bluuebunny/crossref_metadata_2025 huggingface dataset:
An overview of advanced biocompatible and biomimetic materials for creation of replacement structures in the musculoskeletal systems: focusing on cartilage tissue engineering
Authors: Del Bakhshayesh Azizeh Rahmani , Asadi Nahideh , Alihemmati Alireza , Tayefi Nasrabadi Hamid , Montaseri Azadeh , Davaran Soodabeh , Saghati Sepideh , Akbarzadeh Abolfazl , Abedelahi Ali
Published: November 2019

Tissue engineering, as an interdisciplinary approach, is seeking to create tissues with optimal performance for clinical applications. Various factors, including cells, biomaterials, cell or tissue culture conditions and signaling molecules such as growth factors, play a vital role in the engineering of tissues. In vivo microenvironment of cells imposes complex and specific stimuli on the cells, and has a direct effect on cellular behavior, including proliferation, differentiation and extracellular matrix (ECM) assembly. Therefore, to create appropriate tissues, the conditions of the natural environment around the cells should be well imitated. Therefore, researchers are trying to develop biomimetic scaffolds that can produce appropriate cellular responses. To achieve this, we need to know enough about biomimetic materials. Scaffolds made of biomaterials in musculoskeletal tissue engineering should also be multifunctional in order to be able to function better in mechanical properties, cell signaling and cell adhesion. Multiple combinations of different biomaterials are used to improve above-mentioned properties of various biomaterials and to better imitate the natural features of musculoskeletal tissue in the culture medium. These improvements ultimately lead to the creation of replacement structures in the musculoskeletal system, which are closer to natural tissues in terms of appearance and function. The present review article is focused on biocompatible and biomimetic materials, which are used in musculoskeletal tissue engineering, in particular, cartilage tissue engineering.
Effects of endogenous inflammation signals elicited by nerve growth factor, interferon-γ, and interleukin-4 on peripheral nerve regeneration
Authors: Liao Chien-Fu , Chen Chung-Chia , Lu Yu-Wen , Yao Chun-Hsu , Lin Jia-Horng , Way Tzong-Der , Yang Tse-Yen , Chen Yueh-Sheng
Published: November 2019

Background

Large gap healing is a difficult issue in the recovery of peripheral nerve injury. The present study provides in vivo trials of silicone rubber chambers filled with collagen containing IFN-γ or IL-4 to bridge a 15 mm sciatic nerve defect in rats. Fillings of NGF and normal saline were used as the positive and negative controls. Neuronal electrophysiology, neuronal connectivity, macrophage infiltration, location and expression levels of calcitonin gene-related peptide and histology of the regenerated nerves were evaluated.

Results

At the end of 6 weeks, animals from the groups of NGF and IL-4 had dramatic higher rates of successful regeneration (100 and 80%) across the wide gap as compared to the groups of IFN-γ and saline controls (30 and 40%). In addition, the NGF group had significantly higher NCV and shorter latency compared to IFN-γ group (P < 0.05). The IL-4 group recruited significantly more macrophages in the nerves as compared to the saline controls and the NGF-treated animals (P < 0.05).

Conclusions

The current study demonstrated that NGF and IL-4 show potential growth-promoting capability for peripheral nerve regeneration. These fillings in the bridging conduits may modulate local inflammatory conditions affecting recovery of the nerves.
Correction to: Contributions of Vitamin D in the management of depressive symptoms and cardiovascular risk factors: study protocol for a randomized, double-blind, placebo-controlled clinical trial
Authors: Porto Catarina Magalhães , de Paula Santana da Silva Tatiana , Sougey Everton Botelho
Published: November 2019

An error occurred during the publication of the original article [1] which led to the text being incorrectly converted into Portuguese.
Bone marrow mesenchymal stem cells in rheumatoid arthritis, spondyloarthritis, and ankylosing spondylitis: problems rather than solutions?
Authors: Berthelot Jean-Marie , Le Goff Benoit , Maugars Yves
Published: November 2019

Background

Bone marrow mesenchymal stem cells (BM-MSCs) can dampen inflammation in animal models of inflammatory rheumatisms and human osteoarthritis. They are expected to be a solution for numerous human conditions. However, in rheumatoid arthritis (RA) and spondyloarthritis (SpA), subsets of subchondral BM-MSCs might conversely fuel synovitis and enthesitis.

Main text

Abnormal behaviour of BM-MSCs and/or their progeny has been found in RA and SpA. BM-MSCs also contribute to the ossifying processes observed in ankylosing spondylitis. Some synovial fibroblastic stem cells probably derive from BM-MSCs, but some stem cells can also migrate through the bare zone area of joints, not covered by cartilage, into the synovium. BM-MSCs can also migrate in the synovium over tendons. Sub-populations of bone marrow stem cells also invade the soft tissue side of enthesis via small holes in the bone cortex. The present review aims (1) to make a focus on these two aspects and (2) to put forward the hypothesis that lasting epigenetic changes of some BM-MSCs, induced by transient infections of the bone marrow close to the synovium and/or entheses (i.e. trained immunity of BM-MSCs and/or their progeny), contribute to the pathogenesis of inflammatory rheumatisms. Such hypothesis would fit with (1) the uneven distribution and/or flares of arthritis and enthesitis observed at the individual level in RA and SpA (reminiscent of what is observed following reactive arthritis and/or in Whipple’s disease); (2) the subchondral bone marrow oedema and erosions occurring in many RA patients, in the bare zone area; and (3) the frequent relapses of RA and SpA despite bone marrow transplantation, whereas most BM-MSCs resist graft preconditioning.

