Development of minimized mixing molecular orbital method for designing organic ferromagnets.

Abstract: Predicting the high spin stability of organic radicals correctly for designing organic ferromagnets remains a significant challenge. We have developed a method with an index (L(min)) for predicting the high spin stability of conjugated organic radicals at the restricted open-shell Hartree-Fock level. Unitary transformations were performed for localizing the coefficients of nonbonding molecular orbitals, and subsequently the localized coefficients were used to calculate L(min) that indicates the high spin stability of conjugated organic radicals. This method can be combined with the elongation method to treat huge high spin open-shell systems. Thus, this method is useful for designing organic ferromagnets.

organic ferromagnets
high spin stability
restricted open-shell Hartree-Fock
nonbonding molecular orbital


Development of the breastfeeding support scale to measure breastfeeding support from lay and professional persons, and its predictive validity in Japan.

Abstract:
Background
International and national organizations recommend exclusive breastfeeding for the first 6 months of life, but many women stop earlier. Lay and professional persons can support mothers' efforts to overcome breastfeeding difficulties. Considering breastfeeding support to comprise emotional support, practical help, and information offered to women who desire to breastfeed (by professionals, family members, and others), we developed and tested a scale to measure it in Japan.

Methods
A total of 31 items were generated by literature review and from the authors' clinical experiences. Those items were tested with 243 mothers who visited public health centers in Tokyo for their infant's health check-up 3 months after birth. Breastfeeding support and infant feeding status were then assessed 5 months after birth. All the data were collected by using self-administered questionnaires.

Results
On the basis of the results of factor analysis, the number of items was reduced to 11. There were three factors: support from breastfeeding peers and from people in specifically named healthcare professions, practical help, and support from people the mother can rely on to help meet emotional needs and address breastfeeding concerns. Internal-consistency reliability (alpha) of scores on the 11-item scale was 0.83 when measured 3 months postpartum and 0.85 when measured 5 months postpartum. Higher scores on the 11-item scale 3 months postpartum were associated with more breastfeeding exclusivity both at that time (Kruskal-Wallis test, chi-squared = 14.871, df = 3, n = 211, p = 0.002, eta-squared = 0.071) and also 5 months postpartum (Kruskal-Wallis test, chi-squared = 8.556, df = 3, n = 159, p = 0.036, eta-squared = 0.054). Further, the area under the Receiver Operating Characteristic curve was 0.73 (95% CI [0.57-0.88]), which indicates that scores on the 11-item scale 3 months postpartum may be useful to predict which mothers will be less exclusive in breastfeeding 5 months postpartum. In conclusion, scores on this 11-item scale were reasonably reliable and valid for measuring breastfeeding support provided by lay and professional persons to mothers in Japan. Further research is required to evaluate this scale's applicability in other settings.

Breastfeeding
Support
Predictive Validity
Japan
Psychometric testing
Scale development


Introduction to molecular replacement: a time perspective.

Abstract: This article provides an introduction to the crystal phasing technique known as molecular replacement. The available software is reviewed, and the prospects for future developments are considered. Several examples are described in detail to illustrate potential problems. A brief account of past progress is included. The basic crystallographic equations underlying the procedures are given in an appendix.

molecular replacement
crystal phasing
crystallographic equations
crystallographic theory
history
scoring functions
test cases


Comprehensive assessment of the effect of eye plaque tilt on tumor dosimetry.

Abstract:
PURPOSE
Tilting of the posterior plaque margin during eye plaque brachytherapy can lead to tumor underdosing and increased risk of local recurrence. We performed a quantitative analysis of the dosimetric effects of plaque tilt as a function of tumor position, basal dimension, height and plaque type using 3D treatment planning software.

MATERIALS AND METHODS
Posterior and anterior tumors with largest basal dimensions of 6, 12 and 18 mm and heights of 4, 7 and 10 mm were modeled. Both Eye Physics and COMS plaques were simulated and uniformly loaded. Plans were normalized to 85 Gy at the tumor apex. Posterior plaque tilts of 1, 2, 3 and 4 mm were simulated.

RESULTS
Volumetric coverage is more sensitive to tilt than the area coverage. Wide, flat tumors are more susceptible to tilt. Apical dose changed significantly as a function of tumor height and diameter. No other parameter exhibited significant differences. Posterior tumors are slightly more susceptible to tilt due to the use of notched plaques. Plaque type does not significantly alter the effect of plaque tilt.

CONCLUSIONS
Wide, flat tumors are the most susceptible to plaque tilt. Tumor location or plaque type does not have a significant effect on dosimetry changes from plaque tilt. Robust clinical procedures such as the use of mattress sutures, pre- and post-implant ultrasound and post-implant dosimetry can all mitigate the risk associated with plaque tilt.

Studenski|Matthew T|MT|
Markoe|Arnold|A|
Samuels|Stuart E|SE|
Correa|Zelia M|ZM|
Bossart|Elizabeth|E|
Harbour|J William|JW|


Toxicity of Senna occidentalis seeds in laying hens and its effects on egg production.

Abstract: Senna occidentalis is a toxic leguminous plant found in many tropical and subtropical regions of the world and causes poisoning mainly in confined animals. The seeds are the most toxic part of the plant and may be present in animal rations. The main toxic component of the S. occidentalis seed is a dianthrone, an anthraquinone-derived compound that affects mitochondrial function. This study evaluated the effects on egg production of low-level contamination of the S. occidentalis in the laying hens' diet. Forty-eight one-day-old pullets were randomly allocated into two treatment groups: control, birds that received no experimental treatment; and external and internal tegument (ET/IT), birds that received a diet containing 0.2% of ET/IT of S. occidentalis seeds throughout their life cycle (42 weeks). The birds were monitored for clinical signs of poisoning, and the production and quality of eggs were recorded. Necropsies were conducted at the end of the experimental period. None of the layers showed any clinical signs of poisoning, decreases in feed intake or alterations of the body weight gain. A marked reduction in egg production and, consequently, a lower feed efficiency in ET/IT group were measured. Ovaries were the most affected organ in birds from the ET/IT group, and yolk leaking and dysplasia of the inner layer of the vitelline membrane were observed. S. occidentalis was shown to be toxic for laying hens. Considering these results, it is feasible to assume that the constant presence of low concentrations of S. occidentalis seeds in rations represents a threat to the poultry industry.

Gotardo|André T|AT|
Haraguchi|Mitsue|M|
Raspantini|Paulo C F|PCF|
Dagli|Maria L Z|MLZ|
Górniak|Silvana L|SL|

egg production
S. occidentalis
poultry
Cassia occidentalis
chicken


Motor resonance meets motor performance.

Abstract: The aim of the present work is to explore which of two different models better explains facilitation/interference effects when participants have to conditionally react to an observed action with a movement. The Dimensional Overlap model assumes two parallel routes, an automatic route and a rule-based one, that interact only when the stimulus-set and the response-set share some dimensions. In the alternative model, a motor resonance for rule-based reaction, the automatic visuo-motor transformation is always an obligatory step that provides the correct categorization of the observed action as the input for the rule-based route, thus linking the two routes in a serial fashion. We explicitly tested which of the hypotheses fits better the data by asking participants to perform one of two different actions in a two-choice reaction paradigm. In one condition participants were required to perform the opposite action compared to the one they saw (COUNTER task: see A→do B, see B→do A), while in the other they were required to perform two actions that did not share any dimension with the stimulus-set (NEUTRAL task: see A→do C, see B→do D). We predicted an advantage for the NEUTRAL task if the Dimensional Overlap model was correct, while a similar performance was foreseen if the motor resonance-based model was correct. Since the interpretation of these results was not straightforward, we conducted a distributional analysis of participants' response accuracies in order to understand whether a serial or a general parallel model explained better the data. We found clear evidence that participants responded above chance before the motor representation of the action observed was activated. We conclude that two separate systems in the human brain can transform observed actions in own motor representations. One is stimulus-driven, while the second is rule-driven. Likely, their activity is mutually independent along parallel pathways.

D000704:Analysis of Variance
D005260:Female
D006225:Hand
D006801:Humans
D007100:Imitative Behavior
D008297:Male
D008960:Models, Psychological
D009039:Motion Perception
D009483:Neuropsychological Tests
D010775:Photic Stimulation
D011597:Psychomotor Performance
D011930:Reaction Time
D055815:Young Adult

Dimensional Overlap
Action understanding
Embodied cognition
Imitation
Mirror neurons
Simulation


Evaluation of shear bond strength of repair acrylic resin to Co-Cr alloy.

Abstract:
PURPOSE
The purpose of this study was to investigate the impact of different surface treatment methods and thermal ageing on the bond strength of autopolymerizing acrylic resin to Co-Cr.

MATERIALS AND METHODS
Co-Cr alloy specimens were divided into five groups according to the surface conditioning methods. C: No treatment; SP: flamed with the Silano-Pen device; K: airborne particle abrasion with Al2O3; Co: airborne particle abrasion with silica-coated Al2O3; KSP: flamed with the Silano-Pen device after the group K experimental protocol. Then, autopolymerized acrylic resin was applied to the treated specimen surfaces. All the groups were divided into two subgroups with the thermal cycle and water storage to determine the durability of the bond. The bond strength test was applied in an universal test machine and treated Co-Cr alloys were analyzed by scanning electron microscope (SEM). Two-way analysis of variance (ANOVA) was used to determine the significant differences among surface treatments and thermocycling. Their interactons were followed by a multiple comparison' test performed uing a post hoc Tukey HSD test (α=.05).

RESULTS
Surface treatments significantly increased repair strengths of repair resin to Co-Cr alloy. The repair strengths of Group K, and Co significantly decreased after 6,000 cycles (P<.001).

CONCLUSION
Thermocycling lead to a significant decrease in shear bond strength for air abrasion with silica-coated aluminum oxide particles. On the contrary, flaming with Silano-Pen did not cause a significant reduction in adhesion after thermocycling.

Külünk|Safak|S| Külünk|Tolga|T| Saraç|Duygu|D| Cengiz|Seda|S| Baba|Seniha|S|

Repair acrylic resin
Co-Cr alloy
Repair strength


Evaluation of carbapenem-resistant Enterobacteriaceae in an Italian setting: report from the trench.

Abstract: The spread of carbapenem resistant Enterobacteriaceae (CRE) has recently become a matter of concern in public health, mainly due to the wide distribution of carbapenemase genes. Italy is a country considered endemic for the spread of blaKPC Klebsiella pneumoniae (KP). The aim of this study was to depict the epidemiological trend of CRE in one Italian hospital over a long period (3 years surveillance, from May 2011 to April 2014). Based on defined MIC cut-off for specific carbapenems, 164 strains isolated from 146 different patients were analyzed both phenotypically and genotypically to establish the resistance genes. Molecular typing was performed using the RAPD technique. 77 strains were demonstrated to harbor the blaKPC gene (73 KP, 4 Escherichia coli - EC), 51 strains the blaVIM gene (44 KP, 3 EC, 2 Enterobacter cloacae and 2 Klebsiella oxytoca), 8 the blaNDM gene (3 KP, 4 EC and one Providencia stuartii), 3 the blaOXA-48 gene (2 KP, 1 EC), whereas 25 out of the 164 isolates (of different genera and species) had a negative multiplex-PCR amplification for all the targets tested. 39 out of the 164 strains analyzed (23.8%) revealed discrepancies between the MICs obtained with automated instrument and gradient MICs of more than two logs of difference; the broth microdilution provided a better agreement with the results obtained with the gradient MIC. The use of RAPD allowed to distinguish different clusters, closely related, both for blaKPC and for blaVIM KP.

