Safety and efficacy of STENOROL® (halofuginone hydrobromide) as a feed additive for chickens for fattening and turkeys.

Abstract: Following a request from the European Commission, the Panel on Additives and Products or Substances used in Animal Feed (FEEDAP) was asked to deliver a scientific opinion on the coccidiostat STENOROL ® containing halofuginone hydrobromide (halofuginone HBr) as active substance. The FEEDAP Panel was not able to conclude on the safety of STENOROL ® for chickens and turkeys for fattening at the highest proposed use level. No incompatibilities or interactions with feedingstuffs, carriers, other approved additives or medicinal drugs are expected. Halofuginone HBr does not have antimicrobial activity at the highest dose proposed; it is not expected to exert adverse effects on chicken gut microbiota or select for resistance and cross-resistance with other antimicrobials. The Panel cannot conclude on the genotoxic potential of halofuginone HBr since an appropriate in vivo follow-up to exclude the mutagenic effect of the compound was not available. Therefore, the FEEDAP Panel cannot conclude on the safety of halofuginone HBr for the consumer. The additive is toxic by inhalation, dermal and ocular routes and is very irritant to both the eye and the skin. It is considered also a skin sensitiser. Inhalation exposure is considered a risk to persons handling the additive. Since the lack of genotoxic potential of halofuginone HBr has not been adequately demonstrated, it should be considered as an additional potential concern to users handling the additive. Due to limitations in some of the ecotoxicological studies, no conclusions can be drawn on the safety of the additive for the environment. The FEEDAP Panel is not in the position to conclude on the efficacy of STENOROL ® in chickens for fattening and in turkeys for fattening.

|||
Bampidis|Vasileios|V|
Azimonti|Giovanna|G|
Bastos|Maria de Lourdes|ML|
Christensen|Henrik|H|
Dusemund|Birgit|B|
Fašmon Durjava|Mojca|M|
Kouba|Maryline|M|
López-Alonso|Marta|M|
López Puente|Secundino|S|
Marcon|Francesca|F|
Mayo|Baltasar|B|
Pechová|Alena|A|
Petkova|Mariana|M|
Ramos|Fernando|F|
Sanz|Yolanda|Y|
Villa|Roberto Edoardo|RE|
Woutersen|Ruud|R|
Aquilina|Gabriele|G|
Brantom|Paul|P|
Bories|Georges|G|
Cocconcelli|Pier Sandro|PS|
Gropp|Jürgen|J|
Rychen|Guido|G|
Holczknecht|Orsolya|O|
Vettori|Maria Vittoria|MV|

safety and efficacy
halofuginone hydrobromide
chickens for fattening
turkeys
coccidiostats


Identification of KLK10 as a therapeutic target to reverse trastuzumab resistance in breast cancer.

Abstract: Trastuzumab, the first antibody widely used in anti-HER2 targeted therapy, dramatically improved the overall outcome of HER2 positive breast cancer patients. However, trastuzumab resistance emerged as a major problem in its clinical application. In order to explore mechanisms underlying trastuzumab resistance, we performed RNA-Seq to analyze the gene expression variation in trastuzumab resistant breast cancer cell line. The sequencing result was then combined with the relevant data in TCGA database to conduct a co-expression analysis. We found a series of differentially expressed genes with potential contributions to trastuzumab resistance. Among them, KLK10 was verified to be a potential therapeutic target for reversing trastuzumab resistance. In summary, this study provides a new clue to screen molecular targets and predictive biomarkers for trastuzumab resistance.

Wang|Zhuo|Z| Ruan|Beihong|B| Jin|Yi|Y| Zhang|Yulong|Y| Li|Jiaqiu|J| Zhu|Liyuan|L| Xu|Wenxia|W| Feng|Lifeng|L| Jin|Hongchuan|H| Wang|Xian|X|

D015972:Gene Expression Regulation, Neoplastic


Inhibitory Effects of the Lactobacillus rhamnosus GG Effector Protein HM0539 on Inflammatory Response Through the TLR4/MyD88/NF-кB Axis.

Abstract: Inflammatory bowel disease (IBD) is a chronic and relapsing intestinal inflammatory condition with no effective treatment. Probiotics have gained wide attention because of their outstanding advantages in intestinal health issues. In previous studies, a novel soluble protein, HM0539, which is derived from Lactobacillus rhamnosus GG (LGG), showed significant protective effects against murine colitis, but no clear precise mechanism for this effect was provided. In this study, we hypothesized that the protective function of HM0539 might be derived from its modulation of the TLR4/Myd88/NF-κB axis signaling pathway, which is a critical pathway widely involved in the modulation of inflammatory responses. To test this hypothesis, the underlying anti-inflammatory effects and associated mechanisms of HM0539 were determined both in lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages and in dextran sulfate sodium (DSS)-induced murine colitis. Our results showed that HM0539 inhibited the expression of cyclooxygenase-2 (COX-2) and the expression inducible nitric oxide synthase (iNOS) by down-regulating the activation of their respective promoter, and as a result this inhibited the production of prostaglandin E2 (PGE2) and nitric oxide (NO). Meanwhile, we demonstrated that HM0539 could ultimately modulate the activation of distal NF-κB by reducing the activation of TLR4 and suppressing the transduction of MyD88. However, even though the overexpression of TLR4 or MyD88 obviously reversed the effect of HM0539 on LPS-induced inflammation, HM0539 still retained some anti-inflammatory activity. Consistent with the in vitro findings, we found that HM0539 inhibited to a great extent the production of inflammatory mediators associated with the suppression of the TLR4/Myd88/NF-κB axis activation in colon tissue. In conclusion, HM0539 was shown to be a promising anti-inflammatory agent, at least in part through its down-regulation of the TLR4-MyD88 axis as well as of the downstream MyD88-dependent activated NF-κB signaling, and hence might be considered as a potential therapeutic option for IBD.

Li|Yubin|Y| Yang|Shaojie|S| Lun|Jingxian|J| Gao|Jie|J| Gao|Xuefeng|X| Gong|Zelong|Z| Wan|Yu|Y| He|Xiaolong|X| Cao|Hong|H|

D053594:Myeloid Differentiation Factor 88

Lactobacillus rhamnosus GG
inflammatory response
TLR4/MyD88/NF-кB axis
colitis
postbiotics


Comparison of current tonometry techniques in measurement of intraocular pressure.

Abstract:
PURPOSE
To compare four tonometry techniques: Goldmann applanation tonometer (GAT), Dynamic contour tonometer (DCT), Non-contact tonometer (NCT), and Ocular Response Analyzer (ORA) in the measurement of intraocular pressure (IOP) and the impact of some corneal biomechanical factors on their performance.

METHODS
In this cross-sectional study, volunteers with normal ophthalmic examination and no history of eye surgery (except for uncomplicated cataract surgery) or trauma were selected. Twenty-five subjects were male, and 21 were female. The mean age was 48 ± 19.2 years. Anterior segment parameters were measured with Scheimpflug imaging. IOP was measured with GAT, DCT, NCT, and ORA in random order. A 95% limit of agreement of IOPs was analyzed. The impact of different parameters on the measured IOP with each device was evaluated by regression analysis.

RESULTS
The average IOP measured with GAT, DCT, NCT, and ORA was 16.4 ± 3.5, 18.1 ± 3.4, 16.2 ± 3.9, and 17.3 ± 3.4 mmHg, respectively. The difference of IOP measured with NCT and GAT was not significant (P = 0.382). Intraocular pressure was significantly different between GAT with DCT and IOPCC (P < 0.001 and P = 0.022, respectively). The 95% limit of agreement of DCT, NCT, and IOPCC with GAT was -5.7 to 2.5, -4.1 to 4.7, and -5.3-3.7 mmHg, respectively. Simple regression model corneal resistance factor (CRF) and central corneal thickness (CCT) and multivariate model CRF had a significant relationship with IOP measured with the four devices.

CONCLUSION
Although the mean difference of measured IOP by NCT, DCT, and ORA with GAT was less than 2 mmHg, the limit of agreement was relatively large. CCT and CRF were important influencing factors in the four types of tonometers.

Kouchaki|Behrooz|B| Hashemi|Hassan|H| Yekta|Abbasali|A| Khabazkhoob|Mehdi|M|

Tonometry
Intraocular pressure
Goldmann applanation tonometer
Dynamic contour tonometer
Non-contact tonometer
Ocular response analyze


Acute HSV and anti-NMDA encephalitis occurring as a neurosurgical complication.

Abstract: We present a 24-year-old man with a 2-year history of progressive right-sided monocular vision loss with no other symptoms. An MRI showed a meningioma compressing the right optic nerve and the cavernous sinus. The tumour was partially resected. Eight days after discharge the patient was admitted with fever, a severe stabbing headache, insomnia, nausea and vomiting. A FilmArray panel and a cerebral biopsy were performed which were positive for herpes simplex virus 1 (HSV-1). An MRI of the brain showed asymmetric bilateral lesions in the frontobasal region with predominance of the right side. Acyclovir was started and continued until completing 21 days. A month after discharge, he started experiencing insomnia, trichotillomania, limb tremor, persistence of abulia, apathy and emotional lability. An HSV-1 encephalitis relapse was suspected, acyclovir and foscarnet were started. Due to the poor response to antiviral therapy CSF was tested, which was positive for anti-NMDA receptor encephalitis. A treatment course of intravenous immunoglobulin was started with a favourable outcome.

Toro|Jaime|J|
Rivera|Juan Sebastian|JS|
Moutran-Barroso|Habib|H|
Valencia-Enciso|Natalia|N|

infection (neurology)
medical education
neuroimaging
neurooncology


Assessing the Heterogeneity of Complaints Related to Tinnitus and Hyperacusis from an Unsupervised Machine Learning Approach: An Exploratory Study.

Abstract:
INTRODUCTION
Subjective tinnitus (ST) and hyperacusis (HA) are common auditory symptoms that may become incapacitating in a subgroup of patients who thereby seek medical advice. Both conditions can result from many different mechanisms, and as a consequence, patients may report a vast repertoire of associated symptoms and comorbidities that can reduce dramatically the quality of life and even lead to suicide attempts in the most severe cases. The present exploratory study is aimed at investigating patients' symptoms and complaints using an in-depth statistical analysis of patients' natural narratives in a real-life environment in which, thanks to the anonymization of contributions and the peer-to-peer interaction, it is supposed that the wording used is totally free of any self-limitation and self-censorship.

METHODS
We applied a purely statistical, non-supervised machine learning approach to the analysis of patients' verbatim exchanged on an Internet forum. After automated data extraction, the dataset has been preprocessed in order to make it suitable for statistical analysis. We used a variant of the Latent Dirichlet Allocation (LDA) algorithm to reveal clusters of symptoms and complaints of HA patients (topics). The probability of distribution of words within a topic uniquely characterizes it. The convergence of the log-likelihood of the LDA-model has been reached after 2,000 iterations. Several statistical parameters have been tested for topic modeling and word relevance factor within each topic.

RESULTS
Despite a rather small dataset, this exploratory study demonstrates that patients' free speeches available on the Internet constitute a valuable material for machine learning and statistical analysis aimed at categorizing ST/HA complaints. The LDA model with K = 15 topics seems to be the most relevant in terms of relative weights and correlations with the capability to individualizing subgroups of patients displaying specific characteristics. The study of the relevance factor may be useful to unveil weak but important signals that are present in patients' narratives.

