Improving dispersion stability of hydrochloric acid hydrolyzed cellulose nano-crystals.

Abstract: Cellulose nano-crystals (CNC) have attracted great interests as a novel nanostructured material in recent years, thanks to their excellent mechanical properties, high surface area and lightweight and biocompatibility etc. Due to its low charged group content, CNC prepared from the hydrochloric acid hydrolysis has poor dispersibility in water, which hinders its further applications. In this work, well-dispersed cellulose nano-crystals are successfully prepared using a two-step method, consisting of hydrochloric acid hydrolysis, followed by adsorption of hexadecyl trimethyl ammonium bromide (CTAB) onto CNC. Results show that CTAB at a low concentration (0.13-0.47 mM) provides effective steric barriers to minimize the CNC aggregation, which is supported by TEM images and particle size distribution of CNC. At high CTAB concentrations (>0.5 mM), CNC aggregation occurs, which is due to the "bridging" effect of CTAB.

Shang|Zhen|Z|
An|Xingye|X|
Seta|Frederikus Tunjung|FT|
Ma|Mingshuai|M|
Shen|Mengxia|M|
Dai|Lin|L|
Liu|Hongbin|H|
Ni|Yonghao|Y|

Hexadecyl trimethyl ammonium bromide (CTAB)


Long Non-coding MIR205HG Depletes Hsa-miR-590-3p Leading to Unrestrained Proliferation in Head and Neck Squamous Cell Carcinoma.

Abstract: Over 70% of head & neck squamous cell carcinoma (HNSCC) patients carry TP53 oncogenic mutations. Here we studied the role of specific tumor-derived mutant p53 proteins in the aberrant transcription of long non-coding (lnc) MIR205HG gene in head and neck cancer cells. Methods: To understand the role of lncMIR205HG, that we showed to be transcriptionally regulated by mutant p53 in HNSCC, we have employed siRNA and shRNA in CAL27 and FaDu HNSCC cell lines to suppress p53 gene expression in ChIP assays and RT-qPCR. We validated our findings in a cohort of 522 HNSCC patients from The Cancer Genome Atlas Data Portal (TCGA). We further evaluated our results in 63 HNSCC tumor samples collected at our institute, 32 of which were characterized by mutated TP53 (missense mutations) while 31 were characterized by wild-type TP53. Results: Maturation of pre-MIR205HG transcript produces two non-coding RNAs, lncMIR205HG and hsa-miR-205-5p. Down-regulation of lncMIR205HG expression significantly reduced cell proliferation, cell migration and clonogenic activity of head and neck cancer cells. Expression of MIR205HG was significantly increased in HNSCC with mutated TP53 when compared with matched non-tumoral tissues. Furthermore, MIR205HG expression levels were significantly higher in tumoral samples with mutant p53 than in tumoral tissues expressing wild-type p53. Mechanistically, MIR205HG depletes endogenous miR-590-3p leading to increased cyclin B, cdk1, and YAP protein expression. Conclusions: Taken together, these findings identify a transcriptional and post-transcriptional molecular network that includes mutant p53 protein, lncMIR205HG, YAP, and other proliferation-related genes, which are enriched in HNSCC patients with poor prognosis.

Di Agostino|Silvia|S|
Valenti|Fabio|F|
Sacconi|Andrea|A|
Fontemaggi|Giulia|G|
Pallocca|Matteo|M|
Pulito|Claudio|C|
Ganci|Federica|F|
Muti|Paola|P|
Strano|Sabrina|S|
Blandino|Giovanni|G|

D060888:Real-Time Polymerase Chain Reaction

D020133:Reverse Transcriptase Polymerase Chain Reaction

D000077195:Squamous Cell Carcinoma of Head and Neck


Novel insights into the pathophysiology and clinical aspects of diabetic nephropathy.

Abstract: Diabetic nephropathy (DN) is a well-described complication of diabetes mellitus and the leading cause of end stage renal disease (ESRD). Although increased albuminuria has been the gold standard for screening, data suggests that renal damage starts long before the onset of clinically apparent increases in macro and even micro-albuminuria. Clinical practice guidelines for the prevention of DN have been traditionally focused on the control of serum glucose, blood pressure and dyslipidemia, with some focus on the renin-angiotensin-aldosterone system (RAAS) as a main target for successful therapy. Recent evidence has led to a better understanding of the underlying mechanisms of the pathophysiology of this disease and suggests that various novels pathways can be targeted to delay and even prevent the progression of DN. Hence a more comprehensive therapeutic approach to therapy is on the horizon, carrying the promise for a more successful and impactful management. This review will highlight new insights into the pathophysiology, clinical aspects and future diagnostic and therapeutic modalities for DN.

Diabetic nephropathy
Nephropathy
Diabetes mellitus
End stage renal disease
Albuminuria
Proteinuria


A two-year prospective study of small poultry flocks in Ontario, Canada, part 2: causes of morbidity and mortality.

Abstract: Non-commercial poultry flocks (referred to as "small flocks") have become increasingly popular in Canada. Despite this popularity, little is known about the main causes of morbidity and mortality (health status) in these flocks. We assessed the baseline prevalence of infectious and non-infectious diseases among Ontario's small poultry flocks by conducting a prospective surveillance study over a 2-y period. With the owner's consent, for each bird ( n = 245) submitted to the Animal Health Laboratory, we performed a postmortem examination, including ancillary tests to reach a diagnosis. Infectious diseases were the most common primary cause of clinical signs or death (62%), with multifactorial respiratory diseases (21%) and Marek's disease (11%) being most frequent. Multifactorial respiratory diseases were commonly caused by coinfection with bacteria (e.g., Mycoplasma gallisepticum and M. synoviae, Escherichia coli, Avibacterium spp.) and viruses, such as infectious bronchitis and infectious laryngotracheitis viruses. No federally reportable diseases were diagnosed. The health status of small flocks in Ontario has not been reported previously, to our knowledge, and the data presented herein will produce helpful baseline information for the development of technology transfer material directed to owners and veterinarians, which will ultimately aid in the control of diseases among these flocks.

prospective study
health status
prevalence
mycoplasma
Marek’s disease
backyard flocks
epidemiology
infectious bronchitis virus
infectious laryngotracheitis virus
mixed respiratory infection


Selective screening for distal renal tubular acidosis in recurrent kidney stone formers: initial experience and comparison of the simultaneous furosemide and fludrocortisone test with the short ammonium chloride test.

Abstract:
BACKGROUND
Distal renal tubular acidosis (dRTA) is associated with renal stone disease, and it often needs to be considered and excluded in some recurrent calcium kidney stone formers (KSFs). However, a diagnosis of dRTA, especially when 'incomplete', can be missed and needs to be confirmed by a urinary acidification (UA) test. The gold standard reference test is still the short ammonium chloride (NH4Cl) test, but it is limited by gastrointestinal side effects and occasionally failure to ingest sufficient NH4Cl. For this reason, the furosemide plus fludrocortisone (F+F) test has been proposed as an easier and better-tolerated screening test. The aim of the present study was to assess the usefulness of the F+F test as a clinical screening tool for dRTA in a renal stone clinic.

METHODS
We studied 124 patients retrospectively in whom incomplete dRTA was suspected: 71 had kidney stones only, 9 had nephrocalcinosis only and 44 had both. A total of 158 UA tests were performed: 124 F+F and 34 NH4Cl; both tests were completed in 34 patients.

RESULTS
The mean age was 45.4 ± 15 years, and 49% of patients were male. The prevalence of complete and incomplete dRTAs was 7 and 13.7%, respectively. Of the 34 patients tested using both tests, 17 (50%) were abnormal and 4 (12%) were normal. Thirteen (39%) patients were abnormal by F+F, but normal by NH4Cl [sensitivity 100% (95% CI 80-100), specificity 24% (95% CI 7-50), positive predictive value 57% (95% CI 37-75), negative predictive value 100% (95% CI 40-100)].

CONCLUSIONS
The F+F test is characterized by an excellent sensitivity and negative predictive value, and the diagnosis of incomplete dRTA can be excluded reliably in a patient who acidifies their urine normally with this test. However, its lack of specificity is a drawback, and if there is any doubt, an abnormal F+F test may need to be confirmed by a follow-up NH4Cl test. Ideally, a prospective blinded study in unselected KSFs is needed to accurately assess the reliability of the F+F test in diagnosing, rather than excluding, dRTA.

Shavit|Linda|L|
Chen|Lucia|L|
Ahmed|Fayha|F|
Ferraro|Pietro Manuel|PM|
Moochhala|Shabbir|S|
Walsh|Steven B|SB|
Unwin|Robert|R|

furosemide and fludrocortisone testrenal tubular acidosis


A computational study of the dechlorination of β-hexachlorocyclohexane (β-HCH) catalyzed by the haloalkane dehalogenase LinB.

Abstract: LinB, a haloalkane dehalogenase from Sphingomonas paucimobilis UT26, is known to metabolize halohydrocarbons to halide ions and the respective alcohols. Its broad substrate specificity allowed its consideration for bioremediation. Herein, we have shown its catalytic action toward β-hexachlorocyclohexane (β-HCH) - an example of large-size substrates that can be accommodated in its active site. We have analyzed the capability of combined QM/MM schemes to describe in detail the SN2 dechlorination reaction between β-HCH and Asp108 in the active site of LinB. Free energy surfaces have been calculated using one and two dimensional potentials of mean force (PMF) obtained at the PM3/MM (MM=amberff99SB, TIP3P) level of theory. The overestimated energetic barriers by the PM3 Hamiltonian were corrected using a DFT functional (M06-2X). The resulted activation energies (16 and 19 kcal mol(-1) from 1D and 2D-PMF profiles, respectively) for the dechlorination reaction of β-HCH in the active site of LinB enzyme are in qualitative agreement with the experimentally determined value of 17 kcal mol(-1). The binding of β-HCH to the active site of LinB has been compared to the binding of smaller 1-chlorobutane (1-CB) and larger δ-hexabromocyclododecane (δ-HBCD).


Current status of fish vaccines in Japan.

Abstract: Aquaculture is an important industry in Japan for the sustainable production of fish. It contributes to the diversity of Japanese traditional food culture, which uses fish such as "sushi" and "sashimi". In the recent aquaculture setting in Japan, infectious diseases have been an unavoidable problem and have caused serious economic losses. Therefore, there is an urgent need to overcome the disease problem to increase the productivity of aquaculture. Although our country has developed various effective vaccines against fish pathogens, which have contributed to disease prevention on fish farms, infectious diseases that cannot be controlled by conventional inactivated vaccines are still a problem. Therefore, other approaches to developing effective vaccines other than inactivated vaccines are required. This review introduces the vaccine used in Japan within the context of the current status of finfish aquacultural production and disease problems. This review also summarizes the current research into vaccine development and discusses the future perspectives of fish vaccines, focusing on the problems associated with vaccine promotion in Japan.

Matsuura|Yuta|Y| Terashima|Sachiko|S| Takano|Tomokazu|T| Matsuyama|Tomomasa|T|

Plecoglossus altivelis poxvirus-like virus


Obstructive heart failure with Cardiobacterium hominis infective endocarditis.

