Cloning a Chymotrypsin-Like 1 (CTRL-1) Protease cDNA from the Jellyfish Nemopilema nomurai.

Abstract: An enzyme in a nematocyst extract of the Nemopilema nomurai jellyfish, caught off the coast of the Republic of Korea, catalyzed the cleavage of chymotrypsin substrate in an amidolytic kinetic assay, and this activity was inhibited by the serine protease inhibitor, phenylmethanesulfonyl fluoride. We isolated the full-length cDNA sequence of this enzyme, which contains 850 nucleotides, with an open reading frame of 801 encoding 266 amino acids. A blast analysis of the deduced amino acid sequence showed 41% identity with human chymotrypsin-like (CTRL) and the CTRL-1 precursor. Therefore, we designated this enzyme N. nomurai CTRL-1. The primary structure of N. nomurai CTRL-1 includes a leader peptide and a highly conserved catalytic triad of His(69), Asp(117), and Ser(216). The disulfide bonds of chymotrypsin and the substrate-binding sites are highly conserved compared with the CTRLs of other species, including mammalian species. Nemopilema nomurai CTRL-1 is evolutionarily more closely related to Actinopterygii than to Scyphozoan (Aurelia aurita) or Hydrozoan (Hydra vulgaris). The N. nomurai CTRL1 was amplified from the genomic DNA with PCR using specific primers designed based on the full-length cDNA, and then sequenced. The N. nomurai CTRL1 gene contains 2434 nucleotides and four distinct exons. The 5' donor splice (GT) and 3' acceptor splice sequences (AG) are wholly conserved. This is the first report of the CTRL1 gene and cDNA structures in the jellyfish N. nomurai.

Heo|Yunwi|Y|
Kwon|Young Chul|YC|
Bae|Seong Kyeong|SK|
Hwang|Duhyeon|D|
Yang|Hye Ryeon|HR|
Choudhary|Indu|I|
Lee|Hyunkyoung|H|
Yum|Seungshic|S|
Shin|Kyoungsoon|K|
Yoon|Won Duk|WD|
Kang|Changkeun|C|
Kim|Euikyung|E|

D000595:Amino Acid Sequence
D000818:Animals
D001483:Base Sequence
D001665:Binding Sites
D020134:Catalytic Domain
D053818:Chymases
D002918:Chymotrypsin
D003001:Cloning, Molecular
D018076:DNA, Complementary
D019143:Evolution, Molecular
D007700:Kinetics
D010664:Phenylmethylsulfonyl Fluoride
D010802:Phylogeny
D011485:Protein Binding
D037401:Scyphozoa
D015842:Serine Proteinase Inhibitors
D013329:Structure-Activity Relationship
D013379:Substrate Specificity

cloning a chymotrypsin-like 1 (CTRL-1) protease


Contrasting roles of dynamics in protein allostery: NMR and structural studies of CheY and the third PDZ domain from PSD-95.

Abstract: Allosteric regulation is a ubiquitous phenomenon exploited in biological processes to control cells in a myriad of ways. It is also of emerging interest in the design of functional proteins and therapeutics. Even though allostery was proposed over 50 years ago and has been studied intensively from a structural perspective, many key details of allosteric mechanisms remain mysterious. Over the last decade significant attention has been paid to the "dynamic component" of allostery, as opposed to the analysis of rigid structures. Nuclear magnetic resonance spectroscopy and its ability to detect conformationally dynamic processes at atomic resolution have played an important role in expanding our understanding of allosteric mechanisms and opening up new questions. This article focuses on work that highlights how protein dynamics can factor into allosteric processes in distinct ways. Two cases are contrasted. The first considers the "traditionally allosteric" protein CheY, which undergoes a conformational change as a key element of its allostery. The second considers the more rarely observed "dynamic allostery" in a PDZ domain, in which allosteric behavior arises from changes in internal structural dynamics. Interestingly, the dynamic processes in these two contrasting examples occur on different timescales. In the case of the PDZ domain, subsequent experimental and computational work is reviewed to reveal a more complete picture of this interesting case of allostery.

Allostery
NMR
CheY
PDZ domain
PSD-95
Protein dynamics
Dynamic allostery


Prophylactic noninvasive positive pressure ventilation in the weaning of difficult-weaning tracheotomy patients.

Abstract:
Background
Prophylactic noninvasive positive pressure ventilation (NPPV) reduces reintubation in endotracheal intubation patients. However, the efficacy of using the prophylactic NPPV in the weaning of tracheotomy patients is unclear.

Methods
We performed prophylactic NPPV in 11 tracheotomy patients who passed a spontaneous breathing trial (SBT), removed the tracheotomy tube, and closed the incision (intervention group). We matched another 11 tracheotomy patients who also passed an SBT but weaning and removing of tracheotomy tube were managed as conventional methods (control group).

Results
Patients in the control group had reinstitution of mechanical ventilation 36 times after the initial SBT success. Compared with the control group, the interventional group had fewer weaning days (3.0±2.1 vs. 11.3±9.2, P=0.01) from initial SBT success to successful weaning and shorter intensive care unit (ICU) length of stay (11.6±4.2 vs. 20.3±11.6, P=0.03) after initial SBT success. The interventional group had lower nosocomial pneumonia rates after initial SBT success (0/11 vs. 2/11), lower ICU mortality (0/11 vs. 2/11), lower hospital mortality (0/11 vs. 3/11), and higher successful weaning rate (11/11 vs. 8/11), but it didn't reach significant difference. Also, there was no significant difference between groups in total duration of ventilation (25.5±13.3 vs. 34.7±24.2 days), hospital stay after initial SBT success (24.0±22.3 vs. 37.4±31.3 days), total ICU stay (35.7±15.3 vs. 45.0±29.5 days), and total hospital stay (48.7±33.1 vs. 68.6±52.6 days).

Conclusions
Prophylactic NPPV may be useful to accelerate weaning, and shorten ICU stay after initial SBT success in tracheotomy patients.

Liang|Guo-Peng|GP| Zeng|Yi-Hua|YH| Chen|Bai-Xu|BX| Kang|Yan|Y|


Evaluation of the production of exopolysaccharides by newly isolated Halomonas strains from Tunisian hypersaline environments.

Abstract: Ten Halomonas strains were screened from different Tunisian hypersaline environments for the production of exopolysaccharides (EPS), characterized and identified basing on 16S rRNA gene sequencing. EPS production was therefore studied using two different culture media M1 (complex medium) and M2 (semi-complex medium). Selected isolates produced different EPS amounts ranging from 86 to 170 mg L-1 and 26 to 105 mg L-1 when grown on M1 and M2, respectively. The use of M1 encouraged stronger bacterial growth associated with greater EPS production compared to M2. Nevertheless, the highest EPS yield (YEPS/X) was observed for strains grown on M2. When cultivated on M1, all isolates produced EPS exhibiting almost the same monosaccharide profile with mannose, glucose and arabinose being the main monomers. However, the produced EPS on M2 were characterized by heterogeneous monosaccharide profiles among the different species, mostly consisting of glucomannan that could be a versatile material used for many further applications.

Joulak|Ichrak|I|
Finore|Ilaria|I|
Nicolaus|Barbara|B|
Leone|Luigi|L|
Moriello|Aniello Schiano|AS|
Attia|Hamadi|H|
Poli|Annarita|A|
Azabou|Samia|S|

Exopolysaccharides (EPS)
Monosaccharide profile
Halomonas spp.
Medium composition


Different on the abundance of Pampus argenteus in Persian Gulf exceeding in variety comparing to Gulf of Oman.

Abstract: Silver pomfret fish (Stromateidae) is a family of Perciformes order. One species of this family is Pampus argenteus known as silver pomfret and lives in different parts of the Persian Gulf and Gulf of Oman. Therefore, the genetic relationship between its populations is so important. In this study, eight samples of Pampus argenteus were collected from four locations involved: Emam Khomeyni, Bushehr and Bandar Abbas in Persian Gulf and Chabahar in Gulf of Oman. Cytochrome b gene and D-loop region of mitochondrial DNA on these samples are analyzed. These genes are carried out using PCR with specific mtDNA primers and sequenced. Then, the evolutionary history was inferred by using the maximum-likelihood method. Evolutionary analyses were conducted in MEGA7. According to the phylogenetic trees, with translocations in Persian Gulf to Gulf of Oman, similarity decreases slowly. Chabahar1 sample in phylogenetic tree of cytochrome b is phylogenetically near China Sea samples. The reason may be migration from ocean to gulf throughout the centuries and Chabahar is in Gulf of Oman and locationally near the Arabian Sea and Indian Ocean. In D-loop region, results are similar to cytochrome b excepting one sample (Emam Khomeyni1). D-Loop in samples shows modification more than cytochrome b for the reason absence of protein product.

Sheibaninia|Atena|A|
Nejatkhah Manavi|Parisa|P|
Houshmand|Massoud|M|

Pampus argenteus
Persian Gulf
Gulf of Oman
cytochrome b
D-loop


CD47 promotes ovarian cancer progression by inhibiting macrophage phagocytosis.

Abstract: Targeting CD47 efficiently enhances macrophage phagocytosis in both physiological and pathological conditions. Anti-CD47 antibodies have been shown to inhibit the progression of several types of cancer. However, the mechanism of anti-CD47 monoclonal antibody (mAb) treatment remains controversial. In this study, we confirmed that CD47 protein is highly expressed in ovarian cancer, and is correlated with poor clinical characteristics and prognosis. CD47 knockdown in the ovarian cancer cell line, SK-OV-3, promoted phagocytosis by macrophages in vitro and inhibited tumor growth in vivo. These data combined suggest that CD47 inhibition is a potential strategy for cancer treatment. Using an anti-CD47 mAb, we found that CD47 inhibition in both SK-OV-3 cells and primary cancer cells was able to recapitulate our knockdown results and led to an increase in the number of infiltrating macrophages. In addition, the CD133+ tumor initiating cells expressed a high level of CD47, and anti-CD47 mAb treatment was able to trigger the phagocytosis of this cell population. In conclusion, our results indicate that CD47 inhibits macrophage phagocytosis of ovarian cancer cells, and down-regulation of CD47 or inhibiting CD47 by mAb was able to reverse the negative effect. Thus, CD47 antibody therapy may be a promising strategy to treat ovarian cancer.

Liu|Ran|R| Wei|Huiting|H| Gao|Peng|P| Yu|Hu|H| Wang|Ke|K| Fu|Zheng|Z| Ju|Baohui|B| Zhao|Meng|M| Dong|Shangwen|S| Li|Zhijun|Z| He|Yifeng|Y| Huang|Yuting|Y| Yao|Zhi|Z|

D023041:Xenograft Model Antitumor Assays

CD47
ovarian cancer
macrophage
phagocytosis
monoclonal antibody


The tradeoffs between food supply and demand from the perspective of ecosystem service flows: A case study in the Pearl River Delta, China.