Conclusion

Some BM-MSCs might be more the problem than the solution in inflammatory rheumatisms. Subchondral bone marrow BM-MSCs and their progeny trafficking through the bare zone area of joints or holes in the bone cortex of entheses should be thoroughly studied in RA and SpA respectively. This may be done first in animal models. Mini-arthroscopy of joints could also be used in humans to specifically sample tissues close to the bare zone and/or enthesis areas.
Evidence-based models of care for the treatment of alcohol use disorder in primary health care settings: protocol for systematic review
Authors: Rombouts Susan A. , Conigrave James , Louie Eva , Haber Paul , Morley Kirsten C.
Published: November 2019

Background

Alcohol use disorder (AUD) is highly prevalent and accounts globally for 1.6% of disability-adjusted life years (DALYs) among females and 6.0% of DALYs among males. Effective treatments for AUDs are available but are not commonly practiced in primary health care. Furthermore, referral to specialized care is often not successful and patients that do seek treatment are likely to have developed more severe dependence. A more cost-efficient health care model is to treat less severe AUD in a primary care setting before the onset of greater dependence severity. Few models of care for the management of AUD in primary health care have been developed and with limited implementation. This proposed systematic review will synthesize and evaluate differential models of care for the management of AUD in primary health care settings.

Methods

We will conduct a systematic review to synthesize studies that evaluate the effectiveness of models of care in the treatment of AUD in primary health care. A comprehensive search approach will be conducted using the following databases; MEDLINE (1946 to present), PsycINFO (1806 to present), Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials (CENTRAL) (1991 to present), and Embase (1947 to present).

Reference searches of relevant reviews and articles will be conducted. Similarly, a gray literature search will be done with the help of Google and the gray matter tool which is a checklist of health-related sites organized by topic. Two researchers will independently review all titles and abstracts followed by full-text review for inclusion. The planned method of extracting data from articles and the critical appraisal will also be done in duplicate. For the critical appraisal, the Cochrane risk of bias tool 2.0 will be used.

Discussion

This systematic review and meta-analysis aims to guide improvement of design and implementation of evidence-based models of care for the treatment of alcohol use disorder in primary health care settings. The evidence will define which models are most promising and will guide further research.

Protocol registration number

PROSPERO CRD42019120293.
Lower and upper bounds for lifespan of solutions to viscoelastic hyperbolic equations with variable sources and damping terms
Authors: Dai Lili , Zhang Zhuo
Published: November 2019

The aim of this paper is to study bounds for lifespan of solutions to the following equation:
$$ u_{tt}-\Delta u+ \int _{0}^{t}g(t-\tau )\Delta u(\tau )\,d\tau + \vert u_{t} \vert ^{m(x,t)-2}u _{t}= \vert u \vert ^{p(x,t)-2}u $$utt−Δu+∫0tg(t−τ)Δu(τ)dτ+|ut|m(x,t)−2ut=|u|p(x,t)−2u under homogeneous Dirichlet boundary conditions. It is worth pointing out that it is not a trivial generalization for constant-exponent problems because we have to face some essential difficulties in studying such problems. The first difficulty is that the monotonicity of the energy functional fails. Another one is that there exists a gap between the norm and the modular to the generalized function space, which leads to the failure of the Poincaré inequality for modular form. To overcome such difficulties, the authors construct control function and apply new energy estimates to establish the quantitative relationship between the source $\int _{\varOmega }|u|^{p(x,t)}\,dx$∫Ω|u|p(x,t)dx and the initial energy, and then obtain the finite-time blow-up of solutions for a positive initial energy, especially, the authors only assume that $p_{t}(x,t)$pt(x,t) is integrable rather than uniformly bounded. Such weak conditions are seldom seen for the variable exponent case. At last, an estimate of lower bound for lifespan is established by applying differential inequality argument and energy inequalities.
High in vitro survival rate of sheep in vitro produced blastocysts vitrified with a new method and device
Authors: Ledda Sergio , Kelly Jen M. , Nieddu Stefano , Bebbere Daniela , Ariu Federica , Bogliolo Luisa , Natan Dity , Arav Amir
Published: November 2019

Background

To advance the use of embryo vitrification in veterinary practice, we developed a system in which embryo vitrification, warming and dilution can be performed within a straw. Ovine in vitro produced embryos (IVEP) were vitrified at either early (EBs: n = 74) or fully expanded blastocyst stage (FEBs: n = 195), using a new device named “E.Vit”, composed by a 0.25-mL straw with a 50-μm pore polycarbonate grid at one end. Embryos at each stage (EBs and FEBs) were vitrified by either Two-step (TS) or Multi-step (MS; 6 different concentrations of vitrification solutions) protocol. Non-vitrified embryos (n = 102) were maintained in in vitro culture as a control. Warming consisted of placing the straws directly into 1.5 mL tubes containing a TCM-199 solution with three decreasing concentrations of sucrose. Blastocyst re-expansion, embryo survival and hatching rate were evaluated at 2, 24 and 48 h post warming. The number of apoptotic cells was determined by TUNEL assay.

