bluuebunny/crossref_metadata_2025 huggingface dataset:
Assessment of unintended volume loss of six closed system transfer devices
Authors: Kulju Stephen , McIntosh Bruce A , Fuller Helen JA , Arnold Tim , Gunnar William
Published: November 2019

Introduction

Closed system transfer devices (CSTDs) are used to prepare and administer hazardous drugs. Previous studies have explored the vapor and fluid containment performance of CSTDs. A less obvious consideration is the effect of CSTD use on the intended dose for small volume administrations. We assessed six CSTDs to determine if they contribute to volume loss and delivery of less than the intended dose during simulated drug administration.

Methods

Using an analytical balance, we obtained the mass of each CSTD at four points during simulated drug preparation and subcutaneous administration using sterile water. We used the masses to determine the average volume loss ( VL) for each CSTD.

Results

Using ANOVA, we identified significant differences in volume loss ( VL) among the mean VL (F(6,59) = 18.45, p = 6.19 × 10−12) for the six CSTDs and control (no CSTD). Four CSTDs had a VL that was statistically different than the control (p < 0.05); the VL for two CSTDs was not statistically different than the control (p > 0.05). Volume loss did not depend on administration volume.

Conclusion

Volume loss performance varied among CSTDs. Volume loss may be clinically significant for small volumes but is not likely clinically significant for larger volumes. It is the authors’ opinion that 3 mL represents a reasonable administration threshold below which volume loss should be considered clinically significant. Users should consider volume loss in context of the tasks, drugs, users, and environments where CSTDs will be used. The United States Pharmacopeia (USP) General Chapter <800>: Hazardous Drugs–Handling in Healthcare Settings recognizes the lack of CSTD performance standards. USP <800> recommends independent performance evaluation of CSTDs based on peer-reviewed studies. Our study adds to the comparative performance evaluations of CSTDs available on the market at the time of this review.
A castrate-resistant metastatic prostate cancer patient with severe pancytopenia, successfully treated with docetaxel chemotherapy
Authors: Kunthur Anuradha
Published: November 2019

Introduction

Prognosis of metastatic castrate-resistant prostate cancer is poor with a median survival of 12 to 36 months. Bone metastasis is common, and bone marrow metastasis occurs later in the disease course. The median survival in these patients after bone marrow involvement is less than six months. We report a case of castrate-resistant prostate cancer patient presented with severe pancytopenia due to bone marrow involvement of prostate cancer, treated successfully with docetaxel chemotherapy. Post chemotherapy, the patient became transfusion independent and prostate-specific antigen improved to 0.1 ng/ml from 1051 ng/ml.

Case report

A 70-year-old gentleman with a history of metastatic prostate cancer on androgen deprivation therapy and polycythemia vera presented to emergency room with dizziness and melena. Workup revealed severe pancytopenia with platelet count of 12k and hemoglobin of 4.5 gm/dl. Bone marrow biopsy confirmed diffuse involvement of bone marrow with prostate cancer. Prostate-specific antigen was 1051 gm/dl. Management and outcome: The patient received 14 units of packed red blood cell, 10 units of platelet transfusion within one week. Docetaxel chemotherapy was started along with thrombopoietin agonist romiplostim and pegylated filgrastim. He received five cycles of docetaxel treatment. Post chemotherapy, the patient became transfusion independent and prostate-specific antigen improved to 1.17 ng/ml from 1051 ng/ml. The patient is still alive one year after the presentation with good quality of life and the prostate-specific antigen further improved to 0.1 ng/dl.

Conclusion

This case suggests that selected patients with severe pancytopenia, due to bone marrow infiltration of prostate cancer, can be treated with docetaxel chemotherapy and romiplostim support with significant response. Docetaxel treatment may be beneficial to unpack the marrow and for quicker response in patients with good performance status.
Fatigue in multiple sclerosis is associated with multimodal interoceptive abnormalities
Authors: Gonzalez Campo Cecilia , Salamone Paula C , Rodríguez-Arriagada Nicolás , Richter Fabian , Herrera Eduar , Bruno Diana , Pagani Cassara Fátima , Sinay Vladimiro , García Adolfo M , Ibáñez Agustín , Sedeño Lucas
Published: November 2019

Background:

Fatigue ranks among the most common and disabling symptoms in multiple sclerosis (MS). Recent theoretical works have surmised that this trait might be related to alterations across interoceptive mechanisms. However, this hypothesis has not been empirically evaluated.

Objectives:

To determine whether fatigue in MS patients is associated with specific behavioral, structural, and functional disruptions of the interoceptive domain.

Methods:

Fatigue levels were established via the Modified Fatigue Impact Scale. Interoception was evaluated through a robust measure indexed by the heartbeat detection task. Structural and functional connectivity properties of key interoceptive hubs were tested by magnetic resonance imaging (MRI) and resting-state functional MRI. Machine learning analyses were employed to perform pairwise classifications.

Results:

Only patients with fatigue presented with decreased interoceptive accuracy alongside decreased gray matter volume and increased functional connectivity in core interoceptive regions, the insula, and the anterior cingulate cortex. Each of these alterations was positively associated with fatigue. Finally, machine-learning analysis with a combination of the above interoceptive indices (behavioral, structural, and functional) successfully discriminated (area under the curve > 90%) fatigued patients from both non-fatigued and healthy controls.