Barbarini|D|D|
Russello|G|G|
Brovarone|F|F|
Capatti|C|C|
Colla|R|R|
Perilli|M|M|
Moro|M L|ML|
Carretto|E|E|

D019105:Random Amplified Polymorphic DNA Technique


Effective Therapy Against Severe Anxiety Caused by Cancer: A Case Report and Review of the Literature.

Abstract: Anxiety can make it difficult for patients to manage their illness. Therefore, it is important to reduce their anxiety if possible. However, few studies have examined the efficacy of drugs in the treatment of anxiety in patients with cancer. Our case had failed to respond to benzodiazepines, and it was difficult to use a selective serotonin reuptake inhibitor (SSRI) as the next drug. This case report describes the effective use of quetiapine to treat anxiety. We report this rare case along with a literature review. Few studies have assessed the treatment of anxiety in patients with rare cancers. In our case, quetiapine effectively alleviated anxiety associated with cystic adenoid carcinoma. However, in clinical practice, it is possible that anxiety is treated without differentiating the effects of cancer status, e.g. life prognosis, treatment progress. In our patient, benzodiazepines had no effect on anxiety. Thus, different drugs may be required to treat anxiety associated with cancer. The present study demonstrated that quetiapine is a useful modality for the palliative care of patients with rare cancer and intractable anxiety. Quetiapine may be an effective alternative to benzodiazepines (BZ) and SSRIs for treating anxiety in patients with cancer. However, further investigation is needed to clarify the efficacy of treatments for anxiety associated with rare cancers.

anxiety
quetiapine
rare cancer
adenoid cystic carcinoma
restlessness


SERPINI1 regulates epithelial-mesenchymal transition in an orthotopic implantation model of colorectal cancer.

Abstract: An increasingly accepted concept is that the progression of colorectal cancer is accompanied by epithelial-mesenchymal transition (EMT). In our study, in order to characterize the properties of EMT in 16 colorectal cancer cell lines, the cells were first orthotopically implanted into nude mice, and the tumors in vivo, as well as cells cultured in vitro, were immunostained for EMT markers. The immunostaining revealed that seven of the cells had an epithelial phenotype with a high expression of E-cadherin, whereas other cells showed opposite patterns, such as a high expression of vimentin (CX-1, COLO205, CloneA, HCT116, and SW48). Among the cells expressing vimentin, some expressed vimentin in the orthotopic tumors but not in the cultured cells (SW480, SW620, and COLO320). We evaluated these findings in combination with microarray analyses, and selected five genes: CHST11, SERPINI1, AGR2, FBP1, and FOXA1. Next, we downregulated the expression of SERPINI1 with siRNA in the cells, the results of which showed reverse-EMT changes at the protein level and in the cellular morphology. Along with immunohistochemical analyses, we confirmed the effect of the intracellular and secreted SERPINI1 protein of SW620 cells, which supported the importance of SERPINI1 in EMT. The development of therapeutic strategies targeting EMT is ongoing, including methods targeting the transforming growth factor-β signaling pathway as well as the Wnt pathway. SERPINI1 is an important regulator of EMT. Our findings help to elucidate the signaling pathways of EMT, hopefully clarifying therapeutic pathways as well.

Matsuda|Yasufumi|Y| Miura|Koh|K| Yamane|Junko|J| Shima|Hiroshi|H| Fujibuchi|Wataru|W| Ishida|Kazuyuki|K| Fujishima|Fumiyoshi|F| Ohnuma|Shinobu|S| Sasaki|Hiroyuki|H| Nagao|Munenori|M| Tanaka|Naoki|N| Satoh|Kennichi|K| Naitoh|Takeshi|T| Unno|Michiaki|M|

D020411:Oligonucleotide Array Sequence Analysis

SERPINI1
epithelial-mesenchymal transition
Colorectal cancer
microarray analysis
orthotopic implantation mouse model


Concurrent saturation transfer contrast in in vivo brain by a uniform magnetization transfer MRI.

Abstract: The development of chemical exchange saturation transfer (CEST) and magnetization transfer (MT) contrast in MRI has enabled the enhanced detection of metabolites and biomarkers in vivo. In brain MRI, the separation between CEST and MT contrast has been particularly difficult due to overlaps in the frequency responses of the contrast mechanisms. We demonstrate here that MT and CEST contrast can be separated in the brain by the so-called uniform-MT (uMT) technique, thus opening the door to addressing long-standing ambiguities in this field. These methods could be useful for keeping track of important endogenous metabolites and for providing an improved understanding of neurological and neurodegenerative disorders. Examples are shown from white and gray matter regions in healthy volunteers and patients with multiple sclerosis, which demonstrated that the MT effects in the brain were asymmetric and that the uMT method could make them uniform.

Lee|Jae-Seung|JS|
Xia|Ding|D|
Ge|Yulin|Y|
Jerschow|Alexej|A|
Regatte|Ravinder R|RR|

Magnetization transfer
MRI
Chemical exchange saturation transfer
Multiple sclerosis


Metrics for the Human Proteome Project 2016: Progress on Identifying and Characterizing the Human Proteome, Including Post-Translational Modifications.

Abstract: The HUPO Human Proteome Project (HPP) has two overall goals: (1) stepwise completion of the protein parts list-the draft human proteome including confidently identifying and characterizing at least one protein product from each protein-coding gene, with increasing emphasis on sequence variants, post-translational modifications (PTMs), and splice isoforms of those proteins; and (2) making proteomics an integrated counterpart to genomics throughout the biomedical and life sciences community. PeptideAtlas and GPMDB reanalyze all major human mass spectrometry data sets available through ProteomeXchange with standardized protocols and stringent quality filters; neXtProt curates and integrates mass spectrometry and other findings to present the most up to date authorative compendium of the human proteome. The HPP Guidelines for Mass Spectrometry Data Interpretation version 2.1 were applied to manuscripts submitted for this 2016 C-HPP-led special issue [ www.thehpp.org/guidelines ]. The Human Proteome presented as neXtProt version 2016-02 has 16,518 confident protein identifications (Protein Existence [PE] Level 1), up from 13,664 at 2012-12, 15,646 at 2013-09, and 16,491 at 2014-10. There are 485 proteins that would have been PE1 under the Guidelines v1.0 from 2012 but now have insufficient evidence due to the agreed-upon more stringent Guidelines v2.0 to reduce false positives. neXtProt and PeptideAtlas now both require two non-nested, uniquely mapping (proteotypic) peptides of at least 9 aa in length. There are 2,949 missing proteins (PE2+3+4) as the baseline for submissions for this fourth annual C-HPP special issue of Journal of Proteome Research. PeptideAtlas has 14,629 canonical (plus 1187 uncertain and 1755 redundant) entries. GPMDB has 16,190 EC4 entries, and the Human Protein Atlas has 10,475 entries with supportive evidence. neXtProt, PeptideAtlas, and GPMDB are rich resources of information about post-translational modifications (PTMs), single amino acid variants (SAAVSs), and splice isoforms. Meanwhile, the Biology- and Disease-driven (B/D)-HPP has created comprehensive SRM resources, generated popular protein lists to guide targeted proteomics assays for specific diseases, and launched an Early Career Researchers initiative.

Omenn|Gilbert S|GS|
Lane|Lydie|L|
Lundberg|Emma K|EK|
Beavis|Ronald C|RC|
Overall|Christopher M|CM|
Deutsch|Eric W|EW|

metrics
splice isoforms
PeptideAtlas
GPMDB
neXtProt
guidelines
Human Protein Atlas
N-termini
PTMs (post-translational modifications)
SAAV (single amino acid variants)


Effects of heat-killed Lactobacillus casei subsp. casei 327 intake on defecation in healthy volunteers: a randomized, double-blind, placebo-controlled, parallel-group study.

Abstract: Lactobacillus casei subsp. casei 327 (L. casei 327) was isolated from brown rice. A preliminary study showed that intake of 50 mg of heat-killed L. casei 327 is effective in improving defecation. In this study, we conducted a randomized, double-blind, placebo-controlled, parallel-group trial to investigate the effect of intake of heat-killed L. casei 327 (25 mg: approximately 5 × 1010 bacteria) on defecation in healthy volunteers with relatively low defecation frequencies. We selected 104 healthy Japanese adults with relatively low defecation frequencies (approximately 3-5 times a week) by screening and pretrial tests. Subjects (n=52 in each group) were randomly given a tablet containing L. casei 327 (group A) or a placebo tablet (group P) daily for 2 weeks. After eliminating data for 9 subjects who met the exclusion criteria for efficacy analysis, data for 95 subjects were analyzed. The defecation frequency and number of defecation days during the intake period and their changes from the pretrial period were significantly higher in group A than in group P. The fecal volume during the intake period was higher in group A than group P, but the difference was not statistically significant. However, the change from the pretrial period was significantly higher in group A than in group P. There were no significant differences between groups in the values of fecal shape, color, odor, and feeling after defecation. These results suggested that intake of L. casei 327 improves defecation in healthy adults who have relatively low defecation frequencies.

Saito|Yuhi|Y| Mihara|Toshihiro|T| Oki|Mamoru|M| Kumagai|Takehisa|T|

Lactobacillus casei
defecation
healthy volunteers
clinical study
lactic acid bacteria


Open oral cavity has little effects on upper airway aerodynamics in children with obstructive sleep apnea syndrome: A computational fluid dynamics study based on patient-specific models.

Abstract: Obstructive sleep apnea syndrome (OSAS) is a common disorder with recurrent pharyngeal airway collapse and sleep disruption. Recently, great progress has been made in investigating the physical mechanism of OSAS development and treatment using computational fluid dynamics (CFD). However, previous studies always neglected the oral cavity artificially in the patient's upper airway CFD model, but did not give any specific explanation. The oral cavity effect on the OSAS upper airway flow is still a matter of unclear. This paper reconstructed the patient-specific upper airway models based on the cone beam computed tomography images of ten children subjects (seven boys and three girls) and used CFD to simulate both the steady and unsteady expiration and inspiration states in the upper airway model with or without the oral cavity. A series of pressure measurement experiments based on the in vitro 1:1 scaled airway model were performed to validate the reliability of the present CFD methods. Finally, the CFD results indicate that the open oral cavity is almost a region of flow stasis with constant pressure, and both the upper airway aerodynamics with and without the oral cavity have the similar trends, with the maximum average relative difference less than 6%. The present study shows that the open oral cavity causes very little impacts on the upper airway flow of the children patients with OSAS using the nasal respiration only, and confirms the reasonability of ignoring the oral cavity for CFD simulation.

