, and GST was significantly improved and the daily sperm production was significantly increased. Furthermore, C. album administration significantly protected Mercury-induced sperm DNA damage. The results of the extract treatment group were compared with those of vitamin C in detoxifying the oxidative stress and restoring the sperm parameters.

Conclusion

C. album showed protection against Mercury-induced oxidative stress by ameliorating antioxidant enzyme activity, daily sperm production, and DNA damage in rat testes. This suggests that C. album could be beneficial against toxicity induced by an environmental toxicant.
Electric vagal nerve stimulation inhibits inflammation and improves early postoperation cognitive dysfunction in aged rats
Authors: Xiong Jun , Wang Huijun , Bao Yin , Guo Yuliang , Sun Yongxing
Published: November 2019

Background

This study aimed to evaluate effects of electric vagal nerve stimulation on early postoperation cognitive dysfunction in aged rats.

Methods

A total of 33 male Sprague Dawley rats were selected and assigned randomly to three groups, control group (C, n = 10), splenectomy group (S, n = 10) and splenectomy+vagal nerve stimulation group (SV, n = 13). Behavior and memory of rats were evaluated by Open Field Test and Morris Water Maze. Levels of TNF-α, IL-6 and IL-10 in serum were measured by ELISA. The level of TNF-α protein in hippocampus was assessed by Western blotting. rt-PCR was used to detect mRNA expression of NF-κB in hippocampus.

Results

During anesthesia/operation, vital life signs of rats were stable. In SV group, vagal nerve stimulation decreased heart rate lower than 10% of basic level and kept it at a stable range by regulating stimulation intensity. After stimulation stop, heart rate returned to the basic level again. This indicated that the model of vagal nerve stimulation was successful. Serum levels of TNF-α and IL-6 increased by the operation/anesthesia, but they decreased with vagal nerve stimulation (all P < 0.05). TNF-α protein and mRNA expression of NF-κB in hippocampus were also eliminated by vagal nerve stimulation compared to S group (P < 0.05). Results of Morris Water Maze showed escape latency of postoperation in S group was significantly longer than C group (P < 0.05), and times of crossing platform in S group was lower than that of C group (P < 0.05). Although escape latency of postopration in SV group was shorter than that of S group, there was no significant difference between two groups. Meanwhile there were no significant differences of behavior test in Open Field test between three groups, although vagal nerve stimulation improved partly active explore behavior compared to S group.

Conclusion

The inflammation caused by operation and general anesthesia was an important reason of early postoperation cognitive dysfunction, and electric vagal nerve stimulation could inhibit the inflammation. Meanwhile, vagal nerve stimulation could ameliorate early postoperation cognitive dysfunction partly, but its protective effects were not enough and should be studied and improved in future.
Impact of AKAP6 polymorphisms on Glioma susceptibility and prognosis
Authors: Zhang Ming , Zhao Yonglin , Zhao Junjie , Huang Tingqin , Wu Yuan
Published: November 2019

Purpose

Glioma is the most common primary malignant brain tumor with high mortality and poor prognosis. Our aim was to clarify the correlation betweenKinase-anchored protein 6(AKAP6) gene polymorphisms and glioma susceptibility and prognosis in Chinese Han population.

Methods

Five single-nucleotide polymorphisms (SNPs) ofAKAP6were genotyped by Agena MassARRAY in 575 glioma patients and 500 healthy controls. Logistic regression model was utilized to calculate odds ratios (OR) and 95% confidence intervals (CI). The associations between polymorphisms and survival were assessed using the log-rank test, Kaplan-Meier analysis and Cox regression model.

Results

We found that rs2239647 polymorphism was strongly associated with an increased risk of glioma (OR = 1.90,p = 0.007) and a worse prognosis for glioma, especially in high-grade glioma (HR = 1.67,p = 0.034). Stratified analysis showed that rs2239647 increased the risk of glioma in female (OR = 1.62,p = 0.016). Whereas, rs4261436 (HR = 0.70,p = 0.045) and rs17522122 (HR = 0.75,p = 0.016) were associated with better prognosis of astrocytoma. In addition, we also found that surgical methods and chemotherapy are critical factors for the prognosis of glioma patients.

