Effect of Toothpastes with Different Abrasives on Eroded Human Enamel: An in situ/ex vivo Study.

Abstract: The aim of the present study was to investigate the abrasive effect of CaCO3 and SiO2-based fluoride-free experimental toothpastes on eroded human permanent dental enamel and evaluate the effectiveness of waiting periods between acid exposure and tooth brushing. Twelve volunteers wore palatal appliances containing human enamel blocks for two periods of five days each. The appliances were immersed in a soft drink for five minutes four times a day (9:00 am, 11:00 am, 2:00 pm and 4:00 pm). On two occasions, two blocks were not submitted to additional treatment; two blocks were brushed (30 s) either with a CaCO3 or SiO2 toothpaste immediately after erosion and two blocks were brushed 1 h after erosion. Thus, the sample was divided into six groups: erosion alone (CaCO3 and SiO2 control); brushing with fluoride-free toothpaste (CaCO3 immediate and 1 h after erosion; SiO2 immediate and 1 h after erosion). Significant differences in wear depth were found between the enamel blocks in the CaCO3 immediate and 1 h after erosion groups and the blocks in the CaCO3 control group (p=0.001; p=0.022). No significant differences were found regarding the change in roughness and wear depth between blocks submitted to immediate abrasion and 1 h after erosion (CaCO3 and SiO2). The data revealed that surface roughness and wear depth is increased when erosion is combined with dental abrasion, regardless of the abrasive used. Waiting for 1 h to brush the eroded blocks offered no protective effect.

Ferreira|Meire Coelho|MC|
Ramos-Jorge|Maria Letícia|ML|
Delbem|Alberto Carlos Botazzo|AC|
Vieirac|Ricardo de Sousa|Rde S|

dental enamel
Carbonated beverages
tooth abrasion
tooth erosion
toothpaste.


The head fixation based on skull cap: An improved protocol used in single unit recording in the vestibular system.

Abstract: Single unit recording has an important application in neuroscience, especially in the vestibular system such as visual stabilization, posture maintenance, spatial orientation and cognition. However, single unit recording conducted in living animals is a demanding technique and non-ideal mechanical stability between the recording location of nerve tissues and the tip of microelectrode always results in failure to obtain successful recordings in the vestibular system. In order to improve the mechanical stability during single unit recording, we constructed a novel head fixation method based on skull cap. This article describes in detail how to construct this novel head fixation. Following the step-by-step procedure mentioned in this article will provide a high-quality mechanical stability for single unit recording in the vestibular system, allowing us to successfully record the nonlinear neural dynamic response over a big magnitude motion stimulation. This improvement of head fixation contributes to the in-depth understanding of the vestibular system.

Ren|Pengyu|P| Li|Bowen|B| Dong|Shiyao|S| Lyu|Boqiang|B| Gong|Shouping|S| Zhang|Qing|Q| Qu|Jianqiang|J| Han|Peng|P|

Head fixation
Skull cap
Improved protocol
Single unit recording
The vestibular system


A New Chemical Pathway Yielding A-Type Vitisins in Red Wines.

Abstract: A new chemical pathway yielding A-type vitisins in red wines is proposed herein from the reaction between anthocyanins and oxaloacetic acid (OAA). This new chemical path is thought to occur in the first stages of the wine production even during the fermentation process. This is due to the revealed high reactivity of OAA with anthocyanins compared with the already known precursor (pyruvic acid, PA). In model solutions at wine pH (3.5), when malvidin-3-O-glucoside (mv-3-glc) is in contact with OAA and PA a decrease in the OAA concentration is observed along with the formation of A-type vitisin. Moreover, part of the OAA is also chemically converted into PA in model solutions. The reaction yields were also determined for OAA and PA using different mv-3-glc:organic acid molar ratios (1:0.5, 1:1, 1:5, 1:10; 1:50, and 1:100) and these values were always higher for OAA when compared to PA, even at the lowest molar ratio (1:0.5). The reaction yields were higher at pH 2.6 in comparison to pH 1.5 and 3.5, being less affected at pH 3.5 for OAA. These results support the idea that OAA can be at the origin of A-type vitisins in the first stages of wine production and PA in the subsequent ageing process.

Araújo|Paula|P|
Fernandes|Ana|A|
de Freitas|Victor|V|
Oliveira|Joana|J|

D002851:Chromatography, High Pressure Liquid


Removal of linear alkylbenzene sulfonate (LAS) by a cetyltrimethylammonium bromide (CTAB)-aided coagulation-filtration process.

Abstract: ABSTRACTThis paper reports on the removal of linear alkylbenzene sulfonate (LAS) by conventional and cetyltrimethylammonium bromide (CTAB)-aided coagulation-filtration processes. The addition of CTAB led to the formation of CTAB-LAS aggregates, whose surface charge was negative at a CTAB-LAS molar ratio < 1 and positive at a molar ratio > 1. The efficacy of the coagulation-filtration process strongly depended on the electrostatic interactions between hydroxide floc and both free LAS and CTAB-LAS aggregate. Since free LAS is anionic, its adsorption onto the hydroxide floc was enhanced when the floc was positively charged. Ferric hydroxide floc (pH < 6.0) and aluminum hydroxide floc (pH < 7.4) showed positive surface charges and were thereby effective in removing free LAS. The optimal coagulation pH for removing the CTAB-LAS aggregate depended on the CTAB/LAS molar ratio. A higher coagulation pH was effective in removing LAS under the CTAB/LAS molar ratio > 1. However, in this case, excessive free CTAB remained after coagulation-filtration. Therefore, the lower coagulation pH with a CTAB/LAS molar ratio < 1, with the hydroxide floc and CTAB-LAS aggregate being positively and negatively charged, respectively, was recommended for LAS removal. In chemical industry wastewater, the optimal CTAB dose was higher than that in synthetic wastewater due to coexistent chemicals scavenging CTAB. Consequently, coagulation-filtration using a ferric chloride coagulant under the CTAB/LAS molar ratio of 0.7-2.0 and pH 4.5 was recommended for LAS removal from chemical industry wastewater, where the observed LAS removal efficiency reached 91 ± 3% without any deterioration of COD removal.

Coagulation
filtration
hexadecyltrimethylammonium bromide
linear-dodecylbenzene sulfonate
surface-active agent


Chronic pain, somatic unexplained complaints and multimorbidity: A mutimorbidity painful syndrome?

Abstract:
INTRODUCTION
Chronic illnesses are a major research challenge due to its implications in aging and quality of life of adults and elders, and it can be associated with chronic illnesses and other complaints. The objective of this study was to investigate the role of morbidities (chronic diseases with or without somatic unexplained symptoms) and somatic unexplained complaints in a hypothetical model of a multimorbidity painful syndrome. Our hypothesis is that chronic pain should be considered part of a syndrome that includes other chronic diseases and pathological states, especially conditions with somatic unexplained symptoms, and fibromyalgia is one of the evidence on that.

METHODS
A pilot sample of 306 subjects was investigated in this study (254; 83.0% with chronic pain). The following features were investigated: demographic data, chronic diseases (classified as with or without somatic unexplained symptoms), medications in use, pain characteristics, fulfillment of diagnostic criteria of fibromyalgia, and somatic unexplained complaints (gastric complaints, sleep disturbances, numbness, and the dry mucosa score). Statistical analysis included descriptive data, tested with chi-square, Fisher's exact, nonparametric Kolmogorov-Smirnoff, Student's t test; data normalization with Z-score; Pearson's coefficient for correlation, two-steps cluster classification, multivariate linear regression, LASSO and logistic regression.

RESULTS
Both groups of chronic diseases were more prevalent in the group of patients (p < 0.001 and p = 0.013, respectively), which had higher frequency of somatic unexplained complaints (gastrointestinal, dry mucosa and numbness) than controls. There was a high positive correlation between number of pain areas and somatic unexplained symptoms score (R2 = 0.626; p < 0.001), and diseases with these symptoms were a risk factor for chronic pain (R2 = 0.5748) and fibromyalgia (AIC = 5.8952).

CONCLUSIONS
Diseases with somatic unexplained symptoms and somatic unexplained complaints were associated with chronic pain, including fibromyalgia. They may be risks factors for pain spread. The findings support that chronic pain could be further investigated as part of a multimorbid syndrome, which should be better assessed to improve aging and quality of life of patients.

Siqueira|Silvia R D T de|SRDT|
de Siqueira|Jose Tadeu T|JTT|
Teixeira|Manoel Jacobsen|MJ|

Chronic diseases with somatic unexplained symptoms


Targeting the Hedgehog Pathway for Locally Advanced and Metastatic Basal Cell Carcinoma.

Abstract: Basal cell caricnoma (BCC), the most common periocular magliancy, is treated with complete surgical excision. However, in patients not amenable to surgery or when surgical resection means loss of vital organs or disfiguring procedures due to locally advanced or metastatic disease, targeting the hedgehog pathway offers a novel treatment approach for such patients. Mutation in PTCH1 and SMO has been identified in patients with basal cell nevoid syndrome as well as in patients with sporadic BCC. Inhibition of SMO by vismodegib or sonidegib, the two sonic hedgehog inhibitor drugs approved by the Food and Drug Administration in the United States, has shown overall response rate for locally advanced and metastatic BCC around 50%. The most common side effects were muscle cramps, weight loss, fatigue, and lost appetite. Resistance to vismodegib has been attributed to mutation in SMO or activation of RAS/MAPK pathway. New research into dual inhibition aims to overcome this resistance and provide more lasting response.

D000818:Animals
D000970:Antineoplastic Agents
D002280:Carcinoma, Basal Cell
D005134:Eye Neoplasms
D053823:Hedgehog Proteins
D006801:Humans

Hedgehog pathway
basal cell carcinoma
vismodegib
sonidegib
hedgehog inhibitors
locally advanced BCC
targeted therapy


New research with diets and epilepsy.

Abstract: The ketogenic diet is not a new treatment for the treatment of epilepsy, but the degree of literature now available seems to have given it a new lease of life. Over the past 12 years, there has been more scientific data on both benefits and effect of the ketogenic diet. Data demonstrate a clear benefit in efficacy. We also have a clearer idea in utilization, type of diet to use, and in whom. Questions however remain and further work is required, not least in recognizing likely candidates and in simplifying administration.


Molecular investigations of the bat tick Argas vespertilionis (Ixodida: Argasidae) and Babesia vesperuginis (Apicomplexa: Piroplasmida) reflect "bat connection" between Central Europe and Central Asia.

Abstract: Argas vespertilionis is a geographically widespread haematophagous ectoparasite species of bats in the Old World, with a suspected role in the transmission of Babesia vesperuginis. The aims of the present study were (1) to molecularly screen A. vespertilionis larvae (collected in Europe, Africa and Asia) for the presence of piroplasms, and (2) to analyze mitochondrial markers of A. vespertilionis larvae from Central Asia (Xinjiang Province, Northwestern China) in a phylogeographical context. Out of the 193 DNA extracts from 321 A. vespertilionis larvae, 12 contained piroplasm DNA (10 from Hungary, two from China). Sequencing showed the exclusive presence of B. vesperuginis, with 100% sequence identity between samples from Hungary and China. In addition, A. vespertilionis cytochrome oxidase c subunit 1 (cox1) and 16S rRNA gene sequences had 99.1-99.2 and 99.5-100% similarities, respectively, between Hungary and China. Accordingly, in the phylogenetic analyses A. vespertilionis from China clustered with haplotypes from Europe, and (with high support) outside the group formed by haplotypes from Southeast Asia. This is the first molecular evidence on the occurrence of B. vesperuginis in Asia. Bat ticks from hosts in Vespertilionidae contained only the DNA of B. vesperuginis (in contrast with what was reported on bat ticks from Rhinolophidae and Miniopteridae). Molecular taxonomic analyses of A. vespertilionis and B. vesperuginis suggest a genetic link of bat parasites between Central Europe and Central Asia, which is epidemiologically relevant in the context of any pathogens associated with bats.

