Hydrogels in ophthalmic applications.

Abstract: More and more people worldwide are affected by severe eye diseases eventually leading to visual impairment or blindness. In most cases, the treatment involves the application of ophthalmic dosage forms such as eye drops, suspensions or ointments. Unfortunately, some of the therapeutic approaches have major shortcomings, especially in the treatment of the posterior segment of the eye, where many vision-threatening diseases originate. Therefore, research focuses on the development of new materials (e.g., for vitreous substitution) and more advanced drug delivery systems. Hydrogels are an extremely versatile class of materials with many potential applications in ophthalmology. They found widespread application as soft contact lenses, foldable intraocular lenses, in situ gelling formulations for ophthalmic drug delivery and ocular adhesives for wound repair; their use as vitreous substitutes and intravitreal drug delivery systems is currently under investigation. In this article, we review the different applications of hydrogels in ophthalmology with special emphasis placed on the used polymers and their suitability as ocular drug delivery systems.

Kirchhof|Susanne|S|
Goepferich|Achim M|AM|
Brandl|Ferdinand P|FP|

Hydrogels
Vitreous substitutes
Drug delivery
Ophthalmology
Contact lenses
Intraocular lenses
Polymers
Tissue engineering


Studies on the ultrastructure in Anacardium occidentale L. leaves from Amazon in northern Brazil by scanning microscopy.

Abstract: Leaves surfaces have various structures with specific functions and contribute to the relationship with the environment. On morphological studies are analyzed various parameters, ranging from macro scale through the micro scale to the nanometer scale, which contribute to the study of taxonomy, pharmacognosy, and ecology, among others. Functional structures found in leaves are responsible for the wide variety of surfaces and some behaviors are given in terms of cellular adaptation and the presence or absence of wax. This study reports the characterization of Anacardium occidentale L. leaf surface and the techniques used therein. A set of scanning electron microscope (SEM) and atomic force microscope (AFM) images performed on fresh leaf allowed observation of textured and heterogeneous profiles on both sides. SCANNING 38:329-335, 2016. © 2015 Wiley Periodicals, Inc.

Ramos|Glenda Quaresma|GQ|
Cotta|Eduardo Adriano|EA|
da Fonseca Filho|Henrique Duarte|HD|

leaf surface
AFM
Anacardium occidentale L
ESEM
abaxial
adaxial
stomata


Responsive Asthma Care for Teens (ReACT): development protocol for an adaptive mobile health intervention for adolescents with asthma.

Abstract:
INTRODUCTION
Asthma is a leading cause of youth morbidity in the USA, affecting >8% of youth. Adherence to inhaled corticosteroids (ICS) can prevent asthma-related morbidity; however, the typical adolescent with asthma takes fewer than 50% of their prescribed doses. Adolescents are uniquely vulnerable to suboptimal asthma self-management due to still-developing executive functioning capabilities that may impede consistent self-regulation and weaken attempts to use problem solving to overcome barriers to ICS adherence.

METHODS AND ANALYSIS
The aims of this project are to improve adherence to ICS as an important step towards better self-management among adolescents aged 13-17 years diagnosed with asthma by merging the efficacious behaviour change strategies found in behavioural health interventions with scalable, adaptive mobile health (mHealth) technologies to create the Responsive Asthma Care for Teens programme (ReACT). ReACT intervention content will be developed through an iterative user-centred design process that includes conducting (1) one-on-one interviews with 20 teens with asthma; (2) crowdsourced feedback from a nationally representative panel of 100 adolescents with asthma and (3) an advisory board of youth with asthma, a paediatric pulmonologist and a behavioural health expert. In tandem, we will work with an existing technology vendor to programme ReACT algorithms to allow for tailored intervention delivery. We will conduct usability testing of an alpha version of ReACT with a sample of 20 target users to assess acceptability and usability of our mHealth intervention. Participants will complete a 4-week run-in period to monitor their adherence with all ReACT features turned off. Subsequently, participants will complete a 4-week intervention period with all ReACT features activated. The study started in October 2018 and is scheduled to conclude in late 2019.

ETHICS AND DISSEMINATION
Institutional review board approval was obtained at the University of Kansas and the University of Florida. We will submit study findings for presentation at national research conferences that are well attended by a mix of psychologists, allied health professionals and physicians. We will publish study findings in peer-reviewed journals read by members of the psychology, nursing and pulmonary communities.

Cushing|Christopher C|CC|
Fedele|David A|DA|
Patton|Susana R|SR|
McQuaid|Elizabeth L|EL|
Smyth|Joshua M|JM|
Prabhakaran|Sreekala|S|
Gierer|Selina|S|
Koskela-Staples|Natalie|N|
Ortega|Adrian|A|
Fleming|Kandace K|KK|
Nezu|Arthur M|AM|


Exploring the Charge Transport in Conjugated Polymers.

Abstract: Conjugated polymers came to an unprecedented epoch that the charge transport is limited only by small disorder within aggregated domains. Accurate evaluation of transport performance is thus vital to optimizing further molecule design. Yet, the routine method by means of the conventional field-effect transistors may not satisfy such a requirement. Here, it is shown that the extrinsic effects of Schottky barrier, access transport through semiconductor bulk, and concurrent ambipolar conduction seriously influence transport analysis. The planar transistors incorporating ohmic contacts free of access and ambipolar conduction afford an ideal access to charge transport. It is found, however, that only the planar transistors operating in low-field regime are reliable to explore the inherent transport properties due to the energetic disorder lowering by the lateral field induced by high drain voltage. This work opens up a robust approach to comprehend the delicate charge transport in conjugated polymers so as to develop high-performance semiconducting polymers for promising plastic electronics.

charge transport
conjugated polymers
device physics
organic transistors


A Rare Case of Ataxia-Telangiectasia-Like Disorder With MRE11 Mutation.

Abstract: The prototypical disorder for the early-onset cerebellar ataxia with cerebellar atrophy is ataxia telangiectasia (AT). AT belongs to "DNA-repair defects" or "DNA-repair deficiency" disorders. The ATM (Ataxia-telangiectasia mutated kinase) gene mutated in AT is central to deoxyribonucleic acid (DNA) damage response (DDR) signaling. Other genes implicated in DDR signaling are MRE11A (Meiotic recombination 11). Mutation of this gene results in ataxia-telangiectasia-like disorder (ATLD). We report a boy who presented with mild cerebellar ataxia and dystonia with cerebellar atrophy on brain imaging. Clinical exome sequencing showed compound heterozygous variants in MRE11 gene. He was diagnosed as ATLD, which has not been reported in Indian subcontinent so far.

Mahale|Rohan R|RR|
Reddy|Nishanth|N|
Mathuranth|Pavagada|P|
Mailankody|Pooja|P|
Padmanabha|Hansashree|H|
Retnaswami|Chandra Sadnavalli|CS|

Ataxia-telangiectasia-like disorders
cerebellar ataxia
cerebellar atrophy


Lysine-specific demethylase 2A expression is associated with cell growth and cyclin D1 expression in colorectal adenocarcinoma.

Abstract:
OBJECTIVE
Lysine-specific demethylase 2A (KDM2A), a specific H3K36me1/2 demethylase, has been reported to be closely associated with several types of cancer. In this study, we aimed to investigate the expression and function of KDM2A in colorectal adenocarcinoma.

METHODS
A total of 215 colorectal adenocarcinoma specimens were collected, and then subjected to immunohistochemistry assay to evaluate the expression levels of KDM2A, cyclin D1 and other proteins in colorectal adenocarcinoma tissues. Real-time polymerase chain reaction, Western blot, and other molecular biology methods were used to explore the role of KDM2A in colorectal adenocarcinoma cells.

RESULTS
In this study, we report that the expression level of KDM2A is high in colorectal adenocarcinoma tissues, and this high expression promotes the proliferation and colony formation of colorectal adenocarcinoma cells, as demonstrated by KDM2A knockdown experiments. In addition, the expression of KDM2A is closely associated with cyclin D1 expression in colorectal adenocarcinoma tissues and cell lines.

CONCLUSIONS
Our study reveals a novel role for high-expressed KDM2A in colorectal adenocarcinoma cell growth, and that the expression of KDM2A is associated with that of cyclin D1 in colorectal adenocarcinoma.

Cao|Lin-Lin|LL| Du|Changzheng|C| Liu|Hangqi|H| Pei|Lin|L| Qin|Li|L| Jia|Mei|M| Wang|Hui|H|

demethylase
cyclin D1
Colorectal adenocarcinoma
KDM2A


Thoracic endovascular aortic repair for symptomatic penetrating aortic ulcers and intramural hematomas is associated with poor outcomes.

Abstract:
BACKGROUND
The natural history of penetrating aortic ulcers (PAUs) and intramural hematomas (IMHs) of the aorta has not been well described. Although repair is warranted for rupture, unremitting chest pain, or growth, no threshold has been established for treating those found incidentally. Thoracic endovascular aortic repair (TEVAR) offers an attractive approach for treating these pathologic entities. However, the periprocedural and postoperative outcomes have not been well defined.

METHODS
Patients aged ≥18 years identified in the Vascular Quality Initiative database who had undergone TEVAR for PAUs and/or IMHs from January 2011 to February 2020 were included. We identified 1042 patients, of whom 809 had follow-up data available. The patient demographics and comorbidities were analyzed to identify the risk factors for major adverse events (MAEs) and postoperative and late mortality.

RESULTS
The cohort was 54.8% female, and 69.9% were former smokers, with a mean age of 71.1 years. Comorbidities were prevalent, with 57.8% classified as having American Society of Anesthesiologists class 4. Of the 1042 patients, 89.8% had hypertension, 28.3% chronic obstructive pulmonary disease, 17.9% coronary artery disease, and 12.2% congestive heart failure. Patients were predominately symptomatic (74%), and 44.5% had undergone nonelective repair. The MAE incidence was 17%. The independent predictors of MAEs were a history of coronary artery disease, nonwhite race, emergent procedural indication, ruptured presentation, and deployment of two or more endografts. In-hospital mortality was 4.3%. Of the index hospitalization mortalities, 73% were treatment related. For the 809 patients with follow-up (mean, 25.1 ± 19 months), the all-cause mortality was 10.6%. The predictors of late mortality during follow-up included age >70 years, ruptured presentation, and a history of chronic obstructive pulmonary disease and end-stage renal disease. A subset analysis comparing symptomatic (74%) vs asymptomatic (26%) patients demonstrated that the former were frequently women (58.2% vs 45.3%; P < .001), with a greater incidence of MAEs (20.6% vs 6.9%; P < .001), including higher in-hospital reintervention rates (5.9% vs 1.5%; P = .002) and mortality (5.6% vs 0.7%; log-rank P = .015), and a prolonged length of stay (6.9 vs 3.7 days; P < .0001), despite similar procedural risks. During follow-up, late mortality was greater in the symptomatic cohort (12.2% vs 6.5%; log-rank P = .025), with all treatment-related mortalities limited to the symptomatic group.

CONCLUSIONS
We found significantly greater morbidity and mortality in symptomatic patients undergoing repair compared with asymptomatic patients, despite similar baseline characteristics. Asymptomatic patients treated with TEVAR had no treatment-related mortality during follow-up, with the overall prognosis largely dependent on preexisting comorbidities. These findings, in conjunction with increasing evidence highlighting the risk of disease progression and attendant morbidity associated with these aortic entities, suggest a need for natural history studies and definitive guidelines on the elective repair of IMHs and PAUs.

