Heavy metals in soils around non-ferrous smelteries in China: Status, health risks and control measures.

Abstract: Non-ferrous smelting is a primary cause of serious soil pollution. Contamination and health risks of heavy metals in soils around various types of non-ferrous smelteries in China were assessed using data from peer-reviewed papers published between 2000 and 2019. Development in the relevant environmental policy in China was discussed. The studied non-ferrous smelting sites were mainly located in provinces that produced non-ferrous metals on a large scale. The average concentrations of the heavy metals in soils around the non-ferrous smelteries (in mg per kg of soil) were as follows: Cd, 19.8; Cu, 265; Pb, 1536; and Zn, 1371; the concentrations greatly exceeded their corresponding background values. The smelting sites with high soil contamination in terms of metal concentrations, geo-accumulation (Igeo), and pollution index (PI) were mainly distributed in several provinces of China, including Guangxi, Gansu, Hunan, Hubei, Chongqing, and Liaoning. Soils near smelteries that processed copper were the most polluted based on Igeo and PI. The accumulation of Cd and Pb in soils around non-ferrous smelteries would pose potentially high risks to residents. A series of environmental policies have proven successful in lowering the emissions of contaminants from the non-ferrous in China. The findings of the study suggested that the strategies to control soil pollution around non-ferrous smelteries should primarily focus on Cd and Pb.

Jiang|Zhichao|Z| Guo|Zhaohui|Z| Peng|Chi|C| Liu|Xu|X| Zhou|Ziruo|Z| Xiao|Xiyuan|X|

D002681:China
D004784:Environmental Monitoring
D006304:Health Status
D019216:Metals, Heavy
D018570:Risk Assessment
D012987:Soil
D012989:Soil Pollutants

Non-ferrous smelting
Environmental policy
Soil contamination
Health risk assessment


Interference of phosphane copper (I) complexes of β-carboline with quorum sensing regulated virulence functions and biofilm in foodborne pathogenic bacteria: A first report.

Abstract: Foodborne pathogens are one of the major cause of food-related diseases and food poisoning. Bacterial biofilms and quorum sensing (QS) mechanism of cell-cell communication have also been found to be associated with several outbreaks of foodborne diseases and are great threat to food safety. Therefore, In the present study, we investigated the activity of three tetrahedrally coordinated copper(I) complexes against quorum sensing and biofilms of foodborne bacteria. All the three complexes demonstrated similar antimicrobial properties against the selected pathogens. Concentration below the MIC i.e. at sub-MICs all the three complexes interfered significantly with the quorum sensing regulated functions in C. violaceum (violacein), P. aeruginosa (elastase, pyocyanin and alginate production) and S. marcescens (prodigiosin). The complexes demonstrated potent broad-spectrum biofilm inhibition in Pseudomonas aeruginosa, E. coli, Chromobacterium violaceum, Serratia marcescens, Klebsiella pneumoniae and Listeria monocytogenes. Biofilm inhibition was visualized using SEM and CLSM images. Action of the copper(I) complexes on two key QS regulated functions contributing to biofilm formation i.e. EPS production and swarming motility was also studied and statistically significant reduction was recorded. These results could form the basis for development of safe anti-QS and anti-biofilm agents that can be utilized in the food industry as well as healthcare sector to prevent food-associated diseases.

Al-Shabib|Nasser A|NA|
Husain|Fohad Mabood|FM|
Khan|Rais Ahmad|RA|
Khan|Mohammad Shavez|MS|
Alam|Mohammad Zubair|MZ|
Ansari|Firoz Ahmad|FA|
Laeeq|Sameen|S|
Zubair|Mohammad|M|
Shahzad|Syed Ali|SA|
Khan|Javed Masood|JM|
Alsalme|Ali|A|
Ahmad|Iqbal|I|

Quorum sensing
Biofilm
Pathogens
Food safety
Copper compounds


Design of mannosylated oral amphotericin B nanoformulation: efficacy and safety in visceral leishmaniasis.

Abstract: The aim of this study was to evaluate mannose-anchored thiolated chitosan (MTC) based nanocarriers (NCs) for enhanced permeability, improved oral bioavailability and anti-parasitic potential of amphotericin B (AmB). Transgenic Leishmania donovani parasites expressing red fluorescent protein DsRed2 and imaging-flow cytometry was used to investigate parasitic burdens inside bone marrow-derived macrophages ex vivo. Cytokine estimation revealed that MTC nanocarriers activated the macrophages to impart an explicit immune response by higher production of TNF-α and IL-12 as compared to control. Cells treated with MTC NCs showed a significantly higher magnitude of nitrite and propidium iodide (PI) fluorescence intensity in contrast to cells treated with AmB. Concerning to apparent permeability coefficient (Papp) results, the MTC NCs formulation displayed more specific permeation across the Caco-2 cell monolayer as compared to AmB. The half-life of MTC NCs was about 3.3-fold persistent than oral AmB used as positive control. Also, t oral bioavailability of AmB was increased to 6.4-fold for MTC NCs compared to AmB for positive control. Acute oral evaluation indicated that MTC NCs were significantly less toxic compared to the AmB. Based on these findings, MTC NCs seems to be promising for significant oral absorption and improved oral bioavailability of AmB in leishmaniasis chemotherapy.

Sarwar|Hafiz Shoaib|HS|
Sohail|Muhammad Farhan|MF|
Saljoughian|Noushin|N|
Rehman|Anees Ur|AU|
Akhtar|Sohail|S|
Nadhman|Akhtar|A|
Yasinzai|Masoom|M|
Gendelman|Howard E|HE|
Satoskar|Abhay R|AR|
Shahnaz|Gul|G|

Oral bioavailability
permeation
acute toxicity
mannose receptors
thiolated chitosan nanocarriers


Home Exercise Interventions in Frail Older Adults.

Abstract:
Purpose of Review
Frailty is characterized by decreased physiological reserve and increased risk of falls, disability, hospitalization, and mortality. Frail older adults may benefit from exercise interventions targeting their multiple problems and functional deficits; however, most research focuses on center-based interventions, which may present accessibility challenges for frail older adults. Therefore, the purpose of this review is to summarize the most recently published home-based exercise interventions for frail older adults living at home.

Recent Findings
Eight manuscripts met inclusion criteria. Research interventions consisted of a variety of modes (strength, strength/nutrition, strength/flexibility/balance/endurance), duration (12 weeks to 6 months), frequency (2-7 days/week), and delivery methods (volunteer-led, videos on a tablet, manuals/brochures). Investigators examined the effects of home-based exercise on a variety of outcomes to include feasibility, frailty status, physical performance, lean body mass, skeletal muscle mass, other physiological outcomes, mental health, nutritional status, and incidence of falls in frail.

Summary
This review demonstrates the feasibility and effectiveness of home-based exercise interventions to improve frailty, functional performance, nutritional status, and incidence of falls in frail older adults. However, the limited literature available provides conflicting reports regarding benefits for mental health outcomes and no evidence of a beneficial effect on skeletal muscle or lean mass. Future research is needed to shed light on the optimal components of home exercise programs most important for maximizing benefits for frail older adults, as well as the most effective delivery method.

Stookey|Alyssa D|AD|0000-0001-9052-354X
Katzel|Leslie I|LI|


Electroclinical phenotypes and outcomes in TBC1D24-related epilepsy.

Abstract: TBC1D24 is a newly recognized gene in which variations lead to variable clinical phenotypes including drug-resistant epilepsy. We report four patients with novel variants of TBC1D24 demonstrating drug-resistant focal epilepsy, developmental delays, and head growth deceleration. All patients had seizure semiologies consisting of prolonged, unilateral, focal clonic activity of the arm, leg or face, in addition to generalized clonic or myoclonic seizures. Ictal EEG characteristics included epilepsia partialis continua, epilepsy of infancy with migrating focal seizures, and other focal seizures with indiscrete interictal-ictal transitions. Two seemingly unrelated Navajo patients with identical variations experienced super-refractory status epilepticus at 9 months of age, with one achieving resolution with ketogenic diet therapy. Our series suggests that TBC1D24-related epilepsy can manifest with hypotonia, developmental delays, and a variety of focal-onset seizures prone to electroclinical dissociation.

Appavu|Brian|B|
Guido-Estrada|Natalie|N|
Lindstrom|Kristin|K|
Grebe|Theresa|T|
Kerrigan|John F|JF|
Troester|Matthew|M|

malignant migrating partial seizures in infancy


Serum metabolic profile characteristics of offspring rats before and after birth caused by prenatal caffeine exposure.

Abstract: Epidemiological investigations have confirmed that prenatal caffeine intake could increase the incidence rate of intrauterine growth retardation (IUGR) and multiple diseases after birth. Based on liquid chromatography-mass spectrometry, we analyzed serum metabolic profiles of offspring rats before and after birth in IUGR model induced by prenatal caffeine exposure (PCE). We discovered that differential metabolites in PCE fetuses mainly manifested as amino acids and lipid metabolism. In adulthood, PCE offspring showed less and inconsistent types of differential metabolites compared to those in utero, which still exhibited gender differences. The main differential metabolites induced by PCE, including phospholipids, platelet-activating factor, arachidonic acid, bile acid, sphingosine-1-phosphoric acid, indoxyl sulfuric acid, and cortexolone, may participate in the pathological and physiological processes of organ toxicities. This study demonstrated the short- and long-term developmental toxicity and gender differences of caffeine, providing new ideas for exploring the early warning and drug intervention targets of IUGR offspring.

Chen|Guanghui|G| Zhang|Qi|Q| Ai|Can|C| Huang|Songqiang|S| Zhang|Huizhen|H| Guo|Xiaoyu|X| Wang|Wenju|W| Hua|Weiying|W| Bi|Huichang|H| Wang|Hui|H|

D011297:Prenatal Exposure Delayed Effects

Prenatal caffeine exposure
Lipid metabolism
Developmental toxicity
Fetal-origin disease
Metabolomics


The Hypothermic Effect of Hydrogen Sulfide Is Mediated by the Transient Receptor Potential Ankyrin-1 Channel in Mice.

Abstract: Hydrogen sulfide (H2S) has been shown in previous studies to cause hypothermia and hypometabolism in mice, and its thermoregulatory effects were subsequently investigated. However, the molecular target through which H2S triggers its effects on deep body temperature has remained unknown. We investigated the thermoregulatory response to fast-(Na2S) and slow-releasing (GYY4137) H2S donors in C57BL/6 mice, and then tested whether their effects depend on the transient receptor potential ankyrin-1 (TRPA1) channel in Trpa1 knockout (Trpa1) and wild-type (Trpa1) mice. Intracerebroventricular administration of Na2S (0.5-1 mg/kg) caused hypothermia in C57BL/6 mice, which was mediated by cutaneous vasodilation and decreased thermogenesis. In contrast, intraperitoneal administration of Na2S (5 mg/kg) did not cause any thermoregulatory effect. Central administration of GYY4137 (3 mg/kg) also caused hypothermia and hypometabolism. The hypothermic response to both H2S donors was significantly (p < 0.001) attenuated in Trpa1 mice compared to their Trpa1 littermates. Trpa1 mRNA transcripts could be detected with RNAscope in hypothalamic and other brain neurons within the autonomic thermoeffector pathways. In conclusion, slow- and fast-releasing H2S donors induce hypothermia through hypometabolism and cutaneous vasodilation in mice that is mediated by TRPA1 channels located in the brain, presumably in hypothalamic neurons within the autonomic thermoeffector pathways.