Conclusions

This study firstly provided evidence for the impact ofAKAP6polymorphisms on susceptibility and prognosis of glioma, suggestingAKAP6variants might have potential roles in the etiology of glioma.
A rare case of a completely thrombosed bilobed giant intracranial aneurysm of the anterior cerebral artery with spontaneous parent vessel thrombosis: case report
Authors: Chihi Mehdi , Jabbarli Ramazan , Gembruch Oliver , Teuber-Hanselmann Sarah , Darkwah Oppong Marvin , Pierscianek Daniela , Radbruch Alexander , Glas Martin , Stettner Mark , Sure Ulrich
Published: November 2019

Background

A huge spherical intracranial mass can sometimes be misdiagnosed, due to the lack of typical radiographic features. Thrombosed giant intracranial aneurysms (GIAs) are an uncommon but still a possible differential diagnosis that must be kept in mind to guarantee the best surgical approach and resection of the lesion. We describe an extremely rare case of a huge bifrontal mass mimicking a cystic echinococcosis, in which the surgery unveiled a completely thrombosed GIA of the left anterior cerebral artery (ACA).

Case presentation

A 61-year-old patient complained about intermittent weakness of the right leg, mild holocephalic headache, beginning cognitive deficits and lethargy. Magnetic resonance imaging (MRI) showed a huge partially calcified and bilobed frontal mass with peripheral edema. Based on a time-resolved angiography with interleaved Stochastic trajectories MRI (TWIST-MRI), a vascular origin of the lesion was considered unlikely. Therefore, the surgery was performed under the suspicion of a cystic echinococcosis but revealed a bilobed GIA of the left ACA with a parent vessel thrombosis. Although only a limited left frontal craniotomy was performed, a proximal control of the parent vessel could be ensured, and the aneurysm was successfully clipped. The patient showed postoperatively no new neurological deficits.

Conclusions

Completely thrombosed GIAs with parent vessel thrombosis are rare lesions that might be misdiagnosed if typical radiographic features are missing. Thus, in case of an intracranial spherical mass with signs of intralesional hemorrhage and mural calcifications, presence of a completely thrombosed GIA should be considered as a possible differential diagnosis.
Bone microarchitectural parameters can detect oxytocin induced changes prior to bone density on mitigating bone deterioration in rabbit osteoporosis model using micro-CT
Authors: Qiu Yuyou , Tang Cuisong , Serrano-Sosa Mario , Hu Jian , Zhu Jingqi , Tang Guangyu , Huang Chuan , Huang Mingqian
Published: November 2019

Background

This study is aimed to determine the efficacy of X-Ray Microtomography (micro-CT) in predicting oxytocin (OT) treatment response in rabbit osteoporosis(OP) model.

Methods

Sixty-five rabbits were randomly divided into three groups: control group, ovariectomy (OVX) -vehicle and OVX-oxytocin group. The controls underwent sham surgery. OVX-vehicle and OVX-oxytocin groups were subjected to bilateral OVX. The rabbits in OVX-oxytocin group were injected with oxytocin. In the 0th, 4th, 8th, 10th and 12th weeks post OVX operation, bone mineral density (BMD) and bone micro-architectural parameters were measured in three groups.

Results

Bone mineral density (BMD), bone volume fraction (BV/TV), Trabecular Number (Tb.N), and Trabecular Thickness (Tb.Th) decreased, while Trabecular Spacing (Tb.Sp) and Structure Model Index (SMI) increased overtime in all the three groups. In OVX-oxytocin group, the bone deterioration tendency is slowing down compared with that of the OVX-vehicle group. The BMD of the OVX-oxytocin group was significantly lower than those in the OVX-vehicle group at 12th week (P = 0.017). BV/TV and Tb.Sp in OVX-oxytocin group changed significantly from 8th week (P = 0.043) and 12th week (P = 0.014), which is earlier than that of BMD and other bone micro-architectural parameters.