DISCUSSION/CONCLUSION
We claim that the LDA non-supervised approach would permit to gain knowledge on the patterns of ST- and HA-related complaints and on patients' centered domains of interest. The merits and limitations of the LDA algorithms are compared with other natural language processing methods and with more conventional methods of qualitative analysis of patients' output. Future directions and research topics emerging from this innovative algorithmic analysis are proposed.

Tinnitus
Hyperacusis
Machine learning
Computational predictive medicine
Text mining


Severe periodontitis associated with chronic kidney disease.

Abstract: The data on Indian population with regard to severity/prevalence of chronic periodontitis in association with chronic kidney disease (CKD) is scarce. We are describing an interesting case of severe periodontitis associated with CKD. The patient had unusual inflammatory gingival overgrowth which persisted even after treatment. By describing this case we want to highlight our current lack of understanding with regard to etiopathogenesis of periodontal disease in CKD patients and need for further research in this area.

periodontitis
Chronic kidney disease
inflammatory gingival overgrowth


Differential role of Dok1 and Dok2 in TLR2-induced inflammatory signaling in glia.

Abstract: Accumulating evidence continues to underpin the role of the innate immune system in pathologies associated with neuroinflammation. Innate immunity is regulated by pattern recognition receptors that detect pathogens, and in the case of Gram-positive bacteria, binding of bacterial lipopeptides to toll-like receptor (TLR)2 is emerging as an important mechanism controlling glial cell activation. In the present study, we employed the use of the synthetic bacterial lipoprotein and a selective TLR2 agonist, Pam3CSK4, to induce inflammatory signaling in microglia and astrocytes. The adaptor proteins, downstream of kinase (Dok)1 and Dok2, are known to have a role in negatively regulating the Ras-ERK signaling cascade, with downstream consequences on pro-inflammatory cytokine expression. Data presented herein demonstrate that TLR2 enhanced the tyrosine phosphorylation of Dok1 and Dok2 in astrocytes and microglia, and that knockdown of these adaptors using small interfering RNA robustly elevated TLR2-induced ERK activation. Importantly, TLR2-induced NF-κB activation, and IL-6 production was exacerbated in astrocytes transfected with Dok1 and Dok2 siRNA, indicating that both Dok proteins negatively regulate TLR2-induced inflammatory signaling in astrocytes. In contrast, Dok1 knockdown attenuated TLR2-induced NF-κB activation and IL-6 production in microglia, while Dok2 siRNA failed to affect TLR2-induced NF-κB activity and subsequent cytokine expression in this cell type. Overall, this indicates that Dok1 and Dok2 are novel adaptors for TLR2 in glial cells and importantly indicates that Dok1 and Dok2 differentially regulate TLR2-induced pro-inflammatory signaling in astrocytes and microglia.

Downer|Eric J|EJ|
Johnston|Daniel G W|DG|
Lynch|Marina A|MA|

D048868:Adaptor Proteins, Signal Transducing

Toll-interleukin-1 receptor (TIR)-domain-containing adaptor-inducing IFN-β

granulocyte macrophage colony stimulating factor

signaling lymphocyte activation molecule

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 U U U U U U U U U U U U U M M M M M U M U U U M U M U M U R M


Complete arterial revascularization using bilateral internal mammary artery in T-graft technique for multivessel coronary artery disease in on- or off-pump approach: does gender lose its historical impact on clinical outcome?

Abstract:
OBJECTIVES
Higher rates of mortality and morbidity have been reported in women undergoing coronary artery bypass grafting (CABG) compared with men. Different revascularization techniques (on-pump and off-pump) might influence this outcome.

METHODS
We retrospectively analysed 3445 consecutively recruited patients (all comers) undergoing complete arterial CABG (CACABG) at a single centre between January 2000 and December 2012. CACABG was performed in all patients using bilateral skeletonized internal mammary artery in T-graft technique, either on-pump (n = 2216) or off-pump (n = 1229). Early results (30-day) and long-term follow-up data were analysed with respect to gender-specific outcome.

RESULTS
Women were older than men in both groups (P < 0.001), and men had a higher body mass index (on-pump: P < 0.001; off-pump: P = 0.02) compared with women. Men displayed a higher extent of coronary artery disease (P < 0.001) and an overall lower ejection fraction (P < 0.001) when undergoing on-pump CABG. No gender differences were observed for late survival (P = 0.74 vs P = 0.52) in on-pump and off-pump procedures, respectively. Late follow-up revealed a higher rate of FitzGibbon A graft patency in men undergoing the on-pump approach (P = 0.006).

CONCLUSIONS
CACABG using bilateral internal mammary artery in T-graft technique showed excellent early and long-term results. No significant gender-specific differences were observed in both groups undergoing CACABG with respect to 30 days mortality and morbidity as well as late survival. However, late follow-up revealed a higher graft patency in men undergoing the on-pump approach, compared to women.

Rieß|Friedrich-Christian|FC|
Behrendt|Christian-Alexander|CA|
Amin|Wagma|W|
Heller|Stefan|S|
Hansen|Lorenz|L|
Winkel|Stephan|S|
Stripling|Jan|J|
Rieß|Henrik Christian|HC|

D047549:Coronary Artery Bypass, Off-Pump

Complete arterial revascularization
Bilateral internal mammary artery
Gender
Coronary artery bypass grafting
Off-pump surgery
On-pump surgery


Genetic relatedness does not retain spatial pattern across multiple spatial scales: dispersal and colonization in the coral, Pocillopora damicornis.

Abstract: Patterns of isolation by distance are uncommon in coral populations. Here, we depart from historical trends of large-scale, geographical genetic analyses by scaling down to a single patch reef in Kāne'ohe Bay, Hawai'i, USA, and map and genotype all colonies of the coral, Pocillopora damicornis. Six polymorphic microsatellite loci were used to assess population genetic and clonal structure and to calculate individual colony pairwise relatedness values. Our results point to an inbred, highly clonal reef (between 53 and 116 clonal lineages of 2352 genotyped colonies) with a much skewed genet frequency distribution (over 70% of the reef was composed of just seven genotypes). Spatial autocorrelation analyses revealed that corals found close together on the reef were more genetically related than corals further apart. Spatial genetic structure disappears, however, as spatial scale increases and then becomes negative at the largest distances. Stratified, random sampling of three neighbouring reefs confirms that reefs are demographically open and inter-reef genetic structuring was not detected. Attributing process to pattern in corals is complicated by their mixed reproductive strategies. Separate autocorrelation analyses, however, show that the spatial distribution of both clones and nonclones contributes to spatial genetic structure. Overall, we demonstrate genetic structure on an intrareef scale and genetic panmixia on an inter-reef scale indicating that, for P. damicornis, the effect of small- and large-scale dispersal processes on genetic diversity are not the same. By starting from an interindividual, intrareef level before scaling up to an inter-reef level, this study demonstrates that isolation-by-distance patterns for the coral P. damicornis are limited to small scales and highlights the importance of investigating genetic patterns and ecological processes at multiple scales.

coral reproduction
lace coral
landscape genetics
larval dispersal


Recombinant Purification of the Periplasmic Portion of the LINC Complex.

Abstract: Recombinant expression of proteins and their complexes is the routine laboratory procedure to generate pure reagents for biochemical and structural studies. Here we present the standard procedure developed in our lab for the production of milligram quantities of stoichiometric SUN-KASH complexes. The protocol was specifically developed for the purification of the periplasmic portion of LINC complexes.

D002846:Chromatography, Affinity
D006801:Humans
D046912:Multiprotein Complexes
D009687:Nuclear Proteins
D033903:Periplasmic Proteins
D059748:Proteolysis
D011994:Recombinant Proteins

LINC complex
Co-expression
Protein purification


Neural correlates of language variability in preschool-aged boys with autism spectrum disorder.

Abstract: Children with autism vary widely in their language abilities, yet the neural correlates of this language variability remain unclear, especially early in development. Diffusion tensor imaging (DTI) was used to examine diffusivity measures along the length of 18 major fiber tracts in 104 preschool-aged boys with autism spectrum disorder (ASD). The boys were assigned to subgroups according to their level of language development (Low: no/low language, Middle: small vocabulary, High: large vocabulary and grammar), based on their raw scores on the expressive language (EL) and receptive language (RL) sections of the Mullen Scales of Early Learning (MSEL). Results indicate that the subgroups differed in fractional anisotropy (FA), mean diffusivity (MD), and radial diffusivity (RD) along the inferior longitudinal fasciculus (ILF) in both hemispheres. Moreover, FA correlated significantly with Mullen EL and RL raw scores, but not ADOS severity score, along the left and right ILF. Subgroups also differed in MD (but not FA) along the left superior longitudinal fasiculus and left corticospinal tract, but these differences were not correlated with language scores. These findings suggest that white matter microstructure in the left and right ILF varies in relation to lexical development in young males with ASD. The findings also support the use of raw scores on language-relevant standardized tests for assessing early language-brain relationships. Autism Res 2017. © 2017 International Society for Autism Research, Wiley Periodicals, Inc. Autism Res 2017, 10: 1107-1119. © 2017 International Society for Autism Research, Wiley Periodicals, Inc.

Naigles|Letitia R|LR|
Johnson|Ryan|R|
Mastergeorge|Ann|A|
Ozonoff|Sally|S|
Rogers|Sally J|SJ|
Amaral|David G|DG|
Nordahl|Christine Wu|CW|

D000067877:Autism Spectrum Disorder
D001921:Brain
D002663:Child Language
D002675:Child, Preschool
D056324:Diffusion Tensor Imaging
D006801:Humans
D008297:Male
D009434:Neural Pathways
D066127:White Matter

DTI
language development
brain imaging
preschoolers


Wine Storage at Cellar vs. Room Conditions: Changes in the Aroma Composition of Riesling Wine.

Abstract: Storage temperature is one of the most important factors affecting wine aging. Along with bottling parameters (type of stopper, SO2 level and dissolved O2 in wine), they determine how fast wine will evolve, reach its optimum and decline in sensory quality. At the same time, lowering of the SO2 level in wine has been a hot topic in recent years. In the current work, we investigated how Riesling wine evolved on the molecular level in warm (~25 °C) and cool (~15 °C) conditions depending on the SO2 level in the wine (low, medium and high), flushing of the bottle's headspace with CO2 and three types of stoppers (Diam 30, Diam 30 origin and Diam 5) with different OIR levels (0.8-1.3 mg) and OTR levels (0.3-0.4 mg/year). It was demonstrated that the evolution of primary and secondary aromas, wine color and low molecular weight sulfur compounds (LMWSCs) during the two years of aging mainly depended on the storage temperature. Variation in the SO2 level and CO2 in the headspace affected mostly certain LMWSCs (H2S, MeSH) and β-damascenone. New aspects of C13-norisprenoids and monoterpenoids behavior in Riesling wine with different levels of SO2 and O2 were discussed. All three types of stoppers showed very close wine preservation properties during the two years of storage. The sensory analysis revealed that, after only six months, the warm stored wines with a low SO level were more oxidized and different from the samples with medium and high SO2 levels. A similar tendency was also observed for the cool stored samples.

Tarasov|Andrii|A| Garzelli|Federico|F| Schuessler|Christoph|C| Fritsch|Stefanie|S| Loisel|Christophe|C|0000-0003-4034-2120 Pons|Alexandre|A| Patz|Claus-Dieter|CD| Rauhut|Doris|D| Jung|Rainer|R|

wine
storage
aroma
Riesling
temperature
aging
stopper
sensory
oxygen
sulfur dioxide


Identification of the skeletal remains of the Czech communist regime crime victim, priest Josef Toufar.

