Effects of Non-Starch Polysaccharides on Inflammatory Bowel Disease.

Abstract: The incidence of inflammatory bowel disease (IBD) has increased considerably over the past few decades. In the present review, we discuss several disadvantages existing in the treatment of IBD and current understandings of the structures, sources, and natures of various kinds of non-starch polysaccharides (NSPs). Available evidences for the use of different sources of NSPs in IBD treatment both in vitro and in vivo are analyzed, including glucan from oat bran, mushroom, seaweed, pectin, gum, prebiotics, etc. Their potential mechanisms, especially their related molecular mechanism of protective action in the treatment and prevention of IBD, are also summarized, covering the anti-inflammation, immune-stimulating, and gut microbiota-modulating activities, as well as short-chain fatty acids (SCFAs) production, anti-oxidative stress accompanied with inflammation, the promotion of gastric epithelial cell proliferation and tissue healing, and the reduction of the absorption of toxins of NSPs, thus ameliorating the symptoms and reducing the reoccurrence rate of IBD. In summary, NSPs exhibit the potential to be promising agents for an adjuvant therapy and for the prevention of IBD. Further investigating of the crosstalk between immune cells, epithelial cells, and gut microorganisms in addition to evaluating the effects of different kinds and different molecular weights of NSPs will lead to well-designed clinical intervention trials and eventually improve the treatment and prevention of IBD.

inflammatory bowel disease (IBD)
non-starch polysaccharide (NSP)
mechanism
SCFAs
intervention
gut microbiota
immune system
pro-inflammatory cytokines


PFO: Button me up, but wait … Comprehensive evaluation of the patient.

Abstract: Patent foramen ovale (PFO) is a slit or tunnel-like communication in the atrial septum occurring in approximately 25% of the population. A wide number of pathological conditions have been linked to its presence, most notably, cryptogenic stroke (CS) and migraine. However, in the setting of a neurological event, it is not often clear whether the PFO is pathogenically related to the index event or an incidental finding. Therefore, a detailed analysis of several clues is needed for understanding PFO's clinical significance, with a frequent case-by-case decision about destination therapy. Indeed, the controversy about PFO's pathogenicity prompted a paradigm shift of research interest from medical therapy with antiplatelets or anticoagulants to percutaneous transcatheter closure, in secondary prevention. Observational data and meta-analysis of observational studies had previously suggested that PFO closure with a device was a safe procedure with a low recurrence rate of stroke. To date, however, recent randomized controlled trials have not shown the superiority of PFO closure over medical therapy. Thus, the optimal strategy for secondary prevention of paradoxical embolism in patients with a PFO remains unclear. Moreover, the latest guidelines for the prevention on stroke restricted indications for PFO closure to patients with deep vein thrombosis and high-risk of its recurrence. Given these recent data, in the present review, we critically discuss current treatment options, pointing out the role of a comprehensive patient evaluation in overcoming PFO closure restrictions and planning the best management for each patient.

Pizzino|Fausto|F|
Khandheria|Bijoy|B|
Carerj|Scipione|S|
Oreto|Giuseppe|G|
Cusmà-Piccione|Maurizio|M|
Todaro|Maria Chiara|MC|
Oreto|Lilia|L|
Vizzari|Giampiero|G|
Di Bella|Gianluca|G|
Zito|Concetta|C|

Patent foramen ovale
Cryptogenic stroke
Transcatheter closure
Device


Exploring the Onset of a Male-Biased Interpretation of Masculine Generics Among French Speaking Kindergarten Children.

Abstract: In French, and other gender marked languages, there are two ways to interpret a grammatical masculine form when used to refer to social roles or occupations [e.g., les magiciens (the magicians  )]. It can refer to a group composed of only men (specific use of the masculine form), or one composed of both women and men (generic use). Studies of adults revealed that the rule that masculine forms can be interpreted as inclusive of either gender is not readily applied. To gain a better understanding of the processes shaping this phenomenon, we present a follow-up study (N = 52) to Lévy et al. (2016) to explore how French-speaking kindergarten children (3-5 years of age) resolve the semantic ambiguity of the grammatical masculine form when presented with role or occupation nouns. In a paradigm where participants' gazes were monitored, children were presented with pictures of a pair of two boys and a pair of one girl and one boy and were prompted to Look at the [role noun. First, the results suggest a stereotype effect in that children more strongly directed their gaze toward the boy-boy picture for stereotypical male role nouns, but toward the girl-boy picture for stereotypical female role nouns. Second, in the non-stereotypical/neutral condition we did not find an indication of any own-sex preference (as in Lévy et al., 2016), but of an influence of the role nouns' grammatical gender, in that children more strongly directed their gaze toward boy-boy pictures than toward girl-boy pictures. We suggest that a specific interpretation of masculine forms might already start to emerge between 3 and 5 years of age, while gender stereotypes are still activated.

Gygax|Pascal Mark|PM|
Schoenhals|Lucie|L|
Lévy|Arik|A|
Luethold|Patrick|P|
Gabriel|Ute|U|

role noun
grammatical gender
gender representation
generic masculine
kindergarten learning


Blood pressure and lipid target adherence in Korean patients receiving angiotensin II receptor blockers/statin regimens.

Abstract:
OBJECTIVES
Hypertension and dyslipidemia are important cardiovascular risk factors. Simultaneously controlling blood pressure (BP) and lipid levels is effective in preventing cardiovascular events and premature death. This study investigated the association between adherence to angiotensin II receptor blocker (ARB)/statin regimens and BP or low density lipoprotein-cholesterol (LDL-C) target attainment in Korean patients with concomitant hypertension and dyslipidemia.

METHODS
In this retrospective, multicenter study, we collected case report forms (CRFs) of hypertensive patients with concomitant dyslipidemia who were prescribed an ARB/statin regimen between 1 April 2014 and 31 March 2015 from 51 outpatient clinics. A total of 672 and 609 patients were eventually included for statistical analyses of BP and LDL-C, respectively. Adherence was measured by medication possession ratio (MPR) for 6 months following the index date.

RESULTS
The overall rates of attaining BP and LDL-C targets were 75.6% and 81.1%, respectively. The mean value of MPR for patients attaining target BP or LDL-C was significantly higher than that for those not attaining target BP or LDL-C. After adjustment for all covariates, increases in the quartiles of MPR were significantly associated with an increased probability of attaining target BP or LDL-C in all models (all p-trend <0.05). Attaining of BP control was significantly higher in quartiles 3 and 4 of MPR (MPR >0.95) than the lowest MPR (quartile 1), whereas attaining LDL-C target was associated with quartile 4 of MPR (MPR >0.97).

CONCLUSION
We identified a strong correlation between medication adherence and BP or LDL-C target achievement in Korean patients with concomitant hypertension and dyslipidemia. The adherence for reaching targets could be different between BP and LDL-C levels.

Kim|Hyun-Jin|HJ| Kim|Eugene|E| Min|Kyoung-Bok|KB| Min|Jin-Young|JY|

Blood pressure
lipids
cardiovascular disease
compliance
efficacy


De novo characterization of transcriptome and gene expression dynamics in epidermis during the larval-pupal metamorphosis of common cutworm.

Abstract: Larval cuticle is degraded and replaced by the pupal counterpart during larval-pupal metamorphosis in the holometabolous insects. In addition to the extrinsic transformation, the epidermis goes through significant changes at molecular levels. To elucidate the intrinsic mechanism of epidermal metamorphosis, the dynamics of chitin content in the cuticle was examined in an important agricultural lepidopteran, the common cutworm, and the transcriptome was analyzed using Illumina sequencing technology. Gene expression profiles during the metamorphosis were further studied by both the digital gene expression (DGE) system and real-time quantitative PCR. The results showed that the chitin content decreased in prepupae and then increased in pupae. A total of 58 million sequencing reads were obtained and assembled into 70,346 unigenes. Over 9000 unigenes were identified to express differentially during the transformation process. As compared with the 6th instar feeding larvae, the most significant changes took place in the proteasome and metabolic pathways in prepupae and pupae, respectively. The cytochrome P450s, VHDLs, chitinase, serine protease and genes involved in sex pheromone biosynthesis changed their mRNA levels remarkably. Three chitinolytic enzymes (chitinase, β-N-acetylglucosaminidase and chitin deacetylase) showed distinct mRNA expression patterns, the former two enzymes revealed the highest expression in prepupae, however the latter one showed its climax mRNA level in pupae. The gene expression patterns suggest that chitinase and β-N-acetylglucosaminidase may be responsible for the degradation of larval cuticles, whereas chitin deacetylase may help to degrade the pupal counterparts. Gene expression dynamics also implied that the chitin of pupal cuticle might be formed by recycling of the degraded chitin of larval cuticle rather than through de novo synthesis. The 20E-induced nuclear receptors seem to be important factors regulating chitin metabolic enzymes during the cuticle remodeling. Our data provide a comprehensive resource for exploring the molecular mechanism of epidermal metamorphosis in insects.

Gu|Jun|J| Huang|Li-Xia|LX| Gong|Yan-Jun|YJ| Zheng|Si-Chun|SC| Liu|Lin|L| Huang|Li-Hua|LH| Feng|Qi-Li|QL|

D018507:Gene Expression Regulation, Developmental

P P P P P P P P P P P P U U U U U U U U U U U U U U U U M U U U U U U U U U U U U M U U U U U U U M M R P M M M U M U U M M U M U U P U M M M U U U


Spillover improved survival in non-invited patients of the colorectal cancer screening programme.

Abstract: Objectives In colorectal cancer screening, randomized clinical trials have shown a 16% mean reduction in colorectal cancer mortality, but the Finnish randomized health services study showed no effect. We quantified spillover (the total indirect effect caused by the programme on the non-invited) and corrected the effectiveness estimate of the Finnish programme. Methods We retrieved from the Finnish Cancer Registry data on all non-invited colorectal cancer patients diagnosed in 1999-2013 in municipalities that adopted screening ( n = 18,948). Patients were stratified by three 5-year diagnostic periods and two calendar periods of programme adoption in the municipality of residence. Follow-up ended on 31 December 2013. We measured the spillover effect in patient survival, based on differences of adjusted estimates of the colorectal cancer-related hazard of death between pairs of consecutive diagnostic periods. Results The spillover effect was estimated as 9 percentage points (95% confidence interval: -1 to 19 percentage points). It was 13 percentage points in men (-1 to 26 percentage points) and 5 percentage points in women (-9 to 20 percentage points). The corrected effect estimate of implementing screening in Finland was 5 percentage points. Conclusions The corrected Finnish effectiveness estimate was consistent with estimates from randomized trials. Indirect effects (spillover) bias the invitee-control contrast. In this case, spillover was an inherent benefit of the Finnish programme.

Miettinen|Joonas|J| Malila|Nea|N| Hakama|Matti|M| Pitkäniemi|Janne|J|

D016032:Randomized Controlled Trials as Topic

Spillover
survival
colorectal cancer
screening
halo effect


Impact of different types of stoppers on sensorial and phenolic characteristics evolution during a bottle storage time of a white wine from Chardonnay grape variety.