Conclusion:

This study offers unprecedented evidence suggesting that disruptions of neurocognitive markers subserving interoception may constitute a signature of fatigue in MS.
Cognitive processing speed in pediatric-onset multiple sclerosis: Baseline characteristics of impairment and prediction of decline
Authors: Wallach Asya I , Waltz Michael , Casper T Charles , Aaen Gregory , Belman Anita , Benson Leslie , Chitnis Tanuja , Gorman Mark , Graves Jennifer , Harris Yolanda , Lotze Timothy E , Mar Soe , Moodley Manikum , Ness Jayne M , Rensel Mary , Rodriguez Moses , Rose John W , Schreiner Teri , Tillema Jan-Mendelt , Waubant Emmanuelle , Weinstock-Guttman Bianca , Charvet Leigh E , Krupp; Lauren B
Published: November 2019

Background:

Cognitive impairment occurs in approximately one-third of pediatric-onset multiple sclerosis (POMS) patients. The Symbol Digit Modalities Test (SDMT), a widely used cognitive screen in adults, has yet to be incorporated early into the standard care of POMS.

Objective:

To screen for cognitive impairment early in the course of POMS and analyze predictive factors.

Methods:

Of the 955 POMS or clinically isolated syndrome (CIS) patients prospectively assessed from March 2014 to July 2018, 500 POMS and 116 CIS patients met inclusion criteria (disease onset before the age of 18, one or more SDMTs, and 8 years or older at the time of testing). Those with relapse were analyzed separately from those who were relapse-free.

Results:

At initial assessment, the mean (interquartile range (IQR)) age at symptom onset was 13.5 years (12.0, 15.9) and the mean (±SD) disease duration was 3.0 ± 2.9 years. Impaired processing speed occurred in 23.4% of POMS and in 16.4% of CIS. On serial testing ( n = 383, mean follow-up: 1.8 years), 14.1% had clinically meaningful decline predicted by older age of multiple sclerosis (MS) onset and male gender. Disease relapse or steroid use led to transient worsening on the SDMT.

Conclusion:

Early in the disease, some POMS and CIS patients are at risk for cognitive impairment and subsequent decline.
A cross-task comparison on visuospatial processing in autism spectrum disorders
Authors: Cardillo Ramona , Lanfranchi Silvia , Mammarella Irene C
Published: November 2019

This study aimed to draw a cross-task comparison on visuospatial processing in autism spectrum disorder without intellectual disability. Participants with autism spectrum disorder were matched with typically developing individuals on general intelligence and perceptual reasoning index. The two groups were subsequently compared on visuospatial processing speed, visuo-perceptual, visuo-constructive, and visuospatial working memory tasks. Our results revealed similar performances between autism spectrum disorder and typically developing individuals on measures of visuospatial processing speed and visuospatial working memory. The autism spectrum disorder group showed slower reaction times than the typically developing group in the visuo-perceptual task, when stimuli were characterized by a minimum level of perceptual cohesiveness, revealing weaker spatial integration abilities. Concerning the visuo-constructive domain, no differences between the autism spectrum disorder and the typically developing group emerged for the unsegmented condition, revealing that our participants with autism spectrum disorder were similar to the typically developing group in the local analysis of the stimuli. The discussion takes into account the role of individual differences on visuospatial intelligence, task requirements, and cognitive domains to clarify the visuospatial processing skills of individuals with autism spectrum disorder.
An open database for benchmarking guided waves structural health monitoring algorithms on a composite full-scale outer wing demonstrator
Authors: Marzani Alessandro , Testoni Nicola , De Marchi Luca , Messina Marco , Monaco Ernesto , Apicella Alfonso
Published: November 2019

This article reports on the creation of an open database of piezo-actuated and piezo-received guided wave signals propagating in a composite panel of a full-scale aeronautical structure. The composite panel closes the bottom part of a wingbox that, along with the leading edge, the trailing edge, and the wingtip, forms an outer wing demonstrator approximately 4.5 m long and from 1.2 to 2.3 m wide. To create the database, a structural health monitoring system, composed of a software/hardware central unit capable of controlling a network of 160 piezoelectric transducers secondarily bonded on the composite panel, has been realized. The structural health monitoring system has been designed to (1) perform electromechanical impedance measurement at each transducer, in order to check for their reliability and bonding strength, and (2) to operate an active guided wave screening for damage detection in the composite panel. Electromechanical impedance and guided wave measurements were performed at four different testing stages: before loading, before fatigue, before impacts, and after impacts. The database, freely available at http://shm.ing.unibo.it/ , can thus be used to benchmarking, on real-scale structural data, guided wave algorithms for loading, fatigue, as well as damage detection, characterization, and sizing. As an example, in this work, a delay and sum algorithm is applied on the post-impact data to illustrate how the database can be exploited.
Depenalization, diversion and decriminalization: A realist review and programme theory of alternatives to criminalization for simple drug possession
Authors: Stevens Alex , Hughes Caitlin Elizabeth , Hulme Shann , Cassidy Rebecca
Published: November 2019