Results

Blastocyst re-expansion (2 h) after warming was higher (P < 0.05) in FEBs group, vitrified with the MS and TS methods (77.90% and 71.25%, respectively) compared with the EBs group (MS: 59.38% and TS: 48.50%, respectively). Survival rates of vitrified FEBs after 24 h IVC were higher (P < 0.001) in both methods (MS and TS) than vitrified EBs (MS: 56.25%; TS: 42.42%) and was higher (P < 0.05) in the MS method (94.19%) compared with those in TS (83.75%). After 48 h of culture the hatching rate for FEBs vitrified in MS system (91.86%) was similar to control (91.89%), but higher than FEB TS (77.5%) and EBs vitrified in MS (37.5%) and TS (33.33%). Number of apoptotic cells were higher in EBs, irrespective of the system used, compared to FEBs. The number of apoptotic cells in FEBs vitrified with MS was comparable to the control.

Conclusions

A high survival rate of IVP embryos can be achieved by the new “E.Vit” device with hatching rates in vitro comparable with control fresh embryos. This method has the potential for use in direct embryo transfer in field conditions.
N368-Tau fragments generated by legumain are detected only in trace amount in the insoluble Tau aggregates isolated from AD brain
Authors: Schlegel Kerstin , Awwad Khader , Heym Roland G. , Holzinger David , Doell Annika , Barghorn Stefan , Jahn Thomas R. , Klein Corinna , Mordashova Yulia , Schulz Michael , Gasparini Laura
Published: November 2019

Intraneuronal insoluble inclusions made of Tau protein are neuropathological hallmarks of Alzheimer Disease (AD). Cleavage of Tau by legumain (LGMN) has been proposed to be crucial for aggregation of Tau into fibrils. However, it remains unclear if LGMN-cleaved Tau fragments accumulate in AD Tau inclusions.

Using an in vitro enzymatic assay and non-targeted mass spectrometry, we identified four putative LGMN cleavage sites at Tau residues N167-, N255-, N296- and N368. Cleavage at N368 generates variously sized N368-Tau fragments that are aggregation prone in the Thioflavin T assay in vitro. N368-cleaved Tau is not detected in the brain of legumain knockout mice, indicating that LGMN is required for Tau cleavage in the mouse brain in vivo. Using a targeted mass spectrometry method in combination with tissue fractionation and biochemical analysis, we investigated whether N368-cleaved Tau is differentially produced and aggregated in brain of AD patients and control subjects. In brain soluble extracts, despite reduced uncleaved Tau in AD, levels of N368-cleaved Tau are comparable in AD and control hippocampus, suggesting that LGMN-mediated cleavage of Tau is not altered in AD. Consistently, levels of activated, cleaved LGMN are also similar in AD and control brain extracts. To assess the potential accumulation of N368-cleaved Tau in insoluble Tau aggregates, we analyzed sarkosyl-insoluble extracts from AD and control hippocampus. Both N368-cleaved Tau and uncleaved Tau were significantly increased in AD as a consequence of pathological Tau inclusions accumulation. However, the amount of N368-cleaved Tau represented only a very minor component (< 0.1%) of insoluble Tau.

Our data indicate that LGMN physiologically cleaves Tau in the mouse and human brain generating N368-cleaved Tau fragments, which remain largely soluble and are present only in low proportion in Tau insoluble aggregates compared to uncleaved Tau. This suggests that LGMN-cleaved Tau has limited role in the progressive accumulation of Tau inclusions in AD.
Learning isolated polysemous words: identifying the intended meaning of language learners in informal ubiquitous language learning environments
Authors: Abou-Khalil Victoria , Helou Samar , Flanagan Brendan , Chen Mei-Rong Alice , Ogata Hiroaki
Published: November 2019

A growing number of language learners use ubiquitous language learning applications to learn anytime and anywhere. Learners translate and learn isolated words inspired by their activities and surroundings. However, isolated words may have several meanings that change depending on the context. Since learners don’t have the opportunity to indicate the meaning they are looking for in an online learning environment, they risk learning translations that do not correspond to their intended meaning. Identifying the intended meaning of the learner is needed to provide them with an appropriate translation. However, isolated words are difficult to disambiguate due to a lack of text around them. To this end, informal ubiquitous learning environments can offer another type of context, one that is formed by the users’ past learning logs. In this work, we propose using the learners’ past vocabulary to disambiguate their intended meaning when they look up isolated words. Accordingly, we propose and evaluate three methods. The first method considers that the intended meaning of the learner is the one that is the most semantically similar to the learner’s past vocabulary. The second method builds on the first method but gives more weight to the vocabulary that the learner logged shortly before the target word. The third method addresses situations where the semantic similarities between the different meanings of the word and the past vocabulary have similar values. In those cases, the method considers that the intended meaning of the learner is the most common meaning in the target language. The three methods were evaluated using 148 logs of SCROLL, a ubiquitous informal language learning environment. The success rates of the three methods were 72.180%, 75.630%, and 83.050% respectively. This work shows that the past activity of language learners in informal ubiquitous language learning environments could be used to identify their intended meaning when learning a new word.
Periodontal disease and risk of benign prostate hyperplasia: a cross-sectional study
Authors: Wu Lan , Li Bing-Hui , Wang Yun-Yun , Wang Chao-Yang , Zi Hao , Weng Hong , Huang Qiao , Zhu You-Jia , Zeng Xian-Tao
Published: November 2019

Background

Both periodontal disease and benign prostatic hyperplasia are age-related diseases that affect millions of people worldwide. Hence, this study aimed to investigate the association between periodontal disease and the risk of benign prostatic hyperplasia.

