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27589755

A Ground-Based Near Infrared Camera Array System for UAV Auto-Landing in GPS-Denied Environment.

This paper proposes a novel infrared camera array guidance system with capability to track and provide real time position and speed of a fixed-wing Unmanned air vehicle (UAV) during a landing process. The system mainly include three novel parts: (1) Infrared camera array and near infrared laser lamp based cooperative long range optical imaging module; (2) Large scale outdoor camera array calibration module; and (3) Laser marker detection and 3D tracking module. Extensive automatic landing experiments with fixed-wing flight demonstrate that our infrared camera array system has the unique ability to guide the UAV landing safely and accurately in real time. Moreover, the measurement and control distance of our system is more than 1000 m. The experimental results also demonstrate that our system can be used for UAV automatic accurate landing in Global Position System (GPS)-denied environments.

['Yang|Tao|T|', 'Li|Guangpo|G|', 'Li|Jing|J|', 'Zhang|Yanning|Y|', 'Zhang|Xiaoqiang|X|', 'Zhang|Zhuoyue|Z|', 'Li|Zhi|Z|']

2016

27670748

Tracking the Fate of Surface Plasmon Resonance-Generated Hot Electrons by In Situ SERS Surveying of Catalyzed Reaction.

Plasmonic catalysis is an emerging process that utilizes surface plasmon resonance (SPR) process to harnesses solar energy for the promotion of catalyzed reactions. In most cases, SPR generated hot electrons (HEs) play an indispensable role in this solar-chemical energy shift process. Therefore, understanding the effectiveness of the HEs in promoting chemical reactions, and identifying the key factors that contribute to this utilization efficiency is of profound importance. Herein, the authors outline an in situ surface enhanced Raman spectroscopy protocol to track the fate of HEs. This is based on the unheeded HEs-acceleration nature of the p-nitirothiophenol hydrogenation reaction. By this way, the authors discover that unlike Au@Pd nanostructures which experience a 20-fold increase in rate constant, HEs primary leak to surrounding H+ /O species through Ag pinholes in Ag@Pd. This work sheds light on why Ag is seldom employed as a plasmonic cocatalyst, and provides a new viewpoint to design plasmonic nanocatalysts with efficient light utilization.

['Liu|Rui|R|', 'He|Zuoliang|Z|', 'Sun|Jiefang|J|', 'Liu|Jingfu|J|', 'Jiang|Guibin|G|']

2016

31047704

Atrial fibrillation case finding in over 65 s with cardiovascular risk factors - Results of initial Scottish clinical experience.

BACKGROUND Atrial fibrillation (AF) is a major preventable risk factor for stroke and may be silent in elderly individuals who are at especially high risk. This paper describes the first phase of implementation of a clinical AF detection programme in a community setting. Objectives were (i) to determine the feasibility of using a handheld ECG recording system for AF detection among individuals aged 65 years or more, who have cardiovascular risk factors. (ii) to estimate the yield of previously undiagnosed atrial fibrillation cases, and the proportion of these who would be suitable for oral anticoagulation. METHODS a handheld ECG monitor was placed in each of 23 primary care practices across Scotland. Eligible patients attending for annual health checks had ECGs recorded, and the ECGs were transmitted and interpreted by two senior cardiologists. ECG quality was rated, and an adjudication made on the rhythm. For patients confirmed with AF, stroke and bleeding risk were estimated using CHA2DS2-VASc and HAS-BLED scoring tools. RESULTS single lead ECGs were recorded in 1805 patients (703 female and 1102 male), mean (SD) age 74.9 (7.1) years. Rhythm regularity could be assessed in 98.7% of ECGs recorded. 92 patients (5.1%) were found to have AF. Median [range]CHA2DS2-VASc score was 4 ([2-7) and median [range] HAS-BLED score was 2 (1-5). CONCLUSION handheld ECG recording can be used to identify AF in the primary care setting, with minimal training. The yield was relatively high.

['Grubb|Neil R|NR|', 'Elder|Douglas|D|', 'Broadhurst|Paul|P|', 'Reoch|Anne|A|', 'Tassie|Emma|E|', 'Neilson|Aileen|A|']

2019

33405813

A Study of Perturbations in Structure and Elastic Modulus of Bone Microconstituents Using Bimodal Amplitude Modulated-Frequency Modulated Atomic Force Microscopy.

Sepsis-related bone diseases are rarely reported although many ICU patients are diagnosed with bone damage after prolonged immobility. In this work, cortical bone of femurs from Sprague-Dawley rats under mild sepsis condition are investigated by using Scanning Probe Microscopy (SPM) to study the influence of sepsis on the changes of structure, chemistry, and elastic modulus of bone microconstituents, i.e., collagen fibers and mineral. The results show that there are significant changes on elastic modulus, shape, and chemical composition of collagen fibers 24 h after the sepsis insult, but all of the changes are recovered to almost normal 96 h after the insult. These phenomena are found to be associated with demineralization of the collagen fiber. For the mineral constituents in bone, the elastic modulus decreases significantly 96 h after the insult, showing slower responses compared with those in the collagen fibers. Particle analysis reveals that the size of the mineral particles decreases continuously and significantly with the time after the sepsis insulting. This work reveals the responding processes of bone microconstituents to sepsis in rat mode and, hence, can provide an insight into the pathogenesis of sepsis related human bone damage.

['Sun|Yao|Y|http://orcid.org/0000-0001-8802-0580', 'Vu|Lien Hong|LH|', 'Chew|Nicholas|N|', 'Puthucheary|Zudin|Z|', 'Cove|Matthew E|ME|', 'Zeng|Kaiyang|K|http://orcid.org/0000-0002-3348-0018']

2019

33443169

Cigarette smoke induces miR-132 in Th17 cells that enhance osteoclastogenesis in inflammatory arthritis.

Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized by joint destruction and severe morbidity. Cigarette smoking (CS) can exacerbate the incidence and severity of RA. Although Th17 cells and the Aryl hydrocarbon receptor (AhR) have been implicated, the mechanism by which CS induces RA development remains unclear. Here, using transcriptomic analysis, we show that microRNA-132 is specifically induced in Th17 cells in the presence of either AhR agonist or CS-enriched medium. miRNA-132 thus induced is packaged into extracellular vesicles produced by Th17 and acts as a proinflammatory mediator increasing osteoclastogenesis through the down-regulation of COX2. In vivo, articular knockdown of miR-132 in murine arthritis models reduces the number of osteoclasts in the joints. Clinically, RA patients express higher levels of miR-132 than do healthy individuals. This increase is further elevated by cigarette smoking. Together, these results reveal a hitherto unrecognized mechanism by which CS could exacerbate RA and further advance understanding of the impact of environmental factors on the pathogenesis of chronic inflammatory diseases.

['Donate|Paula B|PB|0000-0001-8422-8894', 'Alves de Lima|Kalil|K|0000-0002-9149-168X', 'Peres|Raphael S|RS|', 'Almeida|Fausto|F|', 'Fukada|Sandra Y|SY|', 'Silva|Tarcilia A|TA|', 'Nascimento|Daniele C|DC|', 'Cecilio|Nerry T|NT|', 'Talbot|Jhimmy|J|', 'Oliveira|Rene D|RD|0000-0003-0229-6864', 'Passos|Geraldo A|GA|0000-0002-4408-140X', 'Alves-Filho|José Carlos|JC|', 'Cunha|Thiago M|TM|0000-0003-1084-0065', 'Louzada-Junior|Paulo|P|0000-0003-2585-3870', 'Liew|Foo Y|FY|', 'Cunha|Fernando Q|FQ|']

2021

28171787

High-throughput NIR-chemometric methods for chemical and pharmaceutical characterization of sustained release tablets.

The aim of this study was the development and validation of methods based on near-infrared spectroscopy (NIRS) and chemometry, useful for characterization of sustained release (SR) tablets with indapamide, in terms of tablet composition (API and two excipients), in vitro drug release mechanism (k and n Peppas) and crushing strength. A calibration set consisting of 25 different tablets formulations containing API, HPMC and lactose at five different content levels in the range 100±20% relative to a targeted tablet composition, were manufactured by direct compression in order to develop the methods for prediction of tablet composition, and in vitro drug release mechanism. On the other hand, a 15 batches calibration set prepared at five different compression forces was used for development of methods for prediction of crushing strength. Moreover, independent batches were manufactured for validation of all methods Intact tablets were analyzed by transmission mode with NIRS, the spectra were pre-processed, and partial least square (PLS) regression was used to build prediction models. Cross-validation was carried out in order to select the optimal number of PLS factors for all models, and the best model was chosen based on their RMSECV and bias. All developed methods were validated in terms of trueness, precision and accuracy. Based on the validation results, the methods proposed in this work can successfully be applied for routine determination of indapamide, HPMC and lactose content of sustained release tablets, as well as for prediction of their in vitro drug release mechanism (k and n Peppas) and crushing strength.

['Porfire|Alina|A|', 'Filip|Cristina|C|', 'Tomuta|Ioan|I|']

2017

29344481

Choroidal Melanoma Mimicker: A Case of Metastatic Clear-Cell Renal Cell Carcinoma.

Choroidal melanoma is the most common primary intraocular malignancy, yet metastatic disease remains the most common malignancy of the eye. Differentiating these entities is essential as treatment, systemic associations, and prognosis vary dramatically between the two. Established diagnostic criteria are accurate for the diagnosis of uveal melanoma. Yet, metastatic disease may be misdiagnosed as a uveal melanoma in rare cases. We report a case of metastatic clear-cell renal cell carcinoma masquerading as uveal melanoma. A 73-year-old Caucasian man with a history of renal cell carcinoma presented with a 15 × 12 × 7 mm homogenous, pigmented, and acoustically hollow mass without hemorrhage or exudation. The patient was initially treated with plaque radiotherapy with good tumor regression. However, the patient developed pain and vision loss due to total exudative retinal detachment. Subsequent enucleation allowed histopathologic confirmation of clear-cell renal cell carcinoma. Nine years following enucleation, the patient remains in complete remission without evidence of other systemic metastases. Renal cell carcinoma should be considered when evaluating patients with probable uveal melanoma. Delayed-onset ocular metastasis from renal cell carcinoma exhibits an atypical clinical course with the possibility of durable remission following enucleation.

['Komanski|Chris B|CB|', 'Rubino|Shaina M|SM|', 'Meyer|Jacob C|JC|', 'Greven|Craig M|CM|']

2017

30359908

Relationships between eating disorder-specific and transdiagnostic risk factors for binge eating: An integrative moderated mediation model of emotion regulation, anticipatory reward, and expectancy.

Although relationships between negative affect, emotion dysregulation, and binge eating have been well-established, the mechanisms and individual risk factors that account for this relationship have yet to be elucidated. In addition to emotion dysregulation, altered reward functioning and negative affect eating expectancies (i.e., the expectancy that eating will relieve negative affect) are factors that have been previously linked to binge eating, though theoretical frameworks have not provided an integrated conceptualization of relationships between these domains. Therefore, the present study examined an integrative moderated mediation model among a sample of 101 adults with self-reported eating disorder (ED) symptoms who completed a battery of online questionnaires. Results supported the hypothesized model, which demonstrated that eating expectancies mediated the relationship between emotion dysregulation and binge eating frequency, and there was a positive association between emotion dysregulation and eating expectancies among individuals high in anticipatory reward. These findings provide preliminary support for an integrated approach to understanding transdiagnostic and ED-specific risk factors that potentiate binge eating.

['Smith|Kathryn E|KE|', 'Mason|Tyler B|TB|', 'Peterson|Carol B|CB|', 'Pearson|Carolyn M|CM|']

2018

26159811

Theoretical study of the effect of shear deformable shell model, elastic foundation and size dependency on the vibration of protein microtubule.

In this paper, isotropic cylindrical shell model with first order shear deformation theory based on modified couple stress theory is used to investigate the mechanical behavior of microtubules and to consider the size effect in the nano-scale. Besides, partial equations of shell motion with classical and non-classical corresponding boundary conditions are derived from Hamilton׳s principle. The study models the microtubule as a simply supported shell and the Navier procedure is used to solve the vibration problem. To simulate the environment of microtubule, Pasternak foundation is used. The free vibration of the microtubule is examined in the presence and absence of cytoplasm, and the significant parameter, length dependence flexural rigidity is determined based on the new model. Finally, the effect of different system parameters such as length, size effect parameters, shear modulus ratio and substrate parameters on free vibration microtubule is investigated. Comparison of the results of the new model with the classical model and the results obtained by other researchers reveals that the model presented in this paper is more accurate than other models used in this area and in better agreement with experimental data.

['Baninajjaryan|Alireza|A|', 'Tadi Beni|Yaghoub|Y|']

2015

34123615

Severe Mental Illness: A Contraindication to Watchful Waiting in Hernia Management?

Watchful waiting (WW) is a strategy that can be used to manage hernias whereby patients who are asymptomatic or minimally symptomatic are observed until symptoms worsen or complications develop, prompting surgical intervention. The successful implementation of a WW strategy requires patients to report changes in their clinical condition to receive timely care. Patients who have severe mental illness may defer seeking care when appropriate. This case report describes our experience treating a patient with severe mental illness who had a primary ventral hernia managed by WW. She was lost to follow-up and subsequently presented with a strangulated epigastric hernia which fistulized to the skin. The case report highlights the challenges of attempting WW in patients with severe mental illness. We suggest that poorly controlled severe mental illness should be considered a relative contraindication to WW.

['Milne|David M|DM|', 'Naraynsingh|Vijay|V|', 'Goolcharan|Shivan|S|']

2021

32126480

The impact of PUFA on cell responses: Caution should be exercised when selecting PUFA concentrations in cell culture.

Polyunsaturated fatty acids (PUFA) are important components of cellular membranes, serving both structural and signaling functions. Investigation of the functional responses of cells to various PUFA often involves cell culture experiments, which can then inform or guide subsequent in vivo and clinical investigations. In this study, human carcinoma and leukemia cell lines (MCF-7, HepG2, THP-1, Jurkat) were incubated for 3 days in the presence of up to 150 μM of exogenous arachidonic or eicosapentaenoic acids. At concentrations up to 20 μM these PUFA were enriched in cellular phospholipids, but at concentrations of 20 μM or higher cells accumulated large quantities of these PUFA and their elongation products into triglycerides. This coincided with decreased cell proliferation and enhanced apoptosis. Inhibition of DGAT1 but not DGAT2 enhanced the cytotoxic effect of exogenous PUFA suggesting a protective role of PUFA sequestration into TGs. Lower (10 μM) and higher (50 μM) exogenous PUFA concentrations also had different impacts on the expression of PUFA metabolizing enzymes. Overall, these results indicate that caution must be exercised when planning in vitro experiments since elevated concentrations of PUFA can lead to dysfunctional cellular responses that are not predictive of in vivo responses to dietary PUFA.

['Mbarik|Maroua|M|', 'Biam|Roody S|RS|', 'Robichaud|Philippe-Pierre|PP|', 'Surette|Marc E|ME|']

2020

31957469

β1-Adrenoreceptor Autoantibodies in Heart Failure: Physiology and Therapeutic Implications.

Antibodies that activate the β1-AR (β1-adrenoreceptor) can induce heart failure in animal models. These antibodies are often found in patients with heart failure secondary to varying etiologies. Their binding to the β1 receptor leads to prolonged receptor activation with subsequent induction of cellular dysfunction, apoptosis, and arrhythmias. β-blocker therapy while highly effective for heart failure, may not be sufficient treatment for patients who have β1 receptor autoantibodies. Removal of these autoantibodies by immunoadsorption has been shown to improve heart failure in small studies. However, immunoadsorption is costly, time consuming, and carries potential risks. An alternative to immunoadsorption is neutralization of autoantibodies through the intravenous application of small soluble molecules, such as peptides or aptamers, which specifically target and neutralize β1-AR autoantibodies. Peptides may induce immunogenicity. Animal as well as early phase human studies with aptamers have not shown safety concerns to date and have demonstrated effectiveness in reducing autoantibody levels. Novel aptamers have the potential advantage of having a wide spectrum of action, neutralizing a variety of known circulating G-protein coupled receptor autoantibodies. These aptamers, therefore, have the potential to be novel therapeutic option for patients with heart failure who have positive for β1-AR autoantibodies. However, clinical outcomes trials are needed to assess the clinical utility of this novel approach to treat heart failure.

['Düngen|Hans-Dirk|HD|', 'Dordevic|Aleksandar|A|', 'Felix|Stephan B|SB|', 'Pieske|Burkert|B|', 'Voors|Adriaan A|AA|', 'McMurray|John J V|JJV|', 'Butler|Javed|J|']

2020

23129565

Exploring the psychological processes underlying touch: lessons from the Alexander Technique.

UNLABELLED The experience of touch is significant; both in its positive implications and in how it attracts caution and controversy. Accordingly, physical contact within psychological therapy has been shown to improve well-being and the therapeutic relationship, yet the majority of therapists never or rarely use touch. This research aimed to explore psychological processes underlying touch through the Alexander Technique, a psycho-physical technique taught one to one using touch. Six individuals who had received the Alexander Technique were interviewed, and 111 completed surveys. Interview data suggested an incompatibility between touch and the spoken word, which was understood through the way touch lacks verbal discourses in our society. The largely simplistic and dichotomous verbal understanding we have (either only very positive or very negative) could help understand some of the societal-level caution surrounding touch. Touch was seen also as a nurturing experience by interviewees, which influenced inter-personal and intra-personal relational processes. Developmental models were used to frame the way touch strengthened the pupil-teacher relationship and the way pupils' intra-personal psychological change seemed linked to this relational experience. The surveys largely supported these findings, and discussion is made around the notable way pupils negatively interpreted the intention of the survey. Implications for the use of touch in psychological therapies are discussed, as are limitations and ideas for future research. KEY PRACTITIONER MESSAGE Touch is a powerful experience, and physical contact within psychological therapy has been shown to improve well-being and the therapeutic relationship, yet the majority of therapists never or rarely use touch. The AT is an alternative therapeutic approach to psycho-physical well-being that offers an interesting model to study the impact of touch. Findings from those that have used the technique reaffirmed that touch can improve well-being and can be a powerful force in the 'therapeutic relationship'. Accounts drew strong parallels with developmental experiences, which may be of particular interest to those working psychodynamically. Findings also highlighted the lack of discourses our culture has for touch and how the ones we share can be super-imposed onto experiences. This should be kept in mind when discussing all types of physical contact with clients. Outcomes from AT pupils cannot be generalized to those seeking psychological support; however, the findings accentuated the power of holistic working. This is important as we begin to understand more around how emotions are held in the body.

['Jones|T|T|', 'Glover|L|L|']

2014

24426364

Molecular diagnosis of shwachman-diamond syndrome presenting with pancytopenia at an early age: the first report from Turkey.

A three-month-old boy presented with growth failure, skeletal abnormalities, otitis media and pancytopenia. Exocrine pancreatic insufficiency was confirmed by low levels of fecal elastase. He was diagnosed as Shwachman-Diamond syndrome by clinical and laboratory findings. The diagnosis was confirmed by sequence analysis for SBDS gene on chromosome seven revealing compound heterozygous mutation, which are c.258+2T-C and c.183-184TA-CT. Matched unrelated donor screening for hematopoietic stem cell transplantation was initiated. Unfortunately, he died of respiratory difficulty at 5 months of age. Our case is the youngest patient whose presumptive Shwachman-Diamond syndrome diagnosis was confirmed by molecular analysis.

['Gokce|Muge|M|', 'Tuncer|Murat|M|', 'Cetin|Mualla|M|', 'Gumruk|Fatma|F|']

2013

29681594

Postnatal changes of interleukin-18 receptor immunoreactivity in neurons of the retrosplenial cortex in wild-type and interleukin-18 knock out mice.

Interleukin-18 (IL-18), which is involved in the inflammatory response, is also found in the cerebral cortex. IL-18 receptor-immunoreactive (IL-18R-ir) neurons are present in layer V of the retrosplenial cortex (RSC). In the adult IL-18 knock out (KO) mice, no IL-18R-ir neurons but many degenerated neurons are present in layer V of the RSC, suggesting that any changes in the neurons of layer V have occurred during postnatal development. We examined changes of IL-18R expression during postnatal development. In the wild-type mice, many IL-18R-ir neurons were present in layers II, III and VI of the RSC in 2-week-old mice, whereas they were sparsely observed in only layer III in 3-week-old mice. No IL-18R-ir neurons were present in 4- and 5-week-old mice. In older than 6-week-old mice, many IL-18R-ir neurons were present in layers V and VI. The IL-18KO mice showed IL-18R-ir neurons in layers II, III and VI at 2-weeks-old, and a few in layer III at 3-week-old mice, similar to that in the wild-type mice. No IL-18R-ir neurons were found in mice older than 4 weeks of age. Thus, IL-18 or IL-18R seem to be involved in the construction of neural circuits corresponding to events after 3-weeks of age.