Abstract: We illustrate the progression of Cardiobacterium hominis infective endocarditis in a patient with a bioprosthetic mitral valve and decompensated heart failure secondary to an obstructive septic vegetation.

Singh|Anita|A|
Porras|Angel|A|
Ujueta|Francisco|F|
Lo Presti|Saberio|S|
Camps|Nicholas|N|

Heart failure
Cardiobacterium hominis
Infective endocarditis
Septic vegetation


Data on using single- and mixed-mode resins for capture chromatography of recombinant human thioredoxin from Escherichia coli.

Abstract: This paper provides the data collected from screening chromatographic resins for their ability to bind and purify recombinant human thioredoxin from Escherichia coli lysate. This data was used by "Capture chromatography with mixed-mode resins: A case study with recombinant human thioredoxin from Escherichia coli" [1] to determine the optimal resin to use as a capture step to initiate downstream processing of thioredoxin. Five chromatography resins were screened using a 96-well filter plate to experiment on a wide range of pH and conductivity conditions in a shorter amount of time while saving on materials. Thioredoxin-producing E. coli was cultivated, harvested, and lysed according to Ravi et al [1]. Thioredoxin containing lysate was dialyzed into the binding conditions, pH from 5.0 to 9.0 and conductivity from 2.0 to 10.0 mS, applied to each resin and incubated with shaking for 0.5 h. Data gathered after the incubation period consisted of host cell protein and thioredoxin concentrations remaining in the supernatant, which was considered flowthrough for the remainder of this study. Samples containing high concentrations of thioredoxin after the experimental period indicate that thioredoxin did not bind to the resin at those conditions and should not be utilized as a capture step. Additionally, samples that contain low concentrations of host-cell proteins after the experimental period indicate large amounts of host-cell proteins bound to the resin. The corresponding conditions may not contribute to higher purity. Operating all screening experiments at small volumes allows for selecting optimal binding conditions while minimizing the burden on upfront biomass production.

Capture chromatography
Thioredoxin
High-throughput screening
Mixed-mode chromatography


Metastatic Prostate Cancer: Treatment Options.

Abstract:
BACKGROUND
Metastatic prostate cancer (PCa) is associated with considerable diminished overall survival (OS). Standard treatment for metastatic PCa has long been androgen deprivation therapy alone, with patients initially responding to this treatment and then progressing to a castration-resistant phase.

SUMMARY
The advent of novel therapeutic agents has changed this paradigm, with high-level evidence that upfront combination therapy with either docetaxel or new hormonal agents results in improved OS for patients with metastatic hormone-sensitive PCa. In the absence of a comprehensive clinical trial investigating the comparative efficacy and safety of all agents, clinicians are responsible for choosing the most appropriate therapy in close coordination with patients. Furthermore, the same therapeutic agents are also efficient in the castration-resistant phase, leading to the issue of the best therapeutic sequence. Finally, along with systemic therapy and molecular imaging advancements, radiotherapy was investigated in the oligometastatic setting, whether it is to treat the primary tumour or metastases. Key Messages: In this complex landscape, where providers have multiple effective therapeutic options to treat metastatic PCa patients, priority must be given to determine which treatment combination and sequence is best suited to a particular patient, given his comorbidities and preferences.

Achard|Vérane|V|
Putora|Paul Martin|PM|
Omlin|Aurelius|A|
Zilli|Thomas|T|
Fischer|Stefanie|S|

Metastatic hormone-sensitive prostate cancer


Bench-scale assessment of the formation and control of disinfection byproducts from human endogenous organic precursors in swimming pools.

Abstract: In this study, a bench-scale system was utilized to assess the disinfection byproduct (DBP) formation from human endogenous organic matter. Perspiration and urine, constituting the main organic substances in swimming pools, were selected to represent the major human endogenous organics. Results revealed that the continuous input of body fluids into the reactor led to rapid accumulation of endogenous organic matter, which contributed to high concentrations of DBPs in the swimming pool. The increase in nonpurgeable organic carbon (NPDOC) concentration from the perspiration precursor was lower than that from urine during the operation. Moreover, the accumulation of swimmers' body fluids leads to increased DBP precursors, as well as increased chlorine demand and DBP formation in swimming pool water. The concentration of the trihalomethanes (THMs) and haloacetic acids (HAAs) consistently increased during the reaction. More THMs were generated in urine solution, whereas more HAAs were found in perspiration solution. To improve the water quality in swimming pools, ozonation, UV/Chlorine, and UV/H2O2 treatments were evaluated for their efficacy in reducing the DBP precursors. Results revealed that all of the three treatment processes can degrade the DBP precursors in perspiration and urine, eventually decreasing the DBP concentrations. However, only the UV/H2O2 treatment can decrease the formation of DBPs in perspiration and urine. In addition, the results revealed that UV/Chlorine and UV/H2O2 treatments should be operated for a sufficient contact time to prevent the increased production of DBP precursors in water at the early stage of the treatment.

Disinfection byproducts
Swimming pool
Endogenous organic matter
Perspiration
Urine
Advanced oxidation processes


Life-history strategy and extinction risk in the warm desert perennial spring ephemeral Astragalus holmgreniorum (Fabaceae).

Abstract: This study of Astragalus holmgreniorum examines its adaptations to the warm desert environment and whether these adaptations will enable it to persist. Its spring ephemeral hemicryptophyte life-history strategy is unusual in warm deserts. We used data from a 22-year demographic study supplemented with reproductive output, seed bank, and germinant survival studies to examine the population dynamics of this species using discrete-time stochastic matrix modeling. The model showed that A. holmgreniorum is likely to persist in the warm desert in spite of high dormant-season mortality. It relies on a stochastically varying environment with high inter-annual variation in precipitation for persistence, but without a long-lived seed bank, environmental stochasticity confers no advantage. Episodic high reproductive output and frequent seedling recruitment along with a persistent seed bank are adaptations that facilitate its survival. These adaptations place its life-history strategy further along the spectrum from "slower" to "faster" relative to other perennial spring ephemerals. The extinction risk for small populations is relatively high even though mean λ s > 1 because of the high variance in year quality. This risk is also strongly dependent on seed bank starting values, creating a moving window of extinction risk that varies with population size through time. Astragalus holmgreniorum life-history strategy combines the perennial spring ephemeral life form with features more characteristic of desert annuals. These adaptations permit persistence in the warm desert environment. A promising conclusion is that new populations of this endangered species can likely be established through direct seeding.

spring ephemeral
hemicryptophyte
matrix modeling
persistent seed bank
endangered species
Mojave Desert
fast‐slow continuum
population viability analysis


Short communication: Effect of conjugated linoleic acid on concentrations of fat-soluble vitamins in milk of lactating ewes.

Abstract: Conjugated linoleic acids (CLA) are well known as milk fat-reducing feed supplements in diets for lactating ruminants. However, their effects on milk concentrations of fat-soluble vitamins are unknown. This study was performed to investigate the hypothesis that CLA affect the concentrations of retinol and tocopherol in ewe milk. For that purpose, group-housed Merino ewes (101 ± 13.7 kg) nursing twin lambs and fed with a hay:concentrate diet were supplemented with either 45 g of a rumen-protected CLA supplement containing 3.4 g of cis-9,trans-11-CLA and 3.4 g of trans-10,cis-12-CLA (CLA group, n=11) or with 45 g of a hydrogenated vegetable fat (control group, n=12) per ewe per day during the first 6 wk of lactation. Feed intake was recorded daily (concentrate) or weekly (hay) per group. Milk spot samples were collected at the beginning of the experiment (5 ± 2.4 d postpartum) and then weekly after lambs had been separated for 2 h from their mothers. The milk fat content was determined and feed and milk were analyzed for concentrations of α-, γ-, and δ-tocopherol and for retinol by HPLC. Dietary intake of tocopherol and retinol was similar in both groups. Feeding CLA decreased milk fat concentration by 23% on average, and during the first 3 wk of the study milk tocopherol concentration tended to be increased by feeding CLA (+17%), but retinol concentrations were not influenced. When related to milk fat, CLA feeding significantly increased both milk tocopherol (+40%) and retinol (+32%) and these effects were evident during the whole experimental period corresponding to the first half of lactation.

conjugated linoleic acid
lactating ewe
milk fat-soluble vitamin


HER2 gene (ERBB2) amplification is a low-frequency driver with potential predictive value in gallbladder carcinoma.

Abstract: Gallbladder carcinoma (GBC) is an aggressive type of cancer with a dismal prognosis. Recent case reports have highlighted the human epidermal growth factor receptor 2 (HER2) as a promising target for individualized therapy in biliary tract cancer; however, current data on HER2 positivity in GBC is contradictory. This study aimed to assess the proportion of HER2 positivity and its clinical implications in a large and well-characterized European GBC cohort. HER2 status was determined in 186 cases of surgically resected gallbladder adenocarcinoma and a subset of coexistent high-grade biliary intraepithelial neoplasia (BilIN, n = 74) in accordance with the up-to-date consensus for HER2 testing in gastric cancer by immunohistochemistry and dual-color chromogenic in situ hybridization. Positivity for HER2 was observed in 5.4% of all cases (n = 10). In those patients with concomitant high-grade BilIN, two of four positive samples also showed amplification in the precursor lesion, while in the two remaining cases, positivity was either confined to invasive tumor or high-grade BilIN, exclusively. Equivocal staining found in eleven cases was not accompanied by gene amplification. Staging of the HER2-positive group was significantly different from the HER2-negative group with most cases presenting at stage IV, paralleled by a trend towards decreased survival. One patient who received dual HER2 inhibition almost went into full clinical remission despite treatment initiation in a metastasized state. Our results reveal a low prevalence of HER2 positivity and highlight HER2 gene amplification as an early, potentially driving event in gallbladder carcinogenesis. Prospective standardized HER2 testing and randomized control studies are needed to prove clinical efficacy of targeted HER2 inhibition in GBC.

Albrecht|Thomas|T|
Rausch|Melina|M|
Roessler|Stephanie|S|
Geissler|Veronika|V|
Albrecht|Michael|M|
Halske|Christine|C|
Seifert|Carolin|C|
Renner|Marcus|M|
Singer|Stephan|S|
Mehrabi|Arianeb|A|
Vogel|Monika Nadja|MN|
Pathil-Warth|Anita|A|
Busch|Elena|E|
Köhler|Bruno|B|
Rupp|Christian|C|
Weiss|Karl Heinz|KH|
Springfeld|Christoph|C|
Röcken|Christoph|C|
Schirmacher|Peter|P|
Goeppert|Benjamin|B|

Biliary tract cancer
Gallbladder cancer
HER2/neu
Predictive biomarkers
Targeted therapy


Perceptions of final-year medical students towards the impact of gender on their training and future practice.

Abstract:
INTRODUCTION
Following policy implementations to redress previous racial and gender discrepancies, this study explored how gender impacted on the clinical experiences of final-year medical students during their undergraduate training. It also gathered their perceptions and expectations for the future.

METHODS
This cross-sectional, mixed-method study used a purposive sampling method to collect data from the participants (n=94). Each respondent was interviewed by two members of the research team. The quantitative data were entered into Excel and analyzed descriptively. The qualitative data were transcribed and thematically analyzed.