Olah|Emoke|E|
Rumbus|Zoltan|Z|
Kormos|Viktoria|V|0000-0002-3360-2425
Tekus|Valeria|V|0000-0003-2918-4475
Pakai|Eszter|E|
Wilson|Hannah V|HV|
Fekete|Kata|K|
Solymar|Margit|M|
Kelava|Leonardo|L|
Keringer|Patrik|P|
Gaszner|Balazs|B|0000-0003-2830-2732
Whiteman|Matthew|M|
Keeble|Julie|J|
Pinter|Erika|E|0000-0001-9898-632X
Garami|Andras|A|0000-0003-2493-0571


Alkylation of pyridines at their 4-positions with styrenes plus yttrium reagent or benzyl Grignard reagents.

Abstract: A new regioselective alkylation of pyridines at their 4-position was achieved with styrenes in the presence of yttrium trichloride, BuLi, and diisobutylaluminium hydride (DIBAL-H) in THF. Alternatively, similar products were more simply prepared from pyridines and benzyl Grignard reagents. These reactions are not only a useful preparation of 4-substituted pyridines but are also complementary to other relevant reactions usually giving 2-substituted pyridines.

alkylation
pyridine
yttrium
Grignard reagents
regioselectivity


Histone demethylase Jmjd3 is required for the development of subsets of retinal bipolar cells.

Abstract: Di- and trimethylation of lysine 27 on histone H3 (H3K27me2/3) is an important gene repression mechanism. H3K27me2/3-specific demethylase, Jmjd3, was expressed in the inner nuclear layer during late retinal development. In contrast, H3K27 methyltransferase, Ezh2, was highly expressed in the embryonic retina but its expression decreased rapidly after birth. Jmjd3 loss of function in the developing retina resulted in failed differentiation of PKC-positive bipolar cell subsets (rod-ON-BP) and reduced transcription factor Bhlhb4 expression, which is critical for the differentiation of rod-ON-BP cells. Overexpression of Bhlhb4, but not of other BP cell-related genes, such as transcription factors Neurod and Chx10, in Jmjd3-knockdown retina rescued loss of PKC-positive BP cells. Populations of other retinal cell subsets were not significantly affected. In addition, proliferation activity and apoptotic cell number during retinal development were not affected by the loss of Jmjd3. Levels of histone H3 trimethyl Lys27 (H3K27me3) in the Bhlhb4 locus were lower in Islet-1-positive BP cells and amacrine cells than in the Islet-1-negative cell fraction. The Islet-1-negative cell fraction consisted mainly of photoreceptors, suggestive of lineage-specific demethylation of H3K27me3 in the Bhlhb4 locus. We propose that lineage-specific H3K27me3 demethylation of critical gene loci by spatiotemporal-specific Jmjd3 expression is required for appropriate maturation of retinal cells.

Iida|Atsumi|A| Iwagawa|Toshiro|T| Kuribayashi|Hiroshi|H| Satoh|Shinya|S| Mochizuki|Yujin|Y| Baba|Yukihiro|Y| Nakauchi|Hiromitsu|H| Furukawa|Takahisa|T| Koseki|Haruhiko|H| Murakami|Akira|A| Watanabe|Sumiko|S|

D051792:Basic Helix-Loop-Helix Transcription Factors

D056484:Jumonji Domain-Containing Histone Demethylases

D060888:Real-Time Polymerase Chain Reaction

histone methylation
interneuron
progenitor


Successful treatment with 4-phenylbutyrate in a patient with benign recurrent intrahepatic cholestasis type 2 refractory to biliary drainage and bilirubin absorption.

Abstract:
AIM
Benign recurrent intrahepatic cholestasis type 2 (BRIC2) is caused by mutations in ABCB11, a gene encoding the bile salt export pump (BSEP) that mediates biliary bile salt secretion, and presents with repeated intermittent cholestasis with refractory itching. Currently, no effective medical therapy has been established. We previously provided experimental and clinical evidence suggesting the therapeutic potential of 4-phenylbutyrate (4PB) for the cholestatic attacks of BRIC2.

METHODS
After examining the potential therapeutic use of 4PB treatment by in vitro studies, a patient with BRIC2 was treated p.o. with 4PB at gradually increasing doses (200, 350, and 500 mg/kg per day) for 4 months. Biochemical, histological and clinical data were collected.

RESULTS
The patient was diagnosed with BRIC2 because he had non-synonymous mutations (c.1211A>G [p.D404G] and 1331T>C [p.V444A]) in ABCB11, reduced hepatocanalicular expression of BSEP and low biliary bile salt concentrations. In vitro analysis showed that 4PB treatment partially restored the decreased expression of BSEP caused by p.D404G mutation. During the first 2 months of 4PB therapy at 200 and 350 mg/kg per day, the patient had no relief from his symptoms. No beneficial effect was observed after additional treatment with bilirubin absorption and endoscopic nasobiliary drainage. However, after starting treatment at a dose of 500 mg/kg per day, the patient's liver function tests and intractable itching were markedly improved. No apparent side-effects were observed during or after 4PB therapy. The symptoms relapsed within 1.5 months after cessation of 4PB therapy.

CONCLUSION
4PB therapy would have a therapeutic effect on the cholestatic attacks of BRIC2.

Hayashi|Hisamitsu|H| Naoi|Sotaro|S| Hirose|Yu|Y| Matsuzaka|Yusuke|Y| Tanikawa|Ken|K| Igarashi|Koji|K| Nagasaka|Hironori|H| Kage|Masayoshi|M| Inui|Ayano|A| Kusuhara|Hiroyuki|H|


Cyclodextrin-based metal-organic frameworks for pulmonary delivery of curcumin with improved solubility and fine aerodynamic performance.

Abstract: Pulmonary drug delivery has attracted considerable attention in recent years. However, it is still a major challenge to deliver poorly water-soluble drugs to lungs with good solubility and fine aerodynamic performance. In this study, curcumin was loaded into cyclodextrin-based metal-organic frameworks (CD-MOFs) for pulmonary delivery. Compared with micronized curcumin prepared by jet milling, curcumin-loaded CD-MOFs (Cur-CD-MOFs) exhibited excellent aerodynamic performance, which was attributed to the unique porous structure and lower density of CD-MOFs. The dissolution test showed that the drug release rate of Cur-CD-MOFs was much faster than that of micronized curcumin. The all-atom molecular dynamic simulation showed that curcumin molecules were loaded into the hydrophobic cavities of CD-MOFs or entered into the large hydrophilic cavities to form nanoclusters. The elevated wettability of Cur-CD-MOFs and the unique spatial distribution feature of curcumin in porous interior of CD-MOFs might be favorable for the improved dissolution rate. The DPPH radical scavenging test showed that Cur-CD-MOFs had prominent antioxidant activities. Therefore, CD-MOFs were expected to be promising carriers for pulmonary delivery of poorly water-soluble drugs.

Zhou|Yixian|Y| Zhao|Yiting|Y| Niu|Boyi|B| Luo|Qiaorong|Q| Zhang|Yue|Y| Quan|Guilan|G| Pan|Xin|X| Wu|Chuanbin|C|

Curcumin
Solubility
Aerodynamic performance
Dry powder inhalation
Metal–organic framework


Gating of tactile information through gamma band during passive arm movement in awake primates.

Abstract: To make precise and prompt action in a dynamic environment, the sensorimotor system needs to integrate all related information. The inflow of somatosensory information to the cerebral cortex is regulated and mostly suppressed by movement, which is commonly referred to as sensory gating or gating. Sensory gating plays an important role in preventing redundant information from reaching the cortex, which should be considered when designing somatosensory neuroprosthetics. Gating can occur at several levels within the sensorimotor pathway, while the underlying mechanism is not yet fully understood. The average sensory evoked potential is commonly used to assess sensory information processing, however the assumption of a stereotyped response to each stimulus is still an open question. Event related spectral perturbation (ERSP), which is the power spectrum after time-frequency decomposition on single trial evoked potentials (total power), could overcome this limitation of averaging and provide additional information for understanding the underlying mechanism. To this aim, neural activities in primary somatosensory cortex (S1), primary motor cortex (M1), and ventral posterolateral (VPL) nucleus of thalamus were recorded simultaneously in two areas (S1 and M1 or S1 and VPL) during passive arm movement and rest in awake monkeys. Our results showed that neural activity at different recording areas demonstrated specific and unique response frequency characteristics. Tactile input induced early high frequency responses followed by low frequency oscillations within sensorimotor circuits, and passive movement suppressed these oscillations either in a phase-locked or non-phase-locked manner. Sensory gating by movement was non-phase-locked in M1, and complex in sensory areas. VPL showed gating of non-phase-locked at gamma band and mix of phase-locked and non-phase-locked at low frequency, while S1 showed gating of phase-locked and non-phase-locked at gamma band and an early phase-locked elevation followed by non-phase-locked gating at low frequency. Granger causality (GC) analysis showed bidirectional coupling between VPL and S1, while GC between M1 and S1 was not responsive to tactile input. Thus, these results suggest that tactile input is dominantly transmitted along the ascending direction from VPL to S1, and the sensory input is suppressed during movement through a bottom-up strategy within the gamma-band during passive movement.

sensory gating
somatosensory cortex
thalamus
Granger causality
time-frequency representation


Symptomatic Cavernous Malformation Presenting with Seizure without Hemorrhage: Analysis of Factors Influencing Clinical Presentation.

Abstract:
BACKGROUND
Supratentorial cavernous malformations (CMs) can be epileptogenic lesions. However, little is known about clinical comorbidities, medication use, and radiologic features that predict a first seizure presentation without associated CM hemorrhage.

METHODS
We queried a prospective registry of consecutive patients with CM established in January 2015. Data regarding clinical presentation, comorbid conditions, daily medication use, and radiologic CM characteristics were collected. Univariate and multivariate regression analysis was performed assessing variables for presentation with seizure without hemorrhage with P values, odds ratios, and 95% confidence intervals reported.

RESULTS
Of 202 patients, 58.4% were women, and the average age at diagnosis was 43.7 ± 16.5 years. Of the patients, 59.4% were symptomatic. In 40.6%, the CM was an incidental finding. Of the 30 patients who presented with a first-time seizure without concomitant hemorrhage, the mean age at diagnosis was 38.4 ± 14.6 years, and 56.7% were women. Compared with incidental CM, patients with seizure without hemorrhage were younger, had a cortically based, supratentorial lesion, and were less likely to have chronic inflammatory disease or to use aspirin, vitamin D, or statin. Compared with other supratentorial lesions, patients with seizure without hemorrhage more commonly had a temporal lobe CM.

CONCLUSIONS
These prospective data provide possible clues to radiologic factors, clinical comorbidities, and medication influences on seizure presentation in patients with CM. Further multicenter studies would be helpful to determine if disease-modifying agents in addition to epileptic medications or surgery might be helpful.

Agosti|Edoardo|E|
Flemming|Kelly D|KD|
Lanzino|Giuseppe|G|

D020786:Hemangioma, Cavernous, Central Nervous System

Cavernous malformation
Seizure
Clinical presentation
Cavernoma


Multipoint dilution hemofiltration: A new technology for maximum convective clearance.

Abstract: Convection-based renal replacement therapies (RRTs) have the potential to improve patient outcomes when compared to diffusion-based RRT such as hemodialysis (HD), but have limited clearance rates. We propose and characterize multipoint dilution hemofiltration (MPD-HF), a purely convective blood purification technology which removes the fundamental filtration limit associated with convective RRT resulting in clearance rates on par with HD. In MPD-HF, filtration of liquid and solutes occurs along the length of the hollow fibers that convey the blood, and substitution fluid is pushed into the fibers at multiple points along their length. Since multiple filtration and dilution steps are contained within one pass of the blood through the hollow fiber, the fraction of fluid that can be filtered may be increased to allow a high clearance rate that removes a wide range of toxins. In vitro tests yielded an average steady-state filtrate fraction of 68%, exceeding commercial HDF cartridge filtrate fractions by a factor of approximately 3. The molecular weights of molecules cleared spans up to the cutoff of 66 kDa for albumin.