Hornok|Sándor|S|
Szőke|Krisztina|K|
Görföl|Tamás|T|
Földvári|Gábor|G|
Tu|Vuong Tan|VT|
Takács|Nóra|N|
Kontschán|Jenő|J|
Sándor|Attila D|AD|
Estók|Péter|P|
Epis|Sara|S|
Boldogh|Sándor|S|
Kováts|Dávid|D|
Wang|Yuanzhi|Y|

Argas
Babesia
Chiroptera
Phylogeography
Soft tick


Stress velopharyngeal incompetence: Two case reports and options for diagnosis and management.

Abstract: Stress velopharyngeal incompetence (SVPI) commonly affects brass and wind musicians. We present a series of two patients who presented with nasal air emission following prolonged woodwind instrument practice. Neither patient demonstrated audible nasal air emission during speech, but endoscopy revealed localized air escape/bubbling from different sites for each patient with instrument playing only. Both underwent tailored surgical treatment with resolution of symptoms during performance. Diagnosis of SVPI requires examination during the action that induces VPI to allow for directed management. Treatment should be targeted based on nasopharyngoscopy findings.

Raol|Nikhila|N|
Diercks|Gillian|G|
Hersh|Cheryl|C|
Hartnick|Christopher J|CJ|

Velopharyngeal incompetence
VPI
Speech disorder
Stress VPI


Farnesoid X Receptor-Mediated Cytoplasmic Translocation of CRTC2 Disrupts CREB-BDNF Signaling in Hippocampal CA1 and Leads to the Development of Depression-Like Behaviors in Mice.

Abstract:
BACKGROUND
We recently identified neuronal expression of farnesoid X receptor (FXR), a bile acid receptor known to impair autophagy by inhibiting cyclic adenosine monophosphate response element-binding protein (CREB), a protein whose underfunctioning is linked to neuroplasticity and depression. In this study, we hypothesize that FXR may mediate depression via a CREB-dependent mechanism.

METHODS
Depression was induced in male C57BL6/J mice via chronic unpredictable stress (CUS). Subjects underwent behavioral testing to identify depression-like behaviors. A variety of molecular biology techniques, including viral-mediated gene transfer, Western blot, co-immunoprecipitation, and immunofluorescence, were used to correlate depression-like behaviors with underlying molecular and physiological events.

RESULTS
Overexpression of FXR, whose levels were upregulated by CUS in hippocampal CA1, induced or aggravated depression-like behaviors in stress-naïve and CUS-exposed mice, while FXR short hairpin RNA (shRNA) ameliorated such symptoms in CUS-exposed mice. The behavioral effects of FXR were found to be associated with changes in CREB-brain-derived neurotrophic factor (BDNF) signaling, as FXR overexpression aggravated CUS-induced reduction in BDNF levels while the use of FXR shRNA or disruption of FXR-CREB signaling reversed the CUS-induced reduction in the phosphorylated CREB and BDNF levels. Molecular analysis revealed that FXR shRNA prevented CUS-induced cytoplasmic translocation of CREB-regulated transcription coactivator 2 (CRTC2); CRTC2 overexpression and CRTC2 shRNA abrogated the regulatory effect of FXR overexpression or FXR shRNA on CUS-induced depression-like behaviors.

CONCLUSIONS
In stress conditions, increased FXR in the CA1 inhibits CREB by targeting CREB and driving the cytoplasmic translocation of CRTC2. Uncoupling of the FXR-CREB complex may be a novel strategy for depression treatment.

Hu|Wenfeng|W| Wu|Jingjing|J| Ye|Ting|T| Chen|Zhuo|Z| Tao|Jinhua|J| Tong|Lijuan|L| Ma|Kai|K| Wen|Jie|J| Wang|Hui|H| Huang|Chao|C|

D017362:Cyclic AMP Response Element-Binding Protein

D018160:Receptors, Cytoplasmic and Nuclear


A Comprehensive Review of the Genus Pyrola Herbs in Traditional Uses, Phytochemistry and Pharmacological Activities.

Abstract: Pyrola (Pyrolaceae), also known as Luxiancao/in China, was recorded in Sheng Nong's Herbal Classic listed in top grade. Pyrola herbs were used as medicinal plants for a long history with wide-ranging activities such as nourishing kidney-yang, strengthening muscles and bones, activating blood, stopping bleeding, dispelling rheumatism, and eliminating dampness. Currently, the research on Pyrola plants is increasing year by year but there is no comprehensive and detailed review concerning genus Pyrola. This review aims to sum up the updated and comprehensive information about botany and traditional use, phytochemistry, pharmacological activities and safety by analyzing the information available on Pyrola plants via internationally accepted scientific databases. Collectively, more than 100 compounds have been isolated from the Pyrola plants. Furthermore, a total of 33 prescriptions containing Pyrola plants are compiled in this review. Pyrola plants are used as indispensable agents in traditional Chinese medicine due to its activities of antimicrobial, anti-inflammatory, antioxidant, lipidlowering, cardiovascular and cerebrovascular protection, proliferation of osteoblasts promoting, antineoplastic and etc. Further work should be developed on the elucidation of structure-function relationship, understanding of multi-target pharmacological effects, as well as developing its application both in clinical usage and functional food for research and development of Pyrola plants.

Yang|Xiliang|X| She|Jianglian|J| Liu|Jinping|J| Yang|Tao|T| An|Gege|G| Chen|Qingru|Q| Fan|Cheng|C| Li|Shuangjun|S| Liu|Qian|Q| Qian|Chunguo|C| Liu|Ying|Y| Zhou|Yajie|Y| Zhao|Jingyi|J|

Pyrola
Phytochemistry
Pharmacological activity
Botany
Safety
Natural products
Traditional Chinese Medicine.


The role of P2X4 receptors in chronic pain: A potential pharmacological target.

Abstract: Chronic pain is a common symptom of most clinical diseases, which seriously affects the psychosomatic health of patients and brings some pain to patients. Due to its pathological mechanism is very complicated and the treatment of chronic pain has always been a difficult problem in clinical. Normally, drugs are usually used to relieve pain, but the analgesic effect is not good, especially for cancer pain patients, the analgesic effect is poor. Therefore, exploring the pathogenesis and treatment of chronic pain has aroused the interest of many researchers. A large number of studies have shown that the role of ATP and P2X4 receptor (P2X4R) play an important role in the pathogenesis of chronic pain. P2X4R is dependent on ATP ligand-gated ion channel receptor, which can be activated by ATP and plays an important role in the information transmission of nerve system and the formation of pain. Therefore, in this paper, we comprehensively described the structure and biological functions of P2X4R, and outlined behavioral evaluation methods of chronic pain models. Moreover, we also explored the inherent relationship between P2X4R and chronic pain, and described the therapeutic effect of P2X4R antagonist on chronic pain, and provided some valuable help for the treatment of chronic pain.

D058920:Purinergic P2X Receptor Antagonists

Chronic pain
Treatment
P2X4 receptor (P2X4R)
Antagonists or inhibitors: ATP


An assessment of innovative pricing schemes for the communication of value: is price discrimination and two-part pricing a way forward?

Abstract:
INTRODUCTION
With the introduction of new expensive medicines, traditional pricing schemes based on constructs such as price per pill/vial have been challenged. Potential innovative schemes could be either financial-based or performance-based. Within financial-based schemes the use of price discrimination is an emerging option, which we explore in this assessment.

AREAS COVERED
In the short term the price per indication approach is likely to become more prevalent for high cost, high benefit new pharmaceuticals, such as those emerging in oncology (e.g. new combination immunotherapies). 'Two-Part Pricing' (2PP) is a frequently used payment method in other industries, which consists of an Entry Fee, giving the buyer the right to use the product, and a Usage Price charged every time the product is purchased. Introducing 2PP into biopharma could have cross-stakeholder benefits including broader patient access, and improvement in budget/revenue predictability. A concern however is the potential complexity of the negotiation between manufacturer and payer.

EXPERT COMMENTARY
We believe 'price discrimination' and 2PP in particular can be relevant for some new, expensive specialist medicines. A recommended first step would be to initiate pilots to test to what degree the 2PP approach meets stakeholder objectives and is practical to implement within specialty care.

Innovative pricing
pricing scheme
price discrimination
two-part pricing
2PP
biopharma
pharmacoeconomics


Restaging the Biochemical Recurrence of Prostate Cancer with [68Ga]Ga-PSMA-11 PET/CT: Diagnostic Performance and Impact on Patient Disease Management.

Abstract:
BACKGROUND
Detection rates of [68Ga]Ga-PSMA-11 PET/CT on the restaging of prostate cancer (PCa) patients presenting with biochemical recurrence (BCR) have been well documented, but its performance and impact on patient management have not been evaluated as extensively.

METHODS
Retrospective analysis of PCa patients presenting with BCR and referred for [68Ga]Ga-PSMA-11 PET/CT. Pathological foci were classified according to six anatomical sites and evaluated with a three-point scale according to the uptake intensity. The impact of [68Ga]Ga-PSMA-11 PET/CT was defined as any change in management that was triggered by [68Ga]Ga-PSMA-11 PET/CT. The existence of a PCa lesion was established according to a composite standard of truth based on all clinical data available collected during the follow-up period.

RESULTS
We included 294 patients. The detection rate was 69%. Per-patient sensitivity and specificity were both 70%. Patient disease management was changed in 68% of patients, and [68Ga]Ga-PSMA-11 PET/CT impacted this change in 86% of patients. The treatment carried out on patient was considered effective in 89% of patients when guided by [68Ga]Ga-PSMA-11 PET/CT versus 61% of patients when not guided by [68Ga]Ga-PSMA-11 PET/CT (p < 0.001).

CONCLUSIONS
[68Ga]Ga-PSMA-11 PET/CT demonstrated high performance in locating PCa recurrence sites and impacted therapeutic management in nearly two out of three patients.

Fourquet|Aloÿse|A|0000-0002-9013-5085
Lahmi|Lucien|L|
Rusu|Timofei|T|
Belkacemi|Yazid|Y|
Créhange|Gilles|G|
de la Taille|Alexandre|A|
Fournier|Georges|G|
Cussenot|Olivier|O|
Gauthé|Mathieu|M|0000-0002-4882-9366

decision making
positron-emission tomography
prostatic neoplasms


Teaching the basics of autophagy and mitophagy to redox biologists--mechanisms and experimental approaches.

Abstract: Autophagy is a lysosomal mediated degradation activity providing an essential mechanism for recycling cellular constituents, and clearance of excess or damaged lipids, proteins and organelles. Autophagy involves more than 30 proteins and is regulated by nutrient availability, and various stress sensing signaling pathways. This article provides an overview of the mechanisms and regulation of autophagy, its role in health and diseases, and methods for its measurement. Hopefully this teaching review together with the graphic illustrations will be helpful for instructors teaching graduate students who are interested in grasping the concepts and major research areas and introducing recent developments in the field.

Aging
Beclin
LC3
Mitochondria
Neurodegenerative diseases
mTOR


Graphene-Based Nanomaterials in Soil: Ecotoxicity Assessment Using Enchytraeus crypticus Reduced Full Life Cycle.