Abstract: Parish priest Josef Toufar died as a direct consequence of torture committed by Communist State Security Service agents, forcing him to confess that "miraculous" movement of crucifix above the main altar during the Holy Mass held in the Roman-Catholic church in Číhošť was staged by using a technical equipment. Josef Toufar was presumably buried in a mass grave at the cemetery in Prague-Ďáblice under a false name Josef Zouhar. In 2013 the Czech Bishops' Conference grant an approval to begin the process of his beatification. However, the beatification required the exhumation and identification of the remains. In this case report, we describe the process of searching, exhumation, and the combined A-STR/Y-STR DNA analysis of remains of Pater Josef Toufar. His identification was feasible due to kinship analysis: buccal swabs of three family members (niece, grand-niece, and grand-nephew) were available for testing.

Pexa|T|T| Krajsa|J|J| Šaňková|M|M| Velemínský|P|P| Havrda|J|J| Kotrlý|T|T| Drábek|J|J|

Victim
Exhumation
DNA
Personal identification
Totalitarianism


Assessment of Different Types of Strabismus Among Pediatric Patients in a Tertiary Hospital in Jeddah.

Abstract: Background Strabismus, also known as squint, is an ocular disorder in which the eyes do not align properly with each other when looking at an object. The estimated global prevalence of strabismus among children is between 1.3% and 5.7%. This study aimed to assess the various types of strabismus among pediatric patients in Jeddah, in the western region of Saudi Arabia. Methods The medical records of 281 patients with strabismus aged ≤18 years, who presented to the pediatric ophthalmology clinic in King Abdulaziz University Hospital between 2010 and 2019, were retrospectively reviewed. Data were analyzed using the Statistical Package for Social Sciences (SPSS; IBM Corp., Armonk, NY, USA). A p-value of 0.05 or less was considered statistically significant. Results Out of the 281 patients, 141 were (50.2%) female. The average age of the patients was 9.50 ± 4.24 years. The most common type of strabismus was esotropia (177 [63%] patients), followed by exotropia (96 [34.2%] patients), hypertropia (10 [3.6%] patients), and dissociated vertical deviation (four [1.4%] patients). Two-hundred thirty-one (82.8%) patients had bilateral strabismus. A total of 178 patients (63.3%) had no associated conditions with strabismus, whereas 103 (36.7%) had an associated condition. A significant relationship was observed between esotropia and prematurity (p = 0.024). Conclusion Esotropia was the most common type of strabismus among the patients, followed by exotropia. The results of this study showed that males were equally affected as females. We also found a significant relationship between esotropia and prematurity. Implementation of a compulsory nationwide pediatric ophthalmic screening program for children aged one, three, and five years is recommended to enable timely diagnosis of strabismus and any other refractive errors.

Qanat|Ahmed S|AS|
Alsuheili|Abdullah|A|
Alzahrani|Abdulkarim M|AM|
Faydhi|Abdulrahman A|AA|
Albadri|Abdulhadi|A|
Alhibshi|Nizar|N|

strabismus
pediatric
jeddah
saudi arabia
esotropia
exotropia
hypertropia
dissociated vertical deviation


Quality care, public perception and quick-fix service management: a Delphi study on stressors of hospital doctors in Ireland.

Abstract:
OBJECTIVES
To identify and rank the most significant workplace stressors to which consultants and trainees are exposed within the publicly funded health sector in Ireland.

DESIGN
Following a preliminary semistructured telephone interview, a Delphi technique with 3 rounds of reiterative questionnaires was used to obtain consensus. Conducted in Spring 2014, doctors were purposively selected by their college faculty or specialty training body.

SETTING
Consultants and higher specialist trainees who were engaged at a collegiate level with their faculty or professional training body. All were employed in the Irish publicly funded health sector by the Health Services Executive.

PARTICIPANTS
49 doctors: 30 consultants (13 male, 17 female) and 19 trainees (7 male, 12 female). Consultants and trainees were from a wide range of hospital specialties including anaesthetics, radiology and psychiatry.

RESULTS
Consultants are most concerned with the quality of healthcare management and its impact on service. They are also concerned about the quality of care they provide. They feel undervalued within the negative sociocultural environment that they work. Trainees also feel undervalued with an uncertain future and they also perceive their sociocultural environment as negative. They echo concerns regarding the quality of care they provide. They struggle with the interface between career demands and personal life.

CONCLUSIONS
This Delphi study sought to explore the working life of doctors in Irish hospitals at a time when resources are scarce. It identified both common and distinct concerns regarding sources of stress for 2 groups of doctors. Its identification of key stressors should guide managers and clinicians towards solutions for improving the quality of patient care and the health of care providers.

Hayes|Blanaid|B| Fitzgerald|Deirdre|D| Doherty|Sally|S| Walsh|Gillian|G|

D011569:Psychiatric Status Rating Scales

Delphi technique
quality of healthcare
work
stress
physician


Efficacy of Focused Group Discussion on Knowledge and Practices Related to Menstruation among Adolescent Girls of Rural Areas of Rhtc of a Medical College: An Interventional Study.

Abstract:
Context
Learning about menstrual hygiene is vital part of health education for adolescent girls so that they can continue to work and maintain hygienic habits throughout their adult life.

Aim
The aim is to study the efficacy of focused group discussion (FGD) in comparison to didactic lecture method (DL) on knowledge and practices related to menstruation among adolescent girls of rural areas.

Materials and Methods
Community-based interventional study was carried out among 260 adolescent girls. Knowledge and practice were assessed with the help of questionnaire preintervention. During intervention, 130 girls in DL group were given DL and 130 girls in FGD received FGD. After 2 months, all 260 girls were contacted. Their knowledge and practices were assessed using same questionnaire.

Statistical Analysis
Yates corrected Chi-square and Student's t-test was used.

Results
Both methods were equally effective in increasing mean knowledge and practices score (P < 0.05). On comparison of mean postintervention scores between the two groups for knowledge, the FGD method was found to be superior (P < 0.05) but not for practices (P > 0.05).

Conclusion
FGD was more effective than DL method for knowledge related to menstruation but not for practices.

knowledge
practices
menstruation
Adolescent girls
rural areas


Preventing spread of SARS-CoV-2 and preparing for the COVID-19 outbreak in the surgical department: perspectives from two Scandinavian countries.

Abstract: A COVID-19 pandemic was declared on March 11 by the World Health Organization (WHO). The first cases of COVID-19 were confirmed on January 31 in Sweden and on February 26 in Norway. Despite being similar countries with universal healthcare systems, the governmental approaches to mitigation of the epidemic have varied considerably. Norway initiated a societal lockdown effective from March 12, the same day as the first confirmed death. Sweden has initiated a more laxed and gradual strategy based on the appeal for a strong personal sense of responsibility to mitigate the viral spread. In both countries, the first weeks of preparation has seen a strong reduction in elective surgery, with several implemented principles to mitigate SARS-CoV-2 spread and prepare for surgical care for COVID-19 diseases as needed. This invited leading article gives a brief overview of some of the early experiences of the outbreak in two Scandinavian countries.

Lindeman|Robbert-Jan|RJ| Sund|Malin|M| Löfgren|Jenny|J| Basso|Trude|T| Søreide|Kjetil|K|0000-0001-7594-4354

COVID-19
pandemic
organization
viral spread
surgery
Scandinavia
coronavirus
health care system


Effects of calcium silicate cements on dental pulp cells: A systematic review.

Abstract:
OBJECTIVES
The aim of this study was to evaluate the biocompatibility, odontogenic, angiogenic and inflammatory effects of commercially available calcium silicate cements (CSCs) on dental pulp cells.

DATA
In vitro, animal and human in vivo studies reporting on biocompatibility, odontogenic, angiogenic and inflammatory effects of CSCs on dental pulp cells were screened using a systematic review, and a descriptive analysis performed.

SOURCES
We searched Medline via PubMed, Google Scholar and Scopus, followed by hand search and cross-referencing.

STUDY SELECTION
From 7007 identified studies; 38 were included. At least one MTA-type product was evaluated in each study, with ProRooT MTA being the most frequently assessed, followed by Biodentine and iRoot BP Plus. Nearly all CSCs exhibited a high biocompatibility and induced odontogenic and angiogenic effects. There was great heterogeneity in methodology and findings. In vivo, effects differed between materials; also, differences between human or animal pulp cell effects were noted. In vitro, the dilution of the cement, the period of exposure to the CSC and the specific effect measure influenced the outcomes. No CSC was clearly superior to alternatives.

CONCLUSIONS
All commercially available CSCs are biocompatible, exhibit comparable and favorable effects on odontogenic differentiation of dental pulp cells in vitro and can efficiently enhance dentin bridge formation of high quality with minimal inflammation. No specific CSC can be recommended.

CLINICAL SIGNIFICANCE
Most CSCs are highly biocompatible, promoting pulp healing at minimal pulp inflammation. While the variation in methodology limits comparisons across studies, it seems that nearly all CSCs show favorable effects on dental pulp cell. We are unable to recommend one specific material over the others.

Calcium silicate cements
Dental pulp cells
Biocompatibility
Pulp inflammation
Dental pulp response
Direct pulp capping
Odontogenesis
Pulp repair


Evaluation of the effects of sweet potato (Ipomoea batatas (L.) Lam) in broiler diets.

Abstract: Cereal grains such as maize and wheat are used extensively in feed formulations for poultry as the primary source of carbohydrates. High cost of these grains in many developing countries necessitates the evaluation of other ingredients that are grown locally. Sweet potato is one such crop. The study was conducted as a proof of concept experiment to test the hypothesis that in the presence and absence of enzyme, sweet potato roots when included in diets of broiler chickens may affect the total metabolisable energy content of the diets which may exert certain influences on dry matter digestibility of these diets as well as impacting on production and certain gut parameters. A total of 120 chicks were raised on a commercial starter feed from day 0 to 19. On day 22, the birds were individually weighed and allocated to 96 single bird metabolism cages to conduct a 7-day classical apparent metabolisable energy (AME) assay. The test diets contained 0% and 25% sweet potato flour (SPF) with and without enzyme supplementation (Rovabio Excel AP T-flex) and replicated 24 times. AME of the control diet with and without enzyme was 14.05 and 13.91 MJ/kg whilst the AME of the SPF diets with and without enzymes were 13.45 and 13.43 MJ/kg respectively. AME of SPF was 12.08 MJ/kg. Birds fed the SPF had significantly reduced end weights (p = .002) and weight gains (p < .001) leading to significantly higher intake (p = .004) and FCRs (p < .001) in birds. These effects in growth parameters highlight the need to balance dietary protein and total amino acids when using SPF in broiler diets and may not be a negative effect of SPF per say as AME and dry matter digestibility of SPF diets were comparable to the control diet. The level of sucrase activity in the jejunum was significantly (p < .001) lower due to enzyme inclusion. Use of SPF in the current study did not negatively influence the activities of the brush border enzymes maltase and sucrase, gut morphology in the jejunum of broilers or the load of Enterobacteriaceae in the caecal of birds. This finding is promising in that the gut parameters associated with digestive capacity and gut health were not compromised with feeding of SPF to broilers.