D015314:Dialysis Solutions
D004867:Equipment Design
D020342:Finite Element Analysis
D006440:Hemofiltration
D006801:Humans
D007676:Kidney Failure, Chronic
D008955:Models, Cardiovascular
D008970:Molecular Weight
D014118:Toxins, Biological

hemofiltration hemodialysis dialysis dialyzer hemodiafiltration


Predicting network of drug-enzyme interaction based on machine learning method.

Abstract: It is important to correctly and efficiently map drugs and enzymes to their possible interaction network in modern drug research. In this work, a novel approach was introduced to encode drug and enzyme molecules with physicochemical molecular descriptors and pseudo amino acid composition, respectively. Based on this encoding method, Random Forest was adopted to build the drug-enzyme interaction network. After selecting the optimal features that are able to represent the main factors of drug-enzyme interaction in our prediction, a total of 129 features were attained which can be clustered into nine categories: Elemental Analysis, Geometry, Chemistry, Amino Acid Composition, Secondary Structure, Polarity, Molecular Volume, Codon Diversity and Electrostatic Charge. It is further found that Geometry features were the most important of all the features. As a result, our predicting model achieved an MCC of 0.915 and a sensitivity of 87.9% at the specificity level of 99.8% for 10-fold cross-validation test, and achieved an MCC of 0.895 and a sensitivity of 95.7% at the specificity level of 95.4% for independent set test. This article is part of a Special Issue entitled: Computational Proteomics, Systems Biology & Clinical Implications. Guest Editor: Yudong Cai.

Niu|Bing|B| Zhang|Yuchao|Y| Ding|Juan|J| Lu|Yin|Y| Wang|Miao|M| Lu|Wencong|W| Yuan|Xiaochen|X| Yin|Jinyuan|J|

D000465:Algorithms
D001185:Artificial Intelligence
D019295:Computational Biology
D015195:Drug Design
D004791:Enzyme Inhibitors
D006801:Humans
D060066:Protein Interaction Maps
D011506:Proteins
D020539:Sequence Analysis, Protein

Machine learning
Molecular descriptor
Pseudo amino acid composition
Random Forest
CfsSubset
Drug–enzyme interaction


Chitosan hydrogel in combination with marine peptides from tilapia for burns healing.

Abstract: The purpose of this study was to develop a promising burns dressing. Chiosan (CS) has been widely used as biomaterials, in combination with marine peptides (MPs) extracted from seawater cultured Tilapia, the newly developed material Chitosan-Marine Peptides hydrogels (CSMP) in this study showed antibacterial activity, pro-cell proliferation and migration, well burning healing. Pathological examinations by HE staining demonstrated that CSMP had pronounced wound healing efficiencies. In burn wounds treated with CSMP, reepithelialization and collagen fiber deposition were observed on day 7, the epithelium was completely regenerated by day 14, and the wounds were completely healed by day 21. Furthermore, CSMP can up-regulate the expression of FGF2 and VEGF. Collectively, these results suggest that CSMP may enhance cell migration and promote the skin regeneration, which demonstrates the potential application of CSMP in burning healing.

Ouyang|Qian-Qian|QQ| Hu|Zhang|Z| Lin|Zhen-Peng|ZP| Quan|Wei-Yan|WY| Deng|Yi-Feng|YF| Li|Si-Dong|SD| Li|Pu-Wang|PW| Chen|Yu|Y|

D017550:Spectroscopy, Fourier Transform Infrared

D042461:Vascular Endothelial Growth Factor A


Association between IL-17F rs763780 polymorphism and susceptibility of asthma: a meta-analysis.

Abstract: Published data on the association between interleukin-17F (IL-17F) rs763780 polymorphism and asthma susceptibility are inconclusive. To derive a more precise estimation of this association, a meta-analysis was performed. A literature search was conducted in PubMed, Web of Science, Elsevier, Wanfang, and China National Knowledge Infrastructure (CNKI) databases to identify eligible studies. The pooled odds ratios (ORs) and corresponding 95% confidence intervals (CIs) were used to calculate the strength of association. Sensitivity analysis was performed to evaluate the influence of individual studies on the overall effect estimates and funnel plots were inspected for indication of publication bias. Seven studies with a total of 4200 subjects were finally identified. Overall, we found no significant association between IL-17F rs763780 polymorphism and asthma susceptibility (G vs. A: OR = 1.08, 95% CI = 0.81-1.44, P = 0.62; GA vs. AA: OR = 1.11, 95% CI = 0.84-1.47, P = 0.47; GG + GA vs. AA: OR = 1.07, 95% CI = 0.79-1.44, P = 0.65). After categorizing studies into different subgroups on the basis of ethnicity and age, there remained no significant association (all P > 0.05). Sensitivity analysis demonstrated the stability of our results and publication bias was not evident. The present meta-analysis, combining all currently available data, suggests that IL-17F rs763780 polymorphism is not associated with the susceptibility of asthma.

Ke|Rui|R| Xie|Xinming|X| Su|Xiaofan|X| Song|Yang|Y| Yang|Lan|L| Li|Manxiang|M|

IL-17F
asthma
meta-analysis
single nucleotide polymorphism


Structure of FcγRI in complex with Fc reveals the importance of glycan recognition for high-affinity IgG binding.

Abstract: Fc gamma receptor I (FcγRI) contributes to protective immunity against bacterial infections, but exacerbates certain autoimmune diseases. The sole high-affinity IgG receptor, FcγRI plays a significant role in immunotherapy. To elucidate the molecular mechanism of its high-affinity IgG binding, we determined the crystal structure of the extracellular domains of human FcγRI in complex with the Fc domain of human IgG1. FcγRI binds to the Fc in a similar mode as the low-affinity FcγRII and FcγRIII receptors. In addition to many conserved contacts, FcγRI forms additional hydrogen bonds and salt bridges with the lower hinge region of Fc. Unique to the high-affinity receptor-Fc complex, however, is the conformation of the receptor D2 domain FG loop, which enables a charged KHR motif to interact with proximal carbohydrate units of the Fc glycans. Both the length and the charge of the FcγRI FG loop are well conserved among mammalian species. Ala and Glu mutations of the FG loop KHR residues showed significant contributions of His-174 and Arg-175 to antibody binding, and the loss of the FG loop-glycan interaction resulted in an ∼ 20- to 30-fold decrease in FcγRI affinity to all three subclasses of IgGs. Furthermore, deglycosylation of IgG1 resulted in a 40-fold loss in FcγRI binding, demonstrating involvement of the receptor FG loop in glycan recognition. These results highlight a unique glycan recognition in FcγRI function and open potential therapeutic avenues based on antibody glycan engineering or small molecular glycan mimics to target FcγRI for certain autoimmune diseases.

Lu|Jinghua|J|
Chu|Jonathan|J|
Zou|Zhongcheng|Z|
Hamacher|Nels B|NB|
Rixon|Mark W|MW|
Sun|Peter D|PD|

D000595:Amino Acid Sequence
D001665:Binding Sites
D006801:Humans
D007074:Immunoglobulin G
D008969:Molecular Sequence Data
D011134:Polysaccharides
D011487:Protein Conformation
D017452:Receptors, IgG
D017386:Sequence Homology, Amino Acid

glycan recognition
crystal structure
CD64
FcgRI
IgG recognition


An increase of M2 macrophages predicts poor prognosis in patients with diffuse large B-cell lymphoma treated with rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone.

Abstract: Tumor-associated macrophages (TAMs) and regulatory T-cells (Tregs) play an important role in the tumor microenvironment. Here, we investigated the prognostic implications of TAMs and Tregs in 165 diffuse large B-cell lymphomas (DLBCLs) using immunohistochemistry. Survival analysis was performed among 109 DLBCLs treated with rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone (R-CHOP). An increase in CD68 (+) cells was related to improved overall survival (OS) (p = 0.033). By contrast, an increased number of CD163 (+) cells and a higher ratio of CD163/CD68 (+) cells were significantly associated with shorter OS (p = 0.041 and 0.003) and progression-free survival (PFS) (p < 0.001 and 0.002). Patients with increased Tregs tended to have a better prognosis. In multivariate analysis, an increased ratio of CD163/CD68 (+) cells was an independent predictor of shorter OS and PFS. These results suggest that M2 macrophages might have a lymphoma-promoting function in DLBCL and predict poor clinical outcome. Therapeutic approaches targeting M2 macrophages would be valuable for the management of DLBCL in the R era.

Nam|Soo Jeong|SJ|
Go|Heounjeong|H|
Paik|Jin Ho|JH|
Kim|Tae Min|TM|
Heo|Dae Seog|DS|
Kim|Chul Woo|CW|
Jeon|Yoon Kyung|YK|

D000971:Antineoplastic Combined Chemotherapy Protocols

M2 macrophages
diffuse large B-cell lymphoma
tumor-associated macrophages
regulatory T-cells
Tumor microenvironment


A self-adaptive multi-color fluorescent pH probe with the ability of whole cell imaging.

Abstract: Fluorescent pH probes are promising for both in vitro and in vivo pH detections in chemical and biochemical systems. Previously, the multi-color and whole cell pH sensing is a challenge for conventional fluorescent nanomaterials. In this work, we report an N, S co-doped carbon dots (N, S-CDs)-based fluorescent pH probe that can response to different incident light with tunable wavelength. The emission wavelength is tunable and correlated to the excitation wavelength, enabling self-adaptive multi-color sensing. The N, S-CDs was synthesized by a one-step hydrothermal method utilizing glucose, ammonium persulfate and ethylenediamine as precursors. The fluorescence of N, S-CDs shows a good linear relationship against pH values from 3.0 to 10.0 with a linear correlation coefficient of 0.996. The good biocompatibility and small size fulfill the demand of whole cell intracellular imaging. We have demonstrated that the N, S-CDs have successfully applied in HepG2 cells for the self-adaptive multi-color imaging.

Zhuang|Qi|Q| Si|Xiaojing|X| Li|Li|L| Zeng|Hongyan|H| Ding|Yaping|Y|

D002244:Carbon
D005453:Fluorescence
D005456:Fluorescent Dyes
D056945:Hep G2 Cells
D006801:Humans
D006863:Hydrogen-Ion Concentration
D057054:Molecular Imaging
D045663:Quantum Dots
D013050:Spectrometry, Fluorescence

Multi-color
Fluorescence pH probe
Cell imaging
N
S-carbon dots


Computer modelling of connectivity change suggests epileptogenesis mechanisms in idiopathic generalised epilepsy.