Chen|Shuai|S| Wang|Jingying|J| Liu|Dongxu|D| Lei|Li|L| Wu|Wei|W| Liu|Zhenggang|Z| Lee|Chunhian|C|

Oral cavity
Obstructive sleep apnea syndrome (OSAS)
Computational fluid dynamics (CFD)
Upper airway flow
Children patients


Spectroscopic characterization of tablet properties in a continuous powder blending and tableting process.

Abstract: By the advent of continuous pharmaceutical manufacturing, fast and accurate characterization of product quality has become of a major interest. Although it also promotes the real-time release testing approach, so far mainly content uniformity studies were performed by near-infrared (NIR) spectroscopy. This paper proposes the simultaneous application of NIR and Raman spectroscopy to nondestructively analyze the critical quality attributes of continuously produced tablets in a real-time release testing procedure. A face-centered composite design was applied to determine the impact of lubrication and compression force on the properties of a tablet formulation containing caffeine, glucose-monohydrate and magnesium stearate and to provide a systematic comparison of the applicability of spectroscopic methods. Quantitative methods were developed to evaluate different lubrication approaches in a continuous blending and tableting line. The simultaneous application of NIR and Raman spectroscopy revealed that NIR spectroscopy is more suitable to follow the changes of compression force, while Raman spectroscopy could be successfully applied for the detection of overlubrication. The presented approach can be a part of a comprehensive real-time release strategy, where NIR and Raman spectroscopy provide complementary information about multiple critical quality attributes, such as content uniformity, tablet hardness, friability and dissolution.

Nagy|Brigitta|B|
Farkas|Attila|A|
Magyar|Krisztina|K|
Démuth|Balázs|B|
Nagy|Zsombor Kristóf|ZK|
Marosi|György|G|

Real-time release testing
Raman spectroscopy
Lubrication
Continuous blending
NIR spectroscopy
Process analytical technology
Tablet compression


Chromium-Catalyzed Selective Dimerization/Hydroboration of Allenes to Access Boryl-Functionalized Skipped (E,Z)-Dienes.

Abstract: A chromium-catalyzed dimerization/hydroboration of allenes is developed to access synthetically versatile boryl-functionalized skipped dienes with a catalyst generated in situ from CrCl2 and a pyridine-2,6-diimine ligand mes PDI. A variety of allenes reacted with pinacolborane (HBpin) to afford the corresponding boryl-functionalized (E,Z)-1,4-dienes in high yields and with excellent selectivity. Electron paramagnetic resonance (EPR) spectroscopic studies suggest that this chromium-catalyzed reaction probably proceeds through a chromium(I) hydride intermediate.

dimerization
hydroboration
allenes
chromium
homogeneous catalysis


Repair of acute liver damage with immune evasive hESC derived hepato-blasts.

Abstract: Human embryonic stem cells (hESCs) can undergo unlimited self-renewal and differentiate into hepatic cells, including expandable hepato-blasts (HBs) and hepatocyte-like cells (HLCs) in vitro. Therefore, hESC-derived HBs have the potential to become a renewable cell source for cell therapy of serious liver damage. However, one of the key challenges for such cell therapy is the allogeneic immune rejection of hESC-derived HBs. To overcome this challenge, we developed a strategy to protect the hESC-derived HBs from allogeneic immune rejection by ectopically expressing immune suppressive molecules CTLA4-Ig and PD-L1, denoted CP HBs. Like HBs derived from normal hESCs, CP HBs are capable of repairing liver damage in animal models. Using humanized mice (Hu-mice) reconstituted with human immune system, we showed that CP HBs are protected from allogeneic immune system and can survive long-term in Hu-mice. These data support the feasibility to develop CP HBs into a cell therapy to treat serious liver damage.

Liu|Jingfeng|J| Pan|Tingcai|T| Chen|Yan|Y| Liu|Ying|Y| Yang|Fan|F| Chen|Qu|Q| Abbas|Nasir|N| Zhong|Mingyan|M| Zhang|Qianbing|Q| Xu|Yang|Y| Li|Yin-Xiong|YX|


Expression of ESR1 in Glutamatergic and GABAergic Neurons Is Essential for Normal Puberty Onset, Estrogen Feedback, and Fertility in Female Mice.

Abstract: Circulating estradiol exerts a profound influence on the activity of the gonadotropin-releasing hormone (GnRH) neuronal network controlling fertility. Using genetic strategies enabling neuron-specific deletion of estrogen receptor α (Esr1), we examine here whether estradiol-modulated GABA and glutamate transmission are critical for the functioning of the GnRH neuron network in the female mouse. Using Vgat- and Vglut2-ires-Cre knock-in mice and ESR1 immunohistochemistry, we demonstrate that subpopulations of GABA and glutamate neurons throughout the limbic forebrain express ESR1, with ESR1-GABAergic neurons being more widespread and numerous than ESR1-glutamatergic neurons. We crossed Vgat- and Vglut2-ires-Cre mice with an Esr1(lox/lox) line to generate animals with GABA-neuron-specific or glutamate-neuron-specific deletion of Esr1. Vgat-ires-Cre;Esr1(lox/lox) mice were infertile, with abnormal estrous cycles, and exhibited a complete failure of the estrogen positive feedback mechanism responsible for the preovulatory GnRH surge. However, puberty onset and estrogen negative feedback were normal. Vglut2-ires-Cre;Esr1(lox/lox) mice were also infertile but displayed a wider range of deficits, including advanced puberty onset, abnormal negative feedback, and abolished positive feedback. Whereas <25% of preoptic kisspeptin neurons expressed Cre in Vgat- and Vglut2-ires-Cre lines, ∼70% of arcuate kisspeptin neurons were targeted in Vglut2-ires-Cre;Esr1(lox/lox) mice, possibly contributing to their advanced puberty phenotype. These observations show that, unexpectedly, ESR1-GABA neurons are only essential for the positive feedback mechanism. In contrast, we reveal the key importance of ESR1 in glutamatergic neurons for multiple estrogen feedback loops within the GnRH neuronal network required for fertility in the female mouse.

D050599:Vesicular Glutamate Transport Protein 2

D050495:Vesicular Inhibitory Amino Acid Transport Proteins


Investigation of the factors influencing surgical treatment of duodenal gastrointestinal stromal tumors.

Abstract:
BACKGROUND
Duodenal gastrointestinal stromal tumor (DGIST) is a rare tumor with a specific anatomic site and biological characteristics. As the incidence of lymph node metastasis is very low, the main treatment method is surgery. Two main surgical techniques (local resection and Whipple) are performed in patients with DGISTs. The critical question is which surgical technique to choose.

AIM
To identify factors influencing the choice of surgery for DGISTs.

METHODS
The clinicopathological data of patients with DGISTs who underwent surgery between January 1999 and January 2021 were analyzed. We used the Student's t-test or Mann-Whitney U-test and the χ 2 test or Fisher's exact test to determine the differences between the two groups of patients. Furthermore, we used logistic analysis to identify the relevant factors and independent factors related to the type of surgery. The Kaplan-Meier method was used to analyze the patient's survival information and Cox regression analysis was performed to determine prognostic risk factors.

RESULTS
Overall, 86 patients were analyzed, including 43 men (50%) and 43 women (50%). We divided the patients into two groups based on surgical technique (local resection or Whipple surgery). There were no differences in the age, mitotic figures, and complications between the two groups; however, the tumor size, tumor location, risk grade, postoperative hospital stay, and abdominal drainage time were significantly different. Based on univariate logistic analysis, the Whipple procedure was chosen if the tumor size was ≥ 5.0 cm, the tumor was located in the descending part of the duodenum, or the risk grade was medium or high. In our research, the five-year overall survival rate of patients was more than 90%. We also describe two DGIST patients with liver metastases at first diagnosis and analyzed their management in order to provide advice on complicated cases.

CONCLUSION
The Whipple procedure was performed if the primary tumor was in the descending part of the duodenum, tumor size was ≥ 5.0 cm, or the tumor risk grade was medium or high.

Wu|Yun-Zi|YZ| Li|Yang|Y| Wu|Ming|M| Zheng|Xiao-Hao|XH| Tian|Yan-Tao|YT| Xie|Yi-Bin|YB|

Duodenal gastrointestinal stromal tumors


Evaluation of the epidemiological and prognosis significance of ESR2 rs3020450 polymorphism in ovarian cancer.

Abstract:
AIM
To investigate the correlation between the polymorphism of estrogen receptor β gene (ESR2) rs3020450 and cancer susceptibility, and explore the epidemiological significance and the effect of ESR2 expression levels on the prognosis of ovarian cancer.

METHODS
Based on meta-analysis the association between ESR2 rs3020450 polymorphism and cancer susceptibility was estimated and a case-control design was used to verify this result in ovarian cancer. The epidemiological effect of ESR2 rs3020450 polymorphism was assessed by attributable risk percentage (ARP) and population attributable risk percentage (PARP). Kaplan Meier plotters were used to evaluate overall survival (OS) and progression-free survival (PFS) in ovarian cancer patients and GEPIA for the differential expression of ESR2 levels in ovarian cancer and adjacent normal tissues.

RESULTS
The pooled analysis indicated no significant correlation between the ESR2 rs3020450 polymorphism and the cancer susceptibility. In the stratified analysis by cancer types, significantly decreased risk was found in ovarian cancer (AG vs GG: OR = 0.73, 95%CI: 0.53-0.97, P = 0.03). Unconditional logistic regression results of case-control study in ovarian cancer observed significant differences in all comparisons (AG vs GG: OR = 0.81, 95%CI: 0.62-0.98, P = 0.04; AA vs GG: OR = 0.63, 95%CI: 0.42-0.92, P = 0.01 and AG + AA vs GG: OR = 0.73, 95%CI: 0.53-0.96, P < 0.001). Based on meta-analysis and case-control pooled results, ARP and PARP were evaluated respectively in allele (21.95% and7.97%), heterozygote (36.99% and 12.11%) and dominant model (36.84% and 12.97%) of rs3020450 polymorphism in ovarian cancer. The expression levels of ESR2 in normal tissues was significantly higher than that in cancer tissues (OV, Median, 4.7:0.21), and significant correlations were observed between high ESR2 expression levels and long OS (HR = 0.80, 95%CI: 0.70-0.92, P = 0.002) and PFS (HR = 0.767, 95%Cl: 0.67-0.88, P < 0.001).

CONCLUSION
Our results indicated that ESR2 rs3020450 polymorphism was associated with ovarian cancer risk from epidemiological perspective, and high ESR2 expression levels was associated with long survival in patients with ovarian cancer.

Feng|Yajing|Y| Peng|Zhen|Z| Liu|Weigang|W| Yang|Zhongyu|Z| Shang|Jia|J| Cui|Liuxin|L| Duan|Fujiao|F|

D015972:Gene Expression Regulation, Neoplastic

D020022:Genetic Predisposition to Disease

Prognosis
ESR2
Polymorphism
Ovarian cancer
Epidemiological evaluation


Synergistic impact of co-exposures to toxic metals cadmium, lead, and mercury along with perfluoroalkyl substances on the healthy kidney function.