Rokosh|Rae S|RS|
Rockman|Caron B|CB|
Patel|Virendra I|VI|
Milner|Ross|R|
Osborne|Nicholas H|NH|
Cayne|Neal S|NS|
Jacobowitz|Glenn R|GR|
Garg|Karan|K|

D019917:Blood Vessel Prosthesis Implantation

Thoracic endovascular aortic repair
Penetrating aortic ulcer
Intramural hematoma


Oral Cancer-related Inherited Cancer Syndromes: A Comprehensive Review.

Abstract: Oral squamous cell carcinoma is the most common malignancy of the oral cavity, which is usually preceded by a myriad of oral potentially malignant disorders (OPMDs). In the classification of OPMDs, inherited cancer syndromes (ICSs) were proposed as one of the categories. Inherited cancer syndromes are genetic disorders in which inherited genetic mutation in one or more genes predispose the affected individuals to the development of cancer and may also cause its early onset. Many of these syndromes are caused by mutations in tumor suppressor genes, oncogenes, and genes involved in angiogenesis. General dental practitioners frequently come across OPMDs in their day-to-day practice. It becomes of paramount importance to have knowledge about these rare but prognostically important OPMDs. With this view in mind, in this article, efforts have been made to comprehensively discuss about various ICSs that have higher potential of transformation into oral cancer. The ICSs discussed in this article are xeroderma pigmentosum (XP), ataxia telangiectasia (AT), Bloom syndrome (BS), Fanconi's anemia (FA), and Li-Fraumeni syndrome (LFS), with special emphasis on signs, symptoms, and genetic considerations.

Sarode|Gargi S|GS|
Batra|Akshit|A|
Sarode|Sachin C|SC|
Yerawadekar|Sujata|S|
Patil|Shankargouda|S|

D020022:Genetic Predisposition to Disease

Inherited cancer syndromes
Ataxia telangiectasia
Bloom syndrome
Fanconi's anemia
Li-Fraumeni syndrome
Xeroderma pigmentosum.


Extracellular Biocoordinated Zinc Nanofibers Inhibit Malignant Characteristics of Cancer Cell.

Abstract: Inhibition of the heat shock proteins (HSPs) has been considered to be one of the promising strategies for cancer treatment. However, developing highly effective HSP inhibitors remains a challenge. Recent studies on the evolutionarily distinct functions between intracellular and extracellular HSPs (eHSPs) trigger a new direction with eHSPs as chemotherapeutic targets. Herein, the first engineered eHSP nanoinhibitor with high effectiveness is reported. The zinc-aspartic acid nanofibers have specific binding ability to eHSP90, which induces a decrease in the level of the tumor marker-gelatinases, consequently resulting in downregulation of the tumor-promoting inflammation nuclear factor-kappa B signaling, and finally inhibiting cancer cell proliferation, migration, and invasion; while they are harmless to normal cells. Our findings highlight the potential for cancer treatment by altering the key determinants that shape its ability to adapt and evolve using novel nanomaterials.

Xin|Qi|Q|
Zhang|Haihui|H|
Liu|Qian|Q|
Dong|Zejian|Z|
Xiang|Hongyu|H|
Gong|Jian Ru|JR|

nanofiber
Cancer inhibition
NF-kappa B
extracellular heat shock protein
nanobiomedicine


Intravenous vernakalant for the rapid conversion of recent onset atrial fibrillation: systematic review and meta-analysis.

Abstract: Atrial fibrillation is the most common cardiac arrhythmia and is associated with increased mortality and morbidity. Conversion to sinus rhythm is usually appropriate in patients with acute, symptomatic atrial fibrillation in order to reduce symptoms and prevent complications. Electrical cardioversion is the most used and widespread technique, but requires deep sedation and a fasting state. Pharmacological alternatives are burdened by a delayed onset of action and potential proarrhythmic effects. Therefore, new therapeutic options are being sought. Among those, vernakalant, showed a good efficacy profile and a short onset of action, but with conflicting evidence regarding potential serious adverse events. This drug profile will summarize the pharmacology behind this new drug and review recent evidence in terms of safety and efficacy.

Guerra|Federico|F|
Matassini|Maria Vittoria|MV|
Scappini|Lorena|L|
Urbinati|Alessia|A|
Capucci|Alessandro|A|

vernakalant
atrial fibrillation
cardioversion
anti-arrhythmic drugs
ion-channels
rhythm control


Aerobic Exercise Attenuates Acute Lung Injury Through NET Inhibition.

Abstract: Introduction: Aerobic exercise improves lung inflammation in acute lung injury (ALI), but its mechanism remains unknown. Neutrophil extracellular traps (NETs) play an important role in LPS-induced ALI, and a positive correlation exists between NET formation and proinflammatory macrophage polarization. This study investigated whether aerobic exercise reduces the pro-inflammatory polarization of alveolar macrophages (AMs) by inhibiting the excessive release of NETs and then alleviating the inflammatory response of ALI. Methods: C57BL/6 male mice were randomly divided into four groups: sedentary group (CON), sedentary and extra-pulmonary LPS injection group (LPS), 5-weeks aerobic training intervention and LPS injection group (EXE+LPS), and DNase I plus LPS injection group (DNase+LPS). Twenty-four hours after drug injection, bronchoalveolar lavage fluid (BALF), AM, and lung tissues were obtained to detect inflammatory responses, NET formation, macrophage polarization, and protein activation. In the in vitro study, a murine AM cell line, designated MH-S, was stimulated with LPS, purified NETs, and NETs plus DNase I. Results: EXE+LPS and DNase+LPS mice exhibited reduced neutrophil infiltration, decreased NET release, and lower pro-inflammatory polarization of AM compared with LPS mice. Subsequently, Western blot showed inhibition of the phosphorylation of MAPK and NF-κB proteins of AMs in EXE+LPS and DNase+LPS mice compared with LPS mice. Lastly, stimulation of MH-S cells by NETs revealed a trend for pro-inflammatory cell polarization, with NF-κB protein activation at 8 h and ERK1/2 activation at 1, 2, and 8 h. Conclusions: Aerobic exercise alleviated ALI through NET-induced AM pro-inflammatory polarization involving ERK1/2 and NF-κB signaling.

Shi|Yue|Y|
Liu|Tingting|T|
Nieman|David C|DC|
Cui|Yanqiu|Y|
Li|Fei|F|
Yang|Luyu|L|
Shi|Hui|H|
Chen|Peijie|P|

D055371:Acute Lung Injury
D000818:Animals
D065206:Extracellular Traps
D007249:Inflammation
D016676:Macrophages, Alveolar
D008297:Male
D051379:Mice
D008810:Mice, Inbred C57BL
D020556:Neutrophil Infiltration
D010805:Physical Conditioning, Animal
D011897:Random Allocation
D015398:Signal Transduction

aerobic exercise
acute lung injury
inflammation
neutrophil extracellular traps
alveolar macrophages


Optimal mixed control of Axial Flux Permanent Magnet Synchronous generator wind turbines with modular stator structure.

Abstract: Wind turbine systems are constructed using different types of generators, aero-mechanical components and control systems. Due to their ability to work in low speed, Axial Flux Permanent Magnet (AFPM) generators are becoming widespread in wind energy systems which contributes to eliminating the gearbox from the system, noticeable increase in efficiency and decrease in system weight. Due to the modular nature of the stator in AFPM generators, it is possible to control each module independently. In this paper, in addition to obtain the dynamic model of the turbine and AFPM generator, a control strategy is designed based on Mixed Integer Nonlinear Programming (MINLP) to incorporate both pitch angle and the number of active stator modules as control input signals. These control signals are used in order to maximize system efficiency and regulate output voltage in different wind speeds and electrical loads. Simulation results for a typical generator shows the effectiveness of the proposed method in speed control of the generator.

Pirzad|Somayeh|S|
Ghadimi|Ali Asghar|AA|
Abolmasoumi|Amir Hossein|AH|
Jabbari|Ali|A|
Bagheri|Saeed|S|


Designing inhibitors of cytochrome c/cardiolipin peroxidase complexes: mitochondria-targeted imidazole-substituted fatty acids.

Abstract: Mitochondria have emerged as the major regulatory platform responsible for the coordination of numerous metabolic reactions as well as cell death processes, whereby the execution of intrinsic apoptosis includes the production of reactive oxygen species fueling oxidation of cardiolipin (CL) catalyzed by cytochrome (Cyt) c. As this oxidation occurs within the peroxidase complex of Cyt c with CL, the latter represents a promising target for the discovery and design of drugs with antiapoptotic mechanisms of action. In this work, we designed and synthesized a new group of mitochondria-targeted imidazole-substituted analogs of stearic acid TPP-n-ISAs with various positions of the attached imidazole group on the fatty acid (n = 6, 8, 10, 13, and 14). By using a combination of absorption spectroscopy and EPR protocols (continuous wave electron paramagnetic resonance and electron spin echo envelope modulation) we demonstrated that TPP-n-ISAs indeed were able to potently suppress CL-induced structural rearrangements in Cyt c, paving the way to its peroxidase competence. TPP-n-ISA analogs preserved the low-spin hexa-coordinated heme-iron state in Cyt c/CL complexes whereby TPP-6-ISA displayed a significantly more effective preservation pattern than TPP-14-ISA. Elucidation of these intermolecular stabilization mechanisms of Cyt c identified TPP-6-ISA as an effective inhibitor of the peroxidase function of Cyt c/CL complexes with a significant antiapoptotic potential realized in mouse embryonic cells exposed to ionizing irradiation. These experimental findings were detailed and supported by all-atom molecular dynamics simulations. Based on the experimental data and computation predictions, we identified TPP-6-ISA as a candidate drug with optimized antiapoptotic potency.

Jiang|Jianfei|J|
Bakan|Ahmet|A|
Kapralov|Alexandr A|AA|
Ishara Silva|K|K|
Huang|Zhentai|Z|
Amoscato|Andrew A|AA|
Peterson|James|J|
Krishna Garapati|Venkata|V|
Saxena|Sunil|S|
Bayir|Hülya|H|
Atkinson|Jeffrey|J|
Bahar|Ivet|I|
Kagan|Valerian E|VE|

Cytochrome c
Electron paramagnetic resonance
All-atom molecular dynamics simulation
Cardiolipin peroxidation
Free radicals
Imidazole-substituted stearic acid
Mitochondria targeting
Peroxidase inhibitors
Reactive intermediates


Face-to-Face Orientation of Quasiplanar Donor and Acceptor Enables Highly Efficient Intramolecular Exciplex Fluorescence.

Abstract: Intramolecular through-space charge-transfer (TSCT) excited states have been exploited for developing thermally activated delayed fluorescence (TADF) emitters, but the tuning of excited state dynamics by conformational engineering remains sparse. Designed here is a series of TSCT emitters with precisely controlled alignment of the donor and acceptor segments. With increasing intramolecular π-π interactions, the radiative decay rate of the lowest singlet excited state (S1 ) progressively increased together with a suppression of nonradiative decay, leading to significantly enhanced photoluminescence quantum yields of up to 0.99 in doped thin films. A high-efficiency electroluminescence device, with a maximum external quantum efficiency (EQE) of 23.96 %, was achieved and maintains >20 % at a brightness of 1000 cd m-2 . This work sheds light on the importance of conformation control for achieving high-efficiency intramolecular exciplex emitters.

fluorescence
π-π interactions
charge transfer
donor-acceptor systems
luminescence


VEGFR2 and OPG genes modify the risk of subclinical coronary atherosclerosis in patients with familial hypercholesterolemia.

