Exosomes derived from dendritic cells improve cardiac function via activation of CD4(+) T lymphocytes after myocardial infarction.

Abstract: CD4(+) T cell activation plays a key role in facilitating wound healing after myocardial infarction (MI). Exosomes (EXs) secreted from dendritic cells (DCs) can activate T cells in tumor models; however, whether DEXs (DC-EXs) can mediate CD4(+) T cell activation and improve wound healing post-MI remains unknown. This study sought to determine whether DEXs mediate CD4(+) T cell activation and improve cardiac function post-MI in mice. We used supernatants of hypoxic primary or necrotic HL-1 cardiomyocytes to simulate the post-MI cardiomyocyte microenvironment in vitro. Cultured bone marrow-derived DCs (BMDCs) from mice were stimulated with the supernatants of normal (Control group), hypoxic primary or necrotic HL-1 cardiomyocytes (MI group); a subset of BMDCs remained unstimulated (Negative group). DEXs were then isolated from the BMDC supernatants and either incubated with CD4(+) T cells or injected into mice via the tail vein. In this study, we found that the supernatants of both hypoxic primary and necrotic HL-1 cardiomyocytes upregulate DC maturation markers. After the injection of DEXs, a greater number of MI-DEXs are recruited by the mouse spleen and with greater rapidity than control- or negative-DEXs. Confocal imaging and flow cytometry revealed that MI-DEXs exhibited higher uptake by splenic CD4(+) T cells than the control- and negative-DEXs, and this increase was correlated with significantly greater increases in the expression of chemokines and the inflammatory cytokines IFN-γ and TNF by the CD4(+) T cells in vitro and in vivo. In addition, the injection of MI-DEXs improved cardiac function in mice post-MI. These results suggest that DEXs could mediate the activation of CD4(+) T cells through an endocrine mechanism and improve cardiac function post-MI. Our findings provide the basis for a novel strategy for the treatment of MI through the systemic delivery of DEXs.

Liu|Haibo|H| Gao|Wei|W| Yuan|Jie|J| Wu|Chaoneng|C| Yao|Kang|K| Zhang|Li|L| Ma|Leilei|L| Zhu|Jianbing|J| Zou|Yunzeng|Y| Ge|Junbo|J|

Exosomes
Dendritic cells
Myocardial infarction
Chemokines
Cytokines
T-lymphocytes


ICAM-1 targeting, intracellular trafficking, and functional activity of polymer nanocarriers coated with a fibrinogen-derived peptide for lysosomal enzyme replacement.

Abstract: Enzyme replacement is a viable treatment for diseases caused by genetic deficiency of lysosomal enzymes. However, suboptimal access of enzymes to target sites limits this strategy. Polymer nanocarriers (NCs) coated with antibody against intercellular adhesion molecule 1 (ICAM-1), a protein overexpressed on most cells under disease states, enhanced biodistribution and lysosomal delivery of these therapeutics. Whether this can be achieved using more biocompatible ICAM-1-targeting moieties is unknown, since intracellular uptake via this route is sensitive to the receptor epitope being targeted. We examined this using polymer NCs coated with an ICAM-1-targeting peptide derived from the fibrinogen sequence. Scrambled-sequence peptide and anti-ICAM were used as controls. NCs carried acid sphingomyelinase (ASM), used for treatment of type B Niemann-Pick disease, and fluorescence microscopy was employed to examine cellular performance. Peptide-coated/enzyme NCs efficiently targeted ICAM-1 (22-fold over non-specific counterparts; Bmax ∼180 NCs/cell; t1/2 ∼28 min), recognised human and mouse cells (1.2- to 0.7-fold binding vs. antibody/enzyme NCs), were efficiently endocytosed (71% at 1 h chase), and trafficked to lysosomes (30--45% of internalised NCs; 2 h chase). This restored lysosomal levels of sphingomyelin and cholesterol within 5 h chase (∼95% reduction over disease levels), similar to antibody-enzyme NCs. This fibrinogen-derived ICAM-1-targeting peptide holds potential for lysosomal enzyme replacement therapy.

D061307:Human Umbilical Vein Endothelial Cells

ICAM-1 targeting
polymer nanocarriers
fibrinogen-derived peptide
acid sphingomyelinase
enzyme replacement therapy
Niemann–Pick disease
lysosomal storage diseases


Efficacy of a High-Iron Dietary Intervention in Women with Celiac Disease and Iron Deficiency without Anemia: A Clinical Trial.

Abstract:
BACKGROUND AND AIM
Iron deficiency without anemia (IDWA) is a common finding in celiac disease (CD) and can also persist in case of good compliance and clinical response to a strict gluten-free diet (GFD). This scenario usually presents in CD women of child-bearing age in whom the imbalance between menstrual iron loss and inadequate iron intake from their diet plays the major role. A recommended approach to this condition is yet to be established. This study aimed to compare, in this subset of patients, the efficacy of a dietary approach consisting of an iron-rich diet against the traditional pharmacological oral-replacement therapy.

MATERIAL AND METHODS
Between February and December 2016, consecutive CD female patients of child-bearing age as referred to our outpatient center with evidence of IDWA (ferritin <15 ng/mL or 15-20 ng/L with transferrin saturation <15%) were enrolled. After the completion of a 7-day weighed food intake recording to assess the usual iron dietary intake, the patients were randomized in two arms to receive a 12-week iron-rich diet (iron intake >20 mg/die) versus oral iron supplementation with ferrous sulfate (FS) (105 mg/day). Blood tests and dietary assessments were repeated at the end of treatment. The degree of compliance and tolerability to the treatments were assessed every month by means of specific questionnaires and symptoms evaluation.

RESULTS
A total of 22 women were enrolled and divided in the diet group (n = 10, age 37 ± 8 years) and in the FS group (n = 12, age 38 ± 10 years). The food intake records demonstrated an inadequate daily intake of iron in all the enrolled subjects. At the end of the treatments, ferritin levels were higher in the FS group (8.5 (5) versus 34 (30.8), p = 0.002). Compliance and tolerability were similar in both treatment groups (89% versus 87%, p = ns).