RESULTS
The majority of the respondents still perceived clinical practice as male dominated. All respondents agreed that females faced more obstacles in clinical practice than males. This included resistance from some patients, poor mentoring in some disciplines, and less support from hostile nurses. They feared for their personal safety and experienced gender-based stereotyping regarding their competency. Males thought that feminization of the profession may limit their residency choices, and they reported obstacles when conducting intimate examinations and consultations on female patients. Both males and females expressed desire for more normalized work hours to maintain personal relationships.

CONCLUSION
Social redress policies have done much to increase equal access for females to medical schools. Cultural values and attitudes from mentors, peers, and patients still impact on the quality of their clinical experiences and therefore also their decisions regarding future clinical practice. More mentoring and education may help to address some of the perceived obstacles.

Van Wyk|Jacqueline M|JM|
Naidoo|Soornarain S|SS|
Moodley|Kogie|K|
Higgins-Opitz|Susan B|SB|

students
South Africa
challenges
opportunities
racial stereotypes
stigma


Extrinsic and Intrinsic Brain Network Connectivity Maintains Cognition across the Lifespan Despite Accelerated Decay of Regional Brain Activation.

Abstract:
UNLABELLED
The maintenance of wellbeing across the lifespan depends on the preservation of cognitive function. We propose that successful cognitive aging is determined by interactions both within and between large-scale functional brain networks. Such connectivity can be estimated from task-free functional magnetic resonance imaging (fMRI), also known as resting-state fMRI (rs-fMRI). However, common correlational methods are confounded by age-related changes in the neurovascular signaling. To estimate network interactions at the neuronal rather than vascular level, we used generative models that specified both the neural interactions and a flexible neurovascular forward model. The networks' parameters were optimized to explain the spectral dynamics of rs-fMRI data in 602 healthy human adults from population-based cohorts who were approximately uniformly distributed between 18 and 88 years (www.cam-can.com). We assessed directed connectivity within and between three key large-scale networks: the salience network, dorsal attention network, and default mode network. We found that age influences connectivity both within and between these networks, over and above the effects on neurovascular coupling. Canonical correlation analysis revealed that the relationship between network connectivity and cognitive function was age-dependent: cognitive performance relied on neural dynamics more strongly in older adults. These effects were driven partly by reduced stability of neural activity within all networks, as expressed by an accelerated decay of neural information. Our findings suggest that the balance of excitatory connectivity between networks, and the stability of intrinsic neural representations within networks, changes with age. The cognitive function of older adults becomes increasingly dependent on these factors.

SIGNIFICANCE STATEMENT
Maintaining cognitive function is critical to successful aging. To study the neural basis of cognitive function across the lifespan, we studied a large population-based cohort (n = 602, 18-88 years), separating neural connectivity from vascular components of fMRI signals. Cognitive ability was influenced by the strength of connection within and between functional brain networks, and this positive relationship increased with age. In older adults, there was more rapid decay of intrinsic neuronal activity in multiple regions of the brain networks, which related to cognitive performance. Our data demonstrate increased reliance on network flexibility to maintain cognitive function, in the presence of more rapid decay of neural activity. These insights will facilitate the development of new strategies to maintain cognitive ability.

aging
fMRI
salience network
between-/within-network
cross-spectral dynamic causal modelling
resting-state networks


Identification of Key lncRNA-mRNA Pairs and Functional lncRNAs in Breast Cancer by Integrative Analysis of TCGA Data.

Abstract: Long non-coding RNAs (lncRNAs) play an important role in many diseases and are involved in the post-transcriptional regulatory network of tumors. The purpose of this study is to mine new lncRNA-mRNA regulatory pairs and analyze the new mechanism of lncRNA involvement in breast cancer progression. Using breast cancer miRNA and mRNA expression profiling from The Cancer Genome Atlas (TCGA), we identified 59 differentially expressed lncRNAs, 88 differentially expressed miRNAs, and 1,465 differentially expressed mRNAs between breast cancer tissue and adjacent normal breast cancer. Whereafter, four candidate lncRNAs (FGF14-AS2, LINC01235, AC055854.1, and AC124798.1) were identified by the Kaplan-Meier (K-M) plotter. Furthermore, we screened the hub lncRNA (LINC01235) through univariate Cox analysis, multivariate Cox analysis, and qPCR validation, which was significantly correlated with breast cancer stage, ER status, and pathological N. Subsequently, 107 LINC01235-related mRNAs were obtained by combining differentially expressed miRNAs, differentially expressed mRNAs, and LINC01235 targeting miRNAs and mRNAs. The protein-protein interaction (PPI) network was established by Cytoscape software, and 53 key genes were screened. Function and pathway enrichment showed that LINC01235-related key genes might be involved in the process of cell differentiation, cell proliferation, and p53 signal pathway. In addition, LINC01235 has been confirmed to regulate the proliferation, migration, and invasion of MCF-7 cells in in vitro experiments. Furthermore, we screened three mRNAs (ESR1, ADRA2A, and DTL) associated with breast cancer drug resistance from key genes. Through RNA interference experiments in vitro and correlation analysis, we found that there was a negative feedback mechanism between LINC01235 and ESR1/ADRA2A. In conclusion, our results suggest that LINC01235-ESR1 and LINC01235-ADRA2A could serve as important co-expression pairs in the progression of breast cancer, and LINC01235 plays a key role as an independent prognostic factor in patients with breast cancer. The findings of this work greatly increase our understanding of the molecular regulatory mechanisms of lncRNA in breast cancer.

Li|Zhe|Z| Qian|Zheng|Z| Chen|Fei|F| Jiang|Shujun|S| Meng|Lingjia|L| Chen|Jinzhong|J|

breast cancer
LINC01235
proliferation
invasion
prognosis


Accuracy Quantification of the Reverse Engineering and High-Order Finite Element Analysis of Equine MC3 Forelimb.

Abstract: Shape is a key factor in influencing mechanical responses of bones. Considered to be smart viscoelastic and inhomogeneous materials, bones are stimulated to change shape (model and remodel) when they experience changes in the compressive strain distribution. Using reverse engineering techniques via computer-aided design (CAD) is crucial to create a virtual environment to investigate the significance of shape in biomechanical engineering. Nonetheless, data are lacking to quantify the accuracy of generated models and to address errors in finite element analysis (FEA). In the present study, reverse engineering through extrapolating cross-sectional slices was used to reconstruct the diaphysis of 15 equine third metacarpal bones (MC3). The reconstructed geometry was aligned with, and compared against, computed tomography-based models (reference models) of these bones and then the error map of the generated surfaces was plotted. The minimum error of reconstructed geometry was found to be +0.135 mm and -0.185 mm (0.407 mm ± 0.235, P > .05 and -0.563 mm ± 0.369, P > .05 for outside [convex] and inside [concave] surface position, respectively). Minor reconstructed surface error was observed on the dorsal cortex (0.216 mm ± 0.07, P > .05) for the outside surface and -0.185 mm ± 0.13, P > .05 for the inside surface. In addition, a displacement-based error estimation was used on 10 MC3 to identify poorly shaped elements in FEA, and the relations of finite element convergence analysis were used to present a framework for minimizing stress and strain errors in FEA. Finite element analysis errors of 3%-5% provided in the literature are unfortunate. Our proposed model, which presents an accurate FEA (error of 0.12%) in the smallest number of iterations possible, will assist future investigators to maximize FEA accuracy without the current runtime penalty.

Mouloodi|Saeed|S|
Rahmanpanah|Hadi|H|
Burvill|Colin|C|
Davies|Helen M S|HMS|

Reverse engineering
Finite element analysis (FEA)
Equine third metacarpal bone (MC3)
Error of reconstructed geometry
Adaptive mesh refinement
Convergence and error analysis


Survival following reirradiation using intensity-modulated radiation therapy with temozolomide in selected patients with recurrent high grade gliomas.

Abstract:
BACKGROUND
High grade gliomas often recur after initial treatment. Despite so many treatment options, there is no standard treatment for recurrent gliomas. The aim of this study is to offer survival following reirradiation (re-RT) using intensity-modulated radiation therapy (IMRT) with temozolomide in selected patients with recurrent high grade gliomas.

METHODS
We examined the medical records of 21 adult patients with recurrent high grade gliomas who were reirradiated with IMRT at the time of tumor recurrence or progression. Tumor recurrence was shown by gadolinium-enhanced magnetic resonance imaging (MRI) and diagnosis was established by pathology review. Statistical analyses were performed with SPSS version 18.0.1 using Cox regression analyses, log-rank test and Kaplan-Meier method.

RESULTS
Eighteen patients presented by localized recurrence, three patients with diffuse recurrence. Median radiotherapy (RT) dose was 54 Gy. About 81% patients received temozolomide with re-RT. The time interval between two courses RT was median 39.3 months (range, 9.6-140.8 months). The response was checked by MRI. About 24% patients achieved complete response (CR) and 29% patient partial response (PR). Stable disease (SD) was observed in 47% patients. Median follow-up time from diagnosis was 41.4 months (range, 16.6-145.4 months) and 12.3 months (range, 2-27.6 months) from re-RT. Median time to recurrence was 39.3 months (range, 9.6-140.8 months). Median survival after re-RT was 18 months for anaplastic astrocytoma (AA), 14.1 months for glioblastoma multiforme (GBM) (range, 11-17.2 months) (P=0.1) and 7.1 months for patients with Karnofsky performance status (KPS) <70 before re-RT and 17.4 months for KPS >70 (P=0.02).

CONCLUSIONS
re-RT is one of the treatment options for recurrent high grade gliomas and IMRT can be an effective treatment modality for recurrent high grade brain tumors with only mild side effects. Survival is better in patients with good performance status and in recurrent anaplastic tumors after re-RT.

survival
Glioma
reirradiation (re-RT)
glioblastoma
intensity modulated radiotherapy


A decline in patient disclosure of heterosexuality in the English General Practice Patient Survey: a longitudinal analysis of cross-sectional data.

Abstract:
BACKGROUND
Persistent health inequalities in relation to both health care experiences and health outcomes continue to exist among patients identifying with a marginalized sexual orientation (MSO).

OBJECTIVE
To compare the patterns of sexual orientation disclosure within primary care in England over a 5-year period.

METHODS
Descriptive analysis of cross-sectional, repeat measure, fully anonymized survey data of adults responding to the General Practice Patient Survey (GPPS) January 2012 to 2017. Participants from each year varied between 808 332 (2017) and 1 037 946 (2011/2012).

RESULTS
The analysis samples comprised between 396 963 and 770 091 individuals with valid sexual orientation data depending on the year. For males, heterosexual disclosure decreased consistently from 92.3% to 91.2% from 2012 to 2017. Male patients reporting gay, bisexual and/or 'other' sexual orientations increased from 3.1% to 3.9%. For females, a larger reduction in heterosexual disclosure was recorded from 94% to 92.5%. Those reporting as lesbian, bisexual and/or 'other' increased from 1.82% to 2.68%, with the largest increase seen in the reporting of bisexuality, which nearly doubled from 2012 until 2017 (0.56-0.99%).