Abstract:
BACKGROUND AND AIMS
Heterozygous familial hypercholesterolemia (FH) is a genetic disorder characterized by high levels of low-density lipoprotein cholesterol (LDL-C). The magnitude of atherosclerotic cardiovascular disease (ASCVD) risk in FH patients is highly variable, and this can result from genetic factors. The aim of our study was to characterize whether polymorphisms in VEGFR2 and OPG genes could influence the expression of ASCVD in FH patients.

METHODS
We studied 318 FH patients from the SAFEHEART registry, without clinical diagnosis of ASCVD. A coronary tomographic angiography (CTA) was performed to determine and evaluate the presence of coronary stenosis and coronary artery calcium, as measured by coronary calcium score (CCS). Genotyping of OPG rs2073618 and VEGFR2 rs2071559 polymorphisms was performed using TaqMan 5'-exonuclease allelic discrimination assays.

RESULTS
Homozygous GG genotype and G allele of VEGFR2 rs2071559 polymorphism were associated with decreased risk of developing coronary artery stenosis. In the analysis of OPG rs2073618 and VEGFR2 rs2071559 polymorphisms, according to the presence of coronary artery calcium, we found significant differences in both polymorphisms. Homozygous GG genotype and G allele of VEGFR2 rs2071559 polymorphism were associated with decreased risk of accumulation of coronary artery calcium measured by CCS in CTA. Moreover, being a carrier of the GG genotype and G allele of the OPG rs2073618 polymorphism increased the risk of the presence of coronary artery calcium measured by CCS in CTA.

CONCLUSIONS
Polymorphisms in VEGFR2 and OPG genes modify the risk of ASCVD in FH patients.

Miramontes-González|José Pablo|JP|
Usategui-Martín|Ricardo|R|
Pérez de Isla|Leopoldo|L|
Alonso|Rodrigo|R|
Muñiz-Grijalvo|Ovidio|O|
Díaz-Díaz|José Luis|JL|
Zambón|Daniel|D|
Jiménez|Francisco Fuentes|FF|
Martín-Vallejo|Javier|J|
Rodríguez Gude|Ana Elisa|AE|
Jiménez|David León|DL|
Padro|Teresa|T|
González-Sarmiento|Rogelio|R|
Mata|Pedro|P|

D040301:Vascular Endothelial Growth Factor Receptor-2

VEGFR2
OPG
Familial hypercholesterolemia
Polymorphism
SAFEHEART
Coronary calcium and coronary stenosis


Chronic stress enhanced fear memories are associated with increased amygdala zif268 mRNA expression and are resistant to reconsolidation.

Abstract: The chronically stressed brain may present a vulnerability to develop maladaptive fear-related behaviors in response to a traumatic event. In rodents, chronic stress leads to amygdala hyperresponsivity and dendritic hypertrophy and produces a post traumatic stress disorder (PTSD)-like phenotype that includes exaggerated fear learning following Pavlovian fear conditioning and resistance to extinction. It is unknown whether chronic stress-induced enhanced fear memories are vulnerable to disruption via reconsolidation blockade, as a novel therapeutic approach for attenuating exaggerated fear memories. We used a chronic stress procedure in a rat model (wire mesh restraint for 6h/d/21d) to create a vulnerable brain that leads to a PTSD-like phenotype. We then examined freezing behavior during acquisition, reactivation and after post-reactivation rapamycin administration (i.p., 40mg/kg) in a Pavlovian fear conditioning paradigm to determine its effects on reconsolidation as well as the subsequent functional activation of limbic structures using zif268 mRNA. Chronic stress increased amygdala zif268 mRNA during fear memory retrieval at reactivation. Moreover, these enhanced fear memories were unaffected by post reactivation rapamycin to disrupt long-term fear memory. Also, post-reactivation long term memory processing was also associated with increased amygdala (LA and BA), and decreased hippocampal CA1 zif268 mRNA expression. These results suggest potential challenges for reconsolidation blockade as an effective approach in treating exaggerated fear memories, as in PTSD. Our findings also support chronic stress manipulations combined with fear conditioning as a useful preclinical approach to study a PTSD-like phenotype.

Hoffman|Ann N|AN|
Parga|Alejandro|A|
Paode|Pooja R|PR|
Watterson|Lucas R|LR|
Nikulina|Ella M|EM|
Hammer|Ronald P|RP|
Conrad|Cheryl D|CD|

Chronic stress
Amygdala
Reconsolidation
Fear conditioning
Rapamycin
PTSD
Hippocampus
mTOR


Activation of adenosine A2A receptors in the olfactory tubercle promotes sleep in rodents.

Abstract: The olfactory tubercle (OT), an important nucleus in processing sensory information, has been reported to change cortical activity under odor. However, little is known about the physiological role and mechanism of the OT in sleep-wake regulation. The OT expresses abundant adenosine A2A receptors (A2ARs), which are important in sleep regulation. Therefore, we hypothesized that the OT regulates sleep via A2ARs. This study examined sleep-wake profiles through electroencephalography and electromyography recordings with pharmacological and chemogenetic manipulations in freely moving rodents. Compared with their controls, activation of OT A2ARs pharmacologically and OT A2AR neurons via chemogenetics increased non-rapid eye movement sleep for 5 and 3 h, respectively, while blockade of A2ARs decreased non-rapid eye movement sleep. Tracing and electrophysiological studies showed OT A2AR neurons projected to the ventral pallidum and lateral hypothalamus, forming inhibitory innervations. Together, these findings indicate that A2ARs in the OT play an important role in sleep regulation.

Li|Rui|R|
Wang|Yi-Qun|YQ|
Liu|Wen-Ying|WY|
Zhang|Meng-Qi|MQ|
Li|Lei|L|
Cherasse|Yoan|Y|
Schiffmann|Serge N|SN|
de Kerchove d'Exaerde|Alban|A|
Lazarus|Michael|M|
Qu|Wei-Min|WM|
Huang|Zhi-Li|ZL|

Olfactory tubercle
Chemogenetics
Non-rapid eye movement sleep
Adenosine A(2A) receptors


Development of a practical prediction scoring system for severe acute organophosphate poisoning.

Abstract: Acute organophosphorus poisoning (AOPP) is a serious public health issue, especially in the rural areas. This study was designed to establish a scoring system to assess the risk of cases with severe AOPP. A retrospective cohort study was conducted at two independent hospitals. The derivation cohort included 444 patients with AOPP and the validation cohort included 274 patients. A risk score for patients with severe AOPP was developed. The rates of severe AOPP cases were 20.7% and 20.1% in the derivation and validation cohorts, respectively. A scoring system for severe AOPP risk was developed that included: (1) age >50 years, (2) white blood cell count of >15 × 109 /L, (3) plasma cholinesterase of <360 U/L, (4) plasma albumin of <35 g/L, (5) blood pH <7.3, and (6) lactic acid >3.0 mmol/L. The predicted score in severe cases of AOPP had good accuracy in both the derivation (area under the receiver operating characteristic curve [AUC] 0.88, 95% confidence interval [CI], 0.85-0.92) and validation cohorts (AUC 0.83, 95% CI, 0.77-0.90). A practical bedside prediction scoring system was developed for patients with severe AOPP. The routine use of this scoring system could rapidly assist in identifying patients at higher risk who require more intensive care or transfer to a larger better-equipped hospital.

scoring system
acute organophosphate poisoning
public health
rural areas
risk prediction


Surface Modification of Biodegradable Mg-Based Scaffolds for Human Mesenchymal Stem Cell Proliferation and Osteogenic Differentiation.

Abstract: Magnesium alloys with coatings have the potential to be used for bone substitute alternatives since their mechanical properties are close to those of human bone. However, the surface modification of magnesium alloys to increase the surface biocompatibility and reduce the degradation rate remains a challenge. Here, FHA-Mg scaffolds were made of magnesium alloys and coated with fluorohydroxyapatite (FHA). Human mesenchymal stem cells (hMSCs) were cultured on FHA-Mg scaffolds and cell viability, proliferation, and osteogenic differentiation were investigated. The results showed that FHA-Mg scaffolds display a nano-scaled needle-like structure of aggregated crystallites on their surface. The average Mg2+ concentration in the conditioned media collected from FHA-Mg scaffolds (5.8-7.6 mM) is much lower than those collected from uncoated, Mg(OH)2-coated, and hydroxyapatite (HA)-coated samples (32.1, 17.7, and 21.1 mM, respectively). In addition, compared with hMSCs cultured on a culture dish, cells cultured on FHA-Mg scaffolds demonstrated better proliferation and comparable osteogenic differentiation. To eliminate the effect of osteogenic induction medium, hMSCs were cultured on FHA-Mg scaffolds in culture medium and an approximate 66% increase in osteogenic differentiation was observed three weeks later, indicating a significant effect of the nanostructured surface of FHA-Mg scaffolds on hMSC behaviors. With controllable Mg2+ release and favorable mechanical properties, porous FHA-Mg scaffolds have a great potential in cell-based bone regeneration.

biodegradation
human mesenchymal stem cell
magnesium
fluorohydroxyapatite
bone tissue engineering


Studies on the effectiveness of oral pellet vaccine in improving egg production and egg quality in desi chicken.

Abstract:
AIM
To study the effect of Newcastle disease (ND) oral pellet vaccine in egg production and egg quality in desi chicken.

MATERIALS AND METHODS
The study was conducted at Veterinary University Training and Research Centre, Tiruchirapalli, Tamil Nadu. A total of 48-day-old desi chicks obtained from a private hatchery in Namakkal, Tamil Nadu, were maintained under cage system of rearing up to 52 weeks of age as per standard management practices. All the 48 chicks were divided into six groups having eight chicks in each group were subjected to different treatment regimes. All the birds were challenged at 52 weeks of age with 0.5 ml dose of 10(4.0) egg infectious dose 50 virulent ND field virus. 10 eggs from each group were randomly collected during the last 3 days of 8 weeks interval period from 28 to 52 weeks of age and were used to measure the egg quality parameters. The production performance of each group was assessed at 4 weeks interval period from 25 to 52 weeks of age.

RESULTS
In all the six treatment groups with respect to egg production, no significant difference (p≥0.05) was noticed from 25 to 52 weeks of age. Similarly, in egg weight, egg shape index and specific gravity, no significant difference (p≥0.05) was noticed from 28 to 52 weeks of age.

CONCLUSION
From this study, it is concluded that the administration of ND oral pellet vaccine to desi chicken does not affect the egg production performance, egg weight, egg shape index, and specific gravity of egg.

Reetha|T Lurthu|TL|
Rajeswar|J Johnson|JJ|
Harikrishnan|T J|TJ|
Sukumar|K|K|
Srinivasan|P|P|
Kirubakaran|J John|JJ|

effectiveness
oral pellet vaccines
egg production
egg quality
desi chicken


Shear Bond Strength of Composite Cement to Lithium-Disilicate Glass-coated Zirconia Versus Alumina Air-abraded Zirconia.

Abstract:
PURPOSE
To compare the shear bond strength of composite cement to lithium-disilicate glass-ceramic coated zirconia vs to alumina air-abraded zirconia and to analyze the residual stresses on both of lithium-disilicate glass-ceramic coated zirconia vs alumina air-abraded zirconia specimens.