CONCLUSIONS
These findings did not support any equivalent efficacy of an iron-rich diet compared to a FS supplementation in non-anemic iron-deficient women affected by CD. However, the diet appeared a well-tolerated approach, and adequate dietary instructions could effectively increase the daily iron consumption, suggesting a role in the long-term management of IDWA, especially in patients who do not tolerate pharmacological supplementation.

D000328:Adult
D018798:Anemia, Iron-Deficiency
D002446:Celiac Disease
D055050:Diet, Gluten-Free
D019587:Dietary Supplements
D005260:Female
D005293:Ferritins
D005296:Ferrous Compounds
D006801:Humans
D007501:Iron
D000090463:Iron Deficiencies
D019266:Iron, Dietary
D008875:Middle Aged
D015596:Nutrition Assessment
D009752:Nutritional Status
D011446:Prospective Studies
D011795:Surveys and Questionnaires

women
Celiac disease
iron deficiency without anemia
gluten-free diet
iron supplementation
dietary iron


A novel algorithm to improve specificity in ovarian cancer detection.

Abstract:
BACKGROUND
Measurement of autoantibodies (AAbs) to tumor associated antigens has been proposed to aid in the early detection of ovarian cancer with high specificity. Here we describe a multiplex approach to evaluate selected peptide epitopes of p53 protein, and propose a novel approach to increase specificity and potentially sensitivity for discrimination between healthy women and women with cancerous masses.

MATERIALS AND METHODS
20-mer overlapping peptide epitopes of p53, generated by mapping the complete p53 sequence, were evaluated in a multiplex immunoassay for their detection of serum AAbs in patients with ovarian cancer, using Luminex technology. AAbs to the selected peptides and to p53 full length protein were then detected in a multiplex immunoassay evaluating 359 sera from healthy women and 285 sera from patients with early and late stage ovarian cancer. CA-125 levels were measured in all p53 AAb-positive sera.

RESULTS
We considered the AAb results together to identify sera where both the full length protein and at least one selected peptide epitope were positive and chose cutoffs that reduced false positives from these AAbs to 1/359 samples, improving specificity. Using this combined approach, we could identify 7 AAb-positive patients that were negative for CA-125 (concentrations below 35 IU/mL); this represents 26% of the p53 positive patients in the total population.

CONCLUSION
By detecting p53 AAbs in CA-125-negative sera, we demonstrated that combining measurement of AAbs to the full length p53 protein and one or more selected epitopes can potentially improve sensitivity and specificity for ovarian cancer detection.

Arjomandi|Audrey|A|
Delanoy|Michelle L|ML|
Walker|Roger P|RP|
Binder|Steven R|SR|

Algorithm
Ovarian cancer
Multiplex
Biomarker
p53 autoantibody


Expression of Acsm2, a kidney-specific gene, parallels the function and maturation of proximal tubular cells.

Abstract: The acyl-CoA synthetase medium-chain family member 2 (Acsm2) gene was first identified and cloned by our group as a kidney-specific "KS" gene. However, its expression pattern and function remain to be clarified. In the present study, we found that the Acsm2 gene was expressed specifically and at a high level in normal adult kidneys. Expression of Acsm2 in kidneys followed a maturational pattern: it was low in newborn mice and increased with kidney development and maturation. In situ hybridization and immunohistochemistry revealed that Acsm2 was expressed specifically in proximal tubular cells of adult kidneys. Data from the Encyclopedia of DNA Elements database revealed that the Acsm2 gene locus in the mouse has specific histone modifications related to the active transcription of the gene exclusively in kidney cells. Following acute kidney injury, partial unilateral ureteral obstruction, and chronic kidney diseases, expression of Acsm2 in the proximal tubules was significantly decreased. In human samples, the expression pattern of ACSM2A, a homolog of mouse Acsm2, was similar to that in mice, and its expression decreased with several types of renal injuries. These results indicate that the expression of Acsm2 parallels the structural and functional maturation of proximal tubular cells. Downregulation of its expression in several models of kidney disease suggests that Acms2 may serve as a novel marker of proximal tubular injury and/or dysfunction.

Watanabe|Hirofumi|H|0000-0003-0657-5385
Paxton|Robert L|RL|
Tolerico|Matthew R|MR|
Nagalakshmi|Vidya K|VK|
Tanaka|Shinji|S|
Okusa|Mark D|MD|
Goto|Shin|S|
Narita|Ichiei|I|
Watanabe|Seiji|S|
Sequeira-Lοpez|Maria Luisa S|MLS|
Gomez|R Ariel|RA|

D018507:Gene Expression Regulation, Developmental

D015971:Gene Expression Regulation, Enzymologic

acyl-CoA synthetase
acute kidney injury
chronic kidney disease
proximal tubules
epigenetics
fatty acid oxidation


Early Influence of Musical Abilities and Working Memory on Speech Imitation Abilities: Study with Pre-School Children.

Abstract: Musical aptitude and language talent are highly intertwined when it comes to phonetic language ability. Research on pre-school children's musical abilities and foreign language abilities are rare but give further insights into the relationship between language and musical aptitude. We tested pre-school children's abilities to imitate unknown languages, to remember strings of digits, to sing, to discriminate musical statements and their intrinsic (spontaneous) singing behavior ("singing-lovers versus singing nerds"). The findings revealed that having an ear for music is linked to phonetic language abilities. The results of this investigation show that a working memory capacity and phonetic aptitude are linked to high musical perception and production ability already at around the age of 5. This suggests that music and (foreign) language learning capacity may be linked from childhood on. Furthermore, the findings put emphasis on the possibility that early developed abilities may be responsible for individual differences in both linguistic and musical performances.

working memory
musical aptitude
intrinsic singing
phonetic language aptitude
singing ability


Abstract:
INTRODUCTION
Deep dyspareunia negatively affects women's sexual function. There is a known association between deep dyspareunia and endometriosis of the cul-de-sac or uterosacral ligaments in reproductive-age women; however, other factors are less clear in this population.

AIM
To identify anatomic sites and associated clinical factors for deep dyspareunia in reproductive-age women at a referral center.