Conclusion

BV/TV and Tb.Sp changed prior to BMD and other bone micro-architectural parameters with oxytocin intervention, which indicate that they are more sensitive markers for predicting early osteoporosis and treatment monitoring when using micro-CT to evaluate osteoporosis rabbit model.
Psychological factors outmatched morphological markers in predicting limitations in activities of daily living and participation in patients with lumbar stenosis
Authors: Quack V. , Boecker M. , Mueller C. A. , Mainz V. , Geiger M. , Heinemann A. W. , Betsch M. , El Mansy Y.
Published: November 2019

Background

Recent demographic changes have led to a large population of older adults, many of whom experience degenerative disc diseases. Degenerative lumbar spinal stenosis (DLSS) is associated with considerable discomfort and limitations in activities of daily living (ADL). Symptomatic DLSS is one of the most frequent indications for spinal surgery. The aim of this study was to identify sociodemographic variables, morphological markers, depression as well as fear of movement that predict ADL performance and participation in social life in patients with DLSS.

Methods

Sixty-seven patients with DLSS (mean age 62.5 years [11.7], 50.7% females) participated in the study. Predictor variables were age, gender, duration of disease, three morphological markers (severity of the lumbar stenosis, the number of affected segments and presence of spondylolisthesis) as well as self-reported depression and fear of movement. Dependent variables were pain interference with the performance of ADLs, ADLs and participation in social life. Correlations between predictor and dependent variables were calculated before stepwise, linear regression analyses. Only significant correlations were included in the linear regression analyses.

Results

Variance explained by the predictor variables ranged between 12% (R2 = .12; pain interference-physical) and 40% (R2 = .40; ADL requiring lower extremity functioning; participation). Depression and fear of movement were the most powerful predictors for all dependent variables. Among the morphological markers only stenosis severity contributed to the prediction of ADLs requiring lower extremity functioning.

Conclusion

Depression and fear of movement were more important predictors of the execution of ADLs and participation in social life compared to morphological markers. Elevated depressive symptoms and fear of movement might indicate limited adaptation and coping regarding the disease and its consequences. Early monitoring of these predictors should therefore be conducted in every spine centre. Future studies should investigate whether psychological screening or a preoperative psychological consultation helps to avoid operations and enables better patient outcomes.
Lumbar muscles biomechanical characteristics in young people with chronic spinal pain
Authors: Lo Wai Leung Ambrose , Yu Qiuhua , Mao Yurong , Li Wenfeng , Hu Chengpeng , Li Le
Published: November 2019

Background

The prevalence of low back pain is rising among the young adult population. Altered lumbar muscle tone was suggested to be associated with underlying pathologies and symptoms. To date, there is minimum information available on the repeatability of lumbar spine muscle mechanical properties in the young adults who experienced low back pain. This study aimed to assess the reproducibility of mechanical properties of lumbar spinal muscle in young adults with spinal pain by myotonometer and explored the difference in reproducibility when different number of indentations was used.

Methods

Participants who aged between 18 to 25 and reported chronic LBP were recruited. Lumbar muscle tone (Hz) and stiffness (N/m) were assessed by myotonometer on one occasion by two assessors. Parameters were recorded by triple scans and 5-scans mode. Intraclass correlation coefficient (ICC), standard error of measurement (SEM), smallest real difference (SRD), Bland and Altman analysis were used to assess agreement between two measurements. The relationship between muscle mechanical properties and pain score and disability level were assessed by Spearman’s rank correlation coefficient.

Results

The results of ICCs indicated excellent repeatability in triple scans and 5-scans mode for each lumbar level bilaterally (ICC > 0.75). SEM and SRD were smaller in triple scans than 5-scans mode for most levels. Bland and Altman analysis revealed no systematic bias. Spearman’s rank correlation analysis indicated significant high correlations between muscle tone and disability level (r = 0.80, p < 0.05), and between muscle stiffness and disability level (r = 0.81, p < 0.05).