['Hayakawa|Tetsu|T|', 'Hata|Masaki|M|', 'Kuwahara-Otani|Sachi|S|', 'Yagi|Hideshi|H|', 'Okamura|Haruki|H|']

2017

25238112

Complete mitochondrial genome of Ptychobarbus kaznakovi (Teleostei: Cypriniformes: Cyprinidae), and repetitive sequences in the D-loop.

The complete mitochondrial DNA genome of Ptychobarbus kaznakovi was sequenced and characterized. The genome is 16,842 bp in length. Similar with most teleosts, it has two ribosomal RNA (rRNA) genes, 13 protein-coding genes, 22 transfer RNA (tRNA) genes, and one displacement loop (D-loop) region. Conserved sequence blocks, including ETAS, CSB-B, D, E, F, and CSB1-3, were identified in the D-loop, which is similar to other species in Cypriniformes. Nevertheless, a 55 bp tandem repeat array was also identified at 3' end of the D-loop, which is the first finding in Schizothoracinae. Phylogenetic analysis showed that the species of Ptychobarbus (P. dipogon and P. kaznakovi) formed a monophyletic group and represented close relationship to the species without scales in Schizothoracinae.

['Ma|Qingzhan|Q|', 'Wu|Bo|B|', 'Li|Jiuxuan|J|', 'Song|Zhaobin|Z|']

2016

34451290

Recycled Porcine Bone Powder as Filler in Thermoplastic Composite Materials Enriched with Chitosan for a Bone Scaffold Application.

This work aims to synthesize biocompatible composite materials loaded with recycled porcine bone powder (BP) to fabricate scaffolds for in-situ reconstruction of bone structures. Polylactic acid (PLA) and poly(ε-caprolactone) (PCL) were tested as matrices in percentages from 40 wt% to 80 wt%. Chitosan (CS) was selected for its antibacterial properties, in the amount from 5 wt% to 15 wt%, and BP from 20 wt% to 50 wt% as active filler to promote osseointegration. In this preliminary investigation, samples have been produced by solvent casting to introduce the highest possible percentage of fillers. PCL has been chosen as a matrix due to its greater ability to incorporate fillers, ensuring their adequate dispersion and lower working temperatures compared to PLA. Tensile tests demonstrated strength properties (6-10 MPa) suitable for hard tissue engineering applications. Based on the different findings (integration of PLA in the composite system, improvements in CS adhesion and mechanical properties), the authors supposed an optimization of the synthesis process, focused on the possible implementation of the electrospinning technique to develop PCL-BP composites reinforced with PLA-CS microfibers. Finally, biological tests were conducted to evaluate the antibacterial activity of CS, demonstrating the applicability of the materials for the biomedical field.

['Valente|Marco|M|0000-0002-6298-3693', 'Puiggalí|Jordi|J|0000-0002-0640-4474', 'Del Valle|Luis J|LJ|0000-0001-9916-1741', 'Titolo|Gioconda|G|0000-0002-5413-9310', 'Sambucci|Matteo|M|0000-0002-0974-2129']

2021

31938576

A pilot study on searching for peri-nuclear NeuN-positive cells.

The aim of this study was to find out neuron (-like) cells in peripheral organs by cell markers in rats. Adult male Sprague-Dawley rats were anaesthetized. Their organs including brain, heart, lung, liver, kidney, stomach, duodenum, and ileum were harvested. The mRNA and protein in these organs were extracted. RNA sequencing (RNA-Seq) was carried out, and NeuN, a "specific" marker for neuronal soma, was assayed with Western blotting. The sections of the aforementioned organs were obtained after a routine fixation (4% methanal)-dehydration (ethanol)-embedding (paraffin) process. NeuN in the sections and seven non-neuronal cell lines was analyzed by immunofluorescence (IF) or immunohistochemistry (IHC). Neuronal markers, such as Eno2, NeuN (Rbfox3), choline acetyltransferase (Chat), as well as tyrosine hydroxylase (Th), and neuronal-glial markers, e.g., glial fibrillary acidic protein (Gfap), S100b, 2', 3'-cyclic nucleotide 3'-phosphodiesterase (Cnp), and other related markers, were positively expressed in all the organs at mRNA level. NeuN was further analyzed by Western blotting. The IF and IHC assays showed that NeuN-positive cells were distributed in all the peripheral tissues (mainly peri-nuclear NeuN-positive cells) though with different patterns from that in brain (nuclear NeuN-positive cells), and a NeuN-negative tissue could not be found. Especially, NeuN and Myl3 co-expressed in the cytoplasm of myocardial cells, suggesting that NeuN could possess other functions than neuronal differentiation. Also, the protein was positively expressed in seven non-neuronal cell lines. Our findings suggested that NeuN-positive cells exist widely, and without identification of its distribution pattern, the specificity of NeuN for neurons could be limited.

['Yu|Yun|Y|', 'Wu|Meiyu|M|', 'Zhang|Nan|N|', 'Yin|Hua|H|', 'Shu|Bin|B|', 'Duan|Weigang|W|']

2020

24492289

Engineering multivalent antibodies to target heregulin-induced HER3 signaling in breast cancer cells.

The use of antibodies in therapy and diagnosis has undergone an unprecedented expansion during the past two decades. This is due in part to innovations in antibody engineering that now offer opportunities for the production of "second generation" antibodies with multiple specificities or altered valencies. The targeting of individual components of the human epidermal growth factor receptor (HER)3-PI3K signaling axis, including the preferred heterodimerization partner HER2, is known to have limited anti-tumor effects. The efficacy of antibodies or small molecule tyrosine kinase inhibitors (TKIs) in targeting this axis is further reduced by the presence of the HER3 ligand, heregulin. To address these shortcomings, we performed a comparative analysis of two distinct approaches toward reducing the proliferation and signaling in HER2 overexpressing tumor cells in the presence of heregulin. These strategies both involve the use of engineered antibodies in combination with the epidermal growth factor receptor (EGFR)/HER2 specific TKI, lapatinib. In the first approach, we generated a bispecific anti-HER2/HER3 antibody that, in the presence of lapatinib, is designed to sequester HER3 into inactive HER2-HER3 dimers that restrain HER3 interactions with other possible dimerization partners. The second approach involves the use of a tetravalent anti-HER3 antibody with the goal of inducing efficient HER3 internalization and degradation. In combination with lapatinib, we demonstrate that although the multivalent HER3 antibody is more effective than its bivalent counterpart in reducing heregulin-mediated signaling and growth, the bispecific HER2/HER3 antibody has increased inhibitory activity. Collectively, these observations provide support for the therapeutic use of bispecifics in combination with TKIs to recruit HER3 into complexes that are functionally inert.

['Kang|Jeffrey C|JC|', 'Poovassery|Jayakumar S|JS|', 'Bansal|Pankaj|P|', 'You|Sungyong|S|', 'Manjarres|Isabel M|IM|', 'Ober|Raimund J|RJ|', 'Ward|E Sally|ES|']

2014

34494187

Briquettes of acai seeds: characterization of the biomass and influence of the parameters of production temperature and pressure in the physical-mechanical and energy quality.

Agro-industries, leveraged by the high demand of acai products, promote environmental impact through the generation of wastes in several locals in Amazon. The use with bioenergetic purposes has capacity to mitigate these scenario. Thus, the aim of the study was to characterize the biomass of acai seeds and establish the technical parameters of temperature and pressure of work to the production of briquettes of physical, mechanical and thermal quality. Temperatures of 120, 140 and 160 °C; and pressures of 15, 20 and 25 MPa were studied. We analyzed the briquettes mechanical compressive strength, rate of water absorption, rate of volumetric expansion and energy and apparent density. To the characterization of in natura seeds, the proximate analysis, chemical composition (extractives, holocellulose and lignin contents), higher, lower and useful heating value were determined. The proximate analysis indicated biomass thermal resistance, potential to direct burning and conversion by thermochemical processes. The lignin content may increase briquettes compressive strength produced in high temperatures. It was observed that the temperature had more influence in the evaluated briquettes characteristics than the pressure. The compressive strength was greater in 160 °C and 15 MPa briquettes, indicating that the lignin works as binder in this temperature, however, with pressure improvement the resistance is not favored due to the limit of resistance to compaction. The rate of water absorption decreased with the pressure increase and the temperature statistically affected in 140 °C briquettes. We observed volumetric expansion values in consonance to other found in dense biofuels of the literature. Further, the apparent density and energy density were favored by pressure improvement and the temperature helped in the increase of the apparent density. Moreover, the produced briquettes presented gain in the apparent density regarding the in natura biomass and had energy density comparable to coal and adequate to co-firing in boilers.

['de Oliveira|Paulo Renato Souza|PRS|', 'Trugilho|Paulo Fernando|PF|', 'de Oliveira|Tiago José Pires|TJP|http://orcid.org/0000-0001-7537-6342']

2021

33740959

A technical note on contamination from PRF tubes containing silica and silicone.

BACKGROUND Platelet-rich fibrin (PRF) has been widely utilized in modern medicine and dentistry owing to its ability to rapidly stimulate neoangiogenesis, leading to faster tissue regeneration. While improvements over traditional platelet rich plasma therapies (which use chemical additives such as bovine thrombin and calcium chloride) have been observed, most clinicians are unaware that many tubes utilized for the production of 'natural' and '100% autologous' PRF may in fact contain chemical additives without appropriate or transparent knowledge provided to the treating clinician. The aim of this overview article is therefore to provide a technical note on recent discoveries related to PRF tubes and describe recent trends related to research on the topic from the authors laboratories. METHODS Recommendations are provided to clinicians with the aim of further optimizing PRF clots/membranes by appropriate understanding of PRF tubes. The most common additives to PRF tubes reported in the literature are silica and/or silicone. A variety of studies have been performed on their topic described in this narrative review article. RESULTS Typically, PRF production is best achieved with plain, chemical-free glass tubes. Unfortunately, a variety of other centrifugation tubes commonly used for lab testing/diagnostics and not necessarily manufactured for human use have been utilized in clinical practice for the production of PRF with unpredictable clinical outcomes. Many clinicians have noted an increased variability in PRF clot sizes, a decreased rate of clot formation (PRF remains liquid even after an adequate protocol is followed), or even an increased rate in the clinical signs of inflammation following the use of PRF. CONCLUSION This technical note addresses these issues in detail and provides scientific background of recent research articles on the topic. Furthermore, the need to adequately select appropriate centrifugation tubes for the production of PRF is highlighted with quantitative data provided from in vitro and animal investigations emphasizing the negative impact of the addition of silica/silicone on clot formation, cell behavior and in vivo inflammation.

['Miron|Richard J|RJ|', 'Kawase|Tomoyuki|T|', 'Dham|Anika|A|', 'Zhang|Yufeng|Y|', 'Fujioka-Kobayashi|Masako|M|', 'Sculean|Anton|A|']

2021

31034898

Prevalence and vascular risk factors of basal ganglia calcifications in patients at risk for cerebrovascular disease.

BACKGROUND AND PURPOSE Risk factors for and meaning of basal ganglia calcifications outside Fahr syndrome are poorly understood. We aimed to assess the prevalence of basal ganglia calcifications and the association with vascular risk factors. MATERIALS AND METHODS 1133 patients suspected of acute ischemic stroke from the Dutch acute stroke (DUST) study who underwent thin-slice unenhanced brain CT were analyzed. Basal ganglia calcifications were scored bilaterally as absent, mild (dot), moderate (multiple dots or single artery) and severe (confluent). Uni- and multivariable logistic regression analysis was used to determine possible risk factors (age, gender, history of stroke, smoking, hypertension, diabetes mellitus, hyperlipidemia, body mass index (BMI), renal function and family history of cardiovascular disease under 60 years) for presence of basal ganglia calcifications and ordinal regression analysis for severity of basal ganglia calcifications. RESULTS Mean age was 67.4 years (SD: 13.8), 56.8% were male. 337 (29.7%) patients had basal ganglia calcifications, of which 196 (58%) were mild, 103 (31%) moderate, 38 (11%) severe. In multivariable logistic regression analysis, age (OR: 1.02, 95% CI 1.01-1.03, P < 0.01) and BMI (OR: 0.95, 95% CI 0.91-0.98, p 0.01) were significantly associated with the presence of basal ganglia calcifications. Ordinal regression analysis gave comparable results. Age (OR: 1.02, 95% CI 1.01-1.03, P < 0.01) and BMI (OR: 0.95, 95% CI 0.92-0.99, P 0.01) were significantly associated with severity of basal ganglia calcifications. CONCLUSIONS In this study with patients suspected of acute ischemic stroke, basal ganglia calcifications were common and significantly associated with older age and lower BMI.

['de Brouwer|Esther J M|EJM|', 'Kockelkoren|Remko|R|', 'De Vis|Jill B|JB|', 'Dankbaar|Jan Willem|JW|', 'Velthuis|Birgitta K|BK|', 'Takx|Richard Ap|RA|', 'De Jonghe|Annemarieke|A|', 'Emmelot-Vonk|Marielle H|MH|', 'Koek|Huiberdina L|HL|', 'de Jong|Pim A|PA|', '|||']

2020

31668375

Longitudinal Evolution of Markers of Mineral Metabolism in Patients With CKD: The Chronic Renal Insufficiency Cohort (CRIC) Study.

RATIONALE & OBJECTIVE The pathogenesis of disordered mineral metabolism in chronic kidney disease (CKD) is largely informed by cross-sectional studies of humans and longitudinal animal studies. We sought to characterize the longitudinal evolution of disordered mineral metabolism during the course of CKD. STUDY DESIGN Retrospective analysis nested in a cohort study. SETTING & PARTICIPANTS Participants in the Chronic Renal Insufficiency Cohort (CRIC) Study who had up to 5 serial annual measurements of estimated glomerular filtration rate, fibroblast growth factor 23 (FGF-23), parathyroid hormone (PTH), serum phosphate, and serum calcium and who subsequently reached end-stage kidney disease (ESKD) during follow-up (n = 847). EXPOSURE Years before ESKD. OUTCOMES Serial FGF-23, PTH, serum phosphate, and serum calcium levels. ANALYTICAL APPROACH To assess longitudinal dynamics of disordered mineral metabolism in human CKD, we used "ESKD-anchored longitudinal analyses" to express time as years before ESKD, enabling assessments of mineral metabolites spanning 8 years of CKD progression before ESKD. RESULTS Mean FGF-23 levels increased markedly as time before ESKD decreased, while PTH and phosphate levels increased modestly and calcium levels declined minimally. Compared with other mineral metabolites, FGF-23 levels demonstrated the highest rate of change (velocity: first derivative of the function of concentration over time) and magnitude of acceleration (second derivative). These changes became evident approximately 5 years before ESKD and persisted without deceleration through ESKD onset. Rates of changes in PTH and phosphate levels increased modestly and without marked acceleration around the same time, with modest deceleration immediately before ESKD, when use of active vitamin D and phosphate binders increased. LIMITATIONS Individuals who entered the CRIC Study at early stages of CKD and who did not progress to ESKD were not studied. CONCLUSIONS Among patients with progressive CKD, FGF-23 levels begin to increase 5 years before ESKD and continue to rapidly accelerate until transition to ESKD.

['Isakova|Tamara|T|', 'Cai|Xuan|X|', 'Lee|Jungwha|J|', 'Mehta|Rupal|R|', 'Zhang|Xiaoming|X|', 'Yang|Wei|W|', 'Nessel|Lisa|L|', 'Anderson|Amanda Hyre|AH|', 'Lo|Joan|J|', 'Porter|Anna|A|', 'Nunes|Julie Wright|JW|', 'Negrea|Lavinia|L|', 'Hamm|Lee|L|', 'Horwitz|Edward|E|', 'Chen|Jing|J|', 'Scialla|Julia J|JJ|', 'de Boer|Ian H|IH|', 'Leonard|Mary B|MB|', 'Feldman|Harold I|HI|', 'Wolf|Myles|M|', '|||']

2020

31859236

Female Sexual Orgasmic Dysfunction and Genital Sensation Deficiency.

INTRODUCTION Most studies on female sexual dysfunction (FSD), and female sexual orgasmic disorder (FSOD) in particular, have qualitatively examined cultural and educational factors; only few have quantitatively examined physiological factors. AIM The aim of this study was to compare quantitative sensory testing (QST) between women for whom FSOD was their primary complaint and other women with FSD. METHODS In this retrospective study of women who visited a sexual dysfunction clinic, the study group comprised women for whom FSOD was their primary complaint, and the control group comprised other women with FSD. Sexual dysfunction was assessed by the Female Sexual Function Index (FSFI). QST was performed with a thermal and vibration Genito-Sensory Analyzer (GSA; Medoc Ltd, Israel) aimed at the clitoral and vaginal areas. MAIN OUTCOME MEASURE The main outcome was clitoral and vibratory sensory thresholds in accordance with the presence of FSOD. RESULTS The study group comprised 89 (45%) women, with a mean age of 37.6 ± 1.9 years; and the control group comprised 110 (55%) women, with a mean age of 37.5 ± 11.3 years. Both mean FSFI-FSOD and total FSFI scores were significantly lower in the study group than in the control group (0.97 ± 0.94 vs 1.91 ± 1.3, P < 0.001) and (11.9 ± 3.2 vs 15.6 ± 3.6, P < 0.001), respectively. Mean clitoral vibratory sensory thresholds were higher in the study group than in the control group: 2.02 confidence interval (CI) 1.12-2.64 vs 1.55 CI 1.12-2.41, P < 0.001. No statistically significant difference was found between the groups in vaginal vibratory thresholds: 3.7 CI 2.6-6.6 vs 3.4 CI 1.9-5.4, P = 0.14. CLINICAL IMPLICATIONS The findings support the role of the clitoris in obtaining sexual orgasm, thus inferring a possible physiologic cause of FSOD in otherwise healthy women, beyond established psychological causes. STRENGTH & LIMITATIONS Assessments using an objective quantitative measure (QST) and a subjective tool (FSFI) in both the FSOD and control groups are strengths of this study. The retrospective design is a limitation. CONCLUSION QST showed a direct correlation between vibratory clitoral stimulation and FSOD; Compared with the control group, women with FSOD are relatively insensitive to clitoral stimulation, but not to vaginal stimulation. Gruenwald I, Lauterbach R, Gartman I, et al. Female Sexual Orgasmic Dysfunction and Genital Sensation Deficiency. J Sex Med 2020; 17:273-278.

['Gruenwald|Ilan|I|', 'Lauterbach|Roy|R|', 'Gartman|Irena|I|', 'Aharoni|Saar|S|', 'Lowenstein|Lior|L|']

2020

26968620

The early stress responses in fish larvae.

During the life cycle of fish the larval stages are the most interesting and variable. Teleost larvae undergo a daily increase in adaptability and many organs differentiate and become active. These processes are concerted and require an early neuro-immune-endocrine integration. In larvae communication among the nervous, endocrine and immune systems utilizes several known signal molecule families which could be different from those of the adult fish. The immune-neuroendocrine system was studied in several fish species, among which in particular the sea bass (Dicentrarchus labrax), that is a species of great commercial interest, very important in aquaculture and thus highly studied. Indeed the immune system of this species is the best known among marine teleosts. In this review the data on main signal molecules of stress carried out on larvae of fish are considered and discussed. For sea bass active roles in the early immunological responses of some well-known molecules involved in the stress, such as ACTH, nitric oxide, CRF, HSP-70 and cortisol have been proposed. These molecules and/or their receptors are biologically active mainly in the gut before complete differentiation of gut-associated lymphoid tissue (GALT), probably acting in an autocrine/paracrine way. An intriguing idea emerges from all results of these researches; the molecules involved in stress responses, expressed in the adult cells of the hypothalamic-pituitary axis, during the larval life of fish are present in several other localizations, where they perform probably the same role. It may be hypothesized that the functions performed by hypothalamic-pituitary system are particularly important for the survival of the larva and therefore they comprises several other localizations of body. Indeed the larval stages of fish are very crucial phases that include many physiological changes and several possible stress both internal and environmental.

['Pederzoli|Aurora|A|', 'Mola|Lucrezia|L|']

2016

27524284

A structurally diverse library of safe-by-design citrem-phospholipid lamellar and non-lamellar liquid crystalline nano-assemblies.