D000824:Animal Nutritional Physiological Phenomena

dry matter digestibility
apparent metabolisable energy
intake
gut morphology
digestive enzymes
feed conversion ratio
gut microflora


Direct gaze elicits atypical activation of the theory-of-mind network in autism spectrum conditions.

Abstract: Eye contact plays a key role in social interaction and is frequently reported to be atypical in individuals with autism spectrum conditions (ASCs). Despite the importance of direct gaze, previous functional magnetic resonance imaging in ASC has generally focused on paradigms using averted gaze. The current study sought to determine the neural processing of faces displaying direct and averted gaze in 18 males with ASC and 23 matched controls. Controls showed an increased response to direct gaze in brain areas implicated in theory-of-mind and gaze perception, including medial prefrontal cortex, temporoparietal junction, posterior superior temporal sulcus region, and amygdala. In contrast, the same regions showed an increased response to averted gaze in individuals with an ASC. This difference was confirmed by a significant gaze direction × group interaction. Relative to controls, participants with ASC also showed reduced functional connectivity between these regions. We suggest that, in the typical brain, perceiving another person gazing directly at you triggers spontaneous attributions of mental states (e.g. he is "interested" in me), and that such mental state attributions to direct gaze may be reduced or absent in the autistic brain.

von dem Hagen|Elisabeth A H|EA|
Stoyanova|Raliza S|RS|
Rowe|James B|JB|
Baron-Cohen|Simon|S|
Calder|Andrew J|AJ|

theory-of-mind
autism
connectivity
eye gaze


Model-Based Comparative Analysis of Rifampicin and Rifabutin Drug-Drug Interaction Profile.

Abstract: Rifamycins are widely used for treating mycobacterial and staphylococcal infections. Drug-drug interactions (DDI) caused by rifampicin (RIF) are a major issue. We used a model-based approach to predict the magnitude of DDI with RIF and rifabutin (RBT) for 217 cytochrome P450 (CYP) substrates. On average, DDI caused by low-dose RIF were twice as potent as those caused by RBT. Contrary to RIF, RBT appears unlikely to cause severe DDI, even with sensitive CYP substrates.

Tuloup|Vianney|V| France|Mathilde|M| Garreau|Romain|R| Bleyzac|Nathalie|N| Bourguignon|Laurent|L| Tod|Michel|M| Goutelle|Sylvain|S|

rifampicin
rifabutin
drug-drug interaction
pharmacokinetics


Selecting Peritoneal Dialysis in the Older Dialysis Population.

Abstract: Selecting peritoneal dialysis (PD) in older individuals is a complex, multi-step process. At each step, older individuals may not have the opportunity to receive PD unless care is optimized. Older individuals are less likely to complete a PD assessment, because of unstable medical conditions, consideration of palliative care, or reluctance to approach frail patients once they are established on hemodialysis (HD). Older individuals are also more likely to have medical or social conditions that contraindicate PD or to have barriers to self-care PD that may not be overcome with support. Older individuals who are eligible for PD may be reluctant to choose it, leaving HD as the default modality. Finally, receipt of PD may be compromised by urgent HD or PD catheter-related complications at the time of insertion. Despite all these challenges, older patients can do very well on PD, so each step should be well understood and optimized in renal programs to maximize PD use in older patients.

Peritoneal dialysis
barriers
caregivers
education
elderly
patient selection


Inhibitory effect of α-lipoic acid on thioacetamide-induced tumor promotion through suppression of inflammatory cell responses in a two-stage hepatocarcinogenesis model in rats.

Abstract: To investigate the protective effect of α-lipoic acid (a-LA) on the hepatocarcinogenic process promoted by thioacetamide (TAA), we used a two-stage liver carcinogenesis model in N-diethylnitrosamine (DEN)-initiated and TAA-promoted rats. We examined the modifying effect of co-administered a-LA on the liver tissue environment surrounding preneoplastic hepatocellular lesions, with particular focus on hepatic macrophages and the mechanism behind the decrease in apoptosis of cells surrounding preneoplastic hepatocellular lesions during the early stages of hepatocellular tumor promotion. TAA increased the number and area of glutathione S-transferase placental form (GST-P)(+) liver cell foci and the numbers of proliferating and apoptotic cells in the liver. Co-administration with a-LA suppressed these effects. TAA also increased the numbers of ED2(+), cyclooxygenase-2(+), and heme oxygenase-1(+) hepatic macrophages as well as the number of CD3(+) lymphocytes. These effects were also suppressed by a-LA. Transcript levels of some inflammation-related genes were upregulated by TAA and downregulated by a-LA in real-time RT-PCR analysis. Outside the GST-P(+) foci, a-LA reduced the numbers of apoptotic cells, active caspase-8(+) cells and death receptor (DR)-5(+) cells. These results suggest that hepatic macrophages producing proinflammatory factors may be activated in TAA-induced tumor promotion. a-LA may suppress tumor-promoting activity by suppressing the activation of these macrophages and the subsequent inflammatory responses. Furthermore, a-LA may suppress tumor-promoting activity by suppressing the DR5-mediated extrinsic pathway of apoptosis and the subsequent regeneration of liver cells outside GST-P(+) foci.

Fujii|Yuta|Y| Segawa|Risa|R| Kimura|Masayuki|M| Wang|Liyun|L| Ishii|Yuji|Y| Yamamoto|Ryuichi|R| Morita|Reiko|R| Mitsumori|Kunitoshi|K| Shibutani|Makoto|M|

D017392:Thiobarbituric Acid Reactive Substances

Fas (TNFRSF6)-associated via death domain

aldehyde dehydrogenase family 1 member A1

hypoxanthine guanine phosphoribosyl transferase

nuclear factor, erythroid derived 2, like 2

serine (or cysteine) peptidase inhibitor, clade E, member 1

terminal deoxynucleotidyl transferase-mediated nick end labeling

tumor necrosis factor (ligand) superfamily, member 10

tumor necrosis factor receptor superfamily, member 10b

tumor necrosis factor-related apoptosis-inducing ligand

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 U U U U U U U U M U U M U U U U U U U U U R U U M U U U U U U U U U U U U U U U U U M M U M U U M U M M M M U U U U U M M U M U U M U U U M M M M M U


Cinnamon and clove essential oils to improve physical, thermal and antimicrobial properties of chitosan-gum arabic polyelectrolyte complexed films.

Abstract: Chitosan-gum arabic-based polyelectrolyte complexed films with cinnamon essential oil (CEO) and clove essential oil (CLO) were developed. The effect of EO concentrations, types and their combinations on the physical, thermal and antimicrobial properties of films were investigated. The results showed that the incorporation of EOs decreased the ζ-potential and viscosity, but increased the particle size of film-forming dispersions. Films incorporated with CEO and combined EOs exhibited better water barrier properties compared to those with CLO and single EO. Films containing CEO showed lower EO loss and higher thermal stability compared to those containing CLO, and the reason was attributed to the stronger interactions between chitosan, gum arabic and CEO. The combination of EOs resulted in higher retention and delayed release rate in food stimulant, resulting in stronger antimicrobial activities. The performance of films with the CEO and the combined EOs brought new formulation ideas in antimicrobial films.

Xu|Tian|T| Gao|ChengCheng|C| Feng|Xiao|X| Huang|Meigui|M| Yang|Yuling|Y| Shen|Xinchun|X| Tang|Xiaozhi|X|

Clove essential oil
Antimicrobial properties
Polyelectrolyte complexed films
Cinnamon essential oil
Chitosan
Gum arabic


Cross-sectional study to identify the prevalence of and factors associated with laminitis in UK donkeys.

Abstract:
BACKGROUND
Laminitis causes lameness in donkeys, but its prevalence and factors associated with disease remain uncertain.

OBJECTIVES
To determine the prevalence of and identify factors associated with laminitis in donkeys.

STUDY DESIGN
Retrospective cross-sectional study.

METHODS
All donkeys at the Donkey Sanctuary, UK, October 2015 to March 2019 were included. For animals that had laminitis during this period, age, sex, weight, body condition score, and the onset date and type of each episode (first or recurrent, acute or chronic) were recorded. Additionally, management data, foot lesion score, endocrine data, other medical conditions, occurrence of foot trimming, surgical procedures, diagnostic imaging, behavioural modification therapy or movement between farms within the month prior were noted. Controls were animals that did not experience laminitis during this period and similar data were recorded. Multivariable logistic regression modelling assessed the differences between the control group and laminitis outcome groups (first, all laminitis, acute and chronic episodes).

RESULTS
Altogether, 707 animals were included; 364 were control animals; 343 had a first episode of laminitis during the study period, of which 200/343 had no further episodes and 143/343 had recurrent episodes resulting in a total of 512 laminitis episodes and the period prevalence was 48.5% over 42 months. Overall, 180/512 (35%) laminitis episodes were acute and 332/512 (65%) were chronic. Compared with control animals, the laminitic outcome groups were significantly (P < .05) more likely to be younger (first episode), less likely to get extra feed (all four groups) or have an additional medical problem (first episode), and less likely to have undergone dental work, movement, imaging (all four groups) or surgery (first; all laminitis, chronic episodes) in the month preceding the episode.

MAIN LIMITATIONS
These results may not be applicable to the wider donkey population.

CONCLUSIONS
Laminitis commonly affects donkeys, but factors associated with donkey laminitis differ from those reported in horses.

laminitis
donkey
horse
PPID
endocrinopathy
risk factor


Integrative Analysis of Fecal Metagenomics and Metabolomics in Colorectal Cancer.

Abstract: Although colorectal cancer (CRC) is the second leading cause of death in developed countries, current diagnostic tests for early disease stages are suboptimal. We have performed a combination of UHPLC-MS metabolomics and 16S microbiome analyses on 224 feces samples in order to identify early biomarkers for both advanced adenomas (AD) and CRC. We report differences in fecal levels of cholesteryl esters and sphingolipids in CRC. We identified Fusobacterium, Parvimonas and Staphylococcus to be increased in CRC patients and Lachnospiraceae family to be reduced. We finally described Adlercreutzia to be more abundant in AD patients' feces. Integration of metabolomics and microbiome data revealed tight interactions between bacteria and host and performed better than FOB test for CRC diagnosis. This study identifies potential early biomarkers that outperform current diagnostic tools and frame them into the stablished gut microbiota role in CRC pathogenesis.

Clos-Garcia|Marc|M|
Garcia|Koldo|K|0000-0002-6107-9416
Alonso|Cristina|C|
Iruarrizaga-Lejarreta|Marta|M|
D'Amato|Mauro|M|
Crespo|Anais|A|
Iglesias|Agueda|A|
Cubiella|Joaquín|J|
Bujanda|Luis|L|
Falcón-Pérez|Juan Manuel|JM|

integration
metabolomics
microbiome
multiomics
omics
omics integration


Proposed classification for interproximal contacts of primary molars using CBCT: a pilot study.

