Potential of stem cell-derived exosomes to regenerate β islets through Pdx-1 dependent mechanism in a rat model of type 1 diabetes.

Abstract: Type 1 diabetes, has been recognized as an autoimmune disease. Like other immunological conditions, regulation of immune response is a key strategy to control the autoimmunity in diabetic patients. Mesenchymal stem cells have been shown to have a distinct potential in modulating the immune reactions. However, treatment with stem cells is combined with concerns about safety issues. To overcome these concerns, in this study, we have utilized the regenerative potential of exosomes isolated from menstrual blood-derived mesenchymal stem cells to restore the β-cell mass and insulin production in type 1 diabetes. Exosomes are nanovesicles containing various cargos involved in cellular communications. Streptozotocin was used to induce islet destruction and diabetes in male Wistar rats. Then, exosomes were intravenously injected into animals at different time points and in a single or repeated therapeutic doses. After about 6 weeks, animals were euthanized and the pancreas was analyzed for the presence of the regenerated β islets as well as the insulin secretion. The non-fasting blood glucose and the serum insulin level were also monitored during the study. Our results represented that menstrual blood-derived mesenchymal stem cell-derived exosomes enhance the β-cell mass and insulin production in the pancreas of diabetic animals that received repeated doses of exosomes. Immunohistochemistry analysis also confirmed the presence of insulin in the islets of treated animals. Further investigations proposed that exosomes induce the islet regeneration through pancreatic and duodenal homeobox 1 pathway. The exosome tracking also revealed the homing of injected exosomes to the pancreas.

exosome
type 1 diabetes
mesenchymal stem cell
pancreas
menstrual blood
β cell


Infant lower extremity long bone growth rates: comparison of contemporary with early 20th century data using mixed effect models.

Abstract:
OBJECTIVES
Modern reference standards for long bone growth are lacking for infants (≤1 year). This study develops a quantitative framework to characterize lower extremity bone shaft growth during infancy based on radiographic images, and compares it to data from the 1930s.

METHODS
Femoral, tibial, and fibular shaft length measurements (diaphysis plus metaphysis) were collected retrospectively from 70 infants on initial and follow-up skeletal surveys performed for suspected abuse (7/2005-2/2013). These serial skeletal survey data (SSSD) were compared to the Denver Child Research Council data (DCRCD), a 1930's longitudinal dataset from 80 infants. Mixed effects regression models were developed to estimate growth trajectories from these data. Growth trajectories and short-term (≤2 months) growth rates were compared.

RESULTS
Statistically distinct models described the contemporary (SSSD) and historic (DCRCD) datasets; however, there was substantial overlap (77-90%) between their confidence bands for the three measured bones. Based on developed models, the average long bone shafts of the DCRCD are shorter at birth than SSSD (femur: 77.0 vs. 82.3 mm; tibia: 64.4 vs. 68.2 mm; fibula: 61.0 vs. 64.4 mm), but the DCRCD long bone growth rates are faster than SSSD (femur: 0.21 vs. 0.17 mm/day; tibia: 0.16 vs. 0.14 mm/day; fibula: 0.15 vs. 0.14 mm/day). Short-term growth rates of these bones decreased with age. The effect of sexual dimorphism on long bone growth during infancy was non-significant.

CONCLUSION
This study provides reference standards for long bone growth rates during the dynamic period of infancy that may aid clinical assessment, and also inform research studies of disorders associated with altered skeletal growth.

Tsai|Andy|A|
Stamoulis|Catherine|C|
Barber|Ignasi|I|
Kleinman|Paul K|PK|

infant
long bone growth
Denver Child Research Council Data
mixed effects regression model


Strategies for determining the bioactive ingredients of honey-processed Astragalus by serum pharmacochemistry integrated with multivariate statistical analysis.

Abstract: Honey-processed Astragalus is a widely used traditional Chinese medicine that has a better effect on reinforcing "Qi" (vital energy) than the raw one. A comparative study of metabolites analysis between them in rat serum for finding the bioactive ingredients was carried out using serum pharmacochemistry and multivariate statistical analysis. The blood collection methods and time were optimized first. Then the prototypes and metabolites in serum samples after oral administration were investigated by ultra-high-performance liquid chromatography coupled with electrospray ionization quadrupole time-of-flight mass spectrometry integrated with principal component analysis and orthogonal partial least squares discriminant analysis. The contents of metabolites were also analyzed to evaluate the metabolic profile differences. As a result, nine prototypes and 36 metabolites were identified. Only two prototypes and 15 metabolites were different between raw and honey-processed Astragalus. Their biotransformation reactions contained the process of oxidation, demethylation, and hydrolysis in phase I and glucuronide conjugation or sulfate conjugation in phase II. Most of the detected metabolites were transformed from isoflavones and isoflavanes. Our results expand the knowledge about the influence of honey-processing on Astragalus and suggest the different curative effects between raw and honey-processed Astragalus might due to their therapeutic material discrepancy.

serum pharmacochemistry
multivariate statistical analysis
traditional Chinese medicine
metabolites
prototypes


Light-triggered theranostic liposomes for tumor diagnosis and combined photodynamic and hypoxia-activated prodrug therapy.

Abstract: Hypoxia tumor microenvironment is a major challenge for photodynamical therapy (PDT), and hypoxia-activated chemotherapy combined PDT could be promising for enhanced anticancer therapy. In this study, we report an innovative 2-nitroimidazole derivative conjugated polyethylene glycol (PEG) amphoteric polymer theranostic liposome encapsulated a photosensitizer Chlorin e6 (Ce6), hypoxia-activated prodrug Tirapazamine (TPZ) and gene probe for synergistic photodynamic-chemotherapy. Ce6-mediated PDT upon irradiation with a laser induces hypoxia, which leads to the disassembly of the liposome and activates the antitumor activity of TPZ for improved cancer cell-killing. The released co-delivered gene probe could effectively detect the oncogenic intracellular biomarker for diagnosis. Both in vitro and in vivo studies demonstrated the greatly improved anti-cancer activity compared to conventional PDT. This work contributes to the design of hypoxia-responsive multifunctional liposome for tumor diagnosis and hypoxia-activated chemotherapy combined PDT for synergetic therapy, which holds great promise for future cancer therapy.

Zhang|Kai|K| Zhang|Yuedong|Y| Meng|Xiangdan|X| Lu|Huiting|H| Chang|Huan|H| Dong|Haifeng|H| Zhang|Xueji|X|

Liposomes
Photodynamic therapy
Drug delivery
Hypoxia activated prodrug
Tumor hypoxia


Dual function of Langerhans cells in skin TSLP-promoted TFH differentiation in mouse atopic dermatitis.

Abstract:
BACKGROUND
Atopic dermatitis (AD) is among the most common chronic inflammatory skin diseases, usually occurring early in life, and often preceding other atopic diseases such as asthma. TH2 has been believed to play a crucial role in cellular and humoral response in AD, but accumulating evidence has shown that follicular helper T cell (TFH), a critical player in humoral immunity, is associated with disease severity and plays an important role in AD pathogenesis.

OBJECTIVES
This study aimed at investigating how TFHs are generated during the pathogenesis of AD, particularly what is the role of keratinocyte-derived cytokine TSLP and Langerhans cells (LCs).

METHODS
Two experimental AD mouse models were employed: (1) triggered by the overproduction of TSLP through topical application of MC903, and (2) induced by epicutaneous allergen ovalbumin (OVA) sensitization.

RESULTS
This study demonstrated that the development of TFHs and germinal center (GC) response were crucially dependent on TSLP in both the MC903 model and the OVA sensitization model. Moreover, we found that LCs promoted TFH differentiation and GC response in the MC903 model, and the depletion of Langerin+ dendritic cells (DCs) or selective depletion of LCs diminished the TFH/GC response. By contrast, in the model with OVA sensitization, LCs inhibited TFH/GC response and suppressed TH2 skin inflammation and the subsequent asthma. Transcriptomic analysis of Langerin+ and Langerin- migratory DCs revealed that Langerin+ DCs became activated in the MC903 model, whereas these cells remained inactivated in OVA sensitization model.

CONCLUSIONS
Together, these studies revealed a dual functionality of LCs in TSLP-promoted TFH and TH2 differentiation in AD pathogenesis.

Marschall|Pierre|P|
Wei|Ruicheng|R|
Segaud|Justine|J|
Yao|Wenjin|W|
Hener|Pierre|P|
German|Beatriz Falcon|BF|
Meyer|Pierre|P|
Hugel|Cecile|C|
Ada Da Silva|Grace|G|
Braun|Reinhard|R|
Kaplan|Daniel H|DH|
Li|Mei|M|

Langerhans cells
mouse
Atopic dermatitis
TSLP
dendritic cells
T(FH)
T(H)2
allergen sensitization


The Interplay between ESCRT and Viral Factors in the Enveloped Virus Life Cycle.

Abstract: Viruses are obligate parasites that rely on host cellular factors to replicate and spread. The endosomal sorting complexes required for transport (ESCRT) system, which is classically associated with sorting and downgrading surface proteins, is one of the host machineries hijacked by viruses across diverse families. Knowledge gained from research into ESCRT and viruses has, in turn, greatly advanced our understanding of many other cellular functions in which the ESCRT pathway is involved, e.g., cytokinesis. This review highlights the interplay between the ESCRT pathway and the viral factors of enveloped viruses with a special emphasis on retroviruses.

D056827:Endosomal Sorting Complexes Required for Transport

ESCRT
enveloped virus
NEDD4
budding
late domain
retrovirus


Exploring Behavioral Correlates of Afferent Inhibition.

Abstract: (1) Background: Afferent inhibition is the attenuation of the muscle response evoked from transcranial magnetic stimulation (TMS) by a prior conditioning electrical stimulus to a peripheral nerve. It is unclear whether the magnitude of afferent inhibition relates to sensation and movement; (2) Methods: 24 healthy, young adults were tested. Short-latency afferent inhibition (SAI) and long-latency afferent inhibition (LAI) were obtained following median and digital nerve stimulation. Temporal tactile acuity was assessed with a temporal order judgement (TOJ) task, spatial tactile acuity was assessed using a grating orientation task (GOT), and fine manual dexterity was assessed with the Pegboard task; (3) Results: Correlation analyses revealed no association between the magnitude of SAI or LAI with performance on the TOJ, GOT, or Pegboard tasks; (4) Conclusion: The magnitude of SAI and LAI does not relate to performance on the sensory and motor tasks tested. Future studies are needed to better understand whether the afferent inhibition phenomenon relates to human behavior.

Turco|Claudia V|CV|
Locke|Mitchell B|MB|
El-Sayes|Jenin|J|
Tommerdahl|Mark|M|
Nelson|Aimee J|AJ|

afferent inhibition
transcranial magnetic stimulation
SAI
LAI
tactile acuity
manual dexterity


Quantitative dynamic susceptibility contrast perfusion-weighted imaging-guided customized gamma knife re-irradiation of recurrent high-grade gliomas.

Abstract:
INTRODUCTION
Treatment of recurrent high-grade gliomas (rHGG) has always been challenging. This study aimed to explore the treatment effect of quantitative dynamic susceptibility contrast perfusion-weighted imaging (DSC-PWI)-guided gamma knife radiosurgery (GKRS) on rHGG.