CONCLUSION
We found a year-on-year decline in patients reporting a heterosexual identity and an increase in the proportions of people reporting being either gay, bisexual, 'other sexual orientation' or preferring not to say. Heteronormative environments extend to health care settings, which may put increased stress on MSO individuals attending a GP practice. The introduction of environmental signs/symbols to show that a practice is inclusive of MSOs could reduce the potential stress experienced by patients.

Disclosure
General Practice Patient Survey
sexual orientation
primary care
LGB
sexual identity


Tropical sea cucumber fisheries: Changes during the last decade.

Abstract: Tropical sea cucumber fisheries are generally traditional, small-scale, multispecies and poorly managed. Many recent studies have improved our knowledge on the biology and ecology of the commercially important species; the main results are analysed and the remaining gaps discussed. The fisheries and the patterns of trade changes during the last decade are presented from the data available and confirm overexploitation in the traditional Indian Ocean and West Pacific countries and territories. Several Latino-American countries now have active fisheries. Despite the management and conservation issues which have recently received more attention at international, regional and national levels, more measures are still needed at all these levels, to ensure sustainable exploitations of these resources.

D000074067:Conservation of Water Resources

Fisheries Management Trade Beche-de-mer Market holothurian


New score for prediction of morbidity in patients undergoing open pancreaticoduodenectomy.

Abstract:
OBJECTIVE
The Physiological and Operative Severity Score for the enUmeration of Mortality and morbidity (POSSUM) is commonly used to predict the risk of postoperative complications in general surgery. However, use of the POSSUM is not absolutely suitable for open pancreaticoduodenectomy (OPD), which has unique complications such as pancreatic fistula formation. This study was performed to establish a new risk score for assessing the incidence of postoperative complications of OPD.

METHODS
This retrospective case-control study involved 159 patients who underwent standard OPD from 2 January 2017 to 1 February 2019. The risk factors for post-OPD complications were statistically investigated, and a risk score model was established by multivariate logistic regression.

RESULTS
Among all 159 patients, 72 (42.28%) developed complications. A scoring system was developed based on the following five independent variables: sodium concentration of <141.20 mmol/L, white blood cell count of >6.35 × 109/L, pancreatic texture grade, body mass index of >25.06 kg/m2, and basic respiratory diseases. Our risk score model demonstrated better discriminating power, prediction power, and prediction probability than the POSSUM model in the receiver operating characteristic curve analysis.

CONCLUSION
This novel risk score may help to predict postoperative complications after OPD with higher accuracy than the POSSUM system.

Pancreaticoduodenectomy
case-control study
risk factors
scoring system
postoperative morbidity
risk prediction


Expanding the threonine aldolase toolbox for the asymmetric synthesis of tertiary α-amino acids.

Abstract: The direct biochemical synthesis of tertiary α-amino acids with a wide range of diversity was recently reported using natural threonine aldolases LTA from Aeromonas jandei and DTA from Pseudomonas sp. Here, we describe the identification of five novel threonine aldolases which accept alanine and serine as amino acid donors. The enzymes were found by sequence database analysis using known aldolases as template. All enzymes were overexpressed in Escherichia coli and purified, and their biochemical properties were characterized. The new enantiocomplementary L- and D-threonine aldolases catalyze the asymmetric synthesis of β-hydroxy α-methyl- and α-hydroxymethyl-α-amino acids with good conversion and perfect enantioselectivity at α-carbon of the products (e.e. >99 %). The structural basis for the broad donor specificity of these threonine aldolases is analyzed based on crystal structure alignments and amino acid sequences comparison.

Fesko|Kateryna|K|
Strohmeier|Gernot A|GA|
Breinbauer|Rolf|R|

Threonine aldolase
Aldol reactions
Biocatalysis
Enzyme catalysis
Tertiary amino acids


A multicenter study of anorectal pressures and rectal sensation measured with portable manometry in healthy women and men.

Abstract:
BACKGROUND
The equipment and methods for performing anorectal manometry and biofeedback therapy are different and not standardized. Normal values are influenced by age and sex. Our aims were to generate reference values, examine effects of gender and age, and compare anorectal pressures measured with diagnostic and biofeedback catheters and a portable manometry system.

METHODS
In this multicenter study, anorectal pressures at rest, during squeeze, and evacuation were measured with diagnostic and biofeedback catheters using Mcompass™ portable device in healthy subjects. Balloon expulsion time and rectal sensation were evaluated. The effects of age and gender were assessed.

RESULTS
The final dataset comprised 108 (74 women) of 124 participants with normal rectal balloon expulsion time (less than 60 s). During squeeze, anal resting pressure increased by approximately twofold in women and threefold in men. During evacuation, anal pressure exceeded rectal pressure in 87 participants (diagnostic catheter). The specific rectoanal pressures (e.g., resting pressure) were significantly correlated and not different between diagnostic and biofeedback catheters. With the diagnostic catheter, the anal squeeze pressure and rectal pressure during evacuation were greater in men than women (p ≤ 0.02). Among women, women aged 50 years and older had lower anal resting pressure; rectal pressure and the rectoanal gradient during evacuation were greater in older than younger women (p ≤ 0.01).

CONCLUSIONS
Anal and rectal pressures measured with diagnostic and biofeedback manometry catheters were correlated and not significantly different. Pressures were influenced by age and sex, providing reference values in men and women.

constipation
defecatory disorders
diagnosis
fecal incontinence


Meta-analysis of second generation competency to stand trial assessment measures: Preliminary findings.

Abstract:
BACKGROUND
Since the 1990s, standardized competency to stand trial assessment measures have been developed to improve the reliability and validity of expert assessment and opinion in legal settings. This study aimed to meta-analyze the psychometric properties of the four 'second generation' assessment tools: the MacCAT-CA, MacCAT-FP, ECST-R and CAST*MR.

METHOD
A systematic search of published and unpublished studies was undertaken on PsycNet, PubMed, Scopus, Web of Science and Science Direct up until February 2018. Test manuals were sourced and attempts at finding grey literature included contacting study authors and test developers.

RESULTS
Eleven studies were included in the final analysis. The MacCAT-CA, ECST-R and CAST*MR demonstrated acceptable subscale internal consistencies and interrater reliability. The MacCAT-CA and CAST*MR discriminated between competent and incompetent defendants with large effects. The MacCAT-FP had insufficient reliability data and poor discrimination. There was insufficient data to meta-analyze the factor structure, sensitivity, specificity, or effect sizes between types of clinical presentation on any tool.

CONCLUSIONS
Very few studies have investigated the psychometric properties of the selected tools. Many studies were excluded for not providing original data or simply re-reporting the psychometric properties stated in test manuals. Whilst the MacCAT-CA and ECST-R have promising psychometric properties, ongoing construct validation is required.

Blake|Grant A|GA|
Ogloff|James R P|JRP|
Chen|Won Sun|WS|

D011569:Psychiatric Status Rating Scales

Competency to stand trial
Psychometric
MacCAT-CA
ECST-R
Fitness


Anticoagulant active ingredients identification of total saponin extraction of different Panax medicinal plants based on grey relational analysis combined with UPLC-MS and molecular docking.

Abstract:
ETHNOPHARMACOLOGICAL RELEVANCE
In traditional use, Panax medicinal plants (ginseng, red ginseng, notoginseng, Panax japonicus, and Panacis majoris rhizoma) have different bioactivities from each other, even under different dosages, but their chemical compositions are very similar; so the question is, what is the primary effective substance induced the different efficacy, and how to identify them from a group of chemical constituents?

AIM OF THE STUDY
The goal of this research was to provide a strategy to determine the effective substance in Panax genus medicinal plants responsible for the anticoagulant response.

MATERIALS AND METHODS
This research used ultra-high performance liquid chromatography coupled with mass spectrometry (UPLC-MS) to analyze the saponin chemical compositions of different concentration ethanol extraction of notoginseng and the ginseng genus medical plant 75% ethanol extraction (Panax ginseng, red ginseng, Panax japonicus, Panacis majoris rhizome), and used four coagulation factors (PT, TT, APTT, Fib) to evaluate the anticoagulant activity of the extracts. Grey correlation analysis was applied to establish the spectral effect relationship and give the anticoagulant potency of different saponins. Network pharmacology and molecular docking were adopted to clarify and verify the possible mechanisms of anticoagulant action.

RESULTS
The results showed that the blood physiological regulation activities of Panax medicinal plants were different according to the solvent concentration, processing, species and dosage. Overall, the most suitable solvent for extraction of SQ was 75% ethanol; At low dosage (10-100 mg/mL), the anticoagulant effect of Panax medical plants was: ZJS > ZZS > SQ > RS > HS, and at high doses (100-1000 mg/mL) was: SQ > ZJS > ZZS > RS > HS. GRA and molecular docking results showed the contribution of some components (NG-R2, NG-Fc/G-Ra1/G-Ra2, G-Rc, G-Rk3, and G-Rh4) to the whole anticoagulant activity of the drug were increased, while the effect of CS-IVa was just decreased with the increase of dosage; the anticoagulant effect of G-Rg3 (the main anticoagulant component) is mainly related to the targets F2, AR, RHO, ACR, MB, GZMB, B2M, CA2, CAT, and PAPOLA.

CONCLUSION
This study determined the effective substance of anti-coagulation of ginseng genus herbal medicines and the regulation of different anticoagulant effects of TCM by changing various influencing conditions, including processing method, extraction method, and dose. It also provided an effective strategy for effective substances identification of multicomponent, multifunction, and multipurpose herbal medicine.

Ren|Yongshen|Y| Ai|Jiao|J| Liu|Xinqiao|X| Liang|Shuai|S| Zheng|Yao|Y| Deng|Xin|X| Li|Yan|Y| Wang|Jing|J| Deng|Xukun|X| Chen|Lin-Lin|LL|

D002851:Chromatography, High Pressure Liquid

D021241:Spectrometry, Mass, Electrospray Ionization

Panax ginseng total saponin anticoagulant activity


Higher plasma cystatin C is associated with mortality after acute respiratory distress syndrome: findings from a Fluid and Catheter Treatment Trial (FACTT) substudy.

Abstract:
BACKGROUND
Cystatin C is a well-validated marker of glomerular filtration rate in chronic kidney disease. Higher plasma concentrations of cystatin C are associated with worse clinical outcomes in heterogenous populations of critically ill patients and may be superior to creatinine in identifying kidney injury in critically ill patients. We hypothesized that elevated levels of plasma cystatin C in patients with acute respiratory distress syndrome (ARDS) would be associated with mortality risk.

METHODS
In a retrospective study, cystatin C was measured by nephelometry on plasma obtained at enrollment from 919 patients in the Fluid and Catheter Treatment Trial. Multivariable logistic regression was performed testing the association between quartiles of cystatin C and 60-day mortality. Analyses were stratified by acute kidney injury (AKI) status identified in the first 7 days after enrollment by Kidney Disease: Improving Global Outcomes (KDIGO) criteria.

