bluuebunny/crossref_metadata_2025 huggingface dataset:
The relationship between physical activity, mental wellbeing and symptoms of mental health disorder in adolescents: a cohort study
Authors: Bell Sarah Louise , Audrey Suzanne , Gunnell David , Cooper Ashley , Campbell Rona
Published: December 2019

Background

Mental illness is a worldwide public health concern. In the UK, there is a high prevalence of mental illness and poor mental wellbeing among young people. The aim of this study was to investigate whether physical activity is associated with better mental wellbeing and reduced symptoms of mental health disorder in adolescents.

Methods

A cohort of 928 12–13 year olds (Year 8) from six secondary schools in England, who had participated in the AHEAD trial, ‘Activity and Healthy Eating in Adolescence’, were followed up three years later (when 15–16 years old, Year 11). At baseline, physical activity was measured using accelerometers. At follow-up, mental wellbeing was measured using the ‘Warwick Edinburgh Mental Wellbeing Scale’ (WEMWBS) and symptoms of mental health disorder using the ‘Strengths and Difficulties Questionnaire’ (SDQ). Multivariable linear regression analyses were used to investigate associations between physical activity and both mental wellbeing and symptoms of mental health disorder.

Results

794 (86%) of the eligible 928 young people provided valid accelerometer data at baseline. 668 (72%) provided complete mental wellbeing data and 673 (73%) provided complete symptoms of mental health disorder data at follow-up. The multivariable analyses showed no evidence of an association between physical activity volume (counts per minute (cpm)) or intensity (Moderate to Vigorous Physical Activity (MVPA)) and mental wellbeing (WEMWBS overall score) or overall symptoms of mental health disorder (SDQ Total Difficulties Score). However, higher levels of physical activity volume at age 12–13 years were associated with lower scores on the emotional problems subscale of the SDQ at age 15–16 years.

Conclusions

This cohort study found no strong evidence that physical activity is associated with better mental wellbeing or reduced symptoms of mental health disorder in adolescents. However, a protective association between physical activity and the emotional problems subscale of the SDQ was found. This suggests that physical activity has the potential to reduce symptoms of depression and anxiety in adolescents. Future cohort study designs should allow for repeated measures to fully explore the temporal nature of any relationship.
Palmitoylethanolamide counteracts substance P-induced mast cell activation in vitro by stimulating diacylglycerol lipase activity
Authors: Petrosino Stefania , Schiano Moriello Aniello , Verde Roberta , Allarà Marco , Imperatore Roberta , Ligresti Alessia , Mahmoud Ali Mokhtar , Peritore Alessio Filippo , Iannotti Fabio Arturo , Di Marzo Vincenzo
Published: December 2019

Background

Palmitoylethanolamide (PEA) is a pleiotropic endogenous lipid mediator currently used as a “dietary food for special medical purposes” against neuropathic pain and neuro-inflammatory conditions. Several mechanisms underlie PEA actions, among which the “entourage” effect, consisting of PEA potentiation of endocannabinoid signaling at either cannabinoid receptors or transient receptor potential vanilloid type-1 (TRPV1) channels. Here, we report novel molecular mechanisms through which PEA controls mast cell degranulation and substance P (SP)-induced histamine release in rat basophilic leukemia (RBL-2H3) cells, a mast cell model.

Methods

RBL-2H3 cells stimulated with SP were treated with PEA in the presence and absence of a cannabinoid type-2 (CB2) receptor antagonist (AM630), or a diacylglycerol lipase (DAGL) enzyme inhibitor (OMDM188) to inhibit the biosynthesis of the endocannabinoid 2-arachidonoylglycerol (2-AG). The release of histamine was measured by ELISA and β-hexosaminidase release and toluidine blue staining were used as indices of degranulation. 2-AG levels were measured by LC-MS. The mRNA expression of proposed PEA targets (Cnr1, Cnr2, Trpv1, Ppara and Gpr55), and of PEA and endocannabinoid biosynthetic (Napepld, Dagla and Daglb) and catabolic (Faah, Naaa and Mgl) enzymes were also measured. The effects of PEA on the activity of DAGL-α or -β enzymes were assessed in COS-7 cells overexpressing the human recombinant enzyme or in RBL-2H3 cells, respectively.

Results

SP increased the number of degranulated RBL-2H3 cells and triggered the release of histamine. PEA counteracted these effects in a manner antagonized by AM630. PEA concomitantly increased the levels of 2-AG in SP-stimulated RBL-2H3 cells, and this effect was reversed by OMDM188. PEA significantly stimulated DAGL-α and -β activity and, consequently, 2-AG biosynthesis in cell-free systems. Co-treatment with PEA and 2-AG at per se ineffective concentrations downmodulated SP-induced release of histamine and degranulation, and this effect was reversed by OMDM188.

Conclusions

Activation of CB2 underlies the inhibitory effects on SP-induced RBL-2H3 cell degranulation by PEA alone. We demonstrate for the first time that the effects in RBL-2H3 cells of PEA are due to the stimulation of 2-AG biosynthesis by DAGLs.
Increased gait variability during robot-assisted walking is accompanied by increased sensorimotor brain activity in healthy people
Authors: Berger Alisa , Horst Fabian , Steinberg Fabian , Thomas Fabian , Müller-Eising Claudia , Schöllhorn Wolfgang I. , Doppelmayr Michael
Published: December 2019

Background

Gait disorders are major symptoms of neurological diseases affecting the quality of life. Interventions that restore walking and allow patients to maintain safe and independent mobility are essential. Robot-assisted gait training (RAGT) proved to be a promising treatment for restoring and improving the ability to walk. Due to heterogenuous study designs and fragmentary knowlegde about the neural correlates associated with RAGT and the relation to motor recovery, guidelines for an individually optimized therapy can hardly be derived. To optimize robotic rehabilitation, it is crucial to understand how robotic assistance affect locomotor control and its underlying brain activity. Thus, this study aimed to investigate the effects of robotic assistance (RA) during treadmill walking (TW) on cortical activity and the relationship between RA-related changes of cortical activity and biomechanical gait characteristics.