Abstract: Background: Contact areas in primary teeth are known to be broader, flatter, and situated more gingivally than in permanent teeth. The objective of the present study was to evaluate the different types of intact contact areas in primary teeth using cone beam computed tomography (CBCT) among children. Methods: A cross-sectional study was designed with 74 contacts from 28 existing CBCT images of patients aged between 3 and 14 years, obtained from the Indian Dental Education Academy, Chennai, India. The shape of the contact area was observed at three levels, the coronal, middle, and apical thirds, in three different sections of CBCT. The weighted Cohen's kappa values for inter-examiner reliability was 0.893 at baseline. Prevalence of the types of contact areas was expressed in the form of numbers and percentages. Results: Results exhibited four different types of contact areas between the primary molars, namely, O type, X type, I type, and S type, based on the shapes observed; hence, the proposed classification is referred to as OXIS. The most common pattern seen was I (66.2%), followed by X (21.6%), O (9.4%) and the least common was S (2.7%). Conclusion: The three-dimensional evaluation of intact interproximal contact areas between primary molars are of four types.

primary molars
Computed tomography
cross-sectional study
proximal contact


Tumoral LINE-1 hypomethylation is associated with poor survival of patients with intrahepatic cholangiocarcinoma.

Abstract:
BACKGROUND
DNA methylation changes occurring in cancer cells are featured with both promoter CpG island hypermethylation and diffuse genomic hypomethylation. Long interspersed element-1 (LINE-1) is repeated in an interspersed manner with an estimated 500,000 copies per genome. LINE-1 has its CpG sites of the 5' untranslated region methylated heavily in normal cells and undergoes demethylation in association with cancerization. However, little information is available regarding LINE-1 hypomethylation and its prognostic implication in intrahepatic cholangiocarcinomas.

METHODS
A total of 172 cases of intrahepatic cholangiocarcinomas were analyzed for their methylation levels at four CpG sites of LINE-1 using bisulfite pyrosequencing. We examined the relation between tumoral LINE-1 methylation level and clinicopathological features, including survival.

RESULTS
Tumor differentiation, lymphatic invasion, and T stage were associated with a low average methylation level of LINE-1 at the four CpG sites; LINE-1 methylation level tended to be lower in high-grade differentiation, lymphatic emboli, and higher T stage. LINE-1 hypomethylation was significantly linked with lower cancer-specific survival in patients with intrahepatic cholangiocarcinoma and was found to be an independent prognostic parameter.

CONCLUSIONS
Our findings suggest that tumoral LINE-1 hypomethylation could be a molecular biomarker heralding poor prognosis of patients with intrahepatic cholangiocarcinoma. Our findings need to be validated in further study.

D020084:Long Interspersed Nucleotide Elements

Line-1 Cholangiocarcinoma Methylation Pyrosequencing Prognosis


Dynamic Transcriptome Analysis Reveals Uncharacterized Complex Regulatory Pathway Underlying Genotype-Recalcitrant Somatic Embryogenesis Transdifferentiation in Cotton.

Abstract: As a notable illustration of totipotency and plant regeneration, somatic embryogenesis (SE) is the developmental reprogramming of somatic cells toward the embryogenesis pathway, the key step for genetic engineering. Investigations examining the totipotency process are of great fundamental and practical importance in crop biotechnology. However, high-frequency regeneration of cotton via SE has been limited due to genotype-dependent response. The molecular basis deciphering SE genotype recalcitrance remains largely unexplored in cotton. In the current study, to comprehensively investigate the dynamic transcriptional profiling and gene regulatory patterns involved in SE process, a genome-wide RNA sequencing analysis was performed in two cotton genotypes with distinct embryogenic abilities, the highly embryogenic genotype Yuzao 1 (YZ) and the recalcitrant genotype Lumian 1 (LM). Three typical developmental staged cultures of early SE-hypocotyls (HY), nonembryogenic calli (NEC) and primary embryogenic calli (PEC)-were selected to establish the transcriptional profiles. Our data revealed that a total of 62,562 transcripts were present amongst different developmental stages in the two genotypes. Of these, 18,394 and 26,514 differentially expressed genes (DEGs) were identified during callus dedifferentiation (NEC-VS-HY) and embryogenic transdifferentiation (PEC-VS-NEC), respectively in the recalcitrant genotype, 21,842 and 22,343 DEGs in the highly embryogenic genotype. Furthermore, DEGs were clustered into six expression patterns during cotton SE process in the two genotypes. Moreover, functional enrichment analysis revealed that DEGs were significantly enriched in fatty acid, tryptophan and pyruvate metabolism in the highly embryogenic genotype and in DNA conformation change otherwise in the recalcitrant genotype. In addition, critical SE-associated expressed transcription factors, as well as alternative splicing events, were notably and preferentially activated during embryogenic transdifferentiation in the highly embryogenic genotype compared with the recalcitrant genotype. Taken together, by systematically comparing two genotypes with distinct embryogenic abilities, the findings in our study revealed a comprehensive overview of the dynamic gene regulatory patterns and uncharacterized complex regulatory pathways during cotton SE genotype-dependent response. Our work provides insights into the molecular basis and important gene resources for understanding the underlying genotype recalcitrance during SE process and plant regeneration, thereby holding great promise for accelerating the application of biotechnology to cotton for improving its breeding efficiency.

Guo|Huihui|H| Guo|Haixia|H| Zhang|Li|L| Fan|Yijie|Y| Wu|Jianfei|J| Tang|Zhengmin|Z| Zhang|Yao|Y| Fan|Yupeng|Y| Zeng|Fanchang|F|0000-0001-8393-1174

D018507:Gene Expression Regulation, Developmental

D058439:Plant Somatic Embryogenesis Techniques

genotype-recalcitrant
somatic embryogenesis
genotype-dependent response
molecular basis
embryogenic transdifferentiation
dynamic regulatory pathway
embryogenic competence


Outcomes of cataract surgery in eyes with diabetic macular oedema: Data from the Fight Retinal Blindness! Registry.

Abstract:
IMPORTANCE
There are limited data on real-world outcomes of cataract surgery in eyes receiving intravitreal treatments for diabetic macular oedema (DMO).

BACKGROUND
Cataract surgery may exacerbate oedema in some eyes with DMO resulting in inferior outcomes.

DESIGN
Matched, case-controlled retrospective study of observational data in routine clinical practice.

PARTICIPANTS
Eyes receiving intravitreal treatments for DMO tracked in the Fight Retinal Blindness! Registry.

METHODS
Eyes that underwent cataract surgery were identified and matched 1:1 with phakic controls also receiving intravitreal injections for DMO. We also assessed potential factors that were associated with better visual acuity (VA) outcomes.

MAIN OUTCOME MEASURES
Change in VA 6 months after cataract surgery.

RESULTS
Cataract surgery was identified in 208 eyes of 156 patients of which 147 eyes had 6 months of observations before and after surgery. The mean VA 6 months after surgery improved by 10.6 letters and was similar to their matched phakic controls (68.8 vs 69.2 letters; P = 0.8). Mean CST both 6 months before (341 μm) and after (360 μm) surgery were similar (P = 0.08). However, these eyes had thicker maculae and they received more injections than their matched phakic controls both before and after surgery. Eyes with worse VA before surgery and those that had received intravitreal treatment in the 4 weeks preceding surgery were more likely to gain vision.

CONCLUSIONS AND RELEVANCE
Visual outcomes of cataract surgery in eyes receiving intravitreal therapy for DMO were reasonably better. Their maculae were thicker and required more injections in the 6 months before and after surgery than their phakic controls.

Bhandari|Sanjeeb|S|0000-0002-4110-4274
Biechl|Anne C|AC|
Nguyen|Vuong|V|0000-0001-9070-9803
Squirrell|David|D|
Mehta|Hemal|H|
Barthelmes|Daniel|D|
Gillies|Mark C|MC|

vascular endothelial growth factor inhibitor


Bladder distension: An unusual cause of reflux of blood and hemodynamic changes (autonomic dysreflexia) during endovascular coiling.

Abstract: Autonomic dysreflexia due to distended bladder is well known. Reflux of blood during endovascular procedure is also a common observation. It happens due to difference in pressure gradient between arterial pressure and that of infusing solution. Generally it happens when the infusion bottle is empty or the pressure in infusion bottles fall. We present an uncommon situation where distended bladder mechanically resulted in reflux of blood into endovascular catheters as well as alteration in hemodynamic parameters. Both settled once the bladder was empty.

Sharma|Dp|D| Singh|Daljit|D| Ganjoo|P|P| Tandon|M|M|


Therapeutic ultrasound experiments in vitro: Review of factors influencing outcomes and reproducibility.

Abstract: Current in vitro sonication experiments show immense variability in experimental set-ups and methods used. As a result, there is uncertainty in the ultrasound field parameters experienced by sonicated samples, poor reproducibility of these experiments and thus reduced scientific value of the results obtained. The scope of this narrative review is to briefly describe mechanisms of action of ultrasound, list the most frequently used experimental set-ups and focus on a description of factors influencing the outcomes and reproducibility of these experiments. The factors assessed include: proper reporting of ultrasound exposure parameters, experimental geometry, coupling medium quality, influence of culture vessels, formation of standing waves, motion/rotation of the sonicated sample and the characteristics of the sample itself. In the discussion we describe pros and cons of particular exposure geometries and factors, and make a few recommendations as to how to increase the reproducibility and validity of the experiments performed.

Snehota|Martin|M|
Vachutka|Jaromir|J|
Ter Haar|Gail|G|
Dolezal|Ladislav|L|
Kolarova|Hana|H|

D018929:Cell Culture Techniques
D003198:Computer Simulation
D004867:Equipment Design
D019544:Equipment Failure Analysis
D066298:In Vitro Techniques
D008954:Models, Biological
D015203:Reproducibility of Results
D013010:Sonication
D014464:Ultrasonic Therapy

Therapeutic ultrasound
Sonication
Ultrasound exposure
In vitro experiment


Instances of altered gut microbiomes among Irish cricketers over periods of travel in the lead up to the 2016 World Cup: A sequencing analysis.

Abstract:
BACKGROUND
Changes and stresses experienced during travel have the potential to impact the gut microbiome, with travel implicated in the spread of antibiotic resistance genes across continents. The possibility of gut microbiome-mediated negative impacts arising from travel, and consequences for peak performance, would be of particular concern for elite athletes.

METHODS
Faecal samples were collected from male (N = 14) and female (N = 7) cricket players during the build-up to the 2016 Cricket World Cup. Baseline and post-travel samples were collected from all participants and subjected to 16S rRNA amplicon sequencing. Samples from a subset of participants (N = 4) were also analysed by shotgun metagenomic sequencing.

RESULTS
Analysis revealed a single travel time point as having the potential to have an impact on the gut microbiome. Reductions in alpha diversity following travel were observed, accompanied by shifts in the taxonomic profile of the gut microbiome. Antibiotic resistance and virulence genes were also identified as undergoing changes following travel.

CONCLUSIONS
This study reveals that periods of travel, in particular following gastrointestinal distress, may result in gut microbiome disruption. While this analysis was completed in athletes, the findings are applicable to all travelling individuals and considerations should be made surrounding travel in an attempt to reduce these changes.

O' Donovan|Ciara M|CM|
Connor|Brendan|B|
Madigan|Sharon M|SM|
Cotter|Paul D|PD|
O' Sullivan|Orla|O|

Gut microbiome
Travel
Antibiotic resistance
Virulence
Exercise
Gut distress


Experimental analysis of aspect ratio in iliac vein stenosis.

Abstract:
BACKGROUND
Veins are thin-walled tubes. Their lumen is roughly circular with an aspect ratio close to 1:1 under physiologic pressures. When they collapse owing to decreased internal pressure or external compression, the aspect ratio changes. The vertical diameter is usually diminished more than the transverse, with a considerable decrease in the lumen area. The recent emergence of stent correction of many venous compression syndromes, particularly iliac vein stenosis, has brought attention to the importance of the aspect ratio, quite apart from an overall decrease in caliber. The iliac vein pressure is influenced not only by stenosis, but also intra-abdominal pressure, right atrial pressure, and collaterals. We investigated the impact of aspect ratio in an experimental model incorporating these factors.