METHODS
Between April 2014 and July 2016, 26 consecutive patients were treated by quantitative DSC-PWI-guided GKRS as salvage treatment for rHGG. The gross tumor volume (GTV) was defined as the high perfusion area on absolute cerebral blood volume maps, with a cutoff value of 22 ml/100 g. The clinical target volume (CTV) encompassed the GTV by 3 mm. Overall survival (OS) and progression-free survival (PFS) were calculated by the Kaplan-Meier method. Prognostic factors were tested by the log-rank (Mantel-Cox) test.

RESULTS
With a median follow-up of 32 months, the median PFS after GKRS was 8 months (95% CI [6, 12]); the 1- and 2-year survival rates were 30.8 and 11.5%, respectively. The median OS was 25.5 months (95% CI [18, 40]); the 1- and 2-year survival rates were 96.2 and 57.7%, respectively. Pathology grade and CTV were identified as prognostic factors for PFS. However, none of the parameters tested were independent prognostic factors for OS among these selected patients. No severe radiotoxicity was observed among all patients.

CONCLUSIONS
Quantitative DSC-PWI-guided GKRS is feasible for the treatment of rHGG and that these outcomes remain to be validated. Despite this, we think that carefully selected patients can benefit from this treatment method.

Re-irradiation
Brain perfusion
Gamma knife radiotherapy
MRI
Recurrent glioma


miR-21 and miR-146a: The microRNAs of inflammaging and age-related diseases.

Abstract: The first paper on "inflammaging" published in 2001 paved the way for a unifying theory on how and why aging turns out to be the main risk factor for the development of the most common age-related diseases (ARDs). The most exciting challenge on this topic was explaining how systemic inflammation steeps up with age and why it shows different rates among individuals of the same chronological age. The "epigenetic revolution" in the past twenty years conveyed that the assessment of the individual genetic make-up is not enough to depict the trajectories of age-related inflammation. Accordingly, others and we have been focusing on the role of non-coding RNA, i.e. microRNAs (miRNAs), in inflammaging. The results obtained in the latest 10 years underpinned the key role of a miRNA subset that we have called inflammamiRs, owing to their ability to master (NF-κB)-driven inflammatory pathways. In this review, we will focus on two inflammamiRs, i.e. miR-21-5p and miR-146a-5p, which target a variety of molecules belonging to the NF-κB/NLRP3 pathways. The interplay between miR-146a-5p and IL-6 in the context of aging and ARDs will also be highlighted. We will also provide the most relevant evidence suggesting that circulating inflammamiRs, along with IL-6, can measure the degree of inflammaging.

Olivieri|Fabiola|F|
Prattichizzo|Francesco|F|
Giuliani|Angelica|A|
Matacchione|Giulia|G|
Rippo|Maria Rita|MR|
Sabbatinelli|Jacopo|J|
Bonafè|Massimiliano|M|

MicroRNA
Inflammaging
miR-21-5p
miR-146a-5p
NF-κB
Cell senescence


Differential diagnosis and management of a pituitary mass with renal cell carcinoma.

Abstract: The small pituitary mass was incidentally found in 40-years-old women with renal cell carcinoma. The endocrinological and ophthalmological evaluation revealed no deficit and the short-term follow-up was recommended. In 6 months later, the visual disturbance was reported and the size of mass was increased. The tumor was removed totally via the trans-sphenoid approach. The post-operative endocrinological insufficiency was not noticed. During one year of follow-up period, there was no evidence of recurrence without adjuvant radiotherapy. The clinical features of pituitary metastasis from renal cell carcinoma were similar to those of pituitary adenoma. The possibility of pituitary metastasis should be kept in mind in patients with sellar mass and renal cell carcinoma.

Hwang|Joo Min|JM|
Kim|Yong Hwy|YH|
Kim|Tae Min|TM|
Park|Sung Hye|SH|

Pituitary
Renal cell carcinoma
Metastasis


Evaluation of stroke thrombectomy including patients where IV thrombolysis is contraindicated or has failed: a randomized trial of two novel thrombectomy devices.

Abstract:
BACKGROUND
Study was a PROBE design phase II randomized controlled trial (RCT). We assessed trial feasibility and technical efficacy and safety of two novel thrombectomy devices - ERIC (a retriever device) and SOFIA (a distal access catheter) - used alone or in combination depending on operator preference.

METHODS
Four UK neuroscience centers enrolled adults with proximal large artery occlusion (LAO) stroke on imaging where arterial puncture was achievable within 5.5 hours (8.5 hours for posterior circulation) of symptom onset; National Institutes of Health Stroke Scale (NIHSS) ≥6 with limited ischemic change on CT imaging. Randomization was 2:1 into intervention arm (ERIC and/or SOFIA). Patients and core lab were blinded to allocation. Primary outcome was independent core lab adjudication of reperfusion (modified Thrombolysis in Cerebral Infarction (mTICI) scale). Secondary outcomes were modified Rankin score (mRS) at 90 and 365 days (independence and shift analysis), 30-day mortality, symptomatic intracranial hemorrhage (sICH), procedural complications and NIHSS change.

RESULTS
Sixty-six patients were enrolled. TICI 2B/3 reperfusion was achieved in 72% in intervention compared with 90% in control arm on intention to treat (ITT) analysis (P=0.2) and 78% compared with 86% on per protocol analysis (P=0.7). Functional independence at 90 days was 40% (intervention) compared with 43% (control) on ITT analysis (P=1.0). sICH rates were low at 0% and 5%, respectively (P=0.3). The 30-day mortality was 9% intervention compared with 14% control (P=0.7).

CONCLUSIONS
Study indicated feasibility of a phase II RCT trial approach for assessing new thrombectomy devices. In a broad LAO stroke population ERIC and SOFIA were not statistically different from control devices. Larger trials are needed.


Potential ecological risk of heavy metal contamination in sediments and macrobenthos in coastal wetlands induced by freshwater releases: A case study in the Yellow River Delta, China.

Abstract: We investigated the nine heavy metal contents in the sediments and macrobenthos of the Yellow River Delta Wetlands using three experimental areas that received freshwater releases and one reference area that did not. Heavy metal contents, the single-factor contamination index (SFCI), the metal contamination index (MCI), and the biota-sediment accumulation factor (BSAF) were used to evaluate the potential ecological risk and bioaccumulation. We found that As exceeded the national standard value by more than 50%, and that the ranges of SFCI for each metal were generally larger in autumn than in spring. MCI showed no clear pattern, but the BSAF results suggest that Cd bioaccumulates from sediments to macrobenthos. Pollution-resistant species such as Corophium sinense, Chironomus sp., and Einfeldia sp. became dominant in the areas receiving freshwater releases, and provide direct evidence of ecological risk in the wetlands. Our results provide preliminary information to guide managers for ecological risk assessments.

Li|Ming|M| Yang|Wei|W| Sun|Tao|T| Jin|Yuwan|Y|

Heavy metal contamination
Macrobenthos
Freshwater release
Yellow River Delta wetlands
Bioaccumulation


Recent advances of in vitro culture systems for spermatogonial stem cells in mammals.

Abstract:
Background
Spermatogonial stem cells (SSCs) in the mammalian testis are unipotent stem cells for spermatozoa. They show unique cell characteristics as stem cells and germ cells after being isolated from the testis and cultured in vitro. This review introduces recent progress in the development of culture systems for the establishment of SSC lines in mammalian species, including humans.

Methods
Based on the published reports, the isolation and purification of SSCs, identification and characteristics of SSCs, and culture system for mice, humans, and domestic animals have been summarized.

Results
In mice, cell lines from SSCs are established and can be reprogrammed to show pluripotent stem cell potency that is similar to embryonic stem cells. However, it is difficult to establish cell lines for animals other than mice because of the dearth of understanding about species-specific requirements for growth factors and mechanisms supporting the self-renewal of cultured SSCs. Among the factors that are associated with the development of culture systems, the enrichment of SSCs that are isolated from the testis and the combination of growth factors are essential.

Conclusion
Providing an example of SSC culture in cattle, a rational consideration was made about how it can be possible to establish cell lines from neonatal and immature testes.

Sahare|Mahesh G|MG|
Suyatno|||
Imai|Hiroshi|H|0000-0003-3702-2708

spermatogonial stem cell
germ cells
cell lines
pluripotent stem cells
gonocytes


Identifying and characterizing the components related to the brown color of Chinese sugar-smoked chicken during processing.

Abstract: The desired color is a key indicator for consumer acceptability of Chinese sugar-smoked chicken. To investigate the formation of color attributes of Chinese sugar-smoked chicken during processing, color values, structural characteristics, and components of brown pigment were evaluated in 2 groups, which were defined as brown skin (BS) and normal skin (NS) of Chinese sugar-smoked chicken based on their color values. Compared with the NS samples, the BS samples showed significantly lower values of lightness, redness, and yellowness and higher content of malondialdehyde and 5-hydroxymethylfurfural. UV-visible and Fourier-transform infrared spectra suggested that the structure of brown pigment was similar to melanin. The brown pigment consisted of multiple chemical components including the polymer of fructose and glucose, and derivatives produced by lipid oxidation, which were identified by HPLC-tandem mass spectrometry. The polymer content of glucose and fructose, which was demonstrated as sucrose by HPLC analysis, was higher in the BS group than in the NS group. Our results indicated that the higher content of the polymer of glucose and fructose was mainly responsible for the brown color of Chinese sugar-smoked chicken.

Chang|Hong|H| Zhou|Changyu|C| He|Jun|J| Pan|Daodong|D| Wang|Ying|Y| Zhang|Xin|X| Cao|Jinxuan|J|

brown color
Chinese sugar-smoked chicken
FT-IR
HPLC–MS/MS
UV-VIS


Remaining visual field and preserved subjective visual functioning prevent mental distress in patients with visual field defects.

Abstract:
BACKGROUND
Patients with visual field defects after visual pathway lesion may experience reduced vision-related quality of life (vrQoL). It has not been clarified how vrQoL impairments contribute to vision-related mental distress.

METHODS
One hundred and eight subjects with visual field defects caused by optic neuropathies (age M = 57.6; SD = 13.7 years) answered the National Eye Institute Visual-Functioning Questionnaire 39 (NEI-VFQ) for vrQoL and the SF-12 Short Form Health Survey for health-related quality of life. A 10 item composite of NEI-VFQ "visual functioning" and 5 items of "mental-health symptoms due to vision problems" were subjected to Rasch analysis. The test battery comprised static and High Resolution Perimetry (HRP). Regression and path analysis were used to investigate associations between QoL, mental distress, and perimetry results.

RESULTS
A higher level of "visual functioning" was associated with monocular impairment and a larger remaining visual field compared to binocular impairment. Subjective "visual functioning" but not visual field parameters predicted "mental-health symptoms due to vision problems" which was the only variable associated with the SF-12 mental component score. The SF-12 physical component score was less strongly associated with "mental-health symptoms due to vision problems." Here, reaction time in HRP and mean threshold in perimetry were additional significant variables. Path analysis revealed a significant path from remaining visual field via visual functioning on mental health.

CONCLUSION
Subjective consequences of visual impairments in everyday life impact mental health rather than "objective" visual function loss as measured by perimetry. Since a higher extent of vrQoL was related to lower levels of mental distress, the maintenance of vrQoL could reduce and prevent mental distress due to vision problems. Patients with persisting visual field defects may benefit from neuropsychological rehabilitation and supportive therapies.

Gall|Carolin|C|
Brösel|Doreen|D|
Sabel|Bernhard A|BA|


Eutrophication decreased CO2 but increased CH4 emissions from lake: A case study of a shallow Lake Ulansuhai.