Abstract: Ecosystem service flows are a research topic of significant interest, and exploring this topic may mitigate the shortcomings related to the spatial mismatches between supply and demand in the current ecosystem services studies. The Pearl River Delta (PRD) experiences a serious spatial mismatch in ecosystem services in particular the food supply, between the supply areas (hilly areas) and demand areas (central areas). Therefore, this study focused on the PRD as a case study to analyze change trends of food supply-demand ratio (FSDR) at city level, and depict the spatial flow path within and between cities from the perspective of ecosystem service flow with different threshold distance, using an enhanced two-step floating catchment area accessibility method. The results showed that the food demand significantly exceeded the supply, the budget was 3.58 million tons and FSDR was 0.49 in 2015. There were large discrepancies in the FSDR at the city level before and after when considering the ecosystem service flows. The FSDR of cities in the central areas increased 0.1%-30%, due to the ecosystem service flow from the low hilly areas. As delivery distances increased, the size of food flow decreased within cities and increased among cities. This led to a significant decline in the population living in severe undersupplied areas (FSDR＜0.1) and oversupplied areas (FSDR＞1), and an increase in undersupplied areas (0.1＜FSDR＜0.9). Our findings indicate that local governments would benefit from enhancing connections between supply and demand areas to meet the food demand of big cities. This study offers a comprehensive and realistic understanding of the physical situation of ecosystem service consumption by human beings, and provides decision-making information for optimize land use allocation.

Liu|Wei|W|
Zhan|Jinyan|J|
Zhao|Fen|F|
Zhang|Fan|F|
Teng|Yanmin|Y|
Wang|Chao|C|
Chu|Xi|X|
Kumi|Michael Asiedu|MA|

D003247:Conservation of Natural Resources

Ecosystem service flow
Pearl river delta
Provisioning ecosystem service
Road networks
Scenario analysis
Supply - demand ratio


Intramedullary cortical bone strut improves the cyclic stability of osteoporotic proximal humeral fractures.

Abstract:
BACKGROUND
Proximal humeral fractures treated with locking plate can fail due to varus collapse, especially in osteoporotic bone with medial cortex comminution. The use of an intramedullary strut together with locking plate fixation may strengthen fixation and provide additional medial support to prevent the varus malalignment. This study biomechanically investigates the influence of an intramedullary cortical bone strut on the cyclic stability of proximal humeral fractures stabilized by locking plate fixation in a cadaver model.

METHODS
Ten cadaveric humeri were divided into two groups statistically matched for bone density. Each specimen was osteotomized with 10 mm gap at the surgical neck. The non-augmented group stabilized with locking plate alone; in the augmented group, a locking plate was used combined with an intramedullary cortical bone strut. The strut was retrograded into the subchondral bone, and three humeral head screws were inserted into the strut to form a plate-screw-strut mechanism. The cyclic axial load was performed to 450 N for 6000 cycles and then loaded to failure. Construct stiffness, cyclic loading behavior and failure strength were analyzed to identify differences between groups.

RESULTS
The augmented constructs were significantly stiffer than the non-augmented constructs during cycling. On average, the maximum displacements at 6000 cycles for non-augmented and augmented groups were 3.10 ± 0.75 mm and 1.7 ± 0.65 mm (p = 0.01), respectively. The mean peak-to-peak (inter cycle) displacement at 6000 cycles was about 2 times lower for the augmented group (1.36 ± 0.68 mm vs. 2.86 ± 0.51 mm). All specimens showed varus collapse combined with loss of screw fixation of the humeral head. The failure load of the augmented group was increased by 2.0 (SD = 0.41) times compared with the non-augmented group (p < 0.001).

CONCLUSIONS
The stability and strength of the locking plate augmented with an intramedullary strut were significantly increased. For bone with poor quality, the subsidence of the locked screws led larger displacement, decreased the stability of the constructs, however, the plate-screw-strut mechanism provided more rigidity to stabilize the fixation. This study emphasized the importance of intramedullary support for the proximal humeral fractures fixed with a locked plate under cyclic loading, especially in bone with poor quality. This work is based on the results of cadaver model, further in vivo analysis is necessary to determine if the clinical results can be extrapolated from this data.

Hsiao|Chih-Kun|CK| Tsai|Yi-Jung|YJ| Yen|Cheng-Yo|CY| Lee|Cheng-Hung|CH| Yang|Teng-Yao|TY| Tu|Yuan-Kun|YK|

Humeral fractures
Locking plate
Intramedullary strut
Stiffness
Cyclic loading
Osteoporosis


Combination of intensity modulated radiotherapy followed treatment with p38 MAPK activation inhibitor inhibits the proliferation of MCF-7 breast cancer cells.

Abstract: The present study was aimed to investigate the effect of intensity modulated radiotherapy (IMRT) followed by treatment with inhibitor for p38 MAPK, SB203580 on the rate of proliferation in drug resistant MCF-7 breast cancer cells. Interestingly, the results from immuno histochemistry and western blot assays revealed higher level of distribution of activated p38 MAPK in the drug resistant breast cancer tissues compared to the primary tissues. Treatment of the drug resistant MCF-7 cells with SB203580 led to a significant decrease in the phosphorylation of p38 MAPK. Exposure to IMRT caused a significant decrease in the rate of proliferation in drug resistant MCF-7breast cancer cells (P < 0.05). MCF-7 cells were subjected to IMRT for 45 min followed by treatment with SB203580 for 12 h. The results from MTT assay revealed inhibition in the rate of proliferation of MCF-7 cells more efficiently compared to the IMRT or SB203580 when used separately (P < 0.02). The effect of IMRT and SB203580 on inhibition of MCF-7 cell proliferation showed synergistic relation. Since MAPK signaling pathway plays an important role in the development of drug resistance, therefore, inhibition of p38 MAPK activation by the combination of IMRT followed by treatment with inhibitor for p38 MAPK can be a promising strategy for breast cancer treatment. Thus combination of IMRT exposure and treatment with SB203580 can be used for the inhibition of drug resistant breast cancer.

Radiotherapy
Inhibition
Drug resistant
Phosphorylation
Synergistic


Nitric oxide mediates stretch-induced Ca2+ oscillation in smooth muscle.

Abstract: The stretching of smooth muscle tissue modulates contraction through augmentation of Ca(2+) transients, but the mechanism underlying stretch-induced Ca(2+) transients is still unknown. We found that mechanical stretching and maintenance of mouse urinary bladder smooth muscle strips and single myocytes at 30% and 18% beyond the initial length, respectively, resulted in Ca(2+) oscillations. Experiments indicated that mechanical stretching remarkably increased the production of nitric oxide (NO) as well as the amplitude and duration of muscle contraction. Stretch-induced Ca(2+) oscillations and contractility increases were completely abolished by the NO inhibitor L-NAME or eNOS (also known as NOS3) gene inactivation. Moreover, exposure of eNOS-knockout myocytes to exogenous NO donor induced Ca(2+) oscillations. The stretch-induced Ca(2+) oscillations were greatly inhibited by the selective inositol 1,4,5-trisphosphate receptor (IP3R) inhibitor xestospongin C and partially inhibited by ryanodine. Moreover, the stretch-induced Ca(2+) oscillations were also suppressed by the phosphoinositide 3-kinase (PI3K) inhibitor LY294002, but not by the soluble guanylyl cyclase (sGC) inhibitor ODQ. These results suggest that stretching myocyte and maintenance at a certain length results in Ca(2+) oscillations that are NO dependent , and sGC and cGMP independent, and results from the activation of PI3K in smooth muscle.

Nitric oxide
Ca2+ oscillation
eNOS
Ca2+ signaling


Fabrication of Robust and Porous Lead Chloride-Based Metal-Organic Frameworks toward a Selective and Sensitive Smart NH3 Sensor.

Abstract: Organolead halide materials have shown promising optoelectronic properties that are suitable for light-emitting diodes (e.g., strong photoluminescence, narrow emission width, and high charge carrier mobility). However, the vast majority of them have no open porosity or open metal sites for host-guest interactions and are therefore not widely applicable in intrinsic fluorescent sensing of small molecules. Herein, we report a lead chloride-based metal-organic framework (MOF) with high porosity and stability and promising photoluminescent characteristics, performing as a sensitive, selective, and long-term stable fluorescence probe for NH3. For the first time, a homemade dynamic real-time photoluminescence monitoring system was developed, which showed that our haloplumbate-based MOF has an immediate response and an extremely low limit of detection (12 ppm) toward NH3. A variety of experimental characterization and theoretical calculations evidenced that the photoluminescence quenching was ascribed to the coordination between NH3 guests and exposed Pb2+ centers in MOFs. Moreover, a portable on-site smart NH3 detector was designed based on this haloplumbate-MOF using a 3D printer, and the quantitative recovery experiment demonstrated the effective detection of NH3 in the range of 15-150 ppm. This study opens a new pathway to design organolead halide-based MOFs to perform on-site chemical sensing of small molecules and shows their high potential to monitor safety concentrations of NH3 in different industrial sites.

NH3 sensor
photoluminescence
metal halide
metal−organic framework
smart-device


Co-Occurrence and Combinatory Effects of Alternaria Mycotoxins and other Xenobiotics of Food Origin: Current Scenario and Future Perspectives.

Abstract: Mycotoxins are low-molecular weight compounds produced by diverse genera of molds that may contaminate food and feed threatening the health of humans and animals. Recent findings underline the importance of studying the combined occurrence of multiple mycotoxins and the relevance of assessing the toxicity their simultaneous exposure may cause in living organisms. In this context, for the first time, this work has critically reviewed the most relevant data concerning the occurrence and toxicity of mycotoxins produced by Alternaria spp., which are among the most important emerging risks to be assessed in food safety, alone or in combination with other mycotoxins and bioactive food constituents. According to the literature covered, multiple Alternaria mycotoxins may often occur simultaneously in contaminated food, along with several other mycotoxins and food bioactives inherently present in the studied matrices. Although the toxicity of combinations naturally found in food has been rarely assessed experimentally, the data collected so far, clearly point out that chemical mixtures may differ in their toxicity compared to the effect of toxins tested individually. The data presented here may provide a solid foothold to better support the risk assessment of Alternaria mycotoxins highlighting the actual role of chemical mixtures on influencing their toxicity.

Crudo|Francesco|F| Varga|Elisabeth|E| Aichinger|Georg|G| Galaverna|Gianni|G| Marko|Doris|D| Dall'Asta|Chiara|C| Dellafiora|Luca|L|

co-occurrence
combinatory effects
Alternaria mycotoxins
food safety
bioactive compounds
combined toxicity


Neuroblastomas in Eastern China: a retrospective series study of 275 cases in a regional center.

Abstract:
Purpose
Most studies on neuroblastoma (NB) have been conducted in Western countries or Japan. The objective of our study was to analyze clinical and pathological features, MYCN status, surgical methods, and prognosis in Chinese NB patients.

Methods
A retrospective, single-center case series study of 275 NBs was implemented. Clinical manifestations, pathological features, MYCN status, and surgical treatment were analyzed. Log-rank test and Cox hazards models were used to assess overall survivals (OSs).

Results
The cohort consisted of 105 females and 170 males, with an age range of five days to 15 years. MYCN amplification was detected in 21.5% of all cases. The median OS was 15.0 months for MYCN amplified group. The five-year OS rates were 70.8% and 18.3% for MYCN unamplified and amplified groups, respectively, and the comparison of Kaplan-Meier curves for these two groups showed statistical significance (P < .001 by log-rank test). Gross total resection (GTR, n = 111) and subtotal resection (STR, n = 58) were administered in 169 patients at stages 3 and 4 who received chemotherapy and the comparison of Kaplan-Meier curves for different groups in these patients had statistical significance (STR vs. GTR, P = .009; MYCN unamplified vs. amplified, P < .001 by log-rank test, respectively).The multivariate survival analyses showed statistical significance (STR vs. GTR, P = .047; MYCN unamplified vs. amplified, P = .001 by Cox regression model).

Conclusions
MYCN amplification is an independently adverse prognostic factor in Chinese NB patients at stages 3 and 4 and GTR is associated with improved OS compared with STR in these patients.