Methods

Twelve healthy, right-handed volunteers (9 females; M = 25 ± 4 years) performed unassisted walking (UAW) and robot-assisted walking (RAW) trials on a treadmill, at 2.8 km/h, in a randomized, within-subject design. Ground reaction forces (GRFs) provided information regarding the individual gait patterns, while brain activity was examined by measuring cerebral hemodynamic changes in brain regions associated with the cortical locomotor network, including the sensorimotor cortex (SMC), premotor cortex (PMC) and supplementary motor area (SMA), using functional near-infrared spectroscopy (fNIRS).

Results

A statistically significant increase in brain activity was observed in the SMC compared with the PMC and SMA (p < 0.05), and a classical double bump in the vertical GRF was observed during both UAW and RAW throughout the stance phase. However, intraindividual gait variability increased significantly with RA and was correlated with increased brain activity in the SMC (p = 0.05; r = 0.57).

Conclusions

On the one hand, robotic guidance could generate sensory feedback that promotes active participation, leading to increased gait variability and somatosensory brain activity. On the other hand, changes in brain activity and biomechanical gait characteristics may also be due to the sensory feedback of the robot, which disrupts the cortical network of automated walking in healthy individuals. More comprehensive neurophysiological studies both in laboratory and in clinical settings are necessary to investigate the entire brain network associated with RAW.
Genetic perturbations of disease risk genes in mice capture transcriptomic signatures of late-onset Alzheimer’s disease
Authors: Pandey Ravi S. , Graham Leah , Uyar Asli , Preuss Christoph , Howell Gareth R. , Carter Gregory W.
Published: December 2019

Background

New genetic and genomic resources have identified multiple genetic risk factors for late-onset Alzheimer’s disease (LOAD) and characterized this common dementia at the molecular level. Experimental studies in model organisms can validate these associations and elucidate the links between specific genetic factors and transcriptomic signatures. Animal models based on LOAD-associated genes can potentially connect common genetic variation with LOAD transcriptomes, thereby providing novel insights into basic biological mechanisms underlying the disease.

Methods

We performed RNA-Seq on whole brain samples from a panel of six-month-old female mice, each carrying one of the following mutations: homozygous deletions of Apoe and Clu; hemizygous deletions of Bin1 and Cd2ap; and a transgenic APOEε4. Similar data from a transgenic APP/PS1 model was included for comparison to early-onset variant effects. Weighted gene co-expression network analysis (WGCNA) was used to identify modules of correlated genes and each module was tested for differential expression by strain. We then compared mouse modules with human postmortem brain modules from the Accelerating Medicine’s Partnership for AD (AMP-AD) to determine the LOAD-related processes affected by each genetic risk factor.

Results

Mouse modules were significantly enriched in multiple AD-related processes, including immune response, inflammation, lipid processing, endocytosis, and synaptic cell function. WGCNA modules were significantly associated with Apoe−/−, APOEε4, Clu−/−, and APP/PS1 mouse models. Apoe−/−, GFAP-driven APOEε4, and APP/PS1 driven modules overlapped with AMP-AD inflammation and microglial modules; Clu−/− driven modules overlapped with synaptic modules; and APP/PS1 modules separately overlapped with lipid-processing and metabolism modules.

Conclusions

This study of genetic mouse models provides a basis to dissect the role of AD risk genes in relevant AD pathologies. We determined that different genetic perturbations affect different molecular mechanisms comprising AD, and mapped specific effects to each risk gene. Our approach provides a platform for further exploration into the causes and progression of AD by assessing animal models at different ages and/or with different combinations of LOAD risk variants.
Open-chest cardiopulmonary resuscitation versus closed-chest cardiopulmonary resuscitation in patients with cardiac arrest: a systematic review and meta-analysis
Authors: Wang Mao , Lu Xiaoguang , Gong Ping , Zhong Yilong , Gong Dianbo , Song Yi
Published: December 2019

Background

Cardiopulmonary resuscitation is the most urgent and critical step in the rescue of patients with cardiac arrest. However, only about 10% of patients with out-of-hospital cardiac arrest survive to discharge. Surprisingly, there is growing evidence that open-chest cardiopulmonary resuscitation is superior to closed-chest cardiopulmonary resuscitation. Meanwhile, The Western Trauma Association and The European Resuscitation Council encouraged thoracotomy in certain circumstances for trauma patients. But whether open-chest cardiopulmonary resuscitation is superior to closed-chest cardiopulmonary resuscitation remains undetermined. Therefore, the aim of this study was to summarize current studies on open-chest cardiopulmonary resuscitation in a systematic review, comparing it to closed-chest cardiopulmonary resuscitation, in a meta-analysis.

Methods

In this systematic review and meta-analysis, we searched the PubMed, EmBase, Web of Science, and Cochrane Library databases from inception to May 2019 investigating the effect of open-chest cardiopulmonary resuscitation and closed-chest cardiopulmonary resuscitation in patients with cardiac arrest, without language restrictions. Statistical analysis was performed using Stata 12.0 software. The primary outcome was return of spontaneous circulation. The secondary outcome was survival to discharge.