Abstract: Patients with idiopathic generalised epilepsy (IGE) typically have normal conventional magnetic resonance imaging (MRI), hence diagnosis based on MRI is challenging. Anatomical abnormalities underlying brain dysfunctions in IGE are unclear and their relation to the pathomechanisms of epileptogenesis is poorly understood. In this study, we applied connectometry, an advanced quantitative neuroimaging technique for investigating localised changes in white-matter tissues in vivo. Analysing white matter structures of 32 subjects we incorporated our in vivo findings in a computational model of seizure dynamics to suggest a plausible mechanism of epileptogenesis. Patients with IGE have significant bilateral alterations in major white-matter fascicles. In the cingulum, fornix, and superior longitudinal fasciculus, tract integrity is compromised, whereas in specific parts of tracts between thalamus and the precentral gyrus, tract integrity is enhanced in patients. Combining these alterations in a logistic regression model, we computed the decision boundary that discriminated patients and controls. The computational model, informed with the findings on the tract abnormalities, specifically highlighted the importance of enhanced cortico-reticular connections along with impaired cortico-cortical connections in inducing pathological seizure-like dynamics. We emphasise taking directionality of brain connectivity into consideration towards understanding the pathological mechanisms; this is possible by combining neuroimaging and computational modelling. Our imaging evidence of structural alterations suggest the loss of cortico-cortical and enhancement of cortico-thalamic fibre integrity in IGE. We further suggest that impaired connectivity from cortical regions to the thalamic reticular nucleus offers a therapeutic target for selectively modifying the brain circuit for reversing the mechanisms leading to epileptogenesis.

Sinha|Nishant|N|
Wang|Yujiang|Y|
Dauwels|Justin|J|
Kaiser|Marcus|M|
Thesen|Thomas|T|
Forsyth|Rob|R|
Taylor|Peter Neal|PN|

Computational model
Generalised epilepsy
Diagnosis
Diffusion MRI
Epilepsy mechanism


Cooled radiofrequency ablation of the genicular nerves for chronic pain due to osteoarthritis of the knee: a cost-effectiveness analysis based on trial data.

Abstract:
BACKGROUND
For patients with painful knee osteoarthritis, long-term symptomatic relief may improve quality of life. Cooled radiofrequency ablation (CRFA) has demonstrated significant improvements in pain, physical function and health-related quality of life compared with conservative therapy with intra-articular steroid (IAS) injections. This study aimed to establish the cost-effectiveness of CRFA compared with IAS for managing moderate to severe osteoarthritis-related knee pain, from the US Medicare system perspective.

METHODS
We conducted a cost-effectiveness analysis utilizing efficacy data (Oxford Knee Scores) from a randomized, crossover trial on CRFA (NCT02343003), which compared CRFA with IAS out to 6 and 12 months, and with IAS patients who subsequently crossed over to receive CRFA after 6 months. Outcomes included health benefits (quality-adjusted life-years [QALYs]), costs and cost-effectiveness (expressed as cost per QALY gained). QALYs were estimated by mapping Oxford Knee Scores to the EQ-5D generic utility measure using a validated algorithm. Secondary analyses explored differences in the settings of care and procedures used in-trial versus real-world clinical practice.

RESULTS
CRFA resulted in an incremental QALY gain of 0.091 at an incremental cost of $1711, equating to a cost of US$18,773 per QALY gained over a 6-month time horizon versus IAS. Over a 12-month time horizon, the incremental QALY gain was 0.229 at the same incremental cost, equating to a cost of US$7462 per QALY gained versus IAS. Real-world cost assumptions resulted in modest increases in the cost per QALY gained to a maximum of US$21,166 and US$8296 at 6 and 12 months, respectively. Sensitivity analyses demonstrated that findings were robust to variations in efficacy and cost parameters.

CONCLUSIONS
CRFA is a highly cost-effective treatment option for patients with osteoarthritis-related knee pain, compared with the US$100,000/QALY threshold typically used in the US.

D018771:Arthralgia
D059350:Chronic Pain
D003362:Cost-Benefit Analysis
D018592:Cross-Over Studies
D003714:Denervation
D005260:Female
D005938:Glucocorticoids
D017048:Health Care Costs
D006801:Humans
D007036:Hypothermia, Induced
D007270:Injections, Intra-Articular
D007719:Knee Joint
D008297:Male
D006278:Medicare
D009407:Nerve Block
D020370:Osteoarthritis, Knee
D011446:Prospective Studies
D019057:Quality-Adjusted Life Years
D000078703:Radiofrequency Ablation
D013997:Time Factors
D016896:Treatment Outcome
D014481:United States
D055815:Young Adult

CRFA
Intra-articular steroid
Oxford knee score
QALY
Cost-utility analysis
Economic analysis


Socioeconomic factors in timing of esophagectomy and association with outcomes.

Abstract:
BACKGROUND AND OBJECTIVES
Disparities in esophageal cancer are well-established. The standard treatment for locally advanced esophageal cancer is chemoradiation followed by surgery. We sought to evaluate the association between socioeconomic factors, time to surgery, and patient outcomes.

METHODS
All patients ≥18 years old diagnosed with T2/3/4 or node-positive esophageal cancer between 2004 and 2016 and who underwent chemoradiation and esophagectomy in the National Cancer Database were included. Multivariable regression was used to assess the association between socioeconomic variables and time to surgery (grouped into <56, 56-84, and 85-112 days).

RESULTS
A total of 12 157 patients were included. Five-year overall survival was 39%, 35%, and 35% for the three groups examined. Postoperative 30- and 90-day mortality was increased in both the 56-84 days to surgery group (odds ratio [OR]: 1.30 and 1.20, respectively) and the 85-112 days group (OR: 1.37 and 1.56, respectively) when compared to <56 days. Patients of a minority race, public insurance, or lower income were more likely to have a longer time to surgery.

CONCLUSION
Longer time to surgery is associated with increased postoperative mortality and is more common in patients with lower socioeconomic status. Further research exploring reasons for delays to esophagectomy among disadvantaged patients could help target interventions to reduce disparities.

esophagectomy
combined modality therapy
healthcare disparities
postoperative complications


A phase II study of endoscopic submucosal dissection for superficial esophageal neoplasms (KDOG 0901).

Abstract:
BACKGROUND
Most previous studies of endoscopic submucosal dissection (ESD) for superficial esophageal neoplasms were retrospective; prospective studies are scant.

OBJECTIVE
To prospectively assess the efficacy and safety of ESD for superficial esophageal neoplasms.

DESIGN
Phase II study.

SETTING
University hospital.

PATIENTS
Fifty-two patients (median age 68 years; 48 men) who had a histologic diagnosis of superficial esophageal cancer without metastasis on CT or high-grade intraepithelial neoplasia (HGIN) were enrolled from April 2009 through November 2011.

INTERVENTION
ESD was used to treat 56 lesions. All procedures were done by 4 endoscopists who each had previously performed ESD in more than 100 patients with gastric tumors.

MAIN OUTCOME MEASUREMENTS
The primary endpoint was the R0 resection rate, and secondary endpoints were the safety and the rate of accurately diagnosing tumor depth on endoscopic examination.

RESULTS
The median treatment time was 69 minutes (24-168 minutes). The histopathologic diagnosis was squamous cell carcinoma in 49 lesions, HGIN in 5, and tubular adenocarcinoma in 2. The en bloc resection rate and R0 resection rate were 100% and 94.6%, respectively. The rates of adverse events during ESD and after ESD were 22.2% and 53.8%, respectively, but most events were mild. One patient (1.9%) had mediastinal emphysema without perforation. The rate of accurately diagnosing tumor depth on endoscopic examination was 76.8%.

LIMITATIONS
Single-center, nonrandomized study.

CONCLUSION
Our study showed that ESD was an effective and relatively safe treatment for superficial esophageal neoplasms. ESD may be a useful treatment option for superficial esophageal neoplasms in hospitals with endoscopists who are experts in performing ESD for gastric tumors. (

CLINICAL TRIAL REGISTRATION NUMBER
UMIN000002047.).

Higuchi|Katsuhiko|K| Tanabe|Satoshi|S| Azuma|Mizutomo|M| Katada|Chikatoshi|C| Sasaki|Tohru|T| Ishido|Kenji|K| Naruke|Akira|A| Katada|Natsuya|N| Koizumi|Wasaburo|W|

deeper submucosal invasion (≥200 μm below the muscularis mucosae)

minute submucosal invasion (<200 μm below the muscularis mucosae)


Zinc Deficiency Induces Oxidative Damage and Causes Spleen Fibrosis.

Abstract: Zinc (Zn) is an essential trace element for animals. Zn controls the action of more than 300 enzymes and plays an important role in the regulation of gene expression. Evidence has shown that Zn has an antioxidant function, and oxidative damage can occur with Zn deficiency. To assess the effect of Zn deficiency-induced spleen fibrosis, Zn-deficient mice, normal mice, and high-Zn mice were generated and assessed. The Zn content of the spleen in each group was determined, and histopathological examination of the spleens of each group was performed. In the film, we found that the spleens of the Zn-deficient group had high levels of proteinaceous material exudation, interstitial broadening, and lymphocyte reduction, with increased collagen, α-SMA expression, antioxidants, and oxygen free radicals. Zn deficiency inhibited the expression of antioxidants in mice, and the activity of oxygen free radicals in Zn-deficient mice was increased. The detection of α-SMA, collagen 1, and TGF-β by fluorescence quantitative PCR revealed that the expression index increased in Zn-deficient mice. In addition, to verify the effect of Zn deficiency on the extracellular matrix (ECM) regulatory system, MMPs were determined by real-time PCR, and the expression in the Zn deficiency group was lower than that in the normal group and high-Zn group. The MMP-2 and MMP-13 analyses showed that the expression of the high-Zn group was significantly higher than that of the normal group, indicating that Zn plays an important role in its expression. The above experimental analysis showed that Zn deficiency induces oxygen free radical damage, which further leads to spleen fibrosis.

Zinc
Spleen
Fibrosis
Oxygen free radical
Extracellular matrix


Utrophin suppresses low frequency oscillations and coupled gating of mechanosensitive ion channels in dystrophic skeletal muscle.

Abstract: An absence of utrophin in muscle from mdx mice prolongs the open time of single mechanosensitive channels. On a time scale much longer than the duration of individual channel activations, genetic depletion of utrophin produces low frequency oscillations of channel open probability. Oscillatory channel opening occurred in the dystrophin/utrophin mutants, but was absent in wild-type and mdx fibers. By contrast, small conductance channels showed random gating behavior when present in the same patch. Applying a negative pressure to a patch on a DKO fiber produced a burst of mode II activity, but channels subsequently closed and remained silent for tens of seconds during the maintained pressure stimulus. In addition, simultaneous opening of multiple MS channels could be frequently observed in recordings from patches on DKO fibers, but only rarely in wild-type and mdx muscle. A model which accounts for the single-channel data is proposed in which utrophin acts as gating spring which maintains the mechanical stability a caveolar-like compartment. The state of this compartment is suggested to be dynamic; its continuity with the extracellular surface varying over seconds to minutes. Loss of the mechanical stability of this compartment contributes to pathogenic Ca(2+) entry through MS channels in Duchenne dystrophy.

utrophin
skeletal muscle
mechanosensitive channel
dystrophin
Duchenne muscular dystrophy
TRPV4
calcium
calcium entry
muscular dystrophy


Effects of nanoparticles exposure and PON1 genotype on heart rate variability.

Abstract:
OBJECTIVES
This study was to assess the association between different NPs exposure and PON1 genotype on Heart Rate Variability (HRV) parameters among workers.

METHODS
This study included 235 non-CVD subjects handled to nanomaterials (NM) and 185 non-exposed controls without CVD from 14 NM plants. All participants completed short-term HRV measurements, and were collected blood specimens to measure PON1 activities and the genotype of the PON1 Q192R polymorphism.

RESULTS
In a multivariate regression model, this study observed a positive relationship between nano-Ag exposure and HRV time-domain (RMSSD) and frequency-domain (HF). After adjusting for confounders, the results showed positive associations between RR homozygosity, PON1 paraoxonase/arylesterase activities with HRV, and was particularly noteworthy in RMSSD and HF.