METHODS
Inflow was provided from a header tank at 25 mm Hg pressure into a Penrose tubing enclosed in a polyethylene cylinder pressurized (Starling pressure) to simulate intra-abdominal pressures of 5 and 10 mm Hg. The Penrose drained into an outflow tank with a pressure of 7 mm Hg, simulating right atrial pressure. Stenosis was simulated with a series of three-dimensional, printed plastic nozzles with caliber areas of 50, 100, and 200 mm2 and varying in aspect ratios of 1:1 to 1:4. The flow and pressure in this system was monitored with the use of overflow collaterals in some experiments.

RESULTS
Free flow from the header tank through the Penrose (zero Starling pressure) with a 200 mm2 circle nozzle into the outflow tank with zero pressure resulted in flow pressure of approximately 1.5 mm Hg. Using nozzles of a smaller caliber or an increased aspect ratio resulted in an increase of flow pressures of up to approximately 3.7 mm Hg. Flow into an outflow tank of 7 mm Hg simulating right atrial pressure further increased flow pressures by approximately 7 mm Hg. The addition of Starling pressures of 5 and 10 mm Hg simulating abdominal pressure increased flow pressure even further to the 10 to 17 mm Hg range. When the Starling pressure was dominant, the additional contribution of nozzle caliber stenosis or aspect ratio reduction to the overall flow pressure ranged from 2 to 6 mm Hg. Collateral overflow varied inversely with collateral resistance. Some experiments yielded an anomalous flow/pressure phenomena known to occur in collapsible tube flows.

CONCLUSIONS
A decrease in the caliber or the aspect ratio of iliac vein stenosis was among several other factors that generate peripheral venous hypertension in an experimental model. Increased intra-abdominal pressure is a major influence that amplifies the pressure effects of aspect ratio or caliber reduction.

Aspect ratio
Iliac vein stenosis
Intra-abdominal pressure
Venous hypertension
Iliac vein caliber
Peripheral venous pressure


A 24-Year Follow-up Study on Recidivism in Male Mentally Disordered Sexual Offenders With and Without Psychotic Disorders.

Abstract: There is a lack of knowledge on mentally disordered sex offenders (MDSOs) targeting adult victims, especially regarding recidivism patterns and the specific subgroup with psychiatric disorders. This paper presents index offense data, clinical data, and recidivism patterns over up to 24 years in a cohort of 146 MDSOs, with and without psychotic disorders, sentenced in Sweden between 1993 and 1997. At the time of the offense, all offenders were affected by clinical, developmental, and criminal history factors. MDSOs with psychotic disorders only marginally differed from those without, the former being less likely to have been institutionalized during childhood, intoxicated during the index offense, or diagnosed with a personality disorder, substance use disorder, or paraphilic disorder. In the cohort, 3.4% of the MDSOs were reconvicted for a new sex offense over 2 years, 9.6% over 5 years, 13.0% over 10 years, and 17.1% over the entire follow-up period of 24 years. In MDSOs with psychotic disorders, no subjects were reconvicted during the first 2 years, while 2.6% were reconvicted over 5 years, 5.3% over 10 years, and 7.9% over 24 years. Recidivism rates for violent and general reoffenses were 39.0% and 37.7%, respectively, for the cohort of MDSOs, and subjects with psychotic disorders reoffended significantly later in general offenses. In conclusion, MDSOs with psychotic disorders showed the same recidivism pattern as MDSOs without psychotic disorders. Furthermore, recidivism research may preferably focus on follow-up periods of 5-10 years since most offenders appear to recidivate within this timeframe.

Baudin|Christian|C| Nilsson|Thomas|T| Wallinius|Märta|M| Sturup|Joakim|J| Andiné|Peter|P|

follow-up
recidivism
psychotic disorder
mentally disordered sex offenders
sex offenses
rape


The surgical treatment of epilepsy.

Abstract: In 2009, the Commission for Epilepsy Surgery of the Italian League Against Epilepsy (LICE) conducted an overview about the techniques used for the pre-surgical evaluation and the surgical treatment of epilepsies. The recognition that, in selected cases, surgery can be considered the first-line approach, suggested that the experience gained by the main Italian referral centers should be pooled in order to provide a handy source of reference. In light of the progress made over these past years, some parts of that first report have accordingly been updated. The present revision aims to harmonize the general principles regulating the patient selection and the pre-surgical work-up, as well as to expand the use of epilepsy surgery, that still represents an underutilized resource, regrettably. The objective of this contribution is drawing up a methodological framework within which to integrate the experiences of each group in this complex and dynamic sector of the neurosciences.

Epilepsy surgery
Pre-surgical evaluation
Drug-resistant
Neuromodulation
Palliative surgery
Surgically remediable syndrome


Washing with water alone versus soap in maintaining remission of eczema.

Abstract:
BACKGROUND
There is no consensus on the use of soap in skin care for atopic dermatitis in Japan. Thus, this study aimed to evaluate the efficacy of soap to maintain eczema remission in atopic dermatitis patients during the fall-winter period in Japan.

METHODS
This assessor-blinded, pragmatic randomized, non-inferiority study enrolled atopic dermatitis patients whose eczema was controlled by regular steroid ointment application less than or equal to 2 days / week (tacrolimus ointment was permitted). For 8 ± 3 weeks, participants washed their upper and lower limbs on one side with soap (soap side) and on the other side with water alone (water side). The primary outcome was an Eczema Area and Severity Index score at week 8 ± 3.

RESULTS
Twenty-nine participants were analyzed. The Eczema Area and Severity Index scores at week 8 ± 3 of the water and soap sides were 0.0 (0.0-0.4) and 0.0 (0.0-0.4), respectively (P = 0.18). The difference between both sides was -0.02 (-0.11-0.08), and the limits of the 95% confidence interval did not reach the prespecified non-inferiority margin. The average Patient-Oriented Eczema Measure score was 1.27 ± 1.7 and 1.32 ± 1.8 for the water and soap sides, respectively (P = 0.92). The total number of additional steroid ointment applications was four (0-20) times and six (0-23) times, respectively (P = 0.98). Participants were categorized according to self-assessments of the usefulness of soap, with 2, 24, and 3 participants in the water-effective, invariant, and soap-effective groups, respectively.

CONCLUSIONS
For children with controlled atopic dermatitis, washing with water alone was not inferior to washing with soap for maintaining remission of eczema during the fall-winter period in Japan.

soap
skin care
atopic dermatitis
fall-winter
detergent


Dopamine D1 Receptor-Mediated Regulation of Per1, Per2, CLOCK, and BMAL1 Expression in the Suprachiasmatic Nucleus in Adult Male Rats.

Abstract: Photic and non-photic inputs are reported to affect clock gene expressions and behavioral activities in the SCN. However, it is not known whether dopaminergic input mediates these regulatory effects on clock genes. The present study examined the molecular effects of dopamine D1 agonist on Per1, Per2, CLOCK, and Bmal1 expressions in the SCN and its effect on behavioral activities to determine the role of dopamine D1 receptor in regulation of these gene expressions and behavioral activities in adult male Wistar rats. To examine the molecular effects of dopamine D1 agonist day and night, we injected 20 mg/kg SKF38393 to the first group of rats at 6 a.m. and the second group at 6 p.m. We also injected saline to the third and fourth groups of rats at 6 a.m. and 6 p.m. as control groups. All rats were sacrificed 2 h following the injections. The real-time PCR technique was used to evaluate the clock gene expression. In addition, to examine the effects of dopamine D1 agonists on behavioral activities, we injected 20 mg/kg SKF38393 to SKF receiving group and saline to control group. The behavioral activities of the rats were monitored on the running wheel for 21 days, 1 week following the injections. SKF injections increased the Per2 and CLOCK expressions in the daytime and significantly decreased the Per1 and Bmal1 expressions. However, at night, SKF injections increased only Per2 expressions significantly and decreased the Per1, CLOCK, and Bmal1 genes expressions. Both saline receiving groups showed that all gene expressions were significantly higher except Per2 during nighttime. SKF injection increased the running wheel activity during nighttime significantly. Based on the obtained result, clock gene expression and behavioral activities in adult male Wistar rats may be altered or monitored by administration of exogenous dopamine.


Evaluation of temporal bone cholesteatoma and the correlation between high resolution computed tomography and surgical finding.

Abstract:
BACKGROUND
Acquired cholesteatomas are commonly seen in patients less than 30 years. There is a typical history of recurrent middle ear infections with tympanic membrane perforation. The diagnosis of cholesteatoma is usually made on otologic examination.

OBJECTIVE
The aim of the work was to study the role of high resolution computed tomography (HRCT) in detecting, evaluating, and diagnosing middle ear cholesteatoma.

PATIENTS AND METHODS
This was a prospective study that included 56 consecutive patients with chronic suppurative otitis media, unsafe type cholesteatomas. Each patient was subjected to full clinical evaluation, and HRCT examination. Intravenous contrast media was used in some patients with suspected intracranial complication. Preoperative radiological data were correlated with data related to surgical findings.

RESULTS
The study showed that a high incidence of cholesteatoma in the third decade of life. The scutum and lateral attic wall were the most common bony erosions in the middle ear bony wall (64.3%), and the incus was the most eroded ossicle in the middle ear (88.2%). Sclerosing of mastoid air cells were encountered in 60.7% of patients and the lateral semicircular canal was affected in 9%, while facial canal erosion was found in 21.4%. Temporal bone complications are more common than intracranial complications. HRCT findings were compared with operative features; the comparative study included the accuracy and sensitivity of HRCT in detecting cholesteatoma (92.8%), its location and extension (96.4%), ossicular chain erosion (98%), labyrinthine fistula and intracranial complications (100%).

CONCLUSION
The important role of HRCT scannig lies on the early detection of cholesteatoma, and more conservative surgical procedures can be used to eradicate the disease.

Gomaa|Mohammed A|MA|
Abdel Karim|Abdel Rahim A|AR|
Abdel Ghany|Hosny S|HS|
Elhiny|Ahmed A|AA|
Sadek|Ahmed A|AA|

cholesteatoma
high resolution computed tomography


Towards a subcutaneous optical biosensor based on thermally hydrocarbonised porous silicon.

Abstract: Advanced biosensors in future medicine hinge on the evolvement of biomaterials. Porous silicon (pSi), a generally biodegradable and biocompatible material that can be fabricated to include environment-responsive optical characteristics, is an excellent candidate for in vivo biosensors. However, the feasibility of using this material as a subcutaneously implanted optical biosensor has never been demonstrated. Here, we investigated the stability and biocompatibility of a thermally-hydrocarbonised (THC) pSi optical rugate filter, and demonstrated its optical functionality in vitro and in vivo. We first compared pSi films with different surface chemistries and observed that the material was cytotoxic despite the outstanding stability of the THC pSi films. We then showed that the cytotoxicity correlates with reactive oxygen species levels, which could be mitigated by pre-incubation of THC pSi (PITHC pSi). PITHC pSi facilitates normal cellular phenotypes and is biocompatible in vivo. Importantly, the material also possesses optical properties capable of responding to microenvironmental changes that are readable non-invasively in cell culture and subcutaneous settings. Collectively, we demonstrate, for the first time, that PITHC pSi rugate filters are both biocompatible and optically functional for lab-on-a-chip and subcutaneous biosensing scenarios. We believe that this study will deepen our understanding of cell-pSi interactions and foster the development of implantable biosensors.