Abstract: The objective of this work was to study the correlation between the variation of phenolic compounds and sensory characteristics in white wine during bottle storage and to explore the compounds that affected sensory evolution. Chardonnay (Vitis vinifera L. cv.) dry white wines were bottled under six types of stoppers and stored for 18 months. The composition of phenolic compounds was analyzed, and the sensory attributes of these wines were evaluated by professional panel. Multivariate statistical analysis demonstrated that bottle aging period exhibited a more important effect on phenolic compound evolution than stopper type. Most of the phenolic compounds disappeared after 18 months of bottle storage, whereas the wine sensory attributes were significantly improved after 15-month of bottle aging. No strong correlation existed between the phenolic variation and the dissolved oxygen content. Wine color characteristics developed towards better quality accompanying with the reduction of detectable hydroxycinnamic acid derivatives and flavan-3-ols, while the wine mouth-feel was related mainly to gallic acid and ferulic acid ester. This work provided some references for wine producers to select appropriate storage duration for bottled white wine.

Xing|Ran-Ran|RR| Liu|Di|D| Li|Zheng|Z| Tian|Yuan|Y| Zhang|Xiao-Xu|XX| Li|Jing-Ming|JM| Pan|Qiu-Hong|QH|

White wine
Phenolic compounds
Bottle aging
Multivariate analysis
Sensory analysis


Translational Control of the Myogenic Program in Developing, Regenerating, and Diseased Skeletal Muscle.

Abstract: Translational control of genes that code for protein allows a cell to rapidly respond to changes in its environment, in part because translational control of gene expression does not depend on upstream events required to produce an mRNA molecule. The importance of translational control has been highlighted by studies concerning muscle development, regeneration, and disease. Translational control of specific mRNAs is achieved by microRNAs and RNA-binding proteins, which are particularly relevant to developmental myogenesis, where they ensure the stepwise differentiation of multipotent progenitors to committed myogenic progenitors that ultimately fuse into slow- or fast-type myofibers that make up skeletal muscle. The importance of translational control is also illustrated in muscle disease, where deregulated microRNA expression accelerates or delays progression of disease. Skeletal muscle is also unique for its remarkable capacity to regenerate after injury, which requires the activity of quiescent muscle stem cells, named satellite cells for their position underneath the basal lamina of the myofiber. Mitotically quiescent satellite cells are primed to activate the cell cycle and myogenic program, a unique feature that requires specific regulation of mRNA translation converging with pathways that regulate global protein synthesis. Emerging concepts in translational control of gene expression have shed light on multiple layers of control over the myogenic program. In parallel, the development and regeneration of skeletal muscle represents a unique, relevant, and highly defined context within which new concepts in translational control of gene expression should emerge.

Translational control
MicroRNA
RNA-binding proteins
Myogenesis
Muscular dystrophy
Skeletal muscle regeneration
eIF2α phosphorylation


Endoplasmic Reticulum Stress and Unfolded Protein Response Pathways: Potential for Treating Age-related Retinal Degeneration.

Abstract: Accumulation of misfolded proteins in the endoplasmic reticulum (ER) and their aggregation impair normal cellular function and can be toxic, leading to cell death. Prolonged expression of misfolded proteins triggers ER stress, which initiates a cascade of reactions called the unfolded protein response (UPR). Protein misfolding is the basis for a variety of disorders known as ER storage or conformational diseases. There are an increasing number of eye disorders associated with misfolded proteins and pathologic ER responses, including retinitis pigmentosa (RP). Herein we review the basic cellular and molecular biology of UPR with focus on pathways that could be potential targets for treating retinal degenerative diseases.

Unfolded Protein Response
Age-related Retinal Degeneration
Misfolded Protein
ER Stress
Retinal Degenerative Diseases
Protein Aggregation


Dynamic sleep MRI in obstructive sleep apnea: a systematic review and meta-analysis.

Abstract:
PURPOSE
The objective of this study is to systematically review the international literature for dynamic sleep magnetic resonance imaging (MRI) as a diagnostic tool in obstructive sleep apnea (OSA), to perform meta-analysis on the quantitative data from the review, and to discuss its implications in future research and potential clinical applications.

STUDY DESIGN
A comprehensive review of the literature was performed, followed by a detailed analysis of the relevant data that has been published on the topic.

METHODS
Clinical key, Uptodate, Ovid, Ebscohost, Pubmed/MEDLINE, Scopus, Dynamed, Web of Science and The Cochrane Library were systematically searched. Once the search was completed, dynamic sleep MRI data were analyzed.

RESULTS
Nineteen articles reported on 410 OSA patients and 79 controls that underwent dynamic sleep MRI and were included in this review. For meta-analysis of dynamic sleep MRI data, eight articles presented relevant data on 160 OSA patients. Obstruction was reported as follows: retropalatal (RP) 98%, retroglossal (RG) 41% and hypopharyngeal (HP) in 5%. Lateral pharyngeal wall (LPW) collapse was found in 35/73 (48%) patients. The combinations of RP + RG were observed in 24% and RP + RG + LPW in 16%. If sedation was used, 98% of study participants fell asleep compared to 66% of unsedated participants.

CONCLUSIONS
Dynamic sleep MRI has demonstrated that nearly all patients have retropalatal obstruction, retroglossal obstruction is common and hypopharyngeal obstruction is rare. Nearly all patients (98%) who are sedated are able to fall asleep during the MRI. There is significant heterogeneity in the literature and standardization is needed.

Sleep
Sleep MRI
Obstructive sleep apnea
Cine MRI
Dynamic MRI


Prediction and scale in savanna ecosystems.

Abstract: Contents Summary 52 I. Introduction 52 II. Determinants of savanna vegetation structure 53 III. Are trees in savannas really more heterogeneous? 53 IV. Are trees in savannas a 'slow' variable? 54 V. Are trees in savannas spatially patterned? 55 VI. Conclusions 55 Acknowledgements 55 References 56 SUMMARY: Savannas are highly variable systems, and predicting variation, especially in the tree layer, represents a major unresolved challenge for forecasting biosphere responses to global change. Prediction to date has focused on disentangling interactions between resource limitation and chronic disturbances to identify what determines local savanna vegetation heterogeneity. By focusing at too fine a scale, this approach overlooks: sample size limitation arising from sparse tree distributions; stochasticity in demographic and environmental processes that is preserved as heterogeneity among tree populations with slow dynamics; and spatial self-organization. Renewed focus on large (1-50 ha) permanent plots and on spatial patterns of tree-layer variability at even larger landscape spatial scales (≥1000s of ha) promises to resolve these limitations, consistent with the goal of predicting large-scale biosphere responses to global change.

scale
savanna
heterogeneity
self-organization
demographic stochasticity
environmental stochasticity
tree cover


Pilot Study of a Single Dose of Orally Administered Tapentadol Suspension in Hispaniolan Amazon Parrots (Amazona ventralis).

Abstract: Tapentadol is an analgesic agent that acts as both a µ-opioid receptor agonist and a norepinephrine reuptake inhibitor. It is a common therapeutic agent in human medicine for management of acute and chronic pain, and it is currently being investigated for use in veterinary medicine. Tapentadol was evaluated in Hispaniolan Amazon parrots (Amazona ventralis) because there is only 1 other oral opioid-like analgesic agent, tramadol, which has been evaluated in an avian species. The effectiveness of tramadol after administration to a patient involves a complex physiologic metabolism and has been found to have variable pharmacokinetics between species. Because of the lack of active metabolites from tapentadol, less interspecific variation was expected. Seven Hispaniolan Amazon parrots were used to evaluate the pharmacokinetics of tapentadol after a single 30 mg/kg PO administration of a compounded 5 mg/mL tapentadol suspension. Blood samples were collected before (time 0) and 0.25, 0.5, 0.75, 1, 1.5, 3, and 6 hours after administration, following a balanced, incomplete-block design. Plasma tapentadol concentrations were measured by high-pressure liquid chromatography with mass spectrometry. Results revealed detectable plasma concentrations in only 2 of 7 birds (29%), and the bird with the highest plasma levels had a peak concentration (Cmax) of 143 ng/mL and a half-life (T 1/2) of 24.8 minutes. The variable plasma concentrations and short half-life of this drug in Hispaniolan Amazon parrots suggests that this drug would be of limited clinical use in this species; however, it is possible that this drug will be more bioavailable in other avian species.

Duvall|Abigail|A|
Tully|Thomas N|TN|
Carpenter|James W|JW|
KuKanich|Butch|B|
Beaufrère|Hugues|H|
Magnin|Geraldine C|GC|

tapentadol
Hispaniolan Amazon parrot
Amazona ventralis
avian
pharmacokinetic
analgesia


A student centric method for calculation of fatty acid energetics: Integrated formula and web tool.

Abstract: Mitochondrial beta-oxidation is one of the most common modes of fatty acids' oxidation in most organisms, particularly mammals. Biochemistry undergraduate curriculum often contains the description of the process, with emphasis on ATP calculations for various types of fatty acids. During our decade long teaching experience in biochemistry, we observed the difficulty faced by students in calculating energetics of several fatty acids beyond palmitic acid. We developed a canonical formula by mathematical transformations and logical derivation to aid the calculation in a much simpler manner to ease both teaching and learning experience. ATP yield of even-numbered fatty acids may be calculated using a formula [(7C - 6 - 1.5 D) - 2(D-2)], andadenosine triphosphate (ATP) yield for odd-numbered fatty acids can be calculated using [(7C - 19 - 1.5 D) - 2(D-2)], where C is the number of carbon atoms in fatty acids, D is the number of double bonds. The unbold part of the formulae is limited to polyunsaturated fatty acids. Moreover, we integrated these formulae into an HTML based web-interface for handily calculations, which is likely to augment fatty acids oxidation learning-teaching processes easier. This tool has been recently tested in our classroom programs on biochemistry and received an excellent feedback from the learners. Also, the mathematical formula is ready for being incorporated into standard biochemistry textbooks. The webtool as an opensource biochemical calculator can be effectively used in classrooms by both instructors and students while solving comprehension based questions on lipid metabolism.

integrated formula
beta-oxidation
ATP calculator
fatty acid oxidation
lipid energetics


Application of a Lithium-ion Selective Metallacrown to Extraction-Spectrophotometric Determination of Lithium in Saline Water.

Abstract: The solvent-extraction behavior of Li+ and Na+ with a Li+ selective metallacrown, [{Ru(η6-3,5-dimethylanisole)(2,3-pyridinediolate)}3], was investigated in the presence of organic dye anions, 3',3″,5',5″-tetrabromophenolphthalein ethyl ester ([TBPE]-), 2,6-dichloroindophenolate, and picrate ([pic]-). Each alkali metal ion was extracted as a 1:1:1 ternary complex of the metal ion, metallacrown, and anion. The Li+/Na+ extraction selectivity is anion dependent and highest with [pic]-. Therefore, we devised an extraction-spectrophotometric determination method for Li+ in saline water based on the extraction of Li+ using the metallacrown and [pic]- for high selectivity and subsequent replacement of [pic]- in the extracted species with [TBPE]- for high sensitivity. When applying this to artificial seawater samples containing known concentrations of Li+, a linear relationship was observed between the absorbance at 571 nm of the organic phase and the Li+ concentration in the samples. By this method, the determination of Li+ at the sub-ppm level in natural seawater is possible.


Prognostic value of the Fas/Fas ligand system in breast cancer.

Abstract: Fas and its ligand (FasL) are known to play a crucial role in the genetically controlled mechanism of cell death, and their deregulation in cancer cells is involved in the immune escape of the tumor. The aim of this review is to analyze the current knowledge on the prognostic value of Fas/FasL in breast cancer patients. Both the results of other authors and our own experiences indicate that the lack of Fas ligand, and particularly Fas, is related to a significantly worse prognosis. It probably results from the resistance of Fas-deficient breast tumors to the mechanisms of apoptosis. On the other hand, some results suggest that the Fas/FasL-dependent mechanisms of tumor spread may be different for various target tissues. The expression of the Fas/Fas-ligand system has potential prognostic application in view of current knowledge, and consequently should be considered as an additional prognostic factor in breast cancer patients.