RESULTS
Cystatin C was significantly higher among those patients who died compared to those who survived to 60 days [1.2 (0.9-1.9) mg/L vs. 0.8 (0.6-1.2) mg/L, p < 0.001]. Compared to the lower three quartiles, subjects in the highest quartile of cystatin C had a significantly higher odds of death at 60 days [OR 1.8 (1.2-2.6), p = 0.003 in adjusted analyses]; the odds of death incrementally rose in higher cystatin C quartiles compared to the lowest quartile (OR 1.1, 1.8, and 2.5). In adjusted analyses stratified by AKI status, compared to subjects in the lower three quartiles, subjects in the highest quartile of cystatin C with AKI had a significantly higher odds of death at 60 days both in participants with AKI [OR 1.6 (1.0-2.4), p = 0.048] and those without AKI [OR 2.4 (1.2-5.0), p = 0.017]. In adjusted analyses, there was no significant association between sex-stratified baseline creatinine quartiles and mortality.

CONCLUSIONS
Higher plasma levels of cystatin C on enrollment were strongly associated with mortality at 60 days in patients with ARDS with and without AKI identified by creatinine-based definitions. Compared to creatinine, cystatin C may be a better biomarker of kidney function in patients with ARDS and therefore identify patients with multiple organ failure at higher risk of death.

Acute respiratory distress syndrome (ARDS)


Finite element analysis of the effect of sagittal angle on ankle joint stability in posterior malleolus fracture: A cohort study.

Abstract:
OBJECTIVE
Aim of this study was to establish three-dimensional finite element model of the posterolateral-oblique type of posterior malleolus fracture with different sagittal angle and to explore the effect of sagittal angle on ankle joint stability.

METHODS
CT data of ankle were collected from a normal male volunteer.Established finite element model of the normal ankle and verified its reliability. Five posterior malleolus fracture models with different sagittal angles were established. Finite element analysis(FEA)was carried out to simulate the conditions of vertical loading in neutral position with a total weight of 600 N.Recorded the data and did statistical analyses.

RESULTS
(1) The contact area was 483.55 mm2 and the maximum contact stress was 3.793 MPa in the model of the normal ankle joint. (2) There was a positive correlation between the sagittal angle(SA)and the contact area(CA)(r = 0.925,P < 0.05). Regression equation was CA = 316.755 + 1.749* SA. The correlation between the sagittal angle and the maximum contact stress(MCS)was negative (r = -0.988,P < 0.01). Regression equation was MCS = 5.214-0.018*SA. There was a negative correlation between the sagittal angle of fracture and relative displacement(RD)(r = -0.950,P < 0.05). Regression equation was RD = 1.388-0.009*SA.

CONCLUSION
The greater the sagittal angle of fracture was, The more stable the ankle joint was. The sagittal angle of fracture could be used as a relative index to reflect ankle stability for posterior malleolus fracture.

Guan|Ming|M| Zhao|Jing|J| Kuang|Yong|Y| Li|Guang|G| Tan|Jun|J|

D000328:Adult
D064386:Ankle Fractures
D000843:Ankle Joint
D015331:Cohort Studies
D020342:Finite Element Analysis
D005593:Fracture Fixation, Internal
D006801:Humans
D007593:Joint Instability
D008297:Male

Finite element analysis
Sagittal angle
Posterior malleolus fracture
Ankle stability


Impact of Community-Based Nutrition Education on Geophagic Behavior and Dietary Knowledge and Practices among Rural Women in Nakuru Town, Kenya: A Pilot Study.

Abstract:
OBJECTIVE
Geophagia, the deliberate consumption of rocks, soil, or clay, is prevalent in developing countries, particularly sub-Saharan Africa. Health risks associated with this behavior include parasitosis, heavy metal poisoning, nutrient deficiencies, and poor birth outcomes. This pilot study was designed to reduce geophagic practices and improve nutrition among rural Kenyan women.

METHODS
The researchers used snowball sampling to recruit participants (n = 135; aged 15-49 years) from low socioeconomic areas who consumed geophagic materials. Interviews were carried out before and after a nutrition intervention implemented by trained community health volunteers.

RESULTS
Nutrition education focusing on geophagia significantly (P < .001) decreased the practice in 77% of participants. Postintervention interviews also demonstrated substantial improvement in understanding the concept of making half the plate vegetables using the healthy plate model.

CONCLUSIONS AND IMPLICATIONS
Nutrition education can be useful for reducing geophagia (a largely ignored, unsafe dietary behavior) and enhancing nutritional knowledge in African women.

Iron-Segev|Sharon|S|
Lusweti|Janerose Nasimiyu|JN|
Kamau-Mbuthia|Elizabeth|E|
Stark|Aliza H|AH|

D007722:Health Knowledge, Attitudes, Practice

nutrition education
geophagia
women of reproductive age
women's dietary diversity score


Use of a 2-tier histologic grading system for canine cutaneous mast cell tumors on cytology specimens.

Abstract:
BACKGROUND
Mast cell tumors (MCT) represent the most common malignant skin tumor in the dog. Diagnosis of an MCT can be achieved through cytologic examination of a fine-needle aspirate. However, the grade of the tumor is an important prognostic marker and currently requires histologic assessment. Recently a 2-tier histologic grading system based on nuclear features including number of mitoses, multinucleated cells, bizarre nuclei, and karyomegaly was proposed.

OBJECTIVES
The aim of this study was to assess if the cytomorphologic criteria proposed in the 2-tier histologic grading system are applicable to cytology specimens.

METHODS
A total of 141 MCT specimens reported as grade I, II, or III according to the Patnaik system with both histologic specimens and fine-needle aspirates available were histologically and cytologically reevaluated in a retrospective study.

RESULTS
According to the 2-tier grading system, 38 cases were diagnosed histologically as high-grade and 103 as low-grade MCT. Cytologic grading resulted in 36 high-grade and 105 low-grade tumors. Agreement between histologic and cytologic grading based on the 2-tier grading system was achieved in 133 cases (sensitivity 86.8%, specificity 97.1%, kappa value 0.853), but 5 high-grade tumors on histology were classified as low-grade on cytology.

CONCLUSION
Cytologic grading of MCT in the dog is helpful for initial assessment. However, the reliability of cytology using the 2-tier grading system is considered inadequate at this point. Prospective studies including clinical outcome should be pursued to further determine diagnostic accuracy of cytologic mast cell grading.

Hergt|Franziska|F|
von Bomhard|Wolf|W|
Kent|Michael S|MS|
Hirschberger|Johannes|J|

D000818:Animals
D004283:Dog Diseases
D004285:Dogs
D008407:Mast Cells
D054705:Mastocytoma, Skin
D060787:Neoplasm Grading
D015203:Reproducibility of Results
D012189:Retrospective Studies

dog
fine-needle aspirates
Cytomorphologic criteria
nuclear abnormalities


NO2 inhalation enhances asthma susceptibility in a rat model.

Abstract: Nitrogen dioxide (NO2) is a major air pollutant. Epidemiologic studies have found that NO2 exposure is associated with an increased risk of asthma. Nevertheless, the potential molecular mechanisms remain unclear. In this study, we investigated the effect of NO2 inhalation on the occurrence of allergic airway inflammation and its underlying mechanisms. Firstly, male Wistar rats were exposed to 2 and 5 mg/m3 NO2 (28 days, 5 h/day). The results showed that NO2 exposure could induce pulmonary inflammatory response, mucus formation, and Th1/Th2 imbalance in the lung of normal rats, resulting in allergic asthma-like features. Secondly, male Wistar rats were exposed to 5 mg/m3 NO2 (42 days, 5 h/day), sensitized with ovalbumin (OVA), challenged with aerosolized OVA, and characterized in asthma models. Results showed that NO2 exposure aggravated lung inflammation in the OVA-sensitized rats, accompanied by the increase in inflammatory cell infiltration, mucus hypersecretion, and collagen deposition. Furthermore, NO2 exposure promoted the increase in the expression of mucin gene (MUC5AC) and pro-inflammatory factors [interleukin (IL)-1β, intercellular adhesion molecule-1 (ICAM-1), and IL-6] as well as serum OVA-specific immunoglobulin E (IgE) production. Taken together, we established that NO2 exposure promotes allergic airway inflammation and increases the asthma susceptibility. The underlying mechanisms involve the promotion of activation of interleukin-4/signal transducer and activator of transcription-6 (IL-4/STAT6) pathway [IL-4 receptor (IL-4R) α, janus kinase (JAK) 1, JAK 3, and STAT6] and related transcription factor [T cell-specific protein-tyrosine kinase (Lck), extracellular-regulated kinase (ERK)1/2, and nuclear factor-κB (NF-κB)]. In particular, the imbalance of Th1/Th2 cell differentiation [IL-4, interferon (IFN)-γ, GATA-binding protein-3 (GATA-3), and T-box expressed in T cells (T-bet)] plays a pivotal role in NO2-induced inflammatory responses. These findings may provide a better understanding of mechanism of NO2-associated respiratory diseases.

Han|Ming|M| Ji|Xiaotong|X| Li|Guangke|G| Sang|Nan|N|

Nitrogen dioxide
Airway inflammation
Allergic asthma
IL-4/STAT6 pathway
Th1/Th2 differentiation


Tissue Engineering Models for the Study of Breast Neoplastic Disease and the Tumor Microenvironment.

Abstract: The development of adequate experimental models is crucial to furthering the current mechanistic understanding of the etiopathogenesis, subsequent growth, and ultimate metastasis of breast cancer, to develop targeted diagnostics and therapeutics such as the identification of new treatments for multidrug-resistant tumors and triple-negative breast cancers. The utility of new therapeutic options is limited by the platforms currently used to test their efficacy in vitro. The use of three-dimensional models, which incorporate patient-specific, primary cells, offers significant advantages over traditional two-dimensional models by providing a means of accurately recapitulating the complex tumor microenvironment. Advances in breast cancer models, in turn, stand to contribute to more efficacious breast cancer therapeutics. Herein, we review the recent advances in experimental models of breast cancer and suggest methods by which these can be used to further our understanding of said cancer. Impact statement This review provides a comprehensive look at the development of experimental models for breast cancer, the pitfalls identified therein, and the creative solutions that have overcome these challenges. Collectively, we tell a story of the many compounding efforts that have been successful in more accurately modeling the origin and progression of this disease in a patient-specific manner. By providing a thorough and detailed account of model development thus far, we provide the necessary foundation for those who seek to contribute to the important work of modeling breast cancer toward the development of increasingly accurate diagnostics and therapeutics. These advances will ultimately serve to benefit patients, providers, cancer biologists, and anyone participating in cancer research.

Premaratne|Ishani D|ID|
Toyoda|Yoshiko|Y|
Celie|Karel-Bart|KB|
Brown|Kristy A|KA|
Spector|Jason A|JA|

tissue engineering
breast cancer
3D model
precision medicine


Assessment of long-term cryopreservation for production of hCTLA4Ig in transgenic rice cell suspension cultures.