Abstract: Impact of co-exposures to toxic metals cadmium, lead, and mercury along with perfluoroalkyl substances on the healthy kidney function was evaluated among US adults aged > = 20 years by analyzing data (N = 7857) from National Health and Nutrition Examination Survey for 2003-2014. Perfluoroalkyl substances selected for analysis were: perfluorooctanoic acid (PFOA), perfluorooctane sulfonate (PFOS), perfluorohexane sulfonate (PFHxS), and perfluorononanoic acid (PFNA). High levels of exposures to Cd, Pb, total Hg, and PFAS were said to occur if their observed levels in blood/serum were greater than 75th percentiles. A healthy kidney function was defined if estimated glomerular filtration rate was found to be > = 60 mL/min/1.73 m2 and urine albumin creatinine ratio was ≤ 30 mg/g creatinine. Adjusted odds of a healthy kidney function due to co-exposures to high levels of Cd along with high levels of PFOA, PFOS, and PFNA were found to be 0.713, 0.576, and 0.640 respectively. Adjusted odds of a healthy kidney function due to co-exposures to high levels of Pb along with high levels of PFOA, and PFNA were found to be 0.657, and 0.671 respectively. Co-exposures to high levels of Hg as measured by the total mercury in blood was not found to affect the odds of a healthy kidney function.

Co-exposures
Toxic metals
Cadmium
Lead
Kidney function
PFAS


Design and Engineering of Antimicrobial Peptides Based on LPcin-YK3, an Antimicrobial Peptide Derivative from Bovine Milk.

Abstract: We have previously derived a novel antimicrobial peptide, LPcin-YK3(YK3), based on lactophoricin and have successfully studied and reported on the relationship between its structure and function. In this study, antimicrobial peptides with improved antimicrobial activity, less cytotoxicity, and shorter length were devised and characterized on the basis of YK3, and named YK5, YK8, and YK11. The peptide design was based on a variety of knowledge, and a total of nine analog peptides consisted of one to three amino acid substitutions and C-terminal deletions. In detail, tryptophan substitution improved the membrane perturbation, lysine substitution increased the net charge, and excessive amphipathicity decreased. The analog peptides were examined for structural characteristics through spectroscopic analytical techniques, and antimicrobial susceptibility tests were used to confirm their activity and safety. We expect that these studies will provide a platform for systematic engineering of new antibiotic peptides and generate libraries of various antibiotic peptides.

D052978:Disk Diffusion Antimicrobial Tests

Antimicrobial peptide
lactophoricin
tryptophan
amphipathicity
modification
net positive charge


A search for microorganisms producing medium-chain alkanes from aldehydes.

Abstract: Microorganisms with medium-chain alkane-producing activity are promising for the bio-production of drop-in fuel. In this study, we screened for microorganisms producing tridecane from tetradecanal. The activity of aldehyde decarbonylation was found in a wide range of microbes. In particular, the genus Klebsiella in the Enterobacteriaceae family was found to have a high ability to produce alkanes from aldehydes via enzyme catalyzed reaction.

Ito|Masakazu|M| Kambe|Hiromi|H| Kishino|Shigenobu|S| Muramatsu|Masayoshi|M| Ogawa|Jun|J|

Medium-chain alkanes
Aldehyde decarbonylase
Biofuel
Hydrocarbon
Klebsiella sp.


Psychoeducational Challenges in Spanish Children With Dyslexia and Their Parents' Stress During the COVID-19 Pandemic.

Abstract:
Background
Research during 2020 has been rapidly attending to the impact of COVID-19 on various dimensions of wellbeing (e.g., physical, psychological, lifestyle and routines) on adults and children around the world. However, less attention has focused on the psychoeducational impact on children and their families. To our knowledge, no currently available studies have looked specifically at the impact of COVID-19 on students with dyslexia and their families. Research on this topic is needed to offer greater support for this population of students and their families.

Objective
The main objective of this paper is to examine the psychoeducational impact of the required COVID-19 quarantine in Spain among children with dyslexia and their families.

Method
A sample of 32 children with dyslexia and their mothers participated in this study.

Measures
Children and adolescents with dyslexia and their mother completed several measures before the required national quarantine in Spain and again during the quarantine. Children completed measures of depression, state anxiety, reading activity, and reading motivation. Mothers provided demographic information and completed measures related to students' emotional and behavioral difficulties as well as parenting stress, parental distress, and a questionnaire about educational problems during quarantine.

Results
Major findings showed that during quarantine, children with dyslexia had increased levels of depression and anxiety symptoms, and parents perceived their children as having more emotional symptoms, hyperactivity-inattention, and conduct problems. During quarantine, children and adolescents with dyslexia also showed less reading activity and less reading motivation. Parents also reported significantly more stress, during quarantine compared to pre-quarantine conditions. Some demographic and psychological variables predicted children's state anxiety as well parental stress. The questionnaire related to impacts of quarantine also revealed several important findings. For example, nearly all parents of children with dyslexia reported (a) difficulties in establishing study routines, (b) that the quarantine negatively affected their child's learning, and (c) that they did not receive sufficient help from teachers on how to support their child's learning. Additionally, the vast majority of the parents were very worried about the child's learning and school success, the child's motivation and interest in reading, the child's peer relations, and the professional skills of the child's teacher.

Conclusion
This study offers a preliminary investigation into this topic and elucidates several psychoeducational challenges that children with dyslexia and their families have experienced during the quarantine in Spain. Study findings highlight the need to provide immediate support for children with dyslexia and emphasizes the importance of developing prevention programs to mitigate any future negative impacts of COVID-19 on children with dyslexia and their parents.

Soriano-Ferrer|Manuel|M|
Morte-Soriano|Manuel Ramón|MR|
Begeny|John|J|
Piedra-Martínez|Elisa|E|

dyslexia
COVID-19
psychoeducational impact
quarantine
parent stress


Short versus Long-Term Antibiotic Prophylaxis in Cesarean Section: A Randomized Clinical Trial.

Abstract:
Objective
The objective of the present study was to compare the efficacy of intravenous (IV) 48 h course of cefuroxime/metronidazole with long-term course using 48 h cefuroxime/metronidazole plus 5 days oral regimen of cefuroxime and metronidazole for the prevention of post cesarean section wound infection.

Methods
Two hundred and forty-eight women were randomized into two equal groups. Women in each arm of the study received IV cefuroxime 750 mg twelve hourly and IV metronidazole 400 mg eight hourly for 48 h. Those in the long-term arm received additional tablets of cefuroxime 500 mg twelve hourly and Tabs 400 mg of metronidazole eight hourly for 5 days. After the surgery, surgical site infections were evaluated. Length of hospital stay and the cost of antibiotics were also assessed.

Results
The wound infection rate was not statistically significantly different between the 2 groups (1.3% vs. 3.3%, P = 0.136). The incidence of endometritis was 2.1%, with no statistically significant difference seen between the two groups (0.4% vs. 1.6%, P = 0.213). Escherichia coli was the most common isolate seen in 36.4% of infected wounds. The short arm group stayed for significantly shorter days in the hospital (2.9 ± 1.0 vs. 3.8 ± 1.1 days,P < 0.001), and the cost of antibiotics was also significantly less in the short arm group (P < 0.001). Organisms associated with nosocomial infections were seen only in the long arm that stayed in the hospital for longer days.

Conclusions
Short-term prophylactic antibiotics are as effective as long-term prophylaxis and have other benefits such as shorter duration of hospital stay, reduced cost of antibiotics, and reduction of nosocomial infections.

Adaji|James A|JA|
Akaba|Godwin O|GO|
Isah|Aliyu Y|AY|
Yunusa|Thairu|T|

Antibiotics
prophylaxis
cesarean section
wound infection
postoperative


Response to ruxolitinib in patients with intermediate-1-, intermediate-2-, and high-risk myelofibrosis: results of the UK ROBUST Trial.

Abstract: Myelofibrosis is characterized by splenomegaly and debilitating constitutional symptoms that negatively impact patients' quality of life. ROBUST, a UK, open-label, phase II study, evaluated the safety and efficacy of ruxolitinib in patients with myelofibrosis (N = 48), including intermediate-1 risk patients. The primary composite endpoint was the proportion of patients achieving treatment success [≥ 50% reduction in palpable spleen length and/or a ≥ 50% decrease in Myelofibrosis Symptom Assessment Form Total Symptom Score (MF-SAF TSS)] at 48 weeks. This was the first time that efficacy of ruxolitinib in myelofibrosis has been evaluated based on these criteria and the first time the MF-SAF was used in a population of patients solely from the United Kingdom. Overall, 50% of patients and 57% of intermediate-1 risk patients, achieved treatment success; reductions in spleen length and symptoms were observed in all risk groups. The majority of patients (66.7%) experienced ≥ 50% reductions from baseline in spleen length at any time. Improvements in MF-SAF TSS were seen in 80.0%, 72.7%, and 72.2% of intermediate-1, intermediate-2, and high-risk patients, respectively. Consistent with other studies of ruxolitinib, the most common haematological adverse events were anaemia and thrombocytopenia. Results indicate that most patients with myelofibrosis, including intermediate-1 risk patients, may benefit from ruxolitinib treatment.

Mead|Adam J|AJ|
Milojkovic|Dragana|D|
Knapper|Steven|S|
Garg|Mamta|M|
Chacko|Joseph|J|
Farquharson|Mira|M|
Yin|John|J|
Ali|Sahra|S|
Clark|Richard E|RE|
Andrews|Chris|C|
Dawson|Meryem Ktiouet|MK|
Harrison|Claire|C|

ruxolitinib
myelofibrosis
symptoms
Myelofibrosis Symptom Assessment Form
Janus kinase inhibitor


Periprosthetic Intertrochanteric Fracture between Hip Resurfacing and Retrograde Nail.

Abstract: Periprosthetic femur fractures present a growing worldwide challenge for orthopaedic surgeons. Fractures around a hip resurfacing implant create unique management problems. When considering fixation, there can be limited options for ideal stabilization and some require creative constructs. We present an interesting case of a periprosthetic intertrochanteric femur fracture between a hip resurfacing implant and retrograde intramedullary nail.

Soin|Sandeep|S| El-Shaar|Rami|R| Taylor|Aaron|A| Ketz|John|J|

Intertrochanteric fracture
Hip resurfacing
Retrograde nail
Femur fracture
Hip implant
Periprosthetic fracture


Study on Relationship Between Fluorescence Properties and Structure of Substituted 8-Hydroxyquinoline Zinc Complexes.

Abstract: Organic light-emitting diodes (OLEDs) produced from 8-hydroxyquinoline metal complexes play a vital role in modern electroluminescent devices. In this manuscript, a series of 8-hydroxyquinoline derivatives were synthesized by different methods and their corresponding zinc metal complexes were prepared. The UV and fluorescence properties of the complexes were measured aiming to understand the effect of substituents at the quinoline ring on the fluorescence properties of the complexes. When the C-5 of 8-hydroxyquinoline was replaced by halogen group, the fluorescence emission wavelengths had been red-shifted, at the same time, blue-shifted of fluorescence emission wavelength was observed when the C-5 position of 8-hydroxyquinoline was substituted by electron-withdrawing group. When the C-4 position of 8-hydroxyquinolie was substituted by methyl or the C-5 position was substituted by sulfonic acid group, the corresponding zinc complexes had higher fluorescence intensity than 8-hydroxyquinolie zinc.