CONCLUSIONS
This study shows a significant increment of RMSSD and HF among workers who handled Nano-Ag materials. These results imply that Nano-Ag and PON1 Q192R genotype can trigger ANS reflexes and alter cardiac frequency and function.

Nanoparticles
Heart rate variability
Nanomaterials
PON1 Q192R polymorphism
Paraoxonase


Hemiparesis after general anesthesia in a patient with migraine with unilateral motor symptoms.

Abstract:
DESIGN
This is a case report.

SETTING
The setting is at a postoperative recovery area.

PATIENTS
A 52-year-old woman with a history of migraine with unilateral motor symptoms developed hemiparesis after undergoing general anesthesia for total thyroidectomy.

INTERVENTIONS
No interventions were performed.

MEASUREMENTS/MAIN RESULTS
Head computed tomography and magnetic resonance imaging were normal. Laboratory studies including basic metabolic panel and complete blood count were also within normal limits.

CONCLUSIONS
General anesthesia may be a trigger for hemiplegic migraine syndromes; however, it behooves the practitioner to rule out acute neurologic and metabolic events before making this diagnosis.

Hadler|Rachel A|RA|
Schiffman|Joshua M|JM|
Augoustides|John G|JG|
Liu|Renyu|R|
Chen|Linda|L|

Anesthesia, general
Disease management
Headache
Migraine disorders
Perioperative period


Predicting performance in the first-year of pharmacy school.

Abstract:
OBJECTIVES
To determine the predictive validity of the Pharmacy College Admission Test (PCAT) scores and other variables for students' success in the first year of doctor of pharmacy (PharmD) programs.

METHODS
PCAT scores, entering grade-point averages (GPAs), demographic characteristics, and GPAs for the first year of pharmacy curriculum were collected from the Pharmacy College Application Service (PharmCAS) and from 22 pharmacy programs.

RESULTS
PCAT scores and entering GPAs were positively correlated with subsequent GPAs after the first year. Regression analyses showed the contribution of PCAT scores and entering GPAs in predicting first-year pharmacy GPAs.

CONCLUSIONS
PCAT scores and prepharmacy GPAs both showed moderate predictive validity in indicating candidates likely to succeed in the first year of the pharmacy program. These findings are consistent with those of previous similar studies.

Meagher|Donald G|DG|
Pan|Tianshu|T|
Perez|Christina D|CD|

D003099:College Admission Test
D003625:Data Collection
D004512:Education, Pharmacy
D004521:Educational Measurement
D005544:Forecasting
D006801:Humans
D012044:Regression Analysis
D012570:School Admission Criteria
D012580:Schools, Pharmacy
D013339:Students, Pharmacy

predictive validity
Pharmacy College Admission Test
assessment
grade point average
student performance


Modes of Interaction of KMT2 Histone H3 Lysine 4 Methyltransferase/COMPASS Complexes with Chromatin.

Abstract: Regulation of gene expression is achieved by sequence-specific transcriptional regulators, which convey the information that is contained in the sequence of DNA into RNA polymerase activity. This is achieved by the recruitment of transcriptional co-factors. One of the consequences of co-factor recruitment is the control of specific properties of nucleosomes, the basic units of chromatin, and their protein components, the core histones. The main principles are to regulate the position and the characteristics of nucleosomes. The latter includes modulating the composition of core histones and their variants that are integrated into nucleosomes, and the post-translational modification of these histones referred to as histone marks. One of these marks is the methylation of lysine 4 of the core histone H3 (H3K4). While mono-methylation of H3K4 (H3K4me1) is located preferentially at active enhancers, tri-methylation (H3K4me3) is a mark found at open and potentially active promoters. Thus, H3K4 methylation is typically associated with gene transcription. The class 2 lysine methyltransferases (KMTs) are the main enzymes that methylate H3K4. KMT2 enzymes function in complexes that contain a necessary core complex composed of WDR5, RBBP5, ASH2L, and DPY30, the so-called WRAD complex. Here we discuss recent findings that try to elucidate the important question of how KMT2 complexes are recruited to specific sites on chromatin. This is embedded into short overviews of the biological functions of KMT2 complexes and the consequences of H3K4 methylation.

KMT2
chromatin
gene expression
transcription
core histone
post-translational modification
histone mark
methylation
WDR5
RBBP5
ASH2L
DPY30
MLL
histone modification
mixed-lineage leukemia


Dropwort (Filipendula hexapetala Gilib.): potential role as antioxidant and antimicrobial agent.

Abstract: The aim of this study was to investigate the antioxidant activity of the methanolic extracts of Filipendula hexapetala Gilib. aerial parts (FHA) and roots (FHR) and their potential in different model systems, as well as antimicrobial activity. According to this, a number of assays were employed to evaluate the antioxidant and antimicrobial potential of F. hexapetala extracts. In addition, the antioxidant activity assays in different model systems were carried out, as well as pH, thermal and gastrointestinal stability studies. The phenolic compounds contents in FHA and FHR were also determined. The results showed that F. hexapetala extracts had considerable antioxidant activity in vitro and a great stability in different conditions. The extracts exhibited antimicrobial activity against most of the tested bacterial and fungal species. Also, the extracts contain high level of phenolic compounds, especially aerial parts extract.

Katanic|Jelena|J|
Mihailovic|Vladimir|V|
Stankovic|Nevena|N|
Boroja|Tatjana|T|
Mladenovic|Milan|M|
Solujic|Slavica|S|
Stankovic|Milan S|MS|
Vrvic|Miroslav M|MM|

Filipendula hexapetala Gilib.
antioxidant activity
antimicrobial activity
stability
phenolic compounds
in vitro digestion


Balloon-assisted endoscopic submucosal dissection for treating small intestinal lipomas: Report of two cases.

Abstract:
BACKGROUND
Most small intestinal lipomas are treated surgically, and some require repeated surgeries for multiple lipomas. However, application of endoscopic submucosal dissection (ESD) technology in the deep small intestine is rarely reported owing to the special anatomical structure of the small intestine, medical equipment limitations, and the lack of relevant experience among endoscopists.

CASE SUMMARY
Two patients with small intestinal lipomas treated at the Air Force Medical Center from November 2015 to September 2019 were selected to undergo balloon-assisted ESD to treat the lipomas and explore the technical feasibility and safety of ESD for treating small intestinal lipomas. The two patients successfully underwent balloon-assisted ESD to treat four small intestinal lipomas, with a complete resection rate of 100% (4/4), without intraoperative or postoperative bleeding, perforation, or other complications. After 3-6 mo of postoperative follow-up, the clinical symptoms caused by the lipomas were significantly relieved or disappeared after treatment.

CONCLUSION
Balloon-assisted ESD is a safe and reliable new method for treating deep intestinal lipomas and shows good clinical feasibility.

Chen|Hong-Yu|HY| Ning|Shou-Bin|SB| Yin|Xin|X| Li|Bai-Rong|BR| Zhang|Jing|J| Jin|Xiao-Wei|XW| Sun|Tao|T| Xia|Zhi-Bo|ZB| Zhang|Xiao-Peng|XP|

Endoscopic submucosal dissection
Small intestinal lipoma
Balloon-assisted endoscopy
Case report
Gastrointestinal tumor


Arts Therapies Interventions and Their Outcomes in the Treatment of Eating Disorders: Scoping Review Protocol.

Abstract: Arts therapies (AsTs) are considered a valuable intervention for people with eating disorders, however the range of research studies and the comparison between the types of arts therapies are unknown. The goal of the future scoping review is to explore the therapeutic outcomes addressed by arts therapists in research studies on people with eating disorders and compare the different types of arts-based interventions. This scoping review will be conducted in accordance with the Joanna Briggs Institute methodology. Included will be research studies and sources oriented towards people with eating disorders of all ages and AsTs of any type (art therapy, drama therapy, music therapy, dance/movement therapy, and expressive therapies). There is no language/publication period limitation. The following databases will be searched: CINAHL Plus, EMBASE, MEDLINE (OvidSP), ProQuest Central, PsycINFO, PubMed, Scopus, and Web of Science. Sources of unpublished studies and grey literature will include Google Scholar, MedNar, clinical trials, and current controlled trials. Titles/abstracts and full texts of studies will be assessed against the inclusion criteria, and the data extracted by two independent reviewers. Based on the results, we will compare the types of AsTs according to the research designs, country/settings, intervention methods/materials, adverse effects reported, and therapeutic outcomes related to AsTs.

art therapy
art therapy
eating disorder
drama therapy
music therapy
dance/movement therapy
anorexia
arts therapies
bulimia
dance movement psychotherapy
dance therapy


Construction of a teaching package on promoting prosocial internet use and preventing antisocial Internet use.

Abstract: In the construction of the teaching package on the Internet use, two major moral characters, respect and responsibility, form the core theoretical basis. The respect character consists of respect for others and self-respect while the responsibility character contains social, civil, and global responsibility. There are a total of nine units on the Internet use in the junior secondary curriculum. There are two units in Secondary One curriculum: the first unit deals with cheating behavior and privacy issues concerning the Internet, and the second one discusses the effect of excessive use of the Internet on life and study. In Secondary Two curriculum, we discuss the following social phenomena on the Internet with students: online shopping, pornographic materials on internet, and infringement of a copyright. Finally, we have designed four units on the Internet use in Secondary Three curriculum which focuses more on the relationship between the Internet use and our health. We try to answer the question on how we can use the Internet healthily and also the possibility on how it may hurt us. Similar to the second unit in Secondary One curriculum, we have designed three more units on discussing the effects of excessive use of the Internet with students. We would like to alert students that ineffective use of the Internet will hurt us mentally and physically. For illustrative purposes, two units in the Secondary One and Two curriculums are outlined in this paper.

Ma|Hing Keung|HK|
Chu|Miranda K Y|MK|
Chan|Winnie W Y|WW|

Teaching package
prosocial Internet use
antisocial Internet use


The potential of spectral and hyperspectral-imaging techniques for bacterial detection in food: A case study on lactic acid bacteria.

Abstract: Official methods for the detection of bacteria are based on culture techniques. These methods have limitations such as time consumption, cost, detection limits and the impossibility to analyse a large number of samples. For these reasons, the development of rapid, low-cost and non-destructive analytical methods is a task of growing interest. In the present study, the capability of spectral and hyperspectral techniques to detect bacterial surface contamination was investigated preliminarily on gel cultures, and subsequently on sliced cooked ham. In more detail, two species of lactic acid bacteria (LAB) were considered, namely Lactobacillus curvatus and Lactobacillus sakei, both of which are responsible for common alterations in sliced cooked ham. Three techniques were investigated, with different equipment, respectively: a macroscopic hyperspectral scanner operating in the NIR (10,470-5880cm(-1)) region, a FT-NIR spectrophotometer equipped with a transmission arm as the sampling tool, working in the 12,500-5800cm(-1) region, and a FT-MIR microscopy operating in the 4000-675cm(-1) region. Multivariate exploratory data analysis, in particular principal component analysis (PCA), was applied in order to extract useful information from original data and from hyperspectrograms. The results obtained demonstrate that the spectroscopic and imaging techniques investigated can represent an effective and sensitive tool to detect surface bacterial contamination in samples and, in particular, to recognise species to which bacteria belong.

Foca|Giorgia|G| Ferrari|Carlotta|C| Ulrici|Alessandro|A| Sciutto|Giorgia|G| Prati|Silvia|S| Morandi|Stefano|S| Brasca|Milena|M| Lavermicocca|Paola|P| Lanteri|Silvia|S| Oliveri|Paolo|P|

D005504:Food Analysis
D005516:Food Microbiology
D005519:Food Preservation
D019344:Lactic Acid
D007778:Lactobacillus
D008461:Meat Products

Cooked ham
Lactic acid bacteria (LAB)
Principal component analysis (PCA)
FT-IR microscopy
FT-NIR spectroscopy
Hyperspectral imaging


Survival Rate on a 10-Year Follow-Up of Total Wrist Replacement Implants: A 23-Patient Case Series.