Abstract: For the commercialization of plant-made pharmaceuticals (PMPs) using transgenic plant cell cultures, the establishment of a cell-banking system has been known to be an essential process. Plant cells are traditionally maintained by repeated subcultures. However, this method has several problems including genetic instability of transformed cell lines, time- and cost-consuming. In this study, long-term cryopreserved rice suspension cells were firstly investigated for the production of human cytotoxic T-lymphocyte antigen 4-immunoglobulin (hCTLA4Ig). The cryopreserved cells for 5 years were regrowed to callus successfully and then suspended into the liquid medium. Consequently, the maximum cell mass and the hCTLA4Ig production were similar levels compared to those of the non-cryopreserved cells (control) even though hCTLA4Ig productivity was 1.7-fold higher than that of control. To further assess the level of improvements in hCTLA4Ig productivity in cryopreserved cells, hCTLA4Ig production profiles were statistically assessed between data of the cryopreserved cells for 5 years and annual data of non-cryopreserved cells maintained by subculture for 5 years. These results also indicate that hCTLA4Ig productivity in cryopreserved cells for 5 years was significantly increased (p-value: <0.001, 95% confidence interval) and it could be related to cell lysis resulting in release of hCTLA4Ig which was confirmed by the measurement of electrolyte leakage. In conclusion, we show that the long-term cryopreservation of transgenic rice cells was possible to support stable cell lines for the production of PMPs.

Kwon|Jun-Young|JY| Jeong|Sun-Hee|SH| Choi|Ji-Won|JW| Pak|Yun-Young|YY| Kim|Dong-Il|DI|

Long-term cryopreservation
hCTLA4Ig
Cell-banking system
RAmy3D promoter
Transgenic rice cell culture


Clinical effectiveness of adjunctive antimicrobial photodynamic therapy for residual pockets during supportive periodontal therapy: A systematic review and meta-analysis.

Abstract:
PURPOSE
To evaluate the clinical efficacy of antimicrobial photodynamic therapy (aPDT) adjunctive to scaling and root planing (SRP) in the treatment of residual pockets for chronic periodontitis patients on supportive periodontal therapy (SPT).

METHOD
Bibliographic databases of MEDLINE and Cochrane Library were thoroughly searched up to July 2016 for eligible randomized controlled trials (RCTs). Mean differences (MD) and the corresponding 95% confidence intervals (CI) were synthesized for probing depth (PD) reduction and clinical attachment level (CAL) gain. The I2 test and Q statistics were employed to assess inter-study heterogeneity. Subgroup analysis was performed based on the enrollment of smokers.

RESULT
Four RCTs fulfilling the eligibility criteria were included. Pooled estimates demonstrated statistically significant improvements in both PD reduction (MD=0.69, CI: 0.11-1.28, p=0.02) and CAL gain (MD=0.60, CI: 0.11-1.10, p=0.02) for SRP+aPDT versus SRP alone. Meta-analysis of studies with smokers failed to produce a significant additional effect in PD (MD=0.32, CI: -0.30 to 0.94, p=0.31) and CAL (MD=0.42, CI: -0.26 to 1.09, p=0.23) when SRP was associated with aPDT. However, significant enhancements in PD reduction (MD=1.23, CI: 0.74-1.72, p<0.001) and CAL gain (MD=0.96, CI: 0.31-1.62, p=0.004) were observed for studies excluding smokers.

CONCLUSION
Pooled evidence indicates an additional clinical improvement in the maintenance of residual pockets in favor of SRP+aPDT compared with SRP alone. Subgroup analysis demonstrates an adverse impact of smoking on clinical effect of the combined therapy. Substantial heterogeneity and the paucity of included studies undermine the statistical power of this meta-analysis. Future well-designed and large-scale clinical trials evaluating the adjunctive efficacy of aPDT in periodontal maintenance phase are critically needed.

D016032:Randomized Controlled Trials as Topic

Antimicrobial photodynamic therapy
Residual pockets
Supportive periodontal therapy
Meta-analysis
Scaling and root planing
Chronic periodontitis


Transient receptor potential ankyrin 1 channels are involved in spontaneous peptide hormone release from astrocytes.

Abstract: Astrocytes, a large population of glial cells, detect neurotransmitters and respond by increasing intracellular Ca2+ concentration ([Ca2+]i) and releasing chemical molecules called gliotransmitters. Recently discovered Ca2+ influx through transient receptor potential ankyrin 1 (TRPA1) channels is reported to cause spontaneous [Ca2+]i increase in astrocytes. While several physiological functions of TRPA1-mediated spontaneous Ca2+ signal have been revealed, relation with gliotransmitter release, especially peptide hormone exocytosis is largely unknown. We therefore explored the [Ca2+]i and exocytosis dynamics in rat astrocyte cell line C6 cells and primary astrocytes. TRPA1-mediated spontaneous [Ca2+]i transients were observed in both C6 cells and primary astrocytes. Total internal reflection fluorescence microscopy revealed that Venus-tagged brain-derived neurotrophic factor and neuropeptide Y were released spontaneously from astrocytes. Activation of TRPA1 channels enhanced the frequency of peptide hormone exocytosis, and inhibition of TRPA1 channels decreased the number of peptide hormone exocytosis. These results suggest that TRPA1-mediated spontaneous [Ca2+]i increase modulates the spontaneous release of peptide hormones from astrocytes.

Takizawa|Mai|M| Harada|Kazuki|K| Nakamura|Kazuaki|K| Tsuboi|Takashi|T|

Transient receptor potential ankyrin 1
Astrocytes
Brain-derived neurotrophic factor
Neuropeptide Y
Live cell imaging
Total internal reflection microscopy


Fundamentals of quality and safety in diagnostic radiology.

Abstract: The most fundamental aspects of quality and safety in radiology are reviewed, including a brief history of the quality and safety movement as applied to radiology, the overarching considerations of organizational culture, team building, choosing appropriate goals and metrics, and the radiologist's quality "tool kit."

D003952:Diagnostic Imaging
D017146:Models, Organizational
D015279:Organizational Culture
D061214:Patient Safety
D017410:Practice Guidelines as Topic
D058996:Quality Improvement
D011871:Radiology
D017751:Safety Management
D014481:United States

Just Culture
Quality management
patient safety
practice quality improvement


1-Phenyl-dihydrobenzoindazoles as novel colchicine site inhibitors: Structural basis and antitumor efficacy.

Abstract: The colchicine site inhibitors (CSIs) showed promising prospects as antitumor agents due to their vascular disrupting activities besides antimitotic activities. 1-Phenyl-dihydrobenzoindazole was found as a novel scaffold of CSI without the cis-trans isomerization problem. The X-ray co-crystal structure of the lead compound with tubulin was determined, which revealed the binding mode including special water-bridged hydrogen bonds. The structure also provided guidance for the structural optimization of this type of CSI, which led to the discovery of the most potent inhibitor A3, with growth IC50 lower than 1 nM against human colon cancer cell lines and tubulin polymerization IC50 of 1.6 μM. In addition, its water-soluble prodrug B1 showed good in vivo antitumor activity on two human colon cancer xenograft nude mice models, encouraging further study of this type of antitumor compound.

Jiang|Junhang|J| Zhang|Hao|H| Wang|Chongqing|C| Zhang|Qingsen|Q| Fang|Shaoyu|S| Zhou|Ruolan|R| Hu|Jian|J| Zhu|Ju|J| Zhou|Youjun|Y| Luo|Cheng|C| Zheng|Canhui|C|

D023041:Xenograft Model Antitumor Assays

Colchicine site inhibitors
X-ray co-crystal structure
Water-soluble prodrug
Cis-trans photoisomerization
Microtubule-targeting agents


Continuous cultivation strategy for yeast industrial wastewater-based polyhydroxyalkanoate production.

Abstract: Polyhydroxyalkanoates (PHAs) present an eco-friendly alternative for conventional plastics. Industrial wastewater from the food industry is a copious source of organic carbon that can be recovered in the form of PHA. However, the wastewater composition varies considerably among the different industries demanding for an industry-specific investigation of the PHA production process. Wastewater from the yeast industry, besides its high concentration in organic carbon, also contains a high ammonium concentration which might decrease the PHA production. Thus, this study aims to investigate PHA production using yeast industry wastewater via an enriched mixed microbial culture (MMC). A less explored cultivation strategy, i.e., continuous cultivation for PHA production was evaluated and compared to the widely used batch cultivation. PHA accumulating MMC was enriched using a sequencing batch reactor (SBR) operated under aerobic dynamic feeding. An MMC dominated by the Thauera species was successfully enriched in the SBR. Experimental results showed that ammonium is indeed required for PHA accumulation and the complete absence of ammonium negatively affects the accumulation process. Using wastewater, batch and continuous feeding strategies, respectively, yielded the PHA accumulation of 72 % and 65 % per dry cell weight. Despite the slightly lower PHA accumulation with continuous cultivation, four times more biomass growth was produced. Consequently, higher theoretical PHA production (270 t/year) can be expected using continuous cultivation in half of the reactor volume (45 m3). Therefore, this study asserts the viability of continuous cultivation as a feasible investigatory tool and PHA production strategy.


Emphasis on various subtopics in the anatomy curriculum for chiropractic training: An international survey of chiropractors and anatomists.

Abstract:
OBJECTIVE
The aim of this study was to conduct an international survey of the perceived optimal level of anatomy teaching from anatomy academics and practicing chiropractors. We hypothesized that the optimum level of anatomical understanding for chiropractic students does not differ between the anatomists teaching the students and practicing chiropractors.

METHODS
The opinion of anatomists teaching in a chiropractic course (n = 16) was compared to practicing chiropractors (n = 589). The students' level of understanding was based on the revised Bloom's taxonomy for 16 different curriculum areas. Anatomists were recruited by contacting the accredited chiropractic courses worldwide. Snowball sampling was used for the practicing chiropractors. Independent-samples Mann-Whitney U tests were used to compare the results of anatomists and chiropractors.

RESULTS
Opinions differed between anatomists and chiropractors on 9 out of the 16 questions. Where opinions differed, chiropractors recommended a higher standard of anatomical knowledge. The level suggested by chiropractors for these curriculum areas is equal to the "evaluating" level where chiropractic students can remember, understand, apply, and analyze anatomical knowledge to be able to justify a clinical decision.

CONCLUSION
Compared to anatomists working in chiropractic programs, chiropractors suggest a higher standard of anatomy be taught to undergraduates. Collaboration between chiropractors and anatomists would likely be beneficial in creating or modifying anatomy curricula for chiropractic students.

Chapman|Peter D|PD|
Meyer|Amanda|A|
Young|Kenneth|K|
Wibowo|Daniel|D|
Walker|Bruce|B|

Anatomy Curriculum Chiropractic Education


Effect of short chain inulin on the rheological and sensory characteristics of reduced fat set coconut milk yoghurt.

Abstract: The effect of short-chain inulin on the rheological and sensory properties of reduced fat set coconut milk yoghurt was studied with whole fat coconut milk yoghurt as reference. The concentration of short-chain inulin was varied at 0, 5, 10, 15, and 20% w/v respectively. All the yoghurt samples displayed higher elastic modulus G' than viscous modulus G". However, 15% inulin yoghurt had the highest value for G' & G". The 15 and 20% inulin yoghurts displayed high yield stress (1036.7 ± 2.39 & 368.23 ± 0.30 Pa). Addition threshold of 15% was established, beyond this level there was a significant decrease in the yield stress, firmness, cohesiveness and consistency values of the reduced fat yoghurts. Using Pearson correlation analysis, no correlation was observed between firmness and yield stress, Similarly, there was significant correlation between the yield stress and instrumental viscosity r = 0.957; p < 0.01. Furthermore, all yoghurt samples displayed strain thinning behavior except whole fat yoghurt. Carbohydrate was affected by inulin incorporation. Addition of short chain inulin improved sensorial characteristics such as taste, and flavor, but did not display significant difference in color and odor of yoghurt samples. This article is protected by copyright. All rights reserved.