Conclusions

This study found that lumbar spinal muscle tone and stiffness were repeatable parameters when measured by myotonometer. The reproducibility of muscle mechanical parameters did not appear to differ between the two scanning modes with different number of indentations. Muscle tone and stiffness measured by myotonometer may therefore be reliable as outcome measures to assess intervention induced changes. The lack of significant association between intensity of pain and mechanical properties of paraspinal muscles may suggest that muscle properties measured at rest might not be related to pain level at rest but more related to pain elicited during movement.
Tunnel engineering to accelerate product release for better biomass-degrading abilities in lignocellulolytic enzymes
Authors: Lu Zhenghui , Li Xinzhi , Zhang Rui , Yi Li , Ma Yanhe , Zhang Guimin
Published: November 2019

Background

For enzymes with buried active sites, transporting substrates/products ligands between active sites and bulk solvent via access tunnels is a key step in the catalytic cycle of these enzymes. Thus, tunnel engineering is becoming a powerful strategy to refine the catalytic properties of these enzymes. The tunnel-like structures have been described in enzymes catalyzing bulky substrates like glycosyl hydrolases, while it is still uncertain whether these structures involved in ligands exchange. Till so far, no studies have been reported on the application of tunnel engineering strategy for optimizing properties of enzymes catalyzing biopolymers.

Results

In this study, xylanase S7-xyl (PDB: 2UWF) with a deep active cleft was chosen as a study model to evaluate the functionalities of tunnel-like structures on the properties of biopolymer-degrading enzymes. Three tunnel-like structures in S7-xyl were identified and simultaneously reshaped through multi-sites saturated mutagenesis; the most advantageous mutant 254RL1 (V207N/Q238S/W241R) exhibited 340% increase in specific activity compared to S7-xyl. Deconvolution analysis revealed that all three mutations contributed synergistically to the improved activity of 254RL1. Enzymatic characterization showed that larger end products were released in 254RL1, while substrate binding and structural stability were not changed. Dissection of the structural alterations revealed that both the tun_1 and tun_2 in 254RL1 have larger bottleneck radius and shorter length than those of S7-xyl, suggesting that these tunnel-like structures may function as products transportation pathways. Attributed to the improved catalytic efficiency, 254RL1 represents a superior accessory enzyme to enhance the hydrolysis efficiency of cellulase towards different pretreated lignocellulose materials. In addition, tunnel engineering strategy was also successfully applied to improve the catalytic activities of three other xylanases including xylanase NG27-xyl from Bacillus sp. strain NG-27, TSAA1-xyl from Geobacillus sp. TSAA1 and N165-xyl from Bacillus sp. N16-5, with 80%, 20% and 170% increase in specific activity, respectively.

Conclusions

This study represents a pilot study of engineering and functional verification of tunnel-like structures in enzymes catalyzing biopolymer. The specific activities of four xylanases with buried active sites were successfully improved by tunnel engineering. It is highly likely that tunnel reshaping can be used to engineer better biomass-degrading abilities in other lignocellulolytic enzymes with buried active sites.
A genomic survey of transposable elements in the choanoflagellate Salpingoeca rosetta reveals selection on codon usage
Authors: Southworth Jade , Grace C. Alastair , Marron Alan O. , Fatima Nazeefa , Carr Martin
Published: November 2019

Background

Unicellular species make up the majority of eukaryotic diversity, however most studies on transposable elements (TEs) have centred on multicellular host species. Such studies may have therefore provided a limited picture of how transposable elements evolve across eukaryotes. The choanoflagellates, as the sister group to Metazoa, are an important study group for investigating unicellular to multicellular transitions. A previous survey of the choanoflagellateMonosiga brevicollisrevealed the presence of only three families of LTR retrotransposons, all of which appeared to be active.Salpingoeca rosettais the second choanoflagellate to have its whole genome sequenced and provides further insight into the evolution and population biology of transposable elements in the closest relative of metazoans.

Results

Screening the genome revealed the presence of a minimum of 20 TE families. Seven of the annotated families are DNA transposons and the remaining 13 families are LTR retrotransposons. Evidence for two putative non-LTR retrotransposons was also uncovered, but full-length sequences could not be determined. Superfamily phylogenetic trees indicate that vertical inheritance and, in the case of one family, horizontal transfer have been involved in the evolution of the choanoflagellates TEs. Phylogenetic analyses of individual families highlight recent element activity in the genome, however six families did not show evidence of current transposition. The majority of families possess young insertions and the expression levels of TE genes vary by four orders of magnitude across families. In contrast to previous studies on TEs, the families present inS. rosettashow the signature of selection on codon usage, with families favouring codons that are adapted to the host translational machinery. Selection is stronger in LTR retrotransposons than DNA transposons, with highly expressed families showing stronger codon usage bias. Mutation pressure towards guanosine and cytosine also appears to contribute to TE codon usage.