Alternatives to criminalization for the simple possession of illicit drugs are increasingly of interest to policy makers. But there is no existing theoretically based, empirically tested framework that can inform development and evaluation. This article presents a realist programme theory of such alternatives. It bases this on a realist review, which followed the Realist and Meta-narrative Evidence Syntheses: Evolving Standards (RAMESES). It describes the systematic process of searching the literature in English on nine relevant countries (Australia, Czech Republic, Denmark, Germany, Jamaica, Netherland, Portugal, the UK, the USA) for information on alternative measures in three categories: depenalization; diversion; and decriminalization. It shows how these measures – in theory and in practice – combine with pre-existing social conditions and institutional contexts to trigger mechanisms across three causal pathways (normative; criminal justice; and health and social services). It shows how some posited causal processes are more empirically supported than others. Alternative measures can reduce harms imposed by criminal justice processes without increasing drug use or related health and crime harms, but this depends on specific combinations of contexts, mechanisms and outcomes.
Health promotion in adults with Down’s syndrome: Experiences of caregivers
Authors: Borthwick Claire , Inchley Joanna , Jones Jill
Published: November 2019

Individuals with Down’s syndrome rely on caregivers to support lifestyle behaviour change. It is therefore important to understand how caregivers put health recommendations into practice. Through conducting semi-structured interviews, the present study sought to understand the facilitators and barriers that caregivers faced when implementing health promotion advice. Five interviews were conducted with paid support staff and four with family carers of individuals attending a specialist multidisciplinary Down’s syndrome health promotion screening clinic. Three main themes emerged in their accounts, including active promotion of weight management by caregivers, benefits of working practices such as record keeping and communication channels and the importance of having access to social care services and recreational activities. These findings have important implications for professionals working in specialised healthcare settings who may be able to tailor communication and services to better meet the needs of individuals with Down’s syndrome and their caregivers.
Atomic polarizability: A periodic descriptor
Authors: Choudhary Shalini , Ranjan Prabhat , Chakraborty Tanmoy
Published: November 2019

Atomic polarizability is an essential theoretical construct to define and correlate many physicochemical properties. It exhibits periodicity and has a relationship with other periodic descriptors. Although a number of scales are available to compute atomic polarizability, the final scale is yet to be designed. In this venture, we have invoked a new empirical approach to compute the atomic polarizability of 103 elements of the periodic table, considering the conjoint action of other periodic descriptors, namely effective nuclear charge (Zeff) and absolute radii (r). The proposed approach is [Formula: see text], where “e” represents the electronic charge, Zeff is the effective nuclear charge, r is the absolute radius, and α is the polarizability. Our computed atomic polarizability follows all sine qua non of the periodicity. Our model significantly exhibits the relativistic effect too. A close agreement between our computed data and other available theoretical and experimental results demonstrates the efficacy of our proposed approach. Furthermore, we have established the polarizability equalization principle in terms of our computed data.
School Nurses on the Front Lines of Health Care: How to Help Students With Autism Spectrum Disorder Navigate a Meltdown in School
Authors: Lucas Christy , Mahler Kelly , Tierney Cheryl D. , Olympia Robert P.
Published: November 2019

Through a presented case scenario, this article describes the assessment and management of behaviors associated with autism spectrum disorder (ASD) in the pediatric population, with mnemonics as a memory tool. Although students present mainly to the school nurses’ office with physical complaints, there are many mental health concerns in the school-age population with emotional and physical consequences, particularly among students with ASD. Typically considered a developmental disorder, ASD affects communication and behavior with a wide range of symptoms that can vary in severity from person to person. It is important to understand the presentation and management of common pediatric mental health issues at school to be on the front line of your students’ health.
Anticoagulation in pulmonary arterial hypertension: a decision analysis
Authors: Jose Arun , Eckman Mark H. , Elwing Jean M.
Published: November 2019

Systemic anticoagulation may be beneficial in pulmonary arterial hypertension, but there is no randomized clinical trial data to guide therapeutic decision making, and current guidelines do not account for patient preferences or quality of life. Decision analytic models to evaluate the potential risks and benefits of systemic anticoagulation in pulmonary arterial hypertension patients, focusing on the benefit in quality‐adjusted life years, may be helpful in clarifying this uncertainty. We constructed a 31‐state Markov decision analytic model to explore anticoagulation and no anticoagulation strategies. Modeled patient characteristics included gender, use of central catheter‐based pulmonary arterial hypertension therapy, type of pulmonary arterial hypertension (idiopathic, idiopathic pulmonary arterial hypertension, or connective‐tissue associated, connective tissue disease‐pulmonary arterial hypertension), and use of oral contraceptive medication by females. Modeled events included mortality, thromboembolic complications, atrial fibrillation, stroke, and anticoagulation bleeding. Deterministic and probabilistic sensitivity analyses were performed. Anticoagulation was favored in all idiopathic pulmonary arterial hypertension cases, with a gain of 0.43–0.51 quality‐adjusted life years, and detrimental in all connective tissue disease‐pulmonary arterial hypertension cases, with a loss of 0.66–1.89 quality‐adjusted life years. Anticoagulation would need to demonstrate a hazard ratio for pulmonary arterial hypertension mortality of 0.95 or better to be favored. In our model, idiopathic pulmonary arterial hypertension patients benefit from anticoagulation in terms of quality‐adjusted life years, and connective tissue disease‐pulmonary arterial hypertension patients were harmed, with a hazard ratio for pulmonary arterial hypertension mortality of 0.95 or better being required to favorably impact quality‐adjusted life years. These results suggest that anticoagulation significantly improves quality adjusted life years and should be offered to all idiopathic pulmonary arterial hypertension patients. Shared decision models based on these results may help clarify therapeutic decision‐making uncertainty in pulmonary arterial hypertension patients.
The Platforms of Podcasting: Past and Present
Authors: Sullivan John L.
Published: November 2019