MATERIALS AND METHODS
One hundred eighty zirconia disks (diameters 10 mm and 5 mm, 4.5 mm thick) were divided into two groups: lithium-disilicate glass-ceramic coating followed by hydrofluoric acid etching and Monobond N Primer (LiDi) or alumina air-abrasion (AA). For each group, two different sizes of identically pre-treated zirconia specimens were bonded with Multilink Speed Cement. A total of 90 specimens were stored in distilled water at 37°C for 24 h and then assigned to three subgroups (n = 15/test group): 1. short-term test; 2. thermocycling for 5000 cycles; 3. thermocycling for 10,000 cycles. Bond strength was tested in shear mode and results were analyzed using two-way ANOVA, followed by one-way ANOVA and Tukey's HSD (α = 0.05). Failure mode and surfaces were analyzed with optical and scanning electron microscopy. X-ray diffraction was used to analyze t-m phase transformation and residual stresses on mechanically pre-treated LiDi and AA surfaces.

RESULTS
The LiDi groups recorded higher mean bond strength than AA groups after thermocycling (p < 0.05). Thermocycling did not affect the bond strength of either LiDi or AA groups (p > 0.05). Most of specimens in AA groups exhibited mixed failure. Alumina air-abraded surfaces exhibited higher residual compressive stresses than did surfaces with a lithium-disilicate glass-ceramic coating.

CONCLUSION
Following thermocycling, composite-zirconia bond strength of specimens with a lithium-disilicate glass-ceramic coating was greater than that of alumina air-abraded specimens.

Thammajaruk|Putsadeeporn|P| Buranadham|Supanee|S| Guazzato|Massimiliano|M| Wang|Yu|Y|

D000537:Aluminum Oxide
D001840:Dental Bonding
D008094:Lithium
D008422:Materials Testing
D019279:Resin Cements
D013499:Surface Properties
D015040:Zirconium

shear bond strength
zirconia
scanning electron microscopy (SEM)
x-ray diffraction (XRD)
composite cement


Relative Influence of Socioeconomic, Psychological and Sensory Characteristics, Physical Activity and Diet on 5-Year Weight Gain in French Adults.

Abstract: Individual characteristics, dietary intake and physical activity influence weight status; however, the contribution of each factor to weight change has not been studied. The objective was to confirm a conceptual framework by simultaneously assessing the relative influence of socioeconomic, psychological and sensory characteristics, physical activity, and dietary intake on five-year weight gain in French adults. Individual characteristics, physical activity, and dietary data were assessed at baseline in 8014 participants in the NutriNet-Santé cohort. Self-reported anthropometric data were collected at baseline and five years later. Structural equation models, stratified by baseline body mass index (BMI), were used to perform analyses. Dietary restraint was a direct predictor of weight gain, with a stronger effect than age or intake of energy-dense foods, both in non-overweight and overweight participants. In non-overweight individuals only, intake of nutrient-dense foods and physical activity were inversely associated with weight gain. Regarding dietary intake, fat liking was the most important predictor of nutrient-dense food intake and was also related to energy-dense food intake. In these models, dietary restraint appears to be a direct predictor of weight gain and fat liking is a strong determinant of dietary intake. The influence of dietary restraint on weight gain, not explained by diet, warrants further investigation.

Lampuré|Aurélie|A|0000-0002-7188-0258 Castetbon|Katia|K| Hanafi|Mohamed|M| Deglaire|Amélie|A| Schlich|Pascal|P| Péneau|Sandrine|S| Hercberg|Serge|S|0000-0002-3168-1350 Méjean|Caroline|C|

physical activity
weight gain
individual characteristic
dietary intake
structural equation modelling
determinant


Influence of the IL17A locus in giant cell arteritis susceptibility.

Abstract:
OBJECTIVE
Different lines of evidence have highlighted the role of IL-17A in the inflammatory process occurring in giant cell arteritis (GCA). The aim of the present study was to assess whether the IL17A locus influences GCA susceptibility and its clinical subphenotypes.

METHODS
We carried out a large meta-analysis including a total of 1266 biopsy-proven GCA patients and 3779 healthy controls from four European populations (Spain, Italy, Germany and Norway). Five IL17A polymorphisms (rs4711998, rs8193036, rs3819024, rs2275913 and rs7747909) were selected by tagging and genotyped using TaqMan assays. Allelic combination and dependency tests were also performed.

RESULTS
In the pooled analysis, two of the five analysed polymorphisms showed evidence of association with GCA (rs2275913: PMH=1.85E-03, OR=1.17 (1.06-1.29); rs7747909: PMH=8.49E-03, OR=1.15 (1.04-1.27)). A clear trend of association was also found for the rs4711998 variant (PMH=0.059, OR=1.11 (1.00-1.23)). An independent effect of rs2275913 and rs4711998 was evident by conditional regression analysis. In addition, the haplotype harbouring the risk alleles better explained the observed association than the polymorphisms independently (likelihood p value <10(-05)).

CONCLUSIONS
Polymorphisms within the IL17A locus show a novel association with GCA. This finding supports the relevant role of the Th17 cells in this vasculitis pathophysiology.

Márquez|A|A|
Hernández-Rodríguez|J|J|
Cid|M C|MC|
Solans|R|R|
Castañeda|S|S|
Fernández-Contreras|M E|ME|
Ramentol|M|M|
Morado|I C|IC|
Narváez|J|J|
Gómez-Vaquero|C|C|
Martínez-Taboada|V M|VM|
Ortego-Centeno|N|N|
Sopeña|B|B|
Monfort|J|J|
García-Villanueva|M J|MJ|
Caminal-Montero|L|L|
de Miguel|E|E|
Blanco|R|R|
|||
Palm|O|O|
Molberg|O|O|
Latus|J|J|
Braun|N|N|
Moosig|F|F|
Witte|T|T|
Beretta|L|L|
Santaniello|A|A|
Pazzola|G|G|
Boiardi|L|L|
Salvarani|C|C|
González-Gay|M A|MA|
Martín|J|J|

Giant Cell Arteritis
Cytokines
Gene Polymorphism


The antioxidant effect of Asparagus cochinchinensis (Lour.) Merr. shoot in D-galactose induced mice aging model and in vitro.

Abstract:
BACKGROUND
An increasing number of plant components and their extracts have been shown to have beneficial health effects in humans. We aimed to explore the antioxidant effects of the aqueous extract of Asparagus cochinchinensis (Lour.) Merr. shoot in vivo and in vitro.

METHODS
A total of 80 Kun Ming mice were randomly divided into four groups (20/group). The mice in the control group received a daily subcutaneous injection of saline. A daily injection of D-galactose was administered to the aging model group, the vitamin C (Vc) group (positive control group), and the extract treatment group. Regular measurement of blood cells, nitric oxide synthase (NOS), catalase (CAT) activities, superoxide dismutase (SOD) activities, nitric oxide (NO), and malondialdehyde (MDA) concentration, and the expressions of NOS, SOD, and glutathione peroxidase (GPX) in serum levels were obtained. Furthermore, the microstructure of mice viscera was observed using hematoxylin and eosin staining.

RESULTS
The aqueous extract of A. cochinchinensis (Lour.) Merr. had similar 1,1-diphenyl-2-picrylhydrazyl radical 2,2-diphenyl-1-(2,4,6-trinitrophenyl) hydrazyl (DPPH·) [or 2,2'-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) (ABTS+)] and higher hydroxyl radicals (or superoxide anion; p < 0.05) radical scavenging capabilities to Vc. Moreover, compared with the aging model group, the aqueous extract of A. cochinchinensis (Lour.) Merr. shoot could obviously increase NOS, CAT, and SOD activities and the NO content, and reduce the MDA content (p < 0.05). Additionally, the microstructure of mice viscera was obviously improved and the expressions of NOS, SOD and GPX were also manifestly increased in the treatment group (p < 0.05).

CONCLUSION
The aqueous extract of A. cochinchinensis (Lour.) Merr. shoot had a strong radical scavenging capability in vivo and in vitro, and might be used to diminish radicals in the body and consequently prevent aging.

antioxidant
Asparagus cochinchinensis (Lour.) Merr.
shoot
enzyme activity
gene expression


Solvent Free Lipase Catalysed Synthesis of Ethyl Laurate: Optimization and Kinetic Studies.

Abstract: The current research work represents solvent free enzymatic synthesis of fatty acid ethyl ester; ethyl laurate. Immobilized lipase Fermase CALB™10,000 was used for the synthesis of ethyl laurate from ethanol and lauric acid. The influence of process parameters such as catalyst loading, speed of agitation, mole ratio, molecular sieves and temperature were studied. Fermase CALB™10,000 offered a conversion of 92.46 % at 60 °C in 4 h at optimized condition. The experimental data was best fitted by the Random Bi-Bi model with inhibition of both the substrates i.e. lauric acid and ethanol. The following kinetic parameters were retrieved from the model: Vmax = 1.243 × 103 mmol/min/g enzyme; KA = 0.1283 mmol; KB = 8.51 mmol; KiA = 5.098 mmol; and SSE = 0.0142. The activation energy for the enzymatic esterification was also determined and calculated to be 28.49 kJ/mol. A maximum conversion of 71 % was obtained after 5 successive reuse of Fermase CALB™10,000 lipase.

Gawas|Sarita D|SD|
Jadhav|Sachin V|SV|
Rathod|Virendra K|VK|

Lipase
Random Bi-Bi model
Biocatalysis
Flavour
Solvent free system


The genetics of gout: towards personalised medicine?

Abstract: Over the last decade, there have been major advances in the understanding of the genetic basis of hyperuricaemia and gout as well as of the pharmacogenetics of urate-lowering therapy. Key findings include the reporting of 28 urate-associated loci, the discovery that ABCG2 plays a central role on extra-renal uric acid excretion, the identification of genes associated with development of gout in the context of hyperuricaemia, recognition that ABCG2 variants influence allopurinol response, and the impact of HLA-B*5801 testing in reducing the prevalence of allopurinol hypersensitivity in high-risk populations. These advances, together with the reducing cost of whole genome sequencing, mean that integrated personalised medicine approaches may soon be possible in clinical practice. Genetic data may inform assessment of disease prognosis in individuals with hyperuricaemia or established gout, personalised lifestyle advice, selection and dosing of urate-lowering therapy, and prevention of serious medication adverse effects. In this article, we summarise the discoveries from genome-wide association studies and discuss the potential for translation of these findings into clinical practice.

Dalbeth|Nicola|N|
Stamp|Lisa K|LK|
Merriman|Tony R|TR|

Genetics
Gout
Personalised medicine
Genome-wide association study
Urate


Severe Acute Respiratory Syndrome Coronavirus 2 and Coronavirus Disease 2019: A Clinical Overview and Primer.

Abstract: Following its emergence in December 2019, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) caused what rapidly became a global pandemic. The precise origin and subsequent path of transmission have not yet been established-but like the other novel coronaviruses that it closely resembles, it appears to have evolved naturally in a bat host. The disease caused by SARS-CoV-2 infection, designated as coronavirus disease 2019 (COVID-19), ranges from asymptomatic, to mild self-limited illness, to progressive pneumonia, respiratory compromise, multiorgan failure, and death. In addition, a hyperinflammatory disease state occurs in a subset of patients, and may be seen either during acute infection or following recovery. The search for effective pharmacological management of COVID-19 continues, but several promising candidates have been identified, including the viral nucleoside analog remdesivir. However, despite the existence of literally thousands of clinical trials, the management of COVID-19 remains challenging, and the development of an optimal, evidence-based therapeutic approach is ongoing. The impact of SARS-CoV-2 and COVID-19 on the biobanking world is evolving and profound-in particular, it is likely that many of mysteries surrounding COVID-19 will be solved via the availability of high-quality, large-scale collection, storage, and analysis of patient specimens. The purpose of this review article is therefore to provide a rapid, comprehensive, and relevant overview and primer on SARS-CoV-2 and COVID-19, with attention to the epidemiology, virology, transmission, clinical features, and major therapeutic options currently existent.