METHODS
This study involved the analysis of cross-sectional baseline data from a prospective database of 548 women (87% consent rate) recruited from December 2013 through April 2015 at a tertiary referral center for endometriosis and/or pelvic pain. Exclusion criteria included menopausal status, age at least 50 years, previous hysterectomy or oophorectomy, and not sexually active. We performed a standardized endovaginal ultrasound-assisted pelvic examination to palpate anatomic structures for tenderness and reproduce deep dyspareunia. Multivariable regression was used to determine which tender anatomic structures were independently associated with deep dyspareunia severity and to identify clinical factors independently associated with each tender anatomic site.

MAIN OUTCOME MEASURE
Severity of deep dyspareunia on a numeric pain rating scale of 0 to 10.

RESULTS
Severity of deep dyspareunia (scale = 0-10) was independently associated with tenderness of the bladder (b = 0.88, P = .018), pelvic floor (levator ani) (b = 0.66, P = .038), cervix and uterus (b = 0.88, P = .008), and cul-de-sac or uterosacral ligaments (b = 1.39, P < .001), but not with the adnexa (b = -0.16, P = 0.87). The number of tender anatomic sites was significantly correlated with more severe deep dyspareunia (Spearman r = 0.34, P < .001). For associated clinical factors, greater depression symptom severity was specifically associated with tenderness of the bladder (b = 1.05, P = .008) and pelvic floor (b = 1.07, P < .001). A history of miscarriage was specifically associated with tenderness of the cervix and uterus (b = 2.24, P = .001). Endometriosis was specifically associated with tenderness of the cul-de-sac or uterosacral ligaments (b = 3.54, P < .001).

CONCLUSIONS
In reproductive-age women at a tertiary referral center, deep dyspareunia was independently associated not only with tenderness of the cul-de-sac and uterosacral ligaments but also with tenderness of the bladder, pelvic floor, and cervix and uterus. Yong PJ, Williams C, Yosef A, et al. Anatomic Sites and Associated Clinical Factors for Deep Dyspareunia. Sex Med 2017;5:e184-e195.

Yong|Paul J|PJ|
Williams|Christina|C|
Yosef|Ali|A|
Wong|Fontayne|F|
Bedaiwy|Mohamed A|MA|
Lisonkova|Sarka|S|
Allaire|Catherine|C|

Dyspareunia
Endometriosis
Bladder
Pelvic Floor
Depression
Miscarriage


Pharmacokinetic properties of intramuscular versus oral syrup paracetamol in Plasmodium falciparum malaria.

Abstract:
BACKGROUND
Fever is an inherent symptom of malaria in both adults and children. Paracetamol (acetaminophen) is the recommended antipyretic as it is inexpensive, widely available and has a good safety profile, but patients may not be able to take the oral drug reliably. A comparison between the pharmacokinetics of oral syrup and intramuscular paracetamol given to patients with acute falciparum malaria and high body temperature was performed.

METHODS
A randomized, open-label, two-treatment, crossover, pharmacokinetic study of paracetamol dosed orally and intramuscularly was conducted. Twenty-one adult patients with uncomplicated falciparum malaria were randomized to receive a single 600 mg dose of paracetamol either as syrup or intramuscular injection on day 0 followed by a single dose administered by the alternative route on day 1. Paracetamol plasma concentrations were quantified frequently and modelled simultaneously using nonlinear mixed-effects modelling. The final population pharmacokinetic model was used for dose optimization simulations. Relationships between paracetamol concentrations with temperature and parasite half-life were investigated using linear and non-linear regression analyses.

RESULTS
The population pharmacokinetic properties of paracetamol were best described by a two-compartment disposition model, with zero-order and first-order absorption for intramuscular and oral syrup administration, respectively. The relative bioavailability of oral syrup was 84.4 % (95 % CI 68.2-95.1 %) compared to intramuscular administration. Dosing simulations showed that 1000 mg of intramuscular or oral syrup administered six-hourly reached therapeutic steady state concentrations for antipyresis, but more favourable concentration-time profiles were achieved with a loading dose of 1500 mg, followed by a 1000 mg maintenance dose. This ensured that maximum therapeutic concentrations were reached rapidly during the first 6 h. No significant relationships between paracetamol concentrations and temperature or parasite half-life were found.

CONCLUSIONS
Paracetamol plasma concentrations after oral syrup and intramuscular administration in patients with acute falciparum malaria were described successfully by a two-compartment disposition model. Relative oral bioavailability compared to intramuscular dosing was estimated as 84.4 % (95 % CI 68.2-95.1 %). Dosing simulations showed that a loading dose followed by six-hourly dosing intervals reduced the time delay to reach therapeutic drug levels after both routes of administration. The safety and efficacy of loading dose paracetamol antipyretic regimens now needs to be established in larger studies.

Wattanakul|Thanaporn|T|
Teerapong|Pramote|P|
Plewes|Katherine|K|
Newton|Paul N|PN|
Chierakul|Wirongrong|W|
Silamut|Kamolrat|K|
Chotivanich|Kesinee|K|
Ruengweerayut|Ronnatrai|R|
White|Nicholas J|NJ|
Dondorp|Arjen M|AM|
Tarning|Joel|J|

Pharmacokinetics
Intramuscular
Paracetamol
Falciparum malaria
Antipyretic
NONMEM
Randomized crossover trial


Trans-spinal direct current stimulation modifies spinal cord excitability through synaptic and axonal mechanisms.

Abstract: The spinal cord is extremely complex. Therefore, trans-spinal direct current stimulation (tsDCS) is expected to produce a multitude of neurophysiological changes. Here, we asked how tsDCS differentially affects synaptic and nonsynaptic transmission. We investigated the effects of tsDCS on synaptically mediated responses by stimulating the medullary longitudinal fascicle and recording responses in the sciatic nerve and triceps and tibialis anterior muscles. Response amplitude was increased during cathodal-tsDCS (c-tsDCS), but reduced during anodal-tsDCS (a-tsDCS). After-effects were dependent on the frequency of the test stimulation. c-tsDCS-reduced responses evoked by low-frequency (0.5 Hz) test stimulation and increased responses evoked by high-frequency (400 Hz) test stimulation. a-tsDCS had opposite effects. During and after c-tsDCS, excitability of the lateral funiculus tract (LFT) and dorsal root fibers was increased. However, a-tsDCS caused a complex response, reducing the excitability of LFT and increasing dorsal root fiber responses. Local DC application on the sciatic nerve showed that the effects of DC on axonal excitability were dependent on polarity, duration of stimulation, temporal profile (during vs. after stimulation), orientation of the current direction relative to the axon and relative to the direction of action potential propagation, distance from the DC electrode, and the local environment of the nervous tissue. Collectively, these results indicate that synaptic as well as axonal mechanisms might play a role in tsDCS-induced effects. Therefore, this study identified many factors that should be considered in interpreting results of DCS and in designing tsDCS-based interventions.