Conclusions

S. rosettaincreases the known diversity of choanoflagellate TEs and the complement further highlights the role of horizontal gene transfer from prey species in choanoflagellate genome evolution. Unlike previously studied TEs, theS. rosettafamilies show evidence for selection on their codon usage, which is shown to act via translational efficiency and translational accuracy.
Clinical validation of the Lumipulse G cerebrospinal fluid assays for routine diagnosis of Alzheimer’s disease
Authors: Leitão Maria João , Silva-Spínola Anuschka , Santana Isabel , Olmedo Veronica , Nadal Alicia , Le Bastard Nathalie , Baldeiras Inês
Published: November 2019

Background

Ongoing efforts within the Alzheimer’s disease (AD) field have focused on improving the intra- and inter-laboratory variability for cerebrospinal fluid (CSF) biomarkers. Fully automated assays offer the possibility to eliminate sample manipulation steps and are expected to contribute to this improvement. Recently, fully automated chemiluminescence enzyme immunoassays for the quantification of all four AD biomarkers in CSF became available. The aims of this study were to (i) evaluate the analytical performance of the Lumipulse G β-Amyloid 1-42 (restandardized to Certified Reference Materials), β-Amyloid 1-40, total Tau, and pTau 181 assays on the fully automated LUMIPULSE G600II; (ii) compare CSF biomarker results of the Lumipulse G assays with the established manual ELISA assays (INNOTEST®) from the same company (Fujirebio); and (iii) establish cut-off values and the clinical performance of the Lumipulse G assays for AD diagnosis.

Methods

Intra- and inter-assay variation was assessed in CSF samples with low, medium, and high concentrations of each parameter. Method comparison and clinical evaluation were performed on 40 neurological controls (NC) and 80 patients with a diagnosis of probable AD supported by a follow-up ≥ 3 years and/or positive amyloid PET imaging. A small validation cohort of 10 NC and 20 AD patients was also included to validate the cut-off values obtained on the training cohort.

Results

The maximal observed intra-assay and inter-assay coefficients of variation (CVs) were 3.25% and 5.50%, respectively. Method comparisons revealed correlation coefficients ranging from 0.89 (for Aβ40) to 0.98 (for t-Tau), with those for Aβ42 (0.93) and p-Tau (0.94) in-between. ROC curve analysis showed area under the curve values consistently above 0.85 for individual biomarkers other than Aβ40, and with the Aβ42/40, Aβ42/t-Tau, and Aβ42/p-Tau ratios outperforming Aβ42. Validation of the cut-off values in the independent cohort showed a sensitivity ranging from 75 to 95% and a specificity of 100%. The overall percentage of agreement between Lumipulse and INNOTEST was very high (> 87.5%).

Conclusions

The Lumipulse G assays show a very good analytical performance that makes them well-suited for CSF clinical routine measurements. The good clinical concordance between the Lumipulse G and INNOTEST assays facilitates the implementation of the new method in routine practice.
Human astrovirus infection associated with encephalitis in an immunocompetent child: a case report
Authors: Koukou Georgia , Niendorf Sandra , Hornei Britt , Schlump Jan-U , Jenke Andreas C. , Jacobsen Sonja
Published: November 2019

Background

Until today, classic human astroviruses have not been associated with central nervous system infections in immunocompetent patients.

Case presentation

A 16-month-old Caucasian girl presented with repetitive generalized seizures with a 4-day history of watery diarrhea, which had already gradually improved. Initially, the prolonged seizures ceased after systemic midazolam treatment and were thought to be fever associated. However, her mental status remained altered, and after seizure recurrence, she was transferred to our pediatric intensive care unit. Seizure control was achieved by a combination of high-dose levetiracetam and phenobarbital, but she remained unconscious. An electroencephalogram at this time revealed generalized high voltage theta activity. All laboratory analyses, including extended blood and cerebrospinal fluid analyses, and a brain magnetic resonance imaging were normal.