Non-lamellar liquid crystalline aqueous nanodispersions, known also as ISAsomes (internally self-assembled 'somes' or nanoparticles), are gaining increasing interest in drug solubilisation and bio-imaging, but they often exhibit poor hemocompatibility and induce cytotoxicity. This limits their applications in intravenous drug delivery and targeting. Using a binary mixture of citrem and soy phosphatidylcholine (SPC) at different weight ratios, we describe a library of colloidally stable aqueous and hemocompatible nanodispersions of diverse nanoarchitectures (internal self-assembled nanostructures). This engineered library is structurally stable in human plasma as well as being hemocompatible (non-hemolytic, and poor activator of the complement system). By varying citrem to lipid weight ratio, the nanodispersion susceptibility to macrophage uptake could also be modulated. Finally, the formation of nanodispersions comprising internally V2 (inverse bicontinuous cubic) and H2 (inverse hexagonal) nanoarchitectures was achieved without the use of an organic solvent, a secondary emulsifier, or high-energy input. The tunable binary citrem/SPC nanoplatform holds promise for future development of hemocompatible and immune-safe nanopharmaceuticals.

['Azmi|Intan D M|ID|', 'Wibroe|Peter P|PP|', 'Wu|Lin-Ping|LP|', 'Kazem|Ali I|AI|', 'Amenitsch|Heinz|H|', 'Moghimi|Seyed M|SM|', 'Yaghmur|Anan|A|']

2016

27816805

Adiposity during adolescence and carotid intima-media thickness in adulthood: Results from the 1993 Pelotas Birth Cohort.

BACKGROUND AND AIMS Although several studies have examined the association between adiposity and cardiovascular risk markers, few have explored the issue prospectively in young populations. We sought to test whether higher levels of body mass index (BMI) and subscapular skinfold at different stages of adolescence were associated with carotid intima-media thickness (cIMT) in young adulthood. METHODS In a prospective cohort, we assessed BMI and subscapular skinfold at 11, 15 and 18 years and measured cIMT at 18 years in 3264 individuals. Traditional cardiovascular risk factors and fat mass-mediating effects on cIMT were also assessed. RESULTS Both BMI and subscapular skinfolds were significantly associated with higher cIMT in a cummulative fashion: after controlling for confounders, males and females who persisted overweight/obese at all three assessments, had a mean higher cIMT (5.2 and 3.1 μm, respectively) compared to males and females with normal/healthy BMI at each evaluation (p < 0.001). Moreover, male and females that presented increased fatness in all assessments had a similar pattern of higher cIMT compared to normal/healthy fatness/skinfold at 18 years (mean cIMT 4.6 and 3.0 μm for males and females, respectively; p < 0.001). Associations between adiposity and cIMT were both direct and indirect. Indirect effects were chiefly mediated by fat mass and diastolic blood pressure. CONCLUSIONS Our results suggest adiposity exerts direct and indirect effects during adolescence that result in higher cIMT in young adulthood.

['Menezes|Ana Maria Baptista|AMB|', 'da Silva|Cristiano Tschiedel Belem|CTB|', 'Wehrmeister|Fernando César|FC|', 'Oliveira|Paula Duarte|PD|', 'Oliveira|Isabel O|IO|', 'Gonçalves|Helen|H|', 'Assunção|Maria Cecilia F|MCF|', 'de Castro Justo|Fabiano|F|', 'Barros|Fernando C|FC|']

2016

29462958

Effect of Apium graveolens Extract Administration on the Pharmacokinetics of Captopril in the Plasma of Rats.

Apium graveolens (celery) is an edible and traditionally medicinal plant that is used worldwide, among others for the treatment of hypertension. Combining celery with antihypertensive drugs can affect the pharmacodynamics and pharmacokinetics of the latter drugs. The aim of the study is to assess the effects of administrating the celery extract on captopril pharmacokinetics. Sprague-Dawley strain rats were divided into two groups (n = 6). Group I was given captopril (10 mg/kg Body Weight (BW)) orally, while Group II was pretreated with celery extract orally (40 mg/kg BW) an hour before administration of captopril. The blood samples were withdrawn at various intervals after drug administration. The captopril concentration was determined using liquid chromatography-mass spectrometry (LC-MS/MS) and from the blood data, the values of Ke, Cmax, Tmax, T1/2, and area under the curve (AUC) were calculated. The results showed that oral administration of the celery extract increased Cmax (38.67%), T1/2 (37.84%), and AUC (58.10%) and decreased Ke (27.45%) of captopril in Group II (celery + captopril) compared with Group I (captopril). In conclusion, celery extract can alter the pharmacokinetic of captopril when given in combination. The combination might be beneficial for the treatment of hypertension, as celery causes an increase in the plasma level of captopril, which can enhance its efficacy.

['Siska|Siska|S|', 'Mun Im|Abdul|A|', 'Bahtiar|Anton|A|', 'Suyatna|Franciscus D|FD|']

2018

25661698

The cognitive mechanisms underlying deception: an event-related potential study.

The cognitive view on deception proposes that lying comes with a cognitive cost. This view is supported by the finding that lying typically takes longer than truth telling. Event-related potentials (ERPs) provide a means to unravel the cognitive processes underlying this cost. Using a mock-crime design, the current study (n=20) investigated the effects of deception on the Contingent Negative Variation (CNV), the Lateralized Readiness Potential (LRP), the Correct Response Negativity (CRN), and the stimulus-locked N200 and P300 components. In line with previous research, lying resulted in more errors, longer reaction times (RTs) and longer RT standard deviations compared to truthful responses. A marginally significant effect suggested a stronger CNV for the anticipation of lying compared to the anticipation of truth telling. There were no significant deception effects on the stimulus- and the response-locked LRPs. Unexpectedly, we found a significantly larger CRN for truth telling compared to lying. Additional analyses revealed an enhanced N200 and a decreased P300 for lying compared to truth telling. Our results support the cognitive load hypothesis for lying, yet are mixed regarding the response conflict hypothesis. Results are discussed with regard to the specific characteristics of our design and their theoretical and applied implications.

['Suchotzki|Kristina|K|', 'Crombez|Geert|G|', 'Smulders|Fren T Y|FT|', 'Meijer|Ewout|E|', 'Verschuere|Bruno|B|']

2015

26866859

The effects of combined sewer overflow events on riverine sources of drinking water.

This study was set out to investigate the impacts of Combined Sewer Overflows (CSOs) on the microbiological water quality of a river used as a source of drinking water treatment plants. Escherichia coli concentrations were monitored at various stations of a river segment located in the Greater Montreal Area including two Drinking Water Intakes (DWIs) in different weather conditions (dry weather and wet weather (precipitation and snowmelt period)). Long-term monitoring data (2002-2011) at DWIs revealed good microbiological water quality with E. coli median concentrations of 20 and 30 CFU/100 mL for DWI-1 and DWI-2 respectively. However, E. coli concentration peaks reached up to 510 and 1000 CFU/100 mL for both DWIs respectively. Statistical Process Control (SPC) analysis allowed the identification of E. coli concentration peaks in almost a decade of routine monitoring data at DWIs. Almost 80% of these concentrations were linked to CSO discharges caused by precipitation exceeding 10 mm or spring snowmelt. Dry weather monitoring confirmed good microbiological water quality. Wet weather monitoring showed an increase of approximately 1.5 log of E. coli concentrations at DWIs. Cumulative impacts of CSO discharges were quantified at the river center with an increase of approximately 0.5 log of E. coli concentrations. Caffeine (CAF) was tested as a potential chemical indicator of CSO discharges in the river and CAF concentrations fell within the range of previous measurements performed for surface waters in the same area (∼20 ng/L). However, no significant differences were observed between CAF concentrations in dry and wet weather, as the dilution potential of the river was too high. CSO event based monitoring demonstrated that current bi-monthly or weekly compliance monitoring at DWIs underestimate E. coli concentrations entering DWIs and thus, should not be used to quantify the risk at DWIs. High frequency event-based monitoring is a desirable approach to establish the importance and duration of E. coli peak concentrations entering DWIs.

['Madoux-Humery|Anne-Sophie|AS|', 'Dorner|Sarah|S|', 'Sauvé|Sébastien|S|', 'Aboulfadl|Khadija|K|', 'Galarneau|Martine|M|', 'Servais|Pierre|P|', 'Prévost|Michèle|M|']

2016

26965789

Phonon Scattering Dynamics of Thermophoretic Motion in Carbon Nanotube Oscillators.

Using phonon wave packet molecular dynamics simulations, we find that anomalous longitudinal acoustic (LA) mode phonon scattering in low to moderate energy ranges is responsible for initiating thermophoretic motion in carbon nanotube oscillators. The repeated scattering of a single mode LA phonon wave packet near the ends of the inner nanotube provides a net unbalanced force that, if large enough, initiates thermophoresis. By applying a coherent phonon pulse on the outer tube, which generalizes the single mode phonon wave packet, we are able to achieve thermophoresis in a carbon nanotube oscillator. We also find the nature of the unbalanced force on end-atoms to be qualitatively similar to that under an imposed thermal gradient. The thermodiffusion coefficient obtained for a range of thermal gradients and core lengths suggest that LA phonon scattering is the dominant mechanism for thermophoresis in longer cores, whereas for shorter cores, it is the highly diffusive mechanism that provides the effective force.

['Prasad|Matukumilli V D|MV|', 'Bhattacharya|Baidurya|B|']

2016

33768582

Individual participant data meta-analysis for external validation, recalibration, and updating of a flexible parametric prognostic model.

Individual participant data (IPD) from multiple sources allows external validation of a prognostic model across multiple populations. Often this reveals poor calibration, potentially causing poor predictive performance in some populations. However, rather than discarding the model outright, it may be possible to modify the model to improve performance using recalibration techniques. We use IPD meta-analysis to identify the simplest method to achieve good model performance. We examine four options for recalibrating an existing time-to-event model across multiple populations: (i) shifting the baseline hazard by a constant, (ii) re-estimating the shape of the baseline hazard, (iii) adjusting the prognostic index as a whole, and (iv) adjusting individual predictor effects. For each strategy, IPD meta-analysis examines (heterogeneity in) model performance across populations. Additionally, the probability of achieving good performance in a new population can be calculated allowing ranking of recalibration methods. In an applied example, IPD meta-analysis reveals that the existing model had poor calibration in some populations, and large heterogeneity across populations. However, re-estimation of the intercept substantially improved the expected calibration in new populations, and reduced between-population heterogeneity. Comparing recalibration strategies showed that re-estimating both the magnitude and shape of the baseline hazard gave the highest predicted probability of good performance in a new population. In conclusion, IPD meta-analysis allows a prognostic model to be externally validated in multiple settings, and enables recalibration strategies to be compared and ranked to decide on the least aggressive recalibration strategy to achieve acceptable external model performance without discarding existing model information.

['Ensor|Joie|J|0000-0001-7481-0282', 'Snell|Kym I E|KIE|0000-0001-9373-6591', 'Debray|Thomas P A|TPA|0000-0002-1790-2719', 'Lambert|Paul C|PC|', 'Look|Maxime P|MP|', 'Mamas|Mamas A|MA|', 'Moons|Karel G M|KGM|', 'Riley|Richard D|RD|0000-0001-8699-0735']

2021

27914353

Two-liquid-phase system: A promising technique for predicting bioavailability of polycyclic aromatic hydrocarbons in long-term contaminated soils.

A two-liquid-phase system (TLPS), which consisted of soil slurry and silicone oil, was employed to extract polycyclic aromatic hydrocarbons (PAHs) in four long-term contaminated soils in order to assess the bioavailability of PAHs. Extraction kinetics of six PAHs viz. phenanthrene, fluoranthene, pyrene, benzo(a)anthracene, benzo(a)pyrene, dibenzo(a,h)anthrancene were selected to investigate as they covered the susceptible and recalcitrant PAHs in soil. A parallel experiments were also carried out on the microbial degradation of these PAHs in soil with and without biostimulation (by adding (NH4)2HPO4). The rapidly desorbed fraction of fluoranthene, as indicated by the two-fraction model, was found the highest, ranging from 21.4% to 37.4%, whereas dibenzo(a,h)anthrancene was the lowest, ranging from 8.9% to 20.5%. The rapid desorption of selected PAHs was found to be finished within 24 h. The rapidly desorbed fraction of PAHs investigated using TLPS, was significantly correlated (R2 = 0.95) with that degraded by microorganisms in biostimulation treatment. This suggested that the TLPS-assisted extraction could be a promising technique in determining the bioavailability of aged PAHs in contaminated soils. It also suggested that applying sufficient nutrients in bioremediation of field contaminated soils is crucial. Further work is required to test its application to more hydrophobic organic pollutants in long-term contaminated soils.

['Wang|Congying|C|', 'Wang|Ziyu|Z|', 'Li|Zengbo|Z|', 'Ahmad|Riaz|R|']

2017

31773314

Visible and near-infrared hyperspectral indices explain more variation in lower-crown leaf nitrogen concentrations in autumn than in summer.

Autumn canopy phenological transitions are increasing in length as a consequence of climate change. Here, we assess how well hyperspectral indices in the visible and near-infrared (NIR) wavelengths predict nitrogen (N) concentrations in lower-canopy leaves in the autumn phenological transition as they are generally understudied in leaf trait research. Using a Bayesian framework, we tested how well published indices are able to predict N concentrations in Fagus grandifolia Ehrh., Liriodendron tulipifera L., and Betula lenta L. from mid-summer through senescence, and how related the indices are to autumn phenological change. No indices were able to determine a trend in differences in N in mid-summer leaves. Indices that included wavelengths in the green and NIR ranges were the first indices able to detect a trend and had among the highest correlations with N concentration in both the last green collection and the senescing collection. Models were unique when indices were fit to data from different phenophases. Indices that focused on only the red edge (i.e., the sharp increase in reflectance between the red and NIR wavelengths) had the strongest explanatory power across the autumn phenological transition, but had less explanatory power for individual collections. These indices, as well as those that have been correlated with chlorophyll (CCI) and carotenoids (PRI), were the strongest descriptors of autumn progression. This study provides insights on challenges and capabilities to monitor a leaf's N concentration throughout and across canopy senescence.

['Wheeler|Kathryn I|KI|http://orcid.org/0000-0003-3931-7489', 'Levia|Delphis F|DF|http://orcid.org/0000-0002-7443-6523', 'Vargas|Rodrigo|R|http://orcid.org/0000-0001-6829-5333']

2020

34837300

Establishing a sustainable healthcare environment in low- and middle-income countries.

The dynamics of disease prevalence and healthcare systems continue to change dramatically in low- and middle-income countries (LMICs). This is a result of multiple factors including the demands of an ageing population in the context of increasing life expectancy and the rise of non-communicable diseases putting an additional burden on an already weak healthcare system. Further healthcare deficiency is attributable to additional factors such as low financial budgets, political conflicts and civil war, as well as continuing burden of communicable diseases, which are known to be the major risk to health in LMICs. Surgical needs largely remain unmet despite a Lancet report published in 2015. Various deficient aspects of healthcare systems need to be addressed immediately to provide any hope of creating a sustainable healthcare environment in the coming decades. These include developing strong primary and secondary care structures as well as strengthening tertiary care hospitals with an adequately trained healthcare workforce. The facilities required to improve patients' access to healthcare cannot be developed and sustained solely within the local budget allocation and require major input from international organizations such as the World Bank and the World Health Organization as well as a chain of donor networks. To create and retain a local healthcare workforce, improved training and living conditions and greater financial security need to be provided. Finally, healthcare economics need to be addressed with financial models that can provide insurance and security to the underprivileged population to achieve universal health coverage, which remains the goal of several global organizations promoting equity in high-standard healthcare provision.

['Aslam|Muhammad Z|MZ|https://orcid.org/0000-0001-9417-659X', 'Trail|Matthew|M|https://orcid.org/0000-0003-0131-8064', 'Cassell|Ayun K|AK|', 'Khan|Abdul B|AB|', 'Payne|Steven|S|https://orcid.org/0000-0001-5359-1877']

2021

26874576

Diabetes, Gray Matter Loss, and Cognition in the Setting of Parkinson Disease.

RATIONALE AND OBJECTIVES Parkinson disease (PD) is a progressive neurodegenerative disorder affecting motor and cognitive functions. Prior studies showed that patients with PD and diabetes (DM) demonstrate worse clinical outcomes compared to nondiabetic subjects with PD. Our study aimed at defining the relationship between DM, gray matter volume, and cognition in patients with PD. MATERIALS AND METHODS This study included 36 subjects with PD (12 with DM, 24 without DM, mean age = 66). Subjects underwent high-resolution T1-weighted brain magnetic resonance imaging, [(11)C]dihydrotetrabenazine positron emission tomography imaging to quantify nigrostriatal dopaminergic denervation, clinical, and cognitive assessments. Magnetic resonance images were postprocessed to determine total and lobar cortical gray matter volumes. Cognitive testing scores were converted to z-scores for specific cognitive domains and a composite global cognitive z-score based on normative data computed. Analysis of covariance, accounting for effects of age, gender, intracranial volume, and striatal [(11)C]dihydrotetrabenazine binding, was used to test the relationship between DM and gray matter volumes. RESULTS Impact of DM on total gray matter volume was significant (P = 0.02). Post hoc analyses of lobar cortical gray matter volumes revealed that DM was more selectively associated with lower gray matter volumes in the frontal regions (P = 0.01). Cognitive post hoc analyses showed that interaction of total gray matter volume and DM status was significantly associated with composite (P = 0.007), executive (P = 0.02), and visuospatial domain cognitive z-scores (P = 0.005). These associations were also significant for the frontal cortical gray matter. CONCLUSION DM may exacerbate brain atrophy and cognitive functions in PD with greater vulnerability in the frontal lobes. Given the high prevalence of DM in the elderly, delineating its effects on patient outcomes in the PD population is of importance.

['Petrou|M|M|', 'Davatzikos|C|C|', 'Hsieh|M|M|', 'Foerster|B R|BR|', 'Albin|R L|RL|', 'Kotagal|V|V|', 'Müller|M L|ML|', 'Koeppe|R A|RA|', 'Herman|W H|WH|', 'Frey|K A|KA|', 'Bohnen|N I|NI|']

2016

27796662

Genetic variant of IL-10RA and susceptibility to rheumatoid arthritis in a Chinese population.

The aim of this study was to investigate the relationship between the single-nucleotide polymorphisms (SNPs) of interleukin 10 alpha receptor (IL10RA) gene and rheumatoid arthritis (RA) in a Chinese population. We examined 533 RA patients and 958 subjects as a control group. Three IL-10RA SNPs (rs9610, rs2229113 and rs3135932) were genotyped using TaqMan genotyping assays on Fluidigm 192.24 system. The IL-10RA rs9610 A allele was increased in patient group compared with control subjects (OR = 1.232, 95 % CI = 1.052-1.442, p = 0.030). Significant difference in genotype distribution was found in RA patients and controls (χ2 = 15.32, p < 0.001). We also discovered a statistical significance under the dominant model (GG + AG versus AA: OR = 0.676, 95 % CI = 0.546-0.837, p < 0.001). However, no significant difference was discovered in the recessive model (GG versus AG + AA: OR = 1.013, 95 % CI = 0.754-1.361, p = 0.932). Interestingly, significant differences were detected both in the allele and genotype frequencies of rs9610 between anti-CCP positive patients and anti-CCP negative patients (χ2 = 7.209, p = 0.007; χ2 = 9.061, p = 0.011; respectively). We also found a significant difference in genotype frequency at rs9610 in females compared with males (χ2 = 7.658, p = 0.022). Unfortunately, we failed to find any significant results between two IL-10RA SNPs (rs2229113 and rs3135932) and RA susceptibility. The findings suggest that IL-10RA rs9610 polymorphism might contribute to RA susceptibility.

['Yang|Xiao-Ke|XK|', 'Li|Peng|P|', 'Li|Song|S|', 'Zhang|Chao|C|', 'Li|Bao-Zhu|BZ|', 'Leng|Rui-Xue|RX|', 'Pan|Hai-Feng|HF|', 'Ye|Dong-Qing|DQ|']

2017

32329739

Current and Future Trends in Life Sciences Training: Questionnaire Study.

BACKGROUND Every year, the life science field spends billions of dollars on educational activities worldwide. The continuing professional development of employees, especially in this field, encompasses great challenges. Emerging technologies appear to offer opportunity, but relatively little research has been done on the effectiveness of pedagogies and tools that have been used in the life sciences, and even less research has been devoted to understanding the potential power of emerging options that might determine the field's future. OBJECTIVE In collaboration with the Life Sciences Trainers & Educators Network (LTEN), this study investigated the current state of the pedagogies and tools currently adopted by corporate training professionals in the life sciences as well as the professionals' perceptions of the impacts of emerging technologies on training. METHODS This study adopted a mixed methods approach that included a survey and a follow-up interview. The survey consists of 18 broad questions with 15 subquestions in each of the five specific sectors of the life sciences field. Interviews were conducted by phone and lasted approximately 40 minutes, covering 18 questions designed to follow-up on findings from the survey items. RESULTS Both survey and interview results indicated that the professionals were not satisfied with the status quo and that training and education in this field need to change. Most of the techniques and tools currently used have been used for some time. The professionals surveyed were not satisfied with the current techniques and tools and did not find them cost-effective. In addition, the respondents pictured the future of training in this field to be more engaging and effective. CONCLUSIONS This is the first study in a series designed to better understand education and training in the life sciences on a macro level, in order to build a foundation for progress and evolution of the future landscape. Next steps involve developing strategies for how to extend this vision throughout individual organizations.