Fluorescence
Zinc
8-hydroxyquinoline derivatives
Substituents


Phytochemical analysis of crude extract of Delphinium brunonianum and its effect on hypertension and metabolic perturbations in fructose fed rats.

Abstract: The present study aims at phytochemical profiling and valuating the effect of crude extract of Delphinium brunonianum on fructose mediated rise in blood pressure and metabolic abnormalities in rats. Therefore, rats were fed on fructose (10%w/v) for 6 weeks. Rats in treatment groups received amlodipine 250, 500 and 1000 mg/kg of DB-Cr separately in concurrent to fructose. Various parameters of metabolic perturbations were assessed at the end of study. Further, DB-Cr was analyzed using LC-MS technique. DB-Cr exerted remarkable antihypertensive effect whereas, sympathetic hyperactivity and hyperinsulinemia in these rats was significantly blunted, further, endothelium functionality was successfully restored. LC-MS analysis of DB-Cr revealed the presence of a variety of chemical constituents (41) including quinic acid, scopolin, gingerol, Robinetin 3-rutinoside, KAPA and maleic acid. In conclusion, D. brunonianum possess the potential to combat the fructose mediated hypertension and metabolic perturbations, which may partially be due to its chemical constituents.

Asif|Hira|H|
Alamgeer|||
Bukhari|Ishfaq Ali|IA|
Vohra|Fahim|F|
Afzal|Sibtain|S|
Khan|Sher Wali|SW|
Niazi|Zahid Rasul|ZR|

Delphinium brunonianum
hypertension
LC-MS analysis
metabolic syndrome
oxidative stress


Hyperprolactinemia in association with subclinical hypothyroidism.

Abstract:
BACKGROUND
Hyperprolactinemia is the most common endocrine disorder in hypothalamic-pituitary axis and has been reported in variable levels in patients with overt primary hypothyroidism. We decided to determine the prevalence of hyperprolactinemia and clinical related symptoms in subclinical hypothyroidism patients.

METHODS
In this cross sectional study, prolactin levels of 481 subclinical hypothyroid patients were assessed. Prolactin measurement was performed using chemiluminescent immunoassay. Data were collected and analyzed.

RESULTS
Sixty-two (13%) patients were males and 419 (87%) were females. The mean age of the patients was 32.53±10.13 years. Ninty-eight patients (91 females 7 males) had high prolactin. Prevalence of hyperprolactinemia in subclinical hypothyroidism was 20.4%. (11% in men and 22% in women, p=0.05). There was no correlation between the serum TSH and prolactin level. Clinical symptom prevalence was not different between patients with and without hyperprolactinemia.

CONCLUSION
This study showed that prevalence of hyperprolactinemia in subclinical hypothyroidism is notable and this disorder is more common in female subclinical hypothyroidism than the men.

Bahar|Adele|A| Akha|Ozra|O| Kashi|Zahra|Z| Vesgari|Zakiie|Z|

Hyperprolactinemia
Subclinical hypothyroidism
Clinical symptom


The impact of seismic air gun exposure on the haemolymph physiology and nutritional condition of spiny lobster, Jasus edwardsii.

Abstract: There is a critical knowledge gap regarding the impacts of seismic air gun signals on the physiology of adult crustaceans. We conducted four controlled field experiments to examine the impact of seismic acoustic signals on spiny lobster, Jasus edwardsii. Seismic air gun exposure suppressed total haemocyte count (THC) for up to 120days post-exposure, suggesting a chronic negative impact of immune competency. THC levels after 365days post-exposure, were elevated two fold, potentially indicating an immune response to infection. Haemolymph refractive index was reduced after 120days post exposure in one experiment, suggesting a chronic impairment of nutritional condition. There was no effect of air gun exposure on 24 haemolymph biochemical parameters, hepatopancreas index or survival. Collectively these results indicate that the biochemical haematological homeostasis of J. edwardsii is reasonably resilient to seismic acoustic signals, however, air gun exposure may negatively influence the lobster's nutritional condition and immunological capacity.

Fitzgibbon|Quinn P|QP|
Day|Ryan D|RD|
McCauley|Robert D|RD|
Simon|Cedric J|CJ|
Semmens|Jayson M|JM|

D000824:Animal Nutritional Physiological Phenomena

Crustaceans
Total haemocyte count
Aquatic noise
Invertebrates
Marine noise pollution
Seismic surveys
Southern rock lobster


Translation of cancer immunotherapy from the bench to the bedside.

Abstract: The tremendous success of immune checkpoint blockades has revolutionized cancer management. Our increased understanding of the cell types that compose the tumor microenvironment (TME), including those of the innate and adaptive immune system, has helped to shape additional immune modulatory strategies in cancer care. Pre-clinical and clinical investigations targeting novel checkpoint interactions and key pathways that regulate cancer immunity continue to increase rapidly. Various combinatorial drug regimens are being tested in attempt to achieve durable response and survival rates of patients with cancer. This review provides an overview of specific components of the TME, an introduction to novel immune checkpoints, followed by a survey of present day and future combination immune modulatory therapies. The idea that the immune system can recognize and destroy tumor cells was first described in the cancer immunosurveillance hypothesis of Burnet and Thomas. However, early experimental evidence failed to support the concept. It was not until the late 1990s when seminal papers clearly showed the existence of cancer immunosurveillance, leading to the cancer immunoediting hypothesis. In this century, progress in the understanding of negative regulators of the immune response led to the discovery that inhibition of these regulators in patients with cancer could lead to dramatic and durable remissions. Drs. Tasuku Honjo and James P. Allison were awarded the Nobel Prize in 2018 for their pioneering work in this field. We now see rapid advances in cancer immunology and emerging effective therapies revolutionizing cancer care across tumor types in the clinic, while pre-clinical research is moving from a focus on the malignant cells themselves to dissect the highly heterogenic and complex multi-cellular tumor microenvironment (TME).

Guo|Qianyu|Q|
Huang|Fan|F|
Goncalves|Christophe|C|
Del Rincón|Sonia V|SV|
Miller|Wilson H|WH|

Immune checkpoints
Tumor microenvironment
Cytokine therapies
Oncogenic kinases
Tumor immunology


Selective Alkenylation and Hydroalkenylation of Enol Phosphates through Direct C-H Functionalization.

Abstract: An efficient and selective Rh-catalyzed direct CH functionalization reaction of enol phosphates was developed. The method is applicable to a variety of coupling partners, including activated alkenes, alkynes, and allenes, and leads to the formation of various valuable alkenylated and hydroalkenylated enol phosphates through the action of the phosphate directing group. The versatility and utility of the coupling products were demonstrated through further transformations into synthetically useful building blocks.

alkenylation
hydroalkenylation
enol phosphates
CH activation
rhodium


Noncontiguous finished genome sequence and description of Necropsobacter massiliensis sp. nov.

Abstract: Strain FF6(T) was isolated from the cervical abscess of a 4-year-old Senegalese boy, in Dakar, Senegal. MALDI-TOF MS did not provide any identification. This strain exhibited a 95.17% 16S rRNA sequence identity with Necropsobacter rosorum. Using a polyphasic study including phenotypic and genomic analyses, strain FF6(T) was an aero-anaerobic Gram-negative cocobacillus, oxidase positive, and exhibited a genome of 2,493,927 bp (1 chromosome but no plasmid) with a G+C content of 46.2% that coded 2,309 protein-coding and 53 RNA genes. On the basis of these data, we propose the creation of Necropsobacter massiliensis sp. nov.

Lo|C I|CI|
Padhamanabhan|R|R|
Fall|B|B|
Sambe-Ba|B|B|
Mediannikov|O|O|
Nguyen|T-T|TT|
Prudent|E|E|
Faye|N|N|
Wade|B|B|
Raoult|D|D|
Fournier|P-E|PE|
Fenollar|F|F|

genome
Necropsobacter massiliensis
Senegal
Culturomics
taxono-genomics


Residues of different gel formulations on dentinal walls: A SEM/EDS analysis.

Abstract: The aim of this study was to evaluate the presence of residues of sodium hypochlorite gel, chlorhexidine gel, and EDTA gel on dentinal walls after canal preparation through chemical SEM- elemental chemical microanalysis (EDS) analysis. Forty-eight single-rooted teeth were selected. They had their crowns sectioned and were instrumented with a reciprocating system. The canals were irrigated with 5 mL of saline solution during root canal preparation. After instrumentation, the root canals were irrigated with 3 mL 17% EDTA followed by 1 min of ultrasonic passive activation (3× 20 sec) to remove the smear layer, and then irrigated with 3 mL of saline solution. The specimens were randomized into three groups (n = 12) according to the chemical substance that filled the root canal for 30 min: GI: 5.5% sodium hypochlorite gel; GII: 2% chlorhexidine gel; GIII: 24% EDTA gel; Negative control group: no substance was used. Then, the root canals were irrigated with 6 mL of saline solution followed by 1 min of ultrasonic passive activation (3× 20 sec). After ultrasonic activation, the canals were irrigated with 2 mL saline. The roots were sectioned, and the percentage of each chemical element present in the samples was analyzed through chemical SEM-EDS microanalysis. All experimental groups showed a significantly higher percentage of chemical elements (Na and/or Cl) than the control group (P < 0.03). This in vitro study has shown that, regardless of chemical solutions used even after the final irrigation protocol, chemical residues of different substances remained attached to the root canal walls.

do Nascimento|Angela Longo|AL|
Busanello|Fernanda Hoffmann|FH|
Só|Marcus Vinícius Reis|MV|
Kuga|Milton Carlos|MC|
Pereira|Jefferson Ricardo|JR|
Grecca|Fabiana Soares|FS|

sodium hypochlorite
chlorhexidine
EDTA
electron probe microanalysis
endodontics


The reliability of body pain diagrams in the quantitative measurement of pain distribution and location in patients with musculoskeletal pain: a systematic review.

Abstract:
OBJECTIVE
The purpose of this study was to perform a systematic review of test-retest, intraexaminer, and interexaminer reliability of measuring pain location and distribution using the body pain diagram.

METHODS
We conducted a systematic review of the literature using a search conducted in Medline, CINAHL, and Nursing and Allied Health from inception to March 1, 2012. Articles were screened and selected by pairs of reviewers using predetermined inclusion criteria. Internal validity was assessed independently by 2 reviewers using a modified version of the QUADAS instrument. Articles with adequate internal validity were included in the best evidence synthesis.

RESULTS
We reviewed 10 studies. Of those, 6 were included in the best evidence synthesis. We found varying levels of evidence that pain location and pain distribution can be measured reliably using the body pain diagram in patients with acute and chronic low back pain with or without radiculopathy. The test-retest reliability for measuring pain distribution ranged from intraclass correlation coefficient of 0.58 to 0.94. Similarly, the test-retest reliability for measuring pain location ranged from kappa (κ) of 0.13 to 0.85. The intraexaminer and interexaminer reliability for measuring pain distribution were intraclass correlation coefficient of 0.99 and 0.99, respectively. The intraexaminer and interexaminer reliability for measuring pain location ranged from κ of 0.77 to 0.88 and 0.61 to 1.00, respectively.