Ma|Yangyang|Y| Zheng|Jicui|J| Feng|Jiayan|J| Chen|Lian|L| Dong|Kuiran|K| Xiao|Xianmin|X|

Neuroblastoma
MYCN status
Prognosis
Clinicopathological features
Surgery


A Physical Health Profile of Youths Living with a "Hikikomori" Lifestyle.

Abstract: A cross-sectional study was designed to understand the impacts of "hikikomori" lifestyle on physical health. A total of 104 eligible hikikomori cases were recruited from the social services network of Hong Kong with a mean age of 19.02 ± 3.62 (ranged 13-31) year-old, and had completed the set of questionnaires and a series of anthropometric and physical health measurements. Despite SF36 score of 84.0 indicated good physical functioning in general, participants were lived sedentarily with high incidence of hypertension at 15.4% and prehypertension at 31.7%. Occurrence of hypertension and prehypertension in cases living as hikikomori >6 months were 3 times and 1.5 times higher than those newly onset cases, respectively. The blood pressure levels were correlated with age and all obesity index parameters measured including waist circumference and body mass index. Results also observed a shift of body weight from underweight to overweight and obesity along the hikikomori duration. Half of the hypertensive cases involved the elevation of systolic blood pressure, which suggested higher odds of cardiovascular complications. In conclusion, the hikikomori lifestyle could be a risk behavior that may harm the younger generation physically by promoting obesity and hypertension and probably other chronic illnesses.

Yuen|John W M|JWM|0000-0003-1681-233X
Yan|Yoyo K Y|YKY|
Wong|Victor C W|VCW|0000-0001-5359-8147
Tam|Wilson W S|WWS|
So|Ka-Wing|KW|
Chien|Wai-Tong|WT|0000-0001-5321-5791

physical health
health
hikikomori
hypertension
obesity
adolescent
hidden youth
social withdrawal


Dietary Isoliquiritigenin at a Low Dose Ameliorates Insulin Resistance and NAFLD in Diet-Induced Obesity in C57BL/6J Mice.

Abstract: Isoliquiritigenin (ILG) is a flavonoid constituent of Glycyrrhizae plants. The current study investigated the effects of ILG on diet-induced obesity and metabolic diseases. C57BL/6J mice were fed a normal diet (AIN-76 purified diet), high-fat diet (40 kcal% fat), and high-fat diet +0.02% (w/w) ILG for 16 weeks. Supplementation of ILG resulted in decreased body fat mass and plasma cholesterol level. ILG ameliorated hepatic steatosis by suppressing the expression of hepatic lipogenesis genes and hepatic triglyceride and fatty acid contents, while enhancing β-oxidation in the liver. ILG improved insulin resistance by lowering plasma glucose and insulin levels. This was also demonstrated by the intraperitoneal glucose tolerance test (IPGTT). Additionally, ILG upregulated the expression of insulin signaling-related genes in the liver and muscle. Interestingly, ILG elevated energy expenditure by increasing the expression of thermogenesis genes, which is linked to stimulated mitochondrial biogenesis and uncoupled cellular respiration in brown adipose tissue. ILG also suppressed proinflammatory cytokine levels in the plasma. These results suggest that ILG supplemented at 0.02% in the diet can ameliorate body fat mass, plasma cholesterol, non-alcoholic fatty liver disease, and insulin resistance; these effects were partly mediated by increasing energy expenditure in high-fat fed mice.

D065626:Non-alcoholic Fatty Liver Disease

isoliquiritigenin
insulin resistance
energy expenditure
cytokine
non-alcoholic fatty liver disease


Missed appendicitis after self-induced abortion.

Abstract: Female lower abdominal pain poses diagnostic difficulties for clinicians, especially when little more than the history and physical examination are available. A girl presented with constant lower abdominal pain after taking misoprostol for pregnancy termination. She was eventually referred to a rural District Hospital, where a laparotomy demonstrated acute appendicitis. After treating herself for a self-diagnosed pregnancy with illegally provided misoprostol, this patient presented with persistent lower abdominal pain. The differential diagnosis included ectopic pregnancy and all other causes of female abdominal pain. Yet diagnosing two diseases in the same anatomical area at the same time contradicts diagnostic parsimony. System problems in resource-poor areas can limit access to healthcare services and encourage dispensing potentially dangerous medications without clinicians' authorization. It is dangerous to rely on patients' self-diagnoses while neglecting other diagnoses. More than one diagnosis may be needed to explain temporally and anatomically related symptoms.

Appendicitis abortion misoprostol pregnancy misdiagnosis


Combining Multiple Markers to Improve the Longitudinal Rate of Progression-Application to Clinical Trials on the Early Stage of Alzheimer's Disease.

Abstract: Clinical trials on early stage Alzheimer's disease (AD) are reaching a bottleneck because none of the current disease markers changes appreciably early in the disease process and therefore a huge sample is required to adequately power such trials. We propose a method to combine multiple markers so that the longitudinal rate of progression can be improved. The criterion is to maximize the probability that the combined marker will be decreased over time (assuming a negative mean slope for each marker). We propose estimates to the weights of markers in the optimum combination and a confidence interval estimate to the combined rate of progression through the maximum likelihood estimates and a bootstrap procedure. We conduct simulations to assess the performance of our estimates and compare our approach with the first principal component from a principal component analysis. The proposed method is applied to a real world sample of individuals with preclinical AD to combine measures from two cognitive domains. The combined cognitive marker is finally used to design future clinical trials on preclinical AD, demonstrating a significant improvement in reducing the sample sizes needed to power such trials when compared with individual markers alone.

Xiong|Chengjie|C|
van Belle|Gerald|G|
Chen|Kewei|K|
Tian|Lili|L|
Luo|Jingqin|J|
Gao|Feng|F|
Yan|Yan|Y|
Chen|Ling|L|
Morris|John C|JC|
Crane|Paul|P|

Power
Sample size
Bootstrap estimate
Delta method
Multivariate random coefficients models
Preclinical Alzheimer’s disease (AD)
Randomized clinical trials (RCT)


Anthrax lethal toxin and the induction of CD4 T cell immunity.

Abstract: Bacillus anthracis secretes exotoxins which act through several mechanisms including those that can subvert adaptive immunity with respect both to antigen presenting cell and T cell function. The combination of Protective Antigen (PA) and Lethal Factor (LF) forming Lethal Toxin (LT), acts within host cells to down-regulate the mitogen activated protein kinase (MAPK) signaling cascade. Until recently the MAPK kinases were the only known substrate for LT; over the past few years it has become evident that LT also cleaves Nlrp1, leading to inflammasome activation and macrophage death. The predicted downstream consequences of subverting these important cellular pathways are impaired antigen presentation and adaptive immunity. In contrast to this, recent work has indicated that robust memory T cell responses to B. anthracis antigens can be identified following natural anthrax infection. We discuss how LT affects the adaptive immune response and specifically the identification of B. anthracis epitopes that are both immunogenic and protective with the potential for inclusion in protein sub-unit based vaccines.

Ascough|Stephanie|S|
Ingram|Rebecca J|RJ|
Altmann|Daniel M|DM|

D020929:Mitogen-Activated Protein Kinase Kinases

anthrax
CD4 T cell
protective antigen
lethal factor
epitope
vaccine


Enhancement of Radiotherapy with Human Mesenchymal Stem Cells Containing Gold Nanoparticles.

Abstract: Radiotherapy is a common approach for the treatment of a wide variety of cancer types. Available data indicate that nanoparticles can enhance the effect of radiotherapy. We report the use of human mesenchymal stem cells to selectively deliver gold nanoparticles (GNPs) to MDA-MB-231 breast tumor xenografts in mice for the purpose of enhancing the effect of radiation therapy. Targeted delivery of GNPs to the tumor site, followed by irradiation of the tumor, enabled control of tumor growth. The results indicate that tumor-selective GNP delivery by human mesenchymal stem cells may represent a viable way to enhance the effectiveness of radiotherapy.

Pullambhatla|Mrudula|M|
Rowe|Steven P|SP|
Lisok|Ala|A|
Wang|Yuchuan|Y|
Todd|Gabriele Putz|GP|
Danilkovitch|Alla|A|
Pomper|Martin G|MG|

targeted delivery
MSCs
breast cancer
molecular imaging
nanomedicine
tumor microenvironment


Mechanisms of the action of adenine on anti-allergic effects in mast cells.

Abstract:
INTRODUCTION
Mast cells play an important role in allergic responses.

METHODS
We herein demonstrated the mechanisms of inhibitory effect of adenine on IgE/antigen-induced degranulation and TNF-α release in mast cells.

RESULTS
We found that these effects were dependent on the amino group of adenine because purine only weakly inhibited degranulation. Adenine also inhibited Ca2+ ionophore- and thapsigargin-induced degranulation, however, this inhibitory effect was weaker than that of the antigen. Therefore, the inhibitory effects of adenine on degranulation may be mediated before as well as after the Ca2+ raise under the antigen stimulus. Adenine inhibited antigen-induced Syk and the subsequent induction of AKT and ERK activation under FcϵRI-mediated signal. Adenine also attenuated antigen-induced increase in Ca2+ . Furthermore, adenine inhibited IgE/antigen-induced IKKα/β activation, which is involved in degranulation. Finally, adenine protected mice against anaphylactic allergic responses in vivo.

CONCLUSIONS
The present study revealed a key role of adenine in the attenuation of allergic responses through the inhibition of Syk-mediated signal transduction and IKK-mediated degranulation.

Hosoi|Toru|T|0000-0003-4831-487X
Ino|Shinsuke|S|
Ohnishi|Fumie|F|
Todoroki|Kenichi|K|
Yoshii|Michiko|M|
Kakimoto|Mai|M|
Müller|Christa E|CE|
Ozawa|Koichiro|K|


Different Narrow-Band Light Ranges Alter Plant Secondary Metabolism and Plant Defense Response to Aphids.

Abstract: Light of different wavelengths affects various physiological processes in plants. Short-wavelength radiation (like UV) can activate defense pathways in plants and enhance the biosynthesis of secondary metabolites (such as flavonoids and glucosinolates) responsible for resistance against certain herbivorous insects. The intensity of light-induced, metabolite-based resistance is plant- and insect species-specific and depends on herbivore feeding guild and specialization. In this study, broccoli (Brassica oleracea var. italica) plants were grown for 4 weeks in a climate chamber under conventional fluorescent tubes and were additionally treated with UV-B (310 nm), UV-A (365 or 385 nm), or violet (420 nm) light generated with UV-B tubes or light-emitting diodes (LEDs). The objective was to determine the influence of narrow bandwidths of light (from UV-B to violet) on plant secondary metabolism and on the performance of the cabbage aphid Brevicoryne brassicae (a specialist) and the green peach aphid Myzus persicae (a generalist). Among flavonol glycosides, specific quercetin and kaempferol glycosides increased markedly under UV-B, while among glucosinolates only 4-methoxy-3-indolylmethyl showed a 2-fold increase in plants exposed to UV-B and UV-A. The concentration of 3-indolylmethyl glucosinolate in broccoli plants increased with UV-B treatment. Brevicoryne brassicae adult weights and fecundity were lower on UV-B treated plants compared to UV-A or violet light-treated plants. Adult weights and fecundity of M. persicae were increased under UV-B and UV-A treatments. When specific light wavelengths are used to induce metabolic changes in plants, the specificity of the induced effects on herbivores should be considered.