Abstract: Eutrophic lakes, especially shallow eutrophic lakes, disproportionately contribute to greenhouse gas (GHG) emissions. To investigate the effects of eutrophication on GHG dynamics, we conducted field measurements every three months from January 2019 to October 2019 in Lake Ulansuhai, a shallow eutrophic lake (mean depth of 0.7 m) located in a semi-arid region in Northern China. We found that Lake Ulansuhai was a predominantly source of atmospheric carbon dioxide (CO2); however, it converted to a CO2 sink in July due to eutrophication. It was also a strong source of methane (CH4) with a mean CO2 emission of 35.7 ± 12.1 mmol m-2 d-1 and CH4 emission of 5.9 ± 2.9 mmol m-2 d-1. The CO2 concentrations in most sites and CH4 concentrations in all sites were supersaturated, with the average partial pressure of CO2 (pCO2) being 654±34 μatm and the partial pressure of CH4 (pCH4) being 157±37 μatm. The partial pressures and emissions of the greenhouse gases exhibited substantial seasonal and spatial variations. The correlation analysis between the trophic level index and the partial pressure of the greenhouse gases indicated that eutrophication could significantly decrease the CO2 emissions but increase the CH4 emissions from the lake, resulting in a CH4 and CO2 emission ratio of approximately 2 in terms of global warming potential. Eutrophication decreased the pCO2 in the lake and subsequently increased the pCH4 due to nutrient input, thereby enhancing primary production. The results indicated that shallow eutrophic lakes in arid regions are strong sources of CH4 and that eutrophication could alter the greenhouse gas emission patterns.

Sun|Heyang|H| Lu|Xixi|X| Yu|Ruihong|R| Yang|Jie|J| Liu|Xinyu|X| Cao|Zhengxu|Z| Zhang|Zhuangzhuang|Z| Li|Meixia|M| Geng|Yue|Y|

Eutrophication
Lake Ulansuhai
Greenhouse gas emissions
Partial pressure of greenhouse gases
Temporal and spatial changes


Prevalence of hypertension in Thailand: Hotspot clustering detected by spatial analysis.

Abstract: Spatial pattern detection can be a useful tool for understanding the geographical distribution of hypertension (HT). The aim of this study was to apply the technique of local indicators of spatial association statistics to examine the spatial patterns of HT in the 76 provinces of Thailand. Previous studies have demonstrated that socioeconomic status (SES), economic growth, population density and urbanization have effects on the occurrence of disease. Research has suggested that night-time light (NTL) can be used as a proxy for a number of variables, including urbanization, density, economic growth and SES. To date, there has not been any study on spatial patterns of HT and there is no information on how NTL might correlate with HT. Therefore, this study has investigated NTL as a parameter for detection of hotspots of HT in Thailand. It was found that HT clusters occurred in Bangkok and in metropolitan areas. In addition, significantly low-rate clusters were seen in some provinces in the Northeast and also in southern provinces. These findings should facilitate control and prevention of HT and, therefore, serve as support for researchers, decision-makers, academics and public health officials to propose more sound and effective strategies for the control of HT in Thailand and elsewhere.

Hypertension
Local indices of spatial association
Thailand.
Nighttime light


Effects of ethanol exposure in a familiar or isolated context during infancy on ethanol intake during adolescence.

Abstract: Early exposure to ethanol affects ethanol intake later in life. This early experience encompasses exposure to social stimuli and the pharmacological and orosensory properties of ethanol. The specific contribution of each type of stimulus to subsequent ethanol intake remains unknown. We assessed the intake of various concentrations of ethanol in a familiar or isolated context during infancy and the lingering effects of this experience on ethanol intake during adolescence. On postnatal day 3 (PD3), PD7, and PD11, rats were given 5% ethanol or water in a nursing or isolated context (Experiments 1 and 2). Intake tests (ethanol vs. water) were conducted during adolescence. Experiment 2 matched the amount of fluid ingested during infancy in both contexts and subsequently tested ethanol consumption during adolescence. The results revealed a facilitative effect of the nursing context on fluid intake during the tests in infancy. Pups stimulated with ethanol but not water in the isolated context exhibited an increase in ethanol consumption during adolescence. This effect disappeared when the isolated infants were matched to receive the same amount of ethanol ingested by their nursed counterparts. In Experiment 3, isolated infant rats were exposed to different ethanol concentrations (.0%, 2.5%, 5.0%, and 10.0%), and drug consumption was tested during adolescence. This exposure increased adolescent ethanol intake, regardless of the alcohol concentration (Experiment 3). The common denominators that resulted in enhanced ethanol intake during adolescence were preexposure to ethanol via active consumption of the drug that induced a low-to-moderate level of intoxication in an isolated context.

Miranda-Morales|Roberto Sebastián|RS|
Haymal|Beatriz|B|
Pautassi|Ricardo M|RM|

D002492:Central Nervous System Depressants

ethanol
adolescent
nursing
infant
home environment


Foreign meat identification by DNA breed assignment for the Chinese market.

Abstract: Methods for individual identification are usually employed for traceability, whereas breed identification is useful to detect commercial frauds. In this study, Chinese Yellow Cattle (CYC) samples plus data from six Bos taurus breeds, two Bos indicus breeds, and one composite breed were used to develop an allocation test based on 22 microsatellites. The test allowed discriminating all foreign breeds from the CYC, although some CYC individuals were wrongly allocated as Limousin or Holstein, probably due to the recent introduction of these breeds into China. In addition, CYC evidenced a previously reported Zebu cline (south-north) and a possible structure within the B. taurus component that should be confirmed. An independent test performed with meat samples of unknown breed origin from Argentina allocated 92% of them to either Angus, Hereford, or their crossbreed, but none was identified as CYC. We conclude that the test is a suitable tool to certify meat of foreign breed origin and to detect adulterations of CYC beef labeled as imported meat.

Rogberg-Muñoz|A|A|
Wei|S|S|
Ripoli|M V|MV|
Guo|B L|BL|
Carino|M H|MH|
Castillo|N|N|
Villegas Castagnaso|E E|EE|
Lirón|J P|JP|
Morales Durand|H F|HF|
Melucci|L|L|
Villarreal|E|E|
Peral-García|P|P|
Wei|Y M|YM|
Giovambattista|G|G|

Meat DNA Breed Traceability Microsatellites China


Cardiac dysfunction in children with essential obesity: preliminary data.

Abstract: Obesity in children has been recognized as a major underlying factor of the pathogenesis of several diseases and a reduced life expectancy. This study aims to verify if clinical parameters, such as waist circumference and/or body mass index and biohumoral and inflammatory parameters can help predict cardiac structural and functional alterations, through an echocardiogram test in obese children and adolescents. Children were prospectively enrolled at the AUOC outpatients' department of Emergency Paediatrics, University Hospital, Messina, from June to December 2017. Clinical, metabolic parameters and an inflammation marker (HMGB1) were evaluated and a transthoracic echocardiogram was carried out. Twenty-two obese subjects were prospectively enrolled.HMGB1 values were 12.6 ± 2ng/ml, significantly higher compared to a previously studied healthy control group. A significant positive correlation was found both between total cholesterol levels and HMGB1 values (r=0.846, p=0.000) and between LDL cholesterol and HMBG1 values (r=0.663, p=0.001). No correlation was found between clinical, biohumoral and echocardiograph parameters. In obese children cardiac parameters obtained from echocardiogram tests may be in the normal range. However, other parameters may be altered in the early phase, showing that infantile obesity can compromise myocardial functions, even in the absence of comorbidities. Furthermore, the evaluation of concentrations of HMBG1 could explain how an initial inflammation can trigger the condition of meta-inflammation.

Arrigo|T|T|
Stroscio|G|G|
Impollonia|D|D|
Salvo|V|V|
Scuderi|M G|MG|
Di Benedetto|V|V|
Betta|P|P|
Fusco|M|M|
Sallemi|A|A|
Fede|C|C|
Calabrò|M P|MP|
Salpietro|C|C|
Chimenz|R|R|

D000293:Adolescent
D015992:Body Mass Index
D002648:Child
D008078:Cholesterol, LDL
D024243:HMGB1 Protein
D006331:Heart Diseases
D006801:Humans
D063766:Pediatric Obesity
D000074286:Preliminary Data
D011446:Prospective Studies
D055105:Waist Circumference

children
obesity
echocardiogram test
inflammation
HMGB1


Risk Assessment and Comparative Effectiveness of Left Ventricular Assist Device and Medical Management in Ambulatory Heart Failure Patients: The ROADMAP Study 2-Year Results.

Abstract:
OBJECTIVES
The authors sought to provide the pre-specified primary endpoint of the ROADMAP (Risk Assessment and Comparative Effectiveness of Left Ventricular Assist Device and Medical Management in Ambulatory Heart Failure Patients) trial at 2 years.

BACKGROUND
The ROADMAP trial was a prospective nonrandomized observational study of 200 patients (97 with a left ventricular assist device [LVAD], 103 on optimal medical management [OMM]) that showed that survival with improved functional status at 1 year was better with LVADs compared with OMM in a patient population of ambulatory New York Heart Association functional class IIIb/IV patients.

METHODS
The primary composite endpoint was survival on original therapy with improvement in 6-min walk distance ≥75 m.

RESULTS
Patients receiving LVAD versus OMM had lower baseline health-related quality of life, reduced Seattle Heart Failure Model 1-year survival (78% vs. 84%; p = 0.012), and were predominantly INTERMACS (Interagency Registry for Mechanically Assisted Circulatory Support) profile 4 (65% vs. 34%; p < 0.001) versus profiles 5 to 7. More LVAD patients met the primary endpoint at 2 years: 30% LVAD versus 12% OMM (odds ratio: 3.2 [95% confidence interval: 1.3 to 7.7]; p = 0.012). Survival as treated on original therapy at 2 years was greater for LVAD versus OMM (70 ± 5% vs. 41 ± 5%; p < 0.001), but there was no difference in intent-to-treat survival (70 ± 5% vs. 63 ± 5%; p = 0.307). In the OMM arm, 23 of 103 (22%) received delayed LVADs (18 within 12 months; 5 from 12 to 24 months). LVAD adverse events declined after year 1 for bleeding (primarily gastrointestinal) and arrhythmias.

CONCLUSIONS
Survival on original therapy with improvement in 6-min walk distance was superior with LVAD compared with OMM at 2 years. Reduction in key adverse events beyond 1 year was observed in the LVAD group. The ROADMAP trial provides risk-benefit information to guide patient- and physician-shared decision making for elective LVAD therapy as a treatment for heart failure. (Risk Assessment and Comparative Effectiveness of Left Ventricular Assist Device and Medical Management in Ambulatory Heart Failure Patients [ROADMAP]; NCT01452802).

Starling|Randall C|RC|
Estep|Jerry D|JD|
Horstmanshof|Douglas A|DA|
Milano|Carmelo A|CA|
Stehlik|Josef|J|
Shah|Keyur B|KB|
Bruckner|Brian A|BA|
Lee|Sangjin|S|
Long|James W|JW|
Selzman|Craig H|CH|
Kasirajan|Vigneshwar|V|
Haas|Donald C|DC|
Boyle|Andrew J|AJ|
Chuang|Joyce|J|
Farrar|David J|DJ|
Rogers|Joseph G|JG|
|||

D002316:Cardiotonic Agents
D005080:Exercise Test
D017079:Exercise Tolerance
D006333:Heart Failure
D006353:Heart-Assist Devices
D006801:Humans
D011446:Prospective Studies
D011788:Quality of Life
D018570:Risk Assessment
D016896:Treatment Outcome

left ventricular assist device
heart failure
pharmacological therapy


The nonsurgical nature of patients with subarachnoid or intraparenchymal hemorrhage associated with mild traumatic brain injury.