The bivalve Thyasira cf. gouldi hosts chemoautotrophic symbiont populations with strain level diversity.

Abstract: Invertebrates from various marine habitats form nutritional symbioses with chemosynthetic bacteria. In chemosynthetic symbioses, both the mode of symbiont transmission and the site of bacterial housing can affect the composition of the symbiont population. Vertically transmitted symbionts, as well as those hosted intracellularly, are more likely to form clonal populations within their host. Conversely, symbiont populations that are environmentally acquired and extracellular may be more likely to be heterogeneous/mixed within host individuals, as observed in some mytilid bivalves. The symbionts of thyasirid bivalves are also extracellular, but limited 16S rRNA sequencing data suggest that thyasirid individuals contain uniform symbiont populations. In a recent study, Thyasira cf. gouldi individuals from Bonne Bay, Newfoundland, Canada were found to host one of three 16S rRNA phylotypes of sulfur-oxidizing gammaproteobacteria, suggesting environmental acquisition of symbionts and some degree of site-specificity. Here, we use Sanger sequencing of both 16S RNA and the more variable ribulose-1,5-bisphosphate carboxylase (RuBisCO) PCR products to further examine Thyasira cf. gouldi symbiont diversity at the scale of host individuals, as well as to elucidate any temporal or spatial patterns in symbiont diversity within Bonne Bay, and relationships with host OTU or size. We obtained symbiont 16S rRNA and RuBisCO Form II sequences from 54 and 50 host individuals, respectively, during nine sampling trips to three locations over four years. Analyses uncovered the same three closely related 16S rRNA phylotypes obtained previously, as well as three divergent RuBisCO phylotypes; these were found in various pair combinations within host individuals, suggesting incidents of horizontal gene transfer during symbiont evolution. While we found no temporal patterns in phylotype distribution or relationships with host OTU or size, some spatial effects were noted, with some phylotypes only found within particular sampling sites. The sequencing also revealed symbiont populations within individual hosts that appeared to be a mixture of different phylotypes, based on multiple base callings at divergent sites. This work provides further evidence that Thyasira cf. gouldi acquires its symbionts from the environment, and supports the theory that hosts can harbour symbiont populations consisting of multiple, closely related bacterial phylotypes.

McCuaig|Bonita|B|
Liboiron|France|F|
Dufour|Suzanne C|SC|

16S rRNA
Rubisco
Chemosymbiosis
Phylogeny
Thyasiridae


Fabrication of a Microfluidic Cell Culture Device Using Photolithographic and Soft Lithographic Techniques.

Abstract: Photolithography and soft lithography are two common methods for fabrication of microfluidic cell culture devices. Well-defined microstructures are created by exposing a photoresist to UV-light under a photolithographic mask in which the intended patterns are transparent. The subsequent cross-linking of UV-exposed photoresist generates a reusable master that serves as a template for an elastomer, commonly polydimethylsiloxane (PDMS), that reciprocally recaptures the structures of the master in an optically clear and oxygen-permeable rubber-like material. Connections to the cell culture-containing channels of the device for perfusion of culture medium can be established by inserting tubing through the elastomer. In this protocol, the basic steps for making a standard microfluidic device for cell-based assays from photolithography and soft lithography techniques are outlined.

Microfluidics
Photolithography
Soft lithography
PDMS


Pharmaceutical care of adolescents with diabetes mellitus type 1: the DIADEMA study, a randomized controlled trial.

Abstract:
BACKGROUND
Physiological and psychological changes during puberty and a low adherence to complex treatment regimens often result in poor glycemic control in adolescents with type 1 diabetes mellitus (T1DM). The benefit of pharmaceutical care in adults with diabetes mellitus type 2 has been explored; however, evidence in adolescents with T1DM is scarce.

OBJECTIVE
To evaluate the impact of pharmaceutical care in adolescents with T1DM provided by pharmacists, in collaboration with physicians and diabetes educators on important clinical outcomes (e.g., HbA1c and severe hypoglycemia)

SETTING
At the outpatient Helios Paediatric Clinic and at the 12 regular community pharmacies of the study patients with 14 pharmacists in the Krefeld area, Germany, and at the University Pediatric Clinic with one clinical pharmacist on-site in Sarajevo, Bosnia-Herzegovina.

METHODS
A randomized, controlled, prospective, multicenter study in 68 adolescents with T1DM. The intervention group received monthly structured pharmaceutical care visits delivered by pharmacists plus supplementary visits and phone calls on an as needed basis, for 6 months. The control group received usual diabetic care. Data were collected at baseline and after 3 and 6 months.

MAIN OUTCOME MEASURES
The between-group difference in the change from baseline in glycosylated hemoglobin (HbA1c) and the number of severe hypoglycemic events in both groups.

RESULTS
The improvement from baseline in HbA1c was significantly greater in the intervention group than in the control group after 6 months (change from baseline -0.54 vs. +0.32%, p = 0.0075), even after adjustment for country-specific variables (p = 0.0078). However, the effect was more pronounced after only 3 months (-1.09 vs. +0.23%, p = 0.00002). There was no significant between-group difference in the number of severe hypoglycemia events. (p = 0.1276).

CONCLUSION
This study suggests that multidisciplinary PhC may add value in the management of T1DM in adolescents with inadequate glycemic control. However, the optimal methods on how to achieve sustained, long-term improvements in this challenging population require further study.

Obarcanin|Emina|E| Krüger|Manfred|M| Müller|Petra|P| Nemitz|Verena|V| Schwender|Holger|H| Hasanbegovic|Snijezana|S| Kalajdzisalihovic|Sena|S| Läer|Stephanie|S|

Pharmaceutical care
Adolescents
Glycemic control
Type 1 diabetes mellitus
Pharmacists
Germany
Bosnia-Herzegovina


Multiparametric Quantitative Brain MRI in Neurological and Hepatic Forms of Wilson's Disease.

Abstract:
BACKGROUND
In Wilson's disease (WD), demyelination, rarefaction, gliosis, and iron accumulation in the deep gray matter cause opposing effects on T2 -weighted MR signal. However, the degree and interplay of these changes in chronically treated WD patients has not been quantitatively studied.

PURPOSE
To compare differences in brain multiparametric mapping between controls and chronically treated WD patients with neurological (neuro-WD) and hepatic (hep-WD) forms to infer the nature of residual WD neuropathology.

STUDY TYPE
Cross-sectional.

POPULATION/SUBJECTS
Thirty-eight WD patients (28 neuro-WD, 10 hep-WD); 26 healthy controls.

FIELD STRENGTH/SEQUENCE
3.0T: susceptibility, T2 *, T2 , T1 relaxometry; 1.5T: T2 , T1 relaxometry.

ASSESSMENT
The following 3D regions of interest (ROIs) were manually segmented: globus pallidus, putamen, caudate nucleus, and thalamus. Mean bulk magnetic susceptibility, T2 *, T2 , and T1 relaxation times were calculated for each ROI.

STATISTICAL TESTS
The effect of group (neuro-WD, hep-WD, controls) and age was assessed using a generalized least squares model with different variance for each ROI and quantitative parameter. A general linear hypothesis test with Tukey adjustment was used for post-hoc between-group analysis; P < 0.05 was considered significant.

RESULTS
Susceptibility values were higher in all ROIs in neuro-WD compared to controls and hep-WD (P < 0.001). In basal ganglia, lower T2 and T2 * were found in neuro-WD compared to controls (P < 0.01) and hep-WD (P < 0.05) at 3.0T. Much smaller intergroup differences for T2 in basal ganglia were observed at 1.5T compared to 3.0T. In the thalamus, increased susceptibility in neuro-WD was accompanied by increased T1 at both field strengths (P < 0.001 to both groups), and an increased T2 at 1.5T only (P < 0.001 to both groups).

DATA CONCLUSION
We observed significant residual brain MRI abnormalities in neuro-WD but not in hep-WD patients on chronic anticopper treatment. Patterns of changes were suggestive of iron accumulation in the basal ganglia and demyelination in the thalamus; 3.0T was more sensitive for detection of the former and 1.5T of the latter abnormality.

LEVEL OF EVIDENCE
2 Technical Efficacy Stage: 3 J. Magn. Reson. Imaging 2020;51:1829-1835.

Dezortova|Monika|M|
Lescinskij|Artem|A|
Dusek|Petr|P|0000-0003-4877-9642
Herynek|Vit|V|
Acosta-Cabronero|Julio|J|
Bruha|Radan|R|
Jiru|Filip|F|
Robinson|Simon D|SD|
Hajek|Milan|M|

D001921:Brain
D001931:Brain Mapping
D003430:Cross-Sectional Studies
D006527:Hepatolenticular Degeneration
D006801:Humans
D008279:Magnetic Resonance Imaging

brain
Wilson's disease
relaxation time
magnetic resonance imaging
quantitative susceptibility mapping


Data on optimization of microprojectile bombardment parameters in development of salinity tolerant transgenic lines.

Abstract: This data deals with the optimization of microprojectile bombardment particles for efficient genetic transformation in an indica rice involving AmSOD gene for development of salinity tolerant transgenic lines [1]. In this study, various parameters such as effect of genotypes, helium pressure, osmoticum, explants, flight distance, particle size, particle volume, vacuum, carrier DNA and stopping screen properties have been evaluated to determine their role in transformation of indica rice involving AmSOD gene for development of salinity tolerant Pusa Basmati 1 rice variety. To perform the transformation process, plasmid vector pCAMBIA 1305.2 was used, which harbours GUS Plus™ gene, intron from the castor bean catalase gene, pBR322 ori, kanamycin resistant gene and Xho I site. The transformants have been confirmed using slot blot, polymerase chain reaction and Southern hybridization techniques.

Sarangi|Susmita|S|
Mandal|Chiranjib|C|
Dutta|Sourav|S|
Mukherjee|Pranit|P|
Mondal|Raju|R|
Kumar|S P Jeevan|SPJ|
Choudhury|P Ray|PR|
Singh|Vijay Pratap|VP|
Tripathi|Durgesh Kumar|DK|
Mandal|Asit B|AB|

Microprojectile bombardment
AmSOD gene
Abiotic stress
Basmati rice


Machine learning adaptation of intraocular lens power calculation for a patient group.

Abstract:
BACKGROUND
To examine the effectiveness of the use of machine learning for adapting an intraocular lens (IOL) power calculation for a patient group.

METHODS
In this retrospective study, the clinical records of 1,611 eyes of 1,169 Japanese patients who received a single model of monofocal IOL (SN60WF, Alcon) at Miyata Eye Hospital were reviewed and analyzed. Using biometric metrics and postoperative refractions of 1211 eyes of 769 patients, constants of the SRK/T and Haigis formulas were optimized. The SRK/T formula was adapted using a support vector regressor. Prediction errors in the use of adapted formulas as well as the SRK/T, Haigis, Hill-RBF and Barrett Universal II formulas were evaluated with data from 395 eyes of 395 distinct patients. Mean prediction errors, median absolute errors, and percentages of eyes within ± 0.25 D, ± 0.50 D, and ± 1.00 D, and over + 0.50 D of errors were compared among formulas.

RESULTS
The mean prediction errors in the use of the SRT/K and adapted formulas were smaller than the use of other formulas (P < 0.001). In the absolute errors, the Hill-RBF and adapted methods were better than others. The performance of the Barrett Universal II was not better than the others for the patient group. There were the least eyes with hyperopic refractive errors (16.5%) in the use of the adapted formula.