On day 4, the child gradually became conscious, but was very agitated and not able to walk. Since an electroencephalogram at this time still revealed generalized high voltage theta activity, although she had not received sedative medications for 72 hours, she was diagnosed as having encephalopathy. At that time, results of diagnostic testing of the stool sample were positive for classic astrovirus infection, and we decided to analyze the initially obtained cerebrospinal fluid for astrovirus as well. Cerebrospinal fluid was also found positive for human astrovirus. Sequencing analysis revealed a classic astrovirus genotype 1 with exactly the same nucleotide sequence as in the feces. Clinically, the child gradually improved and was discharged on day 9.

Conclusions

Whereas the new human astrovirus subtypes have been recently associated with central nervous system infection, this is the first case of encephalitis in an immunocompetent child due to classic human astrovirus. Considering that classic human astroviruses are the third most common etiological agents of viral gastroenteritis in children, we believe that human astroviruses as causative agents for central nervous system infections should be considered more often, especially in children and infants with preceding gastroenteritis.
Two functional variants at 6p21.1 were associated with lean mass
Authors: Pei Yu-Fang , Hu Wen-Zhu , Yang Xiao-Lin , Wei Xin-Tong , Feng Gui-Juan , Zhang Hong , Shen Hui , Tian Qing , Deng Hong-Wen , Zhang Lei
Published: November 2019

Background

Low lean body mass is the most important predictor of sarcopenia with strong genetic background. The aim of this study was to uncover genetic factors underlying lean mass development.

Materials and methods

We performed a genome-wide association study (GWAS) of fat-adjusted leg lean mass in the Framingham Heart Study (FHS,N = 6587), and replicated in the Women’s Health Initiative–African American sub-sample (WHI-AA,N = 847) and the Kansas City Osteoporosis Study (KCOS,N = 2219). We also cross-validated significant variants in the publicly available body mass index (BMI) summary results (N~ 700,000). We then performed a series of functional investigations on the identified variants.

Results

Four correlated SNPs at 6p21.1 were identified at the genome-wide significance (GWS,α = 5.0 × 10−8) level in the discovery FHS sample (rs551145, rs524533, rs571770, and rs545970,p = 3.40–9.77 × 10−9), and were successfully replicated in both the WHI-AA and the KCOS samples (one-sidedp = 1.61 × 10−3–0.04). They were further cross-validated by the large-scale BMI summary results (p = 7.0–9.8 × 10−3). Cis-eQTL analyses associated these SNPs with theNFKBIEgene expression. Electrophoresis mobility shift assay (EMSA) in mouse C2C12 myoblast cells implied that rs524533 and rs571770 were bound to an unknown transcription factor in an allelic specific manner, while rs551145 and rs545970 did not. Dual-luciferase reporter assay revealed that both rs524533 and rs571770 downregulated luciferase expression by repressing promoter activity. Moreover, the regulation pattern was allelic specific, strengthening the evidence towards their differential regulatory effects.

Conclusions

Through a large-scale GWAS followed by a series of functional investigations, we identified 2 correlated functional variants at 6p21.1 associated with leg lean mass. Our findings not only enhanced our understanding of molecular basis of lean mass development but also provided useful candidate genes for further functional studies.
Implementation strategies to improve preconception and antenatal care for tobacco smoking, alcohol consumption and weight management: a systematic review protocol
Authors: Doherty Emma , Kingsland Melanie , Wolfenden Luke , Wiggers John , Dray Julia , Hollis Jenna , Elliott Elizabeth J. , Daly Justine B. , Bailey Kylie A. , Attia John , Hunter Mandy , Symonds Ian , Tully Belinda , Tremain Danika , Hodder Rebecca K.
Published: November 2019

Background

Despite existing best practice care recommendations for addressing tobacco smoking, alcohol consumption and weight management in preconception and antenatal care, such recommendations are often not implemented into routine practice. Effective strategies that target known barriers to implementation are key to reducing this evidence to practice gap. The aim of this review is to synthesise the evidence on the effectiveness of implementation strategies in improving the provision of preconception and antenatal care for these modifiable risk factors.