This article explores the role of digital platforms in podcasting (both past and present) and their impacts on the emergent podcast industry structure, content, and governance. Nieborg and Poell’s theoretical framework for understanding the impacts of platformization on culture is leveraged here to better understand the changes underway in podcasting. Like other forms of media, podcasting is being profoundly reshaped by platformization, though these transformations are distinct from other media in several key ways. Because podcasting emerged as a technology at the beginning of the 21st century before the advent of social media and the cloud, its decentralized architecture is structured around RSS, also known as “Really Simple Syndication.” When Apple added RSS aggregation into their iTunes Music Store in 2005, their market dominance in digital audio sales shaped early popular conceptions for the medium. I then outline how platformization is reshaping podcasting today by exploring how the three primary functions of media-related platform services—storage, discovery, and consumption—are shaping producers’ and audience experiences. Market imperatives for audience consumption data, as well as the structural features of platforms, are currently fueling industry consolidation. Even though podcasting is built upon the open architecture of RSS, commercial pressures and the desire of market players to capitalize on the “winner-take-all” features of platforms are shaping the trajectory of the medium’s current development.
The Impact of School-Based Mentoring on the Academic Achievement Gap
Authors: Grey Lorise
Published: November 2019

This study examined data from the Institute of Education Sciences’ evaluation of school-based mentoring (SBM) programs to establish a causal relationship between SBM and reduction of the academic achievement gap between African American and White middle school students. Participation in SBM improved the academic performance of all students. The findings demonstrated a sizable increase in African American students’ grade point average as a result of same-race mentoring. Implications for school counselors seeking to reduce the achievement gap are discussed.
In Vivo Imaging of Molecular Clearance From Human Entorhinal Cortex: A Possible Method for Preclinical Testing of Dementia
Authors: Eide Per K. , Ringstad Geir
Published: November 2019

Accumulation in the brain of metabolic waste products such as amyloid-β and hyperphosporylated tau (tau) is a hallmark of dementia (e.g., Alzheimer’s disease). One possible underlying mechanism is impaired cerebral paravascular (glymphatic) clearance of toxic solutes. Recently, we have provided evidence of glymphatic circulation being present in the human brain, utilizing repeated magnetic resonance imaging (MRI) acquisitions before/after intrathecal injection of an MRI contrast agent, serving as a cerebrospinal fluid (CSF) tracer (glymphatic MRI [gMRI]). In a recent study, we utilized the same methodology to assess glymphatic clearance function within an anatomical region that has a key role in cognitive function—the entorhinal cortex (ERC). gMRI was compared in individuals with the dementia subtype idiopathic normal pressure hydrocephalus (iNPH; n = 30) and reference (REF; n = 8) subjects. We found delayed clearance of CSF tracer from CSF nearby ERC, the ERC itself, and the white matter adjacent to ERC, which was most evident after 24 hr. The observations were interpreted as indicative of impaired glymphatic circulation and further suggested this being a possible mechanism behind accumulation of amyloid-β and tau in ERC and instrumental for dementia in iNPH. We suggest that gMRI may serve as a tool for assessment of early dementia, or even in the preclinical stage.
Only 4.9% (24/494) of original papers on migraine and headache published in Cephalalgia 2014–2018 concerned actual spontaneous or provoked migraine/headache attacks: A comment
Authors: Tfelt-Hansen Peer
Published: November 2019

The aim was to evaluate whether headache experts rarely, if ever, investigate spontaneous or provoked migraine/headache attacks. All the 494 Original Articles in five volumes of Cephalalgia (from 2014 to 2018) were screened and classified as dealing with spontaneous or provoked migraine/headache attacks, or other aspects of migraine/headache. Only 4.9% (24/494) of papers reported on studies of spontaneous and provoked migraine/headache attacks. Investigations of the pathophysiology of spontaneous or provoked migraine/headache attacks in humans could result in the development of better drugs for migraine, and to the identifications of biomarkers for use in personalized medicine.
Rapid genomic DNA variation in newly hybridized carp lineages derived from Cyprinus carpio (♀) × Megalobrama amblycephala (♂)
Authors: Luo Kaikun , Wang Shi , Fu Yeqing , Zhou Pei , Huang Xuexue , Gu Qianhong , Li Wuhui , Wang Yude , Hu Fangzhou , Liu Shaojun
Published: November 2019

Background

Distant hybridization can generate changes in phenotypes and genotypes that lead to the formation of new hybrid lineages with genetic variation. In this study, the establishment of two bisexual fertile carp lineages, including the improved diploid common carp (IDC) lineage and the improved diploid scattered mirror carp (IDMC) lineage, from the interspecific hybridization of common carp (Cyprinus carpio, 2n = 100) (♀) × blunt snout bream (Megalobrama amblycephala, 2n = 48) (♂), provided a good platform to investigate the genetic relationship between the parents and their hybrid progenies.

Result

In this study, we investigated the genetic variation of 12Hoxgenes in the two types of improved carp lineages derived from common carp (♀) × blunt snout bream (♂).Hoxgene clusters were abundant in the first generation of IDC, but most were not stably inherited in the second generation. In contrast, we did not find obvious mutations inHoxgenes in the first generation of IDMC, and almost all theHoxgene clusters were stably inherited from the first generation to the second generation of IDMC. Interestingly, we found obvious recombinant clusters ofHoxgenes in both improved carp lineages, and partially recombinant clusters ofHoxgenes were stably inherited from the first generation to the second generation in both types of improved carp lineages. On the other hand, someHoxgenes were gradually becoming pseudogenes, and some genes were completely pseudogenised in IDC or IDMC.