CONCLUSIONS
Adapting IOL power calculations using machine learning technology with data from a particular patient group was effective and promising.

Machine learning
Adaptation
Intraocular lens power calculation
SRK/T formula
Patient ethnicity
Patient race
Region of patient


Activation of autophagy rescues amiodarone-induced apoptosis of lung epithelial cells and pulmonary toxicity in rats.

Abstract: Amiodarone, bi-iodinated benzofuran derivative, is one of the most frequently prescribed and efficacious antiarrhythmic drugs. Despite its low incidence, amiodarone-induced pulmonary toxicity is of great concern and the leading cause of discontinuation. Autophagy is an essential homeostatic process that mediates continuous recycling of intracellular materials when nutrients are scarce. It either leads to a survival advantage or initiates death processes in cells under stress. In the present study, we investigated the role of autophagy in amiodarone-induced pulmonary toxicity. Amiodarone treatment-induced autophagy in H460 human lung epithelial cells and BEAS-2B normal human bronchial epithelial cells was demonstrated by increased LC3-II conversion, Atg7 upregulation, and autophagosome formation. Autophagic flux, as determined by the lysosomal inhibitor bafilomycin A1, was also increased following amiodarone treatment. To determine the role of autophagy in amiodarone toxicity, amiodarone-induced cell death was evaluated in the presence of 3-methyladenine or by knocking down the autophagy-related genes Atg7. Inhibition of autophagy decreased cellular viability and significantly increased apoptosis. Intratracheal instillation of amiodarone in rats increased the number of inflammatory cells recovered from bronchoalveolar lavage fluid, and periodic acid-Schiff-positive staining in bronchiolar epithelial cells. However, induction of autophagy by rapamycin treatment inhibited amiodarone-induced pulmonary toxicity. In conclusion, amiodarone treatment induced autophagy, which is involved in protection against cell death and pulmonary toxicity.

Lee|Kang-Yo|KY| Oh|Sehee|S| Choi|You-Jin|YJ| Oh|Seon-Hee|SH| Yang|Young-Su|YS| Yang|Mi-Jin|MJ| Lee|Kyuhong|K| Lee|Byung-Hoon|BH|

autophagy
apoptosis
amiodarone
pulmonary toxicity.


Structural and Functional Analysis of Gly212 Mutants Reveals the Importance of Intersubunit Interactions in ASIC1a Channel Function.

Abstract: Acid-sensing ion channels (ASICs) act as pH sensors in neurons. ASICs contribute to pain sensation, learning, fear behavior and to neuronal death after ischemic stroke. Extracellular acidification induces a transient activation and subsequent desensitization of these Na+-selective channels. ASICs are trimeric channels made of identical or homologous subunits. We have previously shown that mutation of the highly conserved Gly212 residue of human ASIC1a to Asp affects the channel function. Gly212 is located in the proximity of a predicted Cl- binding site at a subunit interface. Here, we have measured the function of a series of Gly212 mutants. We show that substitution of Gly212 affects the ASIC1a pH dependence and current decay kinetics. Intriguingly, the mutations to the acidic residues Asp and Glu have opposing effects on the pH dependence and the current decay kinetics. Analysis of molecular dynamics simulation trajectories started with the coordinates of the closed conformation indicates that the immediate environment of residue 212 in G212E, which shifts the pH dependence to more alkaline values, adopts a conformation closer to the open state. The G212D and G212E mutants have a different pattern of intersubunit salt bridges, that, in the case of G212E, leads to an approaching of neighboring subunits. Based on the comparison of crystal structures, the conformational changes in this zone appear to be smaller during the open-desensitized transition. Nevertheless, MD simulations highlight differences between mutants, suggesting that the changed function upon substitution of residue 212 is due to differences in intra- and intersubunit interactions in its proximity.

Bignucolo|Olivier|O| Vullo|Sabrina|S| Ambrosio|Nicolas|N| Gautschi|Ivan|I| Kellenberger|Stephan|S|

ion channel
molecular dynamics
salt bridge
current kinetics
structure-function relationship
subunit interaction


Monitoring of mechanical errors and their dosimetric impact throughout the course of non-coplanar continuous volumetric-modulated arc therapy.

Abstract:
BACKGROUND
Volumetric-modulated Dynamic WaveArc therapy (VMDWAT) is a non-coplanar continuous volumetric modulated radiation therapy (VMAT) delivery technique. Here, we monitored mechanical errors and their impact on dose distributions in VMDWAT using logfiles throughout the course of treatment.

METHODS
Fifteen patients were enrolled (2 skull base tumor patients and 13 prostate cancer patients). VMDWAT plans were created for the enrolled patients. The prescribed dose for the skull base tumor was set as 54 Gy at 1.8 Gy per fraction, and that for the prostate cancer was set as 72 to 78 Gy at 2 Gy per fraction. We acquired logfiles to monitor mechanical errors and their impact on dose distribution in each fraction. The root mean square error (RMSE) in the multi-leaf collimator (MLC), gantry angle, O-ring angle and monitor unit (MU) were calculated using logfiles throughout the course of VMDWAT for each patient. The dosimetric impact of mechanical errors throughout the course of VMDWAT was verified using a logfile-based dose reconstruction method. Dosimetric errors between the reconstructed plans and the original plans were assessed.

RESULTS
A total of 517 datasets, including 55 datasets for the 2 skull base tumor patients and 462 datasets for the 13 prostate cancer patients, were acquired. The RMSE values were less than 0.1 mm, 0.2°, 0.1°, and 0.4 MU for MLC position, gantry angle, O-ring angle, and MU, respectively. For the skull base tumors, the absolute mean dosimetric errors and two standard deviations throughout the course of treatment were less than 1.4% and 1.1%, respectively. For prostate cancer, these absolute values were less than 0.3% and 0.5%, respectively. The largest dosimetric error of 2.5% was observed in a skull base tumor patient. The resultant dosimetric error in the accumulated daily delivered dose distribution, in the patient with the largest error, was up to 1.6% for all dose-volumetric parameters relative to the planned dose distribution.

CONCLUSIONS
MLC position, gantry rotation, O-ring rotation and MU were highly accurate and stable throughout the course of treatment. The daily dosimetric errors due to mechanical errors were small. VMDWAT provided high delivery accuracy and stability throughout the course of treatment.

TRIAL REGISTRATION
UMIN000023870 . Registered: 1 October 2016.

Hirashima|Hideaki|H| Nakamura|Mitsuhiro|M| Miyabe|Yuki|Y| Uto|Megumi|M| Nakamura|Kiyonao|K| Mizowaki|Takashi|T|

Volumetric-modulated dynamic WaveArc therapy (VMDWAT)


Evaluating vertical transmission of sexually transmitted infections to newborns.

Abstract:
INTRODUCTION
Sexually transmitted infections are among the most frequent infections affecting pregnant women. We assessed the transmission of hepatitis B virus, human immunodeficiency virus type 1 and Treponema pallidum to newborns from infected parturients.

METHODOLOGY
An observational, cross-sectional, analytical facility-based survey was conducted among 57 newborns in Irene Neto Maternity, Lubango city, Huíla province, Angola. Hepatitis B virus DNA molecular identification was done through nested PCR. Human immunodeficiency virus type 1 proviral DNA detection was carried out by two successive nested PCRs. Real-time PCR was performed to examine the presence of T. pallidum DNA. Amplicons from PCR positive samples were sequenced for identity search and genotype assignment.

RESULTS
Hepatitis B virus DNA genotype E was detected in 3/41 (7.3%) newborns from HBsAg (hepatitis B surface antigen) positive mothers. To analyse the association between mothers HBeAg (hepatitis B e antigen) positivity and hepatitis B virus vertical transmission to newborns, a Fisher's exact test was performed, showing a highly significant association (p = 0.006). Human immunodeficiency virus type 1 provirus or T. pallidum DNA was not detected in any newborn.

CONCLUSIONS
To prevent hepatitis B virus vertical transmission in Angola it is important to promote universal antenatal screening, expanding hepatitis B virus markers (viral load and/or HBeAg), risk-based infected mothers' antiviral therapy and newborn passive immunoprophylaxis.

Oliveira|Dinamene|D|
Piedade|João|J|
Castro|Rita|R|
Lopes|Ângela|Â|
Martins|Maria do Rosário|MDR|
Pereira|Filomena|F|

vertical transmission
newborns
Treponema pallidum
Angola
HBV
HIV-1


MiR-451a ameliorates alcoholic hepatitis via repressing HDAC8-mediated proinflammatory response.

Abstract: Alcoholic hepatitis (AH) is identified as an inflammatory syndrome with high morbidity and mortality as a result of severe hepatocellular dysfunction and liver injury. Accumulated studies indicated that miRNAs are involved in AH. The potential effect of miR-451a in AH mice was examined in the current study. A mice AH model was established and the miR-451a expression in AH mice compared with the sham group was tested by real-time polymerase chain reaction (qRT-PCR). AH mice were injected with pre-miR-451a lentivirus for miR-451a overexpression and histone deacetylase (HDAC8) lentivirus for HDAC8 overexpression in AH mice. The underlying mechanisms were explored by searching the potential target genes of miR-451a in miRanda database and then we confirmed this. We found that miR-451a expression was significantly decreased in AH mice compared with the sham group. Moreover, miR-451a overexpression alleviated alcohol-induced liver inflammation and injuries of AH mice. Additionally, further mechanism exploration disclosed that HDAC8 was a target of miR-451a. The protective effect of miR-451a on AH in AH mice was abolished by HDAC8 overexpression. In summary, miR-451a ameliorates AH via repressing HDAC8-mediated proinflammatory response.


Inpatient mortality after elective primary total hip and knee joint arthroplasty in Botswana.

Abstract:
PURPOSE
Total hip and knee joint arthroplasty (TJA) rank among the most successful orthopaedic operations. Several developing countries in Africa have started to perform these procedures that are routine in developed countries. The aims of this study were to measure the incidence and assess the determinants of in-hospital mortality after elective primary TJA in our unit and compare it with published data.

METHODS
This was a retrospective study of the first consecutive cohort of patients who underwent elective primary TJA in Princess Marina Hospital, Botswana between March 2009 and October 2015 (6.5 years).

RESULTS
346 elective joint replacements were performed comprising 153 total hip arthroplasties (THA) and 193 total knee arthroplasties (TKA); 36 % of the THA were in female patients and 82 % of TKA were in females. The mean age was 64.5 years (range 26-86). Three patients died giving an inpatient mortality rate of 0.86 %. These three mortalities represent 1.55 % (three out of 193) of all the TKA. There were no deaths after THA. The cause of mortality in two patients was an adverse cardiac event while the third mortality was due to pulmonary embolism.

CONCLUSION
The inpatient mortality rate of 0.86 % following TJA is higher than the reported rates in the developed countries but comparable with data from other developing countries. The inpatient mortality rate following TKA was higher than that following THA and cardiovascular events proved to be the main cause of death. We recommend formal cardiology assessment and close peri-operative monitoring of all patients with a history of cardiovascular disease undergoing TJA.

Lisenda|Laughter|L|0000-0003-1958-3640 Mokete|Lipalo|L| Mkubwa|Joseph|J| Lukhele|Mkhululi|M|

Inpatient mortality
Developing country
Hip and knee replacement


Cost-effectiveness of secukinumab compared to other biologics in the treatment of ankylosing spondylitis in Finland.

Abstract:
Aim
This study assesses the cost-effectiveness of secukinumab vs currently licensed biologics for the treatment of ankylosing spondylitis (AS) from the Finnish health care system perspective.