Results

Seven observational studies were eligible for inclusion in this meta-analysis involving 8548 patients. No comparative randomized clinical trial was reported in the literature. There was no significant difference in return of spontaneous circulation and survival to discharge between open-chest cardiopulmonary resuscitation and closed-chest cardiopulmonary resuscitation in cardiac arrest patients. The odds ratio (OR) were 0.92 (95%CI 0.36–2.31,P > 0.05) and 0.54 (95%CI 0.17–1.78,P > 0.05) for return of spontaneous circulation and survival to discharge, respectively. Subgroup analysis of cardiac arrest patients with trauma showed that closed-chest cardiopulmonary resuscitation was associated with higher return of spontaneous circulation compared with open-chest cardiopulmonary resuscitation (OR = 0.59 95%CI 0.37–0.94,P < 0.05). And subgroup analysis of cardiac arrest patients with non-trauma showed that open-chest cardiopulmonary resuscitation was associated with higher ROSC compared with closed-chest cardiopulmonary resuscitation (OR = 3.12 95%CI 1.23–7.91,P < 0.05).

Conclusions

In conclusion, for patients with cardiac arrest, we should implement closed-chest cardiopulmonary resuscitation as soon as possible. However, for cardiac arrest patients with chest trauma who cannot perform closed-chest cardiopulmonary resuscitation, open-chest cardiopulmonary resuscitation should be implemented as soon as possible.
Efficacy, safety, and cost-effectiveness analysis of adjuvant herbal medicine treatment, Palmijihwang-hwan, for chronic low back pain: a study protocol for randomized, controlled, assessor-blinded, multicenter clinical trial
Authors: Sung Won-Suk , Jeon Sae-Rom , Hong Ye-Jin , Kim Tae-Hun , Shin Seungwon , Lee Hyun-Jong , Seo Byung-Kwan , Park Yeon-Cheol , Kim Eun-Jung , Nam Dong-Woo
Published: December 2019

Background

Low back pain is a common symptom and continuous or recurrent pain results in chronic low back pain (CLBP). While many patients with CLBP have tried various treatments, complementary and alternative medicine including acupuncture and herbal medicine is one of the commonly used treatments. Palmijihwang-hwan is a herbal medicine used frequently in clinical practice but there has been no report of the efficacy, safety, or cost-effectiveness analysis of Palmijihwang-hwan for CLBP.

Methods

This study is a randomized, assessor-blinded, multicenter, clinical trial with two parallel groups. Four Korean medicine hospitals will recruit 84 participants and randomly allocate them into the control or treatment group in a 1:1 ratio. The control group will receive acupuncture treatment at 11 local and 4 distal acupuncture points for 20 min twice a week for 6 weeks. The treatment group will receive the same acupuncture treatment as the control group and also take Palmijihwang-hwan for 6 weeks. The primary outcome will be the change in visual analog scale (VAS) score between baseline (visit 1) and completion of the intervention (visit 12), and secondary outcomes will be pain-related clinical relevance (minimal clinical important difference or the proportion of the participants who decrease more than 30, or 50% on VAS), disability (Roland and Morris Disability Questionnaire), quality of life (EuroQol-5D), global assessment (Patient Global Impression of Change), and economic analysis (cost-effectiveness and cost-utility analysis). Additionally, safety will be assessed.

Discussion

The results of our study will provide the clinical evidence about the efficacy, safety, and cost-effectiveness analysis of Palmijihwang-hwan for CLBP. There will be a chance to provide multiple subdivided influence of this treatment with various outcome measures, but lack of placebo is our limitation.

Trial registration

Clinical Research Information Service, KCT0002998. Registered on 12 July 2018.
Two interventions to treat pain disorders and post-traumatic symptoms among Syrian refugees: protocol for a randomized controlled trial
Authors: Hasha Wegdan , Fadnes Lars T. , Igland Jannicke , Vårdal Rolf , Giusti Line Merete , Strømme Elisabeth Marie , Haj-Younes Jasmin , Heltne Unni , Kumar Bernadette N. , Diaz Esperanza
Published: December 2019

Background

There is a high prevalence of pain and post-traumatic symptoms among refugees and feasible interventions to manage these are needed. However, knowledge about the effect of physiotherapy and psychological group interventions among refugees is scarce. Our aim is to determine whether two different interventions, the Physiotherapy Activity and Awareness Intervention (PAAI) and Teaching Recovery Techniques (TRT), reduce pain and post-traumatic symptoms among refugees from Syria living in Norway.

Methods/design

Syrian adults with either pain disorders or post-traumatic symptoms, or both, will be recruited to this randomized control trial. The trial will include two separate interventions: participants with dominating pain symptoms will be assigned to the PAAI; and those with a predominance of post-traumatic symptoms will be assigned to the TRT intervention. Participants will be randomized to either the immediate intervention group or the delayed intervention group, for each of the interventions (PAAI and TRT). A minimum of 68 participants will be recruited for the PAAI and 78 participants for TRT, in order to detect clinically and statistically significant symptom improvement, assuming 25–30% attrition after recruitment. The main outcomes for the analyses will be pain intensity measured by the Brief Pain Inventory questionnaire and the scores of the Impact of Events Scale — Revised. The effect will be evaluated at the end of interventions lasting 8 weeks (PAAI) and 6 weeks (TRT) using the same instruments after the end of the intervention, and again 4–6 weeks later. Additionally, a qualitative evaluation will be conducted through an embedded process evaluation and personal interviews with participants after each of the interventions is finished.