['Magagna|William|W|https://orcid.org/0000-0002-4264-1135', 'Wang|Nicole|N|https://orcid.org/0000-0003-3195-4205', 'Peck|Kyle|K|https://orcid.org/0000-0002-0981-7020']

2020

29587192

Hand-held optical sensor using denatured antibody coated electro-active polymer for ultra-trace detection of copper in blood serum and environmental samples.

An optimum copper concentration in environment is highly desired for all forms of life. We have developed an ultrasensitive copper sensor which functions from femto to micro molar concentration accurately (R2 = 0.98). The sensor is based on denatured antibody immunoglobulin G (IgG), immobilized on polyaniline (PAni) which in turn is the coating on the core of an optical fiber. The sensing relies on changes in evanescent wave absorbance in the presence of the analyte. The sensor showed excellent selectivity towards Cu (II) ions over all other metal ions. The sensor was tested with lake and marine water samples to determine unknown concentrations of copper ions and the recovery results were within 90-115%, indicating reasonable accuracy. We further integrated the fiber-optic sensor with a miniaturized hand-held instrumentation platform to develop an accurate and field deployable device which can broadly be applicable to determine Cu (II) concentration in a wide range of systems - natural water bodies, soil as well as blood serum.

['Chandra|Sutapa|S|', 'Dhawangale|Arvind|A|', 'Mukherji|Soumyo|S|']

2018

29164592

The moral economy of ready-made food.

The aim of this paper is to develop and apply a framework to explore how moralities of consumption are constituted in and through markets. Using the case of ready-made foods, this paper argues moral economies are comprised through interactions between micro-, meso- and macro-level processes in the form of instituted systems of provision, state regulation, collective food customs promoted though media, NGOs and lifestyle practitioners, and the everyday reflections of consumers. Building on a theoretical framework developed to understand the moral economy of work and employment (Bolton and Laaser 2013), this paper explores how markets for ready-made food are incessantly negotiated in the context of moral ideas about cooking, femininity and individual responsibility. It focuses on 'new' market innovations of fresh ready-to-cook meal solutions and explores how these products are both a response to moralizing discourses about cooking 'properly', as well as an intervention into the market that offers opportunities for new moral identities to be performed. Using data gathered from interviews with food manufacturers and consumers, I advocate for a multi-layered perspective that captures the dynamic interplay between consumers, markets and moralities of consumption.

['Wheeler|Kathryn|K|http://orcid.org/0000-0003-2056-9977']

2018

32948213

Promoting functions of microRNA-29a/199B in neurological recovery in rats with spinal cord injury through inhibition of the RGMA/STAT3 axis.

BACKGROUND The prognostic and therapeutic potential of microRNAs (miRNAs) in spinal cord injury (SCI) has aroused increasing concerns. This study aims to research the functions of miR-29a/199B in the neurological function recovery after SCI and the mechanical mechanism. METHODS A rat model with SCI was induced with sham-operated ones as control. The locomotor function and coordination of rat hindlimbs were determined by a Basso, Beattie, and Bresnahan (BBB) locomotor rating scale and a ladder-climbing test, respectively. Expression of a neurofilament protein NF-200 and synaptophysin in gray matter of rats was determined to evaluate neuronal recovery in a cellular perspective. Binding relationships between miR-29a/199B with RGMA were predicted and validated using luciferase assays. Altered expression of miR-29a/199B and RGMA was introduced to explore their functions in rat neurological functions. The protein level and phosphorylation of STAT3 in gray matter were measured by western blot analysis. RESULTS miR-29a and miR-199B were poorly expressed, while RGMA was abundantly expressed in gray matter at injury sites. Either miR-29a or miR-199B could bind to RGMA. Overexpression of miR-29a/199B or silencing of RGMA led to an increase in BBB locomotor scores, hindlimb coordination ability, and the expression of NF-200 and synaptophysin in gray matter. Further inhibition in miR-29a/199B blocked the promoting roles of RGMA silencing in neurological recovery. Upregulation of miR-29a/199B or downregulation of RGMA suppressed the phosphorylation of STAT3. CONCLUSION This study evidenced that miR-29a and miR-199B negatively regulated RGMA to suppress STAT3 phosphorylation, therefore promoting the neurological function recovery in rats following SCI.

['Yang|Weijie|W|', 'Sun|Ping|P|http://orcid.org/0000-0002-3143-1749']

2020

32959616

Knowledge, Perception, Attitudes and Behavior on Influenza Immunization and the Determinants of Vaccination.

BACKGROUND We sought to determine the knowledge of, perception, attitudes, and behaviors toward influenza virus and immunization, and the determinants of vaccination among students, patients, and Healthcare Workers (HCWs) at the American University of Beirut and its affiliated Medical Center. METHODS We conducted a cross-sectional study between October 2016 and January 2017 utilizing a self-administered questionnaire that was provided to 247 randomly selected adult participants. Data collected included socio-demographic characteristics, prior vaccination against influenza, knowledge, perception, attitudes, and behaviors toward influenza and influenza immunization. A multivariable regression model was used to evaluate for independent associations between the different variables and regular or yearly vaccination as a primary outcome. RESULTS The overall survey response rate was 77%. A substantial proportion of respondents (47.4%) had never received the influenza vaccine. Only 10.2% of students, 19.1% of patients, and 35.6% of HCWs reported regular or yearly influenza vaccine uptake. HCWs had the lowest knowledge score about influenza and its vaccine despite high self-reported levels of knowledge. Barriers to vaccinations included lack of information (31%), fear of adverse effects (29%), and a perception of not being at risk (23%). Several factors were independently associated with regular or yearly vaccination uptake including having children (adjusted OR = 3.8; 95% CI 1.2-12.5), a "very good" self-reported level of knowledge (OR = 16.3; 95% CI 1.4-194.2) and being afraid of the consequences of influenza (OR = 0.2; 95% CI 0.1-0.6). CONCLUSION Adherence rates with regular or yearly vaccination against influenza remain low across all study groups. We were able to identify predictors as well as barriers to vaccination. Future awareness and vaccination campaigns should specifically aim at correcting misconceptions about vaccination, particularly among HCWs, along with addressing the barriers to vaccination. Predictors of vaccination should be integrated in the design of future campaigns.

['Choucair|Khalil|K|0000-0001-8145-3754', 'El Sawda|Jack|J|', 'Assaad|Sarah|S|0000-0002-8104-1546', 'El Chakhtoura|Nadim G|NG|', 'Hassouna|Habiba|H|0000-0002-7088-4679', 'Sidani|Nisreen|N|', 'Yasmin|Mohamad|M|0000-0002-5859-1769', 'Rteil|Ali|A|', 'Kanj|Souha S|SS|', 'Kanafani|Zeina A|ZA|']

2021

33638731

Hierarchical spatial sampling reveals factors influencing arbuscular mycorrhizal fungus diversity in Côte d'Ivoire cocoa plantations.

While many molecular studies have documented arbuscular mycorrhizal fungi (AMF) communities in temperate ecosystems, very few studies exist in which molecular techniques have been used to study tropical AMF communities. Understanding the composition of AMF communities in tropical areas gains special relevance as crop productivity in typically low fertility tropical soils can be improved with the use of AMF. We used a hierarchical sampling approach in which we sampled soil from cocoa (Theobroma cacao L.) plantations nested in localities, and in which localities were nested within each of three regions of Côte d'Ivoire. This sampling strategy, combined with 18S rRNA gene sequencing and a dedicated de novo OTU-picking model, allowed us to study AMF community composition and how it is influenced at different geographical scales and across environmental gradients. Several factors, including pH, influenced overall AMF alpha diversity and differential abundance of specific taxa and families of the Glomeromycotina. Assemblages and diversity metrics at the local scale did not reliably predict those at regional scales. The amount of variation explained by soil, climate, and geography variables left a large proportion of the variance to be explained by other processes, likely happening at smaller scales than the ones considered in this study. Gaining a better understanding of processes involved in shaping tropical AMF community composition and AMF establishment are much needed and could allow for the development of sustainable, productive tropical agroecosystems.

['Rincón|Cristian|C|', 'Droh|Germain|G|', 'Villard|Lucas|L|', 'Masclaux|Frédéric G|FG|', "N'guetta|Assanvo|A|", 'Zeze|Adolphe|A|', 'Sanders|Ian R|IR|http://orcid.org/0000-0002-9591-8214']

2021

27476807

Association Between Restriction of Involuntary Medication and Frequency of Coercive Measures and Violent Incidents.

OBJECTIVE In the German federal state of Baden-Wuerttemberg, involuntary medication of psychiatric inpatients was illegal during eight months from July 2012 until February 2013. The authors examined whether the number and duration of mechanical coercive measures (seclusion and restraint) and the number and severity of violent incidents changed in this period. METHODS A cross-sectional analysis was conducted of admission-related routine data collected in seven psychiatric hospitals in three time periods (period 1, July 2011-February 2012; period 2, July 2012-February 2013; and period 3, July 2013-February 2014). All patients with psychotic disorders and at least one admission during at least one of the three time periods were included (N=2,071), for a total of 3,482 admissions. RESULTS The mean number of mechanical coercive measures and violent incidents per admission increased significantly during period 2, when involuntary medication was not possible, and decreased significantly during period 3. They also differed significantly between periods 1 and 3. The percentage of admissions involving seclusion increased during period 2 significantly and was significantly different during period 1 compared with period 3. The severity of illness and the length of hospitalization did not change over the three periods. CONCLUSIONS Restriction of involuntary medication was associated with a significant increase in use of mechanical coercive measures and violent incidents.

['Flammer|Erich|E|', 'Steinert|Tilman|T|']

2016

27158363

Transplantation of human induced cerebellar granular-like cells improves motor functions in a novel mouse model of cerebellar ataxia.

Stem cell-based reparative approaches have been applied to cerebellum-related disorders during the last two decades. Direct lineage reprogramming of human fibroblasts into functional granular neurons holds great promise for biomedical applications such as cerebellum regeneration and cellbased disease modeling. In the present study, we showed that a combination of Ascl1, Sox2 and OCT4, in a culture subsequently treated with secreted factors (BMP4, Wnt3a and FGF8b), was capable of converting human fibroblasts from the scalp tissue of patients with traumatic brain injury (TBI) into functional human induced cerebellar granular-like cells (hiCGCs). Morphological analysis, immunocytochemistry, gene expression and electrophysiological analysis were performed to identify the similarity of induced neuronal cells to human cerebellum granular cells. Our strategy improved the efficiency for hiCGCs induction, which gave the highest conversion efficiency 12.30±0.88%, and Ath1(+)/Tuj1(+) double positive cells to 5.56±0.80%. We transplanted hiCGCs into the cerebellum of Nmyc(TRE/TRE): tTS mice, a novel mouse model of cerebellar ataxia, and demonstrated that the hiCGCs were able to survive, migrate, proliferate and promote mild functional recovery after been grafted into cerebellum.

['Zhu|Tongming|T|', 'Tang|Hailiang|H|', 'Shen|Yiwen|Y|', 'Tang|Qisheng|Q|', 'Chen|Luping|L|', 'Wang|Zhifu|Z|', 'Zhou|Ping|P|', 'Xu|Feng|F|', 'Zhu|Jianhong|J|']

2016

26251883

New insights into the dimerization of small GTPase Rac/ROP guanine nucleotide exchange factors in rice.

Molecular links between receptor-kinases and Rac/ROP family small GTPases mediated by activator guanine nucleotide exchange factors (GEFs) govern diverse biological processes. However, it is unclear how the Rac/ROP GTPases orchestrate such a wide variety of activities. Here, we show that rice OsRacGEF1 forms homodimers, and heterodimers with OsRacGEF2, at the plasma membrane (PM) and the endoplasmic reticulum (ER). OsRacGEF2 does not bind directly to the receptor-like kinase (RLK) OsCERK1, but forms a complex with OsCERK1 through OsRacGEF1 at the ER. This complex is transported from ER to the PM and there associates with OsRac1, resulting in the formation of a stable immune complex. Such RLK-GEF heterodimer complexes may explain the diversity of Rac/ROP family GTPase signalings.

['Akamatsu|Akira|A|', 'Uno|Kazumi|K|', 'Kato|Midori|M|', 'Wong|Hann Ling|HL|', 'Shimamoto|Ko|K|', 'Kawano|Yoji|Y|']

2015

24955505

Corneal sensitivity and tear function in neurodegenerative diseases.

PURPOSE To measure corneal sensitivity and tear function in neurodegenerative diseases (NDs) and to compare them with age and sex-matched controls. METHODS Twenty patients with Alzheimer's disease (AD), 20 patients with multiple sclerosis (MS), 30 patients with Parkinson's disease (PD), 10 patients with Friedreich's ataxia (FA) and 21 patients with epilepsy (EP) who were recruited from the Kırıkkale University Neurology Department during 2012 were included in this prospective study. Five groups of age and sex-matched subjects were selected as controls. Corneal sensitivity was measured using a Cochet-Bonnet esthesiometer. Tear function tests included tear break-up time (TBUT) and Schirmer's 1 tests. RESULTS Compared to their controls, mean corneal sensitivity was significantly reduced in AD, MS, PD and EP patients (all p < 0.05), mean TBUT level was significantly shorter in patients with AD and MS (all p < 0.05) and mean Schirmer's 1 test score was significantly lower in EP patients (p < 0.05). When all groups were compared with each other, reduction of mean corneal sensitivity in AD and PD groups were significantly more than in FA and MS groups (overall p = 0.034). Mean TBUT levels in AD, MS and PD groups were significantly shorter than in FA and EP groups (overall p = 0.001). Mean Schirmer's 1 test scores in AD and PD groups were significantly lower than in MS, FA and EP groups (overall p = 0.040). CONCLUSIONS Neurodegenerative diseases may be associated with reduced corneal sensitivity and abnormal tear function.

['Örnek|Nurgül|N|', 'Dağ|Ersel|E|', 'Örnek|Kemal|K|']

2015

34419081

Soluble tumor necrosis factor-alpha-induced hyperexcitability contributes to retinal ganglion cell apoptosis by enhancing Nav1.6 in experimental glaucoma.

BACKGROUND Neuroinflammation plays an important role in the pathogenesis of glaucoma. Tumor necrosis factor-alpha (TNF-α) is a major pro-inflammatory cytokine released from activated retinal glial cells in glaucoma. Here, we investigated how TNF-α induces retinal ganglion cell (RGC) hyperexcitability and injury. METHODS Whole-cell patch-clamp techniques were performed to explore changes in spontaneous firing and evoked action potentials, and Na+ currents in RGCs. Both intravitreal injection of TNF-α and chronic ocular hypertension (COH) models were used. Western blotting, immunofluorescence, quantitative real-time polymerase chain reaction (q-PCR), and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) techniques were employed to investigate the molecular mechanisms of TNF-α effects on RGCs. RESULTS Intravitreal injection of soluble TNF-α significantly increased the spontaneous firing frequencies of RGCs in retinal slices. When the synaptic transmissions were blocked, more than 90% of RGCs still showed spontaneous firing; both the percentage of cells and firing frequency were higher than the controls. Furthermore, the frequency of evoked action potentials was also higher than the controls. Co-injection of the TNF-α receptor 1 (TNFR1) inhibitor R7050 eliminated the TNF-α-induced effects, suggesting that TNF-α may directly act on RGCs to induce cell hyperexcitability through activating TNFR1. In RGCs acutely isolated from TNF-α-injected retinas, Na+ current densities were upregulated. Perfusing TNF-α in RGCs of normal rats mimicked this effect, and the activation curve of Na+ currents shifted toward hyperpolarization direction, which was mediated through p38 MAPK and STAT3 signaling pathways. Further analysis revealed that TNF-α selectively upregulated Nav1.6 subtype of Na+ currents in RGCs. Similar to observations in retinas of rats with COH, intravitreal injection of TNF-α upregulated the expression of Nav1.6 proteins in both total cell and membrane components, which was reversed by the NF-κB inhibitor BAY 11-7082. Inhibition of TNFR1 blocked TNF-α-induced RGC apoptosis. CONCLUSIONS TNF-α/TNFR1 signaling induces RGC hyperexcitability by selectively upregulating Nav1.6 Na+ channels, thus contributing to RGC apoptosis in glaucoma.

['Cheng|Shuo|S|', 'Wang|Hong-Ning|HN|', 'Xu|Lin-Jie|LJ|', 'Li|Fang|F|', 'Miao|Yanying|Y|', 'Lei|Bo|B|', 'Sun|Xinghuai|X|', 'Wang|Zhongfeng|Z|http://orcid.org/0000-0002-2279-6885']

2021

29510118

TGF-β mimic proteins form an extended gene family in the murine parasite Heligmosomoides polygyrus.

We recently reported the discovery of a new parasite-derived protein that functionally mimics the immunosuppressive cytokine transforming growth factor (TGF)-β. The Heligmosomoides polygyrus TGF-β Mimic (Hp-TGM) shares no homology to any TGF-β family member, however it binds the mammalian TGF-β receptor and induces expression of Foxp3, the canonical transcription factor of both mouse and human regulatory T cells. Hp-TGM consists of five atypical Complement Control Protein (CCP, Pfam 00084) domains, each lacking certain conserved residues and 12-15 amino acids longer than the 60-70 amino acids consensus domain, but with a recognizable 3-cysteine, tryptophan, cysteine motif. We now report on the identification of a family of nine related Hp-TGM homologues represented in the secreted proteome and transcriptome of H. polygyrus. Recombinant proteins from five of the nine new TGM members were tested for TGF-β activity, but only two were functionally active in an MFB-F11 reporter assay, and by the induction of T cell Foxp3 expression. Sequence comparisons reveal that proteins with functional activity are similar or identical to Hp-TGM across the first three CCP domains, but more variable in domains 4 and 5. Inactive proteins diverged in all domains, or lacked some domains entirely. Testing truncated versions of Hp-TGM confirmed that domains 1-3 are essential for full activity in vitro, while domains 4 and 5 are not required. Further studies will elucidate whether these latter domains fulfill other functions in promoting host immune regulation during infection and if the more divergent family members play other roles in immunomodulation.

['Smyth|Danielle J|DJ|', 'Harcus|Yvonne|Y|', 'White|Madeleine P J|MPJ|', 'Gregory|William F|WF|', 'Nahler|Janina|J|', 'Stephens|Ian|I|', 'Toke-Bjolgerud|Edward|E|', 'Hewitson|James P|JP|', 'Ivens|Alasdair|A|', 'McSorley|Henry J|HJ|', 'Maizels|Rick M|RM|']

2018

31009613

Development of lacrimal gland inflammation in the mouse model of herpes stromal keratitis.

Herpes stromal keratitis (HSK) is a chronic immunoinflammatory condition which develops in response to recurrent herpes simplex virus-1 (HSV-1) infection of the cornea. Patients with HSK often demonstrate the concurrence of corneal desiccation and the loss of blink reflex. However, the relationship between severity of HSK, level of basal tears and inflammation of the lacrimal gland is mostly unexplored. In this study, we compared these variables in extraorbital lacrimal gland (EoLG) after corneal HSV-1 infection in the C57BL/6J mouse model. Our results showed a significant reduction in the volume of tears in infected eyes during the development of HSK. Extensive architectural damage to EoLG, presumably caused by a massive influx of interferon-gamma secreting T cells, was observed during clinical disease period of HSK. A positive correlation between the decrease in tear volume, severity of HSK and the damage to EoLG were evident in infected mice. The presence of infectious virus measured in EoLG during pre-clinical, but not clinical disease period of HSK, suggested that viral cytopathic effects are not the major contributors of extensive damage seen in EoLG. Furthermore, topical administration of lacritin peptide delayed but did not prevent the decrease in tears in HSV-1 infected mice, and had no significant effect in either reducing the severity of HSK or T cell infiltration in EoLG of infected mice. Together, our results showed an interplay between the severity of HSK, inflammation of EoLG, and the reduced level of tears after corneal HSV-1 infection.

['Rao|Pushpa|P|', 'McKown|Robert L|RL|', 'Laurie|Gordon W|GW|', 'Suvas|Susmit|S|']

2019

33779017

Stereoselective Sc(OTf)3 -Catalyzed Aldol Reactions of Disubstituted Silyl Enol Ethers of Aldehydes with Acetals.

Facile and modular access to stereodefined disubstituted aldehyde-derived silyl enol ethers allowed their successful application in a stereoselective aldol reaction affording the products with excellent yields and diastereomeric ratios. The counter-intuitive stereochemical behavior of this Mukaiyama-aldol reaction is accounted for by a non-classical open transition state.