Methods
A semi-Markov model compared secukinumab with adalimumab, adalimumab biosimilar, certolizumab pegol, etanercept, etanercept biosimilar, golimumab, and infliximab in a biologic-naïve population over a lifetime horizon. The Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) was used to assess the treatment response. Efficacy inputs were obtained from the network meta-analysis, and other model inputs were obtained from the published literature and Finnish sources. Main study outcomes included quality-adjusted life years (QALYs) gained and incremental cost-effectiveness ratio in terms of cost per QALY gained. Robustness of results was confirmed by sensitivity analyses and alternative scenario analyses.

Results
Secukinumab achieved highest QALYs (13.1) at lowest expected lifetime cost (€279,872) vs other comparators in biologic-naïve AS patients in the base case analysis, thus it dominated other biologics. Golimumab had a second highest QALYs (12.9) at the total cost of €309,551. Results were sensitive to variation in BASDAI 50 response for secukinumab, baseline Bath Ankylosing Spondylitis Functional Index (BASFI) score across all drugs, change in BASDAI and BASFI scores, and discount rates as observed in the one-way sensitivity analyses. Secukinumab was either dominant or cost-effective treatment in different alternative scenarios.

Conclusion
Secukinumab presented itself to be the dominant (ie, less costly and more effective) treatment vs other comparators for the biologic-naïve patients with AS in Finland.

Purmonen|Timo|T| Puolakka|Kari|K| Mishra|Dinesh|D| Gunda|Praveen|P| Martikainen|Janne|J|

cost-effectiveness
secukinumab
Finland
IL-17
anti-TNF
economic evaluation
health economics
radiographic axial SpA


Differential diagnosis of adrenal mass using imaging modality: special emphasis on f-18 fluoro-2-deoxy-d-glucose positron emission tomography/computed tomography.

Abstract: Adrenal incidentalomas are adrenal masses serendipitously detected during an imaging study performed for reasons unrelated to suspicion of adrenal disease. The incidence of adrenal incidentalomas has increased because of the widespread use of various imaging modalities. In oncology patients with adrenal incidentalomas, the characterization of the adrenal masses is challenging because nearly 50% of incidental adrenal masses are metastatic lesions that need special medical attention. Although unenhanced computed tomography (CT) densitometry, chemical shift magnetic resonance imaging (MRI), delayed contrast-enhanced CT and CT histogram analysis have been used as sensitive and specific modalities for differentiating benign from malignant adrenal masses, F-18 fluoro-2-deoxy-D-glucose positron emission tomography (F-18 FDG PET)/CT is a highly accurate imaging modality compared to CT or MRI, especially when these two imaging modalities are combined. In addition, a semiquantitative analysis using standardized uptake value ratio further improves the diagnostic accuracy of F-18 FDG PET/CT in differentiating benign from malignant adrenal masses. Thus, F-18 FDG PET/CT is very helpful for determining the best therapeutic management, especially for assessing the need for surgery.

Integrated positron emission tomography-computed tomography


Echocardiographic assessment of right ventricular function in inferior wall myocardial infarction and angiographic correlation to proximal right coronary artery stenosis.

Abstract:
BACKGROUND
Presence of right ventricular (RV) infarction imposes a higher risk of adverse events in inferior wall myocardial infarction (IWMI). In this study, we attempted to correlate various indices of RV function assessed by echocardiography with presence of a proximal right coronary artery (RCA) stenosis in patients with first episode of acute IWMI.

METHODS
In a prospective study, patients with first episode of acute IWMI underwent echocardiographic assessment within 24 h of symptom onset and indices of RV function viz. RV fractional area change (RVFAC), tricuspid annular plane systolic excursion (TAPSE), myocardial performance index (MPI) and tissue Doppler velocities from RV free wall were measured. Patients who underwent coronary angiogram (CAG) within one month and they were classified into group 1 and group 2 based on the presence or absence, respectively, of a significant proximal RCA stenosis.

RESULTS
There were 90 patients with first episode of IWMI of which 67 patients underwent CAG. There was significant difference between group 1 (n = 26) and group 2 (n = 41) in TAPSE (13.5 ± 1.3 vs 21.3 ± 1.7, p < 0.001), MPI by tissue Doppler (0.87 ± 0.1 vs 0.55 ± 0.2, p < 0.001) and in tissue Doppler systolic velocity from RV free wall (S' 9.8 ± 1.1 vs 15.0 ± 1.5, p < 0.001). There was a good interobserver correlation for TAPSE, MPI by TDI, and S' velocity. TAPSE ≤ 16 (sensitivity 93%, specificity 100%), MPI-TDI ≥ 0.69 (sensitivity 94.7%, specificity 93.5%), S ≤ 12.3 (sensitivity 90.3%, specificity 94.3%) were useful in predicting presence of proximal RCA stenosis.

CONCLUSION
RV function indices like TAPSE, MPI-TDI and S' velocity are useful in predicting proximal RCA stenosis in first episode of acute IWMI.

Rajesh|Gopalan Nair|GN|
Raju|Deepak|D|
Nandan|Deepak|D|
Haridasan|Vellani|V|
Vinayakumar|Desabandhu|D|
Muneer|Kader|K|
Sajeev|C G|CG|
Babu|Kadangot|K|
Krishnan|M N|MN|

D056989:Inferior Wall Myocardial Infarction

myocardial performance index by pulsed wave Doppler

myocardial performance index by tissue Doppler

right ventricular fractional area change

right ventricular wall motion abnormalities

P P P P P P P P P P P P P P P P P R U U M U U U U U M U U U M R M U U U U M M M R M M R M M M


Relationship of plasma galectin-3 to renal function in patients with heart failure: effects of clinical status, pathophysiology of heart failure, and presence or absence of heart failure.

Abstract:
BACKGROUND
Galectin-3 (GAL-3), a β-galactoside-binding protein, is a new clinical biomarker believed to reflect cardiac remodeling/fibrosis in patients with heart failure (HF). Plasma GAL-3 is inversely related to renal function. It is not known whether the relationship between renal function and GAL-3 is influenced by clinical decompensation, type of HF, or the presence or absence of clinical HF.

METHODS AND RESULTS
Patients were prospectively categorized as having acute decompensated HF or stable HF on the basis of clinical status and as having HF with reduced left ventricular ejection fraction or HF with preserved left ventricular ejection fraction. Plasma GAL-3 was measured by enzyme-linked immunosorbent assay in patients with HF (n=75), control patients without HF (n=32), and control patients without HF with moderate renal insufficiency (n=12). Compared to controls without HF (14±4 ng/mL), GAL-3 was higher in patients with both acute decompensated HF (23±11 ng/mL) and stable HF (22±10 ng/mL) (P<0.001 versus controls for both) but did not differ between acute decompensated HF and stable HF (P=0.75). Likewise, GAL-3 was elevated in both HF with preserved left ventricular ejection fraction (23±9 ng/mL) and HF with reduced left ventricular ejection fraction (22±11 ng/mL) (P<0.001 versus controls for both) but did not differ between HF with preserved ejection fraction and HF with reduced ejection fraction (P=0.37). GAL-3 correlated strongly with estimated glomerular filtration rate, both in patients with HF (r=-0.75, P<0.001) and in patients without HF (r=-0.82, P<0.001), and this relationship was unaffected by the presence or absence of clinical HF.

CONCLUSIONS
Plasma GAL-3 is inversely related to renal function in patients with and without clinical HF. Concentrations of plasma GAL-3 do not seem to depend on the level of compensation or type of HF. Furthermore, the relationship between GAL-3 and renal function seems to be affected little or not at all by the presence or absence of clinical HF.

Gopal|Deepa M|DM|
Kommineni|Maya|M|
Ayalon|Nir|N|
Koelbl|Christian|C|
Ayalon|Rivka|R|
Biolo|Andreia|A|
Dember|Laura M|LM|
Downing|Jill|J|
Siwik|Deborah A|DA|
Liang|Chang-Seng|CS|
Colucci|Wilson S|WS|

galectin-3
heart failure
biomarkers
kidney


Lithium and an EPAC-specific inhibitor ESI-09 synergistically suppress pancreatic cancer cell proliferation and survival.

Abstract: Our previous studies showed that while lithium suppresses proliferation and induces apoptosis in pancreatic cancer cells, the inhibition of exchange proteins directly activated by cyclic adenosine monophosphate (cAMP) (EPAC)1 blocks pancreatic cancer cell migration and invasion. In this study, we further investigated the combinatory effects of lithium and EPAC-specific inhibitor (ESI)-09, an EPAC-specific inhibitor, on pancreatic cancer cell proliferation and viability, and explored whether lithium synergistically cooperates with EPAC inhibition in suppressing pancreatic cancer cell tumorigenicity. The cell viability of pancreatic cancer cell lines PANC-1 and MiaPaCa-2 was measured after 48 h of incubation with different dose combination of lithium and ESI-09. Flow cytometric analysis was carried out to further verify the impact of lithium and ESI-09 upon PANC-1 cell proliferation and apoptosis. To investigate the mechanism that the effects generated by lithium and ESI-09 on PANC-1 cells, the intracellular cAMP level was measured by an ELISA-based cAMP immunoassay. Our data showed that lithium and ESI-09 synergistically inhibit pancreatic cancer cell growth and survival. Furthermore, our results revealed a novel mechanism in which the synergism between lithium and ESI-09 is not mediated by the inhibitory effect of lithium toward GSK3β, but by lithium's ability to suppress cAMP/protein kinase A signaling.

Wang|Xinshuo|X| Luo|Cheng|C| Cheng|Xiaodong|X| Lu|Meiling|M|

D000071679:Glycogen Synthase Kinase 3 beta

D020662:Guanine Nucleotide Exchange Factors

lithium ESI-09 proliferation apoptosis synergism


Limited brain metastases: a narrative review.

Abstract: Limited brain metastases refer to an oligometastatic state in the brain for which focal therapy with stereotactic radiosurgery (SRS) is appropriate. The definition of what is considered "limited" for brain metastases, however, is not well defined. Multiple recent randomized trials show that metastasis-directed therapy with surgery or stereotactic radiation can prolong survival for patients with 1-5 metastases from various primary tumors, but patients with untreated brain metastases were largely excluded from these trials. Stereotactic radiosurgery allows for the treatment of multiple brain metastases while avoiding whole brain radiation (WBRT), which has a known negative impact on neurocognitive function. Randomized trials have shown that stereotactic radiation alone is effective for the treatment of up to 4 brain metastases with decreased neurocognitive side effects and no detriment to overall survival (OS). These data have led to our current definition of "limited" brain metastases. However, more recent data suggests that patients with up to 10 brain metastases can benefit from SRS. Ongoing trials are investigating if patients with up to 15-20 brain metastases may similarly benefit from SRS alone. Advances in systemic therapies which penetrate the blood-brain barrier and have greater activity in central nervous system (CNS) may also expand the population for whom radiosurgery is an appropriate treatment. Immunotherapy may also be synergistic with radiosurgery in some cases. This narrative review will discuss the evolving definition and management of limited brain metastases.

Chaung|Kevin Victor|KV|
Sloan|Andrew Edward|AE|
Choi|Serah|S|

Brain metastases
stereotactic radiosurgery (SRS)
immunotherapy
oligometastatic disease
targeted therapy


MAPLE-PD trial (Mesenteric Approach vs. Conventional Approach for Pancreatic Cancer during Pancreaticoduodenectomy): study protocol for a multicenter randomized controlled trial of 354 patients with pancreatic ductal adenocarcinoma.