Discussion

Our study will determine the feasibility of the implementation of two different interventions and the effect of these interventions among refugees from Syria with pain disorders and/or post-traumatic symptoms.

Trial registration

Clinical Trials.gov, NCT03951909. Retrospectively registered on 19 February 2019.
Age-specific diabetes risk by the number of metabolic syndrome components: a Korean nationwide cohort study
Authors: Lee Min-Kyung , Han Kyungdo , Kwon Hyuk-Sang
Published: December 2019

Background

Metabolic syndrome is associated with an increased risk of diabetes. This study investigated the associations between the number of metabolic syndrome components and diabetes risk by age, sex and BMI.

Methods

Data for 19,475,643 participants ≥ 20 years old with no history of diabetes were obtained between 2009 and 2012 and were accessed using the South Korean National Health Insurance Service. Metabolic syndrome was defined according to the modified criteria of the National Cholesterol Education Program Adult Treatment Panel III. We assessed the risk of diabetes according to the number of metabolic syndrome components after stratifying the study participants into groups by age (20–39, 46–64, ≥ 65 years), sex, and BMI (below or above 25).

Results

During an average of 5.13 years of follow-up, the incidence rates of diabetes increased with the number of metabolic syndrome components. Age and BMI gradually increased with the number of metabolic syndrome components. The multivariable-adjusted hazard ratios (HRs) for incident diabetes were 1.401, 1.862, 2.47, 3.164 and 4.501 for participants with one through five components, respectively, compared with those without metabolic syndrome components. The risk of diabetes was 1.79-, 2.18-, and 3.05-times higher for participants ≥ 65 years; 2.57-, 3.45-, and 5.18-times higher for participants 40–64 years; and 2.55-, 3.89-, and 6.31-times higher for participants 20–39 years of age with three through five components, respectively, compared to those with no components. There was no difference in the risk of diabetes between men and women. The HRs were 5.63 for participants with a BMI ≥ 25 and 3.98 for those with a BMI < 25 among individuals with five components.

Conclusions

The risk of diabetes was more strongly associated with the number of metabolic syndrome components among younger adults. In addition, the risk of diabetes across the number of metabolic syndrome components was greater in participants with a BMI ≥ 25.
Plasma amyloid assay as a pre-screening tool for amyloid positron emission tomography imaging in early stage Alzheimer’s disease
Authors: Lin Szu-Ying , Lin Kun-Ju , Lin Po-Chen , Huang Chin-Chang , Chang Chiung-Chih , Lee Yi-Chung , Hsiao Ing-Tsung , Yen Tzu-Chen , Huang Wen-Sheng , Yang Bang-Hung , Wang Pei-Ning
Published: December 2019

Introduction

Due to the high cost and high failure rate of ascertaining amyloid positron emission tomography positivity (PET+) in patients with earlier stage Alzheimer’s disease (AD), an effective pre-screening tool for amyloid PET scans is needed.

Methods

Patients with mild cognitive impairment (n = 33, 24.2% PET+, 42% females, age 74.4 ± 7.5, MMSE 26.8 ± 1.9) and mild dementia (n = 19, 63.6% PET+, 36.3% females, age 73.0 ± 9.3, MMSE 22.6 ± 2.0) were recruited. Amyloid PET imaging, Apolipoprotein E (APOE) genotyping, and plasma amyloid β (Aβ)1–40, Aβ1–42, and total tau protein quantification by immunomagnetic reduction (IMR) method were performed. Receiver operating characteristics (ROC) analysis and Youden’s index were performed to identify possible cut-off points, clinical sensitivities/specificities, and areas under the curve (AUCs).

Results

Amyloid PET+ participants had lower plasma Aβ1–42 levels than amyloid PET-negative (PET−) subjects. APOE ε4 carriers had higher plasma Aβ1–42 than non-carriers. We developed an algorithm involving the combination of plasma Aβ1–42 and APOE genotyping. The success rate for detecting amyloid PET+ patients effectively increased from 42.3 to 70.4% among clinically suspected MCI and mild dementia patients.

Conclusions

Our results demonstrate the possibility of utilizing APOE genotypes in combination with plasma Aβ1–42 levels as a pre-screening tool for predicting the positivity of amyloid PET findings in early stage dementia patients.
High occurrence of transportation and logistics occupations among vascular dementia patients: an observational study
Authors: van Loenhoud A. C. , de Boer C. , Wols K. , Pijnenburg Y. A. , Lemstra A. W. , Bouwman F. H. , Prins N. D. , Scheltens P. , Ossenkoppele R. , van der Flier W. M.
Published: December 2019

Background

Growing evidence suggests a role of occupation in the emergence and manifestation of dementia. Occupations are often defined by complexity level, although working environments and activities differ in several other important ways. We aimed to capture the multi-faceted nature of occupation through its measurement as a qualitative (instead of a quantitative) variable and explored its relationship with different types of dementia.

Methods

We collected occupational information of 2121 dementia patients with various suspected etiologies from the Amsterdam Dementia Cohort (age 67 ± 8, 57% male; MMSE 21 ± 5). Our final sample included individuals with Alzheimer’s disease (AD) dementia (n = 1467), frontotemporal dementia (n = 281), vascular dementia (n = 98), Lewy body disease (n = 174), and progressive supranuclear palsy/corticobasal degeneration (n = 101). Within the AD group, we used neuropsychological data to further characterize patients by clinical phenotypes. All participants were categorized into 1 of 11 occupational classes, across which we evaluated the distribution of dementia (sub)types with χ2 analyses. We gained further insight into occupation-dementia relationships through post hoc logistic regressions that included various demographic and health characteristics as explanatory variables.