['Wang|Peter-Yong|PY|', 'Massad|Itai|I|', 'Marek|Ilan|I|http://orcid.org/0000-0001-9154-2320']

2021

30993492

Callous-Unemotional Traits and Academic Performance in Secondary School Students: Examining the Moderating Effect of Gender.

Callous-unemotional (CU) traits and male gender are both known risk factors for poor academic outcomes in children and adolescents. However, despite gender differences in CU trait severity, comorbid difficulties and correlates of CU traits, research has yet to examine whether the CU traits and male gender may work together to increase risk for poor academic performance. That is, whether boys high in CU traits perform more poorly across academic disciplines than girls high in these traits. This study therefore aimed to investigate i) the relationships between CU traits, student gender and English, Science and Math grades, and ii) whether gender moderates the association between CU traits and academic outcomes. Participants were 437 children aged 11 to 14 years (mean age 12.50 years; 49% girls; 85% White) attending a state secondary school in England. Students reported on CU traits and externalizing problems and their English, Math and Science grades were gathered from school records. Using hierarchical linear modelling, CU traits were found to be significantly related to lower English, Math and Science grades when controlling for age, gender, sociodemographic disadvantage and externalizing problems. CU traits were significantly related to lower Science grades for boys but not girls. However, gender did not moderate the association between CU traits for English or Math grades. Findings enhance our understanding of how child characteristics may interact to increase the likelihood of poor school outcomes, and therefore help us to identify youth at-risk for poor academic performance.

['Bird|Elisabeth|E|', 'Chhoa|Celine Y|CY|', 'Midouhas|Emily|E|', 'Allen|Jennifer L|JL|0000-0003-3566-3747']

2019

32212021

Structure and development of anthers and connective glands in two species of Stigmaphyllon (Malpighiaceae): are heteromorphic anthers related to division of labour?

Heteranthery has been largely associated with a division of labour between anthers. Most species of Stigmaphyllon (Malpighiaceae) present heteromorphic anthers and glandular connectives of different development; yet, the functional meaning of this condition has never been explored in the genus. The aims of this study were to provide a comparative description of the structure and development of anthers and their connective glands in S. bonariense and S. jatrophifolium and to assess the existence of division of functions. Natural populations were selected to collect flowers at different stages. Anthers were subjected to morpho-anatomical, histochemical and pollen viability studies. For both species, abundance of pollen grains and size of anther and their connective glands were estimated. Three types of stamens are recognized: stamen with small, intermediate and large anthers. Anthers of both species exhibit a similar glandular tissue in the connective, and the histochemical analysis revealed that it produce a mucilagous secretion. The pattern of anther wall development, stainability and release of pollen grains was identical among anther types. For both species, we observed a positive relationship between anther size and abundance of pollen grains, but an inverse relationship between area of anthers and size (area and thickness) of connective glands in small anthers vs. intermediate and large ones. Our results evidence a specialization of anthers related to division of labour between heteromorphic stamens in two species of Stigmaphyllon. Thus, one set of anthers produces large amount of pollen grains for pollination and another sets large quantities of mucilage, which would improve pollen transport (better adherence to pollinator body and dampness maintenance). Nevertheless, heteranthery in both Stigmaphyllon species would represent a transitional state towards the division of labour rather than a stable state.

['Avalos|Adan Alberto|AA|https://orcid.org/0000-0002-9690-1334', 'Pablo|Torretta Juan|TJ|https://orcid.org/0000-0001-8185-4822', 'Lattar|Elsa Clorinda|EC|https://orcid.org/0000-0001-6127-4038', 'Ferrucci|María Silvia|MS|https://orcid.org/0000-0003-4917-1188']

2020

28864419

Epiphycan is specifically expressed in cochlear supporting cells and is necessary for normal hearing.

The study of inner ear specific transcripts has revealed novel information about hereditary hearing loss and a mechanism of normal hearing. In this study, by analyzing a published cDNA library, we focused on Epiphycan (Epyc), a member of the small leucine-rich repeat proteoglycan family, whose transcript is enriched in the inner ear. Epyc mRNA was expressed abundantly and specifically in adult mice cochleae and was localized in supporting cells within the organ of Corti of both neonatal and adult mice. To examine the function of Epyc, we generated Epyc knockout (KO) mice using the CRISPR/Cas9 system. Epyc KO mice cochleae exhibited normal morphology. However, measurement of the auditory brain-stem response in Epyc KO mice revealed an elevated hearing threshold above 16 kHz frequency. This study suggests that Epyc is necessary for normal auditory function.

['Hanada|Yukiko|Y|', 'Nakamura|Yukiko|Y|', 'Ishida|Yusuke|Y|', 'Takimoto|Yasumitsu|Y|', 'Taniguchi|Manabu|M|', 'Ozono|Yoshiyuki|Y|', 'Koyama|Yoshihisa|Y|', 'Morihana|Tetsuo|T|', 'Imai|Takao|T|', 'Ota|Yumi|Y|', 'Sato|Takashi|T|', 'Inohara|Hidenori|H|', 'Shimada|Shoichi|S|']

2017

32440647

Interpersonal and Group Contingencies.

Responding by individuals in groups has been a prominent interest of the field of psychology. Experimental analyses of human behavior have provided some unique findings of the role that the environment, including both social and nonsocial stimuli, may have on individual responding. Cooperative and competitive contingencies, previously evaluated in animal and human operant research, provide unique insight into applied interventions, in particular group contingencies. The current manuscript attempts to bridge these two literatures to foster the development of more effective technologies and lines of experimental or translational research that may better inform interventions in the applied realm.

['Cariveau|Tom|T|', 'Muething|Colin S|CS|', 'Trapp|Whitney|W|']

2020

29860829

Imaging Catalytic Hotspots on Single Plasmonic Nanostructures via Correlated Super-Resolution and Electron Microscopy.

Surface-plasmon (SP) enhanced catalysis on plasmonic nanostructures brings opportunities to increase catalytic efficiency and alter catalytic selectivity. Understanding the underlying mechanism requires quantitative measurements of catalytic enhancement on these nanostructures, whose intrinsic structural heterogeneity presents experimental challenges. Using correlated super-resolution fluorescence microscopy and electron microscopy, here we report a quantitative visualization of SP-enhanced catalytic activity at the nanoscale within single plasmonic nanostructures. We focus on two Au- and Ag-based linked nanostructures that present plasmonic hotspots at nanoscale gaps. Spatially localized higher reaction rates at these gaps vs nongap regions report the SP-induced catalytic enhancements, which show direct correlations with the nanostructure geometries and local electric field enhancements. Furthermore, the catalytic enhancement scales quadratically with the local actual light intensity, attributable to hot electron involvement in the catalytic enhancement mechanism. These discoveries highlight the effectiveness of correlated super-resolution and electron microscopy in interrogating nanoscale catalytic properties.

['Zou|Ningmu|N|', 'Chen|Guanqun|G|0000-0001-8000-0171', 'Mao|Xianwen|X|', 'Shen|Hao|H|0000-0002-2798-5861', 'Choudhary|Eric|E|', 'Zhou|Xiaochun|X|0000-0001-9793-6072', 'Chen|Peng|P|0000-0001-8582-7661']

2018

29152737

Molecular mechanisms of drug resistance in ovarian cancer.

Ovarian cancer is the most lethal malignancy among the gynecological cancers, with a 5-year survival rate, mainly due to being diagnosed at advanced stages, recurrence and resistance to the current chemotherapeutic agents. Drug resistance is a complex phenomenon and the number of known involved genes and cross-talks between signaling pathways in this process is growing rapidly. Thus, discovering and understanding the underlying molecular mechanisms involved in chemo-resistance are crucial for management of treatment and identifying novel and effective drug targets as well as drug discovery to improve therapeutic outcomes. In this review, the major and recently identified molecular mechanisms of drug resistance in ovarian cancer from relevant literature have been investigated. In the final section of the paper, new approaches for studying detailed mechanisms of chemo-resistance have been briefly discussed.

['Norouzi-Barough|Leyla|L|', 'Sarookhani|Mohammad Reza|MR|', 'Sharifi|Mohammadreza|M|0000-0002-1538-9034', 'Moghbelinejad|Sahar|S|', 'Jangjoo|Saranaz|S|', 'Salehi|Rasoul|R|0000-0003-4062-6166']

2018

34281550

Investigating causal relationships between exposome and human longevity: a Mendelian randomization analysis.

BACKGROUND Environmental factors are associated with human longevity, but their specificity and causality remain mostly unclear. By integrating the innovative "exposome" concept developed in the field of environmental epidemiology, this study aims to determine the components of exposome causally linked to longevity using Mendelian randomization (MR) approach. METHODS A total of 4587 environmental exposures extracting from 361,194 individuals from the UK biobank, in exogenous and endogenous domains of exposome were assessed. We examined the relationship between each environmental factor and two longevity outcomes (i.e., surviving to the 90th or 99th percentile age) from various cohorts of European ancestry. Significant results after false discovery rates correction underwent validation using an independent exposure dataset. RESULTS Out of all the environmental exposures, eight age-related diseases and pathological conditions were causally associated with lower odds of longevity, including coronary atherosclerosis (odds ratio = 0.77, 95% confidence interval [0.70, 0.84], P = 4.2 × 10-8), ischemic heart disease (0.66, [0.51, 0.87], P = 0.0029), angina (0.73, [0.65, 0.83], P = 5.4 × 10-7), Alzheimer's disease (0.80, [0.72, 0.89], P = 3.0 × 10-5), hypertension (0.70, [0.64, 0.77], P = 4.5 × 10-14), type 2 diabetes (0.88 [0.80, 0.96], P = 0.004), high cholesterol (0.81, [0.72, 0.91], P = 0.0003), and venous thromboembolism (0.92, [0.87, 0.97], P = 0.0028). After adjusting for genetic correlation between different types of blood lipids, higher levels of low-density lipoprotein cholesterol (0.72 [0.64, 0.80], P = 2.3 × 10-9) was associated with lower odds of longevity, while high-density lipoprotein cholesterol (1.36 [1.13, 1.62], P = 0.001) showed the opposite. Genetically predicted sitting/standing height was unrelated to longevity, while higher comparative height size at 10 was negatively associated with longevity. Greater body fat, especially the trunk fat mass, and never eat sugar or foods/drinks containing sugar were adversely associated with longevity, while education attainment showed the opposite. CONCLUSIONS The present study supports that some age-related diseases as well as education are causally related to longevity and highlights several new targets for achieving longevity, including management of venous thromboembolism, appropriate intake of sugar, and control of body fat. Our results warrant further studies to elucidate the underlying mechanisms of these reported causal associations.

['Huang|Shu-Yi|SY|', 'Yang|Yu-Xiang|YX|', 'Chen|Shi-Dong|SD|', 'Li|Hong-Qi|HQ|', 'Zhang|Xue-Qing|XQ|', 'Kuo|Kevin|K|', 'Tan|Lan|L|', 'Feng|Lei|L|', 'Dong|Qiang|Q|', 'Zhang|Can|C|', 'Yu|Jin-Tai|JT|']

2021

33307956

Brain Gene Expression in Systemic Hypothyroidism and Mouse Models of MCT8 Deficiency: The Mct8-Oatp1c1-Dio2 Triad.

The monocarboxylate transporter 8 (Mct8) protein is a primary thyroxine (T4) and triiodothyronine (T3) (thyroid hormone [TH]) transporter. Mutations of the MCT8-encoding, SLC16A2 gene alter thyroid function and TH metabolism and severely impair neurodevelopment (Allan-Herndon-Dudley syndrome [AHDS]). Mct8-deficient mice manifest thyroid alterations but lack neurological signs. It is believed that Mct8 deficiency in mice is compensated by T4 transport through the Slco1c1-encoded organic anion transporter polypeptide 1c1 (Oatp1c1). This allows local brain generation of sufficient T3 by the Dio2-encoded type 2 deiodinase, thus preventing brain hypothyroidism. The Slc16a2/Slco1c1 (MO) and Slc16a2/Dio2 (MD) double knockout (KO) mice lacking T4 and T3 transport, or T3 transport and T4 deiodination, respectively, should be appropriate models of AHDS. Our goal was to compare the cerebral hypothyroidism of systemic hypothyroidism (SH) caused by thyroid gland blockade with that present in the double KO mice. We performed RNA sequencing by using RNA from the cerebral cortex and striatum of SH mice and the double KO mice on postnatal days 21-23. Real-time polymerase chain reaction was used to confirm RNA-Seq results in replicate biological samples. Cell type involvement was assessed from cell type-enriched genes. Functional genomic differences were analyzed by functional node activity based on a probabilistic graphical model. Each of the three conditions gave a different pattern of gene expression, with partial overlaps. SH gave a wider and highest variation of gene expression than MD or MO. This was partially due to secondary gene responses to hypothyroidism. The set of primary transcriptional T3 targets showed a tighter overlap, but quantitative gene responses indicated that the gene responses in SH were more severe than in MD or MO. Examination of cell type-enriched genes indicated cellular differences between the three conditions. The results indicate that the neurological impairment of AHDS is too severe to be fully explained by TH deprivation only.

['Morte|Beatriz|B|', 'Gil-Ibañez|Pilar|P|', 'Heuer|Heike|H|', 'Bernal|Juan|J|']

2021

34574168

Phenolic Composition and Antioxidant Properties of Cooked Rice Dyed with Sorghum-Leaf Bio-Colorants.

White rice is an important staple food globally. It is a rich source of energy but is low in dietary phenolic antioxidants. This current research aimed at providing scientific evidence for an alternative rice dish that has increased phenolic-antioxidant health-promoting potential by combining white rice with red cowpea beans and cooking with dye sorghum leaves hydrothermal extract, as a source of natural colorant. Boiled white rice and the rice-cowpea-sorghum extract dish were freeze-dried, and the free and bound phenolic compounds of raw and cooked samples were extracted. Phenolic composition, total phenolic content (TPC), and antioxidant activities (measured by 2,2-diphenyl-1-picrylhydrazyl radical scavenging capacity, Trolox equivalent antioxidant capacity, and oxygen radical absorbance capacity methods) of the raw and cooked samples were determined. Combining white rice with cowpea seeds and sorghum leaves extract significantly (p < 0.0001) increased the TPC and antioxidant activities of the rice due to the higher TPC and antioxidant activities of cowpea and sorghum leaves. Although boiling caused substantial losses of flavonoids and anthocyanins in the rice-cowpea-sorghum extract composite meal, the resulting dish had higher TPC and antioxidant activities than boiled white rice. Compositing white rice with phenolic-rich pulses can be an innovative approach to providing alternative healthy rice dishes to consumers.

['Apea-Bah|Franklin Brian|FB|', 'Li|Xiang|X|', 'Beta|Trust|T|']

2021

30685890

Does knee position during wound closure alter patella height following total knee arthroplasty?

BACKGROUND Patella infera is a known complication of total knee arthroplasty, and the method of soft tissue closure is a possible contributing factor. The aim of our study was to evaluate the effect of knee position during surgical closure of capsule, subcutaneous tissue and skin on patella tendon length after total knee arthroplasty. METHODS A three arm retrospective cohort study was conducted in a single institution over a 3-year period; 75 patients were divided, by surgeon preference, into three groups (Flexed, Extended and Hybrid) of 25 patients. All groups had standardized prosthesis, intraoperative and postoperative protocols, and differed in knee position at closure. Patellar tendon length was assessed radiologically using Insall Salvati ratio (ISR) and modified Insall Salvati ratio, with a 12-month follow-up. Intraclass correlation coefficients were used to assess intraobserver variability. RESULTS There was a small but significant difference in preoperative to initial postoperative ISR change between Flexed and Extended groups (Extended group mean ISR change = -0.05; t = -2.31, P = 0.025, independent samples t-test), which was not sustained at 12 months. The incidence of patella infera was similar in Flexed and Extended groups at 12 months with only one case seen in the Hybrid group. CONCLUSION Our study suggests that knee position during soft tissue closure does not have a sustained impact on patella tendon length after knee replacement. A small but statistically significant reduction in patella height was found in the Extended group initially after surgery but this effect was not sustained at 12 months.

['Clark|Shane|S|0000-0003-1808-1024', 'Tee|Lawrence|L|0000-0003-2066-7382', 'Sutherland|Alasdair|A|']

2019

28589655

Cannulation-Related Complications on Veno-Arterial Extracorporeal Membrane Oxygenation: Prevalence and Effect on Mortality.

Cannulation-related complications are a known source of morbidity in patients supported on veno-arterial extracorporeal membrane oxygenation (VA-ECMO). Despite its prevalence, little is known regarding the outcomes of patients who suffer such complications. This is a single institution review of cannulation-related complications and its effect on mortality in patients supported on VA-ECMO from January 2010-2015 using three cannulation strategies: axillary, femoral, and central. Complications were defined as advanced if they required major interventions (fasciotomy, amputation, site conversion). Patients were divided into two groups (complication present vs. not present) and Kaplan-Meier analysis was performed to determine any differences in their survival distributions. There were 103 patients supported on VA-ECMO: 41 (40%), 36 (35%), and 26 (25%) were cannulated via axillary, femoral, and central access, respectively. Cannulation-related complications occurred in 33 (32%) patients and this did not differ significantly between either axillary (34%), femoral (36%), or central (23%) strategies (P = 0.52). The most common complications encountered were hemorrhage and limb ischemia in 19 (18%) and 11 (11%) patients. Hemorrhagic complications did not differ between groups (P = 0.37), while limb ischemia and hyperperfusion were significantly associated with femoral and axillary cannulation, at a rate of 25% (P < 0.01) and 15% (P = 0.01), respectively. There was no difference in the incidence of advanced complications between cannulation groups: axillary (12%) vs. femoral (14%) vs. central (8%; P = 0.75). In addition, no increase in mortality was noted in patients who developed a cannulation-related complication by Kaplan-Meier estimates (P = 0.37). Cannulation-related complications affect a significant proportion of patients supported on VA-ECMO but do not differ in incidence between different cannulation strategies and do not affect patient mortality. Improved efforts at preventing these complications need to be developed to avoid the additional morbidity in an already critical patient population.

['Wong|Joshua K|JK|', 'Melvin|Amber L|AL|', 'Joshi|Devang J|DJ|', 'Lee|Candice Y|CY|', 'Archibald|William J|WJ|', 'Angona|Ron E|RE|', 'Tchantchaleishvili|Vakhtang|V|', 'Massey|Howard T|HT|', 'Hicks|George L|GL|', 'Knight|Peter A|PA|']

2017

32290801

Evolutionary dynamics of culturally transmitted, fertility-reducing traits.

Human populations in many countries have undergone a phase of demographic transition, characterized by a major reduction in fertility at a time of increased resource availability. A key stylized fact is that the reduction in fertility is preceded by a reduction in mortality and a consequent increase in population density. Various theories have been proposed to account for the demographic transition process, including maladaptation, increased parental investment in fewer offspring, and cultural evolution. None of these approaches, including formal cultural evolutionary models of the demographic transitions, have addressed a possible direct causal relationship between a reduction in mortality and the subsequent decline in fertility. We provide mathematical models in which low mortality favours the cultural selection of low-fertility traits. This occurs because reduced mortality slows turnover in the model, which allows the cultural transmission advantage of low-fertility traits to outrace their reproductive disadvantage. For mortality to be a crucial determinant of outcome, a cultural transmission bias is required where slow reproducers exert higher social influence. Computer simulations of our models that allow for exogenous variation in the death rate can reproduce the central features of the demographic transition process, including substantial reductions in fertility within only one to three generations. A model assuming continuous evolution of reproduction rates through imitation errors predicts fertility to fall below replacement levels if death rates are sufficiently low. This can potentially explain the very low preferred family sizes in Western Europe.

['Wodarz|Dominik|D|', 'Stipp|Shaun|S|', 'Hirshleifer|David|D|', 'Komarova|Natalia L|NL|']

2020

32655493

Comprehensive Lipidome Profiling of the Kidney in Early-Stage Diabetic Nephropathy.