Direct current
excitability
trans‐spinal


Soil incubation studies with Cry1Ac protein indicate no adverse effect of Bt crops on soil microbial communities.

Abstract: Bt crops that are transgenic crops engineered to produce Bt toxins which occur naturally with Bacillus thuringiensis (Bt) have been widely planted and its environmental risk assessment has been heavily debated. The effects of Bt crops on soil microbial communities are possible through changing the quantity and quality of C inputs and potential toxic activity of Bt protein on soil organisms. To date, the direct effects of Bt protein on soil microorganisms is unclear. Here we added Cry1Ac, one of the most commonly used Bt protein in Bt crops, to the soil and monitored changes in soil bacterial, fungal and archaeal diversities and community structures using ribosomal DNA-fingerprinting method, as well as their population sizes by real-time PCR over a 100-day period. Despite the fact that variations were observed in the indices of evenness, diversity and population sizes of bacteria, fungi and archaea with different Cry1Ac addition rates up to 100ngg-1 soil, the indices of soil microbial diversities and evennesses did not significantly shift with Cry1Ac protein addition, nor did population sizes change over time. The diversities of the dominant bacteria, fungi and archaea were not significantly changed, given Cry1Ac protein addition rates over a period of 100 days. These results suggested that Bt protein derived by cultivations of transgenic Bt crops is unlikely to cause transient or even persisting significant changes in soil microorganisms in field.

Zhaolei|Li|L| Naishun|Bu|B| Xueping|Chen|C| Jun|Cui|C| Manqiu|Xiao|X| Zhiping|Song|S| Ming|Nie|N| Changming|Fang|F|

Cry1Ac protein
Diversity
Community structure
Bacteria
Fungi
Archaea


PrEP indicators, social capital and social group memberships among gay, bisexual and other men who have sex with men.

Abstract: Efforts to reduce HIV among gay, bisexual and other men who have sex with men include increasing awareness and uptake of pre-exposure prophylaxis (PrEP). Social capital may facilitate engagement in HIV prevention. Membership of social groups including chosen families (i.e. friends as family relationships) - one potential indicator of social capital - may be protective against HIV risk and infection. In this cross-sectional quantitative study, we examined social capital items and social group membership in association with PrEP outcomes. In 2014, the New Orleans arm of the National HIV Behavioral Surveillance recruited 353 HIV-negative men, of whom 46% identified as Black, Latino or Other Race and 54% as Non-Hispanic White, using venue-based sampling to complete a structured survey. Multivariable logistic regression models tested the relations between social group membership and social capital with PrEP indicators. Men who reported community group participation were more likely to be aware of PrEP compared to those who did not. Men in chosen families associated with a family name were least likely to be aware of and willing to take PrEP compared to those not in any other social groups. Social group membership is a potential social capital indicator for assessing HIV prevention among men.

Zarwell|Meagan|M|0000-0002-3562-7415
Ransome|Yusuf|Y|
Barak|Narquis|N|
Gruber|DeAnn|D|
Robinson|William T|WT|

D010342:Patient Acceptance of Health Care


Nursing home quality and financial performance: does the racial composition of residents matter?

Abstract:
OBJECTIVE
To examine the effects of the racial composition of residents on nursing homes' financial and quality performance. The study examined Medicare and Medicaid-certified nursing homes across the United States that submitted Medicare cost reports between the years 1999 and 2004 (11,472 average per year).

DATA SOURCE
Data were obtained from the Minimum Data Set, the On-Line Survey Certification and Reporting, Medicare Cost Reports, and the Area Resource File.

STUDY DESIGN
Panel data regression with random intercepts and negative binomial regression were conducted with state and year fixed effects.

PRINCIPAL FINDINGS
Financial and quality performance differed between nursing homes with high proportions of black residents and nursing homes with no or medium proportions of black residents. Nursing homes with no black residents had higher revenues and higher operating margins and total profit margins and they exhibited better processes and outcomes than nursing homes with high proportions of black residents.

CONCLUSION
Nursing homes' financial viability and quality of care are influenced by the racial composition of residents. Policy makers should consider initiatives to improve both the financial and quality performance of nursing homes serving predominantly black residents.

Chisholm|Latarsha|L| Weech-Maldonado|Robert|R| Laberge|Alex|A| Lin|Feng-Chang|FC| Hyer|Kathryn|K|

Nursing homes
quality
financial performance
racial composition
blacks


Intermittent hypoxia-induced endothelial barrier dysfunction requires ROS-dependent MAP kinase activation.

Abstract: The objective of the present study was to determine the impact of simulated apnea with intermittent hypoxia (IH) on endothelial barrier function and assess the underlying mechanism(s). Experiments were performed on human lung microvascular endothelial cells exposed to IH-consisting alternating cycles of 1.5% O2 for 30s followed by 20% O2 for 5 min. IH decreased transendothelial electrical resistance (TEER) suggesting attenuated endothelial barrier function. The effect of IH on TEER was stimulus dependent and reversible after reoxygenation. IH-exposed cells exhibited stress fiber formation and redistribution of cortactin, vascular endothelial-cadherins, and zona occludens-1 junction proteins along with increased intercellular gaps at cell-cell boundaries. Extracellular signal-regulated kinase (ERK) and c-jun NH2-terminal kinase (JNK) were phosphorylated in IH-exposed cells. Inhibiting either ERK or JNK prevented the IH-induced decrease in TEER and the reorganization of the cytoskeleton and junction proteins. IH increased reactive oxygen species (ROS) levels, and manganese (III) tetrakis (1-methyl-4-pyridyl) porphyrin pentachloride, a membrane-permeable antioxidant, prevented ERK and JNK phosphorylation as well as IH-induced changes in endothelial barrier function. These results demonstrate that IH via ROS-dependent activation of MAP kinases leads to reorganization of cytoskeleton and junction proteins resulting in endothelial barrier dysfunction.