Unilateral radiotherapy for surgically resected lateralized squamous cell carcinoma of the tonsil.

Abstract:
BACKGROUND
The purpose of this study was to determine the rate of contralateral neck recurrence after surgery and unilateral neck radiotherapy, for lateralized tonsillar cancers with ipsilateral neck disease, in order to inform future clinical trial protocols for this disease.

METHODS
Patients with lateralized tonsillar squamous carcinoma (T1-T2, N0-N2b), treated with surgery and unilateral adjuvant radiotherapy in a single United Kingdom center were retrospectively identified. Rates of recurrence in the contralateral, unirradiated neck were analyzed, together with survival and toxicity data.

RESULTS
Of 81 patients included, after a median follow-up of 5.7 years, no contralateral recurrences were identified. Five-year overall survival, progression-free survival, and locoregional control were 91.0%, 93.0%, and 95.4%, respectively.

CONCLUSION
Unilateral radiotherapy is an effective and safe treatment option for the postoperative management of lateralized tonsillar cancers, even in patients with N2b disease, and should be recommended in future clinical trial protocols. © 2016 Wiley Periodicals, Inc. Head Neck 39: 17-23, 2017.

Rackley|Thomas Paul|TP|
Namelo|Wanangwa Clara|WC|
Palaniappan|Nachi|N|
Cole|Naomi|N|
Owens|David M J|DM|
Evans|Mererid|M|

D000328:Adult
D000368:Aged
D000369:Aged, 80 and over
D002294:Carcinoma, Squamous Cell
D018572:Disease-Free Survival
D005260:Female
D006801:Humans
D008297:Male
D008875:Middle Aged
D009364:Neoplasm Recurrence, Local
D009367:Neoplasm Staging
D018714:Radiotherapy, Adjuvant
D012189:Retrospective Studies
D015996:Survival Rate
D014067:Tonsillar Neoplasms
D006113:United Kingdom

unilateral
radiotherapy
squamous cell carcinoma
tonsil
surgery


Non-coding RNA Neat1 and Abhd11os expressions are dysregulated in medium spiny neurons of Huntington disease model mice.

Abstract: Huntington Disease (HD) is a neurodegenerative disorder caused by expanded CAG repeats in the exon1 of huntingtin gene (HTT). The mutant HTT affects the transcriptional profile of neurons by disrupting the activities of transcriptional machinery and alters expression of many genes. In this study, we identified dysregulated non-coding RNAs (ncRNAs) in medium spiny neurons of 4-week-old HD model mouse. Also, we observed the intracellular localizations of Abhd11os and Neat1 ncRNAs by ViewRNA in situ hybridization, which could provide more precise detection, suggesting that it is a useful method to investigate the expression changes of genes with low expression levels.

Park|Hongsun|H| Miyazaki|Haruko|H| Yamanaka|Tomoyuki|T| Nukina|Nobuyuki|N|

D051937:Dopamine and cAMP-Regulated Phosphoprotein 32

Non-coding RNA
Neat1
Abhd11os
Huntington disease
ViewRNA in situ hybridization
Gene expression
Microarray


Molecular dynamics investigation of stereoselective inhibition mechanism of HIF-2α/ARNT heterodimer.

Abstract: Hypoxia-inducible factors (HIFs) are heterodimeric transcription factors related with the onset and progression of solid tumors. Studies demonstrated a class of tetrazole containing chiral inhibitors could stereoselectively disrupt the HIF-2 dimerization and reduce the target gene expression. However, the dynamical features and structural motifs of the HIF-2 heterodimer caused by the binding of enantiomers have not been rationalized at the atomistic level. In this work, molecular dynamics (MD) simulations combined with adaptive steered MD (ASMD) simulations were used to investigate stereoselective interrupting mechanism of HIF-2. Our results decipher that the binding of ligand A (S, R)-24 begets the significant conformation changes of β-sheets and interrupts the HIF-2α/ARNT heterodimerization, which may be attributed to the disruption of the hydrogen bond and salt bridge interactions formed by the 4 foremost residues (Asp240, Arg247, Glu362, and Arg366) and the destruction of hydrophobic interactions on the binding interface. By contrast, the binding of ligand B (R, S)-24 does not disrupt protein dimerization and causes the motion of Fα helix in HIF-2α PAS-B domain to further change the major tunnel for ligand ingress and engress. The present work provides important molecular-level insight into the effect of the binding enantiomers on HIF-2 heterodimerization and bridges the gap between theory and the experimental results, which may conduce to develop highly potent antagonists for intervening the HIF-2-driven tumors.

D051784:Aryl Hydrocarbon Receptor Nuclear Translocator

D051792:Basic Helix-Loop-Helix Transcription Factors

D054730:Protein Interaction Domains and Motifs

disruption
HIF-2 heterodimer
MM-GBSA
molecular dynamics simulation


Caffeine induces sperm detachment from sperm head-to-head agglutination in bull.

Abstract: Sperm head-to-head agglutination is a well-known known phenomenon in mammalian and non-mammalian species. Although several factors have been reported to induce sperm agglutination, information on the trigger and process of sperm detachment from the agglutination is scarce. Since hyperactivated motility is involved in bovine sperm detachment from the oviduct, we focused on caffeine, a well-known hyperactivation inducer, and aimed to determine the role of caffeine in sperm detachment from agglutination. Agglutination rate of bovine sperm was significantly decreased upon incubation with caffeine following pre-incubation without caffeine. Additionally, we observed that bovine sperm were detached from agglutination only when the medium contained caffeine. The detached sperm showed more asymmetrical flagellar beating compared to the undetached motile sperm, regardless of whether before or after the detachment. Intriguingly, some sperm that detached from agglutination re-agglutinated with different sperm agglutination. These findings indicated caffeine as a trigger for sperm detachment from the agglutination in bull. Furthermore, another well-known hyperactivation inducer, thimerosal, also significantly reduced the sperm agglutination rate. Overall, the study demonstrated the complete process of sperm detachment from sperm head-to-head agglutination and proposed that hyperactivated motility facilitates sperm detachment from another sperm. These findings would provide a better understanding of sperm physiology and fertilization process in mammals.

Umezu|Kohei|K| Kurata|Shouhei|S| Hara|Kenshiro|K| Tanemura|Kentaro|K|

Caffeine Agglutination Hyperactivation Thimerosal Spermatozoa


Quality evaluation of Panax ginseng adventitious roots based on ginsenoside constituents, functional genes, and ferric-reducing antioxidant power.

Abstract: In the study, six adventitious root lines of Panax ginseng have been successfully established. HPLC-ESI-MS analysis showed that 20 ginsenosides were identified in root lines, notoginsenoside Fa and notoginsenoside R2 were not found in AR lines. In AR lines, the highest accumulation of total ginsenosides was obtained in five-year main AR (24.87 mg/g). Principal component analysis classified root lines into three groups. Five-year ginseng was mostly similar with five-year main AR, five-year rootlet AR, and four-year rootlet AR in ginsenosides composition of group 1. Besides, gene expressions were consistent with the production of total ginsenosides, and correlation analysis revealed that total ginsenosides biosynthesis was significantly positively correlated with the gene expression of dammarenediol synthase. Five-year rootlet AR showed the highest activity on ferric-reducing antioxidant power test among samples. It provides a scientific evidence for the further exploitation and large-scale production of P. ginseng. PRACTICAL APPLICATIONS: This study provides valuable information for the commercial scale culture of ginseng adventitious roots. This report combines morphology, ginsenoside composition and content, gene expression, and ferric-reducing antioxidant power test to evaluate the quality of P. ginseng adventitious root, and combined with principal component analysis to screen out the high yield and stable ginseng adventitious roots. It would be profitable to use adventitious root culture of P. ginseng instead of field cultivation.

Liang|Wenxia|W| Wang|Shihui|S| Yao|Lu|L| Wang|Juan|J| Gao|Wenyuan|W|0000-0003-0050-501X

D018506:Gene Expression Regulation, Plant

Panax ginseng
adventitious root
gene expression
FRAP assay
PCA
secondary metabolites


Mechanical properties of human atherosclerotic intima tissue.

Abstract: Progression and rupture of atherosclerotic plaques in coronary and carotid arteries are the key processes underlying myocardial infarctions and strokes. Biomechanical stress analyses to compute mechanical stresses in a plaque can potentially be used to assess plaque vulnerability. The stress analyses strongly rely on accurate representation of the mechanical properties of the plaque components. In this review, the composition of intima tissue and how this changes during plaque development is discussed from a mechanical perspective. The plaque classification scheme of the American Heart Association is reviewed and plaques originating from different vascular territories are compared. Thereafter, an overview of the experimental studies on tensile and compressive plaque intima properties are presented and the results are linked to the pathology of atherosclerotic plaques. This overview revealed a considerable variation within studies, and an enormous dispersion between studies. Finally, the implications of the dispersion in experimental data on the clinical applications of biomechanical plaque modeling are presented. Suggestions are made on mechanical testing protocol for plaque tissue and on using a standardized plaque classification scheme. This review identifies the current status of knowledge on plaque mechanical properties and the future steps required for a better understanding of the plaque type specific material properties. With this understanding, biomechanical plaque modeling may eventually provide essential support for clinical plaque risk stratification.

Akyildiz|Ali C|AC|
Speelman|Lambert|L|
Gijsen|Frank J H|FJ|

D001696:Biomechanical Phenomena
D002340:Carotid Artery Diseases
D003324:Coronary Artery Disease
D006801:Humans
D058226:Plaque, Atherosclerotic
D013314:Stress, Mechanical
D017539:Tunica Intima
D061205:Vascular Calcification

Mechanical Properties
Plaque
Atherosclerosis


Potential drugs for the treatment of the novel coronavirus pneumonia (COVID-19) in China.

Abstract: The fight against the novel coronavirus pneumonia (namely COVID-19) that seriously harms human health is a common task for all mankind. Currently, development of drugs against the novel coronavirus (namely SARS-CoV-2) is quite urgent. Chinese medical workers and scientific researchers have found some drugs to play potential therapeutic effects on COVID-19 at the cellular level or in preliminary clinical trials. However, more fundamental studies and large sample clinical trials need to be done to ensure the efficacy and safety of these drugs. The adoption of these drugs without further testing must be careful. The relevant articles, news, and government reports published on the official and Preprint websites, PubMed and China National Knowledge Infrastructure (CNKI) databases from December 2019 to April 2020 were searched and manually filtered. The general pharmacological characteristics, indications, adverse reactions, general usage, and especially current status of the treatment of COVID-19 of those potentially effective drugs, including chemical drugs, traditional Chinese medicines (TCMs), and biological products in China were summarized in this review to guide reasonable medication and the development of specific drugs for the treatment of COVID-19.

Pan|Xiaoqi|X| Dong|Lan|L| Yang|Lian|L| Chen|Dayi|D| Peng|Cheng|C|


The crystal structures of two novel polymorphs of bis-(oxonium) ethane-1,2-di-sulfonate.

Abstract: Two novel crystal forms of bis-(oxonium) ethane-1,2-di-sulfonate, 2H3O-·C2H4O6S2 2-, are reported. Polymorph II has monoclinic (P21/n) symmetry, while the symmetry of form III is triclinic (P ). Both structures display extensive networks of O-H⋯O hydrogen bonds. While this network in Form II is similar to that observed for the previously reported Form I [Mootz & Wunderlich (1970 ▸). Acta Cryst. B26, 1820-1825; Sartori et al. (1994 ▸). Z. Naturforsch. 49, 1467-1472] and extends in all directions, in Form III it differs significantly, forming layers parallel to the ab plane. The sulfonate mol-ecule in all three forms adopts a nearly identical geometry. The other observed differences between the forms, apart from the hydrogen-bonding network, are observed in the crystal density and packing index.

crystal structure
polymorphism
oxonium cation
sulfonate anions


Evaluation of drug interaction potential of Labisia pumila (Kacip Fatimah) and its constituents.