Conclusions

Our results provided important evidence that distant hybridization produces rapid genomic DNA changes that may or may not be stably inherited, providing novel insights into the function of hybridization in the establishment of improved lineages used as new fish resources for aquaculture.
Association between elevated blood glucose level and non-valvular atrial fibrillation: a report from the Guangzhou heart study
Authors: Fu Lu , Deng Hai , Lin Wei-dong , He Shang-fei , Liu Fang-zhou , Liu Yang , Zhan Xian-zhang , Fang Xian-hong , Liao Hong-tao , Wei Wei , Liao Zi-li , Tang Li-hong , Fu Zu-yi , Zheng Mu-rui , Wu Shu-lin , Xue Yu-mei
Published: November 2019

Background

To estimate the prevalence of elevated blood glucose level (EBG, including type 2 diabetes mellitus and impaired fasting glucose), and its association with non-valvular atrial fibrillation (NVAF) in Guangzhou, China.

Methods

The population-based follow-up Guangzhou Heart Study collected baseline data from July 2015 to August 2017 among 12,013 permanent residents aged > 35 from 4 Guangzhou districts. Two streets (Dadong and Baiyun) in the Yuexiu District, and one street (Xiaoguwei) and two towns (Xinzao and Nancun) in the Panyu District were chosen as representative of urban and rural areas, respectively. Each participant completed a comprehensive questionnaire, and underwent physical examination, blood sample collection for laboratory testing, electrocardiography, and other evaluations. Multivariable logistic regression analyses were used to estimate the independent association between hyperglycemia and NVAF prevalence.

Results

The prevalence of EBG in overall study population was 29.9%. Compared with residents without EBG, the odds ratio (OR) for AF among residents with EBG was significantly higher (1.94, 95% confidence interval [CI]: 1.40–2.70, P <  0.001), even after multivariate adjustment for metabolic abnormalities (OR = 1.60, 95% CI: 1.14–2.25, P = 0.007), and driven by women (OR = 1.80, 95% CI: 1.12–2.91, P = 0.016).

Conclusions

In Guangzhou, China, prevalence of EBG is high among residents aged > 35 years and associated with a multivariate adjusted increase in prevalence of NVAF overall and in women.
Differential expression and predictive value of monocyte scavenger receptor CD163 in populations with different tuberculosis infection statuses
Authors: Liu Qianqian , Ou Qinfang , Chen Huaxin , Gao Yan , Liu Yuanyuan , Xu Yuzhen , Ruan Qiaoling , Zhang Wenhong , Shao Lingyun
Published: November 2019

Background

Monocytes are the predominant innate immune cells at the early stage of Mycobacterium tuberculosis (M. tb) infection as the host defense against intracellular pathogens. Understanding the profile of different monocyte subpopulations and the dynamics of monocyte-related biomarkers may be useful for the diagnosis and prognosis of tuberculosis.

Methods

We enrolled 129 individuals comprising patients with pulmonary tuberculosis (PTB) (n = 39), tuberculous pleurisy (TBP) (n = 28), malignant pleural effusion (MPE) (n = 21), latent tuberculosis infection (LTBI) (n = 20), and healthy controls (HC) (n = 21). Surface expression of CD14, CD16, and CD163 on monocytes was detected using flow cytometry. In addition, soluble CD163 (sCD163) was determined by enzyme linked immunosorbent assay.

Results

Higher frequency of CD14+CD16+ (15.7% vs 7.8%, P < 0.0001) and CD14−CD16+ (5.3% vs 2.5%, P = 0.0011) monocytes and a decreased percentage of CD14+CD16− (51.0% vs 70.4%, P = 0.0110) cells was observed in PTB patients than in HCs. Moreover, PTB patients displayed a higher frequency of CD163+ cells in CD16+ monocytes than those in the HC group (40.4% vs 11.3%, P < 0.0001). The level of sCD163 was elevated in TBP patients and was higher in pleural effusion than in plasma (2116.0 ng/ml vs 1236.0 ng/ml, P < 0.0001). sCD163 levels in pleural effusion and plasma could be used to distinguish TBP from MPE patients (cut-off values: 1950.0 and 934.7 ng/ml, respectively; AUCs: 0.8418 and 0.8136, respectively). Importantly, plasma sCD163 levels in TBP patients decreased significantly after anti-TB treatment.

Conclusions

Higher expression of membrane and soluble CD163 in active tuberculosis patients might provide insights regarding the pathogenesis of tuberculosis, and sCD163 may be a novel biomarker to distinguish TBP from MPE and to predict disease severity.
LINC01128 expedites cervical cancer progression by regulating miR-383-5p/SFN axis
Authors: Hu Yi , Ma Yan , Liu Jie , Cai Yanlin , Zhang Mengmeng , Fang Xiaoling
Published: November 2019

Background

Cervical cancer (CC), causing significant morbidity and mortality worldwide, is one of the most common gynecological malignancies in women. SFN has been reported as a potential prognostic marker with apparent high expression in tumors. Nevertheless, the function mechanism of SFN is not clear yet in CC.

Methods

The relative expressions of RNAs were detected by real-time quantitative PCR (RT-qPCR). Colony formation assay, EdU stained assay and CCK-8 assay were to check cell proliferation ability in CC. Flow cytometry and apoptosis related proteins analysis were used to measure cells apoptosis capacity. Luciferase reporter assay and RNA pull down assay were to verify the molecular mechanism.