Abstract: Background  According to current literature, the estimated average survival rate for Remotion, the total wrist implants, is above 90% on an 8-year follow-up. We examined our series of Remotion to calculate its survival rate on a 10-year follow-up. Case Description  A total of 23 cases of total wrist implants were reviewed. The case series included 22 patients, 18 females and 4 males, of an average age of 55 years. The case series included 19 inflammatory rheumatic diseases, 3 Kienböck disease, and 1 posttraumatic arthrosis. Conclusion  The average survival rate of our case series was 95.7% on a 4-year follow-up, 91.3% on a 6-year follow-up, and 69% on a 10-year follow-up. On our review, the QuickDASH score, pain, wrist extension range of motion, and grip strength were improved postoperatively. No difference was shown between preoperative and postoperative values for wrist flexion, pronation, and supination. The case series included a septic case, treated by arthrodesis, and three total wrist implants displacements, two of which were treated by carpal implant, and the remaining one was treated by arthrodesis. Clinical Relevance  The survival rate of the total wrist replacement implant Remotion was estimated to be 69%.

Honecker|Sophie|S|
Igeta|Yuka|Y|
Al Hefzi|Ali|A|
Pizza|Chiara|C|
Facca|Sybille|S|
Liverneaux|Philippe A|PA|


Macrophage Biocompatibility of CoCr Wear Particles Produced under Polarization in Hyaluronic Acid Aqueous Solution.

Abstract: Macrophages are the main cells involved in inflammatory processes and in the primary response to debris derived from wear of implanted CoCr alloys. The biocompatibility of wear particles from a high carbon CoCr alloy produced under polarization in hyaluronic acid (HA) aqueous solution was evaluated in J774A.1 mouse macrophages cultures. Polarization was applied to mimic the electrical interactions observed in living tissues. Wear tests were performed in a pin-on-disk tribometer integrating an electrochemical cell in phosphate buffer solution (PBS) and in PBS supplemented with 3 g/L HA, an average concentration that is generally found in synovial fluid, used as lubricant solution. Wear particles produced in 3 g/L HA solution showed a higher biocompatibility in J774A.1 macrophages in comparison to those elicited by particles obtained in PBS. A considerable enhancement in macrophages biocompatibility in the presence of 3 g/L of HA was further observed by the application of polarization at potentials having current densities typical of injured tissues suggesting that polarization produces an effect on the surface of the metallic material that leads to the production of wear particles that seem to be macrophage-biocompatible and less cytotoxic. The results showed the convenience of considering the influence of the electric interactions in the chemical composition of debris detached from metallic surfaces under wear corrosion to get a better understanding of the biological effects caused by the wear products.

Perez-Maceda|Blanca Teresa|BT|
López-Fernández|María Encarnación|ME|
Díaz|Iván|I|
Kavanaugh|Aaron|A|
Billi|Fabrizio|F|
Escudero|María Lorenza|ML|
García-Alonso|María Cristina|MC|
Lozano|Rosa María|RM|

macrophages biocompatibility
wear particles
polarization
hyaluronic acid
CoCr alloy


Correlates of excessive daytime sleepiness in de novo Parkinson's disease: A case control study.

Abstract:
OBJECTIVE
This study was undertaken to determine the frequency and correlates of excessive daytime sleepiness in de novo, untreated Parkinson's disease (PD) patients compared with the matched healthy controls.

METHODS
Data were obtained from the Parkinson's Progression Markers Initiative, an international study of de novo, untreated PD patients and healthy controls. At baseline, participants were assessed with a wide range of motor and nonmotor scales, including the Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS). Excessive daytime sleepiness was assessed based on the Epworth Sleepiness scale (ESS), with a cutoff of 10.

RESULTS
Four hundred twenty-three PD subjects and 196 healthy controls were recruited into the study. Mean ESS (min, max) score was 5.8 (0, 20) for the PD subjects and 5.6 (0, 19) for healthy controls (P = 0.54). Sixty-six (15.6%) PD subjects and 24 (12%) healthy controls had ESS of at least 10 (P = 0.28). No difference was seen in demographic characteristics, age of onset, disease duration, PD subtype, cognitive status, or utilization of sedatives between the PD sleepiness-positive versus the negative group. The sleepiness-positive group had higher MDS-UPDRS Part I and II but not III scores, and higher depression and autonomic dysfunction scores. Sleepiness was associated with a marginal reduction of A-beta (P = 0.05) but not alpha-synuclein spinal fluid levels in PD.

CONCLUSIONS
This largest case control study demonstrates no difference in prevalence of excessive sleepiness in subjects with de novo untreated PD compared with healthy controls. The only clinical correlates of sleepiness were mood and autonomic dysfunction. Ongoing longitudinal analyses will be essential to further examine clinical and biological correlates of sleepiness in PD and specifically the role of dopaminergic therapy.

Simuni|Tanya|T|
Caspell-Garcia|Chelsea|C|
Coffey|Christopher|C|
Chahine|Lama M|LM|
Lasch|Shirley|S|
Oertel|Wolfgang H|WH|
Mayer|Geert|G|
Högl|Birgit|B|
Postuma|Ron|R|
Videnovic|Aleksandar|A|
Amara|Amy Willis|AW|
Marek|Ken|K|
|||

D006970:Disorders of Excessive Somnolence

Parkinson's disease
biomarkers
daytime somnolence


Bouba or kiki with and without vision: Shape-audio regularities and mental images.

Abstract: 95% of the world's population associate a rounded visual shape with the spoken word 'bouba', and an angular visual shape with the spoken word 'kiki', known as the bouba/kiki-effect. The bouba/kiki-effect occurs irrespective of familiarity with either the shape or word. This study investigated the bouba/kiki-effect when using haptic touch instead of vision, including the role of visual imagery. It also investigated whether the bouba/kiki shape-audio regularities are noticed at all, that is, whether they affect the bouba/kiki-effect itself and/or the recognition of individual bouba/kiki shapes, and finally what mental images they produce. Three experiments were conducted, with three groups of participants: blind, blindfold, and vision. In Experiment 1, the participants were asked to pick out the tactile/visual shape that they associated with the auditory bouba/kiki. Experiment 1 found that the participants who were blind did not show an instant bouba/kiki-effect (in Trial 1), whereas the blindfolded and the fully sighted did. It also found that the bouba/kiki shape-audio regularities affected the bouba/kiki-effect when using haptic touch: Those who were blind did show the bouba/kiki-effect from Trial 4, and those who were blindfolded no longer did. In Experiment 2, the participants were asked to name one tactile/visual shape and a segment of audio together as either 'bouba' or 'kiki'. Experiment 2 found that corresponding shape and audio improved the accuracy of both the blindfolded and the fully sighted, but not of those who were blind - they ignored the audio. Finally, in Experiment 3, the participants were asked to draw the shape that they associated with the auditory bouba/kiki. Experiment 3 found that their mental images, as depicted in their drawings, were not affected by whether they had experienced the bouba/kiki shapes by haptic touch or by vision. Regardless of their prior shape experience, that is, tactile or visual, their mental images included the most characteristic shape feature of bouba and kiki: curve and angle, respectively, and typically not the global shape. When taken together, these experiments suggest that the sensory regularities and mental images concerning bouba and kiki do not have to be based on, or even include visual information.

Mental image
Bouba/kiki-effect
Haptic touch
Sensory regularities
Multisensory integration
Shape recognition


Characterization of Proteoforms with Unknown Post-translational Modifications Using the MIScore.

Abstract: Various proteoforms may be generated from a single gene due to primary structure alterations (PSAs) such as genetic variations, alternative splicing, and post-translational modifications (PTMs). Top-down mass spectrometry is capable of analyzing intact proteins and identifying patterns of multiple PSAs, making it the method of choice for studying complex proteoforms. In top-down proteomics, proteoform identification is often performed by searching tandem mass spectra against a protein sequence database that contains only one reference protein sequence for each gene or transcript variant in a proteome. Because of the incompleteness of the protein database, an identified proteoform may contain unknown PSAs compared with the reference sequence. Proteoform characterization is to identify and localize PSAs in a proteoform. Although many software tools have been proposed for proteoform identification by top-down mass spectrometry, the characterization of proteoforms in identified proteoform-spectrum matches still relies mainly on manual annotation. We propose to use the Modification Identification Score (MIScore), which is based on Bayesian models, to automatically identify and localize PTMs in proteoforms. Experiments showed that the MIScore is accurate in identifying and localizing one or two modifications.

Kou|Qiang|Q| Zhu|Binhai|B| Wu|Si|S| Ansong|Charles|C| Tolić|Nikola|N| Paša-Tolić|Ljiljana|L| Liu|Xiaowen|X|


Working from home during the COVID-19 pandemic: Impact on office worker productivity and work experience.

Abstract:
BACKGROUND
With the COVID-19 pandemic, organizations embraced Work From Home (WFH). An important component of transitioning to WFH is the effect on workers, particularly related to their productivity and work experience.

OBJECTIVES
The objective of this study is to examine how worker-, workspace-, and work-related factors affected productivity and time spent at a workstation on a typical WFH day during the pandemic.

METHODS
An online questionnaire was designed and administered to collect the necessary information. Data from 988 respondents were included in the analyses.

RESULTS
Overall perception of productivity level among workers did not change relative to their in-office productivity before the pandemic. Female, older, and high-income workers were likely to report increased productivity. Productivity was positively influenced by better mental and physical health statuses, having a teenager, increased communication with coworkers and having a dedicated room for work. Number of hours spent at a workstation increased by approximately 1.5 hours during a typical WFH day. Longer hours were reported by individuals who had school age children, owned an office desk or an adjustable chair, and had adjusted their work hours.

CONCLUSION
The findings highlight key factors for employers and employees to consider for improving the WFH experience.

Awada|Mohamad|M| Lucas|Gale|G| Becerik-Gerber|Burcin|B| Roll|Shawn|S|

workstation
work hours
Remote work
office work
socioeconomic impact
workspace


Compound reading in Hebrew text-based neglect dyslexia: the effects of the first word on the second word and of the second on the first.

Abstract: In many Hebrew compounds, which are two-word phrases, the first word is marked morphophonologically, and often also orthographically, as the head of the compound. Because Hebrew is read from right to left, this allowed us to ask whether a right-hand word that is marked orthographically as a compound-head, and hence signals that another word is expected, causes readers with text-based neglect to continue shifting attention to the left and read the second word. We also asked whether the second, left-hand, word affects the reading of the first word. The effect of the second word was assessed in a condition in which the second word semantically disambiguated the first word, a biased heterophonic homograph, and a condition in which the second word formed a compound with the first and hence required reading the first in the morphophonological form of a compound-head. The two participants were Hebrew-speaking men with acquired left text-level neglect dyslexia, without word-based neglect dyslexia. They read 294 two-word compounds and control phrases, composed of five conditions that assessed the effect of the first word on the second word, and of the second on the first. The results indicated that morphosyntax modulates reading in neglect dyslexia. When the first, right-hand, word included an orthographic cue indicating that a second word follows, fewer words on the left were omitted than when no such cue existed. The second word, however, did not affect the reading of the first, and the first word was read as if the patients did not look ahead to the second.