Abstract: Labisia pumila (Kacip Fatimah) is a popular herb in Malaysia that has been traditionally used in a number of women's health applications such as to improve libido, relieve postmenopausal symptoms, and to facilitate or hasten delivery in childbirth. In addition, the constituents of this plant have been reported to possess anticancer, antioxidant, and anti-inflammatory properties. Clinical studies have indicated that cytochrome P450s (CYPs), P-glycoprotein (P-gp), and Pregnane X receptor (PXR) are the three main modulators of drug-drug interactions which alter the absorption, distribution, and metabolism of drugs. Given the widespread use of Kacip Fatimah in dietary supplements, the current study focuses on determining the potential of its constituents to affect the activities of CYPs, P-gp, or PXR using in vitro assays which may provide useful information toward the risk of herb-drug interaction with concomitantly used drugs. Six compounds isolated from the roots of L. pumila (2 saponins and 4 alkyl phenols) were tested, in addition to the methanolic extract. The extract of L. pumila showed a significant time dependent inhibition (TDI) of CYP3A4, reversible inhibition of CYP2C9 and 2C19 and a weak inhibition of 1A2 and 2D6 as well as an inhibition of P-gp and rifampicin-induced PXR activation. The alkyl phenols inhibited CYP3A4 (TDI), CYP2C9, and 2C19 (reversible) while saponins inhibited P-gp and PXR. In conclusion, L. pumila and its constituents showed significant modulation of all three regulatory proteins (CYPs, P-gp, and PXR) suggesting a potential to alter the pharmacokinetic and pharmacodynamic properties of conventional drugs if used concomitantly.

Manda|Vamshi K|VK|
Dale|Olivia R|OR|
Awortwe|Charles|C|
Ali|Zulfiqar|Z|
Khan|Ikhlas A|IA|
Walker|Larry A|LA|
Khan|Shabana I|SI|

Labisia pumila
P-gp
PXR
herb-drug interactions
CYP450 enzymes
Myrsinaceae


A Deep-Learning System for Fully-Automated Peripherally Inserted Central Catheter (PICC) Tip Detection.

Abstract: A peripherally inserted central catheter (PICC) is a thin catheter that is inserted via arm veins and threaded near the heart, providing intravenous access. The final catheter tip position is always confirmed on a chest radiograph (CXR) immediately after insertion since malpositioned PICCs can cause potentially life-threatening complications. Although radiologists interpret PICC tip location with high accuracy, delays in interpretation can be significant. In this study, we proposed a fully-automated, deep-learning system with a cascading segmentation AI system containing two fully convolutional neural networks for detecting a PICC line and its tip location. A preprocessing module performed image quality and dimension normalization, and a post-processing module found the PICC tip accurately by pruning false positives. Our best model, trained on 400 training cases and selectively tuned on 50 validation cases, obtained absolute distances from ground truth with a mean of 3.10 mm, a standard deviation of 2.03 mm, and a root mean squares error (RMSE) of 3.71 mm on 150 held-out test cases. This system could help speed confirmation of PICC position and further be generalized to include other types of vascular access and therapeutic support devices.

Lee|Hyunkwang|H|
Mansouri|Mohammad|M|
Tajmir|Shahein|S|
Lev|Michael H|MH|
Do|Synho|S|

D002405:Catheterization, Central Venous
D002406:Catheterization, Peripheral
D062905:Central Venous Catheters
D016208:Databases, Factual
D000077321:Deep Learning
D004562:Electrocardiography
D005260:Female
D006801:Humans
D008297:Male
D016571:Neural Networks, Computer
D061214:Patient Safety
D010363:Pattern Recognition, Automated
D013902:Radiography, Thoracic
D012189:Retrospective Studies

PICC
Chest radiograph
Computer-aided detection
Deep learning
Machine learning
Radiology workflow


Breast cancer proliferation and deterioration-associated metabolic heterogeneity changes induced by exposure of bisphenol S, a widespread replacement of bisphenol A.

Abstract: Exposure to bisphenol A (BPA) is considered to be associated with the increased incidence of breast cancer. As a widespread replacement of BPA, the effect of bisphenol S (BPS) on breast tumor programming has not been studied. We reported that BPS exposure significantly promoted proliferation and deterioration of breast tumor by nonmonotonic dose response. The mechanisms were investigated by molecular biology and mass spectrometry-based lipidomics, proteomics and imaging. BPS exposure induced the spatially intratumor heterogeneity of morphology-driven lipids and proteins. The more significant proliferation resulted from BPS-10 (10 μg/kg body weight /day) exposure was evidenced by the variations of spatial distribution of lipids related to ceramide-sphingomyelin signaling pathway, proteins related to chromosomal stability and cell proliferation in central necrotic regions of breast tumor. In contrast, the BPS-100 exposure obviously accelerated deterioration of breast tumor by the variations of spatial distribution of proteins that were associated with the stability of nucleic acid structure in peripheral neoplastic regions. Accordingly, dysregulation of metabolism and protein function as well as DNA methylation and hypoxic tumor microenvironment could be applied to predict the possibility of tumorigenesis, proliferation and metastasis that might be caused by other bisphenol analogs.

Zhao|Chao|C| Yong|Ting|T| Zhang|Yinbin|Y| Xiao|Yu|Y| Jin|Yaofeng|Y| Zheng|Chang|C| Nirasawa|Takashi|T| Cai|Zongwei|Z|

Bisphenol S
Imaging mass spectrometry
In situ imaging of protein and lipid
Tumor proliferation


Identification of the Minimal Glycotope of Streptococcus pneumoniae 7F Capsular Polysaccharide using Synthetic Oligosaccharides.

Abstract: Streptococcus pneumoniae causes life-threatening diseases including meningitis, pneumonia and sepsis. Existing glycoconjugate vaccines based on purified capsular polysaccharides are widely used and help to prevent millions of deaths every year. Herein, the total syntheses of oligosaccharides resembling portions of the S. pneumoniae serotype 7F (ST7F) capsular polysaccharide repeating unit are reported. To define minimal glycan epitopes, glycan microarrays containing the synthetic oligosaccharides were used to screen human reference serum and revealed that both side chains of the ST7F play a key role in antigen recognition. The identification of protective minimal epitopes is vital to design efficient semi- and fully-synthetic glycoconjugate vaccines.

minimal glycotopes
Streptococcus pneumoniae
serotype 7F
glycan arrays
total synthesis


Clinical and sonographic assessment of cervical lymph node metastasis in papillary thyroid carcinoma.

Abstract: The purpose of this study was to assess the differences in clinical and sonographic features of papillary thyroid carcinoma (PTC) between cervical lymph node metastatic (CLNM) and nonmetastatic groups. Clinical data of PTC patients (414 patients with 624 malignant nodules) who underwent a preoperative ultrasonography and surgery between June 2010 and March 2015 at Renmin Hospital of Wuhan University were retrospectively analyzed. Clinical factors, preoperative ultrasound features and the final pathological findings were obtained. The differences in the sonographic features of PTC between the CLNM group and the non-CLNM group were analyzed. There were 187 CLNM and 227 non-CLNM patients. The median age at the diagnosis of this cohort was 45.4 years old (ranging from 18 to 77 years). Ultrasonographic parameters that were significantly associated with CLNM [OR=2.569 (1.502, 4.393), P<0.001)] were as follows: the mulifocality of the nodules, size over 2 cm, the presence of microcalcifications, the distance ratio (DR) pattern showing the contact of the nodules with the thyroid capsule, and the extracapsular spread of the nodules. No significant differences in age, gender, thyroid stimulating hormone (TSH) levels and other ultrasonography parameters were found between the CLNM and the non-CLNM groups. Therefore, our results suggest that a larger size, microcalcifications, mulifocality, and the DR pattern showing the contact of the nodules with the thyroid capsule and extracapsular spread are significantly more indicative of CLNM in PTC.

Wu|Qi|Q| Zhang|Yi-Min|YM| Sun|Si|S| Li|Juan-Juan|JJ| Wu|Juan|J| Li|Xiang|X| Zhu|Shan|S| Wei|Wen|W| Sun|Sheng-Rong|SR|

clinical and sonographic assessment
cervical lymph node metastasis
papillary thyroid carcinoma


Impact of Iron Deficiency on Peripheral Artery Disease After Endovascular Therapy.

Abstract: Despite advances in endovascular therapy (EVT), peripheral artery disease (PAD) is a public health problem associated with high cardiovascular mortality. Iron deficiency (ID) is associated with poor clinical outcome in patients with heart disease, but whether ID is associated with the severity and clinical outcome of PAD remains unclear.  A total of 449 patients with PAD who received EVT and who had iron and red blood cell measurement were enrolled. ID was defined as transferrin saturation (TSAT) <20%, based on a previous report. TSAT and hemoglobin decreased with deteriorating Fontaine class. During a median follow-up period of 1,064 days, 71 major adverse cardiovascular and leg events (MACLE) and 47 major adverse cardiovascular events (MACE) were noted. All patients were divided into 2 groups based on the presence of ID. On Kaplan-Meier analysis, patients with ID had higher rates of MACE and MACLE than those without. On multivariate Cox proportional hazard regression analysis, TSAT and hemoglobin were independently associated with MACLE. Addition of TSAT to the known risk factors significantly improved the net reclassification index and integrated discrimination improvement.  ID, as assessed by TSAT, was associated with the severity and clinical outcome of PAD, indicating that it could be a therapeutic target.

Otaki|Yoichiro|Y| Watanabe|Tetsu|T| Takahashi|Hiroki|H| Sugai|Takayuki|T| Yokoyama|Miyuki|M| Tamura|Harutoshi|H| Kato|Shigehiko|S| Nishiyama|Satoshi|S| Arimoto|Takanori|T| Shishido|Tetsuro|T| Watanabe|Masafumi|M|

Iron deficiency
Peripheral artery disease
Clinical outcome


'Solitary idiopathic choroiditis' or a tumour of scleral origin: A case report based hypothesis.

Abstract: We here hypothesize the scleral origin of 'Solitary Idiopathic Choroiditis', a yellowish, nodular lesion that resembles other choroidal tumors. Systemic investigations were done to rule out causes like tuberculosis and sarcoidosis. Multimodal imaging was done for better characterization and to distinguish it from other choroidal lesions. Fundus imaging revealed a yellowish-orange, well-defined nodular lesion resembling solitary idiopathic choroiditis inferotemporal to the disc. Swept source optical coherence tomography (SSOCT) showed a nodular lesion arising from the sclera with compression of overlying choroid. Indocyanine green angiography (ICGA) showed hypofluorescence in all phases of angiogram with displacement of major choroidal vessels along the walls of the mass and loss of overlying choriocapillaries. The same was evident on Swept Source optical coherence tomography angiography (SSOCTA) as well. Fundus autofluorescence (FAF) showed central hypofluoresence with surrounding hyperfluorescence. Ultrasound (USG) B scan revealed a high reflective echo at the apex of the mass with moderate internal reflectivity without any evidence of calcification. Enhanced Infrared (IR) Reflectance imaging revealed a central intense hyerreflective area suggestive of a fibrotic mass. Magnetic reasonance imaging (MRI) revealed a focal hypointense nodular lesion on T2-weighted image. The central white area at the apex with corresponding hypoautofluorescence, a high spike on ultrasound, intense hyperreflectivity on enhanced Infrared reflectance, lack of vascularity and displacement of choroidal vessels is suggestive of a scleral origin of the mass and likely fibrotic nature.