Abstract:
OBJECT
Mild traumatic brain injury (mTBI), as defined by Glasgow Coma Scale (GCS) score of 13 or higher, is a common problem in the United States and worldwide, estimated to affect more than 1 million patients yearly. When associated with intracranial hemorrhage, it is a common reason for neurosurgical consultation and transfer to tertiary care centers. The authors set out to investigate the clinical implications of subarachnoid hemorrhage (SAH) and/or intraparenchymal hemorrhage (IPH) associated with mTBI in hopes of standardization of mTBI clinical care and optimization of resource allocation.

METHODS
The authors performed a retrospective review of 500 consecutively treated patients with mTBI and SAH and/or IPH admitted to a Level I trauma center in Alabama between May 2003 and May 2013. They performed a review of medical records to confirm the diagnosis, determine neurological condition at admission, and assess for episodes of neurological decline or brain injury-related complications including altered mental status, seizures, and hyponatremia.

RESULTS
Of the 500 patients for whom data were reviewed, 304 (60.8%) were male and 196 (39.2%) were female. Average age was 46.3 years. Overall, 63 patients (12.6%) had isolated IPH, 411 (82.2%) had isolated SAH, and 26 (5.2%) had radiographic evidence of both IPH and SAH. One hundred forty-five patients (29%) were transferred an average distance of 64.5 miles. The authors identified no patients who experienced neurological worsening during their hospital course. Two patients experienced hyponatremia that required treatment with sodium supplementation.

CONCLUSIONS
Patients with the constellation of SAH and/or IPH and mTBI do not require neurosurgical consultation, and these findings should not be used as the sole criteria to justify transfer to tertiary referral centers.

Ditty|Benjamin J|BJ|
Omar|Nidal B|NB|
Foreman|Paul M|PM|
Patel|Daxa M|DM|
Pritchard|Patrick R|PR|
Okor|Mamerhi O|MO|

CDC = Centers for Disease Control and Prevention

ICD-9 = International Classification of Diseases, Ninth Revision


Surfactant proteins changes after acute hemodynamic improvement in patients with advanced chronic heart failure treated with Levosimendan.

Abstract: Alveolar-capillary membrane evaluated by carbon monoxide diffusion (DLCO) plays an important role in heart failure (HF). Surfactant Proteins (SPs) have also been suggested as a worthwhile marker. In HF, Levosimendan improves pulmonary hemodynamics and reduces lung fluids but associated SPs and DLCO changes are unknown. Sixty-five advanced HF patients underwent spirometry, cardiopulmonary exercise test (CPET) and SPs determination before and after Levosimendan. Levosimendan caused natriuretic peptide-B (BNP) reduction, peakVO2 increase and VE/VCO2 slope reduction. Spirometry improved but DLCO did not. SP-A, SP-D and immature SP-B reduced (73.7 ± 25.3 vs. 66.3 ± 22.7 ng/mL*, 247 ± 121 vs. 223 ± 110 ng/mL*, 39.4 ± 18.7 vs. 34.4 ± 17.9AU*, respectively); while mature SP-B increased (424 ± 218 vs. 461 ± 243 ng/mL, * = p < 0.001). Spirometry, BNP and CPET changes suggest hemodynamic improvement and lung fluid reduction. SP-A, SP-D and immature SP-B reduction indicates a reduction of inflammatory stress; conversely mature SP-B increase suggests alveolar cell function restoration. In conclusion, acute lung fluid reduction is associated with SPs but not DLCO changes. SPs are fast responders to alveolar-capillary membrane condition changes.

Campodonico|Jeness|J| Mapelli|Massimo|M| Spadafora|Emanuele|E| Ghilardi|Stefania|S| Agostoni|Piergiuseppe|P| Banfi|Cristina|C| Sciomer|Susanna|S|

Surfactant proteins
Alveolar capillary membrane
Gas diffusion


Predicting Non-Suicidal Self-Injury in Young Adults with and without Borderline Personality Disorder: a Multilevel Approach Combining Ecological Momentary Assessment and Self-Report Measures.

Abstract: Non-suicidal self-injury (NSSI) is an increasingly prevalent phenomenon associated with many detrimental outcomes, ranging from poor academic performance to suicide attempts. Research on self-harming behaviors has identified emotion dysregulation, negative affect, and borderline pathology as strong risk factors of NSSI, whereas the potential protective effects of metacognitive skills such as decentering have not yet been explored. The current study combined ecological momentary assessment (EMA) and self-report measures to explore potential risk and protective factors of NSSI in a clinical group of Borderline Personality Disorder (BPD) patients with NSSI (N = 22), a subclinical group of college students with NSSI (N = 19), and a non-clinical healthy control group (N = 23). Participants completed self-report measures of borderline pathology, emotion dysregulation, decentering ability, and negative emotional symptoms, and they used the Sinjur App (EMA instrument) at least three times a day for 15 days to capture negative affect and NSSI in daily life. A multilevel mixed-effect regression analysis with both self-report and EMA measures was conducted to identify predictors of NSSI. The multilevel analysis showed that only momentary frustration directly predicted NSSI. Momentary guilt and anger only predicted NSSI when interacting with more stable traits of borderline pathology and negative emotional symptoms. Most importantly, greater decentering capacity protected against self-injury and attenuated the association between momentary sadness and NSSI. Findings contribute novel knowledge about NSSI, documenting the protective effects of decentering and highlighting the benefit of interventions that target metacognitive emotion regulation skills.

Briones-Buixassa|Laia|L|
Alí|Ítalo|Í|
Schmidt|Carlos|C|
Nicolaou|Stella|S|
Pascual|Juan Carlos|JC|
Soler|Joaquim|J|
Vega|Daniel|D|0000-0002-5621-8987

Non-suicidal self-injury
Borderline personality disorder
Ecological momentary assessment
Self-harm
Emotion dysregulation
Decentering
Youth


A retrospective study analyzing missed diagnosis of lung metastases at their early stages on computed tomography.

Abstract:
Background
Lungs are one of the target organs of metastases of primary lung, breast, liver, colorectal, and esophageal cancer. While computed tomography (CT) is the most widely used modality for detecting lung metastases, it is still very challenging to detect them at the earlier stages. If lung metastases could be found on CT scans at the earliest time points, patients would benefit by beginning treatment earlier. The objective of this study was to demonstrate that CT can reveal lung metastases in many cases at even earlier stages than current radiological practice may find.

Methods
One hundred patients with lung metastases were randomly selected and their surveillance CT scans were analyzed retrospectively. The patients had primary cancer in the breasts, lungs, esophagus, colorectum, and liver. All patients had multiple CT examinations of the lungs and their metastases, if any, were confirmed by subsequent CT scans. The earliest CT scans were examined to determine whether lung metastases at the same locations had been diagnosed or missed. Missed lung metastases, categorized by type of the primary cancer and adjacency to nearby blood vessels, were statistically analyzed.

Results
There were 36/100 (36%) cases of missed lung metastases, including 15 cases of single metastasis and 21 cases of multiple metastases. There were a total of 174 missed loci of lung metastases. Where metastases were missed, there was a statistically significant difference (P<0.001) in their distribution within the sub-regions of the lungs. Adjacency to blood vessels appeared to be a significant factor in metastases being missed during diagnosis (P<0.001).

Conclusions
There was a considerable percentage of early lung metastases that were missed by radiologists but actually appeared on CT scans. The capability of CT to reveal such early metastases opens up an opportunity to move up the time points of detecting lung metastases through clinical and training improvement and technology development such as computer-aided detection.

Chen|Huai|H| Huang|Suidan|S| Zeng|Qingsi|Q| Zhang|Min|M| Ni|Zhiwen|Z| Li|Xiaoling|X| Xu|Xiaoyin|X|

lung metastases
Computed tomography (CT)
early detection


MicroRNAs for the pediatric otolaryngologist.

Abstract: The scope of pediatric otolaryngology is broad and encompasses a wide variety of diseases in which the fundamental phenotype-causing abnormality exists at the level of gene regulation and expression. Development of novel molecular biology instruments to diagnose disease, monitor treatment response, and prevent recurrence will facilitate the delivery of appropriate surgical and adjuvant medical treatments with lower morbidity. MicroRNAs (miRNAs) have emerged as a relatively new class of molecules that directly modulate gene expression and are abnormally expressed in a multitude of disease processes including those within the scope of pediatric otolaryngology. Functionally, miRNAs control multiple cellular functions including angiogenesis, cell proliferation, cell survival, genome stability, and inflammation. These short, non-protein coding RNA molecules are present and stable in tissue, blood, saliva, and urine, making them ideal disease biomarkers. The simple structure of miRNAs and their ability to directly modulate the expression of specific genes lends exciting therapeutic potential to miRNA-based therapies. Here we review the current literature of miRNAs as it relates to diseases within the scope of pediatric otolaryngology, and discuss their potential as diagnostic biomarkers and therapeutic targets.

Strub|Graham M|GM|
Perkins|Jonathan A|JA|

microRNA
Pediatric otolaryngology
miRNA
Biomarker
Molecular diagnostics
Molecular therapy


Amputee socks: Sock thickness changes with normal use.

Abstract:
BACKGROUND
Prosthetic socks are expected to decrease in thickness and have reduced volume accommodation with normal use. It is unknown, however, to what degree they reduce in thickness over time.

OBJECTIVE
The goal of this study was to determine a correlation between the age of a prosthetic sock (defined as the out-of-package time) and the resulting change in thickness under standardized weight-bearing and non-weight-bearing conditions.

STUDY DESIGN
Experimental, mechanical assessment.

METHODS
Used prosthetic socks were donated by donors with transtibial amputation. Sock thickness was measured on a custom instrument under conditions representative of normal use. Stress-thickness response was compared to that of equivalent new socks to quantify the effects of use on sock performance.

RESULTS
Sock thickness changed non-linearly over time. On average, socks were 75% ± 17% of their initial thickness after 1 month, while socks older than 1 month were 72% ± 18% of their initial thickness. The elasticity of socks did not change with age.

CONCLUSION
The volume accommodation provided by used socks cannot be reliably predicted by ply or age. Direct measurement of total sock thickness may provide meaningful insight to quantify prosthetic users' socket fit and guide volume accommodation recommendations.

CLINICAL RELEVANCE
The mean difference in thickness between 3-ply and 5-ply used socks was equal to the standard deviation of each ply group (0.3mm). Therefore, it is possible that a 3-ply sock worn for as a little as 1 month could have a greater thickness than a 5-ply sock worn for a month.

Cagle|John C|JC|
D'Silva|Krittika J|KJ|
Hafner|Brian J|BJ|
Harrison|Daniel S|DS|
Sanders|Joan E|JE|

Prosthetic socks
volume accommodation
limb management
prosthetic fit


A 512-Pixel, 51-kHz-Frame-Rate, Dual-Shank, Lens-less, Filter-less Single Photon Avalanche Diode CMOS Neural Imaging Probe.

Abstract: We present an implantable single photon shank-based imager, monolithically integrated onto a single CMOS IC. The imager comprises of 512 single photon avalanche diodes distributed along two shanks, with a 6-bit depth in-pixel memory and an on-chip digital-to-time converter. To scale down the system to a minimally invasive form factor, we substitute optical filtering and focusing elements with a time-gated, angle-sensitive detection system. The imager computationally reconstructs the position of fluorescent sources within a three-dimensional volume of 3.4 mm × 600 µm × 400 µm.