Methods

A total of 4930 participants were selected from an available health examination that was carried out in 2017, only males were considered for further analysis. All eligible males were divided into benign prostatic hyperplasia and normal groups, the benign prostatic hyperplasia group was then divided into prostate volume ≤ 60 g and > 60 g subgroups; all their periodontal status was extracted and then into normal (CPI score of 0), periodontal disease (CPI score between 1 and 4), and periodontitis (CPI score between 3 and 4) groups. The correlation between periodontal disease and benign prostatic hyperplasia was investigated using logistic regression analyses and greedy matching case-control analysis. Subgroup analysis based on prostate volume was also performed. All analyses were conducted with SAS 9.4 software.

Results

A total of 2171 males were selected for this analysis. The presence of periodontal disease significantly increased the risk of benign prostatic hyperplasia by 1.68 times (OR = 1.68, 95% CI: 1.26–2.24), and individuals with periodontitis showed a higher risk (OR = 4.18, 95% CI: 2.75–6.35). In addition, among matched cases and controls, this association remained robust (periodontal disease: OR = 1.85, 95% CI: 1.30–2.64; periodontitis: OR = 4.83, 95% CI: 2.57–9.07). Subgroup analysis revealed that periodontal disease significantly increased benign prostate hyperplasia risk as well (for prostate volume ≤ 60 g: OR = 1.64, 95% CI: 1.22–2.20; for volume > 60 g: OR = 2.17, 95% CI: 1.04–4.53), and there was a higher risk in the group with a prostate volume greater than 60 g.

Conclusion

Periodontal disease is significantly and positively associated with an increased risk of benign prostatic hyperplasia. Further validation studies should be performed to explore the relationship between periodontal treatment and benign prostate hyperplasia.
Network pharmacology-based assessment to elucidate the molecular mechanism of anti-diabetic action of Tinospora cordifolia
Authors: Khanal Pukar , Patil B. M. , Mandar Bijendra K. , Dey Yadu Nandan , Duyu Taaza
Published: November 2019

Background

Tinospora cordifolia is used traditionally for the treatment of diabetes and is used in various formulations. Scientific evidence is also available for its anti-diabetic potency under various animal models. However, the probable molecular mechanism of Tinospora cordifolia in the treatment of diabetes has not been illuminated yet. Hence, the present study dealt to elucidate the probable molecular mechanism of anti-diabetic effect of Tinospora cordifolia using network pharmacology approach.

Methods

The structural information of bioactive phytoconstituents was retrieved from different open source databases. Compounds were then predicted for their hits with the probable targets involved in the diabetes mellitus. Phytoconstituents were also predicted for their druglikeness score, probable side effects, and ADMET profile. The modulated protein pathways were identified by using the Kyoto Encyclopedia of Genes and Genomes pathway analysis. The interaction between the compounds, proteins, and pathways was interpreted based on the edge count. The docking study was performed using Autodock4.0.

Results

Nine phytoconstituents from Tinospora cordifolia were identified to modulate the pathogenic protein molecules involved in diabetes mellitus. Among them, tembetarine scored highest druglikeness hit and had the maximum interaction with proteins involved in diabetes. Further, neuroactive ligand-receptor interaction was predicted as majorly modulated pathway.

Conclusion

The current study identified an important antidiabetic constituent, tembetarine which modulated the majority of diabetic proteins majorly modulating neuroactive ligand-receptor interaction.
Gene expression profiles of dicyemid life-cycle stages may explain how dispersing larvae locate new hosts
Authors: Lu Tsai-Ming , Furuya Hidetaka , Satoh Noriyuki
Published: November 2019

Metazoans have evolved a great variety of life histories in response to environmental conditions. A unique example is encountered in dicyemid mesozoans. In addition to a highly simplified adult body comprising only ~ 30 cells, dicyemids exhibit a parasitic lifestyle that includes nematogens (asexual reproductive adults), rhombogens (sexual reproductive adults), vermiform larvae generated by nematogens, and infusoriform larvae generated by rhombogens. However, due to the difficulties of observing microscopic endoparasites, the complex life cycle and biological functions of life-cycle stages of dicyemids have remained mysterious. Taking advantage of the recently decoded genome of Dicyema japonicum, we examined genes that undergird this lifestyle. Using stage-specific gene expression profiles, we found that biological processes associated with molecular transport, developmental regulation, and sensory response are specified at different stages. Together with the expression of potential neurotransmitters, we further suggest that apical cells in infusoriform larva probably serve sensory functions, although dicyemids have no nervous system. Gene expression profiles show that more genes are expressed in free-living infusoriform larvae than in the other three stages, and that some of these genes are likely involved in locating new hosts. These data provide molecular information about the unique lifestyle of dicyemids and illustrate how an extremely simplified endoparasite adapted and retained gene sets and morphological characters to complete its life cycle.
Horizontal change of philtrum after orthognathic surgery in patients with facial asymmetry
Authors: Joh Yewon , Park Hyun Soo , Yang Hoon Joo , Hwang Soon Jung
Published: November 2019

Background

Soft tissue asymmetry such as lip canting or deviation of the philtrum is an important influencing factor for unbalanced facial appearance. Lip canting could be improved by the correction of the occlusal canting or positional change of the mentum. Although there are many studies about changes of lip canting, however, postoperative changes of philtrum deviation have not been yet reported. In this study, we investigate the positional change of the philtrum after orthognathic surgery and influencing factors.