UV
Flavonoids
Glucosinolates
Resistance
Brassica oleracea
Brevicoryne brassicae
Myzus persicae


Improved tacrolimus skin permeation by co-encapsulation with clobetasol in lipid nanoparticles: Study of drug effects in lipid matrix by electron paramagnetic resonance.

Abstract: Combined therapy with corticosteroids and immunosuppressant-loaded nanostructured lipid carriers (NLC) could be useful in the treatment of skin diseases. To circumvent NLC loading capacity problems, loaded drugs should have different physicochemical characteristics, such as tacrolimus (TAC) and clobetasol (CLO). Therefore, in the present study, TAC and CLO were encapsulated in NLC (TAC-NLC, CLO-NLC and TAC+CLO-NLC), coated or otherwise with chitosan. Electron paramagnetic resonance (EPR) spectroscopy of different spin labels was used to investigate the impact of drug and oil incorporation on the lipid dynamic behavior of the lipid matrices. In addition, the impact of co-encapsulation on drug release and skin permeation was evaluated. Entrapment efficiency was greater than 90% for both drugs, even when the maximum drug loading achieved for TAC-NLC and CLO-NLC was kept at TAC+CLO-NLC, because TAC is more soluble in the solid lipid and CLO in the liquid lipid. EPR data indicated that both drugs reduced the lipid fluidity near the polar surface of the lipid matrix, which suggests their presence in this region. In addition, EPR data showed that liquid lipid is also present in more superficial regions of the nanoparticle matrix. CLO was released faster than TAC from TAC+CLO-NLC, probably because it is more soluble in the liquid lipid. TAC skin penetration was affected by CLO. A 5-fold increase in TAC penetration was observed from TAC+CLO-NLC when compared to TAC-NLC formulations. Coating also increased TAC and CLO permeation to deeper skin layers (1.8-fold and 1.6-fold, respectively). TAC+CLO-NLC seems to be an effective strategy for topical delivery of TAC and CLO, and thus constitutes promising formulations for the treatment of skin diseases.

Rocha|Priscila Bianca Rodrigues da|PBRD|

D004578:Electron Spin Resonance Spectroscopy

Tacrolimus
Skin permeation
Co-encapsulation
Clobetasol
Nanostructured lipid carriers
Chitosan coating


Circulating 25-hydroxyvitamin D up to 3 decades prior to diagnosis in relation to overall and organ-specific cancer survival.

Abstract: While vitamin D has been associated with improved overall cancer survival in some investigations, few have prospectively evaluated organ-specific survival. We examined the accepted biomarker of vitamin D status, serum 25-hydroxyvitamin D [25(OH)D], and cancer survival in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study. Of 4616 cancer cases with measured serum 25(OH)D, 2884 died of their cancer during 28 years of follow-up and 1732 survived or died of other causes. Proportional hazards regression estimated hazard ratios (HR) and 95% confidence intervals (CI) for the association between pre-diagnostic 25(OH)D and overall and site-specific survival. Serum 25(OH)D was significantly lower among cases who subsequently died from their malignancy compared with those who did not (medians 34.7 vs. 36.5 nmol/L, respectively; p = 0.01). Higher 25(OH)D was associated with lower overall cancer mortality (HR = 0.76, 95% CI 0.67-0.85 for highest vs. lowest quintile, p-trend < 0.0001). Higher 25(OH)D was related to lower mortality from the following site-specific malignancies: prostate (HR = 0.74, 95% CI 0.55-1.01, p-trend = 0.005), kidney (HR = 0.59, 95% CI 0.35-0.98, p-trend = 0.28), and melanoma (HR = 0.39, 95% CI 0.20-0.78, p-trend = 0.01), but increased mortality from lung cancer (HR = 1.28, 95% CI 1.02-1.61, p-trend = 0.19). Improved survival was also suggested for head and neck, gastric, pancreatic, and liver cancers, though not statistically significantly, and case numbers for the latter two organ sites were small. Higher 25(OH)D status years prior to diagnosis was related to improved survival for overall and some site-specific cancers, associations that should be examined in other prospective populations that include women and other racial-ethnic groups.

Cancer
Vitamin D
Mortality
Prospective cohort
Survival analysis


Cassava AGPase genes and their encoded proteins are different from those of other plants.

Abstract: Cassava AGPase and AGPase genes have some unique characteristics. ADP-glucose pyrophosphorylase (AGPase) is a rate-limiting enzyme for starch synthesis. In this study, cassava AGPase genes (MeAGP) were analyzed based on six cultivars and one wild species. A total of seven MeAGPs was identified, including four encoding AGPase large subunits (MeAGPLs 1, 2, 3 and 4) and three encoding AGPase small subunits (MeAGPSs 1, 2 and 3). The copy number of MeAGPs varied in cassava germplasm materials. There were 14 introns for MeAGPLs 1, 2 and 3, 13 introns for MeAGPL4, and 8 introns for other three MeAGPSs. Multiple conservative amino acid sequence motifs were found in the MeAGPs. There were differences in amino acids at binding sites of substrates and regulators among different MeAGP subunits and between MeAGPs and a potato AGPase small subunit (1YP2:B). MeAGPs were all located in chloroplasts. MeAGP expression was not only associated with gene copy number and types/combinations, regions and levels of the DNA methylation but was also affected by environmental factors with the involvement of various transcription factors in multiple regulation networks and in various cis-elements in the gene promoter regions. The MeAGP activity also changed with environmental conditions and had potential differences among the subunits. Taken together, MeAGPs differ in number from those of Arabidopsis, potato, maize, banana, sweet potato, and tomato.

Enzymes
Starch
Binding sites
Evolution
Genome
Subcellular localization
Transcriptome


Implementation of thyroid function tests algorithms by clinical laboratories: A four-year experience of good clinical and diagnostic practice in a tertiary hospital in Greece.

Abstract:
INTRODUCTION
Thyroid Function Tests (TFTs) are among the most commontly ordered tests. Significant overuse of TFTs can occur when instead of using a single TSH test to screen for thyroid disease a full panel (TSH plus FT4 and FT3) is ordered. The aim of our study was to evaluate the effectiveness of the application of a scientifically-established laboratory-controlled algorithm for TFTs to physician's orders for inpatients and to address potential pitfalls of such an approach.

MATERIALS AND METHODS
We collected and analyzed Laboratory Information System data of the TFTs performed between April 2009 and March 2016 in a 739-bed tertiary teaching hospital. Between April 2013 and March 2016, we applied a laboratory controlled algorithm for inpatient TFT assays after TSH and did not perform further tests, unless a justified bypass was requested by the treating physician.

RESULTS
Algorithm application led to significant reductions of TFTs executed per TSH ordered. Compared to the four years preceding the intervention, executed FT4/TSH tests decreased from 93 to 18%, FT3/TSH from 92 to 18%, anti-TG/TSH from 18 to 4% and anti-TPO/TSH from 11 to 3%. Simultaneously, FT4, FT3, anti-TG, and anti-TPO tests ordered in outpatients also displayed a significant gradual decrease.

CONCLUSIONS
Hospital-based laboratories can safely apply a generally accepted TFTs algorithm on physician's orders without any compromise in diagnostic/therapeutic accuracy, thus achieving significant direct cost-reduction and increased physician awareness on current TFT ordering practices. Such an approach, combined with collaboration with ordering physicians, can safeguard patients from the consequences of low-value care practices.

Notas|George|G| Kampa|Marilena|M| Malliaraki|Niki|N| Petrodaskalaki|Maria|M| Papavasileiou|Stathis|S| Castanas|Elias|E|

Thyroid function tests
Low-value care
Anti-thyroid antibodies
Thyroid stimulating hormone
Thyroxine
Tri-iodothyronine


Experiences in anti-tuberculosis treatment in patients with multiple previous treatments and its impact on drug resistant tuberculosis epidemics.

Abstract:
BACKGROUND
Tuberculosis (TB) patients with a history of multiple anti-TB treatments are the 'neglected' group to the free anti-TB treatment policy in China.

OBJECTIVE
To understand the experiences of TB patients with multiple previous treatments with regard to bacteriological diagnosis and treatment regimens, especially for second-line anti-TB drugs, and how this might influence the risks of multidrug and extensively drug-resistant TB (M/XDR-TB).

DESIGN
A cross-sectional study was conducted in 10 county/district TB clinics in five provinces of China. The study participants were TB patients that had at least two previous treatment episodes that lasted longer than 1 month each. Face-to-face interviews and drug susceptibility testing (DST) were conducted with the consenting participants.

RESULTS
A total of 328 TB patients were recruited. The proportion of multidrug-resistant tuberculosis (MDR-TB) was 58.2% in the 287 DST-confirmed patients. Forty-two percent of the patients did not complete their first treatment course. About 23.8% of the participants had a history of taking second-line drugs, and more than 77.8% of them were treated in county TB dispensaries where only sputum microscopy was applied. Multivariate analysis found that the use of second-line drugs was significantly associated with frequency of previous treatments (p<0.01), but not with drug resistance profiles of patients.

CONCLUSIONS
Patients with multiple previous treatments are at extremely high risk of MDR-TB in China. The unregulated use of second-line drugs bring about the threat of XDR-TB epidemic. DST-guided treatment and strict regulations of anti-TB treatment should be assured for the high-risk TB patients for the prevention and control of M/XDR-TB.

Xu|Biao|B|
Zhao|Qi|Q|
Hu|Yi|Y|
Shi|Ying|Y|
Wang|Weibing|W|
Diwan|Vinod K|VK|

drug resistance
tuberculosis
China
second-line anti-tuberculosis drugs
treatment history


Primary total knee arthroplasty in infection sequelae about the native knee.

Abstract: The aim of this study is to assess the results of primary total knee arthroplasty (TKA) after bone or joint sepsis about the native knee and to analyze the risk factors of periprosthetic infection. Sixty-two patients (62 knees), considered to have prior sepsis history to be resolved, underwent primary TKA and were followed during a mean of 6.1years (range, 2-10.4years). Of the 62 patients, periprosthetic infection occurred in 6 after primary TKA (9.7%). Five of 6 patients grew the same organism as prior infection. The number of prior surgeries undertaken for deep infection was found to be an independent risk factor of periprosthetic infection.

Seo|Jai-Gon|JG| Moon|Young-Wan|YW| Park|Sang-Hoon|SH| Han|Kye-Young|KY| Kim|Sang-Min|SM|

total knee arthroplasty
native knee
bone or joint sepsis
periprosthetic infection


Fresh-Water Mollusks as Biomonitors for Ecotoxicity of Nanomaterials.

Abstract: The use of different nanoparticles (NPs) is growing every year since discoveries of their unique properties. The wide use of nanomaterials has raised concerns about their safety and possible accumulation in the aquatic environment. Mussels are being considered as one of the most suitable organisms for bioaccumulation monitoring. Within our study, we focused on developing the method that can be applied in field studies of ecotoxicity and can be nondestructive and informative at early times of exposure, while at the same time being based on changes of physiological parameters of fresh water mussels. The changes in the cardiovascular and neural systems of mollusks (Anodonta anatina and Unio tumidus) were measured as biomarkers of toxic effects. Different monometallic and bimetallic NPs, silicon NPs with various ligands were applied as test substances. Changes in cardiovascular and neural functions were in good correlation with accumulation tests for all tested NPs.

mollusks
ecotoxicity
bioindicators
heart rate
inorganic nanoparticles


Iridium/N-heterocyclic carbene-catalyzed C-H borylation of arenes by diisopropylaminoborane.