Choi|Jaebin|J|
Taal|Adriaan J|AJ|
Pollmann|Eric H|EH|
Lee|Changhyuk|C|
Kim|Kukjoo|K|
Moreaux|Laurent C|LC|
Roukes|Michael L|ML|
Shepard|Kenneth L|KL|

Single photon avalanche diode
CMOS
Compressed sensing
Neural probe
Time-gated fluorescence imaging


Methods for Virtual Screening of GPCR Targets: Approaches and Challenges.

Abstract: Virtual screening (VS) has become an integral part of the drug discovery process and is a valuable tool for finding novel chemical starting points for GPCR targets. Ligand-based VS makes use of biochemical data for known, active compounds and has been applied successfully to many diverse GPCRs. Recent progress in GPCR X-ray crystallography has made it possible to incorporate detailed structural information into the VS process. This chapter outlines the latest VS techniques along with examples that highlight successful applications of these methods. Best practices for increasing the likelihood of VS success, as well as ongoing challenges, are also discussed.

D055808:Drug Discovery
D008024:Ligands
D008958:Models, Molecular
D062105:Molecular Docking Simulation
D056004:Molecular Dynamics Simulation
D011485:Protein Binding
D043562:Receptors, G-Protein-Coupled
D057188:Workflow

Virtual screening
Data fusion
Data mining
Fingerprint similarity
G protein-coupled receptor
Homology modeling
Machine learning
Molecular docking
Pharmacophore search
Shape search


Mepolizumab for Eosinophil-Associated COPD: Analysis of METREX and METREO.

Abstract:
Background
A pre-specified meta-analysis of individual patient data from the 52-week METREX and METREO trials, which investigated mepolizumab for chronic obstructive pulmonary disease (COPD) in patients with blood eosinophil counts ≥150 cells/µL (screening) or ≥300 cells/µL (prior year) and frequent exacerbations, enables more robust characterization of mepolizumab efficacy in COPD and exploration of the relationship between blood eosinophil count and treatment responses.

Methods
In METREX (117106/NCT02105948) and METREO (117113/NCT02105961), randomized patients received mepolizumab or placebo added to existing inhaled corticosteroid (ICS)-based triple maintenance therapy. The annual rate of moderate/severe exacerbations (primary endpoint) was compared between subcutaneous (SC) mepolizumab 100 mg versus placebo (primary comparison of interest) and all doses (100 mg and 300 mg SC) versus placebo in patients with blood eosinophil counts ≥150 cells/µL at screening or ≥300 cells/µL in the prior year. Secondary/other endpoints included time to first moderate/severe exacerbation, exacerbations leading to emergency department visit/hospitalization and health-related quality of life (HRQoL). A predictive model of the relationship between screening blood eosinophil counts and exacerbation rates included data from all randomized patients.

Results
In total, 1510 patients were randomized in METREX and METREO and 1136 patients were included in the pre-specified meta-analysis. From the meta-analysis, mepolizumab 100 mg SC significantly reduced annual moderate/severe exacerbation rates versus placebo by 18% (rate ratio: 0.82; 95% confidence interval: 0.71, 0.95; p=0.006) and delayed time to first moderate/severe exacerbation (hazard ratio: 0.80 [0.68, 0.94]; p=0.006). Mepolizumab 100 mg SC versus placebo numerically reduced exacerbations leading to ED visits/hospitalization and improved HRQoL. A modelling approach demonstrated increasing efficacy for moderate/severe exacerbations with increasing screening blood eosinophil count; this relationship was more pronounced for exacerbations requiring oral corticosteroids (post hoc). The all-doses comparison had similar results.

Conclusion
Mepolizumab reduces exacerbations in patients with eosinophil-associated COPD. Results suggest that blood eosinophil counts (≥150 cells/µL at screening or ≥300 cells/µL in the prior year) allow for identification of patients with COPD who experience exacerbations while treated with maximal ICS-based triple maintenance therapy who are likely to benefit from mepolizumab.

D029424:Pulmonary Disease, Chronic Obstructive

D016032:Randomized Controlled Trials as Topic

mepolizumab COPD eosinophil exacerbation


Production of β-fructofuranosidase with transfructosylating activity by Aspergillus tamarii URM4634 Solid-State Fermentation on agroindustrial by-products.

Abstract: Eight different Aspergillus strains were tested for their ability to produce β-fructofuranosidase (FFase) by Solid-State Fermentation. The Aspergillus tamarii URM4634 strain was selected as the most performant and tested on six different agroindustrial by-products. Soy, wheat and oat brans, which allowed for the highest hydrolytic (UH) and transfructosylating (UTF) activities, were tested individually or in mixtures according to a simplex-centroid mixture design in order to investigate their effects on FFase production at different times. The best results in terms of both enzyme activities were obtained with only soy bran. The influence of substrate, moisture and sucrose levels on FFase production was evaluated, and the highest UH and UTF activities were 229.43 ± 4.88 and 66.93 ± 3.02 U/mL, respectively. The obtained results indicate that A. tamarii FFase may be a biocatalyst with great potential for industrial applications such as sugar inversion and fructo-oligosaccharides production.

Oliveira|Rodrigo Lira de|RL|
Silva|Marcos Fellipe da|MFD|
Converti|Attilio|A|
Porto|Tatiana Souza|TS|

β-Fructofuranosidase
Fermentation
Agroindustrial by-products
Mixture design
Fructo-oligosaccharides


Systematic Identification of Cell-Cell Communication Networks in the Developing Brain.

Abstract: Since the generation of cell-type specific knockout models, the importance of inter-cellular communication between neural, vascular, and microglial cells during neural development has been increasingly appreciated. However, the extent of communication between these major cell populations remains to be systematically mapped. Here, we describe EMBRACE (embryonic brain cell extraction using FACS), a method to simultaneously isolate neural, mural, endothelial, and microglial cells to more than 94% purity in ∼4 h. Utilizing EMBRACE we isolate, transcriptionally analyze, and build a cell-cell communication map of the developing mouse brain. We identify 1,710 unique ligand-receptor interactions between neural, endothelial, mural, and microglial cells in silico and experimentally confirm the APOE-LDLR, APOE-LRP1, VTN-KDR, and LAMA4-ITGB1 interactions in the E14.5 brain. We provide our data via the searchable "Brain interactome explorer", available at https://mpi-ie.shinyapps.io/braininteractomeexplorer/. Together, this study provides a comprehensive map that reveals the richness of communication within the developing brain.

Sheikh|Bilal N|BN|
Bondareva|Olga|O|
Guhathakurta|Sukanya|S|
Tsang|Tsz Hong|TH|
Sikora|Katarzyna|K|
Aizarani|Nadim|N|
Sagar|||
Holz|Herbert|H|
Grün|Dominic|D|
Hein|Lutz|L|
Akhtar|Asifa|A|

Developmental Neuroscience
Neuroscience
Systems Neuroscience
Techniques in Neuroscience


Cold subcutaneous abscesses as the first manifestation of disseminated coccidioidomycosis in an immunocompromised host.

Abstract: Coccidioidomycosis is an endemic fungal infection in the southwestern USA and northern Mexico. It is caused by Coccidioides immitis and C. posadasii. This infection occurs due to the inhalation of airborne arthroconidia, causing a mild pulmonary infection, but most cases are asymptomatic. Disseminated coccidioidomycosis (DC) is a rare entity occurring in less than 1% of all cases, usually in immunocompromised patients, and it carries high risks of morbidity and mortality. The skin is one of the most frequently affected organs and in some cases cutaneous lesions may be the first or only sign of infection. A wide spectrum of clinical lesions may develop, including cold abscess. In immunocompromised hosts, DC represents a diagnostic and therapeutic challenge. Treatment is based on antifungal drugs, such as amphotericin B and azoles, administered for long periods of time and under close follow up to monitor the treatment response and to detect relapse. In the following case report, we present a 35-year-old male patient with systemic lupus erythematosus under immunosuppressive therapy who presented with cold subcutaneous abscesses as the first sign of DC.

cold subcutaneous abscesses
disseminated coccidioidomycosis
coccidioidomycosis
immunocompromised host
systemic lupus erythematosus


Quantitative and targeted proteomics-based identification and validation of drug efficacy biomarkers.

Abstract: Proteomics refers to the large-scale study of proteins, providing comprehensive and quantitative information on proteins in tissue, blood, and cell samples. In many studies, proteomics utilizes liquid chromatography-mass spectrometry. Proteomics has developed from a qualitative methodology of protein identification to a quantitative methodology for comparing protein expression, and it is currently classified into two distinct methodologies: quantitative and targeted proteomics. Quantitative proteomics comprehensively identifies proteins in samples, providing quantitative information on large-scale comparative profiles of protein expression. Targeted proteomics simultaneously quantifies only target proteins with high sensitivity and specificity. Therefore, in biomarker research, quantitative proteomics is used for the identification of biomarker candidates, and targeted proteomics is used for the validation of biomarkers. Understanding the specific characteristics of each method is important for conducting appropriate proteomics studies. In this review, we introduced the different characteristics and applications of quantitative and targeted proteomics, and then discussed the results of our recent proteomics studies that focused on the identification and validation of biomarkers of drug efficacy. These findings may enable us to predict the outcomes of cancer therapy and drug-drug interactions with antibiotics through changes in the intestinal microbiome.

Masuda|Takeshi|T| Mori|Ayano|A| Ito|Shingo|S| Ohtsuki|Sumio|S|

Biomarker
Targeted proteomics
Quantitative proteomics
Cancer
Intestinal microbiome
Personalized medicine
Protein quantification


Predicting Multivariate Responses of Sexual Dimorphism to Direct and Indirect Selection.

Abstract: AbstractSexual dimorphism is often assumed to result from balancing the strength of antagonistic selection in favor of dimorphism against the degree of constraint imposed by the shared genome of the sexes, reflected in the B matrix of genetic intersexual covariances. To investigate the totality of forces shaping dimorphism, we reparameterized the Lande equation to predict changes in trait averages and trait differences between the sexes. As genetic constraints on the evolution of dimorphism in response to antagonistic selection become larger, dimorphism will tend to respond more rapidly to concordant selection (which favors the same direction of change in male and female traits) than to antagonistic selection. When we apply this theory to four empirical estimates of B in Drosophila melanogaster, the indirect responses of dimorphism to concordant selection are of comparable or larger magnitude than the direct responses of dimorphism to antagonistic selection in two suites of traits with typical levels of intersex correlation. Antagonistic selection is more important in two suites of traits where the intersex correlations are unusually low. This suggests that the evolution of sexual dimorphism may sometimes be dominated by concordant selection rather than antagonistic selection.

sexual dimorphism
B matrix
G matrix
sexual conflict


Key Factors Affecting the Flesh Flavor Quality and the Nutritional Value of Grass Carp in Four Culture Modes.