Results

There were significant differences in the distribution of dementia types across occupation groups (χ2 = 85.87, p < .001). Vascular dementia was relatively common in the Transportation/Logistics sector, and higher vascular risk factors partly explained this relationship. AD occurred less in Transportation/Logistics and more in Health Care/Welfare occupations, which related to a higher/lower percentage of males. We found no relationships between occupational classes and clinical phenotypes of AD (χ2 = 53.65, n.s.).

Conclusions

Relationships between occupation and dementia seem to exist beyond the complexity level, which offers new opportunities for disease prevention and improvement of occupational health policy.
Gallbladder hemorrhage during orally administered edoxaban therapy: a case report
Authors: Itagaki Hideya , Katuhiko Suzuki
Published: December 2019

Background

Edoxaban is an orally administered anticoagulant treatment that is used in patients with cerebral infarction, venous thrombosis, or other conditions, with a reported incidence of gastrointestinal hemorrhage at approximately 1%. We encountered the rare case of a patient who developed a gallbladder hemorrhage after the administration of edoxaban.

Case presentation

An 86-year-old Japanese woman visited our gastrointestinal department due to the chief complaint of melena lasting for a week. Her medical history included hypertension and embolic cerebral infarction, and she was taking orally administered carvedilol (5 mg/day) and edoxaban (30 mg/day). Her palpebral conjunctiva was pale during a physical examination, indicating the possibility of anemia. Her blood test results confirmed severe anemia with red blood cells at 1.7 × 106/μL and hemoglobin at 4.7 g/dL. An upper gastrointestinal endoscopy revealed bile and fresh blood on the duodenal bulb and in more distal regions; hemobilia was suspected. A computed tomography scan on the ninth hospitalization day confirmed the hemobilia with a gallbladder fundus high-density signal. She was discharged on the 30th day of hospitalization with only fluid therapy and no progression of anemia. Moreover, she underwent a laparoscopic cholecystectomy 1 month after discharge, but the pathologist did not identify false aneurysms or neoplastic lesions. She has not been shown to develop anemia for 5 months after surgery.

Conclusions

Our case suggests that gallbladder hemorrhage needs to be considered a possible complication for patients on direct oral anticoagulants.
Economic burden of vertigo: a systematic review
Authors: Kovacs Eva , Wang Xiaoting , Grill Eva
Published: December 2019

Background

Vertigo, a highly prevalent disease, imposes a rising burden on the health care system, exacerbated by the ageing of the population; and further, contributes to a wide span of indirect burden due to reduced capacity to work or need of assistance in activities of daily living. The aim of this review was to summarise the evidence on the economic burden of vertigo.

Methods

All original studies published between 2008 and 2018 about the economic evaluation of peripheral or central vestibular vertigo in developed countries were considered eligible, unrestricted to setting, health care provider, or study type.

Results

The electronic search in three databases identified 154 studies from which 16 qualified for inclusion. All studies presented partial economic evaluation referring to a variety of vestibular vertigo including unspecified vertigo. Nine studies presented monetised cost results and seven studies reported health care utilization. Direct costs derived mainly from repeated and not well-targeted consultations at all levels of health care, excessive use of diagnostic imaging, and/or of emergency care. Considerable societal burden was caused by decreased productivity, mainly due to work absenteeism.

Conclusion

To the best of our knowledge, this is the first systematic review of the existing evidence of the economic burden of vertigo. The lack of conclusive evidence revealed apparent targets of future research. First, studies of diagnostics and therapies for vestibular disease should include cost-effectiveness considerations. Population-based studies of health services utilization should include simple vestibular assessments to get more reliable estimates of the burden of disease and associated costs on the level of the general population. Further, clinical and population-based registries that include patients with vestibular disease, should consider collecting long-term data of societal burden. Primary data collection should increasingly include assessment of health care utilization e.g. by linking their diagnoses and outcomes to routine data from health insurances.
Building a Group-Based Opioid Treatment (GBOT) blueprint: a qualitative study delineating GBOT implementation
Authors: Sokol Randi , Albanese Mark , Chew Aaronson , Early Jessica , Grossman Ellie , Roll David , Sawin Greg , Wu Dominic J. , Schuman-Olivier Zev
Published: December 2019

Background

Group-Based Opioid Treatment (GBOT) has recently emerged as a mechanism for treating patients with opioid use disorder (OUD) in the outpatient setting. However, the more practical “how to” components of successfully delivering GBOT has received little attention in the medical literature, potentially limiting its widespread implementation and utilization. Building on a previous case series, this paper delineates the key components to implementing GBOT by asking: (a) What are thecorecomponents to GBOT implementation, and how are they defined? (b) What are themalleablecomponents to GBOT implementation, and what conceptual framework should providers use in determining how to apply these components for effective delivery in their unique clinical environment?

Methods

To create a blueprint delineating GBOT implementation, we integrated findings from a previously conducted and separately published systematic review of existing GBOT studies, conducted additional literature review, reviewed best practice recommendations and policies related to GBOT and organizational frameworks for implementing health systems change. We triangulated this data with a qualitative thematic analysis from 5 individual interviews and 2 focus groups representing leaders from 5 different GBOT programs across our institution to identify the key components to GBOT implementation, distinguish “core” and “malleable” components, and provide a conceptual framework for considering various options for implementing the malleable components.