Abstract: Catalytic C-H borylation of arenes has been widely used in organic synthesis because it allows the introduction of a versatile boron functionality directly onto simple, unfunctionalized arenes. We report herein the use of diisopropylaminoborane as a boron source in C-H borylation of arenes. An iridium(I) complex with 1,3-dicyclohexylimidazol-2-ylidene is found to efficiently catalyze the borylation of arenes and heteroarenes. The resulting aminoborylated products can be converted to the corresponding boronic acid derivatives simply by treatment with suitable diols or diamines.

iridium
boronic acid
C–H borylation
N-heterocyclic carbene


Emerging roles of alternative cleavage and polyadenylation (APA) in human disease.

Abstract: In the messenger RNA (mRNA) maturation process, the 3'-end of pre-mRNA is cleaved and a poly(A) sequence is added, this is an important determinant of mRNA stability and its cellular functions. More than 60%-70% of human genes have three or more polyadenylation (APA) sites and can be cleaved at different sites, generating mRNA transcripts of varying lengths. This phenomenon is termed as alternative cleavage and polyadenylation (APA) and it plays role in key biological processes like gene regulation, cell proliferation, senescence, and also in various human diseases. Loss of regulatory microRNA binding sites and interactions with RNA-binding proteins leading to APA are largely investigated in human diseases. However, the functions of the core APA machinery and related factors during disease conditions remain largely unknown. In this review, we discuss the roles of polyadenylation machinery in relation to brain disease, cardiac failure, pulmonary fibrosis, cancer, infectious conditions, and other human diseases. Collectively, we believe this review will be a useful avenue for understanding the emerging role of APA in the pathobiology of various human diseases.


A cost-effectiveness analysis of screening for silent atrial fibrillation after ischaemic stroke.

Abstract:
AIMS
The purpose of this study was to estimate the cost-effectiveness of two screening methods for detection of silent AF, intermittent electrocardiogram (ECG) recordings using a handheld recording device, at regular time intervals for 30 days, and short-term 24 h continuous Holter ECG, in comparison with a no-screening alternative in 75-year-old patients with a recent ischaemic stroke.

METHODS AND RESULTS
The long-term (20-year) costs and effects of all alternatives were estimated with a decision analytic model combining the result of a clinical study and epidemiological data from Sweden. The structure of a cost-effectiveness analysis was used in this study. The short-term decision tree model analysed the screening procedure until the onset of anticoagulant treatment. The second part of the decision model followed a Markov design, simulating the patients' health states for 20 years. Continuous 24 h ECG recording was inferior to intermittent ECG in terms of cost-effectiveness, due to both lower sensitivity and higher costs. The base-case analysis compared intermittent ECG screening with no screening of patients with recent stroke. The implementation of the screening programme on 1000 patients resulted over a 20-year period in 11 avoided strokes and the gain of 29 life-years, or 23 quality-adjusted life years, and cost savings of €55 400.

CONCLUSION
Screening of silent AF by intermittent ECG recordings in patients with a recent ischaemic stroke is a cost-effective use of health care resources saving costs and lives and improving the quality of life.

Levin|Lars-Åke|LÅ|
Husberg|Magnus|M|
Sobocinski|Piotr Doliwa|PD|
Kull|Viveka Frykman|VF|
Friberg|Leif|L|
Rosenqvist|Mårten|M|
Davidson|Thomas|T|

Cost-effectiveness
Screening
Atrial fibrillation
Ischaemic stroke
QALY
Secondary prevention


Nucleus Accumbens Core and Shell Differentially Encode Reward-Associated Cues after Reinforcer Devaluation.

Abstract:
UNLABELLED
Nucleus accumbens (NAc) neurons encode features of stimulus learning and action selection associated with rewards. The NAc is necessary for using information about expected outcome values to guide behavior after reinforcer devaluation. Evidence suggests that core and shell subregions may play dissociable roles in guiding motivated behavior. Here, we recorded neural activity in the NAc core and shell during training and performance of a reinforcer devaluation task. Long-Evans male rats were trained that presses on a lever under an illuminated cue light delivered a flavored sucrose reward. On subsequent test days, each rat was given free access to one of two distinctly flavored foods to consume to satiation and were then immediately tested on the lever pressing task under extinction conditions. Rats decreased pressing on the test day when the reinforcer earned during training was the sated flavor (devalued) compared with the test day when the reinforcer was not the sated flavor (nondevalued), demonstrating evidence of outcome-selective devaluation. Cue-selective encoding during training by NAc core (but not shell) neurons reliably predicted subsequent behavioral performance; that is, the greater the percentage of neurons that responded to the cue, the better the rats suppressed responding after devaluation. In contrast, NAc shell (but not core) neurons significantly decreased cue-selective encoding in the devalued condition compared with the nondevalued condition. These data reveal that NAc core and shell neurons encode information differentially about outcome-specific cues after reinforcer devaluation that are related to behavioral performance and outcome value, respectively.

SIGNIFICANCE STATEMENT
Many neuropsychiatric disorders are marked by impairments in behavioral flexibility. Although the nucleus accumbens (NAc) is required for behavioral flexibility, it is not known how NAc neurons encode this information. Here, we recorded NAc neurons during a training session in which rats learned that a cue predicted a specific reward and during a test session when that reward value was changed. Although encoding in the core during training predicted the ability of rats to change behavior after the reward value was altered, the NAc shell encoded information about the change in reward value during the test session. These findings suggest differential roles of the core and shell in behavioral flexibility.

West|Elizabeth A|EA|
Carelli|Regina M|RM|

accumbens devaluation behavior motivation rat electrophysiology


Discrimination of cultivated silk and wild silk by conventional instrumental analyses.

Abstract: In Japan, recent trends have seen wild silk preferred over cultivated silk because of its texture. Some cases of fraud have occurred where cultivated silk garments are sold as wild silk. Samples from these cases, morphological observation using light microscope and polarized microscope have been conducted in forensic science laboratories. Sometimes scanning electron microscopy was also carried out. However, the morphology of silk shows quite wide variation, which makes it difficult to discriminate wild and cultivated silks by this method. In this report, silk discrimination was investigated using conventional instrumental analyses commonly available in forensic laboratories, such as Fourier-transfer infrared spectrometry (FT-IR), pyrolysis-gas chromatography/mass spectrometry (pyr-GC/MS) and differential thermal analysis (DTA). By FT-IR, cultivated and wild silk gave similar infrared spectra, but wild silk had a characteristic peak at 965 cm(-1) from the deformation vibration of the carbon-carbon double bond of the indole ring. Comparison of the pyrograms of cultivated and wild silk showed that wild silk had large indole and skatole peaks that cultivated silk did not, and these peaks might arise from tryptophan. The results of thermogravimetry/DTA showed that the endothermic peak was about 40 °C higher for wild silk than for cultivated silk. Using a combination of these results, cultivated and wild silk could be discriminated by common forensic instrumental techniques.

Matsuyama|Yuji|Y| Nagatani|Yoshiaki|Y| Goto|Toshiyuki|T| Suzuki|Shinichi|S|

D017550:Spectroscopy, Fourier Transform Infrared


Improving the mother-infant relationship following postnatal depression: a randomised controlled trial of a brief intervention (HUGS).

Abstract: Postnatal depression (PND) disrupts the crucial mother-infant relationship on which optimal child development depends. However, few well-evaluated, brief mother-infant interaction interventions exist. This randomised controlled trial (RCT) aimed to evaluate the effect of a 4-session, group-based mother-infant interaction intervention ('HUGS'), compared to a control playgroup, both following cognitive-behavioural therapy for PND, on mother-infant relationships and early child development. It was hypothesised that dyads receiving the HUGS intervention would show larger improvements than control dyads. Mothers (n = 77; M age = 32 years) diagnosed with major or minor depressive disorder using the Structured Clinical Interview for the DSM-IV participated with their infants (<12 months). Primary outcomes were observed mother-infant interactions using the Parent Child Early Relational Assessment (ERA) and maternal parenting stress using the Parenting Stress Index (PSI). Data were collected at baseline, post-PND treatment, post-HUGS intervention and 6-month post-HUGS follow-up. Seventy-four percent of HUGS dyads attended at least half of the HUGS sessions (≥2). Significant group differences emerged at the 6-month follow-up (but were not significant immediately post-HUGS). At 6-month follow-up, HUGS dyads showed significantly improved parental positive affective involvement and verbalisation (ERA; F1, 47 = 4.96, p = .03, ηp2 = .10) and less impaired bonding (F1, 45 = 4.55, p = .04, ηp2 = .09) than control dyads. No differences were found on the PSI or on child development outcomes. Both groups improved substantially (around 30 points) on the PSI following PND treatment, so that average scores were below the clinically significant threshold when beginning HUGS and the control playgroup. Findings suggest that incorporating HUGS intervention following PND treatment is effective for improving mother-infant relationships. A longer-term follow-up and larger sample size may be needed for improved mother-infant relationships to show an impact on observable child developmental outcomes. Registered with the Australian New Zealand Clinical Trials Registry (ACTRN12612001110875).

Postnatal depression
randomised controlled trial
Intervention
Child development
Mother-infant interactions


Leishmania (V.) braziliensis infecting bats from Pantanal wetland, Brazil: First records for Platyrrhinus lineatus and Artibeus planirostris.

Abstract: In the New World genus Leishmania parasites are etiological agents of neglected zoonoses known as leishmaniasis. Its epidemiology is very complex due to the participation of several species of sand fly vectors and mammalian hosts, and man is an accidental host. Control is very difficult because of the different epidemiological patterns of transmission observed. Studies about Leishmania spp. infection in bats are so scarce, which represents a large gap in knowledge about the role of these animals in the transmission cycle of these pathogens, especially when considering that Chiroptera is one of the most abundant and diverse orders among mammals. Leishmaniasis in Mato Grosso do Sul, Brazil are remarkably frequent, probably due to the abundance of its regional mastofauna. The recent record of L. braziliensis in bats from this state indicates the need to clarify the role of these mammals in the transmission cycle. In this study we evaluated the presence of Leishmania parasites in the skin of different species of bats, using PCR directed to Leishmania spp. kDNA for screening followed by PCR/RFLP analysis of the hsp70 gene for the identification of parasite species. Leishmania species identification was confirmed by PCR directed to the G6PD gene of L. braziliensis, followed by sequencing of the PCR product. Samples from 47 bats were processed, of which in three specimens (6.38%) was detected the presence of Leishmania sp. kDNA. PCR/RFLP and sequencing identified the species involved in the infection as L. braziliensis in all of them. This is the first report of Leishmania braziliensis in bats from Pantanal ecosystem and the first record of this species in Platyrrhinus lineatus and Artibeus planirostris, bats with a wide distribution in South America. These results reinforce the need to deepen the knowledge about the possibility of bats act as reservoirs of Leishmania spp. especially considering their ability of dispersion and occupation of anthropic environments.

de Castro Ferreira|Eduardo|E|
Pereira|Agnes Antônio Sampaio|AAS|
Silveira|Maurício|M|
Margonari|Carina|C|
Marcon|Glaucia Elisete Barbosa|GEB|
de Oliveira França|Adriana|A|
Castro|Ludiele Souza|LS|
Bordignon|Marcelo Oscar|MO|
Fischer|Erich|E|
Tomas|Walfrido Moraes|WM|
Dorval|Maria Elizabeth Cavalheiros|MEC|
Gontijo|Célia Maria Ferreira|CMF|

Bats
Platyrrhinus lineatus
Artibeus planirostris
Leishmania braziliensis


Photophysical Properties of some 1,3,4-Oxadiazole Derivatives Containing Phenolphtalein, Fluorene and Bisphenol A Units.