Methods

Positional change of the philtrum was evaluated in 41 patients with facial asymmetry who underwent bimaxillary surgery, in relation to other anatomical soft tissue landmarks using a frontal clinical photo. The surgical movement of the maxillary and mandibular dental midline and canting were measured in postero-anterior cephalogram before and 1 day after surgery. The same procedure was repeated in patients with more than 1.5 mm perioperative change of the mandibular dental midline after bimaxillary surgery.

Results

Maxillary dental midline shifting and canting correction did not have a significant correlation with lateral movement of the philtrum midline. However, the mandibular shift had a statistically significant correlation with a lateral movement of the philtrum (p < 0.05) as well as other linear parameters and angle values.

Conclusion

The horizontal change of the philtrum is influenced by lateral mandibular movement in patients with facial asymmetry, rather than maxillary lateral movement.
A rare cause of complete airway obstruction caused by a defective pilot tube of a reinforced endotracheal tube
Authors: Paramaswamy Rathna
Published: November 2019

Background

The common causes of failure to inflate the lungs after placement of an endotracheal tube include mechanical obstruction of the tube by tight gauzes, tongue blade, tube kinking, patient biting on the tube, obstruction of the lumen by blood or foreign body, bronchospasm, haemothorax, tension pneumothorax or equipment malfunction.

Case presentation

We report a case of complete airway obstruction due to herniation of the pilot inflation line into the lumen at the proximal end of a reinforced tube when the tracheal cuff was inflated. Prior to use, the endotracheal tube was tested and functioned normally. The patient was uneventfully reintubated with a new endotracheal tube. With the endotracheal tube, device problems often involve the pilot balloon and cuff assembly and leaks are more common.

Conclusion

This case report highlights an unusual cause of complete proximal lumen obstruction due to a manufacturing defect which could have caused a critical incident in the theatre.
Mental health services in Cambodia: an overview
Authors: Parry Sarah J. , Wilkinson Ewan
Published: November 2019

Mental health services in Cambodia required rebuilding in their entirety after their destruction during conflict in the 1970s. During the late 1990s there was rapid growth and development of professional mental health training and education. Currently, basic mental healthcare is available primarily in urban areas and is provided by a mixture of government, non-government and private services. Despite the initial rapid growth of services and the development of a national mental health strategy in 2010, significant challenges remain in achieving an acceptable, standardised level of mental healthcare nationally.
Association between the timing of consultation-liaison psychiatry interventions and the length of stay in general hospital
Authors: Vulser Hélène , Vinant Victoire , Lanvin Victoria , Chatellier Gilles , Limosin Frédéric , Lemogne Cédric
Published: November 2019

Background

Psychiatric comorbidities are frequent in patients admitted in general hospital and are associated with greater lengths of stay (LOS). Early consultation-liaison psychiatry (CLP) interventions may reduce the LOS but previous studies were underpowered to allow subgroup analyses and have generally not considered the severity of the condition for which patients were admitted (‘disease severity’).

Aims

To investigate the association between the timing of CLP interventions and LOS in a general hospital.

Method

We retrospectively included 4500 consecutive patients admitted in non-psychiatric wards of a university hospital between 2008 and 2016 who had a first CLP intervention. We used general linear models to examine the association between the referral time, defined as log(days before the consultation)/log(LOS), and log(LOS), adjusting for age, gender, year of admission, place of residence, main psychiatric diagnosis, admission to the intensive care unit (ICU), main physical condition and disease severity.

Results

Referral time was associated with log(LOS) (β = 0.31; P <0.001), notably for older patients (β = 0.43; P <0.001) and those admitted to the ICU (β = 0.50; P <0.001), but not for those with psychotic disorders (β = −0.20; P = 0.10). The association was confirmed when considering the expected LOS for each patient. For instance, for an expected LOS of 10 days, a CLP intervention on day 3 compared with day 6 was associated with a reduction of the actual LOS of 2.4 days.

Conclusions

Earlier CLP interventions were associated with a clinically significant shorter LOS in a large population even after adjusting for disease severity. Early CLP interventions may have benefits for both patients and health-related costs.
Sex-specific Estrogen Levels and Reference Intervals from Infancy to Late Adulthood Determined by LC-MS/MS
Authors: Frederiksen Hanne , Johannsen Trine Holm , Andersen Stine Ehlern , Albrethsen Jakob , Landersoe Selma Kløve , Petersen Jørgen Holm , Andersen Anders Nyboe , Vestergaard Esben Thyssen , Schorring Mia Elbek , Linneberg Allan , Main Katharina M , Andersson Anna-Maria , Juul Anders
Published: November 2019

Context

The lack of sensitive and robust analytical methods has hindered the reliable quantification of estrogen metabolites in subjects with low concentrations.

Objective

To establish sex-specific reference ranges for estrone (E1) and estradiol (E2) throughout life and to evaluate sex-differences using the state-of-the-art liquid chromatography tandem mass spectrometry (LC-MS/MS) method for quantification of E1, E2, and estriol (E3).

Design

LC-MS/MS method development and construction of estrogen reference ranges.