Abstract: Graphene-based nanomaterials (GBNs) possess unique physicochemical properties, allowing a wide range of applications in physical, chemical, and biomedical fields. Although GBNs are broadly used, information about their adverse effects on ecosystem health, especially in the terrestrial environment, is limited. Therefore, this study aims to assess the toxicity of two commonly used derivatives of GBNs, graphene oxide (GO) and reduced graphene oxide (rGO), in the soil invertebrate Enchytraeus crypticus using a reduced full life cycle test. At higher exposure concentrations, GO induced high mortality and severe impairment in the reproduction rate, while rGO showed little adverse effect up to 1000 mg/kg. Collectively, our body of results suggests that the degree of oxidation of GO correlates with their toxic effects on E. crypticus, which argues against generalization on GBNs ecotoxicity. Identifying the key factors affecting the toxicity of GBNs, including ecotoxicity, is urgent for the design of safe GBNs for commercial purposes.

terrestrial environment
graphene oxide
reduced graphene oxide
reproduction
hatching success
survival


A study of the prevalence of osteoporosis and hypovitaminosis D in patients with primary knee osteoarthritis.

Abstract:
INTRODUCTION
Osteoarthritis and Osteoporosis are highly prevalent disease, so is hypovitaminosis D. We tried to find out prevalence of osteoporosis and hypovitaminosis D in patients suffering from primary knee Osteoarthritis. We also compared the prevalence of oseotoporosis between general population and patients of primary osteoarthritis.

METHODS
Patients suffering from primary knee OA were taken from Rheumatology OPD of Medical College Hospital and SSKM Hospital Kolkata, India. For each patient age and sex matched friend or relative of same locality was taken in the study as controls. Hospital staffs that come from different part of state was taken in the study as controls. The control population was the representative of general population.

RESULTS
Total number of participants in this study was 206. Out of which there were 98 cases and 108 controls. BMD status correlates significantly with Primary OA. Serum Vitamin D3 status correlates significantly with Osteoarthritis. Age of the patients correlated significantly with both BMD Status and Knee OA but not with the vVitamin D level. There were significant correlation between the Serum Vitamin D3 status and BMD of the subjects.

CONCLUSION
Osteoporosis is prevalent both in general population and patients suffering from Knee Osteoarthritis and may increase the disability. The matter is complicated by the fact hypovitaminosis D is also prevalent in the population and positively correlated with both Osteoporosis and osteoarthrosis, though we cannot comment on further pathogenesis because of cross sectional design of the study.

Ghosh|Biswadip|B| Pal|Tanmoy|T| Ganguly|Satyabrata|S| Ghosh|Alakendu|A|

Osteoporosis
Hypovitaminosis D
Knee osteoarthitis


Interaction between the learners' initial grasp of the object of learning and the learning resource afforded.

Abstract: Two studies are reported in this paper. The object of learning in both is the economic principle of changes in price as a function of changes in the relative magnitude of changes in demand and supply. The patterns of variation and invariance, defining the conditions compared were built into pedagogical tools (text, graphs, and worksheets). The first study is the latest in a series of studies aiming to test the fundamental conjecture of the Variation Theory of Learning that new meanings are acquired from experiencing differences against a background of sameness, rather than experiencing sameness against a background of differences. The study compares the learning outcomes under conditions consistent with the basic conjecture with the learning outcomes under conditions not consistent with the theory. The results support the conjecture. The second study shows, however, that the conditions that are consistent with the theory cannot be decided unless the learners' pre-requisites for the task in question are taken into consideration. One set of the pedagogical tools was found to be highly effective for learners with a better initial grasp of the object of learning, while another set was found to be equally effective for learners with a weaker initial grasp of the object of learning. The two sets were equally ineffective when used for the "wrong" group of learners.

Variation theory
Learning study
Phenomenography


Integrated in Silico and Experimental Approach towards the Design of a Novel Recombinant Protein Containing an Anti-HER2 scFv.

Abstract: Biological therapies, such as recombinant proteins, are nowadays amongst the most promising approaches towards precision medicine. One of the most innovative methodologies currently available aimed at improving the production yield of recombinant proteins with minimization of costs relies on the combination of in silico studies to predict and deepen the understanding of the modified proteins with an experimental approach. The work described herein aims at the design and production of a biomimetic vector containing the single-chain variable domain fragment (scFv) of an anti-HER2 antibody fragment as a targeting motif fused with HIV gp41. Molecular modeling and docking studies were performed to develop the recombinant protein sequence. Subsequently, the DNA plasmid was produced and HEK-293T cells were transfected to evaluate the designed vector. The obtained results demonstrated that the plasmid construction is robust and can be expressed in the selected cell line. The multidisciplinary integrated in silico and experimental strategy adopted for the construction of a recombinant protein which can be used in HER2+-targeted therapy paves the way towards the production of other therapeutic proteins in a more cost-effective way.

D003198:Computer Simulation
D005822:Genetic Vectors
D057809:HEK293 Cells
D015700:HIV Envelope Protein gp41
D006801:Humans
D062105:Molecular Docking Simulation
D015202:Protein Engineering
D011994:Recombinant Proteins
D057127:Single-Chain Antibodies
D000068878:Trastuzumab

human epidermal growth factor receptor 2


Pathological findings at radical prostatectomy of biopsy naïve men diagnosed with MRI targeted biopsy alone without concomitant standard systematic sampling.

Abstract:
OBJECTIVES
To test international society of urological pathology grade group (ISUP GG) concordance rates between multiparametric magnetic resonance imaging (mpMRI) targeted biopsies (TB) vs. standard systematic biopsies (SB) and radical prostatectomy (RP) specimens, in biopsy naïve patients.

MATERIALS AND METHODS
This retrospective single center study included 80 vs. 500 biopsy naïve patients diagnosed with TB vs. SB and treated with RP between 2015 and 2018. First, we compared ISUP GG concordance rates and the percentages of undetected clinically significant prostate cancer (csPCa: ISUP GG  ≥ 3), between TB vs. SB and RP. Second, multivariable logistic regression models tested predictors of concordance rates before and after 1:3 propensity score (PS) matching. Third, among TB patients, univariable logistic regression models tested variables associated with ISUP GG concordance at RP.

RESULTS
Overall, ISUP GG concordance rates were, respectively, 55 vs. 41.4% for TB vs. SB (P = 0.02). However, no differences in concordance rates were observed in patients with biopsy ISUP GG1 (31 vs. 33.9% for TB vs. SB; P = 0.8). Moreover, 15 vs. 18.8% csPCa were missed by TB vs. SB, respectively (P = 0.4). In multivariable logistic regression models, TB were associated with higher concordance rates before (odds ratio [OR]: 1.13; P = 0.04) and after 1:3 PS matching (OR: 1.15; P 0.03), compared to SB. In TB patients, age (OR: 0.98; P = 0.04), maximum cancer core involvement (MCCI; OR: 1.02; P = 0.02) and maximum cancer core length (MCCL; OR: 1.01; P = 0.07) were associated with ISUP GG concordance. Moreover, a trend for lower concordance rates was observed with higher PSA-D (OR: 0.77; P = 0.1). Finally, intermediate lesion location at mpMRI was associated with lowest concordance rates (44%).

CONCLUSION
In biopsy naïve patients treated with RP, TB achieved higher rates of ISUP GG concordance, but same percentages of csPCa missed, compared to SB. Moreover, only patients with ISUP GG ≥2, but not patients with ISUP GG1, exhibited higher concordance rates. Finally, age, MCCI, MCCL, PSA-D, and lesion location were associated with concordance between TB and RP.

Luzzago|Stefano|S|
Petralia|Giuseppe|G|
Maresca|Duilia|D|
Sabatini|Ilaria|I|
Cordima|Giovanni|G|
Brescia|Antonio|A|
Verweij|Fabrizio|F|
Garelli|Giulia|G|
Mistretta|Francesco A|FA|
Cioffi|Antonio|A|
Pricolo|Paola|P|
Alessi|Sarah|S|
Ferro|Matteo|M|
Matei|Deliu-Victor|DV|
Renne|Giuseppe|G|
de Cobelli|Ottavio|O|
Musi|Gennaro|G|

D000081364:Multiparametric Magnetic Resonance Imaging

Multiparametric magnetic resonance imaging


Neuropsychiatric symptoms and the outcome of cognitive trajectories in older adults free of dementia: The Mayo Clinic Study of Aging.

Abstract:
OBJECTIVE
Neuropsychiatric symptoms (NPS) are associated with the risk of incident mild cognitive impairment (MCI) and dementia. We examined associations between NPS and the outcomes of global and domain-specific cognitive trajectories.

METHODS
In this longitudinal study conducted in the setting of the population-based Mayo Clinic Study of Aging, 5081 community-dwelling, nondemented individuals aged ≥50 years (51% males) underwent NPS assessment using Neuropsychiatric Inventory Questionnaire (NPI-Q), and Beck Depression and Anxiety Inventories (BDI-II, BAI). Global and domain-specific (memory, language, attention, and visuospatial skills) cognitive performance was assessed through neuropsychological testing every 15 months. Associations between baseline NPS and trajectories for individual yearly change in cognitive z-scores were calculated using linear mixed-effect models.

RESULTS
Cognition declined regardless of NPS status over the median follow-up of 4.5 years. Presence of NPS was associated with increased cognitive decline. Differences in annualized change in global cognition z-scores for participants with NPS compared to without NPS ranged from -0.018 (95% CI -0.032, -0.004; p = 0.011) for irritability to -0.159 (-0.254, -0.065; p = 0.001) for hallucinations. Associations between NPS and annual decline in global cognition were significant for most NPI-Q-assessed NPS and clinical depression (BDI-II≥13). Participants with NPI-Q-assessed depression, apathy, nighttime behavior, and clinical depression had greater decline in all domain-specific z-scores; presence of delusions and anxiety was associated with more pronounced decline in language, attention and visuospatial skills.

CONCLUSION
NPS were associated with a more accelerated cognitive decline. Clinical assessment and potential treatment of NPS is warranted even in a community setting as NPS may impact cognitive decline in nondemented individuals.

Krell-Roesch|Janina|J|
Syrjanen|Jeremy A|JA|
Machulda|Mary M|MM|
Christianson|Teresa J|TJ|
Kremers|Walter K|WK|
Mielke|Michelle M|MM|
Knopman|David S|DS|
Petersen|Ronald C|RC|
Vassilaki|Maria|M|
Geda|Yonas E|YE|0000-0003-1187-7230

neuropsychiatric symptoms
cognitive trajectory
older adults
longitudinal study
nondemented


Capillary electrophoresis method for analysis of inorganic and organic anions related to habitability and the search for life.

Abstract: In situ missions of exploration require analytical methods that are capable of detecting a wide range of molecular targets in complex matrices without a priori assumptions of sample composition. Furthermore, these methods should minimize the number of reagents needed and any sample preparation steps. We have developed a method for the detection of metabolically relevant inorganic and organic anions that is suitable for implementation on in situ spaceflight missions. Using 55 mM acetic acid, 50 mM triethylamine, and 5% glycerol, more than 21 relevant anions are separated in less than 20 min. The method is robust to sample ionic strength, tolerating high concentrations of background salts (up to 900 mM NaCl and 300 mM MgSO4 ). This is an important feature for future missions to ocean worlds. The method was validated using a culture of Escherichia coli and with high salinity natural samples collected from Mono Lake, California.

Astrobiology
Biosignatures
Carboxylic acids
Contactless conductivity detection
High salinity samples


Differentiation of human pluripotent stem cells to brain microvascular endothelial cell-like cells suitable to study immune cell interactions.