Abstract: The photophysical properties of the three 1,3,4-oxadiazole derivatives containing fluorene (Ox-FL); fluorene and phenolphtaleine (Ox-FL-FF); or fluorene and bisphenol A (Ox-FL-BPA) moieties in the main chain were investigated by the fluorescence and absorption spectroscopy in different solvents and in the solid state. The electronic absorption spectra included a strong absorption band located in the 270-395 nm region, with a maxima around at 302 nm. The fluorescence excitation spectra were also characterized by one broad band, appearing in the wavelength range of 220-340 nm. All samples displayed the emission bands around 356-373 nm and exhibit high quantum yields ranged from 31.61 to 90.77%, in chloroform solution. The sensitivity of the emission spectra on medium characteristics (polarity, acidity and basicity) were evaluated by using the Catalan solvent scale and the fluorescence titration with a dilute acid solution.

Homocianu|Mihaela|M|
Ipate|Alina M|AM|
Hamciuc|Corneliu|C|
Airinei|Anton|A|

Photophysical properties
Emission quantum yields
Light-emitting materials
Optoelectronic applications


An 8-year follow-up of anti-vascular endothelial growth factor treatment with a treat-and-extend modality for neovascular age-related macular degeneration.

Abstract:
PURPOSE
To investigate long-term visual results of treatment with anti-vascular endothelial growth factor (VEGF) agents for neovascular age-related macular degeneration (nAMD) following a treat-and-extend regimen.

METHODS
Retrospective review of 155 patients who initiated treatment with bevacizumab for nAMD in one eye. At the final 8-year visit, 40 patients (26%) remained for follow-up. Mean change in best-corrected visual acuity (BCVA) was calculated compared to baseline values.

RESULTS
Mean BCVA improved significantly from baseline during the first year of treatment, with -0.11 logMAR units equivalent to 6.1 approximate Early Treatment Diabetic Retinopathy Study (approxETDRS) letters (p = <0.001). Mean BCVA was still significantly improved after 4 years of treatment for the entire group of patients and after 6 years of treatment for the subgroup of 40 patients who remained at the final 8-year visit. Thereafter, BCVA gradually declined and at 8 years, there was a mean change of 0.05 logMAR units equivalent to 2.1 approxETDRS letters below baseline (p = 0.530). Mean number of injections during the first year was 6.1 ± 2.8 and during year 8 was 5.4 ± 3.5. At 5 years, fundus autofluorescence showed some degree of macular atrophy in all eyes. At the final 8-year visit, 87.5% of the eyes had stable neovascular lesions with no fluid on optical coherence tomography (OCT).

CONCLUSION
In an everyday clinical setting, treatment of nAMD patients with a treat-and-extend modality provided improvement and stability of vision for several years. After 8 years of follow-up, there was a decline in visual acuity (VA) that could be explained by macular atrophic development.

D042461:Vascular Endothelial Growth Factor A

treat-and-extend bevacizumab AMD aflibercept ranibizumab


Feature Analysis of Smart Shoe Sensors for Classification of Gait Patterns.

Abstract: Gait analysis is commonly used to detect foot disorders and abnormalities such as supination, pronation, unstable left foot and unstable right foot. Early detection of these abnormalities could help us to correct the walking posture and avoid getting injuries. This paper presents extensive feature analyses on smart shoes sensor data, including pressure sensors, accelerometer and gyroscope signals, to obtain the optimum combination of the sensors for gait classification, which is crucial to implement a power-efficient mobile smart shoes system. In addition, we investigated the optimal length of data segmentation based on the gait cycle parameters, reduction of the feature dimensions and feature selection for the classification of the gait patterns. Benchmark tests among several machine learning algorithms were conducted using random forest, k-nearest neighbor (KNN), logistic regression and support vector machine (SVM) algorithms for the classification task. Our experiments demonstrated the combination of accelerometer and gyroscope sensor features with SVM achieved the best performance with 89.36% accuracy, 89.76% precision and 88.44% recall. This research suggests a new state-of-the-art gait classification approach, specifically on detecting human gait abnormalities.

Sunarya|Unang|U|0000-0002-4105-5118
Sun Hariyani|Yuli|Y|0000-0003-0618-3082
Cho|Taeheum|T|
Roh|Jongryun|J|
Hyeong|Joonho|J|
Sohn|Illsoo|I|
Kim|Sayup|S|
Park|Cheolsoo|C|

feature analysis
smart shoes
gait analysis
supination
pronation
pressure sensor
accelerometer
gyroscope


A Rapid, Univariate FT-NIR Procedure to Determine Moisture Concentration in Olive Oil.

Abstract: We recently observed that the weak near-infrared (NIR) band near 5260 cm-1 was relatively more intense for extra virgin olive oil (EVOO) than for refined olive oil (ROO). We also observed that its intensity was diminished upon heating and erroneously presumed that it may be attributed to volatile carbonyl components in EVOO. In the present study we demonstrate for the first time that this band is primarily attributed to a water O-H combination band. To accurately determine the intensity of this weak band, observed on a shifted and sloping baseline, we measured the peak-to-peak (p-p) height of its first derivative. An exponential calibration curve for p-p height versus gravimetrically-determined concentration of spiked water was satisfactorily generated. The calibration curve was first evaluated by using independent sets of gravimetrically prepared test samples. Subsequently, it was used to determine the moisture content, a quality parameter, for a limited set of authenticated reference olive oils whose quality and purity were confirmed by official methods. These concentrations, 0.098-0.12% H2O (w/w) for EVOO, 0.022-0.030% H2O (w/w) for ROO, and 0.028-0.054% H2O (w/w) for pomace olive oil (POO), were consistent with those reported in the literature. For 88 commercial products investigated, the moisture levels fell in the range from 0.026% to 0.13% (w/w). The correlation between moisture content and other olive oil quality parameters has been reported in the literature and has yet to be further investigated.

Fardin-Kia|Ali Reza|AR|
Karunathilaka|Sanjeewa R|SR|
Yakes|Betsy Jean|BJ|
Lee|Kyungeun|K|
Ellsworth|Zachary|Z|
Brückner|Lea|L|
Mossoba|Magdi M|MM|

olive oil
moisture in EVOO
near-infrared spectroscopy
rapid screening


Facile Synthesis of Porous Zn-Sn-O Nanocubes and Their Electrochemical Performances.

Abstract: Porous Zn-Sn-O nanocubes with a uniform size were synthesized through a facile aqueous solution route combined with subsequent thermal treatment. The chemical composition, morphology, and microstructure of Zn-Sn-O nanocubes, which have significant effects on the lithium storage performances, were easily tuned by adjusting the calcination temperature in preparation processes of ZnSn(OH)6 solid nanocubes. Further studies revealed that porous Zn-Sn-O nanocubes prepared at 600 °C exhibited a good rate capability and a high reversible capacity of 700 mAh g-1 at a current density of 200 mA g-1 after 50 cycles, which may be a great potential as anode materials in Lithium-ion batteries.

Li|Bo|B| Li|Xiaomin|X| Zai|Jiantao|J| Qian|Xuefeng|X|

Porous
Nanocubes
Lithium-ion batteries
Zn–Sn–O


Prediction model optimization using full model selection with regression trees demonstrated with FTIR data from bovine milk.

Abstract: Predictive modeling is the development of a model that is best able to predict an outcome based on given input variables. Model algorithms are different processes that are used to define functions that transform the data within models. Common algorithms include logistic regression (LR), linear discriminant analysis (LDA), classification and regression trees (CART), naïve Bayes (NB), and k-nearest neighbor (KNN). Data preprocessing option, such as feature extraction and reduction, and model algorithms are commonly selected empirically in epidemiological studies even though these decisions can significantly affect model performance. Accordingly, full model selection (FMS) methods were developed to provide a systematic approach to select predictive modeling methods; however, current limitations of FMS, such as its dependency on user-selected hyperparameters, have prevented their routine incorporation into analyses for model performance optimization. Here we present the use of regression trees as an innovative method to apply FMS. Regression tree FMS (rtFMS) requires the development of a model for every combination of predictive modeling method options under consideration. The iterated, cross-validation performances of these models are then passed through a regression tree for selection of a final model. We demonstrate the benefits of rtFMS using a milk Fourier transform infrared spectroscopy dataset, wherein we build prediction models for two blood metabolic health parameters in dairy cows, nonesterified fatty acids (NEFA) and β-hydroxybutyrate acid (BHBA). The goal for building NEFA and BHBA prediction models is to provide a milk-based screening tool for metabolic health in dairy cattle that can be incorporated automatically in milk analysis routines. These models could be used in conjunction with physical exams, cow side tests, and other indications to initiate medical intervention. In contrast to previously reported FMS methods, rtFMS is not a black box, is simple to implement and interpret, it does not have hyperparameters, and it illustrates the relative importance of modeling options. Additionally, rtFMS allows for indirect comparisons among models developed using different datasets. Finally, rtFMS eliminates user bias due to personal preference for certain methods and rtFMS removes the dependency on published comparisons of methods. Thus, rtFMS provides clear benefits over the empirical selection of data preprocessing options and model algorithms.

Tremblay|M|M|
Kammer|M|M|
Lange|H|H|
Plattner|S|S|
Baumgartner|C|C|
Stegeman|J A|JA|
Duda|J|J|
Mansfeld|R|R|
Döpfer|D|D|

Prediction model
Full model selection
Regression tree
Preprocessing
Fourier-transform infrared spectra


The dynamics of the biological membrane surrounding the buffalo milk fat globule investigated as a function of temperature.

Abstract: The biological membrane surrounding fat globules in milk (the MFGM) is poorly understood, despite its importance in digestion and in determining the properties of fat globules. In this study, in situ structural investigations of buffalo MFGM were performed as a function of temperature (4-60°C), using confocal microscopy. We demonstrate that temperature and rate of temperature change affected the lipid domains formed in the MFGM with the lateral segregation (i) of high Tm lipids and cholesterol in a Lo phase for both T<Tm and T>Tm and (ii) of high Tm lipids in a gel phase for T<Tm. Rapid cooling favours nucleation, while slow cooling favours growth, leading to the formation of small and large lipid domains, respectively. Changes in the interfacial properties of the MFGM, as a function of temperature, could modulate the functions of fat globules during processing and digestion.

Nguyen|Hanh T H|HTH|
Madec|Marie-Noëlle|MN|
Ong|Lydia|L|
Kentish|Sandra E|SE|
Gras|Sally L|SL|
Lopez|Christelle|C|

Lipid domain
Confocal laser scanning microscopy
Lipid phase separation
Microstructure variations
Milk fat globule membrane
Sphingomyelin


Multimodal 19 F NMR Dopamine Detection and Imaging with a Nanoparticle-Based Displacement Assay.

Abstract: Nanoconjugates composed of gold nanoparticles (core diameter=1.9 nm) coated with thioundecyl-d-glucopyranosides and fluorinated phenylboronic acids can detect diol-containing derivatives by means of 19 F NMR spectroscopic analysis. The spectra of nanoconjugate solutions display broad signals due to the fast relaxation of the 19 F nuclei caused by nanoparticle grafting. When dopamine is added, the formation of a boronate ester between the analyte and the fluorinated boronic acid causes the release of the latter in solution and consequent sharpening of the NMR signals. Dopamine can be selectively detected through magnetic resonance imaging (MRI) and NMR spectroscopic analysis with respect to glucose and galactose with a detection limit of 20 μm. The chemical shift of the released ester is diagnostic of the recognized analyte. Consequently, the sensor also enables the simultaneous detection of different analytes.