Settings

Population-based cross-sectional cohorts from the greater Copenhagen and Aarhus areas.

Participants

Healthy participants aged 3 months to 61 years (n = 1838).

Results

An isotope diluted LC-MS/MS method was developed and validated for measurements of serum E1, E2, and E3. Limits of detections (LODs) were 3 pmol/L (E1), 4 pmol/L (E2), and 12 pmol/L (E3), respectively. This sensitive method made it possible to differentiate between male and female concentration levels of E1 and E2 in children. In girls, E2 levels ranged from <LOD to 100 pmol/L during mini-puberty, whereas it was ≤20 pmol/L during childhood. E1 and E2 increased with age and pubertal breast stage and varied during the menstrual cycle; E1 was lower than E2 in girls and premenopausal women, and higher than E2 in postmenopausal women. In boys, E1 and E2 increased with age and pubertal stage, whereas little changes with age were observed in men. High E3 concentrations were confirmed in pregnant women.

Conclusion

Reference ranges of simultaneous quantification of E1 and E2 by this novel specific and highly sensitive LC-MS/MS method provide an invaluable tool in clinical practice and in future research studies.
Trials and Tribulations of Viscoelastic-Based Determination of Fibrinogen Concentration
Authors: Ranucci Marco , Di Dedda Umberto , Baryshnikova Ekaterina
Published: November 2019

Acquired fibrinogen deficiency is a major determinant of severe bleeding in different clinical conditions, including cardiac surgery, trauma, postpartum hemorrhage, liver surgery, and transplantation. The existing guidelines recommend to supplement fibrinogen in patients with severe bleeding when the fibrinogen concentration is <1.5 g/L. Viscoelastic tests (VETs) provide a fast determination of the fibrinogen contribution to clot firmness and allow prompt treatment of acquired fibrinogen deficiency. However, different VET devices are presently available on the market, based on different technologies and different activators and platelet inhibitors. The available tests are the functional fibrinogen (FF, thromboelastography), the fibrinogen contribution to clot firmness (fibrinogen determination [FIBTEM], thromboelastometry), and the fibrinogen contribution to clot strength (FCS, sonorheometry). All these tests have a moderate to very good correlation with the Clauss fibrinogen assays; however, when comparing VET-based fibrinogen contribution to clot firmness with Clauss fibrinogen concentration, strong differences occur within the same test under different conditions and between different tests. The most widely studied test is the thromboelastometric FIBTEM; the best predictor of a Clauss fibrinogen <1.5 g/L is placed at a maximum clot firmness around 8 mm of amplitude. Fewer data are available for thromboelastographic FF, but the correspondent value is in the range of 12 mm. Overall, due to an incomplete inhibition of platelet contribution, FF overestimates the fibrinogen contribution with respect to FIBTEM. Data on sonorheometry FCS are limited and conflicting. When addressing the correlation between different tests, it is good in general, but no fixed conversion factors can be proposed, due to a considerable dispersion of the experimental points. In conclusion, VET-based fibrinogen tests are certainly powerful tools that are presently suggested by the existing guidelines; however, when using them for clinical decision-making, users should consider the possible sources of bias, which include the different level of platelet inhibition, the role of platelet count and function, the possible different degrees of blood activation with tissue factor, the important role of factor XIII in stabilizing the fibrin clot, and others.
Micro-computed tomography as a platform for exploring Drosophila development
Authors: Schoborg Todd A. , Smith Samantha L. , Smith Lauren N. , Morris H. Douglas , Rusan Nasser M.
Published: November 2019

Understanding how events at the molecular and cellular scales contribute to tissue form and function is key to uncovering the mechanisms driving animal development, physiology and disease. Elucidating these mechanisms has been enhanced through the study of model organisms and the use of sophisticated genetic, biochemical and imaging tools. Here, we present an accessible method for non-invasive imaging of Drosophila melanogaster at high resolution using micro-computed tomography (µ-CT). We show how rapid processing of intact animals, at any developmental stage, provides precise quantitative assessment of tissue size and morphology, and permits analysis of inter-organ relationships. We then use µ-CT imaging to study growth defects in the Drosophila brain through the characterization of abnormal spindle (asp) and WD repeat domain 62 (Wdr62), orthologs of the two most commonly mutated genes in human microcephaly patients. Our work demonstrates the power of combining µ-CT with traditional genetic, cellular and developmental biology tools available in model organisms to address novel biological mechanisms that control animal development and disease.
RPTPε promotes M2-polarized macrophage migration through ROCK2 signaling and podosome formation
Authors: Lapointe Fanny , Turcotte Sylvie , Roy Joanny , Bissonnette Elyse , Rola-Pleszczynski Marek , Stankova Jana
Published: November 2019