Abstract: We describe the extended endothelial cell culture method (EECM) for the differentiation of human pluripotent stem cells (hPSCs) into brain microvascular endothelial cell (BMEC)-like cells. EECM-BMEC-like cells resemble primary human BMECs in morphology, molecular junctional architecture, and diffusion barrier characteristics. A mature immune phenotype with proper endothelial adhesion molecule expression makes this model distinct from any other hPSC-derived in vitro blood-brain barrier (BBB) model and suitable to study immune cell migration across the BBB in a disease relevant and personalized fashion. For complete details on the use and execution of this protocol, please refer to Lian et al. (2014), Nishihara et al. (2020a).

Nishihara|Hideaki|H|
Gastfriend|Benjamin D|BD|
Kasap|Pelin|P|
Palecek|Sean P|SP|
Shusta|Eric V|EV|
Engelhardt|Britta|B|

Stem Cells
Cell culture
Cell Differentiation
Immunology
Neuroscience


A targeted and adjuvanted nanocarrier lowers the effective dose of liposomal amphotericin B and enhances adaptive immunity in murine cutaneous leishmaniasis.

Abstract:
BACKGROUND
Amphotericin B (AmB), the most effective drug against leishmaniasis, has serious toxicity. As Leishmania species are obligate intracellular parasites of antigen presenting cells (APC), an immunopotentiating APC-specific AmB nanocarrier would be ideally suited to reduce the drug dosage and regimen requirements in leishmaniasis treatment. Here, we report a nanocarrier that results in effective treatment shortening of cutaneous leishmaniasis in a mouse model, while also enhancing L. major specific T-cell immune responses in the infected host.

METHODS
We used a Pan-DR-binding epitope (PADRE)-derivatized-dendrimer (PDD), complexed with liposomal amphotericin B (LAmB) in an L. major mouse model and analyzed the therapeutic efficacy of low-dose PDD/LAmB vs full dose LAmB.

RESULTS
PDD was shown to escort LAmB to APCs in vivo, enhanced the drug efficacy by 83% and drug APC targeting by 10-fold and significantly reduced parasite burden and toxicity. Fortuitously, the PDD immunopotentiating effect significantly enhanced parasite-specific T-cell responses in immunocompetent infected mice.

CONCLUSIONS
PDD reduced the effective dose and toxicity of LAmB and resulted in elicitation of strong parasite specific T-cell responses. A reduced effective therapeutic dose was achieved by selective LAmB delivery to APC, bypassing bystander cells, reducing toxicity and inducing antiparasite immunity.

Daftarian|Pirouz M|PM|
Stone|Geoffrey W|GW|
Kovalski|Leticia|L|
Kumar|Manoj|M|
Vosoughi|Aram|A|
Urbieta|Maitee|M|
Blackwelder|Pat|P|
Dikici|Emre|E|
Serafini|Paolo|P|
Duffort|Stephanie|S|
Boodoo|Richard|R|
Rodríguez-Cortés|Alhelí|A|
Lemmon|Vance|V|
Deo|Sapna|S|
Alberola|Jordi|J|
Perez|Victor L|VL|
Daunert|Sylvia|S|
Ager|Arba L|AL|

nanocarrier
leishmaniasis
obligate intracellular parasites
intracellular
adoptive immunity
immunochemotherapy
vaccine


Ex Vivo Expansion of Adult Hematopoietic Stem and Progenitor Cells with Valproic Acid.

Abstract: Umbilical cord blood (UCB) units provide an alternative source of human hematopoietic stem cells (HSCs) for patients who require allogeneic stem cell transplantation but lack a matched donor. However, the limited number of HSCs within each UCB unit remains a major challenge for their use in regenerative medicine and HSC transplantation in adults. Efficient expansion of human HSCs in ex vivo cultures initiated with CD34+ cells isolated from UCBs can overcome this limitation. The method described here utilizes a deacetylase inhibitor, valproic acid (VPA), to rapidly expand to a high degree the numbers of functional HSCs and committed progenitors (HPCs). The expanded HSCs are capable of establishing both short-term and long-term multilineage hematopoietic reconstitution. This highly reproducible and simple protocol can be also applied to expansion of both HSCs and HPCs from different sources including the bone marrow and peripheral blood.

Papa|Luena|L| Djedaini|Mansour|M| Kintali|Manisha|M| Schaniel|Christoph|C| Hoffman|Ronald|R|

D053687:Adult Stem Cells
D018929:Cell Culture Techniques
D002478:Cells, Cultured
D006412:Hematopoietic Stem Cells
D006801:Humans
D014635:Valproic Acid

Ex vivo expansion
Umbilical cord blood (UCB)
Hematopoietic stem cells (HSCs)
Valproic acid (VPA)
Cryopreservation
Hematopoietic progenitor cells (HPCs)


Electrophysiological correlates of fearful and sad distraction on target processing in adolescents with attention deficit-hyperactivity symptoms and affective disorders.

Abstract: In this study we used event-related brain potentials (ERP) as neural markers of cognitive operations to examine emotion and attentional processing in a population of high-risk adolescents with mental health problems that included attention deficit and hyperactivity disorder (ADHD), anxiety, and depression. We included a healthy control group for comparison purposes, and employed a modified version of the emotional oddball paradigm, consisting of frequent distracters (scrambled pictures), infrequent distracters (sad, fearful, and neutral pictures), and infrequent targets (circles). Participants were instructed to make a right hand button press to targets and a left hand button press to all other stimuli. EEG/ERP recordings were taken using a high-density 256-channel recording system. Behavioral data showed that for both clinical and non-clinical adolescents, reaction time (RT) was slowest in response to the fearful images. Electrophysiological data differentiated emotion and target processing between clinical and non-clinical adolescents. In the clinical group we observed a larger P100 and late positive potential (LPP) in response to fearful compared to sad or neutral pictures. There were no differences in these ERPs in the healthy sample. Emotional modulation of target processing was also identified in the clinical sample, where we observed an increase in P300 amplitude, and a larger sustained LPP in response to targets that followed emotional pictures (fear and sad) compared to targets that followed neutral pictures or other targets. There were no differences in these target ERPs for the healthy participants. Taken together, we suggest that these data provide important and novel evidence of affective and attention dysfunction in this clinical population of adolescents, and offer an example of the disruptive effects of emotional reactivity on basic cognition.

Singhal|Anthony|A|
Shafer|Andrea T|AT|
Russell|Matthew|M|
Gibson|Bridget|B|
Wang|Lihong|L|
Vohra|Sunita|S|
Dolcos|Florin|F|

adolescents
attention
emotion
ADHD
anxiety
depression
event-related potentials


Upregulation of AMPK Ameliorates Alzheimer's Disease-Like Tau Pathology and Memory Impairment.

Abstract: The studies have shown that 5'-adenosine monophosphate (AMP)-activated protein kinase (AMPK) is involved in Alzheimer's disease (AD) pathology, but the effects of AMPK on AD-like Tau abnormal phosphorylation and its underlying mechanism remains unclear. Herein, we found that the mRNA expression and activity of AMPK are significantly decreased in the brains of the aging C57 mice and 3 × Tg AD mice when compared with their respective control. Moreover, when downregulation of AMPK with AAV-siAMPK-eGFP in the hippocampus CA3 of 3-month-old C57 mice, the mice display AD-like Tau hyperphosphorylation, fear memory impairment, and glycogen synthase kinase-3β (GSK3β) activity increased. On the other hand, there are also AD-like Tau hyperphosphorylation, impairment of fear memory, and AMPK activity decreased in streptozotocin (STZ) mice. Interestingly, AMPK overexpression could efficiently rescue AD-like Tau phosphorylation and brain impairment in STZ mice. Moreover, the activity of GSK3β and the level of Tau phosphorylation (Ser396 and Thr231 sites) were significantly decreased in HEK293 Tau cells transfected by AMPK plasmid or treated with agonists salicylate (SS), but GSK3β agonists Wortmannin (Wort) could ablate AMPK-mediated Tau dephosphorylation. Taken together, the study indicated that AMPK reduces Tau phosphorylation and improves brain function and inhibits GSK3β in AD-like model. These findings proved that AMPK might be a new target for AD in the future.


Bone Regeneration Improves with Mesenchymal Stem Cell Derived Extracellular Vesicles (EVs) Combined with Scaffolds: A Systematic Review.

Abstract: Scaffolds associated with mesenchymal stem cell (MSC) derivatives, such as extracellular vesicles (EVs), represent interesting carriers for bone regeneration. This systematic review aims to analyze in vitro and in vivo studies that report the effects of EVs combined with scaffolds in bone regeneration. A methodical review of the literature was performed from PubMed and Embase from 2012 to 2020. Sixteen papers were analyzed; of these, one study was in vitro, eleven were in vivo, and four were both in vitro and in vivo studies. This analysis shows a growing interest in this upcoming field, with overall positive results. In vitro results were demonstrated as both an effect on bone mineralization and proangiogenic ability. The interesting in vitro outcomes were confirmed in vivo. Particularly, these studies showed positive effects on bone regeneration and mineralization, activation of the pathway for bone regeneration, induction of vascularization, and modulation of inflammation. However, several aspects remain to be elucidated, such as the concentration of EVs to use in clinic for bone-related applications and the definition of the real advantages.

bone regeneration
mesenchymal stem cell
extracellular vesicles
scaffolds
angiogenesis
exosome
hydrogels
tissue inflammation


Defining phenotypic and functional heterogeneity of glioblastoma stem cells by mass cytometry.

Abstract: Most patients with glioblastoma (GBM) die within 2 years. A major therapeutic goal is to target GBM stem cells (GSCs), a subpopulation of cells that contribute to treatment resistance and recurrence. Since their discovery in 2003, GSCs have been isolated using single-surface markers, such as CD15, CD44, CD133, and α6 integrin. It remains unknown how these single-surface marker-defined GSC populations compare with each other in terms of signaling and function and whether expression of different combinations of these markers is associated with different functional capacity. Using mass cytometry and fresh operating room specimens, we found 15 distinct GSC subpopulations in patients, and they differed in their MEK/ERK, WNT, and AKT pathway activation status. Once in culture, some subpopulations were lost and previously undetectable ones materialized. GSCs that highly expressed all 4 surface markers had the greatest self-renewal capacity, WNT inhibitor sensitivity, and in vivo tumorigenicity. This work highlights the potential signaling and phenotypic diversity of GSCs. Larger patient sample sizes and antibody panels are required to confirm these findings.

Galdieri|Luciano|L|
Jash|Arijita|A|
Malkova|Olga|O|
Mao|Diane D|DD|
DeSouza|Patrick|P|
Chu|Yunli E|YE|
Salter|Amber|A|
Campian|Jian L|JL|
Naegle|Kristen M|KM|
Brennan|Cameron W|CW|
Wakimoto|Hiroaki|H|
Oh|Stephen T|ST|
Kim|Albert H|AH|
Chheda|Milan G|MG|


TACR3 mutations disrupt NK3R function through distinct mechanisms in GnRH-deficient patients.

Abstract: Neurokinin B (NKB) and its G-protein-coupled receptor, NK3R, have been implicated in the neuroendocrine control of GnRH release; however, little is known about the structure-function relationship of this ligand-receptor pair. Moreover, loss-of-function NK3R mutations cause GnRH deficiency in humans. Using missense mutations in NK3R we previously identified in patients with GnRH deficiency, we demonstrate that Y256H and Y315C NK3R mutations in the fifth and sixth transmembrane domains (TM5 and TM6), resulted in reduced whole-cell (79.3±7.2%) or plasma membrane (67.3±7.3%) levels, respectively, compared with wild-type (WT) NK3R, with near complete loss of inositol phosphate (IP) signaling, implicating these domains in receptor trafficking, processing, and/or stability. We further demonstrate in a FRET-based assay that R295S NK3R, in the third intracellular loop (IL3), bound NKB but impaired dissociation of Gq-protein subunits from the receptor compared with WT NK3R, which showed a 10.0 ± 1.3% reduction in FRET ratios following ligand binding, indicating activation of Gq-protein signaling. Interestingly, R295S NK3R, identified in the heterozygous state in a GnRH-deficient patient, also interfered with dissociation of G proteins and IP signaling from wild-type NK3R, indicative of dominant-negative effects. Collectively, our data illustrate roles for TM5 and TM6 in NK3R trafficking and ligand binding and for IL3 in NK3R signaling.