Gabrielli|Luca|L| Carril|Monica|M| Padro|Daniel|D| Mancin|Fabrizio|F|

nanoparticles
boronic esters
NMR spectroscopy
chemosensors
self-organization


Protease supplementation attenuates the intestinal health damage caused by low-protein diets in Pekin ducks.

Abstract: The objective of this study was to investigate the effects of low-protein diets with low digestibility of feed ingredients on intestinal damage and to explore whether the protease supplementation can alleviate the damage in Pekin ducks. A total of 576 Pekin ducklings (6 replicate pens, 16 ducks/pen) were randomly assigned to 6 dietary treatments (3 × 2 factorial arrangement) in a randomized complete block design. Factors were CP levels (13.5%, 15.5%, and 17.5%) and protease (0 or 20,000U/kg). Compared with the diets containing 17.5% CP, low-protein diets (13.5% CP) showed suppressed (P < 0.05) growth performance and feed intake (FI); reduced (P < 0.05) serum-free arginine, isoleucine, leucine, methionine, phenylalanine, valine, and proline as well as the cecal acetate and propionate concentration; increased (P < 0.05) plasma and ileal mucosal tumor necrosis factor-α (TNF-α) concentration; and downregulated (P < 0.05) mRNA expression of TNF-α, nuclear transcription factor-κb, interferon gamma, and Occludin in ileal mucosa. Irrespective of the dietary CP levels, protease supplementation significantly increased (P < 0.05) the serum-free glutamic acid concentration while decreasing (P < 0.05) the plasma endotoxin, IL-6, and the cecal isovalerate concentration. A significant interactive effect was observed between low-protein diets and protease supplementation (P < 0.05) on serum-free arginine concentration, the ratio of ileal villus height to crypt depth, and the IL-6 concentration in ileal mucosa. These results indicated that low-protein diets could damage intestinal integrity to induce systemic inflammation response and at last to suppress growth performance. Protease supplementation could partly attenuate the negative effects on gut health caused by low-protein diets in Pekin ducks.

Wang|Q D|QD|
Li|S|S|
Zhang|K Y|KY|
Zhang|Y|Y|
Bai|S P|SP|
Ding|X M|XM|
Wang|J P|JP|
Peng|H W|HW|
Tian|G|G|
Xuan|Y|Y|
Su|Z W|ZW|
Zeng|Q F|QF|

D000824:Animal Nutritional Physiological Phenomena

protease
intestinal health
low-protein diet
Pekin duck
serum free amino acid


18-year temporal trend of multiple sclerosis in southern Iran.

Abstract:
BACKGROUND
Multiple Sclerosis (MS) imposes significant burdens on patients, their families, and national healthcare systems particularly when there is a resource constraint. Proper prioritization and resource allocation are therefore essential for any effective disease management. Accordingly, we sought to assess the temporal profile of MS incidence over the past two decades in southeast Iran.

METHODS
A longitudinal design was employed using data from the Iranian multiple sclerosis registry system from March 2001 to March 2019 (n=6034). Annual age-standardized incidence rates of MS (cases of clinically isolated syndrome were also included) were calculated and the trend of incidence from 2001 to 2018 was analyzed.

RESULTS
The age-adjusted incidence rate of MS raised from 1.72/100,000 in 2001 to 11.29/100,000 in 2018 (average of 18-year incidence rate was 6.30/100,000), indicating a notable rise in the incidence of MS (P-Value<0.001). However, the female to male ratio of 3.62 remained relatively stable during the study period.

CONCLUSION
Our study suggests that, in Fars province, the incidence of MS has been remarkably rising over the past two decades. We recommend further studies to better understand the determinants of this pattern. Implementing effective policies in lowering the burden of MS is another important step in this regard.

Mobasheri|Farzaneh|F|
Fararouei|Mohammad|M|
Hasanzadeh|Jafar|J|
Jaberi|Abbas Rahimi|AR|


High-performance bioanalysis based on ion concentration polarization of micro-/nanofluidic devices.

Abstract: Micro-/nanofluidics has received considerable attention over the past two decades, which allows efficient biomolecule trapping and preconcentration due to ion concentration polarization (ICP) within nanostructures. The rich scientific content related to ICP has been widely exploited in different applications including protein concentration, biomolecules sensing and detection, cell analysis, and water purification. Compared to pure microfluidic devices, micro-/nanofluidic devices show a highly efficient sample enrichment capacity and nonlinear electrokinetic flow feature. These two unique characterizations make the micro-/nanofluidic systems promising in high-performance bioanalysis. This review provides a comprehensive description of the ICP phenomenon and its applications in bioanalysis. Perspectives are also provided for future developments and directions of this research field.

Wang|Chen|C| Wang|Yang|Y| Zhou|Yue|Y| Wu|Zeng-Qiang|ZQ| Xia|Xing-Hua|XH|

Bioanalysis
Micro-/nanofluidics
Preconcentration
Nonlinear electrokinetic flow
Ionic concentration polarization (ICP)


Cognitive Assessment Tools Recommended in Geriatric Oncology Guidelines: A Rapid Review.

Abstract: Cognitive assessment is a cornerstone of geriatric care. Cognitive impairment has the potential to significantly impact multiple phases of a person's cancer care experience. Accurately identifying this vulnerability is a challenge for many cancer care clinicians, thus the use of validated cognitive assessment tools are recommended. As international cancer guidelines for older adults recommend Geriatric Assessment (GA) which includes an evaluation of cognition, clinicians need to be familiar with the overall interpretation of the commonly used cognitive assessment tools. This rapid review investigated the cognitive assessment tools that were most frequently recommended by Geriatric Oncology guidelines: Blessed Orientation-Memory-Concentration test (BOMC), Clock Drawing Test (CDT), Mini-Cog, Mini-Mental State Examination (MMSE), Montreal Cognitive Assessment (MoCA), and Short Portable Mental Status Questionnaire (SPMSQ). A detailed appraisal of the strengths and limitations of each tool was conducted, with a focus on practical aspects of implementing cognitive assessment tools into real-world clinical settings. Finally, recommendations on choosing an assessment tool and the additional considerations beyond screening are discussed.

Tuch|Gina|G|
Soo|Wee Kheng|WK|
Luo|Ki-Yung|KY|
Frearson|Kinglsey|K|
Oh|Ek Leone|EL|
Phillips|Jane L|JL|0000-0002-3691-8230
Agar|Meera|M|
Lane|Heather|H|

screening
aged
clinical decision-making
cognition/physiology
cognitive dysfunction/diagnosis
dementia/diagnosis
geriatric assessment/methods
medical oncology/standards


Machine-Learning Monitoring System for Predicting Mortality Among Patients With Noncancer End-Stage Liver Disease: Retrospective Study.

Abstract:
BACKGROUND
Patients with end-stage liver disease (ESLD) have limited treatment options and have a deteriorated quality of life with an uncertain prognosis. Early identification of ESLD patients with a poor prognosis is valuable, especially for palliative care. However, it is difficult to predict ESLD patients that require either acute care or palliative care.

OBJECTIVE
We sought to create a machine-learning monitoring system that can predict mortality or classify ESLD patients. Several machine-learning models with visualized graphs, decision trees, ensemble learning, and clustering were assessed.

METHODS
A retrospective cohort study was conducted using electronic medical records of patients from Wan Fang Hospital and Taipei Medical University Hospital. A total of 1214 patients from Wan Fang Hospital were used to establish a dataset for training and 689 patients from Taipei Medical University Hospital were used as a validation set.

RESULTS
The overall mortality rate of patients in the training set and validation set was 28.3% (257/907) and 22.6% (145/643), respectively. In traditional clinical scoring models, prothrombin time-international normalized ratio, which was significant in the Cox regression (P<.001, hazard ratio 1.288), had a prominent influence on predicting mortality, and the area under the receiver operating characteristic (ROC) curve reached approximately 0.75. In supervised machine-learning models, the concordance statistic of ROC curves reached 0.852 for the random forest model and reached 0.833 for the adaptive boosting model. Blood urea nitrogen, bilirubin, and sodium were regarded as critical factors for predicting mortality. Creatinine, hemoglobin, and albumin were also significant mortality predictors. In unsupervised learning models, hierarchical clustering analysis could accurately group acute death patients and palliative care patients into different clusters from patients in the survival group.

CONCLUSIONS
Medical artificial intelligence has become a cutting-edge tool in clinical medicine, as it has been found to have predictive ability in several diseases. The machine-learning monitoring system developed in this study involves multifaceted analyses, which include various aspects for evaluation and diagnosis. This strength makes the clinical results more objective and reliable. Moreover, the visualized interface in this system offers more intelligible outcomes. Therefore, this machine-learning monitoring system provides a comprehensive approach for assessing patient condition, and may help to classify acute death patients and palliative care patients. Upon further validation and improvement, the system may be used to help physicians in the management of ESLD patients.

noncancer-related end-stage liver disease


Understanding Wood Surface Chemistry and Approaches to Modification: A Review.

Abstract: Wood was designed, after millions of years of evolution, to perform in a wet environment. Nature is programmed to recycle it, in a timely way, back to the basic building blocks of carbon dioxide and water. All recycling chemistries start with an invasion of the wood surface. The surface of wood is porous, hygroscopic, viscoelastic, and anisotropic that is better defined in interface/interphase zones. This surface is dynamic and in constant change with changing humidity, temperature, oxygen levels, ultraviolet energy, microorganisms and stress. This chapter is a review of the chemical properties of a wood surface and performance issues associated with it.

interface
interphase
absorption
adsorption
coatings
decay
fungi
hardness
mold
water repellency
weathering


Hepatitis B virus preS1 deletion is related to viral replication increase and disease progression.

Abstract:
AIM
To investigate the clinical implications of hepatitis B virus (HBV) preS1 deletion.

METHODS
We developed a fluorescence resonance energy transfer-based real-time polymerase chain reaction (RT-PCR) that can detect four genotypes (wild type, 15-bp, 18-bp and 21-bp deletion). The PCR method was used in two cohorts of Korean chronic HBV subjects with genotype C infections. Cohort I included 292 chronic HBV subjects randomly selected from Cheju National University Hospital (Jeju, South Korea) or Seoul National University Hospital (Seoul, South Korea), and cohort II included 90 consecutive chronic HBV carriers recruited from Konkuk University Hospital (Seoul, South Korea); the cohort II patients did not have hepatocellular carcinoma or liver cirrhosis.

RESULTS
The method proposed in this study identified 341 of 382 samples (89.3%). Deletion variants were identified in 100 (29.3%) of the 341 detected samples. In both cohorts, the subjects with deletions had a significantly higher Hepatitis B virus e antigen (HBeAg)-positive seroprevalence [cohort I, wild (51.0%) vs deletion (75.0%), P < 0.001; cohort II, wild (69.2%) vs deletion (92.9%), P = 0.002] and higher HBV DNA levels [cohort I, wild (797.7 pg/mL) vs deletion (1678.9 pg/mL), P = 0.013; cohort II, wild (8.3 × 10(8) copies/mL) vs deletion (2.2 × 10(9) copies/mL), P = 0.049], compared to subjects with wild type HBV.

CONCLUSION
HBV genotype C preS1 deletion may affect disease progression in chronic HBV subjects through an extended duration of HBeAg seropositive status and increased HBV replications.