Methods

Randomised and non-randomised study designs will be eligible for inclusion if they have a parallel control group. We will include studies that either compare an implementation strategy to usual practice or compare two or more strategies. Participants may include any health service providing preconception or antenatal care to women and/or the health professionals working within such a service. The primary outcome will be any measure of the effectiveness of implementation strategies to improve preconception and/or antenatal care for tobacco smoking, alcohol consumption and/or weight management (including care to improve nutrition and/or physical activity). Secondary outcomes will include the effect of the implementation strategy on women’s modifiable risk factors, estimates of absolute costs or cost-effectiveness and any reported unintentional consequences. Eligible studies will be identified via searching Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE, Maternity and Infant Care, CINAHL, ProQuest Dissertations and Theses and other sources (e.g. contacting experts in the field). Study selection, data extraction and risk of bias will be assessed independently by two review authors and differences resolved by a third reviewer. If data permits, we will conduct fixed-effects or random-effects meta-analysis where appropriate. If studies do not report the same outcome or there is significant heterogeneity, results will be summarised narratively.

Discussion

This review will identify which implementation strategies are effective in improving the routine provision of preconception and antenatal care for tobacco smoking, alcohol consumption and weight management. Such a review will be of interest to service providers, policy makers and implementation researchers seeking to improve women’s modifiable risk factors in preconception and antenatal care settings.

Systematic review registration

PROSPERO CRD42019131691
We Can Quit2 (WCQ2): a community-based intervention on smoking cessation for women living in disadvantaged areas of Ireland—study protocol for a pilot cluster randomised controlled trial
Authors: Hayes Catherine , Ciblis Aurelia , Darker Catherine , Dougall Nadine , Vance Joanne , O’Connell Nicola , Dobbie Fiona , Loudon Kirsty , Burke Emma , Devane Declan , Bauld Linda
Published: November 2019

Background

Tobacco use is the leading cause of preventable death in Ireland with almost 6000 smokers dying each year from smoking-related diseases. The ‘We Can Quit2’ (WCQ2) study is a pilot pragmatic two-arm, parallel-group, cluster randomised trial that aims to explore the feasibility and acceptability of trial processes including recruitment and to estimate parameters to inform sample size estimates needed for an effectiveness trial. This future trial will assess the effectiveness of a community-based smoking cessation intervention for women living in disadvantaged areas on short- and medium-term cessation rates.

Methods/design

Four matched pairs of districts (eight clusters) selected by area level of deprivation, geographical proximity, and eligibility for free medical services will be randomised to receive either WCQ (behavioural support + access to Nicotine Replacement Therapy (NRT)) delivered over 12 weeks by trained Community Facilitators (CFs) or to a form of usual care, a one-to-one smoking cessation service delivered by Smoking Cessation Officers from Ireland’s national health service, the Health Service Executive (HSE). Within each cluster, 24–25 women will be recruited (97 per arm; 194 in total) in 4 phases with consent obtained prior to cluster randomisation. The outcome measures will assess feasibility and acceptability of trial processes, including randomisation. Outcome data for a future definitive intervention (biochemically validated smoking abstinence) will be collected at end of programme (12 weeks) and at 6 months. WCQ2 has an embedded process evaluation using both qualitative and quantitative methods. This will be conducted (semi-structured client and CF interviews, intervention delivery checklist, and diary) to explore acceptability of trial processes, intervention fidelity, trial context, and implementation. Trial processes will be assessed against domains of the PRECIS-2 wheel to inform a future definitive trial design.

Discussion

Data from this pilot trial will inform the design and sample size for a full cluster randomised trial to determine the effectiveness of an intervention tailored to disadvantaged women in improving smoking cessation rates. It will provide transferable learning on the systems and implementation strategies needed to support effective design of future pragmatic community-based trials which address health promotion interventions for women in disadvantaged communities.