Abstract:
BACKGROUND
The mesenteric approach is an artery-first approach to pancreaticoduodenectomy for pancreatic cancer, which starts with the dissection of connective tissues around the superior mesenteric artery. The procedure aims for early confirmation of resectability by checking the surgical margin around the superior mesenteric artery first during the operation. It also aims to decrease intraoperative blood loss by early ligation of the inferior pancreaticoduodenal artery and to increase R0 rate by complete clearance of the lymph nodes around the superior mesenteric artery and pancreatic head plexus II, the most favorable positive margin site for pancreatic ductal adenocarcinoma. Furthermore, it aims to avoid the spread of cancer cells during operation (nontouch isolation technique). The MAPLE-PD (Mesenteric Approach vs. Conventional Approach for Pancreatic Cancer during Pancreaticoduodenectomy) trial investigates whether the mesenteric approach can prolong the survival of patients with pancreatic ductal adenocarcinoma who undergo pancreaticoduodenectomy compared with the conventional approach.

METHODS/DESIGN
The MAPLE-PD trial is a Japanese multicenter randomized controlled trial that compares the surgical outcomes between the mesenteric and conventional approaches to pancreaticoduodenectomy. Patients with pancreatic ductal adenocarcinoma scheduled to undergo pancreaticoduodenectomy are randomized before operation to either a conventional approach (arm A) or a mesenteric approach (arm B). In arm A, the operation starts with Kocher's maneuver. At the final step of the removal procedure, the connective tissues around the superior mesenteric artery are dissected. In arm B, the operation starts with dissection of the connective tissues around the superior mesenteric artery and ends with Kocher's maneuver. In total, 354 patients from 15 Japanese high-volume centers will be randomized. The primary endpoint is overall survival by intention-to-treat analysis. Secondary endpoints include intraoperative blood loss, R0 rate, and recurrence-free survival.

DISCUSSION
If the MAPLE-PD trial shows the oncological benefits of the mesenteric approach for patients with pancreatic ductal adenocarcinoma, this procedure may become a standard approach to pancreaticoduodenectomy.

TRIAL REGISTRATION
ClinicalTrials.gov, NCT03317886 . Registered on 23 October 2017. University Hospital Medical Information Network Clinical Trials Registry, UMIN000029615 . Registered on 15 January 2018.

Mesenteric approach
Conventional approach
Pancreaticoduodenectomy
Pancreatic ductal adenocarcinoma
Artery-first approach
Superior mesenteric artery
Borderline resectable pancreatic cancer
R0 resection
Resectable pancreatic cancer


Backwash ileitis in ulcerative colitis: Are there MR enterographic features that distinguish it from Crohn disease?

Abstract:
OBJECTIVE
To reveal the MR enterography (MRE) findings that distinguish backwash ileitis (BWI) from terminal ileitis due to Crohn's disease (CD) and to determine the usability of barium studies manifestations (ileocecal valve (ICV) gaping, terminal ileum dilatation) in MRE for the diagnosis of BWI in ulcerative colitis (UC) patients by pointing at the diagnostic performance of these imaging findings.

SUBJECTS-METHODS
The study population consisted of patients who were diagnosed as ulcerative colitis (UC), and underwent 1.5 T MRI between August 2011 and November 2017 to rule out small bowel involvement. The matched controls were comprised of Crohn's patients examined at the same period. Ileocolonoscopic/ histopathologic findings were accepted as reference standard. Mural/extramural changes in bowel segments, ileocecal valve (ICV) gaping, terminal ileum dilatation, restricted diffusion and anatomical extent of involvement were evaluated. In UC patients, the association between ICV gaping and terminal ileum dilatation and BWI was assessed by χ2 test. The diagnostic accuracy of these two findings in BWI was determined.

RESULTS
Sixty patients were included in the study (30 UC; 30 CD; mean age, 43 years in both groups). Ileocecal valve gaping and terminal ileum dilatation were significantly more frequent among BWI patients (p < 0.001) in UC. Patients with BWI showed a higher rate of pancolitis (88.9%). Median terminal ileum wall thickness was found to be significantly greater in patients with CD (p < 0.001).

CONCLUSION
In patients with definite diagnosis of UC, ileocecal valve gaping and terminal ileum dilatation suggest the development of BWI. However, these findings cannot be use to differentiate cause of terminal ileitis in patients with unconfirmed diagnosis and do not give reliable information about the causative factor of ileitis.

Erden|Ayse|A|
Kuru Öz|Diğdem|D|
Gürsoy Çoruh|Ayşegül|A|
Erden|İlhan|İ|
Özalp Ateş|Funda Seher|FS|
Törüner|Murat|M|

Backwash ileitis
Ulcerative colitis
MR enterography
Crohn's disease


Effect of the capsular tension ring on refractive outcome after phacoemulsification.

Abstract: Purpose: To evaluate how capsular tension rings (CTR) affect refractive outcomes following cataract extraction by phacoemulsification complicated by zonular instability. Study design: Retrospective. Methods: In a retrospective case-control study, the 29 eyes of 29 patients with CTRs were compared with the 29 eyes of patients without zonular instability following routine phacoemulsification, with mean arithmetic refractive prediction error (ArRPE) and mean absolute refractive prediction error (AbRPE) as primary outcome measures. Results: A comparison of eyes with and without CTRs according to the SRK/ T formula revealed no statistically significant difference in ArRPE (0.52 vs. 0.45 D, p = 0.570) or AbRPE (0.52 vs. 0.55 D, p = 0.799). Postoperative hypermetropic shift occurred in most cases in both groups, although the mean difference between eyes with CTR (22/ 29) and without CTR (25/ 29) was not statistically significant (p = 0.315). Conclusion: Implanting CTRs did not consistently affect refractive outcomes versus routine phacoemulsification. Results suggest that intraocular lens power can be calculated as usual when CTRs are used. Abbreviations: CTR = capsular tension ring, ArRPE = arithmetic refractive prediction errors, AbRPE = absolute refractive prediction errors, IOL = intraocular lens, WTW = white-to-white, ACD = anterior chamber depths, AL = axial lengths, RPE = refractive prediction error.

capsular tension ring
refraction
phacoemulsification surgery


Clinical Outcomes of Repeat Aortic Valve Replacement for Subaortic Pannus in Mechanical Aortic Valve.

Abstract:
BACKGROUND
This study aimed to evaluate the early and late clinical outcomes after repeat aortic valve replacement (AVR) for subaortic pannus in patients with mechanical valves. Methods and Results: Between 2001 and 2017, 51 patients (median age, 59 years; 42 women) with prosthetic aortic stenosis (AS) caused by pannus ingrowth underwent repeat AVR because of acute malfunction of monoleaflet valve (3 patients), severe prosthetic AS (30 patients), and moderate prosthetic AS at the time of tricuspid or mitral valve surgery (18 patients). The median follow-up duration was 100 (interquartile range, 64-138) months. Double valve replacement was performed in 45 (88%) patients. Median time interval from previous operation was 161 (interquartile range, 121-194) months. The explanted mechanical AV was monoleaflet and bileaflet in 16 (31%) and 34 (67%) patients, respectively. Concomitant procedures included 16 mitral valve replacements (14 repeat) and 36 tricuspid valve surgeries (15 replacements, 21 repairs). No hospital deaths or cases of heart block occurred. Overall survival and event-free survival rates at 10 years were 88% and 51%, respectively. Late complications included recurrent prosthetic AS (4 patients), new paravalvular leakage of the mitral valve (5 patients), and severe tricuspid regurgitation (2 patients).

CONCLUSIONS
Although repeat AVR for subaortic pannus had acceptable early and late survival, recurrent prosthetic AS was frequently observed during late follow-up.

Park|Pyo Won|PW|
Park|Byungjoon|B|
Jeong|Dong Seop|DS|
Sung|Kiick|K|
Kim|Wook Sung|WS|
Lee|Young Tak|YT|
Park|Seung Woo|SW|

D019918:Heart Valve Prosthesis Implantation

Aortic valve
Pannus
Prosthesis
Reoperation


Integration of the M6 Cyberknife in the Moderato Monte Carlo platform and prediction of beam parameters using machine learning.

Abstract:
PURPOSE
This work describes the integration of the M6 Cyberknife in the Moderato Monte Carlo platform, and introduces a machine learning method to accelerate the modelling of a linac.

METHODS
The MLC-equipped M6 Cyberknife was modelled and integrated in Moderato, our in-house platform offering independent verification of radiotherapy dose distributions. The model was validated by comparing TPS dose distributions with Moderato and by film measurements. Using this model, a machine learning algorithm was trained to find electron beam parameters for other M6 devices, by simulating dose curves with varying spot size and energy. The algorithm was optimized using cross-validation and tested with measurements from other institutions equipped with a M6 Cyberknife.

RESULTS
Optimal agreement in the Monte Carlo model was reached for a monoenergetic electron beam of 6.75 MeV with Gaussian spatial distribution of 2.4 mm FWHM. Clinical plan dose distributions from Moderato agreed within 2% with the TPS, and film measurements confirmed the accuracy of the model. Cross-validation of the prediction algorithm produced mean absolute errors of 0.1 MeV and 0.3 mm for beam energy and spot size respectively. Prediction-based simulated dose curves for other centres agreed within 3% with measurements, except for one device where differences up to 6% were detected.

CONCLUSIONS
The M6 Cyberknife was integrated in Moderato and validated through dose re-calculations and film measurements. The prediction algorithm was successfully applied to obtain electron beam parameters for other M6 devices. This method would prove useful to speed up modelling of new machines in Monte Carlo systems.

Wagner|A|A|
Brou Boni|K|K|
Rault|E|E|
Crop|F|F|
Lacornerie|T|T|
Van Gestel|D|D|
Reynaert|N|N|

Cyberknife
Monte Carlo
Machine learning
Treatment planning


i2b2 to Optimize Patients Enrollment.

Abstract: i2b2 data-warehouse could be a useful tool to support the enrollment phase of clinical studies. The aim of this work is to evaluate its performance on two clinical trials. We developed also an i2b2 extension to help in suggesting eligible patients for a study. The work showed good results in terms of ability to implement inclusion/exclusion criteria, but also in terms of identified patients actually enrolled and high number of patients suggested as potentially enrollable.

Bucalo|Mauro|M| Gabetta|Matteo|M| Chiudinelli|Lorenzo|L| Larizza|Cristiana|C| Bellasi|Antonio|A| Zambelli|Alberto|A| Barbarini|Nicola|N|

D016247:Information Storage and Retrieval

patients enrollment
clinical data-warehouse
patients recruitment


Pseudoceramide-containing physiological lipid mixture reduces adverse effects of topical steroids.

Abstract:
PURPOSE
Various therapeutic approaches have been suggested for preventing or reducing the adverse effects of topical glucocorticoids, including skin barrier impairment. Previously, we have shown that impairment of skin barrier function by the highest potency topical glucocorticoid, clobetasol 17-propinate (CP), can be partially prevented by co-application of a physiological lipid mixture containing pseudoceramide, free fatty acids, and cholesterol (multi-lamellar emulsion [MLE]). Skin atrophic effects of CP were also partially reduced by MLE. In this study, the preventive effects of MLE on the lowest potency topical glucocorticoid, hydrocortisone (HC), were investigated using animal models.

METHODS
Anti-inflammatory activity of topical HC was evaluated using a 12-O-tetradecanoylphobol-13-acetate-induced skin edema model. Topical steroid induced adverse effects were evaluated using hairless mouse.