Metabolic changes associated with diabetes are reported to lead to the onset of early-stage diabetic nephropathy (DN). Furthermore, lipotoxicity is implicated in renal dysfunction. Most studies of DN have focused on a single or limited number of lipids, and the lipidome of the kidney during early-stage DN remains to be elucidated. In the present study, we aimed to comprehensively identify lipid abnormalities during early-stage DN; to this end, we established an early-stage DN rat model by feeding a high-sucrose and high-fat diet combined with administration of low-dose streptozotocin. Using a high-coverage, targeted lipidomic approach, we established the lipid profile, comprising 437 lipid species and 25 lipid classes, of the kidney cortex in normal rats and the DN rat model. Our findings additionally confirmed that the DN rat model had been successfully established. We observed distinct lipidomic signatures in the DN kidney, with characteristic alterations in side chain composition and degree of unsaturation. Glyceride lipids, especially cholesteryl esters, showed a significant increase in the DN kidney cortex. The levels of most phospholipids exhibited a decline, except those of phospholipids with side chain of 36:1. Furthermore, the levels of lyso-phospholipids and sphingolipids, including ceramide and its derivatives, were dramatically elevated in the present DN rat model. Our findings, which provide a comprehensive lipidome of the kidney cortex in rats with DN, are expected to be useful for the identification of pathologically relevant lipid species in DN. Furthermore, the results represent novel insights into the mechanistic basis of DN.

['Hou|Biyu|B|', 'He|Ping|P|', 'Ma|Peng|P|', 'Yang|Xinyu|X|', 'Xu|Chunyang|C|', 'Lam|Sin Man|SM|', 'Shui|Guanghou|G|', 'Yang|Xiuying|X|', 'Zhang|Li|L|', 'Qiang|Guifen|G|', 'Du|Guanhua|G|']

2020

26307962

α-Glucosidase Inhibitors from Vauquelinia corymbosa.

The α-glucosidase inhibitory activity of an aqueous extract and compounds from the aerial parts of V. corymbosa was demonstrated with yeast and rat small intestinal α-glucosidases. The aqueous extract inhibited yeast α-glucosidase with a half maximal inhibitory concentration (IC50) of 28.6 μg/mL. Bioassay-guided fractionation of the extract led to the isolation of several compounds, including one cyanogenic glycoside [prunasin (1)], five flavonoids [(-)-epi-catechin (2), hyperoside (3), isoquercetin (4), quercitrin (5) and quercetin-3-O-(6''-benzoyl)-β-galactoside (6)] and two simple aromatic compounds [picein (7) and methylarbutin (8)]. The most active compound was 6 with IC50 values of 30 μM in the case of yeast α-glucosidase, and 437 μM in the case of the mammalian enzyme. According to the kinetic analyses performed with rat and yeast enzymes, this compound behaved as mixed-type inhibitor; the calculated inhibition constants (Ki) were 212 and 50 μM, respectively. Molecular docking analyses with yeast and mammalian α-glucosidases revealed that compound 6 bind differently to these enzymes. Altogether, the results of this work suggest that preparations of V. corymbosa might delay glucose absorption in vivo.

['Flores-Bocanegra|Laura|L|', 'Pérez-Vásquez|Araceli|A|', 'Torres-Piedra|Mariana|M|', 'Bye|Robert|R|', 'Linares|Edelmira|E|', 'Mata|Rachel|R|']

2015

30301847

Is mitochondrial gene expression coordinated or stochastic?

Mitochondrial biogenesis is intimately dependent on the coordinated expression of the nuclear and mitochondrial genomes that is necessary for the assembly and function of the respiratory complexes to produce most of the energy required by cells. Although highly compacted in animals, the mitochondrial genome and its expression are essential for survival, development, and optimal energy production. The machinery that regulates gene expression within mitochondria is localised within the same compartment and, like in their ancestors, the bacteria, this machinery does not use membrane-based compartmentalisation to order the gene expression pathway. Therefore, the lifecycle of mitochondrial RNAs from transcription through processing, maturation, translation to turnover is mediated by a gamut of RNA-binding proteins (RBPs), all contained within the mitochondrial matrix milieu. Recent discoveries indicate that multiple processes regulating RNA metabolism occur at once but since mitochondria have a new complement of RBPs, many evolved de novo from nuclear genes, we are left wondering how co-ordinated are these processes? Here, we review recently identified examples of the co-ordinated and stochastic processes that govern the mitochondrial transcriptome. These new discoveries reveal the complexity of mitochondrial gene expression and the need for its in-depth exploration to understand how these organelles can respond to the energy demands of the cell.

['Lee|Richard G|RG|', 'Rudler|Danielle L|DL|', 'Rackham|Oliver|O|', 'Filipovska|Aleksandra|A|0000-0002-6998-8403']

2018

31660876

Chromosomal and plasmid-mediated fluoroquinolone resistance in human Salmonella enterica infection in Ghana.

BACKGROUND Salmonella infection poses significant public health threat globally, especially in resource-limited countries. Emergence and spread of antibiotic resistant strains to fluoroquinolones have led to treatment failures and increased mortality in Salmonella infection. However, there is dearth of information regarding mechanisms of resistance to fluoroquinolones in Ghana. This study therefore sought to identify chromosomal mutations and plasmid-mediated resistance as possible mechanisms of fluoroquinolone resistance from clinical isolates in Ghana. METHODS This was a retrospective study of archived isolates biobanked at Kumasi Centre for Collaborative Research in Tropical Medicine, Ghana. Isolates were obtained from blood, stool and oropharynx samples at two hospitals, between May, 2016 and January, 2018. Salmonella identification was done using standard microbiological protocols and antibiotic susceptibility testing performed by Kirby-Bauer disc diffusion method. Isolates with intermediate susceptibility and/or resistance to nalidixic acid and/or ciprofloxacin were selected and examined for chromosomal mutations by Sanger sequencing and plasmid-mediated resistance by PCR. RESULTS Of 133 biobanked isolates cultured, 68 (51.1%) and 16 (12%) were identified as Salmonella Typhi and non-typhoidal Salmonella (NTS), respectively. Sequence analysis of gyrA gene revealed the presence of 5 different nonsynonymous mutations, with the most frequent mutation (Ile203Ser) occurring in 12 out of 13 isolates tested. Gyrase B (gyrB) gene had 1 nonsynonymous mutation in 3 out of 13 isolates, substituting phenylalanine with leucine at codon 601 (Phe601Leu). No mutation was observed in parC and parE genes. Two NTS isolates were found to harbour qnrS plasmid-mediated resistant gene of molecular size 550 bp with high ciprofloxacin MIC of 0.5 μg/ml. CONCLUSION This study reports for the first time in Ghana plasmid-mediated fluoroquinolone resistant gene qnrS in Salmonella clinical isolates. Nonsynonymous mutations of gyrA and gyrB genes likely to confer Salmonella reduced susceptibility to ciprofloxacin were also reported.

['Acheampong|Godfred|G|', 'Owusu|Michael|M|', 'Owusu-Ofori|Alex|A|', 'Osei|Isaac|I|', 'Sarpong|Nimako|N|', 'Sylverken|Augustina|A|', 'Kung|Hung-Jui|HJ|', 'Cho|Shu-Ting|ST|', 'Kuo|Chih-Horng|CH|', 'Park|Se Eun|SE|', 'Marks|Florian|F|', 'Adu-Sarkodie|Yaw|Y|', 'Owusu-Dabo|Ellis|E|http://orcid.org/0000-0003-4232-4292']

2019

32849965

Cardiotoxicity by Anthracycline Regimen Chemotherapy Prolonged T Peak to T End Interval.

Background Myocardial necrosis may occur due to anthracycline (doxorubicin/adriamycin) chemotherapy usage. Furthermore, myocardial necrosis can affect the heterogeneity of heart conduction system and lead to repolarization abnormalities. The aim of this study was to investigate the effect of cardiotoxicity caused by anthracycline to repolarization abnormalities measured by T peak to T end (TpTe) interval. Methods This was a single center prospective cohort study with linear regression from October 2018 to May 2019. The subjects of the study were breast cancer patients after completing administration of chemotherapy with fluorouracil, adriamycin and cyclophosphamide (FAC) regimen (containing anthracycline) for 6 months. Myocardial necrosis was assessed by high sensitive (hs)-troponin I, and the heterogeneity of repolarization was measured by TpTe interval. Results This study involved 25 breast cancer patients after chemotherapy in the 6-month FAC regimen. The mean age is 46 ± 7 years, and the cumulative dose of anthracycline is 591 ± 52 mg/m2. The mean level of hs-troponin I is 90.5 ± 44.7 ng/L and the TpTe interval is 108.2 ± 10 ms. The results of linear regression analysis showed a positive correlation between hs-troponin I and TpTe interval (r: 0.421, P: 0.036) after controlling for one confounding variable (cumulative dose of anthracycline). Conclusions Cardiotoxicity caused by accumulative dose of anthracycline may lead to myocardial necrosis which was shown by elevated hs-troponin I levels. This process may lead to heterogeneity conduction system that affect the repolarization phase of cardiac cycle which was shown by increased TpTe interval.

['Iqbal|Mohammad|M|', 'Victory|Viky|V|', 'Astuti|Astri|A|', 'Febrianora|Mega|M|', 'Karwiky|Giky|G|', 'Achmad|Chaerul|C|', 'Akbar|Mohammad Rizki|MR|']

2020

23639223

Risk factors for scald injury in children under 5 years of age: a case-control study using routinely collected data.

Scald injury is common, accounting for half of all burns in pre-school children. Most scalds are preventable and health professionals can play an important role in targeting interventions to those at greatest risk. However, the potential for routinely collected medical data to be used to identify high risk children has not been well explored. We used a matched case-control study to identify risk factors for first scald injury in children under 5 using a large, nationally representative database of routinely collected primary care records. Among 986 cases and 9240 controls, male gender, age (2 years), higher birth order, single-parent families and increasing index of material deprivation were associated with increased odds of scald injury. Older maternal age at childbirth was associated with decreased odds of scald injury. Children at risk of scald injury can be identified from routinely collected primary care data and primary care practitioners can use this information to target evidence-based safety interventions.

['Shah|M|M|', 'Orton|E|E|', 'Tata|L J|LJ|', 'Gomes|C|C|', 'Kendrick|D|D|']

2013

34861087

Bioremediation of trichloroethylene-polluted groundwater using emulsified castor oil for slow carbon release and acidification control.

In this study, the emulsified castor oil (ECO) substrate was developed for a long-term supplement of biodegradable carbon with pH buffering capacity to anaerobically bioremediate trichloroethylene (TCE)-polluted groundwater. The ECO was produced by mixing castor oil, surfactants [sapindales and soya lecithin (SL)], vitamin complex, and a citrate/sodium phosphate dibasic buffer system together for slow carbon release. Results of the emulsification experiments and microcosm tests indicate that ECO emulsion had uniform small droplets (diameter = 539 nm) with stable oil-in-water characteristics. ECO had a long-lasting, dispersive, negative zeta potential (-13 mv), and biodegradable properties (viscosity = 357 cp). Approximately 97% of TCE could be removed with ECO supplement after a 95-day operational period without the accumulation of TCE dechlorination byproducts (dichloroethylene and vinyl chloride). The buffer system could neutralize acidified groundwater, and citrate could be served as a primary substrate. ECO addition caused an abrupt TCE adsorption at the initial stage and the subsequent removal of adsorbed TCE. Results from the next generation sequences and real-time polymerase chain reaction (PCR) indicate that the increased microbial communities and TCE-degrading bacterial consortia were observed after ECO addition. ECO could be used as a pH-control and carbon substrate to enhance anaerobic TCE biodegradation effectively. PRACTITIONER POINTS: Emulsified castor oil (ECO) contains castor oil, surfactants, and buffer for a slow carbon release and pH control. ECO can be a long-term carbon source for trichloroethylene (TCE) dechlorination without causing acidification. TCE removal after ECO addition is due to adsorption and reductive dechlorination mechanisms. Citrate (contained in buffer system) can serve as a primary substrate for TCE dechlorination enhancement. ECO addition causes increased bacterial diversity, Dehalococcoides sp., and hydrogen-producing gene (hydA).

['Chen|Wei-Ting|WT|https://orcid.org/0000-0001-7089-6998', 'Chen|K F|KF|', 'Surmpalli|R Y|RY|', 'Zhang|Tiancheng|T|', 'Ou|Jiun-Hau|JH|', 'Kao|Chih-Ming|CM|https://orcid.org/0000-0002-6151-7076']

2021

32410309

In Situ Formation of Polymeric Nanoassemblies Using an Efficient Reversible Click Reaction.

Polymer-drug conjugates are promising as strategies for drug delivery, because of their high drug loading capacity and low premature release profile. However, the preparation of these conjugates is often tedious. In this paper, we report an efficient method for polymer-drug conjugates using an ultrafast and reversible click reaction in a post-polymerization functionalization strategy. The reaction is based on the rapid condensation of boronic acid functionalities with salicylhydroxamates. The polymer, bearing the latter functionality, has been designed such that the reaction with boronic acid bearing drugs induces an in situ self-assembly of the conjugates to form well-defined nanostructures. We show that this method is not only applicable for molecules with an intrinsic boronic acid group, but also for the other molecules that can be linked to aryl boronic acids through a self-immolative linker. The linker has been designed to cause traceless release of the attached drug molecules, the efficiency of which has been demonstrated through intracellular delivery.

['Liu|Bin|B|0000-0003-1736-9392', 'Wu|Ruiling|R|', 'Gong|Shuai|S|', 'Xiao|Hang|H|', 'Thayumanavan|S|S|0000-0002-6475-6726']

2020

33599864

Delayed initiation of adjuvant chemotherapy among women with breast cancer in Addis Ababa, Ethiopia.

PURPOSE Chemotherapy within 90 days following surgery for non-metastatic breast cancer is the standard of care. There are no data, however, on the extent of time to initiation of chemotherapy (TTC) in Africa settings, including Ethiopia. METHODS A total of 223 women with stage I-III breast cancer treated with surgery and adjuvant chemotherapy during 2017-2019 in Addis Ababa, Ethiopia, were included in the analysis. Based on information from medical records, we calculated TTC from date of surgery and completion of planned chemotherapy, with TTC > 90 days considered delayed and receipt of 85% of planned therapy as complete. Multivariable Poisson regression with robust variance was used to assess whether TTC > 90 days was associated with sociodemographic or clinical factors. RESULTS The median TTC was 63 days. Chemotherapy initiation was delayed in 30% (95% CI 24.4-36.6%) of patients, with the risk significantly higher in low-income women. For example, the risk of delay in women with lowest quartile family monthly income group (US$ < 61) was 3.98 (95% CI 1.67-9.46) higher than in those women with highest quartile family income group (US$ > 194). Remarkably, adjuvant chemotherapy was completed in 95% of patients. CONCLUSIONS A staggering one-in-three women with breast cancer in Addis Ababa, Ethiopia, delay to initiation of adjuvant chemotherapy, with the delay more common in low-income women and yet with remarkably high degree of treatment adherence. These findings underscore the need for public policy to expand health care to low-income population to improve breast cancer care and other health outcomes in the country.

['Gebremariam|Alem|A|http://orcid.org/0000-0003-2173-6685', 'Assefa|Mathewos|M|', 'Addissie|Adamu|A|', 'Worku|Alemayehu|A|', 'Dereje|Nebiyu|N|', 'Abreha|Aynalem|A|', 'Tigeneh|Wondemagegnehu|W|', 'Pace|Lydia E|LE|', 'Kantelhardt|Eva Johanna|EJ|', 'Jemal|Ahmedin|A|']

2021

28971076

Faculty-Student Caring Interaction in Nursing Education: An Integrative Review.

Faculty- student caring relationship in nursing education has been offered as enhancing students' learning experiences to care , desire to care for others and self-actu-alization. This review therefore was carried out to analyze faculty-student caring interactions in nursing education. This concept analysis of caring in the nursing education was conducted based on Broom methodology of integrative review. The literature was consisted of two books from two known theorists, and 47 relevant articles. They retrieved from English data bases including MEDLINE, CINAHL, ERIC, SCOPUS, and SID, with based on the keywords of caring and "nursing education", during the period 2005-2014. Caring in nursing education refers to faculty-student interaction based on ethical and human values. The development of values and moral principles in education, flexibility in educational processes, application of objective patterns in learning, and dynamism in educational processes are identified as caring concept attributes in teaching-learning process. This requires environmental support, constant human relationship, and knowing. Internalization of values, achieving self-esteem, peace, and towards human evolution were the main achievements of the concept of caring in nursing education. The details obtained from the dimensions of "caring" concept in this study could be utilized by nursing education researchers and designers in order to develop content and structure for educational programs.

['Salehian|Maryam|M|', 'Heydari|Abbas|A|', 'Aghebati|Nahid|N|', 'Karimi Moonaghi|Hossein|H|']

2017

31563482

Relations between mandible-only advancement surgery, the extent of the posterior airway space, and the position of the hyoid bone in Class II patients: a three-dimensional analysis.

The objective of the present study was to evaluate the relation between mandibular advancement, the three-dimensional extent of the posterior airway space (PAS), and the position of the hyoid bone, using cone-beam computed tomography (CT). Twenty-eight Class II patients (21 women (mean (SD) age 29 (9) years) and seven men (mean (SD) age 23 (6) years)), who had had mandibular-only advancement surgery (Obwegeser-Dal Pont) were included in the study. In each case, cone-beam CT scans were taken one week before and six months after operation, and a retrospective analysis made of the alterations of several airway variables (volume, mean cross-sectional area, and diameter) and the three-dimensional extent of mandibular and hyoid movement, by using IPlan® cranial software. A linear regression was also done to correlate mandibular advancement, the movement of the hyoid bone, and airway variables. There were significant postoperative increases in all volumetric PAS variables, and in most diametric and spherical variables (p<0.05). There was also a significant linear relation between forward displacement of the mandible and the movement of the hyoid bone (p<0.05). These results show that mandible-only advancement surgery causes an increase in most dimensions of the PAS. This intervention can be assumed to reduce airway resistance and therefore might be a suitable treatment option for patients with obstructive sleep apnoea syndrome.

['Rückschloß|T|T|', 'Ristow|O|O|', 'Berger|M|M|', 'Engel|M|M|', 'Freudlsperger|C|C|', 'Hoffmann|J|J|', 'Seeberger|R|R|']

2019

32014338

CAD/CAM supported production process of standardized enamel and dentin tooth discs with different thicknesses for in vitro material testing.

OBJECTIVE The production of similar specimens for material testing is very difficult and crucial. This has much influence on the results of an experiment. With CAD design and new printing technologies it is possible to create individual devices to produce specimens for different testing situations. In this study different devices were designed for the standardized production of tooth discs for testing with bonded materials. METHODS The different devices were designed using optimized CAD for 3D printing. After the design, the different parts of the devices were printed using a desktop SLA 3D printer with high precision. Three different tools were needed for the generation of a standardized disc. After the production, the different devices were tested on natural teeth. RESULTS It is possible to generate very precise tools for the creation of round tooth discs. 40 tooth discs divided into 4 groups with a thickness of 2.0 mm, 2.5 mm, 3.0 mm and 3.5 mm and a constant diameter of 5 mm were produced. For all groups the median of the diameter and thickness was under +/-0.05 mm and the lower and the upper quartile were all under +/-0.06 mm. SIGNIFICANCE With this new approach the creation of very precise and uniform tooth discs is possible. The whole process for the creation of the tooth discs was standardized.

['Höhne|Christian|C|', 'Schmitter|Marc|M|']

2020

32439509

The involvement of a regucalcin in suppressing hemocyte apoptosis in Pacific oyster Crassostrea gigas.

Regucalcin (RGN), also known as senescence marker protein-30 (SMP30), plays a vital role in the regulation of Ca2+ homeostasis. In the present study, a regucalcin (designated as CgRGN) was identified from Pacific oyster Crassostrea gigas. The complete cDNA sequence of CgRGN was of 1059 bp, containing an open reading frame of 933 bp which encoded a protein of 310 amino acids. The deduced amino acid sequence of CgRGN shared similarity with other RGNs from the genome of C. gigas as well as other species. The mRNA transcripts of CgRGN were universally detected in all tested tissues, with higher level in hepatopancreas, labial palp, and gills. The relative expression level of CgRGN in hemocytes was significantly up-regulated (p < 0.05) at 3, 12, 72, and 96 h after the stimulation of lipopolysaccharide (LPS). After CgRGN expression was interfered by specific CgRGN-dsRNA, the hemocytes apoptosis rate increased dramatically at 12 h post LPS stimulation (1.56 fold, p < 0.01), compared to the control group. The caspase-3 activity in hemocytes and NO concentration in hemolymph increased significantly (p < 0.05) in dsCgRGN injection oysters. These results collectively indicated that CgRGN could suppress LPS-induced apoptosis and be involved in the immune response of oysters.

['Lian|Xingye|X|', 'Huang|Shu|S|', 'Han|Shuo|S|', 'Yi|Qilin|Q|', 'Wang|Weilin|W|', 'Sun|Jiejie|J|', 'Wang|Lingling|L|', 'Song|Linsheng|L|']

2020

32767436

Bioactivity and antibacterial activity of strontium and silver ion releasing titanium.