Trial registration

Concurrent to publication. Controlled trials ISRCTN74721694.
The Optimal Cut-off of BIPSS in Differential Diagnosis of ACTH-dependent Cushing’s Syndrome: Is Stimulation Necessary?
Authors: Chen Shi , Chen Kang , Wang Shirui , Zhu Huijuan , Lu Lin , Zhang Xiaobo , Tong Anli , Pan Hui , Wang Renzhi , Lu Zhaolin
Published: November 2019

Contexts

Bilateral inferior petrosal sinus sampling (BIPSS) can differentiate Cushing’s disease (CD) and ectopic adrenocorticotropin (ACTH) syndrome (EAS). The traditional cutoff of inferior petrosal sinus to peripheral (IPS:P) ACTH gradient was 2 before stimulation and 3 after stimulation, which yielded unsatisfactory sensitivity in some studies.

Objectives

To determine the optimal cutoff in BIPSS before or after desmopressin stimulation and to evaluate the necessity of stimulation.

Design and Setting

Single-center retrospective study (2011–2018) along with meta-analysis.

Patients

226 CD and 24 EAS patients with confirmed diagnosis who underwent BIPSS with desmopressin stimulation.

Results

In the meta-analysis of 25 studies with 1249 CD and 152 EAS patients, the traditional cutoff yielded sensitivity of 86% and 97% and specificity of 98% and 100% before and after stimulation, respectively. We then analyzed the data from our center. With the traditional cutoff, the sensitivity was 87.2% (197/226) and 96.5% (218/226) before and after stimulation, and specificity was both 100% (25/25), which were close to the results of meta-analysis. Receiver operating characteristic analysis revealed that the optimal cutoff was 1.4 before stimulation and 2.8 after stimulation. With the new cutoff, the sensitivity was 94.7% (214/226) and 97.8% (221/226) while the specificity remained 100% (25/25) before and after stimulation. Among the 7 CD patients (7/226; 3.1%) for whom stimulation was necessary to get correct diagnosis, none has a pituitary lesion >6 mm by magnetic resonance imaging, and their sampling lateralization rate (P = .007) and peak ACTH level at dominant inferior petrosal sinus (P = .011) were lower than those among CD patients with IPS:P >1.4 before stimulation.

Conclusions

The optimal cutoff for IPS:P in BIPSS is different from the commonly-used one. The optimal cutoff value can yield satisfactory accuracy even without stimulation, and stimulation may be unnecessary for those with pituitary adenoma >6 mm.
Gnrh3 Regulates PGC Proliferation and Sex Differentiation in Developing Zebrafish
Authors: Feng Ke , Cui Xuefan , Song Yanlong , Tao Binbin , Chen Ji , Wang Jing , Liu Shaojun , Sun Yonghua , Zhu Zuoyan , Trudeau Vance L , Hu Wei
Published: November 2019

Gonadotropin-releasing hormone (Gnrh) plays important roles in reproduction by stimulating luteinizing hormone release, and subsequently ovulation and sperm release, ultimately controlling reproduction in many species. Here we report on a new role for this decapeptide. Surprisingly, Gnrh3-null zebrafish generated by CRISPR/Cas9 exhibited a male-biased sex ratio. After the dome stage, the number of primordial germ cells (PGCs) in gnrh3-/- fish was lower than that in wild-type, an effect that was partially rescued by gnrh3 overexpression. A terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) analysis revealed no detectable apoptosis of PGCs in gnrh3-/- embryos. Proliferating PGCs could be detected in wild-type embryos, while there was no detectable signal in gnrh3-/- embryos. Compared with wild type, the phosphorylation of AKT was not significantly different in gnrh3-/- embryos, but the phosphorylation of ERK1/2 decreased significantly. Treatment with a Gnrh analog (Alarelin) induced ERK1/2 phosphorylation and increased PGC numbers in both wild-type and gnrh3-/- embryos, and this was blocked by the MEK inhibitor PD0325901. The relative expression of sox9a, amh, and cyp11b were significantly upregulated, while cyp19a1a was significantly downregulated at 18 days post-fertilization in gnrh3-/- zebrafish. Taken together, these results indicate that Gnrh3 plays an important role in early sex differentiation by regulating the proliferation of PGCs through a MAPK-dependent path.