CONCLUSIONS
We found important variations in the test-retest reliability of pain location and distribution across different test-retest scenarios and across body regions. The intraexaminer and interexaminer reliability for the measurement of pain distribution and pain location using the body pain diagram in patients with acute and chronic low back pain with or without radiculopathy are adequate.

Southerst|Danielle|D| Côté|Pierre|P| Stupar|Maja|M| Stern|Paula|P| Mior|Silvano|S|

D000208:Acute Disease
D000328:Adult
D001830:Body Surface Area
D002908:Chronic Disease
D005069:Evaluation Studies as Topic
D019317:Evidence-Based Medicine
D005260:Female
D006801:Humans
D017116:Low Back Pain
D008297:Male
D008875:Middle Aged
D059352:Musculoskeletal Pain
D015588:Observer Variation
D010147:Pain Measurement
D015203:Reproducibility of Results
D012680:Sensitivity and Specificity
D012720:Severity of Illness Index

Pain
Pain Measurement
Reproducibility of Results


Diaporthe amygdali, a species complex or a complex species?

Abstract: Delimitation of species boundaries within the fungal genus Diaporthe has been challenging, but the analyses of combined multilocus DNA sequences has become an important tool to infer phylogenetic relationships and to circumscribe species. However, analyses of congruence between individual gene genealogies and the application of the genealogical concordance principle have been somehow overlooked. We noted that a group of species including D. amygdali, D. garethjonesii, D. sterilis, D. kadsurae, D. ternstroemia, D. ovoicicola, D. fusicola, D. chongqingensis and D. mediterranea, commonly known as D. amygdali complex, occupy a monophyletic clade in Diaporthe phylogenies but the limits of all species within the complex are not entirely clear. To assess the boundaries of species within this complex we employed the Genealogical Concordance Phylogenetic Species Recognition principle (GCPSR) and coalescence-based models: General Mixed Yule-Coalescent (GMYC) and Poisson Tree Processes (PTP). The incongruence detected between individual gene phylogenies, as well as the results of coalescent methods do not support the recognition of lineages within the complex as distinct species. Moreover, results support the absence of reproductive isolation and barriers to gene flow in this complex, thus providing further evidence that the D. amygdali species complex constitutes a single species. This study highlights the relevance of the application of the GCPSR principle, showing that concatenation analysis of multilocus DNA sequences, although being a powerful tool, might lead to an erroneous definition of species limits. Additionally, it further shows that coalescent methods are useful tools to assist in a more robust delimitation of species boundaries in the genus Diaporthe.

Phylogeny
GMYC
PTP
Coalescent models
Species delimitation
Systematics


Aniba canelilla (Kunth) Mez (Lauraceae): A Review of Ethnobotany, Phytochemical, Antioxidant, Anti-Inflammatory, Cardiovascular, and Neurological Properties.

Abstract: Aniba canelilla (Kunth) Mez, popularly known as "casca preciosa" (precious bark), falsa canela (cinnamon-scented) Casca-do-maranhão (bark of maranhão), and Folha-preciosa (precious leaf), is an aromatic species of the Lauraceae family, widely distributed in the Amazon region. In traditional medicine, it is indicated for the treatment of a great diversity of diseases, including digestive, respiratory, inflam]matory, painful, and central nervous system disorders, it is administered mainly in the form of tea or decoction orally. Its essential oil is referred to as a natural antioxidant for food preservation and disease control, showing great potential for use in the cosmetics, perfumery, and pharmaceutical products sector. The present review aimed to discuss critically and comprehensively the ethnobotanical characteristics, phytochemical constitution, and scientifically tested biological properties of A. canelilla, systematizing the knowledge about the species and proposing new perspectives for research and development. The chemical composition of A. canelilla includes 1-nitro-2-phenylethane, metyleugenol, eugenol, safrol, anabasin, anbin, tannin, α-pinene, b-pinene, b-felandren, b-caryophyllene, b-sesquifelandren, p-cymene, linalool, α-copaene, and spatulenol. Researches with ethanolic extracts, essential oils, and major constituents (1-nitro-2-phenylethane and metyleugenol) have revealed antioxidant, antinociceptive, anti-inflammatory, cardio-modulating, hypotensive (vasorelaxant), hypnotic, anxiolytic, anticholinesterase, and antibiotic properties (trypanomicidal, leishmanicidal, and antifungal). Some of these effects are potentially beneficial for aging-related diseases treatment, such as cardio and cerebrovascular, chronic inflammatory, neurological, and degenerative diseases. However, it is necessary to advance in the research of its clinical use and development of therapeutic products.

Souza-Junior|Fabio J C|FJC|
Luz-Moraes|Daniele|D|
Pereira|Felype S|FS|
Barros|Mayra A|MA|
Fernandes|Luanna M P|LMP|
Queiroz|Letícia Y|LY|
Maia|Cristiane F|CF|
Maia|José Guilherme S|JGS|
Fontes-Junior|Enéas A|EA|

Aniba canelilla (Kunth) Mez
1-nitro-2-phenylethane
biological activities
folk medicine
methyleugenol
toxicity


Evaluation of a healthy ageing intervention for frail older people living in the community.

Abstract:
AIM
To evaluate a healthy ageing intervention in the form of a program of physical and social activity for frail older people living in the community.

METHODS
New members of an activity program were surveyed before and after attending the program and interviewed face-to-face prior to the program, immediately after the program and through a telephone interview two months following the program.

RESULTS
Program participants reported better health, social function and mental well-being; greater engagement in household and leisure activities; and increased enjoyment and confidence through participating in the program. Some participants could not attend the whole program due to poor health or difficulties securing transport.

CONCLUSION
The results suggest the program was successful in enhancing the health and well-being of those community-dwelling older adults who stayed in the program. However, the high drop-out rate suggests that flexibility is required in community-based healthy ageing programs.

McNamara|Beverley|B|
Rosenwax|Lorna|L|
Lee|Elinda A L|EA|
Same|Anne|A|

D000367:Age Factors
D000368:Aged
D000375:Aging
D015444:Exercise
D005260:Female
D016330:Frail Elderly
D015577:Geriatric Assessment
D006293:Health Promotion
D006302:Health Services Research
D006299:Health Services for the Aged
D000070497:Healthy Lifestyle
D006801:Humans
D057187:Independent Living
D007407:Interviews as Topic
D008297:Male
D008603:Mental Health
D008875:Middle Aged
D010352:Patient Dropouts
D015397:Program Evaluation
D011788:Quality of Life
D012919:Social Behavior
D013689:Telephone
D013997:Time Factors

evaluation
healthy ageing
intervention
community
social activity
physical activity


Nickel Oxide Nanoparticles Induce Oxidative DNA Damage and Apoptosis in Kidney Cell Line (NRK-52E).

Abstract: Increasing use of nickel oxide (NiO) nanoparticles in different applications results in high occupational and environmental exposure to them. However, the effect of NiO nanoparticles on human health is still poorly documented. It was aimed to investigate the toxic potentials of NiO nanoparticles on NRK-52E kidney epithelial cells. The following assays were used: the nanoparticle characterization by transmission electron microscopy (TEM) and dynamic light scattering (DLS); the determination of cellular uptake and morphologic changes by TEM and inductively coupled plasma-mass spectrometry (ICP-MS); MTT and neutral red uptake (NRU) assays for cytotoxicity; comet assay for genotoxicity; the determination of malondialdehyde (MDA), 8-hydroxydeoxyguanosine (8-OHdG), protein carbonyl (PC) and glutathione (GSH) levels by enzyme-linked immune sorbent assays (ELISA) for the potential of oxidative damage; and Annexin V-FITC apoptosis detection assay with propidium iodide (PI) for apoptosis. The nanoparticles were taken up by the cells and induced dose-dependent DNA damage by comet assay and oxidative damage evidenced by increasing levels of MDA, 8-OHdG, PC and depletion of GSH. At ≥294.0 μg/mL concentration, NiO nanoparticles caused 50% inhibition in cell viability by the cytotoxicity assays. Also, they showed apoptotic/necrotic effects on the cells as well as some morphological changes. We have indicated that their cellular damage effects should raise concern about the safety associated with their applications in consumer products.

Nickel oxide nanoparticles
Apoptosis
Genotoxicity
Nephrotoxicity
Oxidative stress


An Inexpensive Staining Alternative for Gelatin Zymography Gels.

Abstract: Zymography is a widely used electrophoretic method to determine proteolytic activities in samples from various sources. The method is based on copolymerizing a suitable protein substrate within a sodium dodecyl sulfate-polyacrylamide gel. Following electrophoretic separation of the protease containing samples and a suitable incubation period, degradation of the substrate can be visualized through staining with Coomassie blue. Sites of proteolysis become visible as white bands on a dark blue background. However, this staining protocol requires considerable amounts of ethanol and acetic acid to remove unbound dye molecules. In this report, we describe a new staining protocol using Ponceau S which offers substantial advantages in terms of assay usability and cost reduction, especially when performing large quantities of zymograms or in resource-limited settings. Fast and reproducible staining of zymograms with our protocol is demonstrated, and reliable quantitation of proteolytic activity in comparison to the standard Coomassie staining procedure is shown.

gelatin zymography
Coomassie
Ponceau
inexpensive staining method


Dietary consumption of monosodium L-glutamate induces adaptive response and reduction in the life span of Drosophila melanogaster.

Abstract: Adaptive response is the ability of an organism to better counterattack stress-induced damage in response to a number of different cytotoxic agents. Monosodium L-glutamate (MSG), the sodium salt of amino acid glutamate, is commonly used as a food additive. We investigated the effects of MSG on the life span and antioxidant response in Drosophila melanogaster (D. melanogaster). Both genders (1 to 3 days old) of flies were fed with diet containing MSG (0.1, 0.5, and 2.5-g/kg diet) for 5 days to assess selected antioxidant and oxidative stress markers, while flies for longevity were fed for lifetime. Thereafter, the longevity assay, hydrogen peroxide (H2 O2 ), and reactive oxygen and nitrogen species levels were determined. Also, catalase, glutathione S-transferase and acetylcholinesterase activities, and total thiol content were evaluated in the flies. We found that MSG reduced the life span of the flies by up to 23% after continuous exposure. Also, MSG increased reactive oxygen and nitrogen species and H2 O2 generations and total thiol content as well as the activities of catalase and glutathione S-transferase in D. melanogaster (P < .05). In conclusion, consumption of MSG for 5 days by D. melanogaster induced adaptive response, but long-term exposure reduced life span of flies. This study may therefore have public health significance in humans, and thus, moderate consumption of MSG is advocated by the authors.

monosodium L-glutamate
adaptive response
Drosophila melanogaster
antioxidant response
oxidative stress
longevity


Interactions of star-like polyelectrolyte micelles with hydrophobic counterions.