Cysteinyl-leukotrienes (cys-LTs) have well-characterized physiopathological roles in the development of inflammatory diseases. We have previously found that protein tyrosine phosphatase ε (PTPε) is a signaling partner of CysLT1R, a high affinity receptor for leukotriene D4 (LTD4). There are two major isoforms of PTPε, receptor-like (RPTPε) and cytoplasmic (cyt-)PTPε, both of which are encoded by the PTPRE gene but from different promoters. In most cells, their expression is mutually exclusive, except in human primary monocytes, which express both isoforms. Here, we show differential PTPε isoform expression patterns between monocytes, M1 and M2 human monocyte-derived macrophages (hMDMs), with the expression of glycosylated forms of RPTPε predominantly in M2-polarized hMDMs. Using PTPε-specific siRNAs and expression of RPTPε and cyt-PTPε, we found that RPTPε is involved in monocyte adhesion and migration of M2-polarized hMDMs in response to LTD4. Altered organization of podosomes and higher phosphorylation of the inhibitory Y-722 residue of ROCK2 was also found in PTPε-siRNA-transfected cells. In conclusion, we show that differentiation and polarization of monocytes into M2-polarized hMDMs modulates the expression of PTPε isoforms and RPTPε is involved in podosome distribution, ROCK2 activation and migration in response to LTD4.
Epidermal growth factor receptor signaling suppresses αvβ6 integrin and promotes periodontal inflammation and bone loss
Authors: Bi Jiarui , Koivisto Leeni , Dai Jiayin , Zhuang Deshu , Jiang Guoqiao , Larjava Milla , Shen Ya , Bi Liangjia , Liu Fang , Haapasalo Markus , Häkkinen Lari , Larjava Hannu
Published: November 2019

In periodontal disease (PD), bacterial biofilms cause gingival inflammation, leading to bone loss. In healthy individuals, αvβ6 integrin in junctional epithelium maintains anti-inflammatory transforming growth factor-β1 (TGF-β1) signaling, whereas its expression is lost in individuals with PD. Bacterial biofilms suppress β6 integrin expression in cultured gingival epithelial cells (GECs) by attenuating TGF-β1 signaling, leading to an enhanced pro-inflammatory response. In the present study, we show that GEC exposure to biofilms induced activation of mitogen-activated protein kinases and epidermal growth factor receptor (EGFR). Inhibition of EGFR and ERK stunted both the biofilm-induced ITGB6 suppression and IL1B stimulation. Furthermore, biofilm induced the expression of endogenous EGFR ligands that suppressed ITGB6 and stimulated IL1B expression, indicating that the effects of the biofilm were mediated by autocrine EGFR signaling. Biofilm and EGFR ligands induced inhibitory phosphorylation of the TGF-β1 signaling mediator Smad3 at S208. Overexpression of a phosphorylation-defective mutant of Smad3 (S208A) reduced the β6 integrin suppression. Furthermore, inhibition of EGFR signaling significantly reduced bone loss and inflammation in an experimental PD model. Thus, EGFR inhibition may provide a target for clinical therapies to prevent inflammation and bone loss in PD.

This article has an associated First Person interview with the first author of the paper.
Untargeted metabolomics to understand the basis of phenotypic differences in amphotericin B-resistant Leishmania parasites
Authors: Pountain Andrew W. , Barrett Michael P.
Published: November 2019

Background: Protozoan Leishmania parasites are responsible for a range of clinical infections that represent a substantial challenge for global health. Amphotericin B (AmB) is increasingly used to treat Leishmania infection, so understanding the potential for resistance to this drug is an important priority. Previously we described four independently-derived AmB-resistant L. mexicana lines that exhibited resistance-associated genetic lesions resulting in altered sterol content. However, substantial phenotypic variation between these lines, including differences in virulence attributes, were not fully explained by these changes.

Methods: To identify alterations in cellular metabolism potentially related to phenotypic differences between wild-type and AmB-resistant lines, we extracted metabolites and performed untargeted metabolomics by liquid chromatography-mass spectrometry.

Results: We observed substantial differences in metabolite abundance between lines, arising in an apparently stochastic manner. Concerted remodeling of central carbon metabolism was not observed; however, in three lines, decreased abundance of several oligohexoses was observed. Given that the oligomannose mannogen is an important virulence factor in Leishmania, this could relate to loss of virulence in these lines. Increased abundance of the reduced forms of the oxidative stress-protective thiols trypanothione and glutathione was also observed in multiple lines.

Conclusions: This dataset will provide a useful resource for understanding the molecular basis of drug resistance in Leishmania, and suggests a role for metabolic changes separate from the primary mechanism of drug resistance in determining the phenotypic profile of parasite lines subjected to experimental selection of resistance.
What Safety are We Entitled to Expect of Self-driving Vehicles?
Authors: Liivak Taivo
Published: November 2019

A manufacturer of self-driving vehicles could face claims involving assertions of the product’s defectiveness. Under the Product Liability Directive, a product is deemed defective when it does not provide the safety that a person is entitled to expect. Efforts to ascertain the possibility of defectiveness connected with a self-driving vehicle could necessitate evaluating the design of the vehicle, matters of human–machine interaction, and the role of the human in the relevant incident of damage. This article lays groundwork by considering the capabilities of self-driving vehicles, the role and expectations of human beings, and legislation aimed at ensuring safety and preventing damage. This discussion concretely situates the concept of the safety of self-driving vehicles in the context of product liability law, which is inherently preoccupied mainly with the consequences.
Modern Methods of Staff Onboarding
Authors: Kashtanova YEkatyerina
Published: November 2019