Compounds
Neglect
Neglect dyslexia
Hebrew.
Morphology
Syntax


Poly(amino acid) Multilayers Modified Dendritic Mesoporous Silica Nanoparticles Achieve Effective Enzyme Stability for Ultrasensitive Immunoassay.

Abstract: Enzyme-linked immunosorbent assay (ELISA) is one of the most common techniques in biomedical detection; however, the poor sensitivity in early diagnosis for some diseases seriously limits its application. In this work, we developed an ultrasensitive ELISA system that is based on horseradish peroxidase (HRP)-loaded dendritic mesoporous silica nanoparticles (DMSN) modified with poly(amino acid) multilayers (defined as DSHP). A large amount of HRP adsorption was achieved in center-radial mesoporous channels of DMSN because of the high specific surface area and large pore size, leading to significant signal amplification. Additionally, DSHP could not only effectively maintain HRP activity for at least 10 days but also provide preferable protection for HRP activity even at high temperatures or a wide pH range. Moreover, the DSHP system exhibited admirable signal amplification performance with a limit of detection of 0.667 fM and a wide detectable range from 6.67 × 10-4 to 6.67 × 105 pM, whose sensitivity was 104 times higher than that of the conventional ELISA. We believe that the DSHP will offer a new strategy for signal amplification of the ELISA system in clinical diagnosis.


Electrochemotherapy, a local treatment for squamous cell carcinoma in patients with recessive dystrophic epidermolysis bullosa.

Abstract: Epidermolysis Bullosa (EB) is a rare group of diseases caused by genetic variants in skin structural proteins. EB is characterized by varying degrees of skin fragility, blisters and impaired wound healing, and is classified based on the ultrastructural levels of skin cleavage-simplex, junctional, dystrophic, and Kindler Syndrome. Squamous cell carcinoma (SCC) is the most severe complication and most common cause of death of patients with EB, particularly in those with recessive dystrophic Epidermolysis Bullosa (RDEB). To date, the first line of treatment of SCC in patients with RDEB is surgery, despite the high risk of recurrence. Radiotherapy and systemic therapy have been avoided due to its skin toxicity. Recently, electrochemotherapy (ECT) has been proposed as a potential treatment. We report eight sessions of ECT using bleomycin for treatment of SCC in five patients with EB. After 8 weeks all patients showed an objective response. Four patients (seven ECT sessions) had a complete response. The treatment was well tolerated, with mild adverse effects, such as local pain, erythema, and ulceration. Our results demonstrate that ECT is a potential treatment for SCC in patients with RDEB.

chemotherapy
electroporation
genodermatoses
non-melanoma
skin cancer


Comparison of Two Rabbit Models with Deficiency of Corneal Epithelium and Limbal Stem Cells Established by Different Methods.

Abstract: Limbal stem cell defect model is an important animal model that provides a basis for the study of ocular surface diseases. The rabbit cornea is of moderate size and is widely used in such studies as an experimental animal model. At present, the main modeling methods are alkali burns, and corneal limbus girdling and corneal epithelium doctoring. Each method has its own characteristics. In this study, we observed rabbit models with severe ocular surface defect established by the two methods and changes after amniotic membrane transplantation. In the first, second, third, and fourth week after operation, the clinical manifestations, corneal transparency, and new vessels were observed according to the standard rating scale of ocular surface, compared between the two methods, and then statistically analyzed. In the fourth week after operation, the rabbits were sacrificed and their corneas and corneal limbus were extracted from sclera, embedded by optimum cutting temperature compound, frozen, and sliced for hematoxylin and eosin staining and pathological examination. There were two groups in this study. Group 1 (alkali burns) had more severe complications, such as, conjunctiva, nubecula, new vessel hyperplasia, and so on, compared to group 2 (corneal limbus girdling and corneal epithelium doctoring). In addition, there were striking differences in corneal transparency and new vessels between the two groups (p < 0.05). Corneal transparency in group 1 was lower than in group 2. New vessels in group 1 were less in the first 2 weeks, but obviously increased compared to group 2 in the subsequent weeks. Alkaline burn could be used to study new vessel hyperplasia, while corneal limbus girdling and corneal epithelium doctoring are more suitable for studying stem cell transdifferentiation, interactive roles of stem cells and microenvironment, and so on.

Zhang|Hening|H| Lin|Shaochun|S| Zhang|Min|M| Li|Qijiong|Q| Li|Weihua|W| Wang|Wencong|W| Zhao|Minglei|M| Xie|Yaojue|Y| Li|Zhiquan|Z| Huang|Mian|M| Wang|Zhichong|Z| Zhang|Xiulan|X| Huang|Bing|B|

rabbit
ocular surface
corneal limbus girdling
amniotic membrane
alkaline burn


Time to Amyloid Positivity and Preclinical Changes in Brain Metabolism, Atrophy, and Cognition: Evidence for Emerging Amyloid Pathology in Alzheimer's Disease.

Abstract: Background: Aβ pathology is associated with longitudinal changes of brain metabolism, atrophy, and cognition, in cognitively healthy elders. However, Aβ information is usually measured cross-sectionally and dichotomized to classify subjects as Aβ-positive or Aβ-negative, making it difficult to evaluate when brain and cognitive changes occur with respect to emerging Aβ pathology. In this study, we use longitudinal Aβ information to combine the level and rate of change of Aβ to estimate the time to Aβ-positivity for each subject and test this temporal proximity to significant Aβ pathology for associations with brain structure, metabolism, and cognition. Methods: In 89 cognitively healthy elders with up to 10 years of follow-up, we estimated the points at which rates of fluorodeoxyglucose (FDG) PET, MRI, and cognitive and functional decline begin to accelerate with respect to the time to Aβ-positivity. Points of initial acceleration in rates of decline were estimated using mixed-effects models with penalized regression splines. Results: Acceleration of rates of FDG PET were observed to occur 20+ years before the conventional threshold for Aβ-positivity. Subtle signs of cognitive dysfunction were observed 10+ years before Aβ-positivity. Conclusions: Aβ may have subtle associations with other hallmarks of Alzheimer's disease before Aβ biomarkers reach conventional thresholds for Aβ-positivity. Therefore, we propose that emerging Aβ pathology occurs many years before cognitively healthy elders reach the current threshold for Aβ positivity (preclinical AD). To allow prevention in the earliest disease stages, AD clinical trials may be designed to also include subjects with Aβ biomarkers in the sub-threshold range.

Insel|Philip S|PS|
Ossenkoppele|Rik|R|
Gessert|Devon|D|
Jagust|William|W|
Landau|Susan|S|
Hansson|Oskar|O|
Weiner|Michael W|MW|
Mattsson|Niklas|N|
|||

preclinical
metabolism
atrophy
cognition
Alzheimer's disease
β-amyloid


Cell and Tissue Therapy for the Treatment of Chronic Liver Disease.

Abstract: Liver disease is an important clinical problem, impacting 600 million people worldwide. It is the 11th-leading cause of death in the world. Despite constant improvement in treatment and diagnostics, the aging population and accumulated risk factors led to increased morbidity due to nonalcoholic fatty liver disease and steatohepatitis. Liver transplantation, first established in the 1960s, is the second-most-common solid organ transplantation and is the gold standard for the treatment of liver failure. However, less than 10% of the global need for liver transplantation is met at the current rates of transplantation due to the paucity of available organs. Cell- and tissue-based therapies present an alternative to organ transplantation. This review surveys the approaches and tools that have been developed, discusses the distinctive challenges that exist for cell- and tissue-based therapies, and examines the future directions of regenerative therapies for the treatment of liver disease.

Bram|Yaron|Y|
Nguyen|Duc-Huy T|DT|
Gupta|Vikas|V|
Park|Jiwoon|J|
Richardson|Chanel|C|
Chandar|Vasuretha|V|
Schwartz|Robert E|RE|

liver
cell therapy
stem cell biology
tissue engineering


Toxicity in Neonicotinoids to Folsima candida and Eisenia andrei.

Abstract: We compared the toxicity of the neonicotinoids imidacloprid, thiacloprid, thiamethoxam, acetamiprid, and clothianidin in terms of the survival and reproduction of 2 species of soil invertebrates, Folsomia candida and Eisenia andrei. Tests were performed using LUFA 2.2 natural soil, following standard protocols aimed at answering 2 questions: 1) Is there a difference in the toxicity between pure compound and its formulation? and 2) Is there a difference in the sensitivity of the species exposed to the same compound? For E. andrei, formulations and pure compounds had similar toxicity to both endpoints tested. For F. candida, acetamiprid and imidacloprid had different toxicities, with acetamiprid being 4 times more toxic to survival (median lethal concentration [LC50] 0.12 mg active substance [a.s.]/kg dry soil) and imidacloprid being 4 times more toxic to reproduction of the springtail (median effect concentration [EC50] 0.25 mg a.s./kg dry soil) than their commercial formulations. The most toxic compound to E. andrei was acetamiprid (LC50 0.80 and EC50 0.35-0.40 mg a.s./kg), and the most toxic to F. candida was clothianidin (LC50 0.07 and EC50 0.05 mg a.s./kg). Estimated risk ratios indicated that only one application/yr of clothianidin in the formulation Poncho® may pose a threat to the populations of springtails and earthworms. Environ Toxicol Chem 2020;39:548-555. © 2019 The Authors. Environmental Toxicology and Chemistry published by Wiley Periodicals, Inc. on behalf of SETAC.

van Gestel|Cornelis A M|CAM|0000-0002-5651-0208

Soil invertebrates
Risk assessment
Soil ecotoxicology


USP44 suppresses proliferation and enhances apoptosis in colorectal cancer cells by inactivating the Wnt/β-catenin pathway via Axin1 deubiquitination.

Abstract: Colorectal cancer (CRC) is the leading cause of cancer death, and its 5-year survival rate remains unsatisfactory. Recent studies have revealed that ubiquitin-specific protease 44 (USP44) is a cancer suppressor or oncogene depending on the type of neoplasm. However, its role in CRC remains unclear. Here, we found that the USP44 expression level was markedly decreased in CRC, and USP44 overexpression inhibited proliferation while enhancing apoptosis in CRC cells, suggesting that USP44 is a cancer suppressor in CRC. We then investigated if USP44 functioned through regulating the Wnt/β-catenin pathway. We found that USP44 overexpression increased the Axin1 protein while decreasing β-catenin, c-myc, and cyclin D1 proteins, suggesting that USP44 inhibited the activation of the Wnt/β-catenin pathway. Moreover, we found that two Wnt/β-catenin activators, LiCl and SKL2001, both attenuated oeUSP44-mediated proliferation and apoptosis in CRC cells. Collectively, these data points indicated that USP44 inhibited proliferation while promoting apoptosis in CRC cells by inhibiting the Wnt/β-catenin pathway. Interestingly, we observed that USP44 overexpression did not affect the Axin1 mRNA level. Further study uncovered that USP44 interacted with Axin1 and reduced the ubiquitination of Axin1. Furthermore, Axin1 knock-down abolished the effects of oeUSP44 on proliferation, apoptosis, and Wnt/β-catenin activity in CRC cells. Taken together, this study demonstrates that USP44 inhibits proliferation while enhancing apoptosis in CRC cells by inactivating the Wnt/β-catenin pathway via Axin1 deubiquitination. USP44 is a cancer suppressor in CRC and a potential target for CRC therapy.

Huang|Tong|T| Zhang|Qingquan|Q| Ren|Wei|W| Yan|Bing|B| Yi|Liang|L| Tang|Tielun|T| Lin|Hai|H| Zhang|Yongjiu|Y|

D017209:Apoptosis
D060466:Axin Protein
D045744:Cell Line, Tumor
D049109:Cell Proliferation
D015179:Colorectal Neoplasms
D055785:Gene Knockdown Techniques
D006801:Humans
D043222:Ubiquitin Thiolesterase
D060449:Wnt Signaling Pathway


Global variability in leaf respiration in relation to climate, plant functional types and leaf traits.