RESULTS
The results showed that the anti-inflammatory activity was not altered by co-application of either MLE or hydrobase. However, co-application of MLE and 1.0% HC showed less impairment in the epidermal permeability barrier function, skin hydration, and skin surface pH compared with hydrobase. Stratum corneum integrity, evaluated by measuring trans-epidermal water loss after repeated tape stripping, showed less damage with MLE co-application. Long-term application of topical HC induced skin atrophy, measured by a reduction in skinfold and epidermal thickness and in the number of epidermal proliferating cell nucleus antigen (PCNA)-positive keratinocytes. Co-application of MLE did not affect the skinfold or epidermal thickness, but the number of PCNA-positive keratinocytes was less decreased with MLE use.

CONCLUSIONS
These results suggest that co-application of MLE is effective in reducing the local adverse effects of low-potency topical glucocorticoids and supports the therapeutic efficacy of physiological lipid mixtures on skin barrier function.

Kim|Hyun Jung|HJ|
Park|Hyun Jung|HJ|
Yun|Jae Nam|JN|
Jeong|Se Kyoo|SK|
Ahn|Sung Ku|SK|
Lee|Seung Hun|SH|

topical glucocorticoids
Epidermal permeability barrier function
multilamellar emulsion


Assessing Preknowledge Cheating via Innovative Measures: A Multiple-Group Analysis of Jointly Modeling Item Responses, Response Times, and Visual Fixation Counts.

Abstract: Many approaches have been proposed to jointly analyze item responses and response times to understand behavioral differences between normally and aberrantly behaved test-takers. Biometric information, such as data from eye trackers, can be used to better identify these deviant testing behaviors in addition to more conventional data types. Given this context, this study demonstrates the application of a new method for multiple-group analysis that concurrently models item responses, response times, and visual fixation counts collected from an eye-tracker. It is hypothesized that differences in behavioral patterns between normally behaved test-takers and those who have different levels of preknowledge about the test items will manifest in latent characteristics of the different data types. A Bayesian estimation scheme is used to fit the proposed model to experimental data and the results are discussed.

response times
eye-tracking
gaze-fixation counts
item response theory
joint modeling
technology enhanced assessment


Strategies and perspectives to develop SARS-CoV-2 detection methods and diagnostics.

Abstract: To develop diagnostics and detection methods, current research is focussed on targeting the detection of coronavirus based on its RNA. Besides the RNA target, research reports are coming to develop diagnostics by targeting structure and other parts of coronavirus. PCR based detection system is widely used and various improvements in the PCR based detection system can be seen in the recent research reports. This review will discuss multiple detection methods for coronavirus for developing appropriate, reliable, and fast alternative techniques. Considering the current scenario of COVID-19 diagnostics around the world and an urgent need for the development of reliable and cheap diagnostic, various techniques based on CRISPR technology, antibody, MIP, LAMP, microarray, etc. should be discussed and tried.

Jalandra|Rekha|R|
Yadav|Amit K|AK|
Verma|Damini|D|
Dalal|Nishu|N|
Sharma|Minakshi|M|
Singh|Rajeev|R|
Kumar|Anil|A|
Solanki|Pratima R|PR|


Prevalence of oral tori and exostosis in Malaysian population - A cross-sectional study.

Abstract:
Introduction
Oral tori and exostosis are non-pathological bony protuberances seen on the alveolar surfaces of the jaw bones. These are commonly seen on the palatal surfaces of the maxilla [torus palatinus (TP)] and around the premolars in the lingual surface of the mandible [torus mandibularis (TM)]. The aim of this cross-sectional study was to determine the prevalence of tori/exostosis in the Malaysian population.

Methodology
A total of 2666 patients were examined for the presence of tori and exostosis in the maxilla and mandible and were categorized into TP, TM, and exostosis (facial/labial). Collected data was analysed for obtaining descriptive statistics.

Results
882 subjects were noticed with oral tori/exostosis among the population studied with a prevalence rate of 33%. TP was seen more in females (35%), compared to males (20%), and this difference was statistically significant (p value < 0.001). Highest prevalence of TP was seen in Malays (43%), followed by Chinese (31%) and Indians (21%), which was statistically significant (p value < 0.00).

Discussion
High prevalence of tori and exostosis was seen in the population studied. Though harmless, in certain circumstances, their presence necessitates changes in the denture design during fabrication of prosthesis, which the dentist should be mindful.

Kumar Singh|Ashish|A|
Sulugodu Ramachandra|Srinivas|S|
Arora|Shelly|S|
Dicksit|Daniel Devaprakash|DD|
Kalyan|C G|CG|
Singh|Priyanshi|P|

Prevalence
Torus palatinus
Torus mandibularis
Malaysia


Challenges and Opportunities for Academic Journals to Serve the Older Population in Western Pacific Region.

Abstract:
Background/aim
Annals of Geriatric Medicine and Research held its inaugural international editorial board virtual meeting on September 16, 2021, to brainstorm ideas for sustainable growth. This special article summarizes the key concepts obtained from the webinar proceedings, with further development of ideas from ensuing discussions occurring after the meeting.

Methods
From the initial discussion points provided by eight editorial board members, including six presenters, email discussions further enriched these ideas to construct the current special article. The key points discussed were: 1) impactful research and impact factors, 2) international and Asian perspectives, and 3) challenges to sustainable growth.

Results
The editors noted the existing gap between the impact factor and research impact as a challenge for the growth paths of regional journals. However, they agreed that persevering with impactful research would ultimately translate into parallel and gradual gains in impact, which is, therefore, consistent with the organic growth of the journal. Acknowledging challenges in navigating between unique Asian perspectives and international outlooks, the editors encouraged academic journals to serve as bridges linking international evidence with the richness of local perspectives. For sustainable growth, the editors suggested that journals may be forged into the academic ecosystems of the region, diversify value streams, and establish themselves as reputable brands in disciplines.

Conclusion
By combining these discussions, we proposed the 'IMPACT' strategy for journals on the growth path in the region, which stands for 1) IMmersive user experience encompassing authors, reviewers, and readers; 2) Pasteur's quadrant use-inspired research; 3) Asia-Pacific context; 4) Collaborative; and 5) Translation to practice and policy.

Jung|Hee-Won|HW|
Lim|Wee Shiong|WS|
Cesari|Matteo|M|
Auyeung|Tung Wai|TW|
Kojima|Taro|T|
Ga|Hyuk|H|
Cameron|Ian D|ID|
Lim|Jae-Young|JY|

journals
aging
cultural diversity
publishing
regional health planning


Effects of injectable trace element and vitamin supplementation during the gestational, peri-parturient, or early lactational periods on neutrophil functions and pregnancy rate in dairy cows.

Abstract: The aim of this study was to evaluate effects of injectable trace element and vitamin combination on phagocytic, oxidative burst activity of neutrophils and reproductive outcomes in dairy cows. Cows were to assigned to the following groups: (1) injectable trace element supplementation (ITES, n = 44, containing zinc, manganese, copper, selenium); (2) injectable vitamin supplementation (VIT, n = 48, containing vitamins A, D3, E); (3) ITES + VIT (n = 46); and (4) control (CON, n = 44). Cows were administered four injections between 230 and 260 days of the gestational period, on day of parturition, and 30 days postpartum. Neutrophil function was assessed at 10 days before and after calving. Phagocytosis was greater in cows of the ITES + VIT group at 10 days prepartum (P < 0.05) while oxidative burst was similar among groups. There were greater non-esterified fatty acid (NEFA) concentrations in cows of the ITES+VIT group at 10 days prepartum (P < 0.05). Cows supplemented with ITES+ VIT had less SOD activity than those supplemented with ITES or vitamin during the pre- to post-partum transition period (P < 0.05). The total odds of pregnancy were greater in cows supplemented with trace element and/or vitamin (P < 0.05). In conclusion, supplementation of ITES and/or VIT resulted in an increased total pregnancy rate. Vitamin or trace element supplementation did not differ with the control group in both the prepartum and postpartum period for immune variables. There, however, was greater phagocytosis in cows supplemented with vitamin and trace elements during the prepartum period that might be related to metabolic-induced inflammation.

Yazlık|Murat Onur|MO|
Çolakoğlu|Hatice Esra|HE|
Pekcan|Mert|M|
Kaya|Ufuk|U|
Küplülü|Şükrü|Ş|
Kaçar|Cihan|C|
Polat|Mert|M|
Vural|Mehmet Rıfat|MR|

Dairy cow
Immunity
Antioxidant
Fertility


Synergistic pathogenesis of chicken infectious anemia virus and J subgroup of avian leukosis virus.

Abstract: As important immunosuppressive viruses, chicken infectious anemia virus (CIAV) and subgroup J avian leukosis virus (ALV-J) have caused huge economic losses to the poultry industry globally. Recently, the co-infection of CIAV and ALV-J frequently occurred in the domestic chicken flocks in China. However, the synergistic pathogenesis of CIAV and ALV-J has not been fully investigated. Here, a co-infection study was performed to further understand the potential synergistic pathogenesis of CIAV and ALV-J. In vitro study showed that CIAV could promote the replication of ALV-J in HD11 cells, but ALV-J could not increase the replication of CIAV. Chicken infection study showed both CIAV and ALV-J with synergistic effects caused significant body weight loss to the infected chickens. Although ALV-J had no effect on CIAV viral shedding and tissue load, CIAV did significantly increase ALV-J viremia, viral shedding and tissue load in the co-infection group. Moreover, both CIAV and ALV-J could significantly inhibit the humoral immunity to H9N2 influenza virus and serotype 4 fowl adenovirus (FAdV-4). All these data demonstrate the synergistic pathogenesis for the co-infection of CIAV and ALV-J, and highlight the positive effect of CIAV on the pathogenesis of ALV-J.

Zhang|Jun|J| Ma|Li|L| Li|Tuofan|T| Li|Luyuan|L| Kan|Qiuqi|Q| Yao|Xiaohui|X| Xie|Quan|Q| Wan|Zhimin|Z| Shao|Hongxia|H| Qin|Aijian|A| Ye|Jianqiang|J|

D000818:Animals
D001353:Avian Leukosis
D001354:Avian Leukosis Virus
D017727:Chicken anemia virus
D002645:Chickens
D053127:Influenza A Virus, H9N2 Subtype
D011201:Poultry Diseases

synergistic pathogenesis
chicken infectious anemia virus
immunosuppression
subgroup J avian leukosis virus
co-infection


C57BL/6 Background Attenuates mHTT Toxicity in the Striatum of YAC128 Mice.

Abstract: Mouse models are frequently used to study Huntington's disease (HD). The onset and severity of neuronal and behavioral pathologies vary greatly between HD mouse models, which results from different huntingtin expression levels and different CAG repeat length. HD pathology appears to depend also on the strain background of mouse models. Thus, behavioral deficits of HD mice are more severe in the FVB than in the C57BL/6 background. Alterations in medium spiny neuron (MSN) morphology and function have been well documented in young YAC128 mice in the FVB background. Here, we tested the relevance of strain background for mutant huntingtin (mHTT) toxicity on the cellular level by investigating HD pathologies in YAC128 mice in the C57BL/6 background (YAC128/BL6). Morphology, spine density, synapse function and membrane properties were not or only subtly altered in MSNs of 12-month-old YAC128/BL6 mice. Despite the mild cellular phenotype, YAC128/BL6 mice showed deficits in motor performance. More pronounced alterations in MSN function were found in the HdhQ150 mouse model in the C57BL/6 background (HdhQ150/BL6). Consistent with the differences in HD pathology, the number of inclusion bodies was considerably lower in YAC128/BL6 mice than HdhQ150/BL6 mice. This study highlights the relevance of strain background for mHTT toxicity in HD mouse models.