Abstract: Flavor and nutritional value are important qualities of freshwater fish products, but the key factors affecting these quality parameters remain unclear. In this study, four typical aquaculture modes, including the commercial feed treatment (control), faba bean treatment (FBT), grass powder treatment (GPT), and waving water treatment with commercial feed (WWT), were used to explore the regulatory effect of water quality and feed (eaten and uneaten) on the flesh flavor and nutrition in grass carp (Ctenopharyngodon idella), a freshwater fish of the largest global production. During the culture period (90 days), water quality parameters of the four modes were measured every 15 days, and the flavor quality was evaluated by volatile flavor compounds detection and electronic nose analyzer. Flesh crude protein, crude fat, free fatty acid and free amino acid profiles were also determined. The results showed that, in the late period, the FBT mode had the poorest water quality with highest concentrations of nitrite and nitrate, while the GPT mode has the best water quality among the four modes. Most flesh flavor compounds found in the flesh of the control, GPT and WWT modes were pleasant. In the FBT mode with the poorest water quality, on the other hand, we found lower flavor quality (higher contribution of fishy compounds), higher water content, and lower contents of crude protein, crude fat, free fatty acids and free amino acids, compared to the other three modes. Correlation analyses showed that nitrite and nitrate are probably key water quality factors affecting the flavor quality and nutritional values besides eaten feed and uneaten feed factors. This study can serve as an important reference for ecological regulation and feeding administration of flesh quality in freshwater aquaculture fish.

Zhang|Junming|J| Kaneko|Gen|G|0000-0003-4295-5123 Sun|Jinhui|J| Wang|Guangjun|G| Xie|Jun|J| Tian|Jingjing|J| Li|Zhifei|Z| Gong|Wangbao|W| Zhang|Kai|K| Xia|Yun|Y| Yu|Ermeng|E|0000-0001-6348-9884

flavor quality
nutritional value
water quality factors
grass carp modes


Diversity and distribution of arbuscular mycorrhizal fungi along altitudinal gradients in Mount Taibai of the Qinling Mountains.

Abstract: Elevational patterns of plant and animal diversity have been studied for centuries; however, the effects of land elevation on arbuscular mycorrhizal (AM) fungal diversity remains unclear. We examined AM fungal diversity and distribution along 19 elevation belts in Mount Taibai of the Qinling Mountains, with the aim to assess the altitudinal diversity patterns. In total, 63 AM fungal taxa belonging to 12 genera were discovered. Mycorrhizal colonization rates on roots; AM fungal spore density; and fungal species richness, evenness, and diversity had different patterns in terms of the changes of elevation. Root colonization followed a cubical parabolic pattern, with a peak and a foot at an elevation of about 2000 and 3000 m above sea level, respectively. Species richness decreased monotonically from the lowest to the highest elevations. Spore density and α-diversity exhibited a unimodal pattern and peaked at an elevation of 2107 and 1350 m, respectively. Species evenness increased monotonically at an elevation of between 1050 and 2250 m. β-Diversity also presented a basically incremental pattern along altitudinal gradients. Our findings suggest that elevation changes were the main factor governing the patterns of AM fungal diversity.

Shi|Zhaoyong|Z| Wang|Fayuan|F| Zhang|Kai|K| Chen|Yinglong|Y|

champignons de mycorhizes arbusculaires (MA)


Anxiety- and Depressive-Like Behaviors are Associated with Altered Hippocampal Energy and Inflammatory Status in a Mouse Model of Crohn's Disease.

Abstract: Depression and anxiety are common comorbid disorders observed in patients with inflammatory bowel disease (IBD). Increasing line of evidence indicates that immune-inflammatory responses are involved in co-occurrence of mood disorders and IBD. However, the mechanisms through which immune-inflammatory pathways modulate this comorbidity are not yet understood. This study investigated the role of innate immunity in the development of behavioral abnormalities associated with an animal model of Crohn's disease (CD). To do this, we induced colitis in male adult mice by intrarectal (i.r.) injection of DNBS (Dinitrobenzene sulfonic acid). After 3 days, we performed behavioral tests for anxiety- and depressive-like behaviors as well as tissue collection. Our results showed that DNBS-induced colonic inflammatory responses were accompanied by infiltration of inflammatory cells, and increased expression of genes involved in toll-like receptor signaling pathway in intestinal tissue. Furthermore, the DNBS-treated mice showed depressive- and anxiety-like behaviors which were associated with increased expression of the inflammatory genes and abnormal mitochondrial function in the hippocampus. These results suggest that peripheral inflammation is able to increase the transcriptional level of the genes in toll-like receptor pathway, induces abnormal mitochondrial function in the hippocampus, and these negative effects may be involved in the co-occurrence of anxiety and depression in early stages of CD.

Haj-Mirzaian|Arya|A|
Amiri|Shayan|S|
Amini-Khoei|Hossein|H|
Hosseini|Mir-Jamal|MJ|
Haj-Mirzaian|Arvin|A|
Momeny|Majid|M|
Rahimi-Balaei|Maryam|M|
Dehpour|Ahmad Reza|AR|

depression
anxiety
hippocampus
toll-like receptor pathway
Crohn’s disease
oxidative stress


Insight Into the Pico- and Nano-Phytoplankton Communities in the Deepest Biosphere, the Mariana Trench.

Abstract: As photoautotrophs, phytoplankton are generally present in the euphotic zone of the ocean, however, recently healthy phytoplankton cells were found to be also ubiquitous in the dark deep sea, i.e., at water depths between 2000 and 4000 m. The distributions of phytoplankton communities in much deeper waters, such as the hadal zone, are unclear. In this study, the vertical distribution of the pico- and nano-phytoplankton (PN) communities from the surface to 8320 m, including the epipelagic, mesopelagic, bathypelagic, and hadal zones, were investigated via both 18S and p23S rRNA gene analysis in the Challenger Deep of the Mariana Trench. The results showed that Dinoflagellata, Chrysophyceae, Haptophyta, Chlorophyta, Prochloraceae, Pseudanabaenaceae, Synechococcaceae, and Eustigmatophyceae, etc., were the predominant PN in the Mariana Trench. Redundancy analyses revealed that depth, followed by temperature, was the most important environmental factors correlated with vertical distribution of PN community. In the hadal zone, the PN community structure was considerably different from those in the shallower zones. Some PN communities, e.g., Eustigmatophyceae and Chrysophyceae, which have the heterotrophic characteristics, were sparse in shallower waters, while they were identified with high relative abundance (94.1% and 20.1%, respectively) at the depth of 8320 m. However, the dinoflagellates and Prochloraceae Prochlorococcus were detected throughout the entire water column. We proposed that vertical sinking, heterotrophic metabolism, and/or the transition to resting stage of phytoplankton might contribute to the presence of phytoplankton in the hadal zone. This study provided insight into the PN community in the Mariana Trench, implied the significance of phytoplankton in exporting organic matters from the euphotic to the hadal zone, and also hinted the possible existence of some undetermined energy metabolism (e.g., heterotrophy) of phytoplankton making themselves adapt and survive in the hadal environment.

Guo|Ruoyu|R| Liang|Yantao|Y| Xin|Yu|Y| Wang|Long|L| Mou|Shanli|S| Cao|Chunjie|C| Xie|Ruize|R| Zhang|Chuanlun|C| Tian|Jiwei|J| Zhang|Yongyu|Y|

pico- and nano-phytoplankton
Mariana Trench
deep sea
18S rRNA
plastid 23S rRNA


The vasoactive peptide MR-pro-adrenomedullin in COVID-19 patients: an observational study.

Abstract:
OBJECTIVES
Midregional pro-adrenomedullin (MR-proADM) is a vasoactive peptide with key roles in reducing vascular hyperpermeability and thereby improving endothelial stability during infection. While MR-proADM is useful for risk stratification in patients with sepsis, clinical data about prediction accuracy in patients with severe acute respiratory syndrome coronavirus 2 disease (COVID-19) is currently missing.

METHODS
We included consecutively adult patients hospitalized for confirmed COVID-19 at a tertiary care center in Switzerland between February and April 2020. We investigated the association of MR-proADM levels with in-hospital mortality in logistic regression and discrimination analyses.

RESULTS
Of 89 included COVID-19 patients, 19% (n=17) died while in the hospital. Median admission MR-proADM levels (nmol/L) were increased almost 1.5-fold increased in non-survivors compared to survivors (1.3 [interquartile range IQR 1.1-2.3]) vs. 0.8 [IQR 0.7-1.1]) and showed good discrimination (area under the curve 0.78). An increase of 1 nmol/L of admission MR-proADM was independently associated with a more than fivefold increase in in-hospital mortality (adjusted odds ratio of 5.5, 95% confidence interval 1.4-21.4, p=0.015). An admission MR-proADM threshold of 0.93 nmol/L showed the best prognostic accuracy for in-hospital mortality with a sensitivity of 93%, a specificity of 60% and a negative predictive value of 97%. Kinetics of follow-up MR-proADM provided further prognostic information for in-hospital treatment.

CONCLUSIONS
Increased levels of MR-proADM on admission and during hospital stay were independently associated with in-hospital mortality and may allow a better risk stratification, and particularly rule-out of fatal outcome, in COVID-19 patients.

Gregoriano|Claudia|C| Koch|Daniel|D| Kutz|Alexander|A| Haubitz|Sebastian|S| Conen|Anna|A| Bernasconi|Luca|L| Hammerer-Lercher|Angelika|A| Saeed|Kordo|K| Mueller|Beat|B| Schuetz|Philipp|P|


Transurethral resection of the prostate provides more favorable clinical outcomes compared with conservative medical treatment in patients with urinary retention caused by benign prostatic obstruction.

Abstract:
BACKGROUND
To evaluate the long-term surgical outcomes of patients with urinary retention (UR) caused by a benign prostatic obstruction (BPO) who underwent transurethral resection of the prostate (TURP), and compare their outcomes with those of patients who received medication without surgical intervention.

METHODS
This retrospective cohort study analyzed claims data collected during the period of 1997-2012 from Taiwan's National Health Insurance Research Database. We examined geriatric adverse events among patients who had received a diagnosis of symptomatic benign prostatic hyperplasia and whom experienced UR, and compared those who received TURP and medication only. Primary outcomes included urinary tract infection (UTI), UR, inguinal hernia, hemorrhoids, stroke, acute myocardial infarction, and bony fracture. We excluded patients who had concomitant prostate cancer, bladder cancer, or a long-term urinary catheter indwelling, as well as those who did not receive α-blocker medication regularly. Those aged <50 or >90 years were also excluded. The enrolled patients were categorized into TURP (n = 1218) and medication only (n = 795) groups. After 1:1 propensity score matching, we recorded and compared patients' characteristics, postoperative clinical outcomes, and geriatric adverse events.

RESULTS
The TURP cohort had a lower incidence of UTI and UR during the postoperative follow-up period from 2 months to 3 years than did the medication only group (20.7% vs. 28.9% and 12.5% vs. 27.6%, respectively, p < 0.001). The life-long bone fracture incidence was also lower in the TURP cohort (7.9% vs. 9.2%, p = 0.048). The incidence of other outcomes during the postoperative follow-up period did not differ between the two groups.

CONCLUSIONS
Compared with conservative treatment, TURP provides more favorable clinical outcomes in patients with UR caused by BPO. Patients who underwent TURP had a lower risk of UTI, repeat UR episodes, and emergent bony fracture. Thus, early surgical intervention should be considered for such patients.

Lin|Yu-Hsiang|YH| Hou|Chen-Pang|CP| Chen|Tien-Hsing|TH| Juang|Horng-Heng|HH| Chang|Phei-Lang|PL| Yang|Pei-Shan|PS| Chen|Chien-Lun|CL| Tsui|Ke-Hung|KH|

D010043:Outcome and Process Assessment, Health Care

D020728:Transurethral Resection of Prostate

Outcome
Benign prostate hyperplasia
Alfa-blocker
Prostatectomy
Urine retention


Rapidly oscillating microbubbles force development of micro- and mesoporous interfaces and composition gradients in solids.