Makarenko|Vladislav V|VV|
Usatyuk|Peter V|PV|
Yuan|Guoxiang|G|
Lee|May M|MM|
Nanduri|Jayasri|J|
Natarajan|Viswanathan|V|
Kumar|Ganesh K|GK|
Prabhakar|Nanduri R|NR|

D020929:Mitogen-Activated Protein Kinase Kinases

microvascular endothelial cells
junction proteins
cytoskeleton proteins
oxidative stress


The peptidic antidepressant spadin interacts with prefrontal 5-HT(4) and mGluR(2) receptors in the control of serotonergic function.

Abstract: This study investigates the mechanism of action of spadin, a putative fast-acting peptidic antidepressant (AD) and a functional blocker of the K(+) TREK-1 channel, in relation with the medial prefrontal cortex (mPFC)-dorsal raphé (DRN) serotonergic (5-HT) neurons connectivity. Spadin increased 5-HT neuron firing rate by 113%, an augmentation abolished after electrolytic lesion of the mPFC. Among the few receptor subtypes known to modulate TREK-1, the stimulation of 5-HT4 receptors and the blockade of mGluR2/3 ones both activated 5-HT impulse flow, effects also suppressed by mPFC lesion. The combination of spadin with the 5-HT4 agonist RS 67333 paradoxically reduced 5-HT firing, an effect reversed by acutely administering the 5-HT1A agonist flesinoxan. It also had a robust synergetic effect on the expression of Zif268 within the DRN. Together, these results strongly suggest that 5-HT neurons underwent a state of depolarization block, and that the mechanisms underlying the influences exerted by spadin and RS 67333 are additive and independent from each other. In contrast, the mGluR2/3 antagonist LY 341495 occluded the effect of spadin, showing that it likely depends on mPFC TREK-1 channels coupled to mGluR2/3 receptors. These in vivo electrophysiological data were confirmed by in vitro Ca(2+) cell imaging performed in cultured cortical neurons. Altogether, our results indicate that spadin, as a natural compound, constitutes a very good candidate to explore the "glutamatergic path" of fast-acting AD research. In addition, they provide the first evidence of 5-HT depolarization block, showing that the combination of 5-HT activators for strategies of AD augmentation should be performed with extreme caution.

Moha ou Maati|Hamid|H|
Bourcier-Lucas|Céline|C|
Veyssiere|Julie|J|
Kanzari|Ameni|A|
Heurteaux|Catherine|C|
Borsotto|Marc|M|
Haddjeri|Nasser|N|
Lucas|Guillaume|G|

D018691:Excitatory Amino Acid Antagonists

D024683:Potassium Channels, Tandem Pore Domain

D058828:Serotonin 5-HT4 Receptor Agonists

Spadin
Medial prefrontal cortex
5-HT neurons
5-HT4 receptors
mGluR2/3 receptors
5-HT depolarization block


The construction and testing of the portable Hg(2+) ultrasonic calibrator for the control of mercury speciation systems.

Abstract: During fuel combustion mercury, as Hg(0) and Hg(2+) forms, is emitted to the atmosphere. Effective reduction of mercury emission requires applying speciation systems for emission control and research. An important part of all mercury determination and speciation systems are the calibrators. Calibrators are responsible for the accuracy of mercury determination and, in consequence, the effective reduction of mercury emission. The aim of the work was to construct a portable HgCl2 calibrator. The purpose of the device was the control of mercury speciation systems for continuous measurements and study of HgCl2 sorption. As a result of previously conducted research, the portable Hg(2+) ultrasonic calibrator was designed, constructed and tested. The ultrasonic calibrator generates a stable stream of HgCl2 (RSD=2.8% for CHg=28µg/m(3)). The correlation between theoretical and reading concentration of HgCl2 was R(2)=0.9983. The average recovery of HgCl2 was 95%. The advantages of the ultrasonic Hg(2+) calibrator are: high accuracy and selectivity, low pressure of HgCl2 stream and very low cost of production. The calibrator was successfully tested, both in the laboratory and in the power plant, during a preliminary study on HgCl2 sorption on a fly ash filter.

Ultrasonic calibrator
Mercury speciation
Flue gases
HgCl(2)


Non-Contact Heart Rate and Blood Pressure Estimations from Video Analysis and Machine Learning Modelling Applied to Food Sensory Responses: A Case Study for Chocolate.

Abstract: Traditional methods to assess heart rate (HR) and blood pressure (BP) are intrusive and can affect results in sensory analysis of food as participants are aware of the sensors. This paper aims to validate a non-contact method to measure HR using the photoplethysmography (PPG) technique and to develop models to predict the real HR and BP based on raw video analysis (RVA) with an example application in chocolate consumption using machine learning (ML). The RVA used a computer vision algorithm based on luminosity changes on the different RGB color channels using three face-regions (forehead and both cheeks). To validate the proposed method and ML models, a home oscillometric monitor and a finger sensor were used. Results showed high correlations with the G color channel (R² = 0.83). Two ML models were developed using three face-regions: (i) Model 1 to predict HR and BP using the RVA outputs with R = 0.85 and (ii) Model 2 based on time-series prediction with HR, magnitude and luminosity from RVA inputs to HR values every second with R = 0.97. An application for the sensory analysis of chocolate showed significant correlations between changes in HR and BP with chocolate hardness and purchase intention.

Gonzalez Viejo|Claudia|C|
Fuentes|Sigfredo|S|0000-0002-0377-5085
Torrico|Damir D|DD|
Dunshea|Frank R|FR|0000-0003-3998-1240

heart rate
blood pressure
machine learning modelling
computer vision
non-intrusive sensors


Skeletal Muscle Myofibrillar Protein Abundance Is Higher in Resistance-Trained Men, and Aging in the Absence of Training May Have an Opposite Effect.