To overcome problems associated with loosening of orthopedic implants and surgical site infections, we developed a novel, titanium (Ti)-based material that releases both strontium and silver ions (CaSrAg-Ti) based on alkali-and-heat treatment. The results of commercially pure Ti (cp-Ti), Ti that releases Sr ions only (CaSr-Ti), and the novel CaSrAg-Ti material were compared. Mechanical tests were performed to evaluate the in vivo bonding properties of CaSrAg-Ti and the bone-implant contact (BIC) ratio in histological specimens was determined at 4 and 8 weeks after implantation in a rat femur. Also, the in vitro antibacterial activities of this material against methicillin-susceptible Staphylococcus aureus (MSSA) were evaluated after a 24 h incubation period by assaying colony-forming units. In addition, antibacterial activities were evaluated in vivo at 7 days after implantation in a rat subcutaneous pocket model. There was direct contact between the bone and CaSrAg-Ti in histological specimens and no apparent signs of argyrosis in any rat. The bone-bonding strength and the BIC ratio were increased by 2.7- and 2.3-fold for CaSrAg-Ti vs. cp-Ti at 4 weeks and 2.2- and 2.0-fold at 8 weeks, respectively. As compared with cp-Ti, the number of viable MSSA remaining on CaSrAg-Ti was reduced by 100 ± 0% in vitro and 94.2 ± 6.9% in vivo. Ti that releases Sr and Ag ions is a promising material that exhibits both bone-bonding properties and anti-MSSA activities.

['Masamoto|Kazutaka|K|0000-0003-2126-8463', 'Fujibayashi|Shunsuke|S|', 'Yamaguchi|Seiji|S|', 'Otsuki|Bungo|B|', 'Okuzu|Yaichiro|Y|', 'Kawata|Tomotoshi|T|', 'Goto|Koji|K|', 'Shimizu|Takayoshi|T|', 'Shimizu|Yu|Y|', 'Kawai|Toshiyuki|T|0000-0003-3988-6411', 'Hayashi|Makoto|M|', 'Morizane|Kazuaki|K|0000-0002-0355-2391', 'Imamura|Masashi|M|', 'Ikeda|Norimasa|N|', 'Takaoka|Yusuke|Y|', 'Matsuda|Shuichi|S|']

2021

26611904

Correlations of magnetic resonance imaging findings with clinical symptom severity and prognosis of frozen shoulder.

PURPOSE To evaluate the correlation between indirect magnetic resonance (MR) arthrographic imaging findings and the clinical symptoms and prognosis of patients with frozen shoulder. METHODS Indirect MR arthrography was performed for 52 patients with primary frozen shoulder (mean age 55.1 ± 9.0 years) and 52 individuals without frozen shoulder (mean age 53.1 ± 10.7 years); capsular thickening and enhancement of the axillary recess as well as soft tissue thickening of the rotator interval were evaluated. Clinical symptom severity was assessed using the Visual Analogue Scale for Pain (VAS Pain), simple shoulder test (SST), Constant score, American Shoulder and Elbow Surgeons (ASES) score, and range of motion (ROM). At 6-month follow-up, we evaluated whether MR arthrography findings correlated with the clinical symptoms and prognosis. RESULTS Capsular thickening and enhancement of the axillary recess as well as soft tissue thickening of the rotator interval were significantly greater in the patient group than in the controls (p < 0.001). Capsular thickening of the axillary recess did not correlate with clinical symptoms or ROM (n.s.); however, capsular enhancement correlated with clinical symptom severity according to VAS Pain (p = 0.005), SST (p = 0.046), and ASES scores (p = 0.009). Soft tissue thickening of the rotator interval did not correlate with clinical symptom severity, but was associated with external rotation limitation (p = 0.002). However, none of the parameters correlated with clinical symptoms at 6-month follow-up. CONCLUSIONS Indirect MR arthrography provided ancillary findings, especially with capsular enhancement, for evaluating clinical symptom severity of frozen shoulder, but did not reflect the prognosis. MR findings in frozen shoulder should not replace clinical judgments regarding further prognosis and treatment decisions. LEVEL OF EVIDENCE IV.

['Yoon|Jong Pil|JP|', 'Chung|Seok Won|SW|', 'Lee|Byung Joo|BJ|', 'Kim|Hyung Sup|HS|', 'Yi|Jae Hyuck|JH|', 'Lee|Hyun-Joo|HJ|', 'Jeong|Won-Ju|WJ|', 'Moon|Sung Gyu|SG|', 'Oh|Kyung-Soo|KS|', 'Yoon|Seok Tae|ST|']

2017

33118082

Optimization of sampling frequency for coastal seawater quality monitoring.

The selection of an appropriate sampling frequency is very important in monitoring coastal seawater quality. The present study sought to optimize the sampling frequency for coastal seawater quality monitoring. We combined mathematical models with natural and human activities by the analytic hierarchy process method. The study was designed to consider historical monitoring data, regulated seawater quality standard, tide, land use, and ship activities in optimizing coastal seawater sampling frequency in Ha Long Bay, Vietnam. The study results indicated that monitoring activities should focus in points having high human activities as well as high concentration of TSS, ammonium, and oil. Points S1-S8 should have high sampling frequency (16-30 samples/year), whereas points S23-S28 can have low sampling frequency (3-5 samples/year). In a year, monitoring activities should be focused in June, July, and August with the number of samples of 42, 54, and 44 pear year (weighting values 0.120, 0.161, and 0.112), respectively. It should consider the mathematical aspects associated with natural and human factors when calculating sampling frequency for coastal seawater quality monitoring. Proposed optimization method can be applied for other coastal regions.

['Do|Huu Tuan|HT|http://orcid.org/0000-0002-2207-8349', 'Phan Thi|Lan Anh|LA|']

2020

31454824

Restoration of Height after 11 Years of Letrozole Treatment in 11β-Hydroxylase Deficiency.

11β-hydroxylase deficiency (11β-OHD) is the second most common form of congenital adrenal hyperplasia (CAH). Males with 11β-OHD CAH are often diagnosed late with a significantly advanced bone age leading to a poor height prognosis due to early closure of epiphysis. Delaying epiphyseal fusion by treatment of aromatase inhibitors (AIs) might be a useful strategy in patients with very advanced bone ages. However, there are limited data regarding the effect on final height and long-term safety of this approach. We report our experience with 11 years of letrozole treatment and 17 years of follow-up in a boy with 11β-OHD. He presented at 2 years and 11 months of age with a bone age of 13 years (predicted adult height, PAH, 129.5 cm). Letrozole was added after 1 year of glucocorticoid treatment due to no improvement in height prognosis (130 cm), and continued until the age of 14 years and 11 months. He also received GnRH analog treatment at 10 years and 3 months of age for 2.5 years due to central activation of puberty. He reached a final height of 165.2 cm (35.2 cm above his PAH). This long-term treatment with letrozole was associated with changes in vertebral morphology such as vertebral body end-plate changes, Schmorl nodes, and mild protrusions in the intervertebral discs. Testicular volumes, gonadotropins, testosterone, and anti-Müllerian hormone were normal at age 20 years. A spermiogram showed a normal count but impaired sperm motility and morphology. This unique case represents the longest duration of AI treatment reported in CAH and the first case in which letrozole was started before puberty with the final height reported. We conclude that AIs may restore height in selected patients with CAH with very advanced bone age and severely compromised height prognosis.

['Atay|Zeynep|Z|', 'Turan|Serap|S|', 'Buğdaycı|Onur|O|', 'Guran|Tulay|T|', 'Bereket|Abdullah|A|']

2019

33083279

Dietary Restriction Suppresses Steatosis-Associated Hepatic Tumorigenesis in Hepatitis C Virus Core Gene Transgenic Mice.

Background and Aims Dietary restriction (DR) is a preventive strategy for obesity, metabolic syndrome, cardiovascular disease, and diabetes. Although an interconnection between obesity, metabolic syndrome, fatty liver, and hepatocellular carcinoma has been documented, the mechanism and impact of DR on steatosis-derived hepatocarcinogenesis are not fully understood. This study aimed to evaluate whether DR can prevent hepatic tumorigenesis. Methods Male hepatitis C virus core gene transgenic (HCVcpTg) mice that develop spontaneous age-dependent insulin resistance, hepatic steatosis, and ensuing liver tumor development without apparent hepatic fibrosis, were fed with either a control diet ad libitum (control group) or 70% of the same control diet (DR group) for 15 months, and liver phenotypes were investigated. Results DR significantly reduced the number and volume of liver tumors. DR attenuated hepatic oxidative and endoplasmic reticulum stress and markedly suppressed nuclear factor-κB, signal transducer and activator of transcription 3 (STAT3) and STAT5, and phosphorylation of extracellular signal-regulated kinase, leading to downregulation of several pro-oncogenic mediators, such as cyclin D1. Serum insulin and insulin-like growth factor 1 levels, as well as hepatic expression of insulin receptor substrate 1/2, phosphatidylinositol-3 kinase, and serine/threonine-protein kinase AKT, were downregulated by DR. A transcriptome analysis revealed that STAT3 signaling and lipogenesis were the most suppressed hepatocarcinogenic pathways affected by DR. Additionally, DR stimulated autophagy and p62/sequestosome 1 degradation, enhanced phosphorylation of AMP-activated protein kinase α, increased fibroblast growth factor 21 expression, and attenuated expression of senescence-associated secretory phenotypes. Conclusion DR suppressed steatosis-associated hepatic tumorigenesis in HCVcpTg mice, mainly due to attenuation of pathways involved in inflammation, cellular stress, cell proliferation, insulin signaling, and senescence. These findings support the notion that persistent 30% reduction of daily food intake is beneficial for preventing steatosis-associated hepatocarcinogenesis caused by HCV core protein.

['Jia|Fangping|F|', 'Diao|Pan|P|', 'Wang|Xiaojing|X|', 'Hu|Xiao|X|', 'Kimura|Takefumi|T|', 'Nakamuta|Makoto|M|', 'Nakamura|Ibuki|I|', 'Shirotori|Saki|S|', 'Sato|Yoshiko|Y|', 'Moriya|Kyoji|K|', 'Koike|Kazuhiko|K|', 'Gonzalez|Frank J|FJ|', 'Nakayama|Jun|J|', 'Aoyama|Toshifumi|T|', 'Tanaka|Naoki|N|']

2020

24504855

In situ butanol recovery from Clostridium acetobutylicum fermentations by expanded bed adsorption.

Although butanol is a promising biofuel, its fermentative production suffers from inhibition caused by end product toxicity. The in situ removal of butanol from cultures via expanded bed adsorption offers an effective strategy for mitigating the effects of product toxicity while eliminating the need to clarify cultures via microfiltration. The hydrophobic polymer resin Dowex Optipore L-493 was found to be both an effective butanol adsorbent and suitable for use in expanded bed adsorption. Recirculation rates through the adsorption column were strongly correlated with and ultimately controlled rates of butanol uptake from the media which, reaching as high as 41.1 g/L h, easily exceed those of its production in a typical fermentation. Vacuum application with vapor collection was found to be an effective means of adsorbent regeneration, with an average of 81% butanol recovery possible, with butanol concentrations in the cold trap reaching as high as 85.8 g/L. Integration of expanded bed adsorption with a fed-batch Clostridium acetobutylicum ATCC 824 fermentation and its continuous operation for 38.5 h enabled the net production (i.e., in solution and adsorbed) of butanol and total solvent products at up to 27.2 and 40.7 g/L of culture, respectively, representing 2.2- and 2.3-fold improvements over conventional batch culture. While adsorbent biofouling was found to be minimal, further investigation of biofouling in longer-term studies will provide useful and further insight regarding the robustness of the process strategy.

['Wiehn|Michael|M|', 'Staggs|Kyle|K|', 'Wang|Yuchen|Y|', 'Nielsen|David R|DR|']

2014

31399081

Reproducible changes in the gut microbiome suggest a shift in microbial and host metabolism during spaceflight.

BACKGROUND Space environment imposes a range of challenges to mammalian physiology and the gut microbiota, and interactions between the two are thought to be important in mammalian health in space. While previous findings have demonstrated a change in the gut microbial community structure during spaceflight, specific environmental factors that alter the gut microbiome and the functional relevance of the microbiome changes during spaceflight remain elusive. METHODS We profiled the microbiome using 16S rRNA gene amplicon sequencing in fecal samples collected from mice after a 37-day spaceflight onboard the International Space Station. We developed an analytical tool, named STARMAPs (Similarity Test for Accordant and Reproducible Microbiome Abundance Patterns), to compare microbiome changes reported here to other relevant datasets. We also integrated the gut microbiome data with the publically available transcriptomic data in the liver of the same animals for a systems-level analysis. RESULTS We report an elevated microbiome alpha diversity and an altered microbial community structure that were associated with spaceflight environment. Using STARMAPs, we found the observed microbiome changes shared similarity with data reported in mice flown in a previous space shuttle mission, suggesting reproducibility of the effects of spaceflight on the gut microbiome. However, such changes were not comparable with those induced by space-type radiation in Earth-based studies. We found spaceflight led to significantly altered taxon abundance in one order, one family, five genera, and six species of microbes. This was accompanied by a change in the inferred microbial gene abundance that suggests an altered capacity in energy metabolism. Finally, we identified host genes whose expression in the liver were concordantly altered with the inferred gut microbial gene content, particularly highlighting a relationship between host genes involved in protein metabolism and microbial genes involved in putrescine degradation. CONCLUSIONS These observations shed light on the specific environmental factors that contributed to a robust effect on the gut microbiome during spaceflight with important implications for mammalian metabolism. Our findings represent a key step toward a better understanding the role of the gut microbiome in mammalian health during spaceflight and provide a basis for future efforts to develop microbiota-based countermeasures that mitigate risks to crew health during long-term human space expeditions.

['Jiang|Peng|P|', 'Green|Stefan J|SJ|', 'Chlipala|George E|GE|', 'Turek|Fred W|FW|', 'Vitaterna|Martha Hotz|MH|0000-0001-6243-2093']

2019

33742547

Molecular mechanisms regulating Proteinase-Activated Receptors (PARs).

Proteinase-activated receptors (PARs) are a four-member family of G protein-coupled receptors defined by their irreversible proteolytic mechanism of activation. PARs have emerged as important regulators of various physiological responses and are implicated in numerous pathological conditions. Importantly, PAR1 and PAR4 are critical regulators of platelet function, while PAR2 is well established as a driver of inflammatory responses. PAR-targeted drug development efforts are therefore of great interest. In this review, we provide an overview of recent advances in our understanding of molecular mechanisms underlying PAR activation, effector interaction, and signaling. We also provide an overview of the diverse proteolytic enzymes that are now established as PAR regulators and describe the ability of different enzymes to elicit biased signaling through PARs. Finally, we highlight recent advances in the development of PAR-targeted pharmacological agents and discuss recent structure-activity relationship studies.

['Chandrabalan|Arundhasa|A|', 'Ramachandran|Rithwik|R|0000-0001-9557-9905']

2021

28079938

An enigmatic Hawaiian moth is a missing link in the adaptive radiation of Schiedea.

Shifts in pollination may drive adaptive diversification of reproductive systems within plant lineages. The monophyletic genus Schiedea is a Hawaiian lineage of 32 extant species, with spectacular diversity in reproductive systems. Biotic pollination is the presumed ancestral condition, but this key element of the life history and its role in shaping reproductive systems has remained undocumented. We observed floral visitors to two species of Schiedea and conducted field experiments to test pollinator effectiveness. We used choice tests to compare attraction of pollinators to species hypothesized to be biotically vs wind-pollinated. Pseudoschrankia brevipalpis (Erebidae), a recently described moth species known only from O'ahu, visited hermaphroditic Schiedea kaalae and S. hookeri and removed nectar from their unique tubular nectary extensions. Pseudoschrankia brevipalpis effectively pollinates S. kaalae; single visits to emasculated flowers resulted in pollen transfer. In choice tests, P. brevipalpis strongly preferred these hermaphroditic species over two subdioecious species capable of wind pollination. A shift from biotic to abiotic pollination is clearly implicated in the diversification of reproductive systems within Schiedea. Abundant pollination by a previously unknown native moth in experimental and restored populations suggests the potential for restoration to re-establish native plant-pollinator interactions critical for production of outcrossed individuals with high fitness.

['Weller|Stephen G|SG|', 'Sakai|Ann K|AK|', 'Campbell|Diane R|DR|', 'Powers|John M|JM|', 'Peña|Sean R|SR|', 'Keir|Matthew J|MJ|', 'Loomis|Alexander K|AK|', 'Heintzman|Scott M|SM|', 'Weisenberger|Lauren|L|']

2017

26275512

Ocular injury in the United States: Emergency department visits from 2006-2011.

INTRODUCTION Ocular complaints represent a sizeable burden to emergency departments, accounting for an estimated 2.4 million ED visits annually. We sought to characterise visits associated with ocular injury and examine factors contributing to inpatient admission. METHODS We searched the Nationwide Emergency Department Sample between 2006 and 2011 and identified cases in which patients presented with a primary or secondary diagnosis of ocular trauma. We described these cases according to age, sex, external mechanism of injury, payer status, and identified relationships between these variables. Logistic regression models were employed to identify crude and adjusted relative odds of admission to inpatient status based on patient demographics, mechanism of injury, payer status, and the existence of multiple injuries. RESULTS Between 2006 and 2011, a total of 5541,434 visits were made to EDs in the United States with a primary or other diagnosis of ocular trauma; ocular trauma was the primary diagnosis in 77.9% of these cases. Overall, mean age at presentation was 33.8 years and the majority of patients were male (64.8%). Male sex, older age, being struck by or against an object, the existence of multiple injuries, and Medicaid as a primary payer were all associated with significantly higher odds of hospital admission. DISCUSSION The distribution of primary external mechanism of injury suggested that individuals are at higher risks for different injury types at each successive stage of life. Age and injury mechanism were correlated with odds of admission to inpatient status, with the highest odds among older adults who had been injured by being struck by or against an object. CONCLUSIONS Ocular injury plays a substantial role in the ED. Further work is necessary to determine whether developing and implementing age- and sex-appropriate prevention strategies could reduce the incidence of ocular injury and reduce morbidity related to these types of injuries.

['Haring|R Sterling|RS|', 'Canner|Joseph K|JK|', 'Haider|Adil H|AH|', 'Schneider|Eric B|EB|']

2016

27451909

The Art of the Radiology Report: Practical and Stylistic Guidelines for Perfecting the Conveyance of Imaging Findings.

The radiology report is the culmination of image acquisition, meticulous interpretation, and the generation of deliberate and thoughtful recommendations. It is essentially a translation of images into words, and as such must convey as much pertinent detail needed by the clinician in as concise a format as possible. Several important factors affect the overall quality of the finished report. Active voice helps to convey information more confidently, and in a manner that is easier to read and understand. The use of several words and phrases is frowned upon, as it makes the radiologist sound uncertain. The manner in which the impression is stated can significantly influence the ordering physician's decision as to whether to follow the radiologist's recommendations. Critical findings must be promptly communicated to the appropriate health care provider, and documented in the final report. By following the guidelines illustrated in this article, radiologists will learn how to create a perfected report, which will be concise, convey important findings while answering the clinical question posed, and will be favorably viewed by the requesting physician.

['Lukaszewicz|Andrew|A|', 'Uricchio|Joseph|J|', 'Gerasymchuk|Grygori|G|']

2016

27542643

Management of Gastrointestinal Stromal Tumors.

Gastrointestinal stromal tumors had the reputation for poor outcomes because of their lack of response to nonsurgical interventions. The discovery of gain-of-function mutations involving receptor tyrosine kinase growth factor receptors altered the biological understanding and management. Beginning in 2000, management of these tumors has changed dramatically because of the availability of tyrosine kinase inhibitors. The role of surgery continues to be refined. This article reviews how surgery and systemic therapy are being used, incorporating definitions of risk. Decisions on how to treat a patient is based on the risk of progression, pathologic characteristics, and tumor location.

['von Mehren|Margaret|M|']

2016

26293001

Validation of an integral conceptual model of frailty in older residents of assisted living facilities.

OBJECTIVE The aim of this cross-sectional study was to examine the validity of an integral model of the associations between life-course determinants, disease(s), frailty, and adverse outcomes in older persons who are resident in assisted living facilities. METHODS Between June 2013 and May 2014 seven assisted living facilities were contacted. A total of 221 persons completed the questionnaire on life-course determinants, frailty (using the Tilburg Frailty Indicator), self-reported chronic diseases, and adverse outcomes disability, quality of life, health care utilization, and falls. Adverse outcomes were analyzed with sequential (logistic) regression analyses. RESULTS The integral model is partially validated. Life-course determinants and disease(s) affected only physical frailty. All three frailty domains (physical, psychological, social) together affected disability, quality of life, visits to a general practitioner, and falls. Contrary to the model, disease(s) had no effect on adverse outcomes after controlling for frailty. Life-course determinants affected adverse outcomes, with unhealthy lifestyle having consistent negative effects, and women had more disability, scored lower on physical health, and received more personal and informal care after controlling for all other predictors. CONCLUSION The integral model of frailty is less useful for predicting adverse outcomes of residents of assisted living facilities than for community-dwelling older persons, because these residents are much frailer and already have access to healthcare facilities. PRACTICAL IMPLICATIONS The present study showed that a multidimensional assessment of frailty, distinguishing three domains of frailty (physical, psychological, social), is beneficial with respect to predicting adverse outcomes in residents of assisted living facilities.