Results

SFN was highly expressed in CC tissues and CC cell lines compared with normal tissues and normal cell line. After interfering SFN, cell proliferation, migration and invasion ability was inhibited as well as cell apoptosis ability was promoted. In subsequence, miR-383-5p exhibited conspicuous low expression in CC tissues. And miR-383-5p was found to bind to SFN and have anti-cancerous effects in CC. Moreover, LINC01128 displayed remarkable high expression in CC tissues. Besides, LINC01128 shortage could reduce the expression of SFN at mRNA and protein levels. And the affinity between LINC01128 and miR-383-5p was verified. In the end, it was proved that LINC01128 could enhance cell proliferation, migration and invasion as well as inhibit cell apoptosis by binding with miR-383-5p and upregulating SFN.

Conclusion

LINC01128 expedited cells cellular process in CC by binding with miR-383-5p to release SFN.

Graphical Abstract
Association between high fear-avoidance beliefs about physical activity and chronic disabling low back pain in nurses in Japan
Authors: Fujii Tomoko , Oka Hiroyuki , Takano Kenichiro , Asada Fuminari , Nomura Takuo , Kawamata Kayo , Okazaki Hiroshi , Tanaka Sakae , Matsudaira Ko
Published: November 2019

Background

High prevalence of low back pain (LBP) in nurses has been reported globally. Ergonomic factors and work-related psychosocial factors have been focused on as risk factors. However, evidence on the role of fear-avoidance beliefs (FABs) concerning LBP in nurses is lacking. This study examined LBP prevalence and the association between FABs and chronic disabling LBP that interfered with work and lasted ≥ 3 months.

Methods

Female nurses (N = 3066; mean age = 35.8 ± 10.6 years) from 12 hospitals in Japan participated. A self-reported questionnaire was used to collect information on sociodemographics, LBP, work-related factors, and psychological distress. FABs about physical activity were assessed using a subscale from the FAB Questionnaire (score range = 0–24). The participants were asked to choose one of four statements regarding their LBP in the past 4 weeks: 1) I did not have LBP, 2) I had LBP without work difficulty, 3) I had LBP with work difficulty but without requiring absence from work, and 4) I had LBP requiring absence from work. If the participant had LBP in the past 4 weeks, it was also inquired if the LBP had lasted for ≥ 3 months. Chronic disabling LBP was defined as experiencing LBP with work difficulty in the past 4 weeks which had lasted for ≥ 3 months. In the nurses who had experienced any LBP in the past 4 weeks, we examined the association between FABs and experiencing chronic disabling LBP using multiple logistic regression models adjusting for pain intensity, age, body mass index, smoking status, psychological distress, hospital department, weekly work hours, night shift work, and the12 hospitals where the participants worked.

Results

Four-week and one-year LBP prevalence were 58.7 and 75.9%, respectively. High FABs (≥ 15) were associated with chronic disabling LBP (adjusted odds ratio = 1.76, 95% confidence interval [1.21–2.57], p = 0.003).

Conclusions

LBP is common among nurses in Japan. FABs about physical activity might be a potential target for LBP management in nurses.

Trial registration

UMIN-CTR UMIN000018087. Registered: June 25, 2015.
What motivates informal caregivers of people with dementia (PWD): a qualitative study
Authors: Zahed Shakiba , Emami Maryam , Bazargan-Hejazi Shahrzad , Eslami Ahmad Ali , Barekatain Majid , Zamani-Alavijeh Fereshteh
Published: November 2019

Background

The burden of caring for People with Dementia (PWD) is heavy; identifying incentives that motivate them in providing care is essential in facilitating and optimizing care. This study aims to explore and describe these motivating factors.

Methods

We conducted this qualitative study between January 2016 and January 2017 in Isfahan, Iran. Data were extracted through in-depth, semi-structured interviews with 19 caregivers of PWD. These data were then examined through thematic content analysis.

Results

We identified four categories of psychological motives based on the caregivers’ feedback and experience. These include 1) Moral-based motives, 2) Religious, and spiritual motives; 3) Financial motives, and 4) Wicked motives.

Conclusions

Our results revealed several aspects of caregivers’ motives. They include moral, religious, and spiritual aspects; sharing housing accommodations, and the likelihood of inheriting a portion of the patient’s assets based on unspoken rules and informal arrangements in the family, and wicked and immoral aspects. These findings can inform future efforts in enhancing the experiences of caregivers of PWD, and subsequently, the quality of care these patients receive. It further suggests that family members, members of a religious and spiritual organization, as well as social media, could play important roles in setting the stage.
The role of SCF ubiquitin-ligase complex at the beginning of life
Authors: Xie Jiayan , Jin Yimei , Wang Guang
Published: November 2019

As the largest family of E3 ligases, the Skp1-cullin 1-F-box (SCF) E3 ligase complex is comprised of Cullins, Skp1 and F-box proteins. And the SCF E3 ubiquitin ligases play an important role in regulating critical cellular processes, which promote degradation of many cellular proteins, including signal transducers, cell cycle regulators, and transcription factors. We review the biological roles of the SCF ubiquitin-ligase complex in gametogenesis, oocyte-to-embryo transition, embryo development and the regulation for estrogen and progestin. We find that researches about the SCF ubiquitin-ligase complex at the beginning of life are not comprehensive, thus more in-depth researches will promote its eventual clinical application.
Analyzing the impact of trade and investment agreements on pharmaceutical policy: provisions, pathways and potential impacts
Authors: Gleeson Deborah , Lexchin Joel , Labonté Ronald , Townsend Belinda , Gagnon Marc-André , Kohler Jillian , Forman Lisa , Shadlen Kenneth C.
Published: November 2019