Abstract: Resistance training generally increases skeletal muscle hypertrophy, whereas aging is associated with a loss in muscle mass. Interestingly, select studies suggest that aging, as well as resistance training, may lead to a reduction in the abundance of skeletal muscle myofibrillar (or contractile) protein (per mg tissue). Proteomic interrogations have also demonstrated that aging, as well as weeks to months of resistance training, lead to appreciable alterations in the muscle proteome. Given this evidence, the purpose of this small pilot study was to examine total myofibrillar as well as total sarcoplasmic protein concentrations (per mg wet muscle) from the vastus lateralis muscle of males who were younger and resistance-trained (denoted as YT, n = 6, 25 ± 4 years old, 10 ± 3 self-reported years of training), younger and untrained (denoted as YU, n = 6, 21 ± 1 years old), and older and untrained (denoted as OU, n = 6, 62 ± 8 years old). The relative abundances of actin and myosin heavy chain (per mg tissue) were also examined using SDS-PAGE and Coomassie staining, and shotgun proteomics was used to interrogate the abundances of individual sarcoplasmic and myofibrillar proteins between cohorts. Whole-body fat-free mass (YT > YU = OU), VL thickness (YT > YU = OU), and leg extensor peak torque (YT > YU = OU) differed between groups (p < 0.05). Total myofibrillar protein concentrations were greater in YT versus OU (p = 0.005), but were not different between YT versus YU (p = 0.325). The abundances of actin and myosin heavy chain were greater in YT versus YU (p < 0.05) and OU (p < 0.001). Total sarcoplasmic protein concentrations were not different between groups. While proteomics indicated that marginal differences existed for individual myofibrillar and sarcoplasmic proteins between YT versus other groups, age-related differences were more prominent for myofibrillar proteins (YT = YU > OU, p < 0.05: 7 proteins; OU > YT = YU, p < 0.05: 11 proteins) and sarcoplasmic proteins (YT = YU > OU, p < 0.05: 8 proteins; OU > YT&YU, p < 0.05: 29 proteins). In summary, our data suggest that modest (~9%) myofibrillar protein packing (on a per mg muscle basis) was evident in the YT group. This study also provides further evidence to suggest that notable skeletal muscle proteome differences exist between younger and older humans. However, given that our n-sizes are low, these results only provide a preliminary phenotyping of the reported protein and proteomic variables.

myofibrillar protein
aging
resistance training
proteomics
sarcoplasmic protein


Identifying Distinct Latent Classes of Adverse Childhood Experiences Among US Children and Their Relationship with Childhood Internalizing Disorders.

Abstract: This study aimed to determine the relationship between latent classes of adverse childhood experience (ACEs) and internalizing disorders (anxiety and depression) among US children. The 2016 National Survey of Children's Health data for children aged 6-17 was used. Latent class analysis was performed to identify distinct sub-types of ACE exposures and survey-weighted logistic regression models were employed to determine whether these classes were associated with any or comorbid childhood internalizing disorders, after controlling for meaningful covariates. Four latent classes were identified: income hardship, divorce, mental health or substance abuse exposure, and high ACEs overall. Children in three of the four classes were significantly more likely to have any childhood internalizing disorder when compared to children reporting no ACEs, while children in all classes were significantly more likely to have a comorbid history of anxiety and depression. Thus, children exposed to ACEs should receive necessary mental health screenings and treatments.

Anxiety
Depression
Mental health
Adverse childhood experience classes
Child health


Neonatal aphakia is associated with altered levels of dopamine metabolites in the non-human primate retina.

Abstract: Neonatal aphakia is associated with retardation of the axial elongation of the neonatal eye. In contrast, form deprivation increases axial elongation, an effect that has been associated with decreased retinal dopamine metabolism. The present investigation was conducted to test the hypothesis that neonatal aphakia induces an effect on the levels of retinal dopamine opposite to form deprivation. Lensectomy and vitrectomy were performed on the right eyes of rhesus monkeys at approximately 1 week of age; their left eyes were unmanipulated. Axial length was measured by A-scan ultrasonography. Prior to surgery, mean axial length of the right and left eyes was identical. Following lens removal, both eyes continued to elongate, however the aphakic eyes elongated at a slower rate resulting in a significant shorter axial length compared to that of the unmanipulated eye. Removal of the crystalline lens had no effect on steady-state dopamine levels in either central or peripheral retina. However, levels of the dopamine metabolites, 3,4-dihydroxyphenylacetic acid and homovanillic acid were significantly elevated in central retina, but not in the peripheral retina of aphakic eyes. Our results support the hypothesis that dopamine is a component of the retinal signaling pathways that are involved in the regulation of eye growth and emmetropization.

Iuvone|P Michael|PM|
Haque|Rashidul|R|
Fernandes|Alcides|A|
Lambert|Scott R|SR|

D002851:Chromatography, High Pressure Liquid

Primate
Retina
Eye growth
Emmetropization
Neuromodulators


A randomized controlled trial of uterine exteriorization versus in situ repair of the uterine incision during cesarean delivery.

Abstract:
OBJECTIVE
To compare extra-abdominal repair of the uterine incision at cesarean delivery with in situ repair.

METHODS
The present study was a double-blind randomized controlled trial conducted at a university hospital in Egypt during 2012-2013, and included women with an indication for cesarean delivery. Extra-abdominal repair was used in group 1 (n=500) and in situ repair in group 2 (n=500). The primary outcome measure was the surgery duration.

RESULTS
Surgery duration was significantly longer in group 1 than group 2 (49.9±2.3 minutes vs 39.9±1.8 minutes; P<0.001). More patients in group 1 than in group 2 had postoperative moderate-to-severe pain (165 [33.0%] vs 115 [23.0%]; P=0.001) and needed additional postoperative analgesia (100 [20.0%] vs 50 [10.0%]; P<0.001). Moreover, mean time to bowel movement was longer in group 1 than in group 2 (17.0±2.7 hours vs 14.0±1.9 hours; P<0.001).

CONCLUSION
In situ uterine closure is more advantageous than extra-abdominal repair in terms of surgery duration, postoperative pain and need for additional analgesia, and return of bowel movement. ClinicalTrials.gov:NCT01723605.

Exteriorization
In situ repair
Cesarean delivery
Uterine repair site


Development of an in vitro ocular test system for the prediction of all three GHS categories.