Noel|Sekoni D|SD|
Abreu|Ana Paula|AP|
Xu|Shuyun|S|
Muyide|Titilayo|T|
Gianetti|Elena|E|
Tusset|Cintia|C|
Carroll|Jessica|J|
Latronico|Ana Claudia|AC|
Seminara|Stephanie B|SB|
Carroll|Rona S|RS|
Kaiser|Ursula B|UB|

D048049:Extracellular Signal-Regulated MAP Kinases

D031541:Fluorescence Resonance Energy Transfer

D043802:GTP-Binding Protein alpha Subunits, Gq-G11

neurokinin B
GPCR
hypogonadotropic hypogonadism
tachykinins


Sleep in mothers of children with epilepsy and its relation to their children's sleep.

Abstract: We conducted a cross-sectional study to examine sleep in mothers of children with epilepsy and its relation to their children's sleep. A total of 133 dyads of mothers and children with epilepsy aged 1.5-6 years were recruited between 2015 and 2018 from a children's hospital in northern Taiwan. Participating families provided demographic and health information, with children wearing an actigraphy monitor for 7 days and mothers completing sleep and depressive mood questionnaires. We found that 76 (57.1%) of the mothers had poor sleep quality, with 65 (48.9%) mothers having a clinically significant depressive symptom score. Mean actigraphic wake after sleep onset in children was 1.42 (standard deviation = 0.51) hours, with 126 (94.7%) of the children having a clinically significant sleep disturbance score. Multivariate regression analyses showed that higher depressive symptom scores in mothers (β = 0.14; p < .01) and higher sleep disturbance scores in children (β = 0.07; p = .04) were associated with poorer maternal sleep quality, even when maternal demographic characteristics and the child's clinical and epilepsy variables were considered. Findings from our study suggest that sleep disturbances are a shared problem for mothers and their children with epilepsy. Sleep in both mothers and their children with epilepsy should be evaluated in pediatric neurologic practices, with maternal depressive symptoms screened concurrently. Future pediatric epilepsy studies are warranted to examine whether a family-based intervention program would be effective to improve sleep in mother-child dyads and to promote better health and functioning of the entire family.

Tsai|Shao-Yu|SY|0000-0002-2874-5202 Lee|Wang-Tso|WT| Lee|Chien-Chang|CC| Jeng|Suh-Fang|SF| Weng|Wen-Chin|WC|

D007722:Health Knowledge, Attitudes, Practice

sleep mother children epilepsy actigraphy depression nursing


Species delimitation and systematics of the green pythons (Morelia viridis complex) of melanesia and Australia.

Abstract: Molecular data sets and the increasing use of integrative systematics is revealing cryptic diversity in a range of taxa - particularly in remote and poorly sampled landscapes like the island of New Guinea. Green pythons (Morelia viridis complex) are one of the most conspicuous elements of this island's fauna, with large numbers taken from the wild to supply international demand for exotic pets. We test hypotheses about species boundaries in green pythons from across New Guinea and Australia with mitochondrial genomes, 389 nuclear exons, and comprehensive assessment of morphological variation. Strong genetic structuring of green python populations and species delimitation methods confirm the presence of two species, broadly occurring north and south of New Guinea's central mountains. Our data also support three subspecies within the northern species. Subtle but consistent morphological divergence among the putative taxa is concordant with patterns of molecular divergence. Our extensive sampling identifies several zones of hitherto unknown biogeographical significance on the island of New Guinea. We revise the taxonomy of the group, discuss the relevance of our findings in the context of Papuan biogeography and the implications of our systematic changes for the conservation management of these taxa.

Natusch|Daniel J D|DJD|
Esquerré|Damien|D|
Lyons|Jessica A|JA|
Hamidy|Amir|A|
Lemmon|Alan R|AR|
Moriarty Lemmon|Emily|E|
Riyanto|Awal|A|
Keogh|J Scott|JS|
Donnellan|Stephen|S|

Cryptic diversity
New Guinea
Biogeography
CITES
Chondropython
Indonesia
Papua


Social Determinants of Health and Oral Cavity Cancer Treatment and Survival: A Competing Risk Analysis.

Abstract:
OBJECTIVE
Competing risk analysis is a powerful assessment for cancer risk factors and covariates. This method can better elucidate insurance status and other social determinants of health covariates in oral cavity cancer treatment, survival, and disparities.

STUDY DESIGN
Retrospective cohort study using the Surveillance, Epidemiology, and End Results (SEER) database.

METHODS
Data regarding patient characteristics, clinical stage at diagnosis, treatment, and survival data for 20,271 patients diagnosed with oral cavity cancer was extracted from the SEER 18 Regs Research Data including Hurricane Katrina Impacted Louisiana Cases from 1973 to 2014. All statistical analyses were performed using SAS 9.5 (SAS Institute Inc., Cary, NC). The Fine-Gray method for assessing impact, risk, and covariates was employed.

RESULTS
Medicaid patients presented with later stage disease, larger tumor size, more distant metastases, and more lymph node involvement at diagnosis compared to insured patients. Medicaid patients were less likely to receive cancer-directed surgery. Medicaid status was also associated with worse cancer-specific survival (subhazard ratios 1.87, 95% confidence interval 1.72-2.04, P < .0001) after adjustment for all covariates.

CONCLUSION
This is the first study examining specifically how Medicaid status and social determinants of health covariates impact oral cavity cancer treatment and outcomes and is the first using methods validated for complex covariates. Patients with Medicaid present with more extensive oral cavity disease burden are less likely to receive definitive therapy and have significantly worse overall survival than those with other forms of insurance. This better identifies disparities and the need for improving health literacy, specifically for the at-risk Medicaid population, and can guide clinicians.

LEVEL OF EVIDENCE
NA Laryngoscope, 130:2160-2165, 2020.

Agarwal|Pratima|P|0000-0002-6502-9045
Agrawal|Ravi R|RR|
Jones|Eric A|EA|
Devaiah|Anand K|AK|0000-0002-4375-0421

social determinants of health
Oral cavity cancer
healthcare disparities
insurance, socioeconomic


Gross anatomy and histology of the olfactory rosette of the shark Heptranchias perlo.

Abstract: Sharks belonging to the family Hexanchidae have six or seven gill slits, unlike all other elasmobranchs, which have five gill slits. Their olfactory organs have a round shape, which is common for holocephalans, but not for elasmobranchs. Thus, the shape of the olfactory organ represents a further, less striking, peculiarity of this family among elasmobranchs. Despite that, the microscopic anatomy and histology of the olfactory organ have not yet been studied in any species of this family. Here, an anatomical and histological description of the olfactory organ of the sharpnose sevengill shark Heptranchias perlo is given. The organ is a rosette, with a central raphe and 31-34 primary lamellae, which bear secondary lamellae with a more or less branched shape. The elastic connective capsule which envelops the olfactory rosette possibly changes its shape along with water influx. In the olfactory epithelium, the supporting cells also have a secretory function, while no specialized mucous cells are visible; regarding this feature the olfactory epithelium of H. perlo differs from that of other chondrichthyan species. The immunohistochemical investigation of the sensory epithelium shows the absence of immunoreactivity for Gαolf in receptor neurons, which confirms previous observations in Chondrichthyes.

Ferrando|Sara|S|
Gallus|Lorenzo|L|
Amaroli|Andrea|A|
Gambardella|Chiara|C|
Waryani|Baradi|B|
Di Blasi|Davide|D|
Vacchi|Marino|M|

Hexanchidae
Sharpnose sevengill shark
Chondrichthyes
Olfaction


Spontaneous regression of squamous cell carcinoma in the setting of dental infection and needle biopsy.

Abstract: To our knowledge, this is the first reported case of spontaneous regression of squamous cell carcinoma within a lymph node. We speculate that prior dental infection, fever, and biopsy incited an antitumor immune reaction.

spontaneous regression
squamous cell carcinoma
dental infection
fine needle aspiration


A physiological characterization in controlled bioreactors reveals a novel survival strategy for Debaryomyces hansenii at high salinity.

Abstract: Debaryomyces hansenii is traditionally described as a halotolerant non-conventional yeast and has served as a model organism for the study of osmotolerance and salt tolerance mechanisms in eukaryotic systems for the past 30 years. However, unraveling of D. hansenii's biotechnological potential has always been difficult due to the persistent limitations in the availability of efficient molecular tools described for this yeast. Additionally, there is a lack of consensus and contradictory information along the recent years that limits a comprehensive understanding of its central carbon metabolism, mainly due to a lack of physiological studies in controlled and monitored environments. Moreover, there is little consistency in the culture conditions (media composition, temperature, and pH among others) used by different groups, which makes it complicated when trying to get prevalent conclusions on behavioral patterns. In this work, we present for the first time a characterization of D. hansenii in batch cultivations using highly controlled lab-scale bioreactors. Our findings contribute to a more complete picture of the central carbon metabolism and the external pH influence on the yeast's ability to tolerate high Na+ and K+ concentrations, pointing to a differential effect of both salts, as well as a positive effect in cell performance when low environmental pH values are combined with a high sodium concentration in the media. Finally, a novel survival strategy at very high salinity (2 M) is proposed for this yeast, as well as potential outcomes for its use in industrial biotechnology applications. TAKE AWAY: High salt concentrations stimulate respiration in Debaryomyces hansenii. Sodium exerts a stronger positive impact on cell performance than potassium. μmax is higher at a combination of low pH, high salt, and high temperature. Concentrations of 2 M salt result in slower growth but increased biomass yield. The positive effect of salts is enhanced at low glucose concentration.

Navarrete|Clara|C|
Frost|August T|AT|
Ramos-Moreno|Laura|L|
Krum|Mette R|MR|
Martínez|José L|JL|0000-0002-4490-8534

bioreactors
Debaryomyces hansenii
non-conventional yeast
salt tolerance
batch fermentation
osmotic stress


Economic cost and quality of life of family caregivers of schizophrenic patients attending psychiatric hospitals in Ghana.

Abstract:
BACKGROUND
Low and middle income countries face many challenges in meeting their populations' mental health care needs. Though family caregiving is crucial to the management of severe mental health disabilities, such as schizophrenia, the economic costs borne by family caregivers often go unnoticed. In this study, we estimated the household economic costs of schizophrenia and quality of life of family caregivers in Ghana.

METHODS
We used a cost of illness analysis approach. Quality of life (QoL) was assessed using the abridged WHO Quality of Life (WHOQOL-BREF) tool. Cross-sectional data were collected from 442 caregivers of patients diagnosed with schizophrenia at least six months prior to the study and who received consultation in any of the three psychiatric hospitals in Ghana. Economic costs were categorized as direct costs (including medical and non-medical costs of seeking care), indirect costs (productivity losses to caregivers) and intangible costs (non-monetary costs such as stigma and pain). Direct costs included costs of medical supplies, consultations, and travel. Indirect costs were estimated as value of productive time lost (in hours) to primary caregivers. Intangible costs were assessed using the Zarit Burden Interview (ZBI). We employed multiple regression models to assess the covariates of costs, caregiver burden, and QoL.