Results

We identified 6 core components to GBOT implementation that optimize clinical outcomes, comply with mandatory policies and regulations, ensure patient and staff safety, and promote sustainability in delivery. These included consistent group expectations, team-based approach to care, safe and confidential space, billing compliance, regular monitoring, and regular patient participation. We identified 14 malleable components and developed a novel conceptual framework that providers can apply when deciding how to employ each malleable component that considers empirical, theoretical and practical dimensions.

Conclusion

While further research on the effectiveness of GBOT and its individual implementation components is needed, the blueprint outlined here provides an initial framework to help office-based opioid treatment sites implement a successful GBOT approach and hence potentially serve as future study sites to establish efficacy of the model. This blueprint can also be used to continuously monitor how components of GBOT influence treatment outcomes, providing an empirical framework for the ongoing process of refining implementation strategies.
Total hip arthroplasty for intertrochanteric fracture fixation failure
Authors: Liu Liyun , Sun Yongqiang , Wang Linlin , Gao Qiankun , Li Ang , Wang Jialin , Gao Yanzheng
Published: December 2019

Background

Intertrochanteric fracture is a common fracture suffered by elderly patients. Total hip arthroplasty (THA) is regarded as a salvage operation to restore hip joint function after fixation failure, which remains somewhat controversial due to some clinical potential issues.

Methods

18 elderly patients (average age 70.3 years) each with intertrochanteric fracture fixation failure treated with THA between September 2013 and October 2016 were retrospectively analyzed. Internal fixation treatments involved 5 patients who had received proximal femoral nail anti-rotation, 7 who received locking proximal femur plates and 6 who received dynamic hip screws. All patients were treated with THA using biological acetabular prosthesis and hip arthroplasty (HA) coating skillet femoral prosthesis, with the greater trochanter fixed using wire or steel when necessary. Patients’ Harris scores pre- and post-treatment, SF-36 Health Questionnaire score and digital radiology (DR) were used for joint prostheses initial stability and survival evaluation.

Results

15 patients completed follow-up periods ranging between 19 and 54 months (mean 26.2 months; 1 patient died from a pulmonary embolism, 1 patient died from pulmonary heart disease 1 year after surgery and 1 patient withdrew for personal reasons). There were no joint infections, periprosthetic fractures or dislocations. The average Harris score increased significantly, from 32.68 ± 12.04 points before surgery to 91.08 ± 5.9 points at 24 months post-treatment. SF-36 scores were significantly increased.

Conclusion

THA as salvage treatment for failed internal fixation of intertrochanteric femoral fractures in elderly patients significantly reduced hip pain and restored joint function, and early clinical outcomes were satisfactory.
HIF1/2-exerted control over glycolytic gene expression is not functionally relevant for glycolysis in human leukemic stem/progenitor cells
Authors: Wierenga Albertus T. J. , Cunningham Alan , Erdem Ayşegül , Lopera Nuria Vilaplana , Brouwers-Vos Annet Z. , Pruis Maurien , Mulder André B. , Günther Ulrich L. , Martens Joost H. A. , Vellenga Edo , Schuringa Jan Jacob
Published: December 2019

Background

Hypoxia-inducible factors (HIF)1 and 2 are transcription factors that regulate the homeostatic response to low oxygen conditions. Since data related to the importance of HIF1 and 2 in hematopoietic stem and progenitors is conflicting, we investigated the chromatin binding profiles of HIF1 and HIF2 and linked that to transcriptional networks and the cellular metabolic state.

Methods

Genome-wide ChIPseq and ChIP-PCR experiments were performed to identify HIF1 and HIF2 binding sites in human acute myeloid leukemia (AML) cells and healthy CD34+ hematopoietic stem/progenitor cells. Transcriptome studies were performed to identify gene expression changes induced by hypoxia or by overexpression of oxygen-insensitive HIF1 and HIF2 mutants. Metabolism studies were performed by 1D-NMR, and glucose consumption and lactate production levels were determined by spectrophotometric enzyme assays. CRISPR-CAS9-mediated HIF1, HIF2, and ARNT−/− lines were generated to study the functional consequences upon loss of HIF signaling, in vitro and in vivo upon transplantation of knockout lines in xenograft mice.

Results

Genome-wide ChIP-seq and transcriptome studies revealed that overlapping HIF1- and HIF2-controlled loci were highly enriched for various processes including metabolism, particularly glucose metabolism, but also for chromatin organization, cellular response to stress and G protein-coupled receptor signaling. ChIP-qPCR validation studies confirmed that glycolysis-related genes but not genes related to the TCA cycle or glutaminolysis were controlled by both HIF1 and HIF2 in leukemic cell lines and primary AMLs, while in healthy human CD34+ cells these loci were predominantly controlled by HIF1 and not HIF2. However, and in contrast to our initial hypotheses, CRISPR/Cas9-mediated knockout of HIF signaling did not affect growth, internal metabolite concentrations, glucose consumption or lactate production under hypoxia, not even in vivo upon transplantation of knockout cells into xenograft mice.