Abstract: Hydrophobicity of a counterion has a profound effect on the interaction with polyelectrolytes similar to that of multivalency. Specifically, understanding this interaction in weak polyelectrolyte micelles might assist in developing nanocarriers for pH-controlled encapsulation and release. We used star-like weak polyelectrolyte micelles of polystyrene-block-poly(2-vinyl pyridine) (PS-P2VP) with fixed aggregation number as a model polyelectrolyte, and cobalt bis(1,2-dicarbollide) (COSAN) as a model hydrophobic anion. We used NMR to assess the mobility of the polymer segments in the presence of varying amounts of COSAN, and at varying protonation degrees of the polyelectrolyte. Same experiments with indifferent electrolyte (NaCl) were used as a control. Furthermore, we used coarse-grained simulations to obtain a detailed picture of the effect of hydrophobic counterions on the conformation of the micelles. A small amount of hydrophobic counterions causes morphological changes within the micelles, whereas a bigger amount causes precipitation. This was confirmed both in simulations and in experiments. Furthermore, adsorption of the counterions induces ionization of the collapsed segments of the polyelectrolyte. Although the COSAN/P2VP system is rather specific, the generic model used in the coarse-grained simulations shows that the observed behavior is a consequence of synergy of hydrophobic and electrostatic attraction between polyelectrolytes and hydrophobic counterions. Our study provides general insights into the molecular mechanisms of these interactions.

Fernandez-Alvarez|Roberto|R| Nová|Lucie|L| Uhlík|Filip|F| Kereïche|Sami|S| Uchman|Mariusz|M| Košovan|Peter|P| Matějíček|Pavel|P|

Star-like polyelectrolyte
Micelle
Weak polyelectrolyte
Anionic boron cluster compound
Ionic surfactant
Ionization equilibrium


Heavy metal exposure through artificial diet reduces growth and survival of Spodoptera litura (Lepidoptera: Noctuidae).

Abstract: Insect physiology is affected by the presence of toxins in the surrounding environment of insects as well as their food sources. The objective of this study was to determine the effect of heavy metal exposure to two low concentrations (50 μg/g and 150 μg/g) of lead (Pb) and zinc (Zn) through artificial diet to the larvae on biological parameters of Asian armyworm (Spodoptera litura Fabricius) (Lepidoptera: Noctuidae). Both Pb and Zn, even at low concentrations, had relatively high toxic effects on S. litura larvae (P < 0.01). S. litura larval weight and length suffered the maximum reduction when the larvae were fed on diet mixed with the high Pb concentration (150 μg/g) tested compared to the other treatments. At the same Pb concentration (150 μg/g), values of larva growth index, pupa growth index, immature growth index, standardized growth index, and fitness index were 4.66, 7.33, 7.82, 5.35, and 10.00 times lower, respectively, than those of control. At the same Zn concentration (150 μg/g), values of larval growth index, pupal growth index, immature growth index, standardized growth index, and fitness index were 5.61, 3.00, 3.04, 3.23, and 9.24 times lower, respectively, than those of control. The survival rate of S. litura larvae was also lower (12.5%) when the larvae were fed on diet mixed with Pb at 150 μg/g after 10 days of observation. Overall, the presence of those heavy metals in the environment, even at low concentrations, would exert an adverse impact on larvae development of this insect. From this point of view, findings could provide a basis for long-term evaluation of heavy metal risk and its impact on populations of important agricultural pests.

Ali|Sajjad|S|
Ullah|Muhammad Irfan|MI|
Saeed|Muhammad Farhan|MF|
Khalid|Samina|S|
Saqib|Muhammad|M|
Arshad|Muhammad|M|
Afzal|Muhammad|M|
Damalas|Christos A|CA|

Lead
Zinc
Larvae
Asian armyworm
Bioindicator
Pollution
Stress


A review on COVID-19 forecasting models.

Abstract: The novel coronavirus (COVID-19) has spread to more than 200 countries worldwide, leading to more than 36 million confirmed cases as of October 10, 2020. As such, several machine learning models that can forecast the outbreak globally have been released. This work presents a review and brief analysis of the most important machine learning forecasting models against COVID-19. The work presented in this study possesses two parts. In the first section, a detailed scientometric analysis presents an influential tool for bibliometric analyses, which were performed on COVID-19 data from the Scopus and Web of Science databases. For the above-mentioned analysis, keywords and subject areas are addressed, while the classification of machine learning forecasting models, criteria evaluation, and comparison of solution approaches are discussed in the second section of the work. The conclusion and discussion are provided as the final sections of this study.

Rahimi|Iman|I|
Chen|Fang|F|
Gandomi|Amir H|AH|0000-0002-2798-0104

COVID-19
Forecasting
Analysis
SEIR
SIR
Time series


New evidence for a pain personality? A critical review of the last 120 years of pain and personality.

Abstract:
BACKGROUND
Personality traits may influence development and adjustment to ongoing pain. Over the past 120 years, there has been considerable research into the relationship between pain and personality. This paper presents new evidence for common personality traits found amongst chronic pain sufferers. In particular, it evaluates evidence for Cloninger's biopsychosocial model of personality in distinguishing typical personality features of chronic pain sufferers. It evaluates this evidence in the context of the past 120 years of research including psychodynamic formulations, MMPI studies, personality disorder investigations, and the influence of neuroticism on chronic pain.

METHODS
A literature search was conducted using PubMed, Medline, PsycINFO, SCOPUS and Cochrane library. Search terms included chronic pain, pain, personality, neuroticism, harm avoidance, self-directedness, attachment, Temperament and Character Inventory (TCI-R), MMPI, MMPI-2, NEO-PI, EPI, Millon Clinical Multiaxial Inventory, Millon Behavioral Health Inventory, Millon Behavioral Medicine Diagnostic, the Personality Assessment Inventory, the Locus of Control Construct and different combinations of these terms.

CONCLUSIONS
Recent descriptive studies using Cloninger's Temperament and Character Inventory (TCI-R) suggest that higher harm avoidance and lower self-directedness may be the most distinguishing personality features of chronic pain sufferers. High harm avoidance refers to a tendency to be fearful, pessimistic, sensitive to criticism, and requiring high levels of re-assurance. Low self-directedness often manifests as difficulty with defining and setting meaningful goals, low motivation, and problems with adaptive coping. Evidence for this personality profile is found across a wide variety of chronic pain conditions including fibromyalgia, headache and migraine, temporomandibular disorder, trigeminal neuropathy, musculo-skeletal disorders and heterogeneous pain groups. Limitations are also discussed. For example, high harm avoidance is also found in those suffering anxiety and depression. While many studies control for such factors, some do not and thus future research should address such confounds carefully. The evidence is also evaluated within the context of past research into the existence of 'a pain personality'. Psychodynamic formulations are found to be deficient in objective scientific methods. MMPI studies lack sufficient evidence to support 'a pain personality' and may be confounded by somatic items in the instrument. More recent neuroticism studies suggest a relationship between neuroticism and pain, particularly for adjustment to chronic pain. Personality disorders are more prevalent in chronic pain populations than non-pain samples.

CLINICAL IMPLICATIONS
Because harm avoidance reflects a tendency to developed conditioned fear responses, we suggest that higher harm avoidance may create more vulnerability to developing a fear-avoidance response to chronic pain. Furthermore, lower self-directedness may contribute to keeping a sufferer within this vicious cycle of fear, avoidance and suffering. Moreover, we suggest that harm avoidance and self-directedness are broader and more complex constructs than current clinical targets of CBT such as fear-avoidance and self-efficacy. Thus, assessing such personality traits may help to address the complexity of chronic pain presentations. For example, it may help to identify and treat sufferers more resistant to treatment, more prone to comorbidity and more vulnerable to entering the vicious cycle of chronic pain, suffering and disability.

Naylor|Brooke|B|
Boag|Simon|S|
Gustin|Sylvia Maria|SM|

Personality
Chronic pain
Neuroticism
Harm avoidance
Self-directedness


What is so frightening about spiders? Self-rated and self-disclosed impact of different characteristics and associations with phobia symptoms.

Abstract: Spider phobia is a common and impairing mental disorder, yet little is known about what characteristics of spiders that spider phobic individuals find frightening. Using screening data from a clinical trial, we explored which characteristics that spider-fearful individuals (n = 194) rated as having the greatest impact on fear, used factor analysis to group specific characteristics, and explored linear associations with self-reported phobia symptoms. Second, a guided text-mining approach was used to extract the most common words in free-text responses to the question: "What is it about spiders that you find frightening?" Both analysis types suggested that movement-related characteristics of spiders were the most important, followed by appearance characteristics. There were, however, no linear associations with degree of phobia symptoms. Our findings reveal the importance of targeting movement-related fears in in-vivo exposure therapy for spider phobia and using realistically animated spider stimuli in computer-based experimental paradigms and clinical interventions such as Virtual Reality exposure therapy.

D063367:Virtual Reality Exposure Therapy

Spider
phobia
virtual reality
biolocomotion
text mining


Systemic Consequences of Pulmonary Hypertension and Right-Sided Heart Failure.

Abstract: Pulmonary hypertension (PH) is a feature of a variety of diseases and continues to harbor high morbidity and mortality. The main consequence of PH is right-sided heart failure which causes a complex clinical syndrome affecting multiple organ systems including left heart, brain, kidneys, liver, gastrointestinal tract, skeletal muscle, as well as the endocrine, immune, and autonomic systems. Interorgan crosstalk and interdependent mechanisms include hemodynamic consequences such as reduced organ perfusion and congestion as well as maladaptive neurohormonal activation, oxidative stress, hormonal imbalance, and abnormal immune cell signaling. These mechanisms, which may occur in acute, chronic, or acute-on-chronic settings, are common and precipitate adverse functional and structural changes in multiple organs which contribute to increased morbidity and mortality. While the systemic character of PH and right-sided heart failure is often neglected or underestimated, such consequences place additional burden on patients and may represent treatable traits in addition to targeted therapy of PH and underlying causes. Here, we highlight the current state-of-the-art understanding of the systemic consequences of PH and right-sided heart failure on multiple organ systems, focusing on self-perpetuating pathophysiological mechanisms, aspects of increased susceptibility of organ damage, and their reciprocal impact on the course of the disease.

Rosenkranz|Stephan|S|
Howard|Luke S|LS|
Gomberg-Maitland|Mardi|M|
Hoeper|Marius M|MM|

pulmonary hypertension
right-sided heart failure
cognitive function
immune system
kidney dysfunction
liver dysfunction
sleep


The Role of CREB, SRF, and MEF2 in Activity-Dependent Neuronal Plasticity in the Visual Cortex.