Abstract: In the present study we considered a new approach that allows the individual quantification of damages induced in the epithelium and stroma of an in vitro hemi-cornea model after chemical treatment. We aimed at a stand-alone test system for classification according to the classification of the globally harmonized system of classification and labelling of chemicals (GHS). We have modified a previously developed 3D hemi-cornea model by the insertion of a collagen membrane between epithelium and stroma. This membrane allows the separation and independent assessment of these compartments after topical exposure to potential eye irritants. The cell viability quantified by MTT assay was used as the toxicological endpoint. The prediction model based on the results obtained from 30 test chemicals uses a single exposure period and the combination of cut-off values in tissue viability from both epithelium and stroma. The in vitro-in vivo concordance of the test system is 77%. All of the GHS category 1, 80% of the GHS category 2 and 50% of the GHS not categorized chemicals are predicted correctly. In conclusion, the test system predicts and discriminates GHS category 1 and GHS category 2 chemicals, but is over-predictive for GHS not categorized materials.

Bartok|M|M| Gabel|D|D| Zorn-Kruppa|M|M| Engelke|M|M|

Eye irritation
Prediction model
GHS classification
Human hemi-cornea model
Predictive capacity


Autologous intratympanic blood patch for presumed perilymphatic fistulas.

Abstract:
OBJECTIVE
To assess an alternative to bed rest and surgery for suspected perilymphatic fistulas using intratympanic blood injections.

METHOD
A review was conducted of patients' history, physical and audiometric data, before and after treatment by intratympanic blood injections performed from 2009 to 2015.

RESULTS
Twelve ears were identified, with trauma associated with air travel, water sports or nose blowing. Ten of these cases had hearing loss, six had vestibular symptoms. Four cases had audiological and vestibular symptoms, two had vestibular symptoms only, and six had audiological symptoms only. Time-to-treat varied from 1 day to 30 days. Magnetic resonance imaging scans were obtained for five cases. Ten cases received steroids. Six out of seven cases showed improvement of hearing loss. Five cases showed positive fistula test results, four with documented resolution. Seven cases had full resolution of all symptoms, four had near-full resolution and one had no improvement.

CONCLUSION
Intratympanic blood injections offer an effective alternative to conservative or surgical therapy. Advantages include sooner time-to-treat, lower financial costs and decreased psychosocial burdens. It allows a more flexible and liberal use of a potential definite treatment for perilymphatic fistula.

Blood Fistula Injections Hearing Barotrauma Dizziness Tinnitus


Goji berry (Lycium barbarum L.) juice reduces lifespan and premature aging of Caenorhabditis elegans: Is it safe to consume it?

Abstract: Goji berry fruit is considered a healthy food. However, studies on its effects on aging and safety are rare. This study is the first to evaluate the effects of goji berry juice (GBJ) on oxidative stress, metabolic markers, and lifespan of Caenorhabditis elegans. GBJ caused toxicity, reduced the lifespan of C. elegans by 50%, and increased the reactive oxygen species (ROS) production by 45-50% at all tested concentrations (1-20 mg/µL) of GBJ. Moreover, the highest concentration of GBJ increased lipid peroxidation by 80% and altered the antioxidant enzymes. These effects could be attributed to a pro-oxidant effect induced by GBJ polyphenols and carotenoids. Moreover, GBJ increased lipofuscin, glucose levels, number of apoptotic bodies, and lipase activity. The use of mutant strains demonstrated that these effects observed in the worms treated with GBJ were not associated with the Daf-16/FOXO or SKN-1 pathways. Our findings revealed that GBJ (mainly the highest concentration) exerted toxic effects and promoted premature aging in C. elegans. Therefore, its consumption should be carefully considered until further studies in mammals are conducted.

de Freitas Rodrigues|Cristiane|C|
Ramos Boldori|Jean|J|
Valandro Soares|Marcell|M|
Somacal|Sabrina|S|
Emanuelli|Tatiana|T|
Izaguirry|Aryele|A|
Weber Santos Cibin|Francielli|F|
Rossini Augusti|Paula|P|
Casagrande Denardin|Cristiane|C|

Oxidative stress
Antioxidant enzymes
Polyphenols
Lipofuscin
Apoptosis


Cucumber Ribosomal Protein CsRPS21 Interacts With P22 Protein of Cucurbit Chlorotic Yellows Virus.

Abstract: Cucurbit chlorotic yellows virus (CCYV) is a cucurbit-infecting crinivirus. RNA silencing can be initiated as a plant defense against viruses. Viruses encode various RNA silencing suppressors to counteract antiviral silencing. P22 protein encoded by RNA1 of CCYV is a silencing suppressor, but its mechanism of action remains unclear. In this study, the cucumber ribosomal-like protein CsRPS21 was found to interact with P22 protein in vitro and in vivo. A conserved CsRPS21 domain was indispensable for its nuclear localization and interaction with P22. Transient expression of CsRPS21 in Nicotiana benthamiana leaves interfered with P22 accumulation and inhibited P22 silencing suppressor activity. CsRPS21 expression in N. benthamiana protoplasts inhibited CCYV accumulation. Increasing numbers of ribosomal proteins are being found to be involved in viral infections of plants. We identified a P22-interacting ribosomal protein, CsRPS21, and uncovered its role in early viral replication and silencing suppressor activity. Our study increases knowledge of the function of ribosomal proteins during viral infection.

Yang|Xue|X| Wei|Ying|Y| Shi|Yajuan|Y| Han|Xiaoyu|X| Chen|Siyu|S| Yang|Lingling|L| Li|Honglian|H| Sun|Bingjian|B| Shi|Yan|Y|

ribosomal protein
P22
cucurbit chlorotic yellows virus
silencing suppressor
virus accumulation


Origin of major ions in monthly rainfall events at the Bamenda Highlands, Northwest Cameroon.