Application of the Intervention Mapping Framework to Develop an Integrated Twenty-first Century Core Curriculum-Part Two: Translation of MPH Core Competencies into an Integrated Theory-Based Core Curriculum.

Abstract: In the twenty-first century, the dynamics of health and health care are changing, necessitating a commitment to revising traditional public health curricula to better meet present day challenges. This article describes how the College of Public Health at the University of South Florida utilized the Intervention Mapping framework to translate revised core competencies into an integrated, theory-driven core curriculum to meet the training needs of the twenty-first century public health scholar and practitioner. This process resulted in the development of four sequenced courses: History and Systems of Public Health and Population Assessment I delivered in the first semester and Population Assessment II and Translation to Practice delivered in the second semester. While the transformation process, moving from traditional public health core content to an integrated and innovative curriculum, is a challenging and daunting task, Intervention Mapping provides the ideal framework for guiding this process. Intervention mapping walks the curriculum developers from the broad goals and objectives to the finite details of a lesson plan. Throughout this process, critical lessons were learned, including the importance of being open to new ideologies and frameworks and the critical need to involve key-stakeholders in every step of the decision-making process to ensure the sustainability of the resulting integrated and theory-based curriculum. Ultimately, as a stronger curriculum emerged, the developers and instructors themselves were changed, fostering a stronger public health workforce from within.

Corvin|Jaime A|JA|
DeBate|Rita|R|
Wolfe-Quintero|Kate|K|
Petersen|Donna J|DJ|

competencies
public health
MPH foundational core
experiential learning
pedagogy


Measurement of Reverse Triiodothyronine Level and the Triiodothyronine to Reverse Triiodothyronine Ratio in Dried Blood Spot Samples at Birth May Facilitate Early Detection of Monocarboxylate Transporter 8 Deficiency.

Abstract: Monocarboxylate transporter 8 (MCT8) deficiency is an X-chromosome-linked neurodevelopmental disorder resulting from impaired thyroid hormone transport across the cell membrane. The diagnosis of MCT8 deficiency is typically delayed owing to the late appearance of signs and symptoms as well as the inability of standard biomarkers of neonatal screening to provide early detection. In this study, we report, for the first time, the ability to detect MCT8 deficiency at birth using dried blood spot (DBS) samples.  We retrospectively measured triiodothyronine (T3), thyroxine (T4), and reverse T3 (rT3) levels in DBS samples obtained at 4-5 days of life from 6 infants with genetically confirmed MCT8 deficiency and from 110 controls. The latter consisted of 58 healthy term neonates obtained at the same time, 16 were stored for more than 1 year before measurement to match samples from the MCT8-deficient infants. Ten DBS samples were collected at day 1 of life and 42 samples were from prematurely born neonates. Measurements were carried out in extract from eight millimeters diameter DBS using liquid chromatography-tandem mass spectrometry.  Contrary to characteristic iodothyronine abnormalities of MCT8 deficiency during later life, T3 and T4 values were not discriminatory from those of other study groups. In contrast, rT3 was significantly lower. The T3/rT3 ratio was higher in the DBS samples from the MCT8-deficient infants compared with all other groups with no overlap (p < 0.0001).  rT3 and T3/rT3 ratio in DBS samples obtained from neonates can serve as biomarkers to detect MCT8 deficiency at birth.

Iwayama|Hideyuki|H|
Kakita|Hiroki|H|
Iwasa|Masumi|M|
Adachi|Shinsuke|S|
Takano|Kyoko|K|
Kikuchi|Masahiro|M|
Fujisawa|Yasuko|Y|
Osaka|Hitoshi|H|
Yamada|Yasumasa|Y|
Okumura|Akihisa|A|
Hirani|Khemraj|K|
Weiss|Roy E|RE|
Refetoff|Samuel|S|0000-0003-0164-8231

dried blood spot
MCT8 deficiency
reverse T3
LC-MS/MS
newborn screening


Focal choroidal excavaction associated with idiopathic choroidal neovascularization.

Abstract:
CASE REPORT
The case is presented of a 45 year-old man with a focal choroidal excavation associated with choroidal neovascularisation not included in the area of excavation. Clinical features were analysed using retinography, fluorescein angiography, optical coherence tomography, and optical coherence tomography angiography. The patient was treated with 3 intravitreal injections of bevacizumab, with a good response.

DISCUSSION
Focal choroidal excavation can be associated with choroidal neovascularization not included in the area of excavation. Multimodal imaging provides a complete description of clinical features, before and after treatment.

Sánchez-Vicente|J L|JL|
Rueda-Rueda|T|T|
Martínez-Borrego|A C|AC|
Moruno-Rodríguez|A|A|
Molina-Socola|F E|FE|
Contreras-Díaz|M|M|
Medina-Tapia|A|A|
Muñoz-Morales|A|A|
López-Herrero|F|F|

Focal choroidal excavation
Choroidal neovascularisation
Angiography
Optical coherence tomography
Angiotomografía
Excavación focal coroidea
Neovascularización coroidea
Tomografía de coherencia óptica


Plasma L-arginine levels distinguish pulmonary arterial hypertension from left ventricular systolic dysfunction.

Abstract: Pulmonary arterial hypertension (PAH) is a life-threatening condition, characterized by an imbalance of vasoactive substances and remodeling of pulmonary vasculature. Nitric oxide, formed from L-arginine, is essential for homeostasis and smooth muscle cell relaxation in PAH. Our aim was to compare plasma concentrations of L-arginine, asymmetric dimethylarginine (ADMA), and symmetric dimethylarginine (SDMA) in PAH compared to left ventricular systolic dysfunction (LVSD) and healthy subjects. This was an observational, multicenter study comparing 21 patients with PAH to 14 patients with LVSD and 27 healthy subjects. Physical examinations were obtained and blood samples were collected. Plasma levels of ADMA, SDMA, L-arginine, L-ornithine, and L-citrulline were analyzed using liquid chromatography-tandem mass spectrometry (LC-MS/MS). Plasma levels of ADMA and SDMA were higher, whereas L-arginine and L-arginine/ADMA ratio were lower in PAH patients compared to healthy subjects (p < 0.001). Patients with PAH also had lower levels of L-arginine than patients with LVSD (p < 0.05). L-Arginine correlated to 6 min walking distance (6MWD) (r s = 0.58, p = 0.006) and L-arginine/ADMA correlated to WHO functional class (r s = -0.46, p = 0.043) in PAH. In conclusion, L-arginine levels were significantly lower in treatment naïve PAH patients compared to patients with LVSD. Furthermore, L-arginine correlated with 6MWD in PAH. L-arginine may provide useful information in differentiating PAH from LVSD.

L-Arginine
Pulmonary arterial hypertension
Systolic dysfunction
Dimethylarginines
Left heart failure


A cross-cultural exploration of the everyday social participation of individuals with autism spectrum disorders in Australia and Taiwan: An experience sampling study.

Abstract: Individuals with an autism spectrum disorder commonly have limited social participation. This study aimed to examine the similarities and differences of everyday participation among males and females with autism spectrum disorder in Australia and Taiwan, using an experience sampling methodology. A total of 14 Australians (4 males, aged 16-43 years) and 16 Taiwanese (12 males, aged 19-45 years) with autism spectrum disorder who are cognitively able were asked to carry a device which prompted them seven times per day for 7 days, to record everyday participation: where they were, what they were doing, and who they were with. Multilevel analyses were used to identify the relationships between everyday participation and associated factors including gender, country of residence, clinical severity of autism spectrum disorder, and social anxiety. The results showed that Taiwanese participants were more likely to stay at home than Australian participants. However, female participants were more likely to engage in social situations than males. Furthermore, participants with fewer autism spectrum disorder symptoms and those with higher levels of social anxiety were less likely to engage in social interactions. This study sheds light on ways that culture and gender affect social participation and highlights the relationship of social anxiety to social participation. The findings have implications for interventions for social participation.

Chen|Yu-Wei|YW|
Bundy|Anita C|AC|
Cordier|Reinie|R|
Chien|Yi-Ling|YL|
Einfeld|Stewart L|SL|

social interaction
Asperger syndrome
ecological momentary assessment
time use


Altered levels of mitochondrial NFS1 affect cellular Fe and S contents in plants.

Abstract: The ISC Fe-S cluster biosynthetic pathway would play a key role in the regulation of iron and sulfur homeostasis in plants. The Arabidopsis thaliana mitochondrial cysteine desulfurase AtNFS1 has an essential role in cellular ISC Fe-S cluster assembly, and this pathway is one of the main sinks for iron (Fe) and sulfur (S) in the plant. In different plant species it has been reported a close relationship between Fe and S metabolisms; however, the regulation of both nutrient homeostasis is not fully understood. In this study, we have characterized AtNFS1 overexpressing and knockdown mutant Arabidopsis plants. Plants showed alterations in the ISC Fe-S biosynthetic pathway genes and in the activity of Fe-S enzymes. Genes involved in Fe and S uptakes, assimilation, and regulation were up-regulated in overexpressing plants and down-regulated in knockdown plants. Furthermore, the plant nutritional status in different tissues was in accordance with those gene activities: overexpressing lines accumulated increased amounts of Fe and S and mutant plant had lower contents of S. In summary, our results suggest that the ISC Fe-S cluster biosynthetic pathway plays a crucial role in the homeostasis of Fe and S in plants, and that it may be important in their regulation.

Iron
Sulfur
Cysteine desulfurase
Fe–S clusters


Pancreatic Fibrosis and Chronic Pancreatitis: Mini-Review of Non-Histologic Diagnosis for Clinical Applications.

Abstract: Pancreatic fibrosis is the dominant reversible pathological change and diagnostic factor in early chronic pancreatitis, defined by a mechanistic approach proposed in 2016. Main guidelines for chronic pancreatitis were published by the American Pancreas Association in 2014, the Japanese Society of Gastroenterology in 2015, and United European Gastroenterology in 2017. All three sets of guidelines mentioned that the staging of chronic pancreatitis is important but challenging. There are various image modalities for the non-histologic diagnosis of pancreatic fibrosis: (1) shear wave elastography, such as an acoustic radiation force impulse with a cut-off value of 1.4 m/s; (2) strain elastography using grades of strain; (3) endoscopic ultrasonography using the Rosemont criteria or endoscopic ultrasound criteria for early chronic pancreatitis proposed by the Japan Pancreas Society; (4) computed tomography using the Hounsfield scale or number of micro-calcifications; and (5) magnetic resonance imaging using the apparent diffusion coefficient and the T1w flash and T2w HASTE sequences. The clinical applications are to (1) evaluate pancreatic tumors and inflammatory disease; (2) monitor dyspepsia with early chronic pancreatitis; (3) monitor individuals with a high risk of pancreatic cancer; (4) analyze a fatty pancreas with fibrosis; (5) predict a fistula after pancreatic surgery; and (6) predict outcomes for chronic pancreatitis or pancreatic cancer. The selection of tools will be dependent on the clinical scenario. Conclusion: There are various modalities for the non-histologic diagnosis of pancreatic fibrosis. The selection of the optimal device will be dependent on the clinical scenario.

Huang|Chung-Tsui|CT| Lin|Cheng-Kuan|CK| Lee|Tzong-Hsi|TH| Liang|Yao-Jen|YJ|

pancreatic fibrosis
non-histologic diagnosis
early chronic pancreatitis