Conclusion

These data indicate that, while HIFs exert control over glycolysis but not OxPHOS gene expression in human leukemic cells, this is not critically important for their metabolic state. In contrast, inhibition of BCR-ABL did impact on glucose consumption and lactate production regardless of the presence of HIFs. These data indicate that oncogene-mediated control over glycolysis can occur independently of hypoxic signaling modules.
Selection and screening strategies in directed evolution to improve protein stability
Authors: Ren Chang , Wen Xin , Mencius Jun , Quan Shu
Published: December 2019

Protein stability is not only fundamental for experimental, industrial, and therapeutic applications, but is also the baseline for evolving novel protein functions. For decades, stability engineering armed with directed evolution has continued its rapid development and inevitably poses challenges. Generally, in directed evolution, establishing a reliable link between a genotype and any interpretable phenotype is more challenging than diversifying genetic libraries. Consequently, we set forth in a small picture to emphasize the screening or selection techniques in protein stability-directed evolution to secure the link. For a more systematic review, two main branches of these techniques, namely cellular or cell-free display and stability biosensors, are expounded with informative examples.
Breast MRI and tumour biology predict axillary lymph node response to neoadjuvant chemotherapy for breast cancer
Authors: Al-Hattali Samia , Vinnicombe Sarah J. , Gowdh Nazleen Muhammad , Evans Andrew , Armstrong Sharon , Adamson Douglas , Purdie Colin A. , Macaskill E. Jane
Published: December 2019

Background

In patients who have had axillary nodal metastasis diagnosed prior to neoadjuvant chemotherapy for breast cancer, there is little consensus on how to manage the axilla subsequently. The aim of this study was to explore whether a combination of breast magnetic resonance imaging (MRI) assessed response and primary tumour pathology factors could identify a subset of patients that might be spared axillary node clearance.

Methods

A retrospective data analysis was performed of patients with core biopsy-proven axillary nodal metastasis prior to commencement of neoadjuvant chemotherapy (NAC) who had subsequent axillary node clearance (ANC) at definitive breast surgery. Breast tumour and axillary response at MRI before, during and on completion of NAC, core biopsy tumour grade, tumour type and immunophenotype were correlated with pathological response in the breast and the number of metastatic nodes in the ANC specimens.

Results

Of 87 consecutive patients with MRI at baseline, interim and after neoadjuvant chemotherapy who underwent ANC at time of breast surgery, 33 (38%) had no residual macrometastatic axillary disease, 28 (32%) had 1–2 metastatic nodes and 26 (30%) had more than 2 metastatic nodes. Factors that predicted axillary nodal complete response were MRI complete response in the breast (p < 0.0001), HER2 positivity (p = 0.02) and non-lobular tumour type (p = 0.015).

Conclusion

MRI assessment of breast tumour response to NAC and core biopsy factors are predictive of response in axillary nodes, and can be used to guide decision making regarding appropriate axillary surgery.
Time-modified OSEM algorithm for more robust assessment of left ventricular dyssynchrony with phase analysis in ECG-gated myocardial perfusion SPECT
Authors: Kortelainen Matti J. , Koivumäki Tuomas M. , Vauhkonen Marko J. , Hakulinen Mikko A.
Published: December 2019

Background

In ordered subsets expectation maximization (OSEM) reconstruction of electrocardiography (ECG)-gated myocardial perfusion single-photon emission computed tomography (SPECT), it is often assumed that the image acquisition time is constant for each projection angle and ECG bin. Due to heart rate variability (HRV), this assumption may lead to errors in quantification of left ventricular mechanical dyssynchrony with phase analysis. We hypothesize that a time-modified OSEM (TOSEM) algorithm provides more robust results.

Methods

List-mode data of 44 patients were acquired with a dual-detector SPECT/CT system and binned to eight ECG bins. First, activity ratio (AR)—the ratio of total activity in the last OSEM-reconstructed ECG bin and first five ECG bins—was computed, as well as standard deviation SDR-R of the accepted R–R intervals; their association was evaluated with Pearson correlation analysis. Subsequently, patients whose AR was higher than 90% were selected, and their list-mode data were rebinned by omitting a part of the acquired counts to yield AR values of 90%, 80%, 70%, 60% and 50%. These data sets were reconstructed with OSEM and TOSEM algorithms, and phase analysis was performed. Reliability of both algorithms was assessed by computing concordance correlation coefficients (CCCs) between the 90% data and data corresponding to lower AR values. Finally, phase analysis results assessed from OSEM- and TOSEM-reconstructed images were compared.

Results

A strong negative correlation (r = -0.749) was found between SDR-R and AR. As AR decreased, phase analysis parameters obtained from OSEM images decreased significantly. On the contrary, reduction of AR had no significant effect on phase analysis parameters obtained from TOSEM images (CCC > 0.88). The magnitude of difference between OSEM and TOSEM results increased as AR decreased.

Conclusions

TOSEM algorithm minimizes the HRV-related error and can be used to provide more robust phase analysis results.
Correction to: Reduced microbial potential for the degradation of phenolic compounds in the rhizosphere of apple plantlets grown in soils affected by replant disease
Authors: Radl Viviane , Winkler Jana Barbro , Kublik Susanne , Yang Luhua , Winkelmann Traud , Vestergaard Gisle , Schröder Peter , Schloter Michael
Published: December 2019

Following publication of the original article [1], the authors advised that their article had published with an error in the title.
Effect of duration from lingual nerve injury to undergoing microneurosurgery on improving sensory and taste functions: retrospective study
Authors: Nakanishi Takashi , Yamamoto Yuta , Tanioka Kensuke , Shintani Yukari , Tojyo Itaru , Fujita Shigeyuki
Published: December 2019

Background

The prognosis of recovery following microneurosurgery for injured lingual nerves varies among individual cases. This study aimed to investigate if recovery ratios of sensory and taste functions are improved by the microneurosurgery within 6 months after lingual nerve injury.