Kumar|Prashant|P| Chawla|Rohan|R| Balakrishnan|Jyothi|J| Kumar|Atul|A| Kumar|Atin|A|


Performance of Automated Dissection on Formalin-Fixed Paraffin-Embedded Tissue Sections for the 21-Gene Recurrence Score Assay.

Abstract: This study aimed to compare the performance of MilliSect dissection and manual dissection. Twenty-five formalin-fixed paraffin-embedded (FFPE) breast cancer tissue blocks were selected for comparison. Specific areas of interest (AOIs) in invasive carcinoma on tissue sections were transferred to dissection slides by manual macrodissection or the MilliSect instrument. The comparison criteria were 1) the time required for dissection; 2) RNA concentration and purity; 3) RNA quantity of 5 housekeeping genes (by RT-qPCR); and 4) ER, PR, HER2, Ki-67 and recurrence score (RS) values (by the 21-gene assay). Then, tumor-adjacent tissues, including fibrocollagenous and epithelial tissues, from the same selected tissue blocks of 8 of 25 patients were scraped using the mesodissection method, and their RS values were assessed to evaluate the influence of tumor-adjacent tissues on the target AOIs. Ultimately, 4 AOIs of invasive ductal carcinoma (IDC) from 1 tissue block of another 4 patients with lymph node (LN) metastases each, LN tissue and a mixture of IDC and LN tissue from the other tissue block of the same 4 patients were mesodissected to evaluate the influence of infiltrating lymphocyte levels on the RS values of AOIs. In our experience, the MilliSect instrument, which provides process management documentation, required more time than manual macrodissection (on average, approximately 9.1 min per sample versus 5.8 min per sample, respectively). The RNA yield and quality of the dissected tissues were comparable for the 2 methods. However, the tumor-adjacent tissues of the AOIs may influence the RS to some extent. Tumor-infiltrating lymphocytes (TILs) can dramatically increase RSs, far exceeding the influence of tumor-adjacent fibrocollagenous and epithelial tissues. In conclusion, MilliSect mesodissection is comparable to manual dissection. This mesodissection tool may facilitate AOI alignment and the dissection process for the 21-gene RS assay. Samples whose adjacent tissues are intermixed with TILs warrant special attention.

Qi|Peng|P|0000-0002-5048-9604 Bai|Qian-Ming|QM| Yao|Qian-Lan|QL| Yang|Wen-Tao|WT| Zhou|Xiao-Yan|XY|

D015972:Gene Expression Regulation, Neoplastic

D060888:Real-Time Polymerase Chain Reaction

recurrence score
macrodissection
mesodissection
companion diagnostics
microdissection


Role of Magnetic Resonance Enterography in Differentiating between Fibrotic and Active Inflammatory Small Bowel Stenosis in Patients with Crohn's Disease.

Abstract:
OBJECTIVE
To assess the diagnostic accuracy of magnetic resonance imaging (MRI) in prospectively differentiating between fibrotic and active inflammatory small bowel stenosis in patients with Crohn's disease (CD).

MATERIALS AND METHODS
A total of 111 patients with histologically proven CD presenting with clinical and plain radiographic signs of small bowel obstruction underwent coronal and axial MRI scans after oral administration of polyethylene glycol solution. A stenosis was judged present if a small bowel segment had >80% lumen reduction as compared to an adjacent normal loop and mural thickening of >3 mm. At the level of the stenosis, both T2 signal intensity and post-gadolinium T1 enhancement were quantified using a 5-point scale (0: very low; 1: low; 2: moderate; 3: high; and 4: very high). A stenosis was considered fibrotic if the sum of the two values (activity score: AS) did not exceed 1.

RESULTS
A small bowel stenosis was identified in 48 out of 111 patients. Fibrosis was confirmed at histology in all of the 23 patients with AS of 0 or 1, who underwent surgery within 3 days of the MRI examination. In the remaining 25 patients (AS: 2-8), an active inflammatory stenosis was suspected and remission of the obstructive symptoms was obtained by means of medical treatment. One of these patients (AS: 2), however, underwent surgery after 14 days, due to recurrence. MRI had 95.8% sensitivity, 100% specificity, and 97.9% accuracy in the diagnosis of fibrotic stenosis.

CONCLUSION
MRI is reliable in differentiating fibrotic from inflammatory small bowel stenosis in CD.

Crohn's disease
MR enteroclysis
intestinal stenosis
small bowel imaging


Oscillatory magnetic brain activity is related to dissociative symptoms and childhood adversities - A study in women with multiple trauma.

Abstract:
BACKGROUND
Individuals with trauma-related disorders are complex and heterogeneous; part of this complexity derives from additional psychopathology like dissociation as well as environmental adversities such as traumatic stress, experienced throughout the lifespan. Understanding the neurophysiological abnormalities in Post-traumatic stress disorder (PTSD) requires a simultaneous consideration of these factors.

METHODS
Resting state magnetoencephalography (MEG) recordings were obtained from 41 women with PTSD and comorbid depressive symptoms, and 16 healthy women. Oscillatory brain activity was extracted for five frequency bands and 11 source locations, and analyzed in relation to shutdown dissociation and adversity-related measures.

RESULTS
Dissociative symptoms were related to increased delta and lowered beta power. Adversity-related measures modulated theta and alpha oscillatory power (in particular childhood sexual abuse) and differed between patients and controls.

LIMITATIONS
Findings are based on women with comorbid depressive symptoms and therefore may not be applicable for men or groups with other clinical profiles. In respect to childhood adversities, we had no reliable source for the early infancy.

CONCLUSION
Trauma-related abnormalities in neural organization vary with both exposure to adversities as well as their potential to evoke ongoing shutdown responses.

Schalinski|I|I|
Moran|J K|JK|
Elbert|T|T|
Reindl|V|V|
Wienbruch|C|C|

D000069586:Adult Survivors of Child Adverse Events

Dissociation
Childhood adversities
Trauma
PTSD
MEG spontaneous activity


Exploring autistic-like traits relating to empathic attitude and psychological distress in hospital pharmacists.

Abstract:
BACKGROUND
Pharmacists are expected to play a key role in modern cancer care. Research suggests that an empathic approach and attitude in medical staff improves the quality of patient care. An empathic attitude and psychological distress are thought to be associated with autistic-like traits, but little is known about such traits.

OBJECTIVE
In this study, we aimed to clarify the associations among autistic-like traits, empathic attitude in a medical context, and psychological health in hospital pharmacists.

SETTING
Eligibility criteria for inclusion were certified pharmacists working at hospitals for patient care who returned their questionnaires.

METHOD
Eight hundred and twenty-three hospital pharmacists completed a number of self-administered questionnaires anonymously by mail.

MAIN OUTCOME MEASURES
Scores were obtained on the Autism-Spectrum Quotient, the Jefferson Scale of Empathy, the General Health Questionnaire-12, and subscales of the Interpersonal Reactivity Index (Perspective Taking, IRI-Empathic Concern, IRIPersonal Distress). We performed correlation and mediation analyses to confirm that the empathy and general health questionnaires were associated with autism-spectrum quotient scores, and with each IRI subscale.

RESULTS
Complete responses were obtained from 379 pharmacists comprising 151 males (39.8 %) with a mean age of 37.7 ± 10.8 years (missing data, n = 13) and a median of 11 years after qualification as a pharmacist. Autism-Spectrum Quotient scores were inversely correlated with empathy (r = -0.22, p < 0.001) and positively correlated with general health scores (r = 0.40, p < 0.001). In the models with mediation, the inverse correlation between autism-spectrum quotient and empathy scores was mediated indirectly by IRI-Perspective Taking and IRI-Empathic Concern, and the positive correlation between autism-spectrum quotient and general health was mediated indirectly by IRI-Personal Distress. There were also direct effects, with significant effects of autism-spectrum quotient on empathy and general health scores.

CONCLUSION
Our findings suggest that autistic-like traits affect both empathic attitude in a medical context and the psychological health of pharmacists. We recommend that to improve empathy in those with high levels of autistic-like traits, we may need to develop specialized interventions, such as improving communication skills training.

Higuchi|Yuji|Y| Uchitomi|Yosuke|Y| Fujimori|Maiko|M| Koyama|Toshihiro|T| Kataoka|Hitomi|H| Kitamura|Yoshihisa|Y| Sendo|Toshiaki|T| Inagaki|Masatoshi|M|

Hospital pharmacist
Empathy
Japan
Pharmaceutical care


Endoplasmic Reticulum-Plasma Membrane Contact Sites.

Abstract: The endoplasmic reticulum (ER) has a broad localization throughout the cell and forms direct physical contacts with all other classes of membranous organelles, including the plasma membrane (PM). A number of protein tethers that mediate these contacts have been identified, and study of these protein tethers has revealed a multiplicity of roles in cell physiology, including regulation of intracellular Ca2+ dynamics and signaling as well as control of lipid traffic and homeostasis. In this review, we discuss the cross talk between the ER and the PM mediated by direct contacts. We review factors that tether the two membranes, their properties, and their dynamics in response to the functional state of the cell. We focus in particular on the role of ER-PM contacts in nonvesicular lipid transport between the two bilayers mediated by lipid transfer proteins.

D000071737:Stromal Interaction Molecule 1

oxysterol-binding protein (OSBP)–related protein


GC-MS analysis and molecular docking of bioactive compounds of Camellia sinensis and Camellia assamica.

Abstract: The methanol extract of Camellia sinensis (MES) and acetone extract of Camellia assamica (AEA) were subjected to the thin layer chromatography to separate the bioactive compounds. The antimicrobial activity of all the fractions was carried out against pathogenic microorganisms by the agar-well diffusion method. The most effective bioactive fraction of each plant species was analysed by GC-MS. Fraction L of methanol extract of C. sinensis (MES) and fraction 5 of acetone extract of C. assamica (AEA) were found very effective against selected pathogenic strains. GC-MS analysis of this fraction showed the presence of n-heptadecanol-1 (68.63%) in MES and 2',6'dihydroxyacetophenone, bis(trimethylsilyl) (17.58%) in AEA with the highest area. The compounds n-heptadecanol-1 and 2',6'dihydroxyacetophenone, bis(trimethylsilyl) ether were used for docking to analyse its therapeutic potential. The ligand compound n-heptadecanol-1 (HEP) from MES of C. sinensis and 2',6'dihydroxyacetophenone, bis(trimethylsilyl) ether from AEA of C. assamica were docked with the target protein dihydropteoate synthase (DHPS) active sites of Escherichia coli and Staphylococcus aureus active sites via Auto Dock Vina, thereby forecasting the finest binding position of ligands. AutoDock Vina docked results revealed the involvement of binding energy for the establishment of the protein-ligand structure complex, besides generating an interpretation of all apparent molecular interactions accountable for its activity. Further, the protein-ligand complex of MES, EcDHPS + HEP and SaDHPS + HEP exhibiting the best binding affinity were - 4.8 kcal/mol and - 3.6 kcal/mol. The protein-ligand complex of AEA, i.e., EcDHPS + DHA and SaDHPS + DHA exhibited the best binding affinity of - 4.8 kcal/mol and - 4.8 kcal/mol.