Abstract: Progress in understanding of energy transfer in nature and human being requires novel approaches to the processing of solids on demand, in specially those with composition gradients and those thermodynamically and kinetically inaccessible. We demonstrate that rapidly oscillating microbubbles are useful for materials processing, because they manipulate surface temperature and creates temperature gradients in predictable way. Ultrasonic treatment leads to an increase in the surface area of particles up to 180 m2g-1 and the formation of micropores in metal phase and mesopores in metal oxide phase. The spatially and temporally unique energy dissipation conditions promise new interfaces with higher level of complexity and applications among others in catalysis, energy storage, drug delivery.

Andreeva|Daria V|DV|
Cherepanov|Pavel V|PV|
Avadhut|Y S|YS|
Senker|Jürgen|J|

Temperature gradient
Metal particles
Structuring
Ultrasound


Staphylococcus agnetis, a potential pathogen in broiler breeders.

Abstract: In this study, four broiler parent flocks have been followed from the onset of the production period (week 20) until slaughter (week 60). Every week, approximately ten dead broiler breeders, randomly selected among birds dead on their own, were collected and subjected to a full post mortem analysis including bacteriological examination. In total 997 breeders were investigated and for the first time Staphylococcus agnetis was isolated in pure culture from cases of endocarditis and septicemia from 16 broiler breeders. In addition, the cloacal flora from newly hatched chickens originating from the same four flocks were characterized and S. agnetis was found in pure culture of several newly hatched chickens (n=12) and only in one case in combination with another species. Clonality of the isolates was examined by pulsed-field-gel-electrophoresis which showed indistinguishable patterns in isolates from both broiler breeders and broilers. Three isolates were whole genome sequenced to obtain knowledge on virulence genes. The isolates harbored a number of genes encoding different fibrinogen binding proteins and toxins which might be important for virulence. The present findings demonstrate that S. agnetis may be associated with mortality in broiler breeders. No disease was associated with the broilers which were found positive for S. agnetis in the cloaca.

Poulsen|Louise Ladefoged|LL|
Thøfner|Ida|I|
Bisgaard|Magne|M|
Olsen|Rikke Heidemann|RH|
Christensen|Jens Peter|JP|
Christensen|Henrik|H|

Pathogen Endocarditis Disease Poultry Septicaemia


Discrimination of aerosol types over the Tehran city using 5 years (2011-2015) of MODIS collection 6 aerosol products.

Abstract:
Purpose
Tehran, Iran, is an interesting location for aerosol studies because it is affected by anthropogenic pollution and desert dust aerosols. The aim of this study was to discriminate the aerosol types using satellite data over the city.

Method
The study was performed using Level-2 daily Aerosol Optical Depth (AOD) and Ångström Exponent (AE) data from the Moderate Resolution Imaging Spectroradiometer (MODIS) instruments on board the Terra and Aqua satellites for the years 2011 to 2015. As the Deep Blue (DB) AE retrievals are more reliable than the Dark Target (DT) AE retrievals, the study was performed using DB data.

Results
The number of granules with successful retrievals (at least in two pixels with AODs >0.2 over Tehran with high quality assurance) was 200, which indicates that aerosols could be observed in 5.47% (200 from 3652 of Terra and Aqua granules) of the overpasses during the study period. The maximum and minimum values of AOD occurred during May (0.32 ± 0.27) and August (0.18 ± 0.07), respectively. Based on the AOD vs. AE data, aerosols were classified into three different categories: urban/industry (UI), Desert Dust (DD) and Mixed (Mix). To improve the accuracy of the aerosol classification, the analysis was limited to retrievals with AOD values larger than 0.2. The DD, UI and Mix types had 48.5%, 30.5% and 21% contribution in the aerosol days, respectively.

Conclusions
The maximum DD frequency was observed in the spring and summer seasons, while the UI type had its maximum during the cold season. The AOD of the DD type (over Tehran) correlated well with the AOD observations done at the Aerosol Robotic Network (AERONET) site in Zanjan (300 km northwest from Tehran). For the UI type, no relationship with the AERONET AOD was detected. This gives confidence in our aerosol typing as the contribution of dust in the aerosol load is mainly from long-range transport, whereas the urban aerosols originate from local sources. Back trajectories ending in Tehran show that the northeast and west trajectories are two main transport routes for the dust to the study area.

Rezaei|Mohammad|M| Farajzadeh|Manuchehr|M| Mielonen|Tero|T| Ghavidel|Yosef|Y|

Aerosol types
Tehran
MODIS
Back trajectory
Deep blue algorithm


Molecular characterization and taurine regulation of two novel CDOs (CDO1 and CDO2) from Carassius auratus.

Abstract: Cysteine oxygenase (CDO) is a mononuclear nonhemoglobin enzyme that catalyzes the production of taurine through the cysteine (Cys) pathway and plays a key role in the biosynthesis of taurine in mammals. However, the function of CDOs in bony fish remains poorly understood. In this study, we cloned CDO genes (CaCDO1 and CaCDO2) from Carassius auratus. The cDNA sequences of both CaCDO1 and CaCDO2 encoded putative proteins with 201 amino acids, which included structural features typical of the CDO protein family. Multiple sequence alignment and phylogenetic analysis showed that CaCDO1 and CaCDO2 shared high sequence identities and similarities with C. carpio homologs. Quantitative real-time polymerase chain reaction (qRT-PCR) results revealed that CaCDO1 and CaCDO2 were both broadly expressed in all selected tissues and developmental stages in C. auratus but had differing mRNA levels. In addition, compared to those of the taurine-free group, the in vivo mRNA expression levels of both CaCDO1 and CaCDO2 significantly decreased with increasing dietary taurine levels from 1.0 to 9.0 g/kg. Furthermore, in vitro taurine treatments showed similar inhibitory effects on the expression of CaCDO1 and CaCDO2 in the intestines of C. auratus. Our results also showed that the mRNA expression of CaCDO2 in the intestines was higher than that of CaCDO1 in response to in vivo and in vitro taurine supplementation. Overall, these data may provide new insights into the regulation of fish CDO expression and provide valuable knowledge for improving dietary formulas in aquaculture.

Luo|Wenjie|W| Qu|Fufa|F| Song|Peng|P| Xiong|Ding|D| Yin|Yulong|Y| Li|Jianzhong|J| Liu|Zhen|Z|

D018507:Gene Expression Regulation, Developmental

D015971:Gene Expression Regulation, Enzymologic

Taurine regulation
Carassius auratus
Cysteine oxygenase
Expression profile
Molecular cloning


Reminiscence functions over time: consistency of self functions and variation of prosocial functions.

Abstract: The current study examines the temporal stability of the tripartite model of reminiscence functions in which eight separate reminiscence functions map onto three second-order factors which contribute significantly to measurement of an overarching reminiscence latent construct. We collected online responses from 411 adults 50+ years of age. Confirmatory factor analytic models were computed at three points of data collection over 16 months. Invariance analyses were next undertaken to simultaneously compare the measurement properties to assess within-person stability of reminiscence functions over time. The tripartite structure of reminiscence functions was replicated at each point of data collection. As hypothesised, self-positive and self-negative functions are consistent across points of data collection, whereas prosocial functions vary over time. The temporal stability of the self functions may be attributed to enduring characteristics of the individual such as personality traits and life attitudes, as well as their solitary nature. Previous research indicates that consistency of self-positive reminiscence functions has ensuing benefits for physical health and psychological well-being; the opposite is true for self-negative functions. The temporal variation of prosocial functions may be due to the varying availability of others to share memories and their responsiveness to the emotional context.

O'Rourke|Norm|N|
King|David B|DB|
Cappeliez|Philippe|P|

reminiscence functions
Invariance analyses
older adults
psychometric reliability
temporal consistency


Structural bases that underline Trypanosoma cruzi calreticulin proinfective, antiangiogenic and antitumor properties.

Abstract: Microbes have developed mechanisms to resist the host immune defenses and some elicit antitumor immune responses. About 6 million people are infected with Trypanosoma cruzi, the protozoan agent of Chagas' disease, the sixth neglected tropical disease worldwide. Eighty years ago, G. Roskin and N. Klyuyeva proposed that T. cruzi infection mediates an anti-cancer activity. This observation has been reproduced by several other laboratories, but no molecular basis has been proposed. We have shown that the highly pleiotropic chaperone calreticulin (TcCalr, formerly known as TcCRT), translocates from the parasite ER to the exterior, where it mediates infection. Similar to its human counterpart HuCALR (formerly known as HuCRT), TcCalr inhibits C1 in its capacity to initiate the classical pathway of complement activation. We have also proposed that TcCalr inhibits angiogenesis and it is a likely mediator of antitumor effects. We have generated several in silico structural TcCalr models to delimit a peptide (VC-TcCalr) at the TcCalr N-domain. Chemically synthesized VC-TcCalr did bind to C1q and was anti-angiogenic in Gallus gallus chorioallantoic membrane assays. These properties were associated with structural features, as determined in silico. VC-TcCalr, a strong dipole, interacts with charged proteins such as collagen-like tails and scavenger receptors. Comparatively, HuCALR has less polarity and spatial stability, probably due to at least substitutions of Gln for Gly, Arg for Lys, Arg for Asp and Ser for Arg that hinder protein-protein interactions. These differences can explain, at least in part, how TcCalr inhibits the complement activation pathway and has higher efficiency as an antiangiogenic and antitumor agent than HuCALR.

Peña Álvarez|Jaime|J|
Teneb|Jaime|J|
Maldonado|Ismael|I|
Weinberger|Katherine|K|
Rosas|Carlos|C|
Lemus|David|D|
Valck|Carolina|C|
Olivera-Nappa|Álvaro|Á|
Asenjo|Juan A|JA|
Ferreira|Arturo|A|

D054730:Protein Interaction Domains and Motifs

Trypanosoma cruzi calreticulin
Complement
C1q
Molecular dynamics
Protein modeling
Tumor growth


Early Results of Chimney Technique for Type B Aortic Dissections Extending to the Aortic Arch.

Abstract:
OBJECTIVE
To summarize our early experience gained from the chimney technique for type B aortic dissection (TBAD) extending to the aortic arch and to evaluate the aortic remodeling in the follow-up period.

METHODS
From September 2011 to July 2014, 27 consecutive TBAD patients without adequate proximal landing zones were retrograde analyzed. Chimney stent-grafts were deployed parallel to the main endografts to reserve flow to branch vessels while extending the landing zones. In the follow-up period, aortic remodeling was observed with computed tomography angiography.

RESULTS
The technical success rate was 100 %, and endografts were deployed in zone 0 (n = 3, 11.1 %), zone 1 (n = 18, 66.7 %), and zone 2 (n = 6, 22.2 %). Immediately, proximal endoleaks were detected in 5 patients (18.5 %). During a mean follow-up period of 17.6 months, computed tomography angiography showed all the aortic stent-grafts and chimney grafts to be patent. Favorable remodeling was observed at the level of maximum descending aorta and left subclavian artery with expansion of true lumen (from 18.4 ± 4.8 to 25 ± 0.86 mm, p < 0.001 and 27.1 ± 0.62 to 28.5 ± 0.37 mm, p < 0.001) and depressurization of false lumen (from 23.7 ± 2.7 to 8.7 ± 3.8 mm, p < 0.001, from 5.3 ± 1.2 to 2.1 ± 2.1 mm, p < 0.001). While at the level of maximum abdominal aorta, suboptimal remodeling of the total aorta (from 24.1 ± 0.4 to 23.6 ± 1.5 mm, p = 0.06) and true lumen (from 13.8 ± 0.6 to 14.5 ± 0.4 mm, p = 0.08) was observed.