Lee|Seoung-Ae|SA| Kim|Ki-Jeong|KJ| Kim|Hong|H| Choi|Won-Hyuk|WH| Won|Yu-Sub|YS| Kim|Bum-Joon|BJ|

D031541:Fluorescence Resonance Energy Transfer

D060888:Real-Time Polymerase Chain Reaction

Hepatitis B virus
Genotype C
Hepatocellular carcinoma
Hepatitis B virus e antigen
PreS1 start codon deletion


Anti-inflammatory effect of pyroglutamyl-leucine on lipopolysaccharide-stimulated RAW 264.7 macrophages.

Abstract:
AIMS
Food-derived peptides have been reported to yield a variety of health promoting activities. Pyroglutamyl peptides are contained in the wheat gluten hydrolysate. In the present study, we investigated the effect of pyroglutamyl dipeptides on the lipopolysaccharide (LPS)-induced inflammation in macrophages.

MAIN METHODS
RAW 264.7 macrophages were treated with LPS and various concentrations of pyroglutamyl-leucine (pyroGlu-Leu), -valine (pyroGlu-Val), -methionine (pyroGlu-Met), and -phenylalanine (pyroGlu-Phe). Cell viability/proliferation and various inflammatory parameters were measured by the established methods including ELISA and western blotting. The binding of fluorescein isothiocyanate-labeled LPS to RAW 264.7 cells was also measured fluorescently.

KEY FINDINGS
All the tested dipeptides significantly inhibited the secretion of nitric oxide, tumor necrosis factor (TNF)-α, and interleukin (IL)-6 from LPS-stimulated RAW 264.7 macrophages. Above all, pyroGlu-Leu inhibited the secretion of all these inflammatory mediators even at the lowest dose (200μg/ml). PyroGlu-Leu dose-dependently suppressed IκBα degradation and MAPK (JNK, ERK, and p38) phosphorylation in LPS-stimulated RAW 264.7 cells. On the other hand, it did not affect the binding of LPS to the cell surface.

SIGNIFICANCE
Our results indicated that pyroGlu-Leu inhibits LPS-induced inflammatory response via the blocking of NF-κB and MAPK pathways in RAW 264.7 macrophages.

Hirai|Shizuka|S| Horii|Sho|S| Matsuzaki|Yoshiaki|Y| Ono|Shin|S| Shimmura|Yuki|Y| Sato|Kenji|K| Egashira|Yukari|Y|

Pyroglutamyl-leucine
Macrophage
Pyroglutamyl peptide
Wheat gluten hydrolysate
Inflammation


Integrated regulatory network reveals novel candidate regulators in the development of negative energy balance in cattle.

Abstract: Negative energy balance (NEB) is an altered metabolic state in modern high-yielding dairy cows. This metabolic state occurs in the early postpartum period when energy demands for milk production and maintenance exceed that of energy intake. Negative energy balance or poor adaptation to this metabolic state has important effects on the liver and can lead to metabolic disorders and reduced fertility. The roles of regulatory factors, including transcription factors (TFs) and micro RNAs (miRNAs) have often been separately studied for evaluating of NEB. However, adaptive response to NEB is controlled by complex gene networks and still not fully understood. In this study, we aimed to discover the integrated gene regulatory networks involved in NEB development in liver tissue. We downloaded data sets including mRNA and miRNA expression profiles related to three and four cows with severe and moderate NEB, respectively. Our method integrated two independent types of information: module inference network by TFs, miRNAs and mRNA expression profiles (RNA-seq data) and computational target predictions. In total, 176 modules were predicted by using gene expression data and 64 miRNAs and 63 TFs were assigned to these modules. By using our integrated computational approach, we identified 13 TF-module and 19 miRNA-module interactions. Most of these modules were associated with liver metabolic processes as well as immune and stress responses, which might play crucial roles in NEB development. Literature survey results also showed that several regulators and gene targets have already been characterized as important factors in liver metabolic processes. These results provided novel insights into regulatory mechanisms at the TF and miRNA levels during NEB. In addition, the method described in this study seems to be applicable to construct integrated regulatory networks for different diseases or disorders.

Mozduri|Z|Z|
Bakhtiarizadeh|M R|MR|
Salehi|A|A|

integrated regulatory network
negative energy balance
transcription factor
module network
sequence-based information


A novel cause of rebreathing carbon dioxide related to removed CLIC-seal on the Dräger Apollo© anesthesia machine.

Abstract: We present a case report involving two sequential, surgically uneventful, laparoscopic cholecystectomies using the same anesthesia machine (Drager Apollo©) for which the level of inspired carbon dioxide was noted to be elevated following various diagnostic interventions including replacing the sodalime, increasing fresh gas flows, and a full inspection of equipment for malfunction. Eventually it was discovered that a rubber ring seal connecting the Dragersorb CLIC system© to the sodalime canister was inadvertently removed during the initial canister exchange resulting in an apparent bypassing of the absorbent and thus an inability of the exhaled gas to contact the sodalime. To our knowledge this is the first such description of this potential cause of elevated inspired carbon dioxide and should warrant consideration when other conventional interventions have failed.

Rebreathing
Inspired carbon dioxide
Sodalime
Dragersorb CLIC


CHADS2 scores as a predictor of ischemic stroke after radical prostatectomy.

Abstract: Patients with prostate cancer have an increased risk of stroke, but their absolute rate of stroke depends on age and comorbid conditions. The Charlson Comorbidity Index Score (CCIS) is a widely accepted measure for risk adjustment in administrative claims data sets. This study assesses the predictive value of CHADS2 scores and CCIS for stroke among patients with prostate cancer. The study was conducted based on data taken from Taiwan's National Health Insurance Research Database (NHIRD). We identified a total of 5414 participants with nonatrial fibrillation (AF) prostate cancer diagnoses who underwent radical prostatectomy between 1997 and 2011. CHADS2 scores and CCIS were used to stratify the 5-year ischemic stroke risk. All participants were followed from the date of enrollment until ischemic stroke, death, or the end of the 5-year follow-up period. The 5-year risk of ischemic stroke in the present study was 1.7%. Ischemic stroke has a better correlation with CHADS2 (CHADS2 score = 0 to 1: 0.02%, CHADS2 score = 2 to 3: 13.9%, CHADS2 score ≥ 4: 44.4%; AUC = 0.978) than CCIS (CCIS = 0 to 1: 1.6%, CCIS = 2 to 3: 1.7%, CCIS ≥ 4: 3.8%; AUC = 0.520). Our results show that patients with prostate cancer who underwent radical prostatectomy show significantly higher risk of ischemic stroke in high CHADS2 score patients, and the CHADS2 score could be applied for ischemic stroke prediction. Cardiovascular risks evaluation and management are suggested for prostate cancer patients with higher CHADS2 score.

CHADS2 scores
predictor
ischemic stroke
radical prostatectomy
prostate cancer
risk


Muscle architecture and strength: adaptations to short-term resistance training in older adults.

Abstract:
INTRODUCTION
Muscle morphology and architecture changes in response to 6 weeks of progressive resistance training were examined in healthy older adults.

METHODS
In this randomized, controlled design, muscle strength, quality, and architecture were evaluated with knee extension, DEXA, and ultrasound, respectively, in 25 older adults.

RESULTS
Resistance training resulted in significant increases in strength and muscle quality of 32% and 31%, respectively. Cross-sectional area of the vastus lateralis increased by 7.4% (p ≤ 0.05). Physiological cross-sectional area (PCSA) of the thigh, a composite measure of muscle architecture, was related significantly to strength (r = 0.57; p ≤ 0.01) and demonstrated a significant interaction after training (p ≤ 0.05). Change in PCSA of the vastus lateralis was associated with change in strength independent of any other measure.

CONCLUSIONS
Six weeks of resistance training was effective at increasing strength, muscle quality, and muscle morphology in older adult men and women.

Scanlon|Tyler C|TC|
Fragala|Maren S|MS|
Stout|Jeffrey R|JR|
Emerson|Nadia S|NS|
Beyer|Kyle S|KS|
Oliveira|Leonardo P|LP|
Hoffman|Jay R|JR|

muscle quality
echo intensity
exercise
sarcopenia
ultrasonography


Application of green analytical chemistry to a green chemistry process: Magnetic resonance and Raman spectroscopic process monitoring of continuous ethanolic fermentation.

Abstract: Compact 1 H NMR and Raman spectrometers were used for real-time process monitoring of alcoholic fermentation in a continuous flow reactor. Yeast cells catalyzing the sucrose conversion were immobilized in alginate beads floating in the reactor. The spectrometers proved to be robust and could be easily attached to the reaction apparatus. As environmentally friendly analysis methods, 1 H NMR and Raman spectroscopy were selected to match the resource- and energy-saving process. Analyses took only a few seconds to minutes compared to chromatographic procedures and were, therefore, suitable for real-time control realized as a feedback loop. Both compact spectrometers were successfully implemented online. Raman spectroscopy allowed for faster spectral acquisition and higher quantitative precision, NMR yielded more resolved signals thus higher specificity. By using the software Matlab for automated data loading and processing, relevant parameters such as the ethanol, glycerol, and sugar content could be easily obtained. The subsequent multivariate data analysis using partial linear least-squares regression type 2 enabled the quantitative monitoring of all reactants within a single model in real time.

Legner|Robin|R|0000-0001-8641-7672 Wirtz|Alexander|A| Koza|Tim|T| Tetzlaff|Till|T| Nickisch-Hartfiel|Anna|A| Jaeger|Martin|M|0000-0002-7709-2869

NMR and Raman spectroscopy
compact spectrometer
multivariate data analysis
PLS2
bioprocess monitoring
immobilized yeast


Moderate Alcohol Consumption Is Associated With Lower Risk for Heart Failure But Not Atrial Fibrillation.

Abstract:
OBJECTIVES
The aim of this study was to assess the hypothesis that alcohol consumption is associated with onset of atrial fibrillation (AF) and/or heart failure (HF).

BACKGROUND
The connection between ethanol intake and AF or HF remains controversial.

METHODS
The study population was 22,824 AF- or HF-free subjects (48% men, age ≥35 years) randomly recruited from the general population included in the Moli-sani study, for whom complete data on HF, AF, and alcohol consumption were available. The cohort was followed up to December 31, 2015, for a median of 8.2 years (183,912 person-years). Incident cases were identified through linkage to the Molise regional archive of hospital discharges. Hazard ratios were calculated using Cox proportional hazard models and cubic spline regression.

RESULTS
A total of 943 incident cases of HF and 554 of AF were identified. In comparison with never drinkers, both former and occasional drinkers showed comparable risk for developing HF. Drinking alcohol in the range of 1 to 4 drinks/day was associated with a lower risk for HF, with a 22% maximum risk reduction at 20 g/day, independent of common confounders. In contrast, no association of alcohol consumption with onset of AF was observed. Very similar results were obtained after restriction of the analyses to regular or only wine drinkers or according to sex, age, social status, or adherence to the Mediterranean diet.

CONCLUSIONS
Consumption of alcohol in moderation was associated with a lower incidence of HF but not with development of AF.

Di Castelnuovo|Augusto|A|
Costanzo|Simona|S|
Bonaccio|Marialaura|M|
Rago|Livia|L|
De Curtis|Amalia|A|
Persichillo|Mariarosaria|M|
Bracone|Francesca|F|
Olivieri|Marco|M|
Cerletti|Chiara|C|
Donati|Maria Benedetta|MB|
de Gaetano|Giovanni|G|
Iacoviello|Licia|L|
|||

alcohol consumption
atrial fibrillation
heart failure