Abstract: The transcription factors CREB (cAMP response element binding factor), SRF (serum response factor), and MEF2 (myocyte enhancer factor 2) play critical roles in the mechanisms underlying neuronal plasticity. However, the role of the activation of these transcription factors in the different components of plasticity in vivo is not well known. In this study, we tested the role of CREB, SRF, and MEF2 in ocular dominance plasticity (ODP), a paradigm of activity-dependent neuronal plasticity in the visual cortex. These three proteins bind to the synaptic activity response element (SARE), an enhancer sequence found upstream of many plasticity-related genes (Kawashima et al., 2009; Rodríguez-Tornos et al., 2013), and can act cooperatively to express Arc, a gene required for ODP (McCurry et al., 2010). We used viral-mediated gene transfer to block the transcription function of CREB, SRF, and MEF2 in the visual cortex, and measured visually evoked potentials in awake male and female mice before and after a 7 d monocular deprivation, which allowed us to examine both the depression component (Dc-ODP) and potentiation component (Pc-ODP) of plasticity independently. We found that CREB, SRF, and MEF2 are all required for ODP, but have differential effects on Dc-ODP and Pc-ODP. CREB is necessary for both Dc-ODP and Pc-ODP, whereas SRF and MEF2 are only needed for Dc-ODP. This finding supports previous reports implicating SRF and MEF2 in long-term depression (required for Dc-ODP), and CREB in long-term potentiation (required for Pc-ODP).SIGNIFICANCE STATEMENT Activity-dependent neuronal plasticity is the cellular basis for learning and memory, and it is crucial for the refinement of neuronal circuits during development. Identifying the mechanisms of activity-dependent neuronal plasticity is crucial to finding therapeutic interventions in the myriad of disorders where it is disrupted, such as Fragile X syndrome, Rett syndrome, epilepsy, major depressive disorder, and autism spectrum disorder. Transcription factors are essential nuclear proteins that trigger the expression of gene programs required for long-term functional and structural plasticity changes. Our results elucidate the specific role of the transcription factors CREB, SRF, and MEF2 in the depression and potentiation components of ODP in vivo, therefore better informing future attempts to find therapeutic targets for diseases where activity-dependent plasticity is disrupted.

Pulimood|Nisha S|NS|0000-0003-0612-1244
Rodrigues|Wandilson Dos Santos|WDS|
Atkinson|Devon A|DA|0000-0002-6675-1531
Mooney|Sandra M|SM|
Medina|Alexandre E|AE|

D017362:Cyclic AMP Response Element-Binding Protein

CREB
SRF
MEF2
plasticity
visual cortex
transcription factors


Hit-and-run trophallaxis of small hive beetles.

Abstract: Some parasites of social insects are able to exploit the exchange of food between nestmates via trophallaxis, because they are chemically disguised as nestmates. However, a few parasites succeed in trophallactic solicitation although they are attacked by workers. The underlying mechanisms are not well understood. The small hive beetle (=SHB), Aethina tumida, is such a parasite of honey bee, Apis mellifera, colonies and is able to induce trophallaxis. Here, we investigate whether SHB trophallactic solicitation is innate and affected by sex and experience. We quantified characteristics of the trophallactic solicitation in SHBs from laboratory-reared individuals that were either bee-naïve or had 5 days experience. The data clearly show that SHB trophallactic solicitation is innate and further suggest that it can be influenced by both experience and sex. Inexperienced SHB males begged more often than any of the other groups had longer breaks than their experienced counterparts and a longer soliciting duration than both experienced SHB males and females, suggesting that they start rather slowly and gain more from experience. Successful experienced females and males were not significantly different from each other in relation to successful trophallactic interactions, but had a significantly shorter soliciting duration compared to all other groups, except successful inexperienced females. Trophallactic solicitation success, feeding duration and begging duration were not significantly affected by either SHB sex or experience, supporting the notion that these behaviors are important for survival in host colonies. Overall, success seems to be governed by quality rather than quantity of interactions, thereby probably limiting both SHB energy investment and chance of injury (<1%). Trophallactic solicitation by SHBs is a singular example for an alternative strategy to exploit insect societies without requiring chemical disguise. Hit-and-run trophallaxis is an attractive test system to get an insight into trophallaxis in the social insects.

Neumann|Peter|P|
Naef|Jan|J|
Crailsheim|Karl|K|
Crewe|Robin M|RM|
Pirk|Christian W W|CW|

trophallaxis
small hive beetle
solicitation
Aethina tumida
honey bee
Apis mellifera
host–parasite interaction


Switching on the Metathesis Activity of Re Oxo Alkylidene Surface Sites through a Tailor-Made Silica-Alumina Support.

Abstract: Re oxo alkylidene surface species are putative active sites in classical heterogeneous Re-based alkene-metathesis catalysts. However, the lack of evidence for such species questions their existence and/or relevance as reaction intermediates. Using Re(O)(=CH-CH=CPh2)(OtBuF6)3(THF), the corresponding well-defined Re oxo alkylidene surface species can be generated on both silica and silica-alumina supports. While inactive on the silica support, it displays very good activity, even for functionalized olefins, on the silica-alumina support.

Valla|Maxence|M| Stadler|David|D| Mougel|Victor|V| Copéret|Christophe|C|

metathesis
oxo alkylidene
alumina
rhenium
supported catalysts


Overexpression of scavenger receptor and infiltration of macrophage in epicardial adipose tissue of patients with ischemic heart disease and diabetes.

Abstract:
BACKGROUND
Oxidized low-density lipoproteins and scavenger receptors (SRs) play an important role in the formation and development of atherosclerotic plaques. However, little is known about their presence in epicardial adipose tissue (EAT). The objective of the study was to evaluate the mRNA expression of different SRs in EAT of patients with ischemic heart disease (IHD), stratifying by diabetes status and its association with clinical and biochemical variables.

METHODS
We analyzed the mRNA expression of SRs (LOX-1, MSR1, CXCL16, CD36 and CL-P1) and macrophage markers (CD68, CD11c and CD206) in EAT from 45 patients with IHD (23 with type 2 diabetes mellitus (T2DM) and 22 without T2DM) and 23 controls without IHD or T2DM.

RESULTS
LOX-1, CL-P1, CD68 and CD11c mRNA expression were significantly higher in diabetic patients with IHD when compared with those without T2DM and control patients. MSR1, CXCL16, CD36 and CD206 showed no significant differences. In IHD patients, LOX-1 (OR 2.9; 95% CI 1.6-6.7; P = 0.019) and CD68 mRNA expression (OR 1.7; 95% CI 0.98-4.5; P = 0.049) were identified as independent risk factors associated with T2DM. Glucose and glycated hemoglobin were also shown to be risk factors.

CONCLUSIONS
SRs mRNA expression is found in EAT. LOX-1 and CD68 and were higher in IHD patients with T2DM and were identified as a cardiovascular risk factor of T2DM. This study suggests the importance of EAT in coronary atherosclerosis among patients with T2DM.

Santiago-Fernández|Concepción|C|
Pérez-Belmonte|Luis M|LM|
Millán-Gómez|Mercedes|M|
Moreno-Santos|Inmaculada|I|
Carrasco-Chinchilla|Fernando|F|
Ruiz-Salas|Amalio|A|
Morcillo-Hidalgo|Luis|L|
Melero|José M|JM|
Garrido-Sánchez|Lourdes|L|
Jiménez-Navarro|Manuel|M|

Scavenger receptors
Epicardial adipose tissue
Ischemic heart disease
Oxidized low-density lipoprotein
Diabetes mellitus


Resistance a major hindrance to chemotherapy in hepatocellular carcinoma: an insight.

Abstract: Hepatocellular carcinoma (HCC) is one of the leading causes of cancer mortality, accounting for almost 90% of total liver cancer burden. Surgical resection followed by adjuvant and systemic chemotherapy are the most meticulously followed treatment procedures but the complex etiology and high metastatic potential of the disease renders surgical treatment futile in majority of the cases. Another hindrance to the scenario is the acquired resistance to drugs resulting in relapse of the disease. Hence, to provide insights into development of novel therapeutic targets and diagnostic biomarkers, this review focuses on the various molecular mechanisms underlying chemoresistance in HCC. We have provided a comprehensive summary of the various strategies adopted by HCC cells, extending from apoptosis evasion, autophagy activation, drug expulsion to epigenetic transformation as modes of therapy resistance. The role of stem cells in imparting chemoresistance is also discussed. Furthermore, the review also focuses on how this knowledge might be exploited for the development of an effective, prospective therapy against HCC.

HCC Cancer Chemoresistance Apoptosis Autophagy Metastasis


Measuring electronic communication networks in virtual care teams using electronic health records access-log data.

Abstract:
OBJECTIVE
To develop methods for measuring electronic communication networks in virtual care teams using electronic health records (EHR) access-log data.

METHODS
For a convenient sample of 100 surgical colorectal cancer patients, we used time-stamped EHR access-log data extracted from an academic medical center's EHR system to construct communication networks among healthcare professionals (HCPs) in each patient's virtual care team. We measured communication linkages between HCPs using the inverse of the average time between access events in which the source HCPs sent information to and the destination HCPs retrieved information from the EHR system. Social network analysis was used to examine and visualize communication network structures, identify principal care teams, and detect meaningful structural differences across networks. We conducted a non-parametric multivariate analysis of variance (MANOVA) to test the association between care teams' communication network structures and patients' cancer stage and site.

RESULTS
The 100 communication networks showed substantial variations in size and structures. Principal care teams, the subset of HCPs who formed the core of the communication networks, had higher proportions of nurses, physicians, and pharmacists and a lower proportion of laboratory medical technologists than the overall networks. The distributions of conditional uniform graph quantiles suggested that our network-construction technique captured meaningful underlying structures that were different from random unstructured networks. MANOVA results found that the networks' topologies were associated with patients' cancer stage and site.

CONCLUSIONS
This study demonstrates that it is feasible to use EHR access-log data to measure and examine communication networks in virtual care teams. The proposed methods captured salient communication patterns in care teams that were associated with patients' clinical differences.

Zhu|Xi|X|
Tu|Shin-Ping|SP|
Sewell|Daniel|D|
Yao|Nengliang Aaron|NA|
Mishra|Vimal|V|
Dow|Alan|A|
Banas|Colin|C|

Communication networks
Virtual care teams
Electronic health records
Methods


HCV infection and the risk of head and neck cancer: A meta-analysis.

Abstract: Recent evidence has consistently suggested a role for HCV in the etiology of head and neck squamous cell carcinoma (HNSCC), but the conclusions of these studies have often been limited by small sample size. Therefore, a meta-analysis was performed to summarize present evidence on the association between HCV infection and HNSCC. After screening citations from literature search, eight observational studies investigating the association between HCV and cancer(s) of either oral cavity, oropharynx, hypopharynx or larynx were included. For each cancer site, risk ratios from individual studies were displayed in forest plots; pooled risk ratios (RR) and corresponding confidence intervals (CI) were calculated. A significant association was found between HCV infection and cancers of the oral cavity (RR = 2.13; 95%: 1.61-2.83), oropharynx (RR = 1.81; 95% CI: 1.21-2.72), and larynx (RR = 2.57; 95% CI: 1.11-5.94). A similar picture emerged for hypopharyngeal cancer, though this result did not fully reach statistical significance because of the small number of available studies (RR = 2.15; 95% CI: 0.73-6.31). These findings remained similar after exclusion of patients with HIV co-infection. Our results highlighted the importance of surveillance of the upper aerodigestive tract in patients with known chronic HCV infections in order to enable HNSCC early diagnosis. In addition, they could be a reminder of the possibility of undiagnosed HCV infection to the clinicians treating HNSCC.

Borsetto|Daniele|D| Fussey|Jonathan|J| Fabris|Luca|L| Bandolin|Luigia|L| Gaudioso|Piergiorgio|P| Phillips|Veronica|V| Polesel|Jerry|J| Boscolo-Rizzo|Paolo|P|

Head and neck cancer
Cancer risk
Hepatitis C virus
Laryngeal cancer
Oral cancer
Oropharyngeal cancer