CONCLUSION
Based on our limited experience, the chimney technique with thoracic endovascular repair is demonstrated to be promising for TBAD extending to the arch with favorable aortic remodeling.

Huang|Chen|C| Tang|Hanfei|H| Qiao|Tong|T| Liu|Changjian|C| Zhou|Min|M|

D019917:Blood Vessel Prosthesis Implantation

Chimney technique
Type B aortic dissection
Aortic arch
Aortic remodeling
Endovascular repair


Comparative Study on Chloride Binding Capacity of Cement-Fly Ash System and Cement-Ground Granulated Blast Furnace Slag System with Diethanol-Isopropanolamine.

Abstract: Steel bar corrosion caused by chloride was one of the main forms of concrete deterioration. The promotion of chloride binding capacity of cementitious materials would hinder the chloride transport to the surface of steel bar, thereby alleviating the corrosion and mitigating the deterioration. A comparative study on binding capacity of chloride in cement-fly ash system (C-FA) and cement-ground granulated blast furnace slag system (C-GGBS) with diethanol-isopropanolamine (DEIPA) was investigated in this study. Chloride ions was introduced by adding NaCl in paste, and the chloride binding capacity of the paste samples at 7 d and 60 d was examined. The hydration process was discussed via the testing of hydration heat and compressive strength. The hydrates in hardened paste was characterized by X-ray Diffractometry (XRD), Thermo Gravimetric Analysis (TGA), and Scanning Electron Microscope (SEM). The effect of DEIPA on dissolution of aluminate phase and compressive strength was discussed as well. These results showed that DEIPA could facilitate the hydration of C-FA and C-GGBS system, and the promotion effect was higher in C-FA than that in C-GGBS. DEIPA also increased the binding capacity of chloride in C-FA and C-GGBS systems. One reason was the increased chemical binding, because DEIPA facilitated the dissolution of aluminate to benefit the formation of Friedel's salt. Other reasons were the increased physical binding and migration resistance. By contrast, DEIPA presented greater ability to increase chloride binding capacity in C-FA system, because DEIPA showed stronger ability to expedite the dissolution of aluminate of FA than that of GGBS, which benefited the formation of FS, thereby promoting the chemical binding. Such results would give deep insight into using DEIPA as an additive in cement-based materials.

Liu|Huaqing|H| Zhang|Yan|Y| Liu|Jialong|J| Feng|Zixia|Z| Kong|Sen|S|

chloride binding capacity
diethanol-isopropanolamine
fly ash
ground granulated blast furnace slag


Mindfulness-Based Stress Reduction: pilot study of a treatment group for patients with chronic pain in a primary care setting.

Abstract:
AIM
The study objective was to evaluate an eight-week Mindfulness-Based Stress Reduction (MBSR) treatment group for chronic pain in terms of effects on pain disability, subjective ratings of pain and psychological distress related to pain, and activity level and willingness to experience pain. This pilot study evaluated the impact of two eight-week MBSR treatment groups that were delivered in a clinic in Winnipeg, Manitoba.

BACKGROUND
Chronic pain is one of the most common presenting problems in primary care settings.

METHODS
Adult patients with chronic pain were recruited from 20 clinics that are part of a collaborative care programme and outcome measures were administered at baseline and programme completion.

FINDINGS
Despite a modest attendance rate and the short length of programme, a pre-post evaluation involving 17 patients revealed significant and/or clinically relevant improvements in level of pain disability, psychological distress, engagement in life activities, willingness to experience pain, and subjective rating of current pain.


Swim Bladder Disorders in Koi Carp (Cyprinus carpio).

Abstract: Swim bladder disorders and consequent buoyancy problems are encountered in ornamental fish, including koi carp. Nevertheless, beyond clinical and pharmacological management, they are largely underdiagnosed. In this study, nine koi carp showing abdominal swelling and abnormal swimming behavior were investigated. Clinical approach, varying from case to case, included ultrasonographic and X-ray investigations, bacteriological analysis of the collected fluid, antimicrobial susceptibility pattern, and possibly histological analysis. Diagnostic imaging, corroborating gross examination, documented swim bladder deformation/dislocation and serous fluid within the swim bladder chambers of most animals. Bacteria belonging to the Aeromonas hydrophila/caviae group and Shewanella xiamenensis were identified. S. xiamenensis strains showed a sensibility to all tested molecules except for one strain, which was resistant to tetracycline and cyprofloxacin. Antibiotic treatment succeeded in the full recovery of three cases in which S. xiamemensis infection was detected. Chronic aerocystitis was histologically documented where tissue was available. The swim bladder histopathological findings highlighted a chronic process that had compromised the quality of life of the animals. A multidisciplinary clinical-pathological and microbiological approach is highly suggested to recognize swim bladder conditions as early as possible, aiming to drive medical intervention and raising the chances of fish survival.

Sirri|Rubina|R|0000-0002-8603-8418 Mandrioli|Luciana|L| Zamparo|Samuele|S| Errani|Francesca|F| Volpe|Enrico|E| Tura|Giorgia|G| Barbé|Tim|T| Ciulli|Sara|S|

swim bladder disorders
koi carp
ornamental fish
diagnostic imaging
histopathology
microbiology
cyprinid


Multicolor Emission from Ultraviolet GaN-Based Photonic Quasicrystal Nanopyramid Structure with Semipolar InxGa1-xN/GaN Multiple Quantum Wells.

Abstract: In this study, we demonstrated large-area high-quality multi-color emission from the 12-fold symmetric GaN photonic quasicrystal nanorod device which was fabricated using the nanoimprint lithography technology and multiple quantum wells regrowth procedure. High-efficiency blue and green color emission wavelengths of 460 and 520 nm from the regrown InxGa1-xN/GaN multiple quantum wells were observed under optical pumping conditions. To confirm the strong coupling between the quantum well emissions and the photonic crystal band-edge resonant modes, the finite-element method was applied to perform a simulation of the 12-fold symmetry photonic quasicrystal lattices.

Chen|Cheng-Chang|CC|
Lin|Hsiang-Ting|HT|
Chang|Shih-Pang|SP|
Kuo|Hao-Chung|HC|
Hung|Hsiao-Wen|HW|
Chien|Kuo-Hsiang|KH|
Chang|Yu-Choung|YC|
Shih|M H|MH|

Photonic quasicrystal multicolor emission


EZH2 Overexpression as a Useful Prognostic Marker for Aggressive Behaviour in Thyroid Cancer.

Abstract:
BACKGROUND/AIM
Enhancer of zeste homolog 2 (EZH2) is a member of the polycomb group of genes, which are key factors in the regulation of cell proliferation and differentiation. EZH2 is overexpressed in many malignancies. We analyzed EZH2 protein expression levels in different histological subtypes of thyroid cancer to examine its utility as a prognostic factor.

MATERIALS AND METHODS
We examined EZH2 protein expression by immunohistochemistry in tissue samples from 67 cases of poorly differentiated (PDTC) and 48 cases of anaplastic thyroid carcinoma (ATC), and in samples of adjacent normal and differentiated thyroid carcinoma (DTC). We examined differences in expression of EZH2 among various histological types of thyroid cancer, and the relationship between EZH2 expression and patient outcome.

RESULTS
EZH2 protein was expressed in PDTC and ATC, but not in normal thyroid gland or DTC. EZH-positivity increased in the order of DTC, PDTC, and ATC (p<0.01). Higher EZH2 expression correlated with poorer survival in PDTC (p=0.004), and a similar but non-significant trend was observed in ATC (p=0.166). Multivariate analysis identified EZH2 as an independent prognostic factor similar to metastatic status in the Japanese Society of Thyroid Surgery (JSTS) classification of PDTC.

CONCLUSION
EZH2 overexpression is associated with malignant potential in thyroid cancer, and may thus be a useful prognostic marker of aggressive thyroid cancer.

Masudo|Katsuhiko|K| Suganuma|Nobuyasu|N| Nakayama|Hirotaka|H| Oshima|Takashi|T| Rino|Yasushi|Y| Iwasaki|Hiroyuki|H| Matsuzu|Kenichi|K| Sugino|Kiminori|K| Ito|Koichi|K| Kondo|Tetsuo|T| Nakamura|Yoshiyasu|Y| Yoshihara|Mitsuyo|M| Masuda|Munetaka|M| Miyagi|Yohei|Y|

D000071221:Enhancer of Zeste Homolog 2 Protein

EZH2
Thyroid cancer
prognostic factor
epigenetics


Levels of rhizome endophytic fungi fluctuate in Paris polyphylla var. yunnanensis as plants age.

Abstract: Paris polyphylla var. yunnanensis is an important medicinal plant with abundant saponins that are widely used in the pharmaceuticals industry. It is unclear why the levels of active ingredients increase as these plants age. We speculated that the concentrations of those components in the rhizomes are mediated by fungal endophytes. To test this hypothesis, we took both culture-dependent and -independent (metagenomics) approaches to analyze the communities of endophytic fungi that inhabit those rhizomes in plants of different age classes (four, six, and eight years old). In all, 147 isolates representing 18 fungal taxa were obtained from 270 segments (90 per age class). Based on morphological and genetic characteristics, Fusarium oxysporum (46.55% frequency of occurrence) was the predominant endophyte, followed by Leptodontidium sp. (8.66%) and Trichoderma viride (6.81%). Colonization of endophytic fungi was maximized in the eight-year-old rhizomes (33.33%) when compared with four-year-old (21.21%) and six-year-old (15.15%) rhizomes. Certain fungal species were present only at particular ages. For example, Alternaria sp., Cylindrocarpon sp., Chaetomium sp., Paraphaeosphaeria sporulosa, Pyrenochaeta sp., Penicillium swiecickii, T. viride, and Truncatella angustata were found only in the oldest plants. Analysis of (metagenomics) community DNA extracted from different-aged samples revealed that, at the class level, the majority of fungi had the highest sequence similarity to members of Sordariomycetes, followed by Eurotiomycetes and Saccharomycetes. These results were mostly in accord with those we obtained using culture methods. Fungal diversity and richness also changed over time. Our investigation is the first to show that the diversity of fungi in rhizomes of P. polyphylla var. yunnanensis is altered as plants age, and our findings provide a foundation for future examinations of useful compounds.

Endophytic fungi
Paris polyphylla var. yunnanensis
Medicinal plants


Mitotherapy for Fatty Liver by Intravenous Administration of Exogenous Mitochondria in Male Mice.

Abstract: Mitochondrial dysfunction is a major and common mechanism in developing non-alcoholic fatty liver disease (NAFLD). Replacement of dysfunctional mitochondria by functional exogenous mitochondria may attenuate intrahepatic excessive lipid and recover hepatocyte function. However, no data shows that mitochondria can be systemically administrated to animals to date. Here we suggest that mitochondria isolated from hepatoma cells are used as a mitotherapy agent to treat mouse fatty liver induced by high-fat diets. When the mitochondria were intravenously injected into the mice, serum aminotransferase activity and cholesterol level decreased in a dose-dependent manner. Also, the mitotherapy reduced lipid accumulation and oxidation injury of the fatty liver mice, improved energy production, and consequently restored hepatocyte function. The mitotherapy strategy offers a new potential therapeutic approach for treating NAFLD.

Fu|Ailing|A| Shi|Xianxun|X| Zhang|Huajing|H| Fu|Bin|B|

mitotherapy
fatty liver
mitochondrial dysfunction
lipid accumulation
oxidation injury