Rheology
Short-chain inulin
Principal component analysis
Reduced fat coconut yoghurt
Sensory evaluation


Identification of essential hypertension biomarkers in human urine by non-targeted metabolomics based on UPLC-Q-TOF/MS.

Abstract:
BACKGROUND
In recent years, using metabolomics technology to study hypertension has made some progress. However, in actual clinical studies, there are few studies on hypertension related metabonomics with human urine as samples. In this study, the urine samples of patients with essential hypertension (EH) were studied by comparing with healthy people to explore the changes of urine metabolites between hypertensive patients and healthy people in order to find potential biomarkers and metabolic pathways.

METHODS
An ultra performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF/MS) technology was used to analyze the urine metabolites of 75 cases of essential hypertension group (EH) and 75 cases of healthy control group (HC).

RESULTS
According to the PLS-DA pattern recognition analysis, substances with significant differences (P < .05) between the EH group and the HC group were screened out, including 10 potential biomarkers such as L-methionine. The metabolic pathways involved were amino acid metabolism, fatty acid metabolism steroid hormone, biosynthesis and oxidative stress.

CONCLUSION
The non-targeted metabolomics based on UPLC-Q-TOF/MS technology can effectively identify the differential metabolites of potential biomarkers in the urine of essential hypertensive patients and provide a theoretical basis for the treatment of clinical hypertension.

Zhao|Huan|H| Liu|Yijia|Y| Li|Zhu|Z| Song|Yanqi|Y| Cai|Xuemeng|X| Liu|Yuechen|Y| Zhang|Tianpu|T| Yang|Liu|L| Li|Lin|L| Gao|Shan|S| Li|Yubo|Y| Yu|Chunquan|C|

Essential hypertension
Urine
Metabolomics
UPLC-Q-TOF/MS
Markers


Miro, MCU, and calcium: bridging our understanding of mitochondrial movement in axons.

Abstract: Neurons are extremely polarized structures with long axons and dendrites, which require proper distribution of mitochondria and maintenance of mitochondrial dynamics for neuronal functions and survival. Indeed, recent studies show that various neurological disorders are linked to mitochondrial transport in neurons. Mitochondrial anterograde transport is believed to deliver metabolic energy to synaptic terminals where energy demands are high, while mitochondrial retrograde transport is required to repair or remove damaged mitochondria in axons. It has been suggested that Ca(2) (+) plays a key role in regulating mitochondrial transport by altering the configuration of mitochondrial protein, miro. However, molecular mechanisms that regulate mitochondrial transport in neurons still are not well characterized. In this review, we will discuss the roles of miro in mitochondrial transport and how the recently identified components of the mitochondrial calcium uniporter add to our current model of mitochondrial mobility regulation.

Niescier|Robert F|RF|
Chang|Karen T|KT|
Min|Kyung-Tai|KT|

miro
MCU
mitochondria
MICU1
axonal transport


Inflammation and DNA damage induction in surgical patients maintained with desflurane anesthesia.

Abstract: The use of anesthetics during surgical interventions may contribute to disorders in the perioperative period. Desflurane is the newest volatile halogenated anesthetic to be introduced in clinical practice. Considering that inflammation and genotoxicity are linked events, and that little is known regarding possible genetic and inflammatory effects of desflurane in surgical patients, this study evaluated DNA damage, systemic inflammatory cytokines and related gene expression in adult patients without comorbidities who underwent minor otorhinological surgeries under general anesthesia maintained with the inhalational anesthetic desflurane. This study involved a self-controlled design in which venous blood samples were collected from subjects before anesthesia administration and after the surgical procedure. The comet assay was applied to assess DNA lesions, while the cytokines IL-1β, IL-6, IL-8, IL-10, IL-17A and TNF-α were evaluated by flow cytometry. A genotoxic effect was observed (p = 0.027), and pro-inflammatory IL-6 and IL-8 levels were significantly increased after surgery (p = 0.001 and p = 0.02, respectively), whereas the levels of the other cytokines did not significantly change. Considering that serum IL-6 and IL-8 were increased, we further evaluated IL-6 and IL-8 gene expression by quantitative real-time polymerase chain reaction (qPCR). However, IL-6 and IL-8 gene expression was unaltered (p >  0.05). In conclusion, anesthetic maintenance with the modern agent desflurane during minor surgeries led to genotoxic and inflammatory effects without altering the expression of inflammation related-genes the day after surgery in patients without comorbidities.

Arruda|Nayara M|NM|
Braz|Leandro G|LG|
Nogueira|Flávia R|FR|
Souza|Kátina M|KM|
Aun|Aline G|AG|
Figueiredo|Drielle B S|DBS|
Lara|Juliana R|JR|
Silva|Mariane Aparecida P|MAP|
Golim|Marjorie A|MA|
de Carvalho|Lídia R|LR|
Braz|José Reinaldo C|JRC|
Braz|Mariana G|MG|

Gene expression
Inhalation anesthetic
Comet assay
Interleukins


A Multifunctional Brain-Computer Interface Intended for Home Use: An Evaluation with Healthy Participants and Potential End Users with Dry and Gel-Based Electrodes.

Abstract: Current brain-computer interface (BCIs) software is often tailored to the needs of scientists and technicians and therefore complex to allow for versatile use. To facilitate home use of BCIs a multifunctional P300 BCI with a graphical user interface intended for non-expert set-up and control was designed and implemented. The system includes applications for spelling, web access, entertainment, artistic expression and environmental control. In addition to new software, it also includes new hardware for the recording of electroencephalogram (EEG) signals. The EEG system consists of a small and wireless amplifier attached to a cap that can be equipped with gel-based or dry contact electrodes. The system was systematically evaluated with a healthy sample, and targeted end users of BCI technology, i.e., people with a varying degree of motor impairment tested the BCI in a series of individual case studies. Usability was assessed in terms of effectiveness, efficiency and satisfaction. Feedback of users was gathered with structured questionnaires. Two groups of healthy participants completed an experimental protocol with the gel-based and the dry contact electrodes (N = 10 each). The results demonstrated that all healthy participants gained control over the system and achieved satisfactory to high accuracies with both gel-based and dry electrodes (average error rates of 6 and 13%). Average satisfaction ratings were high, but certain aspects of the system such as the wearing comfort of the dry electrodes and design of the cap, and speed (in both groups) were criticized by some participants. Six potential end users tested the system during supervised sessions. The achieved accuracies varied greatly from no control to high control with accuracies comparable to that of healthy volunteers. Satisfaction ratings of the two end-users that gained control of the system were lower as compared to healthy participants. The advantages and disadvantages of the BCI and its applications are discussed and suggestions are presented for improvements to pave the way for user friendly BCIs intended to be used as assistive technology by persons with severe paralysis.

Käthner|Ivo|I|
Halder|Sebastian|S|
Hintermüller|Christoph|C|
Espinosa|Arnau|A|
Guger|Christoph|C|
Miralles|Felip|F|
Vargiu|Eloisa|E|
Dauwalder|Stefan|S|
Rafael-Palou|Xavier|X|
Solà|Marc|M|
Daly|Jean M|JM|
Armstrong|Elaine|E|
Martin|Suzanne|S|
Kübler|Andrea|A|

brain-computer interface
EEG
assistive technology
end-user evaluation
practical electrodes


State Population Influences Athletic Performance Combine Test Scores in High School-Aged American Football Players.

Abstract: This study compared athletic performance differences among high school American football combine participants originating from states of different population sizes. High school-aged American football players (n=7,214) who had participated in athletic performance combines between March 2015 and January 2016 were included in this analysis. Data included combine date and location, school state of origin, football position, class, height, weight, 10-, 20-, and 40-yd dash times, pro-agility, L-cone drill, vertical jump, broad jump, and power push-up. Participants were separated into high- (state population>10,000,000; HIGH; n=2,804), mid- (state population=5,000,000-9,999,999; MID; n=2,911), or low-population (state population<5,000,000; LOW; n=1,499) state of origin. Data were allometrically scaled to account for differences in body mass across high school grade levels and American football positions. All statistical analyses were performed on the allometrically scaled data. LOW athletes performed better than HIGH athletes in the 20-yd dash (p≤0.01). LOW athletes performed better than HIGH and MID in the 40-yd dash, pro-agility, broad jump, and power push-up (p<0.01). LOW and HIGH athletes performed better than MID in the L-cone and vertical jump (p<0.01). When considering population size, athletes originating from LOW states may demonstrate higher levels of athletic performance in football combine events hypothetically due to more opportunities for sports participation and playing time, leading to greater athletic development. Youth and high school coaches in MID and HIGH states might consider providing more opportunities for playing and individualized coaching to encourage long-term athletic development.

Gillen|Zachary M|ZM|
Shoemaker|Marni E|ME|
McKay|Brianna D|BD|
Cramer|Joel T|JT|

power
Sports testing
agility
region size
speed


Sculpting crystals one Burgers vector at a time: Toward colloidal lattice robot swarms.

Abstract: Plastic deformation of crystalline materials with isotropic particle attractions proceeds by the creation and migration of dislocations under the influence of external forces. If dislocations are produced and migrated under the action of local forces, then material shape change can occur without the application of surface forces. We investigate how particles with variable diameters can be embedded in colloidal monolayers to produce dislocations on demand. We find in simulation that when embedded clusters of variable diameter particles are taken through multiple cycles of swelling and shrinking, large cumulative plastic slip is produced by the creation and biased motion of dislocation pairs in the solid for embedded clusters of particular geometries. In this way, dislocations emitted by these clusters (biased "dislocation emitters") can be used to reshape colloidal matter. Our results are also applicable to larger-scale swarms of robotic particles that organize into dense ordered two-dimensional (2D) arrangements. We conclude with a discussion of how dislocations fulfill for colloids the role sought by "metamodules" in lattice robotics research and show how successive applications of shear as a unit operation can produce shape change through slicing and swirling.

colloids
robotics
swarming
active matter
soft matter


Exendin-4 protects HUVECs from t-BHP-induced apoptosis via PI3K/Akt-Bcl-2-caspase-3 signaling.

Abstract:
AIMS
Although the insulinotropic role of glucagon-like peptide-1 (GLP-1) in type 2 diabetes mellitus has been substantiated, its role in cardioprotection remains largely unknown. In this study, we explored the effect and mechanism of exendin-4 on tert-butyl hydroperoxide (t-BHP)-induced apoptosis in human umbilical vein endothelial cells (HUVECs).

METHODS
HUVECs were treated with 100 µmol/L t-BHP for 4 h, following pretreatment with 2.5-25 nmol/L exendin-4. Cell viability was determined using an dimethyl thiazolyl diphenyl tetrazolium salt (MTT) assay. The percentage of apoptotic cells was determined by fluorescence microscopy after Hoechst/PI staining. Expression of cysteine-aspartic acid protease-3(caspase-3), beta-cell lymphoma 2(Bcl-2), protein kinase B(AKT), and phosphorylated AKT was detected by western blotting.