The article presents modern methods and techniques of staff onboarding. As you know, absolutely anyone experiences stress when entering a new organization or a new position. Technology adaptation reduces business costs, allowing the beginner to start as quickly as possible to fully function, increases staff loyalty, strengthens the team and, fi nally, saves time for the newest employee and for the organization. In this regard, the article describes the modern approach to the classifi cation and use of methods of staff onboarding, presents real tools for building onboarding programs. In order to transfer professional knowledge and increase employee involvement, it is proposed to actively use the full range of these methods, and therefore the article discusses the experience of their application.
Analysis of the Most Popular Profession of the Samara Region Based on the Data of the Resource «Headhunter.ru (hh.ru)»
Authors: Kruzhkina K. , Simonova M.
Published: November 2019

The article analyzes the data of the resource “HeadHunter.ru (hh.ru)” in order to identify the popular profession of the Samara Region among employers and applicants. The relevance of this work lies in the fact that currently the labor market has problems with employment not only among young professionals, but also people with experience, and here are the possible causes of these problems. This article helps to visually see the statistics of vacancies and resumes by professional fi eld, as well as statistics on gender, age, education and work experience of applicants. Such statistics can help in solving the problems of employment and employment of citizens of the Samara region, as well as contribute. The paper also presents the calculation of the average salary offered to specialists of a popular profession.
Modern Information Technology in Development of the National Accounting
Authors: Поленова С. , Polenova S.
Published: November 2019

Th e managing subjects, accepting management decisions of the varied nature, lean, in the fi rst place, on given information system of the enterprise, including accounting. Th e aim of the article is consideration of the problems of the shaping reliable and useful information in Russian accounting and reporting when use leading technology to automations of the account process, motivation possible variant their decisions.
Nondestructive Testing and Evaluation of Reinforced Concrete Bridge Decks: A Case Study
Authors: Аме-Иахя Шериф , Amer-Yahia Cherif , Мэджидзэдех Тодд , Majidzadeh Todd
Published: November 2019

В статье описывается детальное исследование покрытий полотна двух мостов с использованием георадара, инфракрасной термографии, дорожного утюга с цепью, картирования трещин, отбора кернов и измерения концентрации ионов хлора. Обсуждается использование георадара для обнаружения дефектов полотна моста на уровне стальной арматуры и использование термографии для идентификации расслоения покрытия. Полученные результаты сравниваются с результатами зондирования покрытий. Обсуждена корреляция между повреждениями, обнаруженными с использованием георадара и термографии, и обычной технологией дорожного утюга с цепью. Методы НК, использованные в этом исследовании, дополняли друг друга для получения максимального объёма информации и более эффективной оценки состояния покрытий мостового полотна. Инфракрасная термография была эффективной при обнаружении неглубокого расслоения. Георадар обнаружил повреждения на уровне арматурнго профиля и повреждения, простирающиеся вверх от коррозионной арматуры примерно на 2,5 см от покрытия. В отличие от дорожного утюга, который обнаруживает разрывы на последней стадии, георадар обнаруживает признаки, связанные с коррозией арматуры, такие как высокое содержание влаги и высокие концентрации хлоридных ионов, на ранних стадиях. Предлагается комплексные меры восстановления этих двух элементов покрытия.
Transsexualism or psychotic disorder? A case study
Authors: Jakubowski Tomasz
Published: November 2019

Celem artykułu jest analiza przypadku mężczyzny z diagnozą schizofrenii paranoidalnej, który doświadcza urojeń i omamów dotyczących zmiany płci, oraz krótki przegląd literatury. Dane zaprezentowane w studium przypadku zostały zebrane podczas wywiadu klinicznego, w ciągu półrocznego procesu diagnostycznego. Wywiad miał postać częściowo ustrukturalizowaną, wykorzystano również baterię testów - Minesocki Wielowymiarowy Inwentarz Osobowości 2 (MMPI-2), Ustrukturalizowany Wywiad Kliniczny do Badania Zaburzeń z Osi I DSM-IV-TR (SCID- I), Ustrukturalizowany Wywiad Kliniczny do Badania Zaburzeń z Osi II DSM-IV-TR (SCID-II), Inwentarz Płci Psychologicznej (IPP), Montrealski Test do Oceny Stanu Poznawczego (MoCA), Skala Inteligencji Wechslera dla Dorosłych (WAIS-R). Opis przypadku osoby, której przypisano po urodzeniu płeć męską, a która identyfikuje się jako kobieta. W trakcie diagnozy zostały stwierdzone u badanego urojenia i omamy, które w obrazie klinicznym zdają się mieć dominujący wpływ na poczucie niezgodności płciowej. Wyniki uzyskane w wykorzystanych narzędziach zdają się potwierdzać hipotezę nt. zasadności postawienia diagnozy schizofrenii paranoidalnej. Biorąc pod uwagę zaprezentowane studium przypadku, w procesie diagnozy transseksualizmu jest szczególnie ważne zróżnicowanie go z zaburzeniami psychotycznymi.
The Use of Apps in Foreign Language Education: A Survey-Driven Study
Authors: Powers Caleb
Published: November 2019

The purpose of this study was to understand why advancements in technology were not being implemented in foreign language education and how those new technologies could improve foreign language education. This study surveyed 114 foreign language students in order to gain information on how they used technology to learn a foreign language. The questions on the survey related to the topics of attitudes toward technology in general, the studentsâ€™ accessibility and academic/personal use of technology tools, and their awareness and usage of specific foreign language learning mobile apps. It was found that apps like Duolingo, Rosetta Stone, and Babbel are more often used than other language learning apps, they fulfill crucial elements of education, and students prioritize facility of use, accessibility, and price when deciding whether to keep an app or not.