Background

Trade and investment agreements negotiated after the World Trade Organization’s Agreement on Trade-Related Aspects of Intellectual Property Rights (TRIPS) have included increasingly elevated protection of intellectual property rights along with an expanding array of rules impacting many aspects of pharmaceutical policy. Despite the large body of literature on intellectual property and access to affordable medicines, the ways in which other provisions in trade agreements can affect pharmaceutical policy and, in turn, access to medicines have been little studied. There is a need for an analytical framework covering the full range of provisions, pathways, and potential impacts, on which to base future health and human rights impact assessment and research. A framework exploring the ways in which trade and investment agreements may affect pharmaceutical policy was developed, based on an analysis of four recently negotiated regional trade agreements. First a set of core pharmaceutical policy objectives based on international consensus was identified. A systematic comparative analysis of the publicly available legal texts of the four agreements was undertaken, and the potential impacts of the provisions in these agreements on the core pharmaceutical policy objectives were traced through an analysis of possible pathways.

Results

An analytical framework is presented, linking ten types of provisions in the four trade agreements to potential impacts on four core pharmaceutical policy objectives (access and affordability; safety, efficacy, and quality; rational use of medicines; and local production capacity and health security) via various pathways.

Conclusions

The analytical framework highlights provisions in trade and investment agreements that need to be examined, pathways that should be explored, and potential impacts that should be taken into consideration with respect to pharmaceutical policy. This may serve as a useful checklist or template for health and human rights impact assessments and research on the implications of trade agreements for pharmaceuticals.
Omalizumab and mepolizumab in the landscape of biological therapy for severe asthma in children: how to choose?
Authors: Giovannini Mattia , Mori Francesca , Barni Simona , de Martino Maurizio , Novembre Elio
Published: November 2019

Severe asthma has a substantial epidemiological impact on children and biological treatments can be an option to take into account, as they target specific molecules and pathways involved in its pathogenesis. Modern medicine is continuously and progressively oriented towards tailored treatments designed specifically for the pathology patterns observed in individual patients and identified as endotypes with associated biomarkers. In this regard, biologic treatments in asthma are one of the best examples. Among the biological drugs currently available, omalizumab is the one with the greatest amount of data on efficacy and safety, and the one we have more real-life clinical experience with. However, mepolizumab will likely be accessible soon globally for clinical use. Moreover, research on biological drugs for the treatment of severe asthma is expanding rapidly, with some molecules currently used in adult patients that could be registered also for pediatric use and new molecules that could be available in the future. On the other hand, due to this potential abundance of therapeutic options, new criteria could become necessary to guide clinicians through an evidence-based choice between omalizumab and these new drugs. For the same reason, more data collected specifically from pediatric clinical trials are necessary. In this review we aim to analyze the factors that could help clinicians make their choice and to highlight the unmet need for a more evidence-based choice.
Murine sepsis phenotypes and differential treatment effects in a randomized trial of prompt antibiotics and fluids
Authors: Seymour Christopher W. , Kerti Samantha J. , Lewis Anthony J. , Kennedy Jason , Brant Emily , Griepentrog John E. , Zhang Xianghong , Angus Derek C. , Chang Chung-Chou H. , Rosengart Matthew R.
Published: November 2019

Background

Clinical and biologic phenotypes of sepsis are proposed in human studies, yet it is unknown whether prognostic or drug response phenotypes are present in animal models of sepsis. Using a biotelemetry-enhanced, murine cecal ligation and puncture (CLP) model, we determined phenotypes of polymicrobial sepsis prior to physiologic deterioration, and the association between phenotypes and outcome in a randomized trial of prompt or delayed antibiotics and fluids.

Methods

We performed a secondary analysis of male C57BL/6J mice in two observational cohorts and two randomized, laboratory animal experimental trials. In cohort 1, mice (n = 118) underwent biotelemetry-enhanced CLP, and we applied latent class mixed models to determine optimal number of phenotypes using clinical data collected between injury and physiologic deterioration. In cohort 2 (N = 73 mice), inflammatory cytokines measured at 24 h after deterioration were explored by phenotype. In a subset of 46 mice enrolled in two trials from cohort 1, we tested the association of phenotypes with the response to immediate (0 h) vs. delayed (2 to 4 h) antibiotics or fluids initiated after physiologic deterioration.

Results

Latent class mixture modeling derived a two-class model in cohort 1. Class 2 (N = 97) demonstrated a shorter time to deterioration (mean SD 7.3 (0.9) vs. 9.7 (3.2) h, p < 0.001) and lower heart rate at 7 h after injury (mean (SD) 564 (55) vs. 626 (35) beats per minute, p < 0.001). Overall mortality was similar between phenotypes (p = 0.75). In cohort 2 used for biomarker measurement, class 2 mice had greater plasma concentrations of IL6 and IL10 at 24 h after CLP (p = 0.05). In pilot randomized trials, the effects of sepsis treatment (immediate vs. delayed antibiotics) differed by phenotype (p = 0.03), with immediate treatment associated with greater survival in class 2 mice only. Similar differential treatment effect by class was observed in the trial of immediate vs. delayed fluids (p = 0.02).