Methods

We retrospectively assessed 70 patients who underwent microneurosurgery at the Wakayama Medical University Hospital for lingual nerve injuries between July 2004 and December 2016. Sensory and taste functions in lingual nerves were preoperatively evaluated using a static two-point discrimination test, an intact superficial pain/tactile sensation test, and a taste discrimination test. They were evaluated again at 12 and at 24 months postoperatively. The abundance ratio of Schwann cells in the excised traumatic neuromas was analyzed with ImageJ software following immunohistochemistry with anti S-100β antibody.

Results

In early cases (microneurosurgery within 6 months after the injury), recovery ratios of sensory and taste functions were not significantly different at 24 months after microneurosurgery compared with later cases (microneurosurgery more than 6 months after the injury). Meanwhile, the ratio of patients with taste recovery within 12 months after microneurosurgery was significantly decreased in late cases compared with early cases. The abundance ratio of Schwann cells in traumatic neuroma was also significantly lower in later cases.

Conclusion

Microneurosurgery more than 6 months after lingual nerve injury did not lead to decreased recovery ratio of sensory and taste functions, but it did lead to prolonged recovery of taste. This delay may be associated with a decrease in the abundance ratio of Schwann cells in traumatic neuromas.
Isolation and selection of highly effective phosphate solubilizing bacterial strains to promote wheat growth in Egyptian calcareous soils
Authors: Mohamed Abdallah E. , Nessim Maher Georg , Abou-el-seoud Islam Ibrahim , Darwish Khaled Mohamed , Shamseldin Abdelaal
Published: December 2019

Background

Forty phosphate solubilizing bacterial (PSB) isolates were isolated from the root zone of wheat plants cultivated in the Delta and the Northwestern coast regions of Egypt. All isolates proofed their ability to dissolve tricalcium phosphate on the National Botanical Research Institute's phosphate growth medium (NBRIP) by producing clear zone and increasing the available phosphorus that ranged between 40 and 707 mg l−1. They were designated as Egyptian native phosphate solubilizing bacteria (ENPSB).

Results

All strains proofed their ability to dissolve tricalcium phosphate on (NBRIP) medium by producing clear zone and increasing the available phosphorus that ranged between 40 and 707 mg l−1. The ENPSB 1, 2, and 3 strains were highly efficient as they gave 707, 653, and 693 mg l−1 soluble phosphorus respectively. Intriguingly, the two highly efficient strains for phosphate solubilization were isolated from the Northwestern coast alkaline soils. Moreover, 75% of strains were also produced profitable amounts of indole acetic acid (IAA) ranged from 0.79 to 50.5 mg l−1. Amazingly, the most efficient strain ENPSB 1 in solubilizing phosphorus (707 mg l−1soluble P) was the best one for producing IAA (50.5 mg l−1). The three efficient strains were identified using the sequencing of 16S rRNA. Sequence analysis of 16S rRNA for selected strains confirmed that the strains ENPSB 1, 2, and 3 were genetically closed to Enterobacter aerogenes; Pantoea sp. and Enteriobacter sp. respectively.

Conclusion

The inoculation by mix cultures of strains (ENPSB 1, 2, and 3) contributed to raising the dry weight and P content of wheat plants by 76% and 12% over the full fertilized plants. Inoculation of soil PSB can be used to solve the deficiency of phosphorus and promote plant growth effectively in calcareous soils.
Lower limb muscle strength and serotonin receptor gene polymorphism as factors associated in women with fibromyalgia
Authors: de Lima Luana Oliveira , Zicarelli Carlos Alexandre Martins , Matsumura Andressa Saori , Moroti-Perugini Layse Rafaela , de Castro Teixeira Denilson , Fernandes Karen Barros Parron , de Oliveira Perrucini Priscila Daniele , Poli-Frederico Regina Célia
Published: December 2019

Background

Fibromyalgia (FM) is a chronic pain syndrome characterized by generalized skeletal muscle chronic pain. Its etiology is not well defined, because there are several factors that may trigger it such as physical and/or emotional stresses, or a genetic susceptibility, involving serotonergic, dopaminergic and catecholaminergic paths. The objective of this study was to investigate the association between the strength of the lower limb, genetic polymorphism of the serotonin receptor gene HTR2A in women with fibromyalgia.

Methods

In this observational study of case-control type 48 women were evaluated who belonged to the group with FM (52 ± 12 years) and 100 women in the control group (58 ± 11 years). Socio demographic and anthropometric data were collected and peripheral blood samples for DNA extraction; genotypic analyzes were performed by means of PCR in real time by TaqMan® system. The lower limb muscle strength was assessed through the test of sitting down and standing up for 30 s. The chi-square test or Fischer Exact was used for possible associations among the variables; the t-test for independent samples was used to compare the averages among the groups; the value of significance adopted was 5%.

Results

There was an association between the polymorphism of the HTR2A gene with FM, demonstrating that carriers of the genotype GG have 24.39 times more likely to develop the syndrome (IC95% 5.15–115.47; p = 0.01). It was observed an association between FM and the test to sit and stand up demonstrating that women with fibromyalgia have lower limb muscle strength (p = 0.01). The study showed that the white race has 3.84 times more likely to develop FM (p = 0.01).

Conclusion

The results of this study suggest that women of Caucasian ethnicity with GG genotype or G allele presented greater risk of developing fibromyalgia and that these patients have lower limb muscle strength compared to the control group.