RESULTS
Total monthly cost to caregivers was US$ 273.28, on average. Key drivers of direct costs were medications (50%) and transportation (27%). Direct costs per caregiver represented 31% of the reported monthly earnings. Mean caregiver burden (measured by the ZBI) was 16.95 on a scale of 0-48, with 49% of caregivers reporting high burden. Mean QoL of caregivers was 28.2 (range: 19.6-34.8) out of 100. Better educated caregivers reported lower indirect costs and better QoL. Caregivers with higher severity of depression, anxiety and stress reported higher caregiver burden and lower QoL. Males reported better QoL.

CONCLUSIONS
These findings highlight the high household burden of caregiving for people living with schizophrenia in low income settings. Results underscore the need for policies and programs to support caregivers.

Opoku-Boateng|Yaw Nyarko|YN|
Kretchy|Irene A|IA|
Aryeetey|Genevieve Cecilia|GC|
Dwomoh|Duah|D|
Decker|Sybil|S|
Agyemang|Samuel Agyei|SA|
Tozan|Yesim|Y|
Aikins|Moses|M|
Nonvignon|Justice|J|

Quality of life
Caregiving
Ghana
Schizophrenia
Economic burden


Pyrolyzed carbon derived from red soil as an efficient catalyst for cephalexin removal.

Abstract: Red soil, a typical soil type in southern China, has been deemed infertile or nutrient-deficient. In this study, red soil was firstly utilized as a substrate for preparing catalysts, which were then successfully applied to the catalytic wet peroxide oxidation (CWPO) of cephalexin. The highest cephalexin removal was 95.23% and TOC removal was 60.58%, with the catalyst pyrolyzed at 500 °C (RC500). The high iron content and proportion of Fe(II) on the surface of RC500 was responsible for the decomposition of H2O2 into· OH. Moreover, the porous structure and existence of other minerals (such as SiO2 and Al2O3) in the catalyst were also significant for enhancing the catalytic activity of RC500. Afterwards, the influencing parameters, including temperature, pH, the dose of H2O2, and catalyst, were examined for cephalexin degradation. It was noteworthy that RC500 was efficient in treating hospital wastewater when using a self-design pilot device. A density functional theory analysis of cephalexin was conducted to establish the possible position attacked by ·OH, and the possibly ruptured one. Meanwhile, the intermediates generated during CWPO were identified. Finally, a reliable degradation pathway of cephalexin was proposed on the basis of the results.

Yu|Li|L| Wang|Li|L| Liu|Yunkang|Y| Sun|Chenglin|C| Zhao|Ying|Y| Hou|Zuojun|Z| Peng|Hongbo|H| Wang|Shengzhe|S| Wei|Huangzhao|H|

Red soil
Cephalexin
Catalytic wet peroxide oxidation
Pyrolysis


Investigating metabolic regulation using targeted neuromodulation.

Abstract: The central nervous system (CNS) plays a vital role in regulating energy balance and metabolism. Over the last 50 years, studies in animal models have allowed us to identify critical CNS regions involved in these processes and even crucial cell populations. Now, techniques for genetically and anatomically targeted manipulation of specific neural populations using light (optogenetic), ligands (chemogenetic), or magnetic fields (radiogenetic/magnetogenetic) allow detailed investigation of circuits involved in metabolic regulation. In this review, we provide a brief overview of recent studies using light- and magnetic field-regulated neural activity to investigate the neural circuits contributing to metabolic control.

metabolism optogenetics radiogenetics magnetogenetics feeding glucose


New approach to accurate interpretation of sickle cell disease newborn screening by applying multiple of median cutoffs and ratios.

Abstract:
BACKGROUND
The main goal of newborn screening (NBS) for sickle cell disease (SCD) is to detect affected neonates so that specific preventive care can be implemented. High-performance liquid chromatography (HPLC) used for NBS has high sensitivity and specificity, but we lack guidelines for quantitative hemoglobin (Hb) fraction interpretation. The purpose of this study was to determine cutoff values to standardize quantitative interpretation in SCD NBS for different clinical situation such as, red blood cell transfusion or beta-thalassemia, which can be real screening pitfalls.

METHODS
Retrospective study of 75,026 samples from the neonatal screening program analyzed in our laboratory. Precise HbA and HbS percentages at birth were recorded and median values established for each gestational age, allowing percentage results to be expressed in normal gestation-specific multiples of the median (MoM). Three threshold values of clinical interest were determined.

RESULTS
High levels of HbA (>2.5 MoM) allowed identification of newborns who received transfusions. Low levels of HbS (≤0.7 MoM) allowed detection of the association between HbS and other mutations of the beta-globin gene (i.e., HbHope, β0-thalassemia, etc.). An HbA/HbS ratio <0.5 to distinguish healthy carriers from SCD with S/β+-thalassemia. The screening accuracy for each threshold was established. The screening accuracy of low-level HbA, which is determinant in identifying the subgroup of patients at risk of β-thalassemia, will be determined prospectively.

CONCLUSIONS
This new approach introduces tools for a quantitative interpretation in SCD NBS by HPLC methods and could allow standardization of interpretation between centers.

Allaf|Bichr|B| Patin|Franck|F| Elion|Jacques|J| Couque|Nathalie|N|0000-0002-5109-0857

interpretation
sickle cell disease
newborn screening
multiple of median
cutoff


Conflicting effects by antibodies against connexin36 during the action of intracellular Cyclic-AMP onto electrical synapses of retinal ganglion cells.

Abstract: Alpha-type retinal ganglion cells (alpha cells) of the same class in mammalian retina are connected by gap junctions. Electrical synapses between alpha cells were examined using combined techniques of dual patch-clamp recordings, intracellular labeling and electron microscopy in the albino rat retina. In simultaneous dual whole-cell recordings from pairs of neighboring alpha cells, bidirectional electrical synapses with symmetrical junction conductance were observed in pairs with cells of the same morphological type. Regulatory domains of gap junction protein subunit connexins in electrical synapses between alpha cells by extracellular and intracellular ligands investigated by dual whole-patch clamp recordings. I examined how passage currents through electrical synapses between alpha cells are modulated by specific antibodies against connexin36 proteins, and extracellular or intracellular application of ligands. Control conditions led us to observe large passage currents between connected cells and adequate transjunctional conductance (Gj) (1.35[Formula: see text][Formula: see text][Formula: see text]0.51[Formula: see text]nS). Experimental results show that high level of intracellular cyclic AMP within examined cells suppress electrical synapses between the neighboring cells. Gj between examined cells reduced to 0.15[Formula: see text][Formula: see text][Formula: see text]0.04[Formula: see text]nS. Under application of dopamine (1.25[Formula: see text][Formula: see text][Formula: see text]0.06[Formula: see text]nS) or intracellular cyclic GMP (0.98[Formula: see text][Formula: see text][Formula: see text]0.23[Formula: see text]nS), however, Gj also remains as in the control level. Intracellular application of an antibody against the cytoplasmic loop of connexin36 reduced Gj (0.98[Formula: see text][Formula: see text][Formula: see text]0.23[Formula: see text]nS). Cocktail of the antibody against cytoplasmic connexin36 and intracellular cyclic AMP leaves Gj as in the level by single involvement of the cytoplasmic antibody. The elimination of Gj by the cytoplasmic antibody was in a dose-dependent manner. These results suggest that binding domains against cyclic AMP may be present in the cytoplasmic sites of connexin proteins to regulate channel opening of gap junctions between mammalian retinal alpha ganglion cells.

electrical synapse
Retinal ganglion cells
gap junction
connexin
cyclic AMP
cytoplasmic antibody
high voltage electron microscopy


Red Blood Cell Dysfunction Induced by High-Fat Diet: Potential Implications for Obesity-Related Atherosclerosis.

Abstract:
BACKGROUND
High-fat diet (HFD) promotes endothelial dysfunction and proinflammatory monocyte activation, which contribute to atherosclerosis in obesity. We investigated whether HFD also induces the dysfunction of red blood cells (RBCs), which serve as a reservoir for chemokines via binding to Duffy antigen receptor for chemokines (DARC).

METHODS AND RESULTS
A 60% HFD for 12 weeks, which produced only minor changes in lipid profile in C57/BL6 mice, markedly augmented the levels of monocyte chemoattractant protein-1 bound to RBCs, which in turn stimulated macrophage migration through an endothelial monolayer. Levels of RBC-bound KC were also increased by HFD. These effects of HFD were abolished in DARC(-/-) mice. In RBCs from HFD-fed wild-type and DARC(-/-) mice, levels of membrane cholesterol and phosphatidylserine externalization were increased, fostering RBC-macrophage inflammatory interactions and promoting macrophage phagocytosis in vitro. When labeled ex vivo and injected into wild-type mice, RBCs from HFD-fed mice exhibited ≈3-fold increase in splenic uptake. Finally, RBCs from HFD-fed mice induced increased macrophage adhesion to the endothelium when they were incubated with isolated aortic segments, indicating endothelial activation.

CONCLUSIONS
RBC dysfunction, analogous to endothelial dysfunction, occurs early during diet-induced obesity and may serve as a mediator of atherosclerosis. These findings may have implications for the pathogenesis of atherosclerosis in obesity, a worldwide epidemic.

Unruh|Dusten|D|
Srinivasan|Ramprasad|R|
Benson|Tyler|T|
Haigh|Stephen|S|
Coyle|Danielle|D|
Batra|Neil|N|
Keil|Ryan|R|
Sturm|Robert|R|
Blanco|Victor|V|
Palascak|Mary|M|
Franco|Robert S|RS|
Tong|Wilson|W|
Chatterjee|Tapan|T|
Hui|David Y|DY|
Davidson|W Sean|WS|
Aronow|Bruce J|BJ|
Kalfa|Theodosia|T|
Manka|David|D|
Peairs|Abigail|A|
Blomkalns|Andra|A|
Fulton|David J|DJ|
Brittain|Julia E|JE|
Weintraub|Neal L|NL|
Bogdanov|Vladimir Y|VY|

atherosclerosis obesity erythrocytes leukocytes


Alumina-mediated photocatalytic degradation of hexachlorobenzene in aqueous system: Kinetics and mechanism.

Abstract: Five kinds of Al2O3 were characterized by SEM, TEM, FT-IR and BET surface area, and then used as carriers to investigate the photochemical removal of hexachlorobenzene (HCB) in aqueous system. The results showed that HCB coated on the surfaces of all Al2O3 could be photodegraded rapidly, and Neutral-Al2O3 presented the best performance. Meanwhile, the efficient removal of HCB in real water matrices, including tap water, river water and secondary clarifier effluent showed the potential practical application of Al2O3. EPR and theoretical calculation revealed the generation of hydroxyl radicals on Al2O3 surface under 500 W Xe lamp irradiation. Nine intermediates and a small amount of Cl- were identified by GC/MS, LC/MS and IC analysis, which was further verified by transition state calculations. These results can provide a new technique for HCB removal in water and wastewaters, and give more insights into the environmental ecological risk assessment of this pollutant.

Pan|Xiaoxue|X|
Wei|Junyan|J|
Qu|Ruijuan|R|
Xu|Shiping|S|
Chen|Jing|J|
Al-Basher|Ghada|G|
Li|Chenguang|C|
Shad|Asam|A|
Dar|Afzal Ahmed|AA|
Wang|Zunyao|Z|

D017550:Spectroscopy, Fourier Transform Infrared

Hexachlorobenzene (HCB)
Theoretical calculation
Alumina
Degradation pathways
Photocatalysis


Study of prebiotic potential and antioxidant activity in Plantago spp. leaves after enzymatic hydrolysis with hemicellulase and xylanase.