Conclusions

We identified two sepsis phenotypes in a murine cecal ligation and puncture model, one of which is characterized by faster deterioration and more severe inflammation. Response to treatment in a randomized trial of immediate versus delayed antibiotics and fluids differed on the basis of phenotype.
547 transcriptomes from 44 brain areas reveal features of the aging brain in non-human primates
Authors: Li Ming-Li , Wu Shi-Hao , Zhang Jin-Jin , Tian Hang-Yu , Shao Yong , Wang Zheng-Bo , Irwin David M. , Li Jia-Li , Hu Xin-Tian , Wu Dong-Dong
Published: November 2019

Background

Brain aging is a complex process that depends on the precise regulation of multiple brain regions; however, the underlying molecular mechanisms behind this process remain to be clarified in non-human primates.

Results

Here, we explore non-human primate brain aging using 547 transcriptomes originating from 44 brain areas in rhesus macaques (Macaca mulatta). We show that expression connectivity between pairs of cerebral cortex areas as well as expression symmetry between the left and right hemispheres both decrease after aging. Although the aging mechanisms across different brain areas are largely convergent, changes in gene expression and alternative splicing vary at diverse genes, reinforcing the complex multifactorial basis of aging. Through gene co-expression network analysis, we identify nine modules that exhibit gain of connectivity in the aged brain and uncovered a hub gene, PGLS, underlying brain aging. We further confirm the functional significance of PGLS in mice at the gene transcription, molecular, and behavioral levels.

Conclusions

Taken together, our study provides comprehensive transcriptomes on multiple brain regions in non-human primates and provides novel insights into the molecular mechanism of healthy brain aging.
Safety and efficacy of a new micronized formulation of the ALIAmide palmitoylglucosamine in preclinical models of inflammation and osteoarthritis pain
Authors: Cordaro Marika , Siracusa Rosalba , Impellizzeri Daniela , D’ Amico Ramona , Peritore Alessio Filippo , Crupi Rosalia , Gugliandolo Enrico , Fusco Roberta , Di Paola Rosanna , Schievano Carlo , Cuzzocrea Salvatore
Published: November 2019

Background

Osteoarthritis is increasingly recognized as the result of a complex interplay between inflammation, chrondrodegeneration, and pain. Joint mast cells are considered to play a key role in orchestrating this detrimental triad. ALIAmides down-modulate mast cells and more generally hyperactive cells. Here we investigated the safety and effectiveness of the ALIAmide N-palmitoyl-d-glucosamine (PGA) in inflammation and osteoarthritis pain.

Methods

Acute toxicity of micronized PGA (m-PGA) was assessed in rats following OECD Guideline No.425. PGA and m-PGA (30 mg/kg and 100 mg/kg) were orally administered to carrageenan (CAR)-injected rats. Dexamethasone 0.1 mg/kg was used as reference. Paw edema and thermal hyperalgesia were measured up to 6 h post-injection, when also myeloperoxidase activity and histological inflammation score were assessed. Rats subjected to intra-articular injection of sodium monoiodoacetate (MIA) were treated three times per week for 21 days with PGA or m-PGA (30 mg/kg). Mechanical allodynia and motor function were evaluated at different post-injection time points. Joint histological and radiographic damage was scored, articular mast cells were counted, and macrophages were immunohistochemically investigated. Levels of TNF-α, IL-1β, NGF, and MMP-1, MMP-3, and MMP-9 were measured in serum using commercial colorimetric ELISA kits. One- or two-way ANOVA followed by a Bonferroni post hoc test for multiple comparisons was used.

Results

Acute oral toxicity of m-PGA resulted in LD50 values in excess of 2000 mg/kg. A single oral administration of PGA and m-PGA significantly reduced CAR-induced inflammatory signs (edema, inflammatory infiltrate, and hyperalgesia), and m-PGA also reduced the histological score. Micronized PGA resulted in a superior activity to PGA on MIA-induced mechanical allodynia, locomotor disability, and histologic and radiographic damage. The MIA-induced increase in mast cell count and serum level of the investigated markers was also counteracted by PGA and to a significantly greater extent by m-PGA.

Conclusions

The results of the present study showed that PGA is endorsed with anti-inflammatory, pain-relieving, and joint-protective effects. Moreover, it proved that particle size reduction greatly enhances the activity of PGA, particularly on joint pain and disability. Given these results, m-PGA could be considered a valuable option in the management of osteoarthritis.
Intestinal parasitic infections and determinant factors among school-age children in Ethiopia: a cross-sectional study
Authors: Dessie Awrajaw , Gebrehiwot Tesfay Gebregzabher , Kiros Berihu , Wami Sintayehu Daba , Chercos Daniel Haile
Published: November 2019

Objective

This study aimed to determine the prevalence of intestinal parasitic infections and associated factors among school-age children in Sebeya primary school, northern Ethiopia, 2017.

Results

The prevalence of intestinal parasites in school-age children was (29.9%). A total of six parasites were detected in this study. E. histolytica/dispar 19.43% (82/422) and G. lamblia 8.29% (35/422) were the predominant ones. Unclean fingernail (AOR = 1.72), defecating in the open field (AOR = 2.82), and being barefooted (AOR = 1.72) were the determinant factors for intestinal parasitic infections. Frequently washing hands reduced the chance of infections by 68%. Furthermore, children in grade 1–4 and 5–6 had higher odds developing the infections than those in grade 7–8 (AOR = 8.21 and AOR = 2.50, respectively).