Tong|Wing Yin|WY|
Sweetman|Martin J|MJ|
Marzouk|Ezzat R|ER|
Fraser|Cara|C|
Kuchel|Tim|T|
Voelcker|Nicolas H|NH|

Biosensor
Silicon
Biodegradation
Biocompatibility
Subcutaneous implant
Cytotoxicity


Potential Therapeutic and Prognostic Values of LSM Family Genes in Breast Cancer.

Abstract: In recent decades, breast cancer (BRCA) has become one of the most common diseases worldwide. Understanding crucial genes and their signaling pathways remain an enormous challenge in evaluating the prognosis and possible therapeutics. The "Like-Smith" (LSM) family is known as protein-coding genes, and its member play pivotal roles in the progression of several malignancies, although their roles in BRCA are less clear. To discover biological processes associated with LSM family genes in BRCA development, high-throughput techniques were applied to clarify expression levels of LSMs in The Cancer Genome Atlas (TCGA)-BRCA dataset, which was integrated with the cBioPortal database. Furthermore, we investigated prognostic values of LSM family genes in BCRA patients using the Kaplan-Meier database. Among genes of this family, LSM4 expression levels were highly associated with poor prognostic outcomes with a hazard ratio of 1.35 (95% confidence interval 1.21-1.51, p for trend = 3.4 × 10-7). MetaCore and GlueGo analyses were also conducted to examine transcript expression signatures of LSM family members and their coexpressed genes, together with their associated signaling pathways, such as "Cell cycle role of APC in cell cycle regulation" and "Immune response IL-15 signaling via MAPK and PI3K cascade" in BRCA. Results showed that LSM family members, specifically LSM4, were significantly correlated with oncogenesis in BRCA patients. In summary, our results suggested that LSM4 could be a prospective prognosticator of BRCA.


Inhibitory Activities of Phenolic Compounds Isolated from Adina rubella Leaves Against 5α-Reductase Associated with Benign Prostatic Hypertrophy.

Abstract: Adina rubella Hance (AR), a plant native to Korea, has been used as traditional medicine for dysentery, eczema, intoxication, and external hemorrhages. Previous phytochemical studies of AR have reported several components, including terpenoids, phenolics, and alkaloids. The current study evaluated the anti-oxidative and anti-inflammatory activities and 5α-reductase inhibition of isolated compounds of AR leaves to find a potential therapeutic agent for benign prostatic hypertrophy (BPH). Repeated chromatographic isolation of an 80% acetone extract of AR leaves yielded seven phenolic compounds: caffeic acid (1), chlorogenic acid (2), methyl chlorogenate (3), quercetin-3-rutinoside (4), kaempferol-3-O-α-l-rhamnopyranosyl-(1→6)-β-d-glucopyranoside (5), hyperoside (6), and grandifloroside (7). Compound 7 is a novel compound in AR. Caffeoyl derivatives 1-3 and 7 showed good anti-oxidative activities. In particular, caffeic acid (1) and grandifloroside (7) showed potent anti-inflammatory activities, and 7 also exhibited potent inhibitory activity against TNF-α and 5α-reductase. Our results show that the extract and grandifloroside (7) from leaves of AR might be developed as a source of potent anti-oxidative and anti-inflammatory agents and therapeutic agent for BPH.

Yin|Jun|J|
Heo|Jun Hyeok|JH|
Hwang|Yoon Jeong|YJ|
Le|Thi Tam|TT|
Lee|Min Won|MW|

5α-reductase
benign prostatic hypertrophy
Adina rubella Hance
anti-oxidative
anti-inflammatory


Effects of gonadotropin administration on clinical outcomes in clomiphene citrate-based minimal stimulation cycle IVF.

Abstract:
Purpose
Exogenous gonadotropins (EGn) have been used occasionally in clomiphene citrate (CC)-based minimal stimulation cycles to compensate insufficient secretion of endogenous gonadotropin; however, the effectiveness of EGn supplementation remains unknown. In the present study, we assessed whether EGn improved pregnancy outcomes in CC-based minimal stimulation cycles.

Methods
A total of 223 patients treated with CC and EGn (CC-EGn group) were matched one to one to patients treated with CC only (CC group) by propensity score matching. Embryonic and pregnancy outcomes were retrospectively compared between the groups.

Results
The numbers of retrieved oocytes, fertilized oocytes, cleaved embryos, and cryopreserved blastocysts were increased in the CC-EGn group compared with the CC group. However, the cumulative live birthrate was comparable between the two groups. Although the increased number of retrieved oocytes was correlated significantly with improvement of the cumulative live birthrate in both groups, the correlation tended to be lower in the CC-EGn group than in the CC group (odds ratio, 1.193 vs 1.553).

Conclusions
In CC-based minimal stimulation cycles, the stimulation should be started with CC only, and EGn administration should be scheduled only if insufficient secretion of endogenous gonadotropin is observed in the late follicular phase.

gonadotropins
clomiphene citrate
cumulative live birthrate
embryo transfer
in vitro fertilization


Effects of pollution on dormant-stage banks of cladocerans and rotifers in a large tropical reservoir.

Abstract: Here, we describe the abundance and composition of the dormant-stage banks of cladocerans and rotifers at two locations in a tropical reservoir (Furnas Reservoir, Minas Gerais, Brazil) that are subject to different anthropogenic impacts. We hypothesized that at the site that received sewage, the density of resting eggs would be higher, but the species richness would be lower. Sediment samples were collected monthly at the two sampling stations. We counted the number of dormant stages and performed hatching experiments in the laboratory. Combining both sampling locations, we found a total of 26 species, 16 cladocerans, and 10 rotifers. Our hypothesis was partially corroborated, since the abundance and richness of dormant stages were significantly higher in the location subjected to wastewater release. Environmental pollution resulting from wastewater release and the cultivation of tilapia in cages is the most likely factor contributing to the higher values of egg density at this location. In contrast, the presence of aquatic macrophytes (a possible result of nutrient enrichment) at the same site may have contributed to the increase in species richness. Finally, our study indicates that the wastewater release in the reservoir can affect the production of dormant stages by cladocerans and rotifers.

Furnas Reservoir
Resting eggs
Wastewater
Diapause
Eutrophication
Zooplankton


Visualization of Phytophthora palmivora Infection in Oil Palm Leaflets with Fluorescent Proteins and Cell Viability Markers.

Abstract: Bud rot (BR) is the most devastating disease affecting oil palm (Elaeis guineensis) crops in Colombia. Its causal agent, Phytophthora palmivora, initiates the infection in immature oil palm leaflets producing necrotic lesions, followed by colonization of opportunistic necrotrophs, which increases disease damage. To improve the characterization of the disease, we transformed P. palmivora using Agrobacterium tumefaciens-mediated transformation (ATMT) to include the fluorescent proteins CFP-SKL (peroxisomal localization), eGFP and mRFP1 (cytoplasmic localization). The stability of some transformants was confirmed by Southern blot analysis and single zoospore cultures; additionally, virulence and in vitro growth were compared to the wild-type isolate to select transformants with the greatest resemblance to the WT isolate. GFP-tagged P. palmivora was useful to identify all of the infective structures that are commonly formed by hemibiotrophic oomycetes, including apoplastic colonization and haustorium formation. Finally, we detected cell death responses associated with immature oil palm tissues that showed reduced susceptibility to P. palmivora infection, indicating that these tissues could exhibit age-related resistance. The aim of this research is to improve the characterization of the initial disease stages and generate cell biology tools that may be useful for developing methodologies for early identification of oil palm materials resistant or susceptible to BR.

cell death responses
age-related resistance
A. tumefaciens-mediated transformation
GFP
propidium iodide


Strategies to Study Desmin in Cardiac Muscle and Culture Systems.

Abstract: Intermediate filament (IF) cytoskeleton comprises the fine-tuning cellular machinery regulating critical homeostatic mechanisms. In skeletal and cardiac muscle, deficiency or disturbance of the IF network leads to severe pathology, particularly in the latter. The three-dimensional scaffold of the muscle-specific IF protein desmin interconnects key features of the cardiac muscle cells, including the Z-disks, intercalated disks, plasma membrane, nucleus, mitochondria, lysosomes, and potentially sarcoplasmic reticulum. This is crucial for the highly organized striated muscle, in which effective energy production and transmission as well as mechanochemical signaling are tightly coordinated among the organelles and the contractile apparatus. The role of desmin and desmin-associated proteins in the biogenesis, trafficking, and organelle function, as well as the development, differentiation, and survival of the cardiac muscle begins to be enlightened, but the precise mechanisms remain elusive. We propose a set of experimental tools that can be used, in vivo and in vitro, to unravel crucial new pathways by which the IF cytoskeleton facilitates proper organelle function, homeostasis, and cytoprotection and further understand how its disturbance and deficiency lead to disease.

Diokmetzidou|Antigoni|A| Tsikitis|Mary|M| Nikouli|Sofia|S| Kloukina|Ismini|I| Tsoupri|Elsa|E| Papathanasiou|Stamatis|S| Psarras|Stelios|S| Mavroidis|Manolis|M| Capetanaki|Yassemi|Y|

Desmin
Muscle
Cardiomyocyte cultures
Desmin assembly
Desmin expression
Desmin localization
Desmin-related knockin
Knockout
Stem cell embryoid bodies
Transgenic animal models
heart


Neutrophil function in healthy aged horses and horses with pituitary dysfunction.

Abstract: Immunosuppression leading to opportunist bacterial infection is a well-recognized sequela of equine pituitary pars intermedia dysfunction (PPID). The mechanisms responsible for immune dysfunction in PPID however, are as of yet poorly characterized. Horses with PPID have high concentrations of hormones known to impact immune function including α-melanocyte stimulating hormone (α-MSH) and insulin. α-MSH and related melanocortins have been shown in rodents and people to impair neutrophil function by decreasing superoxide production (known as oxidative burst activity), migration and adhesion. The goal of this study was to determine if neutrophil function is impaired in horses with PPID and, if so, to determine if plasma α-MSH or insulin concentration correlated with the severity of neutrophil dysfunction. Specifically, neutrophil phagocytosis, oxidative burst activity, chemotaxis and adhesion were assessed. Results of this study indicate that horses with PPID have reduced neutrophil function, characterized by decreased oxidative burst activity and adhesion. In addition, chemotaxis was greater in healthy aged horses than in young horses or aged horses with PPID. Plasma insulin: α-MSH ratio, but not individual hormone concentration was correlated to neutrophil oxidative burst activity. In summary, neutrophil function is impaired in horses with PPID, likely due to altered hormone concentrations and may contribute to increased risk of opportunistic infections. Whether regulation of hormone concentration profiles in horses with PPID using therapeutic intervention improves neutrophil function and reduces infections needs to be explored.

PPID
Oxidative burst activity
Adhesion
Phagocytosis
Chemotaxis
Alpha-melanocyte stimulating hormone


Clinical factors associated with weaning failure in patients requiring prolonged mechanical ventilation.