['Gobbens|Robbert J J|RJ|', 'Krans|Anita|A|', 'van Assen|Marcel A L M|MA|']

2015

25516270

Low birthrates and high levels of female reproductive inactivity may characterize the reproductive biology of wild Peruvian red uakaris (Cacajao calvus ucayalii).

BACKGROUND Birthrates are key parameters for population models and hunting sustainability analyses frequently used in conservation, but for many rare species, these data do not exist. We examine the reproductive organs of endangered red uakari monkeys to calculate birthrates in the wild. METHODS We collected reproductive organs from wild uakari monkeys hunted for subsistence by indigenous hunters and examined them for embryos or fetuses. We extrapolated birth dates to test for breeding seasonality and calculated birthrates. RESULTS Breeding was seasonal, and birthrates were low relative to other neotropical primates. We recorded unexpectedly high numbers of reproductively inactive females compared to other neotropical monkeys. CONCLUSIONS Reproductive inactivity could be due to delayed reproduction or long periods of lactation. Resource availability may also play a role. Slow reproduction and low birthrates in uakaris, relative other primates, could explain why uakaris have a patchy distribution and appear vulnerable to disturbance.

['Mayor|Pedro|P|', 'Bowler|Mark|M|']

2015

24220659

An N-terminal pro-atrial natriuretic peptide (NT-proANP) 'aggregation-prone' segment involved in isolated atrial amyloidosis.

Isolated atrial amyloidosis (IAA) is a common localized form of amyloid deposition within the atria of the aging heart. The main constituents of amyloid fibrils are atrial natriuretic peptide (ANP) and the N-terminal part of its precursor form (NT-proANP). An 'aggregation-prone' heptapeptide ((114)KLRALLT(120)) was located within the NT-proANP sequence. This peptide self-assembles into amyloid-like fibrils in vitro, as electron microscopy, X-ray fiber diffraction, ATR FT-IR spectroscopy and Congo red staining studies reveal. Consequently, remedies/drugs designed to inhibit the aggregation tendency of this 'aggregation-prone' segment of NT-proANP may assist in prevention/treatment of IAA, congestive heart failure (CHF) or atrial fibrillation (AF).

['Louros|Nikolaos N|NN|', 'Iconomidou|Vassiliki A|VA|', 'Tsiolaki|Paraskevi L|PL|', 'Chrysina|Evangelia D|ED|', 'Baltatzis|Georgios E|GE|', 'Patsouris|Efstratios S|ES|', 'Hamodrakas|Stavros J|SJ|']

2014

33404144

Symmetrical glial hyperplasia in the brainstem of fibrodysplasia ossificans progressiva.

Fibrodysplasia ossificans progressiva (FOP) is a rare autosomal dominant disease, characterized by the progressive ossification of skeletal muscles, fascia, tendons, and ligaments. In most cases, the great toes of patients show symmetrical congenital malformations. The causative gene for FOP has been identified as the activin A receptor, type 1 (ACVR1) gene (ACVR1). The ACVR1 R206H mutation is the most common mutation among FOP patients, and the ACVR1 G356D mutation has been identified as a rare mutation in a Japanese FOP patient with slow progression. In addition to musculoskeletal abnormalities, a series of autopsy studies described one FOP case, without genetic testing to identify ACVR1 mutation, showing nodular heterotopia at the edge of the fourth ventricle. Here, we report the general autopsy findings for a 75-year-old man with FOP, caused by the ACVR1 G356D mutation, including the precise examination of brainstem lesions. Postmortem examination revealed unique symmetrical glial hyperplasia of the pons and medulla oblongata. Microscopically, lesions of the pons involving residual neurons and lesions of the medulla oblongata consisted of subependymal cells. Immunohistochemical analysis of these lesions revealed developmental anomalies, with different cellular components. In this report, for the first time, we present the neuropathological description of a patient with genetically confirmed FOP and symmetrical glial hyperplasia of the pons and medulla oblongata. The presented pathological findings, in conjunction with previous reports implying that the glial hyperplasia of the brainstem is common in FOP, suggest that ACVR1 may play an unclarified developmental role in the human brainstem.

['Mori|Shinichiro|S|https://orcid.org/0000-0001-5342-0648', 'Suzuki|Satoshi O|SO|', 'Honda|Hiroyuki|H|https://orcid.org/0000-0002-4225-7248', 'Hamasaki|Hideomi|H|', 'Sakae|Nobutaka|N|', 'Sasagasako|Naokazu|N|', 'Furuya|Hirokazu|H|', 'Iwaki|Toru|T|https://orcid.org/0000-0001-7826-870X']

2021

32998735

Low high-density lipoprotein and increased risk of several cancers: 2 population-based cohort studies including 116,728 individuals.

BACKGROUND Increasing evidence suggests that high-density lipoprotein (HDL) may play a role in cancer development. We tested the hypothesis that low HDL levels are associated with increased risk of cancer. METHODS Individuals from two population-based cohorts, the Copenhagen General Population Study (2003-2015, N = 107 341), and the Copenhagen City Heart Study (1991-1994, N = 9387) were followed prospectively until end of 2016 to assess low plasma HDL cholesterol and apolipoprotein A1 as risk factors for cancer using Cox proportional hazard regression. RESULTS During up to 25 years follow-up, we observed 8748 cancers in the Copenhagen General Population Study and 2164 in the Copenhagen City Heart Study. In the Copenhagen General Population Study and compared to individuals with HDL cholesterol ≥ 2.0 mmol/L (≥ 77 mg/dL), multivariable adjusted hazard ratios (HRs) for any cancer were 1.13 (95% confidence interval 1.04-1.22) for individuals with HDL cholesterol of 1.5-1.99 mmol/L (58-77 mg/dL), 1.18 (1.08-1.30) for HDL cholesterol of 1.0-1.49 mmol/L (39-58 mg/dL), and 1.29 (1.12-1.48) for individuals with HDL cholesterol < 1.0 mmol/L (< 39 mg/dL). Correspondingly, compared to individuals with apolipoprotein A1 ≥ 190 mg/dL, HRs for any cancer were 1.06 (0.96-1.17) for individuals with apolipoprotein A1 of 160-189 mg/dL, 1.18 (1.07-1.30) for apolipoprotein A1 of 130-159 mg/dL, and 1.28 (1.13-1.46) for individuals with apolipoprotein A1 < 130 mg/dL. Among 27 cancer types, low HDL cholesterol and/or apolipoprotein A1 were associated with increased risk of multiple myeloma, myeloproliferative neoplasm, non-Hodgkin lymphoma, breast cancer, lung cancer, and nervous system cancer. Results were overall similar in women and men separately, and in the Copenhagen City Heart Study. CONCLUSIONS Low HDL levels were associated with increased risk of several cancers. Increased risk was most pronounced for hematological and nervous system cancer, and to a minor extent for breast and respiratory cancer.

['Pedersen|Kasper Mønsted|KM|', 'Çolak|Yunus|Y|', 'Bojesen|Stig Egil|SE|', 'Nordestgaard|Børge Grønne|BG|']

2020

27056390

The role of resolvin D1 in the regulation of inflammatory and catabolic mediators in osteoarthritis.

OBJECTIVE AND DESIGN Resolvin D1 (RvD1), an omega-3 fatty acid derivative, has shown remarkable properties in resolving inflammation, promoting tissue repair and preserving tissue integrity. In this study, we investigated RvD1 effects on major processes involved in osteoarthritis (OA) pathophysiology. MATERIALS AND METHODS Human OA chondrocytes were treated with either 1 ng/ml interleukin-1β (IL-1β) or 20 μM 4-hydroxynonenal (HNE), then treated or not with increased concentrations of RvD1 (0-10 μM). RvD1 levels were measured by enzyme immunoassay in synovial fluids from experimental dog model of OA and sham operated dogs obtained from our previous study. Cell viability was evaluated by 3-(4,5-dimethyl-thiazoyl)-2,5-diphenyl-SH-tetrazolium bromide assay. Parameters related to inflammation, catabolism and apoptosis were determined by enzyme-linked immunosorbent assay, Western blotting, and quantitative polymerase chain reaction. Glutathione (GSH) was assessed by commercial kit. The activation of mitogen-activated protein kinases and nuclear factor-kappaB (NF-κB) pathways was evaluated by Western blot. RESULTS We showed that RvD1 levels were higher in synovial fluids from OA joint compared to controls. In OA human chondrocytes, we demonstrated that RvD1 was not toxic up to 10 μM and stifled IL-1β-induced cyclooxygenase 2, prostaglandin E2, inducible nitric oxide synthase, nitric oxide, and matrix metalloproteinase-13. Our study of signalling pathways revealed that RvD1 suppressed IL-1β-induced activation of NF-κB/p65, p38/MAPK and JNK(1/2). Moreover, RvD1 prevented HNE-induced cell apoptosis and oxidative stress, as indicated by inactivation of caspases, inhibition of lactate dehydrogenase release, and increased levels of Bcl2 and AKT, as well as GSH. CONCLUSION This is the first in vitro study demonstrating the beneficial effect of RvD1 in OA. That RvD1 abolishing a number of factors known to be involved in OA pathogenesis renders it a clinically valuable agent in prevention of the disease.

['Benabdoune|Houda|H|', 'Rondon|Elsa-Patricia|EP|', 'Shi|Qin|Q|', 'Fernandes|Julio|J|', 'Ranger|Pierre|P|', 'Fahmi|Hassan|H|', 'Benderdour|Mohamed|M|']

2016

33202873

SEZ6L2 Is an Important Regulator of Drug-Resistant Cells and Tumor Spheroid Cells in Lung Adenocarcinoma.

Many lung cancer deaths result from relapses in distant organs, such as the brain or bones, after standard chemotherapy. For cancer cells to spread to other organs, they must survive as circulating tumor cells (CTCs) in blood vessels. Thus, reducing distant recurrence after chemotherapy requires simultaneously inhibiting drug resistance and CTC survival. Here, we investigated the molecular pathways and genes that are commonly altered in drug-resistant lung cancer cells and lung tumor spheroid (TS) cells. First, RNA sequencing was performed in drug-resistant cells and TS cells originating from H460 and A549 lung cancer cells. Bioinformatic pathway analysis showed that cell cycle-related pathways were downregulated in drug-resistant cells, and cholesterol biosynthesis-related pathways were upregulated in TS cells. Seizure-related 6 homolog-like 2 (SEZ6L2) was selected as a gene that was commonly upregulated in both drug-resistant cells and TS cells, and that showed elevated expression in samples from lung adenocarcinoma patients. Second, the protein expression of SEZ6L2 was analyzed by flow cytometry. The proportions of SEZ6L2 positive cells among both drug-resistant cells and TS cells was increased. Finally, as SEZ6L2 is a transmembrane protein with an extracellular region, the function of SEZ6L2 was disrupted by treatment with an anti-SEZ6L2 antibody. Treatment with the anti-SEZ6L2 antibody reduced drug resistance and TS formation. Overall, our data showed that SEZ6L2 plays an important role in drug resistance and TS formation and may be a therapeutic target for reducing distant recurrence of lung adenocarcinoma.

['Lee|Jang-Seok|JS|', 'Kim|Hee Yeon|HY|', 'Won|Bomyi|B|', 'Kang|Sang Won|SW|', 'Kim|Yong-Nyun|YN|', 'Jang|Hyonchol|H|0000-0003-1436-457X']

2020

28265501

Construction patterns of birds' nests provide insight into nest-building behaviours.

Previous studies have suggested that birds and mammals select materials needed for nest building based on their thermal or structural properties, although the amounts or properties of the materials used have been recorded for only a very small number of species. Some of the behaviours underlying the construction of nests can be indirectly determined by careful deconstruction of the structure and measurement of the biomechanical properties of the materials used. Here we examined this idea in an investigation of Bullfinch (Pyrrhula pyrrhula) nests as a model for open-nesting songbird species that construct a "twig" nest, and tested the hypothesis that materials in different parts of nests serve different functions. The quantities of materials present in the nest base, sides and cup were recorded before structural analysis. Structural analysis showed that the base of the outer nests were composed of significantly thicker, stronger and more rigid materials compared to the side walls, which in turn were significantly thicker, stronger and more rigid than materials used in the cup. These results suggest that the placement of particular materials in nests may not be random, but further work is required to determine if the final structure of a nest accurately reflects the construction process.

['Biddle|Lucia|L|', 'Goodman|Adrian M|AM|', 'Deeming|D Charles|DC|']

2017

32504233

LGBQ+ Self-Acceptance and Its Relationship with Minority Stressors and Mental Health: A Systematic Literature Review.

Many individuals who identify as lesbian, gay, bisexual, queer, and with other non-heterosexual orientations (LGBQ+) experience stigma, prejudice, and/or discrimination because of their sexuality. According to minority stress and identity development theories, these experiences can contribute to difficulties with self-acceptance of sexuality. Lower self-acceptance is considered a risk factor for adverse mental health outcomes. The current review aims to investigate whether self-acceptance of sexuality is associated with minority stressors or difficulties with mental health in LGBQ+ individuals, as well as whether there are differences in self-acceptance between different sexual orientations. Five bibliographic databases were searched. Thirteen studies were identified which used quantitative methodology to investigate associations between self-acceptance, minority stressors, and/or mental health within LGBQ+ samples, or differences in self-acceptance between different sexual orientations. The results from these cross-sectional studies suggested that lower self-acceptance of sexuality was associated with higher levels of self-reported minority stressors, including a lack of acceptance from friends and family, a lack of disclosure to others, and internalized heterosexism. Lower self-acceptance of sexuality was associated with poorer mental health outcomes, including greater global distress, depression symptoms, and lower psychological well-being. There was no significant relationship with suicidality. Studies also found that LGBQ+ individuals had lower general self-acceptance compared to heterosexual participants, bisexual individuals had lower sexuality self-acceptance compared to lesbian/gay individuals, and lesbian women had lower sexuality self-acceptance compared to gay men. Given the potential importance of self-acceptance for LGBQ+ populations, further research is required with more robust methodology. Self-acceptance could be a potential target in clinical interventions for LGBQ+ individuals.

['Camp|Jake|J|http://orcid.org/0000-0002-7243-1227', 'Vitoratou|Silia|S|http://orcid.org/0000-0003-1209-8167', 'Rimes|Katharine A|KA|http://orcid.org/0000-0003-2634-455X']

2020

33807285

Effectiveness of an Intervention Aimed at Improving Information for Patients with High Cardiovascular Risk: INFORISK Clinical Trial.

BACKGROUND The concept of global cardiovascular risk is not usually well understood by patients in consultation. METHODS This was a multicenter, prospective, randomized, open clinical trial of one-year duration to evaluate the effectiveness in reducing global cardiovascular risk with an intervention aimed at high-risk patients to improve information on the cardiovascular risk compared to the usual care. The intervention was focused on providing information about cardiovascular risk in a more understandable way, explaining the best practices to reduce cardiovascular risk, and tailoring information to the individual. RESULTS Four-hundred and sixty-four subjects participated in the study; 59.3% were men, and the mean age was 61.0 (SD 8.0) years. Significant reductions in systolic blood pressure (SBP) (-3.12 mmHg), body mass index (BMI) (-0.34 kg/m2), abdominal circumference (-1.24 cm), and REGICOR cardiovascular risk (-0.63) were observed in the intervention group. Overall, no differences in cardiovascular risk score were observed between groups at the end of follow-up. CONCLUSIONS Providing an easy-to-understand assessment of the cardiovascular risk motivated high-risk patients to adopt a healthier lifestyle and improved cardiovascular risk after one year in the intervention group. Clinicians should assess a patient's baseline understanding of their CV risk using tools other than absolute risk before making treatment recommendations.

['Brotons|Carlos|C|0000-0001-9388-6581', 'Moral|Irene|I|', 'Fernández|Diana|D|', 'Puig|Mireia|M|', 'Vilella|M Teresa|MT|', 'Puig|Teresa|T|', 'Cuixart|LLuís|L|0000-0003-3073-514X', 'Férriz|Gemma|G|', 'Pedro|Anna M|AM|0000-0001-5348-6612', 'Codinachs|Roger|R|0000-0002-2888-1562', 'Rodríguez|Mónica|M|', 'Fuentes|Rubén|R|', 'On Behalf Of Inforisk Study Investigators|||']

2021

23679089

A retrospective study of acute kidney injury in cats and development of a novel clinical scoring system for predicting outcome for cats managed by hemodialysis.

BACKGROUND Information regarding acute kidney injury (AKI) in cats is limited, and there are no reliable tools to objectively assess disease severity and predict outcome. OBJECTIVES To assess clinical signs, clinicopathologic abnormalities, etiology, and outcome of cats with AKI, and to develop models using clinical metrics and empirically derived scores to predict outcome. ANIMALS One hundred and thirty-two client-owned cats. METHODS Retrospective study. Bivariate logistic regression analyses were performed to identify variables predictive of 30-day survival. Continuous variables outside the reference range were divided into quartiles to yield quartile-specific odds ratios (OR) for survival. Models were developed incorporating weighting factors assigned to each quartile based on the OR. A predictive score for each model was calculated for each cat by summing all weighting factors. A second, multivariable logistic regression model was created from actual values of the same variables. Receiver operating characteristic curve analyses were performed to determine the models' performance. Models were further tested using a subset of cases not used in initial assessment. RESULTS Fifty five of 132 cats (42%) remained dialysis-independent for at least 30 days after discharge, and the remaining 77 cats either died (n = 37, 28%) or were euthanized (n = 40, 30%). The most common etiology was ureteral obstruction (n = 46, 35%). Higher scores were associated with decreased probability of survival (P < .001). Models correctly classified outcomes in 75-77% of the cases and 84-89% of the cases in the subsequent evaluation. CONCLUSIONS AND CLINICAL IMPORTANCE Models can provide objective guidance in assessing AKI prognosis and severity, but should be validated in other cohorts of cats.

['Segev|G|G|', 'Nivy|R|R|', 'Kass|P H|PH|', 'Cowgill|L D|LD|']

2013

31685444

CD44-high neural crest stem-like cells are associated with tumour aggressiveness and poor survival in neuroblastoma tumours.

BACKGROUND Neuroblastoma is a paediatric tumour originated from sympathoadrenal precursors and characterized by its heterogeneity and poor outcome in advanced stages. Intra-tumoral cellular heterogeneity has emerged as an important feature in neuroblastoma, with a potential major impact on tumour aggressiveness and response to therapy. CD44 is an adhesion protein involved in tumour progression, metastasis and stemness in different cancers; however, there has been controversies about the significance of CD44 expression in neuroblastoma and its relationship with tumour progression. METHODS We have performed transcriptomic analysis on patient tumour samples studying the outcome of patients with high CD44 expression. Adhesion, invasion and proliferation assays were performed in sorted CD44high neuroblastoma cells. Tumoursphere cultures have been used to enrich in undifferentiated stem-like cells and to asses self-renewal and differentiation potential. We have finally performed in vivo tumorigenic assays on cell line-derived or Patient-derived xenografts. FINDINGS We show that high CD44 expression is associated with low survival in high-grade human neuroblastoma, independently of MYCN amplification. CD44 is expressed in a cell population with neural crest stem-like features, and with the capacity to generate multipotent, undifferentiated tumourspheres in culture. These cells are more invasive and proliferative in vitro. CD44 positive cells obtained from tumours are more tumorigenic and metastatic, giving rise to aggressive neuroblastic tumours at high frequency upon transplantation. INTERPRETATION We describe an unexpected intra-tumoural heterogeneity within cellular entities expressing CD44 in neuroblastoma, and propose that CD44 has a role in neural crest stem-like undifferentiated cells, which can contribute to tumorigenesis and malignancy in this type of cancer. FUNDING Research supported by grants from the "Asociación Española contra el Cáncer" (AECC), the Spanish Ministry of Science and Innovation SAF program (SAF2016-80412-P), and the European Research Council (ERC Starting Grant to RP).

['Vega|Francisco M|FM|', 'Colmenero-Repiso|Ana|A|', 'Gómez-Muñoz|María A|MA|', 'Rodríguez-Prieto|Ismael|I|', 'Aguilar-Morante|Diana|D|', 'Ramírez|Gema|G|', 'Márquez|Catalina|C|', 'Cabello|Rosa|R|', 'Pardal|Ricardo|R|']

2019