Abstract: The leaves of Plantago species have been known as a rich source of polysaccharides, polyphenols, and iridoids. In the recent years, some authors have examined the relative influence of carbohydrate compositions and polyphenols on their antioxidant and prebiotic activity. In this study enzymatic hydrolysis of Plantago major, Plantago lanceolata, and Plantago media leaves with hemicellulase and xylanase was carried out. The chemical composition of the enzyme-derived hydrolysis products was determined. Their antioxidant activity was evaluated using 2,2-diphenyl-2-picryl-hydrazyl-hydrate, ferric reducing antioxidant power, and cupric reducing antioxidant capacity assays. The utilization of the carbohydrate complex from the obtained hydrolysates to stimulate the production of certain glycohydrolases from Lactobacillus plantarum probiotic strains was investigated. The HPLC analysis of the hydrolysis products showed the presence of galactose and arabinose in 1:3 and 1:4 ratios. The highest concentration of total sugars was determined in P. major hydrolysates with hemicellulase (386.71 mg/g dry weight). The antioxidant activity according to the three methods was the highest in P. media hydrolysates, which correlated with their total phenolic concentration. L. plantarum S27 showed the highest values of α-galactosidase activity at the 24-h fermentation process when it was cultivated in a broth with the presence of P. major hydrolysates with hemicellulase and xylanase (0.129 U/mg and 0.133 U/mg, respectively).

Lukova|Paolina|P| Karcheva-Bahchevanska|Diana|D| Mollova|Daniela|D| Nikolova|Mariana|M| Mladenov|Rumen|R| Iliev|Ilia|I|

Prebiotic potential
Plantago spp
Enzymatic hydrolysis
Lactobacillus plantarum
Plant polysaccharide


Clinical experience with insulin detemir, biphasic insulin aspart and insulin aspart in people with type 2 diabetes: Results from North and the oriental region of Morocco cohort of the A1chieve study.

Abstract:
BACKGROUND
The A1chieve, a multicentric (28 countries), 24-week, non-interventional study evaluated the safety and effectiveness of insulin detemir, biphasic insulin aspart and insulin aspart in people with T2DM (n = 66 726) in routine clinical care across four continents.

MATERIALS AND METHODS
Data was collected at baseline, at 12 weeks and at 24 weeks. This short communication presents the results for patients enrolled from Oriental, Morocco.

RESULTS
A total of 180 patients were enrolled in the study. Four different insulin analogue regimens were used in the study. Study patients had started on or were switched to biphasic insulin aspart (n = 146), insulin detemir (n = 22), insulin aspart (n = 6), basal insulin plus insulin aspart (n = 2) and other insulin combinations (n = 4). At baseline glycaemic control was poor for both insulin naïve (mean HbA1c: 9.0%) and insulin user (mean HbA1c: 8.8%) groups. After 24 weeks of treatment, both the study groups showed improvement in HbA1c (insulin naïve: -1.7%, insulin users: -1.6%). SADRs including major hypoglycaemia did not occur in any of the study patients.

CONCLUSION
Starting or switching to insulin analogues was associated with improvement in glycaemic control with a low rate of hypoglycaemia.

Oriental
A1chieve study
insulin analogues
type 2 diabetes mellitus


A versatile platform for generating engineered extracellular vesicles with defined therapeutic properties.

Abstract: Extracellular vesicles (EVs) are an important intercellular communication system facilitating the transfer of macromolecules between cells. Delivery of exogenous cargo tethered to the EV surface or packaged inside the lumen are key strategies for generating therapeutic EVs. We identified two "scaffold" proteins, PTGFRN and BASP1, that are preferentially sorted into EVs and enable high-density surface display and luminal loading of a wide range of molecules, including cytokines, antibody fragments, RNA binding proteins, vaccine antigens, Cas9, and members of the TNF superfamily. Molecules were loaded into EVs at high density and exhibited potent in vitro activity when fused to full-length or truncated forms of PTGFRN or BASP1. Furthermore, these engineered EVs retained pharmacodynamic activity in a variety of animal models. This engineering platform provides a simple approach to functionalize EVs with topologically diverse macromolecules and represents a significant advance toward unlocking the therapeutic potential of EVs.

Dooley|Kevin|K|
McConnell|Russell E|RE|
Xu|Ke|K|
Lewis|Nuruddeen D|ND|
Haupt|Sonya|S|
Youniss|Madeleine R|MR|
Martin|Shelly|S|
Sia|Chang Ling|CL|
McCoy|Christine|C|
Moniz|Raymond J|RJ|
Burenkova|Olga|O|
Sanchez-Salazar|Jorge|J|
Jang|Su Chul|SC|
Choi|Bryan|B|
Harrison|Rane A|RA|
Houde|Damian|D|
Burzyn|Dalia|D|
Leng|Charan|C|
Kirwin|Katherine|K|
Ross|Nikki L|NL|
Finn|Jonathan D|JD|
Gaidukov|Leonid|L|
Economides|Kyriakos D|KD|
Estes|Scott|S|
Thornton|James E|JE|
Kulman|John D|JD|
Sathyanarayanan|Sriram|S|
Williams|Douglas E|DE|

extracellular vesicles
PTGFRN
BASP1
vaccine
EV engineering
IL-12
exosome engineering
exosomes
sacffold


Alkyne-Tagged Apigenin, a Chemical Tool to Navigate Potential Targets of Flavonoid Anti-Dengue Leads.

Abstract: A flavonoid is a versatile core structure with various cellular, immunological, and pharmacological effects. Recently, flavones have shown anti-dengue activities by interfering with viral translation and replication. However, the molecular target is still elusive. Here we chemically modified apigenin by adding an alkyne moiety into the B-ring hydroxyl group. The alkyne serves as a chemical tag for the alkyne-azide cycloaddition reaction for subcellular visualization. The compound located at the perinuclear region at 1 and 6 h after infection. Interestingly, the compound signal started shifting to vesicle-like structures at 6 h and accumulated at 24 and 48 h after infection. Moreover, the compound treatment in dengue-infected cells showed that the compound restricted the viral protein inside the vesicles, especially at 48 h. As a result, the dengue envelope proteins spread throughout the cells. The alkyne-tagged apigenin showed a more potent efficacy at the EC50 of 2.36 ± 0.22, and 10.55 ± 3.37 µM, respectively, while the cytotoxicities were similar to the original apigenin at the CC50 of 70.34 ± 11.79, and 82.82 ± 11.68 µM, respectively. Molecular docking confirmed the apigenin binding to the previously reported target, ribosomal protein S9, at two binding sites. The network analysis, homopharma, and molecular docking revealed that the estrogen receptor 1 and viral NS1 were potential targets at the late infection stage. The interactions could attenuate dengue productivity by interfering with viral translation and suppressing the viral proteins from trafficking to the cell surface.

flavone
alkyne-azide cycloaddition
alkyne-tagged flavonoid
dengue virus
drug discovery
target identification


Enhanced photocatalytic H₂-production activity of bicomponent NiO/TiO₂ composite nanofibers.

Abstract: Hydrogen has been regarded as an ideal candidate for the replacement of conventional fossil fuels due to its environmental friendliness and recycling possibility. In this work, mesoporous NiO/TiO2 bicomponent composite nanofibers were prepared by a electrospinning and calcination method. The H2-production activity of the prepared samples was examined by water splitting using methanol as scavenger under simulated solar Xenon lamp irradiation. The effect of NiO loading on the microstructure and photocatalytic H2-production activity of NiO/TiO2 composite samples was studied and discussed. The results demonstrated that the presence of a small amount of NiO obviously inhibited the growth of TiO2 crystallites. With increasing the NiO content, the average crystallite size further decreased. In contrast, the Brunauer-Emmett-Teller (BET) specific surface areas, pore volumes and average pore size steadily increased. Photocatalytic H2-production experiment confirmed that NiO was an efficient co-catalyst for the photocatalytic H2 production of TiO2. The optimal NiO loading was determined to be 0.25 wt.%, giving a H2-production rate of 337 μmol h(-1) g(-1) with apparent quantum efficiency (QE) of 1.7%, which exceeded the rate on pure TiO2 by more than 7 times. The enhanced H2-production activity was due to the deposition of NiO clusters on the surface of TiO2, which suppressed the recombination of photogenerated electron-hole pairs, reduced the overpotential of hydrogen production and catalyzed production of hydrogen. This work showed that low-cost and earth-abundant NiO could be used as co-catalyst for photocatalytic hydrogen production.

Li|Lingling|L| Cheng|Bei|B| Wang|Yuanxu|Y| Yu|Jiaguo|J|

Electrospinning
NiO/TiO(2) nanofibers
One-dimension
Photocatalytic H(2)-production


The association of wrist circumference with hypertension in northeastern Chinese residents in comparison with other anthropometric obesity indices.

Abstract:
Background
Wrist circumference (WrC) is an easily obtained measure in estimating the body frame and regional fat distribution, and has increasingly used as an obesity index. The aim of our study is to estimate the association of WrC with elevated blood pressure (BP) among northeastern Chinese community-dwelling residents, and compare the strength of this association to other anthropometric obesity indices.

Methods
A total of 2,331 adult participants (761 male participants, and 1,570 female participants) were included. WrC and other five generally used obesity indices, including body mass index (BMI), waist circumference (WC), waist-to-hip ratio (WHR), waist-to-height ratio (WHtR) and neck circumference (NC) were measured. Hypertension was defined as systolic blood pressure (SBP)/diastolic blood pressure (DBP) ≥140/90 mmHg or anti-hypertensive medication use. Multivariable linear and logistic regression models were performed to identify associations of BP and hypertension with per standard deviation (SD) increase of obesity indices. Areas under receiver operative characteristic curves (AUC) were calculated to compare the predicting capacity of WrC and other obesity indices on hypertension.

Results
All of the six obesity indices were positively associated with both SBP and DBP after adjustment for age and gender (P-values of associations of SBP with obesity indices were 0.043 for WrC, and <0.001 for other five indices; P-values of associations of DBP with obesity indices were 0.011 for WrC, 0.031 for WHR, and <0.001 for other four indices), while the association between SBP and WrC showed no statistically significant after further adjusted for life-style and metabolic risk factors (P-value was 0.062). The increases of both SBP and DBP per SD increase of BMI were the largest. The positive associations of five obesity indices but WHR with hypertension were observed after adjustment for all risk factors (P-values were 0.024 for WrC, 0.064 for WHR and <0.001 for other four indices). However, the odd ratios (OR) of WrC was the smallest, while BMI was the largest. Consistently, the AUC of BMI was the largest and statistically larger than that observed for WrC (P-value <0.001).

Conclusions
WrC was associated with hypertension among northeastern Chinese populations. However, the association was not stronger than the other generally used indices, particularly BMI.

Li|Yongfang|Y| Liu|Yuyan|Y| He|Jing|J| Ma|Ping|P| Yu|Luyang|L| Sun|Guifan|G|

Wrist circumference
Hypertension
Obesity
Blood pressure


Stability, across environments, of grain and alcohol yield, in soft wheat varieties grown for grain distilling or bioethanol production.

Abstract:
BACKGROUND
Soft-milling wheat has potential use for both grain whisky distilling and bioethanol production. Varietal comparisons over wide-ranging environments would permit assessment of both grain and alcohol yield potential and also permit the stability across environments, for these parameters, to be compared.

RESULTS
For 12 varieties, analysis of variance showed highly significant effects of variety, site, season and fertiliser application on grain and alcohol yield. There were also significant interactions between these factors and, consequently, varieties varied in stability across environments as well as in mean values for the parameters assessed. Alcohol production per hectare was affected more strongly by variation in grain yield than alcohol yield, but increasing grain protein content reduced alcohol yield and, therefore, utility for grain distilling.