Abstract:
BACKGROUND
For patients requiring prolonged mechanical ventilation (PMV), weaning is difficult and mortality is very high. PMV has been defined recently, by consensus, as constituting ≥21 consecutive days of mechanical ventilation (MV) for ≥6 hours per day. This study aimed to evaluate the clinical factors predicting weaning failure in patients undergoing PMV in medical intensive care unit (ICU).

METHODS
We retrospectively reviewed the clinical and laboratory characteristics of 127 patients who received MV for more than 21 days in the medical ICU at Chonnam National University Hospital in South Korea between January 2005 and December 2014. Patients who underwent surgery or experienced trauma were excluded from this study.

RESULTS
Among the 127 patients requiring PMV, 41 (32.3%) were successfully weaned from MV. The median age of the weaning failure group was higher than that of the weaning success group (74.0 vs. 70.0 years; P=0.003). The proportion of male patients was 58.5% in the weaning success group and 72.1% in the weaning failure group, respectively. The most common reasons for ICU admission were respiratory causes (66.1%) followed by cardiovascular causes (16.5%) in both groups. ICU mortality and in-hospital mortality rates were 55.1% and 55.9%, respectively. In the multivariate analysis, respiratory causes of ICU admission [odds ratio (OR), 3.98; 95% confidence interval (CI), 1.29-12.30; P=0.016] and a high sequential organ failure assessment (SOFA) score on day 21 of MV (OR, 1.47; 95% CI, 1.17-1.85; P=0.001) were significantly associated with weaning failure in patients requiring PMV. The area under the receiver operating characteristic (ROC) curve of the SOFA score on day 21 of MV for predicting weaning failure was 0.77 (95% CI, 0.67-0.87; P=0.000).

CONCLUSIONS
Respiratory causes of ICU admission and a high SOFA score on day 21 of MV could be predictive of weaning failure in patients requiring PMV.

Shin|Hong-Joon|HJ| Chang|Jin-Sun|JS| Ahn|Seong|S| Kim|Tae-Ok|TO| Park|Cheol-Kyu|CK| Lim|Jung-Hwan|JH| Oh|In-Jae|IJ| Kim|Yu-Il|YI| Lim|Sung-Chul|SC| Kim|Young-Chul|YC| Kwon|Yong-Soo|YS|

weaning
mechanical ventilation (MV)
Intensive care unit (ICU)


Evaluation of low-grade glioma structural changes after chemotherapy using DTI-based histogram analysis and functional diffusion maps.

Abstract:
OBJECTIVES
To explore the role of diffusion tensor imaging (DTI)-based histogram analysis and functional diffusion maps (fDMs) in evaluating structural changes of low-grade gliomas (LGGs) receiving temozolomide (TMZ) chemotherapy.

METHODS
Twenty-one LGG patients underwent 3T-MR examinations before and after three and six cycles of dose-dense TMZ, including 3D-fluid-attenuated inversion recovery (FLAIR) sequences and DTI (b = 1000 s/mm(2), 32 directions). Mean diffusivity (MD), fractional anisotropy (FA), and tensor-decomposition DTI maps (p and q) were obtained. Histogram and fDM analyses were performed on co-registered baseline and post-chemotherapy maps. DTI changes were compared with modifications of tumour area and volume [according to Response Assessment in Neuro-Oncology (RANO) criteria], and seizure response.

RESULTS
After three cycles of TMZ, 20/21 patients were stable according to RANO criteria, but DTI changes were observed in all patients (Wilcoxon test, P ≤ 0.03). After six cycles, DTI changes were more pronounced (P ≤ 0.005). Seventy-five percent of patients had early seizure response with significant improvement of DTI values, maintaining stability on FLAIR. Early changes of the 25th percentiles of p and MD predicted final volume change (R(2) = 0.614 and 0.561, P < 0.0005, respectively). TMZ-related changes were located mainly at tumour borders on p and MD fDMs.

CONCLUSIONS
DTI-based histogram and fDM analyses are useful techniques to evaluate the early effects of TMZ chemotherapy in LGG patients.

KEY POINTS
• DTI helps to assess the efficacy of chemotherapy in low-grade gliomas. • Histogram analysis of DTI metrics quantifies structural changes in tumour tissue. • Functional diffusion maps (fDMs) spatially localize the changes of DTI metrics. • Changes in DTI histograms and fDMs precede changes in conventional MRI. • Early changes in DTI histograms and fDMs correlate with seizure response.

Castellano|Antonella|A|
Donativi|Marina|M|
Rudà|Roberta|R|
De Nunzio|Giorgio|G|
Riva|Marco|M|
Iadanza|Antonella|A|
Bertero|Luca|L|
Rucco|Matteo|M|
Bello|Lorenzo|L|
Soffietti|Riccardo|R|
Falini|Andrea|A|

Glioma
Chemotherapy
Diffusion Tensor Imaging
Magnetic Resonance Imaging
Response Evaluation Criteria


Staphylococcus aureus Community-acquired Pneumonia: Prevalence, Clinical Characteristics, and Outcomes.

Abstract:
BACKGROUND
Prevalence of Staphylococcus aureus community-acquired pneumonia (CAP) and its clinical features remain incompletely understood, complicating empirical selection of antibiotics.

METHODS
Using a multicenter, prospective surveillance study of adults hospitalized with CAP, we calculated the prevalence of methicillin-resistant S. aureus (MRSA) and methicillin-susceptible S. aureus (MSSA) among all CAP episodes. We compared the epidemiologic, radiographic, and clinical characteristics of S. aureus CAP (per respiratory or blood culture) with those of pneumococcal (per respiratory or blood culture or urine antigen) and all-cause non-S. aureus CAP using descriptive statistics.

RESULTS
Among 2259 adults hospitalized for CAP, 37 (1.6%) had S. aureus identified, including 15 (0.7%) with MRSA and 22 (1.0%) with MSSA; 115 (5.1%) had Streptococcus pneumoniae Vancomycin or linezolid was administered to 674 (29.8%) patients within the first 3 days of hospitalization. Chronic hemodialysis use was more common among patients with MRSA (20.0%) than pneumococcal (2.6%) and all-cause non-S. aureus (3.7%) CAP. Otherwise, clinical features at admission were similar, including concurrent influenza infection, hemoptysis, multilobar infiltrates, and prehospital antibiotics. Patients with MRSA CAP had more severe clinical outcomes than those with pneumococcal CAP, including intensive care unit admission (86.7% vs 34.8%) and in-patient mortality (13.3% vs 4.4%).

CONCLUSIONS
Despite very low prevalence of S. aureus and, specifically, MRSA, nearly one-third of adults hospitalized with CAP received anti-MRSA antibiotics. The clinical presentation of MRSA CAP overlapped substantially with pneumococcal CAP, highlighting the challenge of accurately targeting empirical anti-MRSA antibiotics with currently available clinical tools and the need for new diagnostic strategies.

Self|Wesley H|WH|
Wunderink|Richard G|RG|
Williams|Derek J|DJ|
Zhu|Yuwei|Y|
Anderson|Evan J|EJ|
Balk|Robert A|RA|
Fakhran|Sherene S|SS|
Chappell|James D|JD|
Casimir|Geoffrey|G|
Courtney|D Mark|DM|
Trabue|Christopher|C|
Waterer|Grant W|GW|
Bramley|Anna|A|
Magill|Shelley|S|
Jain|Seema|S|
Edwards|Kathryn M|KM|
Grijalva|Carlos G|CG|

D002487:Centers for Disease Control and Prevention, U.S.

Staphylococcus aureus
pneumonia
antibiotics


Expression profiles of pro-inflammatory and pro-apoptotic mediators in secondary tethered cord syndrome after myelomeningocele repair surgery.

Abstract:
PURPOSE
The literature on histopathological and molecular changes that might underlie secondary tethered cord syndrome (TCS) after myelomeningocele (MMC) repair surgeries remains sparse. To address this problem, we analyzed specimens, which were obtained during untethering surgeries of patients who had a history of MMC repair surgery after birth.

METHODS
Specimens of 12 patients were analyzed in this study. Clinical characteristics were obtained retrospectively including pre-operative neurological and bowel/bladder-function, contractures and spasticity of lower extremities, leg and back pain, syringomyelia, and conus position on spinal MRI. Cellular marker expression profiles were established. Further, immunoreactivities (IR) of IL-1ß/IL-1R1, TNF-α/TNF-R1, and HIF-1α/-2α were analyzed qualitatively and semi-quantitatively by densitometry. Co-labeling with cellular markers was determined by multi-fluorescence-labeling. Cytokines were further analyzed on mRNA level. Immunostaining for cleaved PARP and TUNEL was performed to detect apoptotic cells.

RESULTS
Astrocytosis, appearance of monocytes, activated microglia, and apoptotic cells in TCS specimens were one substantial finding of these studies. Besides neurons, these cells co-stained with IL-1ß and TNF-α and their receptors, which were found on significantly elevated IR-level and partially mRNA-level in TCS specimens. Staining for HIF-1α/-2α confirmed induction of hypoxia-related factors in TCS specimens that were co-labeled with IL-1ß. Further, hints for apoptotic cell death became evident by TUNEL and PARP-positive cells in TCS neuroepithelia.

CONCLUSIONS
Our studies identified pro-inflammatory and pro-apoptotic mediators that, besides mechanical damaging and along with hypoxia, might promote TCS development. Besides optimizing surgical techniques, these factors should also be taken into account when searching for further options to improve TCS treatment.

Cytokines
Hypoxia
Dysraphism
Real-time RT-PCR


Regulation of the sperm-to-oocyte transition in Caenorhabditis briggsae hermaphrodites by the Cbr-met-2 and Cbr-fem-3 genes.

Abstract: In Caenorhabditis briggsae hermaphrodites, spermatogenesis begins in the L4 larval stage and persists into early adulthood. Oogenesis begins after spermatogenesis; the sperm-to-oocyte transition is irreversible. The timing of this transition is believed to have evolved in response to selection to maximize the intrinsic growth rate. Sperm-to-oocyte transitions occurred early in Cbr-met-2 and Cbr-fem-3 mutants. These early transitions resulted in reduced brood sizes, but had little or no impact on the intrinsic growth rate. In Cbr-met-2; Cbr-fem-3 doubly mutant hermaphrodites, the transition to oogenesis occurred even earlier and brood size was further reduced, indicating that Cbr-met-2 and Cbr-fem-3 regulate the sperm-to-oocyte transition through separate pathways. Mutations in Cbr-met-2 also resulted in an increase in the frequency of males in mutant populations. These increased male frequencies were not caused by increased rates of X nondisjunction during oogenesis in mutant hermaphrodites. Rather, increases in the rates of outcrossing in mutant populations likely were an indirect effect of reduced brood sizes derived from self-fertilization. Based on these observations, it is possible that the timing of the sperm-to-oocyte transition in C. briggsae evolved in response to sexual selection on hermaphrodites to limit rates of outcrossing. Mutations in the orthologous Caenorhabditis elegans gene, Cel-met-2, did not impact the timing of the sperm-to-oocyte transition, consistent with the independent evolution of hermaphroditic reproduction in these species. Although brood sizes were reduced in Cel-met-2 mutant strains, increased male frequencies were not observed. Cbr- and Cel-met-2 mutations also differed in terms of germline mortality, observed in C. elegans, but not in C. briggsae.

Berenson|Aaron L|AL|
Baird|Scott E|SE|0000-0002-8084-9383

spermatogenesis
oogenesis
reproduction
histone methyltransferase