RESULTS
Exendin-4 reduced the percentage of cells undergoing apoptosis when HUVECs were exposed to t-BHP. Exendin-4 downregulated caspase-3 activity and increased Bcl-2 protein levels in t-BHP-treated HUVECs. These exendin-4-mediated effects were blocked in the presence of an inhibitor of phosphoinositide-3 kinase (PI3K). Exendin-4 reversed t-BHP-mediated inhibition of Akt phosphorylation, which was abrogated by the PI3K inhibitor, wortmannin.

CONCLUSION
Our findings suggest that exendin-4 reduces t-BHP-induced apoptosis of HUVECs. Additionally, PI3K/Akt-Bcl-2-caspase-3 signaling is involved in the exendin-4-mediated modulation of HUVECs.

Wang|Linxi|L| Tang|Li|L| Wang|Yanping|Y| Wang|Lijing|L| Liu|Xiaoying|X| Liu|Xiaohong|X| Chen|Zhou|Z| Liu|Libin|L|

HUVECs
Apoptosis
glucagon-like peptide-1
t-BHP
Bcl-2
phosphoinositide-3 kinase


Cataloguing the dead: breathing new life into pseudokinase research.

Abstract: Pseudoenzymes are present within many, but not all, known enzyme families and lack one or more conserved canonical amino acids that help define their catalytically active counterparts. Recent findings in the pseudokinase field confirm that evolutionary repurposing of the structurally defined bilobal protein kinase fold permits distinct biological functions to emerge, many of which rely on conformational switching, as opposed to canonical catalysis. In this analysis, we evaluate progress in evaluating several members of the 'dark' pseudokinome that are pertinent to help drive this expanding field. Initially, we discuss how adaptions in erythropoietin-producing hepatocellular carcinoma (Eph) receptor tyrosine kinase domains resulted in two vertebrate pseudokinases, EphA10 and EphB6, in which co-evolving sequences generate new motifs that are likely to be important for both nucleotide binding and catalysis-independent signalling. Secondly, we discuss how conformationally flexible Tribbles pseudokinases, which have radiated in the complex vertebrates, control fundamental aspects of cell signalling that may be targetable with covalent small molecules. Finally, we show how species-level adaptions in the duplicated canonical kinase protein serine kinase histone (PSKH)1 sequence have led to the appearance of the pseudokinase PSKH2, whose physiological role remains mysterious. In conclusion, we show how the patterns we discover are selectively conserved within specific pseudokinases, and that when they are modelled alongside closely related canonical kinases, many are found to be located in functionally important regions of the conserved kinase fold. Interrogation of these patterns will be useful for future evaluation of these, and other, members of the unstudied human kinome.

pseudokinase
pseudoenzyme
signalling
tribbles
PSKH2
Eph tyrosine kinase
PSKH1
bioinformatics
ephrin receptor
inhibitor
sequence analysis


Changes in endolymphatic hydrops in patients with Ménière's disease treated conservatively for more than 1 year.

Abstract:
CONCLUSION
This study revealed that endolymphatic hydrops (EH) reduced in some cases with Ménière's disease (MD) treated conservatively. It appears that the EH reduction was associated with improvement of the clinical symptoms.

OBJECTIVES
The relationship between the degree of EH and clinical symptoms is not clear at present. The purpose of the present study was to investigate the time course of the relationship in patients with MD treated conservatively.

PATIENTS
Twelve patients with MD treated conservatively for more than 1 year in a university hospital.

METHODS
Twenty ears of 12 patients with MD treated conservatively were evaluated. The presence or absence of vertigo, tinnitus and ear fullness was confirmed when magnetic resonance imaging (MRI) was performed. Using a 3 T MRI scanner, three-dimensional fluid-attenuated inversion recovery (3D-FLAIR) MRI was performed 2 or 3 times 24 hours after intra-tympanic gadolinium injection or 4 hours after intravenous gadolinium injection.

RESULTS
In the three ears in which the symptoms alleviated, EH was reduced in two ears, but EH was reduced in only one of 17 ears in which the symptoms did not alleviate. The Fisher exact test revealed that EH reduction occurred more frequently in ears with alleviation of the symptoms (p < 0.05).

Suga|Kenji|K| Kato|Masahiro|M| Yoshida|Tadao|T| Nishio|Naoki|N| Nakada|Takafumi|T| Sugiura|Saiko|S| Otake|Hironao|H| Kato|Ken|K| Teranishi|Masaaki|M| Sone|Michihiko|M| Naganawa|Shinji|S| Nakashima|Tsutomu|T|

vertigo
tinnitus
Ear fullness
magnetic resonance imaging


Food and meals in caring institutions - a small dive into research.

Abstract: Purpose - With the growing older population, the increasing interest in the elderly's eating habits and the meal situation go hand in hand and are challenges in many countries, including Norway. The purpose of this paper is to investigate, part of an ongoing project in Norway, address four categories of elderly people: healthy elderly (HE), old people with home care, elderly living in institutions, and critical ill elderly. Design/methodology/approach - The aim of this study was to investigate related articles concerning food and the elderly in the four identified categories, defining six different meal experience categories to disclose possible gaps in the research in terms of core product, room, personal service, company, atmosphere, and management control systems (MCS). Database searches, conducted through JSTOR and Web of Science, started with words in combination with "elderly and meal experiences" and were narrowed down to the most relevant papers with words from the six meal experience categories. Ultimately, 21 of 51 downloaded papers from international journals were reviewed. Findings - A comparison of the four elderly groups was made across the six different meal experience categories, which disclosed several gaps. Among the 21 papers, five focused on HE, 12 on older people living with home care, 16 on elderly living in institutions, and one on critical ill elderly. The specific under-researched gaps include room, company, atmosphere, and MCS. Research limitations/implications - Future research will need to investigate these groups more thoroughly, and the research should concentrate on the HE and critical ill in connection with the six meal experience aspects. Originality/value - The combination of meal experience aspects towards different elderly categories is an original perspective on the aim of the literature review.

Elderly
Meal experience
Gaps
Literature review


The interdependence between cardiovascular calcifications in different arterial beds and vascular risk factors in patients at high cardiovascular risk.

Abstract:
OBJECTIVE
The objective was to explore the interdependence between cardiovascular risk factors and cardiovascular calcifications on the cardiac valves and in multiple vascular beds in the chest and abdomen in a high-risk population.

METHODS
276 participants of the SMART study who received a CT scan of the chest and abdominal region within one year were evaluated for the presence of cardiovascular calcifications throughout the body. Cardiovascular calcifications were manually scored in the coronary arteries, the aorta, the supra aortic vessels, the infra aortic vessels, the aortic valve, the renal arteries and the splenic artery. The following clinical risk factors of cardiovascular disease were included in principal component analysis, body mass index, systolic blood pressure, glucose, total cholesterol and carotid intima media thickness (cIMT) as a marker of atherosclerosis.

RESULTS
Principal component analysis yielded three uncorrelated components. The first consisted of cardiovascular calcifications and cIMT (variance = 35.4%), the second contained BMI and glucose (variance = 11.1%), and the third component consisted of systolic blood pressure and cholesterol (variance = 9.0%). Combined these three components explained 56% of the total variance within the dataset. Strong associations were observed among vascular calcifications and cIMT, whereas the association between clinical risk factors and cardiovascular calcifications was weak.

CONCLUSION
The results suggest a single systemic nature of cardiovascular calcifications throughout the body that do not cluster with traditional cardiovascular risk factors.

Takx|Richard A P|RA|
Zanen|Pieter|P|
Leiner|Tim|T|
van der Graaf|Yolanda|Y|
de Jong|Pim A|PA|
|||

Cardiovascular calcification
Clinical risk factors
Principal component analysis
Computed tomography


Comprehensive Host Cell-Based Screening Assays for Identification of Anti-Virulence Drugs Targeting Pseudomonas aeruginosa and Salmonella Typhimurium.

Abstract: The prevalence of bacterial pathogens being resistant to antibiotic treatment is increasing worldwide, leading to a severe global health challenge. Simultaneously, the development and approval of new antibiotics stagnated in the past decades, leading to an urgent need for novel approaches to avoid the spread of untreatable bacterial infections in the future. We developed a highly comprehensive screening platform based on quantification of pathogen driven host-cell death to detect new anti-virulence drugs targeting Pseudomonas aeruginosa (Pa) and Salmonella enterica serovar Typhimurium (ST), both known for their emerging antibiotic resistance. By screening over 10,000 small molecules we could identify several substances showing promising effects on Pa and ST pathogenicity in our in vitro infection model. Importantly, we could detect compounds potently inhibiting bacteria induced killing of host cells and one novel comipound with impact on the function of the type 3 secretion system (T3SS) of ST. Thus, we provide proof of concept data of rapid and feasible medium- to high-throughput drug screening assays targeting virulence mechanisms of two major Gram-negative pathogens.

Pseudomonas aeruginosa
Salmonella Typhimurium
antibiotic resistance
type 3 secretion system
antibiotic drug screening
host-directed therapies
multidrug-resistant pathogens


Neonatal hyperthermia and thermal stress in low- and middle-income countries: a hidden cause of death in extremely low-birthweight neonates.

Abstract:
BACKGROUND
Over 70% of neonatal deaths in Nigeria occur within the first 7 days of life and, despite the millennium development goals, there has been no significant reduction of this figure.

OBJECTIVE
To investigate how rapid changes of temperature outside the physiologically allowable range in extremely low-birthweight infants are associated with increased mortality.

METHODS
Ninety-eight neonatal cases in three Nigerian tertiary-care hospitals were retrospectively recruited; on the basis of birthweight  < 1500 g, this number was reduced to 41 for a two-stage analysis. In the first stage, 34 cases recruited over 24 months were analysed. In the second stage, seven cases recruited over 6 months were analysed; these were neonates managed with a new temperature control technique (the 'handy approach') to enable comparison of outcomes. The mean (SD) birthweight of the infants analysed was 991 g (251), and 28 of them were of extremely low-birthweight (ELBW) [mean (SD) 846 g (128)]. A lifetime temperature plot with a clearly visible reference zone was developed, from which all thermal stresses and their duration associated with mortality were identified and defined on the basis of their characteristics. Methods of quantifying the magnitude and duration of these thermal stresses were devised to enable definition of critical values. This was then applied to calculate a measure of the various thermal stresses which may have contributed to neonatal death.

RESULTS
Hypothermic events were very common in all the infants in the study period, but were not significantly associated with mortality. However, hyperthermic events occurred in 35% of the infants and were more likely to be associated with mortality. Most neonates with prolonged hypothermia culminating in rapid hyperthermia survived. However, all ELBW neonates who experienced prolonged hyperthermia culminating in rapid hypothermia died within 8 hours of the event. There was greater ELBW survival (6/6) in the second stage using the 'handy approach' than in the first stage (2/22).

CONCLUSION
Hyperthermia is a high-risk event in ELBW infants and methods of cooling a high and prolonged temperature must be reviewed.

Amadi|Hippolite O|HO|
Olateju|Eyinade K|EK|
Alabi|Peter|P|
Kawuwa|Mohammed B|MB|
Ibadin|Mike O|MO|
Osibogun|Akin O|AO|

D052577:Infant, Extremely Low Birth Weight

Neonatal hypothermia,
Neonatal incubator,
Neonatal mortality,
Tropical hyperthermia