Abstract: Leaf dark respiration (Rdark ) is an important yet poorly quantified component of the global carbon cycle. Given this, we analyzed a new global database of Rdark and associated leaf traits. Data for 899 species were compiled from 100 sites (from the Arctic to the tropics). Several woody and nonwoody plant functional types (PFTs) were represented. Mixed-effects models were used to disentangle sources of variation in Rdark . Area-based Rdark at the prevailing average daily growth temperature (T) of each site increased only twofold from the Arctic to the tropics, despite a 20°C increase in growing T (8-28°C). By contrast, Rdark at a standard T (25°C, Rdark (25) ) was threefold higher in the Arctic than in the tropics, and twofold higher at arid than at mesic sites. Species and PFTs at cold sites exhibited higher Rdark (25) at a given photosynthetic capacity (Vcmax (25) ) or leaf nitrogen concentration ([N]) than species at warmer sites. Rdark (25) values at any given Vcmax (25) or [N] were higher in herbs than in woody plants. The results highlight variation in Rdark among species and across global gradients in T and aridity. In addition to their ecological significance, the results provide a framework for improving representation of Rdark in terrestrial biosphere models (TBMs) and associated land-surface components of Earth system models (ESMs).

Atkin|Owen K|OK|
Bloomfield|Keith J|KJ|
Reich|Peter B|PB|
Tjoelker|Mark G|MG|
Asner|Gregory P|GP|
Bonal|Damien|D|
Bönisch|Gerhard|G|
Bradford|Matt G|MG|
Cernusak|Lucas A|LA|
Cosio|Eric G|EG|
Creek|Danielle|D|
Crous|Kristine Y|KY|
Domingues|Tomas F|TF|
Dukes|Jeffrey S|JS|
Egerton|John J G|JJ|
Evans|John R|JR|
Farquhar|Graham D|GD|
Fyllas|Nikolaos M|NM|
Gauthier|Paul P G|PP|
Gloor|Emanuel|E|
Gimeno|Teresa E|TE|
Griffin|Kevin L|KL|
Guerrieri|Rossella|R|
Heskel|Mary A|MA|
Huntingford|Chris|C|
Ishida|Françoise Yoko|FY|
Kattge|Jens|J|
Lambers|Hans|H|
Liddell|Michael J|MJ|
Lloyd|Jon|J|
Lusk|Christopher H|CH|
Martin|Roberta E|RE|
Maksimov|Ayal P|AP|
Maximov|Trofim C|TC|
Malhi|Yadvinder|Y|
Medlyn|Belinda E|BE|
Meir|Patrick|P|
Mercado|Lina M|LM|
Mirotchnick|Nicholas|N|
Ng|Desmond|D|
Niinemets|Ülo|Ü|
O'Sullivan|Odhran S|OS|
Phillips|Oliver L|OL|
Poorter|Lourens|L|
Poot|Pieter|P|
Prentice|I Colin|IC|
Salinas|Norma|N|
Rowland|Lucy M|LM|
Ryan|Michael G|MG|
Sitch|Stephen|S|
Slot|Martijn|M|
Smith|Nicholas G|NG|
Turnbull|Matthew H|MH|
VanderWel|Mark C|MC|
Valladares|Fernando|F|
Veneklaas|Erik J|EJ|
Weerasinghe|Lasantha K|LK|
Wirth|Christian|C|
Wright|Ian J|IJ|
Wythers|Kirk R|KR|
Xiang|Jen|J|
Xiang|Shuang|S|
Zaragoza-Castells|Joana|J|

respiration
plant functional types (PFTs)
temperature
aridity
acclimation
climate models
leaf nitrogen (N)
photosynthesis


Antibacterial Susceptibility Pattern of the Pseudomonas aeruginosa and Staphylococcus aureus after Exposure to Electromagnetic Waves Emitted from Mobile Phone Simulator.

Abstract:
Background
The increasing use of telecommunication devices such as Wi-Fi modems and mobile phones in the recent years can change the cellular structure of microorganisms so the generation of electromagnetic waves has led to concern in the community whenever be exposed to these fields and may have harmful effects on human health.

Material and Methods
In this experimental study, standard strains of bacteria were prepared on Mueller-Hinton agar for bacterial growth to obtain 0.5 McFarland turbidity (1.5 × 108 CFU) of bacteria. Antibiotic susceptibility test using the Kirby-Bauer disk diffusion method was done. For Staphylococcus aureus and Pseudomonas aeruginosa, antibiotics susceptibility test was conducted. The test group was exposed to electromagnetic waves emitted by mobile phone simulator with a frequency of 900 MHz and the control group were not exposed.

Results
The results revealed that increasing duration of exposure to electromagnetic waves emitted by the mobile simulators with a frequency of 900 MHz especially after 24 h of exposure, can increase bacterial resistance in S. aureus, and P. aeruginosa.

Conclusion
Several factors can cause bacterial resistance against antibiotics. One of these factors is the electromagnetic waves emitted from mobile simulator with a frequency of 900 MHz, which can increase the permeability of the cell wall of bacteria.

Movahedi|M M|MM|
Nouri|F|F|
Tavakoli Golpaygani|A|A|
Ataee|L|L|
Amani|S|S|
Taheri|M|M|

Pseudomonas aeruginosa
Staphylococcus aureus
Electromagnetic waves
Mobile simulator
Microbial Sensitivity Tests


The Density Code for the Development of a Vaccine?

Abstract: The development of prophylactic vaccines remains largely empirical in nature and rarely have general rules been applied in the strategic decision and the formulation of a viral vaccine. Currently, there are a total of 15 virus agents from 12 unique virus families with vaccines licensed by the U.S. Food and Drug Administration. Extensive structural information on these viral particles and potential mechanisms of protection are available for the majority of these virus pathogens and their respective vaccines. Here I review the quantitative features of these viral surface antigens in relation to the molecular mechanisms of B-cell activation and point out a potential correlation between the density of immunogenic proteins displayed on the surface of the vaccine antigen carrier and the success of a vaccine. These features help us understand the humoral immunity induced by viral vaccines on a quantitative ground and re-emphasize the importance of antigen density on the activation of the immune system. Although the detailed mechanisms behind this phenomenon remain to be explored, it implies that both the size of antigen carriers and the density of immunogenic proteins displayed on these carriers are important parameters that may need to be optimized for the formulation of a vaccine.

D000818:Animals
D000956:Antigens, Viral
D001402:B-Lymphocytes
D004339:Drug Compounding
D055808:Drug Discovery
D006801:Humans
D056724:Immunity, Humoral
D014765:Viral Vaccines
D014777:Virus Diseases

vaccines
B-cell activation
B-cell receptor
immune response
immunology
nanoparticles
particulate antigen
protein density
vaccine delivery


Fast Screening of Corrosion Trends in Metallic Glasses.

Abstract: Corrosion trends in the bulk metallic glass forming alloy system Zr-Cu-Al are studied through a fast screening visual characterization method of thin film alloy libraries prepared by magnetron co-sputtering. Significant distinct brightness changes are present within the Zr-Cu-Al system when the thin film library is immersed in 3.5 wt % NaCl. Through additional quantification of corrosion current density, a correlation between change in brightness and corrosion current density is revealed, suggesting an effective rapid screening of corrosion simply by a visual method. For materials discovery with optimized multiproperties, we utilize the corrosion fast screening results and superimpose them on the composition dependence of the glass forming ability. This allows us to rapidly identify alloys with the best combination of glass forming ability and corrosion resistance, which we then confirm in bulk form.

corrosion
bulk metallic glasses
combinatorial materials science


Does the Degree of Acculturation Influence Breastfeeding Intention and Start or the Frequency of Early Weaning? Results of a Prospective Observational Study.

Abstract:
Objectives
Recent breastfeeding studies from immigration countries have found that acculturation factors influence breastfeeding behaviour in women with a migration background. To date, there has been no systematic investigation for Germany. Therefore, we study whether and how the degree of acculturation within a population of migrant women influences the start, time and duration of breastfeeding.

Patient Population and Methodology
Pregnant women who were admitted to one of the three participating maternity clinics in Berlin for the birth of their child in the one-year study period were surveyed (including sociodemographic details, data on migration/acculturation). These women were interviewed again two or three days post partum (including start of breastfeeding, planned breastfeeding duration, reasons for not breastfeeding). In a subgroup, a telephone interview took place 6 months post partum about the actual breastfeeding duration, contraceptive behaviour post partum and availing of midwife services following delivery. Breastfeeding behaviour was analysed using multivariate regression models, among other things.

Results
The prepartum survey included 7100 women, 6884 women were contacted in the postnatal wards, and the subgroup six months after delivery comprised 605 women. No acculturation-related differences were found in the start of breastfeeding. In the adjusted model, a medium and higher degree of acculturation diminished the chance of planning a long breastfeeding period. More acculturated women show a greater risk of weaning within the first six months than less acculturated women.

Conclusion
The degree of acculturation has relevant significance for some aspects of breastfeeding behaviour in women with a migration background. This should be considered both in breastfeeding promotion programmes and in further national breastfeeding studies.

Brenne|Silke|S| Breckenkamp|Jürgen|J| Borde|Theda|T| David|Matthias|M| Razum|Oliver|O|

acculturation
breastfeeding
breastfeeding behaviour
migration
breastfeeding prevalence


Genetic polymorphisms affecting susceptibility to mercury neurotoxicity in children: summary findings from the Casa Pia Children's Amalgam clinical trial.

Abstract: Mercury (Hg) is neurotoxic, and children may be particularly susceptible to this effect. A current major challenge is identification of children who may be uniquely susceptible to Hg toxicity because of genetic predisposition. We examined the possibility that common genetic variants that are known to affect neurologic functions or Hg handling in adults would modify the adverse neurobehavioral effects of Hg exposure in children. Three hundred thirty subjects who participated as children in the recently completed Casa Pia Clinical Trial of Dental Amalgams in Children were genotyped for 27 variants of 13 genes that are reported to affect neurologic functions and/or Hg disposition in adults. Urinary Hg concentrations, reflecting Hg exposure from any source, served as the Hg exposure index. Regression modeling strategies were employed to evaluate potential associations between allelic status for individual genes or combinations of genes, Hg exposure, and neurobehavioral test outcomes assessed at baseline and for 7 subsequent years during the clinical trial. Among boys, significant modification of Hg effects on neurobehavioral outcomes over a broad range of neurologic domains was observed with variant genotypes for 4 of 13 genes evaluated. Modification of Hg effects on a more limited number of neurobehavioral outcomes was also observed for variants of another 8 genes. Cluster analyses suggested some genes interacting in common processes to affect Hg neurotoxicity. In contrast, significant modification of Hg effects on neurobehavioral functions among girls with the same genotypes was substantially more limited. These observations suggest increased susceptibility to the adverse neurobehavioral effects of Hg among children, particularly boys, with genetic variants that are relatively common to the general human population. These findings advance public health goals to identify factors underlying susceptibility to Hg toxicity and may contribute to strategies for preventing adverse health risks associated with Hg exposure.

Woods|James S|JS|
Heyer|Nicholas J|NJ|
Russo|Joan E|JE|
Martin|Michael D|MD|
Farin|Federico M|FM|

D020262:Mercury Poisoning, Nervous System

Mercury
Neurotoxicity
Children
Neurobehavioral function
Genetic susceptibility