CONCLUSION
To maximise energy production, the best varieties for bioethanol would combine high and stable grain yield with slower reduction of alcohol yield as grain protein increases. For grain distilling, where the energy balance is less important, high alcohol yield will remain the key factor. Data derived using near infrared spectroscopy can be valuable in assessing stability of quality traits across environments.

Swanston|John Stuart|JS|
Smith|Pauline L|PL|
Thomas|William Tb|WT|
Sylvester-Bradley|Roger|R|
Kindred|Daniel|D|
Brosnan|James M|JM|
Bringhurst|Thomas A|TA|
Agu|Reginald C|RC|

alcohol yield
wheat
environmental variation
variety trials
yield stability


Possible involvement of CA1 5-HT1B/1D and 5-HT2A/2B/2C receptors in harmaline-induced amnesia.

Abstract: In the present study, effects of the serotonergic system of the dorsal hippocampus (CA1) on harmaline-induced amnesia were examined. A single-trial step-down passive avoidance task was used for the assessment of memory retention in adult male NMRI mice. Pre-training intra-peritoneal (i.p.) administration of harmaline (1mg/kg) induced impairment of memory retention. Moreover, intra-CA1 administration of 5-HT1B/1D receptor agonist, CP94253 (5 ng/mouse), 5-HT1B/1D receptor antagonist, GR127935 (0.05 and 0.5 ng/mouse), 5-HT2A/2B/2C receptor agonist, α-methyl 5-HT (0.5 ng/mouse) and 5-HT2 receptor antagonist, cinancerine (0.5 ng/mouse) impaired memory acquisition, but did not affect locomotor activity and tail flick. Furthermore, pre-training intra-CA1 injection of subthreshold dose of CP94253 (0.05 ng/mouse) or GR127935 (0.005 ng/mouse) reversed impairment of memory acquisition induced by harmaline (1 mg/kg, i.p.). However, pre-training intra-CA1 infusion of subthreshold dose of α-methyl 5-HT (0.005 ng/mouse) or cinancerine (0.005 ng/mouse) with the administration of harmaline (0.5 and 1 mg/kg, i.p.) heighten impairment of memory acquisition. These findings implicate the involvement of CA1 serotonergic mechanism in harmaline-induced impairment of memory acquisition.

Nasehi|Mohammad|M| Jamshidi-Mehr|Mehdi|M| Khakpai|Fatemeh|F| Zarrindast|Mohammad-Reza|MR|

D000697:Central Nervous System Stimulants

D058825:Serotonin 5-HT1 Receptor Agonists

D058829:Serotonin 5-HT1 Receptor Antagonists

Serotonergic system
Passive avoidance
Memory
Mice
Harmaline


Rapid sequence magnetic resonance imaging in the assessment of children with hydrocephalus.

Abstract:
OBJECTIVE
Recent reports have shown the utility of rapid-acquisition magnetic resonance imaging (MRI) in the evaluation of children with hydrocephalus. Rapid sequence MRI (RS-MRI) acquires clinically useful images in seconds without exposing children to the risks of ionizing radiation or sedation. We review our experience with RS-MRI in children with shunts.

METHODS
Overall image quality, cost, catheter visualization, motion artifact, and ventricular size were reviewed for all RS-MRI studies obtained at Seattle Children's Hospital during a 2-year period. Image acquisition time was 12-19 seconds, with sessions usually lasting less than 3 minutes.

RESULTS
Image quality was very good or excellent in 94% of studies, whereas only one was graded as poor. Significant motion artifact was noted in 7%, whereas 77% had little or no motion artifact. Catheter visualization was good or excellent in 57%, poor in 36%, and misleading in 7%. Small ventricular size was correlated with poor catheter visualization (Spearman's ρ = 0.586; P < 0.00001). RS-MRI imaging cost ∼$650 more than conventional computed tomography (CT).

CONCLUSIONS
Our study supports that RS-MRI is an adequate substitute that allows reduced use of CT imaging and resultant exposure to ionizing radiation. Catheter position visualization remains suboptimal when ventricles are small, but shunt malfunction can be adequately determined in most cases. The cost is significantly more than CT, but the potential for lifetime reduction in radiation exposure may justify this expense in children. Limitations include the risk of valve malfunction after repeated exposure to high magnetic fields and the need for reprogramming with many types of adjustable valves.

O'Neill|Brent R|BR|
Pruthi|Sumit|S|
Bains|Harmanjeet|H|
Robison|Ryan|R|
Weir|Keiko|K|
Ojemann|Jeff|J|
Ellenbogen|Richard|R|
Avellino|Anthony|A|
Browd|Samuel R|SR|

Half Fourier acquisition single shot turbo spin echo

Rapid-sequence magnetic resonance imaging


CT diagnostics of pulmonary embolism: Does iodine delivery rate still affect image quality in iterative reconstruction?

Abstract:
BACKGROUND
Computed tomographic (CT) imaging in suspected pulmonary artery embolism represents the standard procedure. Studies without iterative reconstruction proved beneficial using increased iodine delivery rate (IDR). This study compares image quality in pulmonary arteries on iteratively reconstructed CT images of patients with suspected pulmonary embolism using different IDR.

MATERIAL AND METHODS
1065 patients were included in the study. Patients in group A (n = 493) received an iodine concentration of 40 g/100 ml (IDR 1.6 g/s) and patients in group B (n = 572) an iodine concentration of 35 g/100 ml (IDR 1.4 g/s) at a flow rate of 4 ml/s. A 80-detector spiral CT scanner with iterative reconstruction was used. We measured mean density values in truncus pulmonalis, both pulmonary arteries and segmental pulmonary arteries. Subjectively, the contrast of apical and basal pulmonary arteries was determined on a 4-point Likert scale.

RESULTS
Radiodensity was significantly higher in all measured pulmonary arteries using the increased IDR (p < 0.001). TP: 483.0 HU vs. 393.4 HU; APD: 452.1 HU vs. 372.1 HU; APS: 448.2 HU vs. 374.4 HU; ASP: 443.9 vs. 374.4 HU. Subjectively assessed contrast enhancement in apical (p = 0.077) and basal (p = 0.429) lung sections showed no significant differences.

CONCLUSION
Higher IDR improves objective image quality in all patients with significantly higher radiodensities by iterative reconstruction. Subjective contrast of apical and basal lung sections did not differ. The number of non-sufficient scans decreased with high IDR.

Burdenski|Thomas|T|
Bressem|Keno K|KK|
Adams|Lisa C|LC|
Grauhan|Nils F|NF|
Niehues|Stefan M|SM|

D003287:Contrast Media
D006801:Humans
D007455:Iodine
D011651:Pulmonary Artery
D011655:Pulmonary Embolism
D014057:Tomography, X-Ray Computed

pulmonary embolism
iodine concentration
Computed tomography
contrast media


A systematic review of the effect of oral glucocorticoids on energy intake, appetite, and body weight in humans.

Abstract: Obesity is a serious risk factor for chronic disease, and commonly prescribed oral glucocorticoids (OCS) may be contributing to the prevalence of obesity. The objective of this review was to assess the impact of OCS on obesity in humans through effects on body weight (BW), energy intake, appetite, and body composition. An electronic search of English language peer-reviewed studies from 1973 up to March 2012 was conducted using Medline, CINAHL, EMBASE, and Cochrane databases. Original studies that addressed the effects of OCS on appetite, energy intake, BW, or body composition in adults were considered eligible. Data from 21 studies with objectively measured outcomes were extracted and assessed for quality using standardized tools. The publication year varied from 1986 to 2013, and the sample size, from 6 to 189. Energy intake was measured in 6 studies; BW, in 19 studies; energy expenditure, in 3 studies; body composition, in 6 studies; and appetite was evaluated in 3 studies. Short-term oral glucocorticoid therapy may result in small increases in energy intake but does not appear to result in increased BW, possibly due to an increase in energy expenditure. Long-term therapy may result in clinically significant weight gain. Within-subject variation due to metabolism and physical activity levels confounds the relationship. A dose-response relationship of oral glucocorticoid therapy on energy intake, appetite, BW, or body composition was not found. Additional well-designed, double-blind, placebo-controlled clinical trials that use standardized doses of OCS and assess the effects on appetite, energy intake, BW, and composition are strongly justified to confirm the findings of this review.

Berthon|Bronwyn S|BS|
MacDonald-Wicks|Lesley K|LK|
Wood|Lisa G|LG|

D016032:Randomized Controlled Trials as Topic

Systematic review
Glucocorticoids
Energy intake
Appetite
Body weight
Obesity


Test-retest reliability of Picture My Participation in children with intellectual disability in South Africa.

Abstract:
BACKGROUND
Picture My Participation (PmP) is a promising instrument for measuring the participation in everyday situations of children with intellectual disability (ID), particularly in low- and middle-income countries.

AIM
To explore test-retest reliability of PmP by comparing two repeated measurements of children with ID in an urban context in South Africa.

METHODS
A picture-supported interview with 31 children with ID, aged 7-17 years, was conducted twice, two weeks apart. The children rated their participation, operationalised as attendance and involvement, in 20 everyday activities. Analyses were completed for total scores, for the four subcomponents and at item level.

RESULTS
Test-retest agreement at an item level for both attendance and involvement showed slight/fair agreement for most activities (Kappa = 0.01-0.40), and moderate agreement for some activities (Kappa = 0.41-0.60). Moderate agreement was shown for the total scale and at component level (ICC = 0.5-0.75), except for (firstly) attendance of and involvement in 'Family Activities' (ICC = 0.26 for attendance, 0.33 for involvement), and (secondly) involvement in 'Personal Activities' (ICC = 0.33).

CONCLUSION
The result indicates that PmP can reliably be used at component level and as a screening tool for intervention planning to identify participation and participation restrictions in children with ID.

participation
Low- and middle-income countries
picture-supported interview
cognitive support
everyday functioning
self-rating


Av-UCP single nucleotide polymorphism affects heat production during cold exposure in chicks.

Abstract:
OBJECTIVE
Uncoupling protein one (UCP1) is involved in thermogenesis, especially in non-shivering heat production. In chickens, a single nucleotide polymorphism (SNP) of the av-UCP (avian UCP) gene has been reported to be associated with body weight gain and increased abdominal fat. The purpose of this study was to examine the relationship between the av-UCP gene SNP and heat production in chicks.

METHODS
C/C and T/T male chicks (Rhode Island Red) of av-UCP gene SNP (g. 1270, C > T) were exposed to a low temperature environment (16 °C for 15 min) and their physiological responses were compared.

RESULTS
After cold exposure, mean rectal temperatures of C/C chicks were higher than those of T/T chicks. In pectoral muscle, genes expression of av-UCP and carnitine palmitoyltransferase-1 were higher in C/C chicks than T/T chicks. Hypothalamic expression levels of thyrotropin-releasing hormone and proopiomelanocortin genes were higher in C/C chicks than T/T chicks. Expression of hypothalamic corticotropin-releasing hormone, arginine vasotocin, brain-derived neurotrophic factor and neuropeptide Y genes did not differ between C/C and T/T chicks. In addition, plasma free fatty acid levels in C/C chicks were lower than those of T/T chicks.

CONCLUSION
These results suggest that the av-UCP gene SNP affects non-shivering heat production via the hypothalamo-pituitary-thyroid axis and fatty acid metabolism in the chicken.

Ouchi|Yoshimitsu|Y|
Chowdhury|Vishwajit S|VS|
Cockrem|John F|JF|
Bungo|Takashi|T|

Polymorphism
Chicks
Thermogenesis
Avian UCP
Cold stress