Molecular docking
Camellia sinensis
Camellia assamica
Antimicrobial
TLC


Release from Above- and Belowground Insect Herbivory Mediates Invasion Dynamics and Impact of an Exotic Plant.

Abstract: The enemy-release hypothesis is one of the most popular but also most discussed hypotheses to explain invasion success. However, there is a lack of explicit, experimental tests of predictions of the enemy-release hypothesis (ERH), particularly regarding the effects of above- and belowground herbivory. Long-term studies investigating the relative effect of herbivores on invasive vs. native plant species within a community are still lacking. Here, we report on a long-term field experiment in an old-field community, invaded by Solidago canadensis s. l., with exclusion of above- and belowground insect herbivores. We monitored population dynamics of the invader and changes in the diversity and functioning of the plant community across eight years. Above- and belowground insects favoured the establishment of the invasive plant species and thereby increased biomass and decreased diversity of the plant community. Effects of invertebrate herbivores on population dynamics of S. canadensis appeared after six years and increased over time, suggesting that long-term studies are needed to understand invasion dynamics and consequences for plant community structure. We suggest that the release from co-evolved trophic linkages is of importance not only for the effect of invasive species on ecosystems, but also for the functioning of novel species assemblages arising from climate change.

diversity
plant communities
biological invasions
ecosystem functions
enemy release
herbivorous insects
long-term experiment
productivity
trophic interactions


Management of Spinal Deformities and Evidence of Treatment Effectiveness.

Abstract:
Introduction
The review evaluates the up-to-date evidence for the treatment of spinal deformities, including scoliosis and hyperkyphosis in adolescents and adults.

Material and Methods
The PubMed database was searched for review articles, prospective controlled trials and randomized controlled trials related to the treatment of spinal deformities. Articles on syndromic scoliosis were excluded and so were the articles on hyperkyphosis of the spine with causes other than Scheuermann's disease and osteoporosis. Articles on conservative and surgical treatments of idiopathic scoliosis, adult scoliosis and hyperkyphosis were also included. For retrospective papers, only studies with a follow up period exceeding 10 years were included.

Results
The review showed that early-onset idiopathic scoliosis has a worse outcome than late-onset idiopathic scoliosis, which is rather benign. Patients with AIS function well as adults; they have no more health problems when compared to patients without scoliosis, other than a slight increase in back pain and aesthetic concern. Conservative treatment of adolescent idiopathic scoliosis (AIS) using physiotherapeutic scoliosis-specific exercises (PSSE), specifically PSSR and rigid bracing was supported by level I evidence. Yet to date, there is no high quality evidence (RCT`s) demonstrating that surgical treatment is superior to conservative treatment for the management of AIS. For adult scoliosis, there are only a few studies on the effectiveness of PSSEs and a conclusion cannot as yet be drawn.For hyperkyphosis, there is no high-quality evidence for physiotherapy, bracing or surgery for the treatment of adolescents and adults. However, bracing has been found to reduce thoracic hyperkyphosis, ranging from 55 to 80° in adolescents. In patients over the age of 60, bracing improves the balance score, and reduces spinal deformity and pain. Surgery is indicated in adolescents and adults in the presence of progression of kyphosis, refractory pain and loss of balance.

Discussion
The available evidence reviewed has suggested that different approaches are needed towards the management of different spinal deformities. Specific exercises should be prescribed in children and adolescents with a Cobb angle in excess of 15°. In progressive curves, they should be used in conjunction with bracing. Clarity regarding differences and similarities is given as to what makes PSSE and PSSR specific exercises. As AIS is relatively benign in nature, conservative treatment should be tried when the curve is at a surgical threshold, before surgery is considered. Similarly, bracing and exercises should be prescribed for patients with hyperkyphosis, particularly when the lumbar spine is afflicted. Surgery should be considered only when the symptoms cannot be managed conservatively.

Conclusion
There is at present high quality evidence in support of the conservative treatment of AIS. The current evidence supports the use of PSSE, especially those using PSSR, together with bracing in the treatment of AIS. In view of the lack of medical consequences in adults with AIS, conservative treatment should be considered for curves exceeding the formerly assumed range of conservative indications.There is, however a lack of evidence in support of any treatment of choice for hyperkyphosis in adolescents and spinal deformities in adults. Yet, conservative treatment should be considered first. Yet to date, there is no high quality evidence (RCT`s) demonstrating that surgical treatment is superior to conservative treatment for the management of AIS and hyperkyphosis. Additionally, surgery needs to be considered with caution, as it is associated with a number of long-term complications.

Bettany-Saltikov|Josette|J|
Turnbull|Deborah|D|
Ng|Shu Yan|SY|
Webb|Richard|R|

Scoliosis
Hyperkyphosis
Adult scoliosis
Adolescent idiopathic scoliosis
Exercises
PSSE
PSSR
Bracing
Surgery
Rehabilitation
Scheuermann’s disease


Intercostal to musculocutaneous nerve transfer in patients with complete traumatic brachial plexus injuries: case series.

Abstract:
BACKGROUND
To recover biceps strength in patients with complete brachial plexus injuries, the intercostal nerve can be transferred to the musculocutaneous nerve. The surgical results are very controversial, and most of the studies with good outcomes and large samples were carried out in Asiatic countries. The objective of the study was to evaluate biceps strength after intercostal nerve transfer in patients undergoing this procedure in a Western country hospital.

METHODS
We retrospectively analyzed 39 patients from 2011 to 2016 with traumatic brachial plexus injuries receiving intercostal to musculocutaneous nerve transfer in a rehabilitation hospital. The biceps strength was graded using the British Medical Research Council (BMRC) scale. The variables reported and analyzed were age, the time between trauma and surgery, surgeon experience, body mass index, nerve receptor (biceps motor branch or musculocutaneous nerve), and the number of intercostal nerves transferred. Statistical tests, with a significance level of 5%, were used.

RESULTS
Biceps strength recovery was graded ≥M3 in 19 patients (48.8%) and M4 in 15 patients (38.5%). There was no statistical association between biceps strength and the variables. The most frequent complication was a pleural rupture.

CONCLUSIONS
Intercostal to musculocutaneous nerve transfer is a safe procedure. Still, biceps strength after surgery was ≥M3 in only 48.8% of the patients. Other donor nerve options should be considered, e.g., the phrenic or spinal accessory nerves.

D000055:Accessory Nerve
D000328:Adult
D001917:Brachial Plexus
D020516:Brachial Plexus Neuropathies
D005260:Female
D006801:Humans
D007367:Intercostal Nerves
D008297:Male
D008875:Middle Aged
D018482:Muscle, Skeletal
D009138:Musculocutaneous Nerve
D016067:Nerve Transfer
D011183:Postoperative Complications

Musculocutaneous nerve
Nerve transfer
Brachial plexus
Intercostal nerve


Effects of Sustained Otolith-Only Stimulation on Post-Rotational Nystagmus.

Abstract: Constant velocity rotations in darkness evoke vestibulo-ocular reflex in form of pre- and post-rotational nystagmus under cerebellar supervision. Reorientation of the head with respect to gravity, stimulating otolith and semicircular canal, during post-rotational phase rapidly suppresses the post-rotational nystagmus. We asked if pure otolith stimulation without semicircular canal signal is sufficient for the suppression of post-rotational nystagmus. The experimental paradigm comprised of on-axis rotations in the horizontal plane when the subject was sitting upright, followed by a novel stimulus that combined off-axis centrifugation in the horizontal plane with amplitude matched, yet out-of-phase, on-axis horizontal rotation-double centrifugation. The resultant effect of double centrifugation was pure otolith stimulation that constantly changed direction, yet completely canceled out angular velocity (no horizontal semicircular canal stimulation). Double centrifugation without pre-existing on-axis rotations evoked mixture of horizontal and vertical eye movements, latter reflected the known uncertainty of the vestibular system to differentiate whether the sensory signal is related to low-frequency translations in horizontal plane or head tilts relative to the gravity. Double centrifugation during post-rotational phase suppressed the peak slow phase eye velocity of the post-rotational nystagmus, hence affecting the vestibular ocular reflex gain (eye velocity/head velocity) matrix. The decay time constant, however, was unchanged. Amount of suppression of the peak slow phase eye velocity of the post-rotational nystagmus during double centrifugation correlated with the peak vertical eye velocity evoked by the pure otolith stimuli in the absence of pre-existing on axis rotations. In post-rotational phase, the pure otolith signal affects vestibular ocular reflex gain matrix but does not affect the time constant.

D006801:Humans
D009759:Nystagmus, Pathologic
D009760:Nystagmus, Physiologic
D010037:Otolithic Membrane
D012027:Reflex, Vestibulo-Ocular
D012399:Rotation
D012665:Semicircular Canals
D014785:Vision, Ocular

Vestibulo-ocular reflex
Gravity
Eye movement
Vestibular
Balance
Cerebellum


Estimating temperature-dependent anisotropic hydrogen displacements with the invariom database and a new segmented rigid-body analysis program.

Abstract: Invariom partitioning and notation are used to estimate anisotropic hydrogen displacements for incorporation in crystallographic refinement models. Optimized structures of the generalized invariom database and their frequency computations provide the information required: frequencies are converted to internal atomic displacements and combined with the results of a TLS (translation-libration-screw) fit of experimental non-hydrogen anisotropic displacement parameters to estimate those of H atoms. Comparison with TLS+ONIOM and neutron diffraction results for four example structures where high-resolution X-ray and neutron data are available show that electron density transferability rules established in the invariom approach are also suitable for streamlining the transfer of atomic vibrations. A new segmented-body TLS analysis program called APD-Toolkit has been coded to overcome technical limitations of the established program THMA. The influence of incorporating hydrogen anisotropic displacement parameters on conventional refinement is assessed.

Lübben|Jens|J|
Bourhis|Luc J|LJ|
Dittrich|Birger|B|

segmented rigid-body analysis
generalized invariom database
anisotropic displacement parameters


Smoke-free home initiative in Bantul, Indonesia: Development and preliminary evaluation.

Abstract:
INTRODUCTION
Tobacco control policies in Indonesia are still limited. This study aims to describe the process of the implementation of the smoke-free home (SFH) program in rural areas in Indonesia and to conduct a preliminary evaluation of its implementation.

METHODS
The development of SFH (or Rumah Bebas Asap Rokok) applies the theory of diffusion of innovation with the following stages: innovation, dissemination, adoption, implementation, and evaluation. The preliminary evaluation of the SFH program used an observational method combined with a cross-sectional survey. The population of this study was all houses in Karet hamlet, in Bantul district, Yogyakarta province with 378 houses as population, from which 196 houses were selected as sample using the proportional random sampling technique. Quantitative data analysis used multiple linear regression in Stata 15.1.

RESULTS
SFH is a community-based tobacco control innovation program that began with a community declaration. Preliminary evaluation after one-year implementation showed that 55% and 45% of respondents were smokers and non-smokers, respectively. Among smokers, 95%, 78% and 56% reported not smoking near pregnant women, children, and non-smokers, respectively. Moreover, 52% of respondents reported having a front-door ashtray, and 46% reported guests not smoking; among non-smokers, the corresponding values were 56% and 60%.

CONCLUSIONS
SFH implementation has an impact on the community's smoking pattern. Awareness of smokers to protect women and children from secondhand smoke is very high. While the results are promising, more political and resource support is needed from the local and national policymakers to support SFH initiatives.

Trisnowati|Heni|H|
Kusuma|Dian|D|
Ahsan|Abdillah|A|
Kurniasih|Dwi E|DE|
Padmawati|Retna S|RS|

smoke-free home
preliminary evaluation
rural area
secondhand smoke
smoke-free environment