Abstract: Rainwater characteristics can reveal emissions from various anthropogenic and natural sources into the atmosphere. The physico-chemical characteristics of 44 monthly rainfall events (collected between January and December 2012) from 4 weather stations (Bamenda, Ndop plain, Ndawara and Kumbo) in the Bamenda Highlands (BH) were investigated. The purpose was to determine the sources of chemical species, their seasonal inputs and suitability of the rainwater for drinking. The mean pH of 5 indicated the slightly acidic nature of the rainwater. Average total dissolved solids (TDS) were low (6.7 mg/L), characteristic of unpolluted atmospheric moisture/air. Major ion concentrations (mg/L) were low and in the order K(+) > Ca(2+) > Mg(2+) > Na(+) for cations and NO3(-)≫HCO3(-)>SO4(2-)>Cl(-)>PO4(3-)>F(-) for anions. The average rainwater in the area was mixed Ca-Mg-SO4-Cl water type. The Cl(-)/Na(+) ratio (1.04) was comparable to that of seawater (1.16), an indication that Na(+) and Cl(-) originated mainly from marine (Atlantic Ocean) aerosols. High enrichments of Ca(2+), Mg(2+) and SO(2-)4 to Na(+) ratios relative to seawater ratios (constituting 44% of the total ions) demonstrated their terrigenous origin, mainly from Saharan and Sahelian arid dusts. The K(+)/Na(+) ratio (2.24), which was similar to tropical vegetation ash (2.38), and NO3(-) was essentially from biomass burning. Light (< 100 mm) pre-monsoon and post-monsoon convective rains were enriched in major ions than the heavy (> 100 mm) monsoon rains, indicating a high contribution of major ions during the low convective showers. Despite the acidic nature, the TDS and major ion concentrations classified the rainwater as potable based on the WHO guidelines.

Wirmvem|Mengnjo J|MJ|
Ohba|Takeshi|T|
Fantong|Wilson Y|WY|
Ayonghe|Samuel N|SN|
Hogarh|Jonathan N|JN|
Suila|Justice Y|JY|
Asaah|Asobo Nkengmatia E|AN|
Ooki|Seigo|S|
Tanyileke|Gregory|G|
Hell|Joseph V|JV|

Bamenda Highlands
Cameroon
drinking-water
rainwater chemistry
tropical atmosphere


Diversity of arsenite oxidizing bacterial communities in arsenic-rich deltaic aquifers in West Bengal, India.

Abstract: High arsenic (As) concentration in groundwater has affected human health, particularly in South-East Asia putting millions of people at risk. Biogeochemical cycling of As carried out by different bacterial groups are suggested to control the As fluxes in aquifers. A functional diversity approach in link with As precipitation was adopted to study bacterial community structures and their variation within the As contaminated Bengal Delta Plain (BDP) aquifers of India. Groundwater samples collected from two shallow aquifers in Karimpur II (West Bengal, India), during years 2010 and 2011, were investigated to trace the effects immediately after monsoon period (precipitation) on community structure and diversity of bacterial assemblages with a focus on arsenite oxidizing bacterial phyla for two successive years. The study focused on amplification, clone library generation and sequencing of the arsenite oxidase large sub-unit gene aioA and 16S rRNA marker, with respect to changes in elemental concentrations. New set of primers were designed to amplify the aioA gene as a phylogenetic marker to study taxonomically diverse arsenite oxidizing bacterial groups in these aquifers. The overall narrow distribution of bacterial communities based on aioA and 16S rRNA sequences observed was due to poor nutrient status and anoxic conditions in these As contaminated aquifers. Proteobacteria was the dominant phylum detected, within which Acidovorax, Hydrogenophaga, Albidiferax, Bosea, and Polymorphum were the major arsenite oxidizing bacterial genera based on the number of clones sequenced. The structure of bacterial assemblages including those of arsenite oxidizing bacteria seems to have been affected by increase in major elemental concentrations (e.g., As, Fe, S, and Si) within two sampling sessions, which was supported by statistical analyses. One of the significant findings of this study is detection of novel lineages of 16S rRNA-like bacterial sequences indicating presence of indigenous bacterial communities BDP wells that can play important role in biogeochemical cycling of elements including As.

arsenite oxidation
aquifer
Arsenic
aioA gene
phylogeny


Anal sphincter function as assessed by 3D high definition anorectal manometry.

Abstract:
PURPOSE
High resolution anorectal manometry has been developed over the past years, as well as 3D high definition manometry (HDARM). However, the clinical impact of the results obtained with these new technologies remains to be determined. We thus analyzed various HDARM parameters of anal sphincter function and tested their capacity to discriminate between patients with constipation and those with fecal incontinence.

METHODS
One hundred and fourteen consecutive patients underwent the same HDARM protocol (Medtronic), including 2 short duration voluntary anal contractions (5seconds) and 1 sustained (as long as possible) contraction. Various parameters evaluating the anal sphincter function were measured, based on automatic software analysis and Smartmouse™ item of the software; resting anal pressures, anal pressures and incremental pressures during voluntary squeeze and cough anal reflex. The ability of these parameters to discriminate between patients with fecal incontinence and chronic constipation was assessed using areas under the curves of ROC curves.

RESULTS
All parameters were highly correlated. The most discriminant variable was found to be the mean anal pressure during sustained squeeze. The 3D lambda aspect of the anal sphincter during voluntary contraction was as frequently absent in both groups of patients (13% in patients with chronic constipation, versus 23% in those with fecal incontinence, P=0.18). There was a significant correlation between the fecal incontinence Wexner score and the voluntary anal contraction variables.

CONCLUSIONS
Several parameters to assess the quality of voluntary anal contraction have been proposed. We observed with HDARM that the most discriminant parameter was the mean anal pressure during sustained squeeze. This may help to standardize and simplify HDARM protocols.

Mion|François|F| Garros|Aurélien|A| Subtil|Fabien|F| Damon|Henri|H| Roman|Sabine|S|

Anorectal manometry
Constipation
Fecal incontinence
Human
Sensitivity and specificity


Organophosphate pesticides and PON1 L55M in Parkinson's disease progression.

Abstract:
BACKGROUND
Parkinson's disease (PD) has motor and non-motor features that contribute to its phenotype and functional decline. Organophosphate (OP) pesticides and PON1 L55M, which influences OP metabolism, have been implicated in multiple mechanisms related to neuronal cell death and may influence PD symptom progression.

OBJECTIVE
To investigate whether ambient agricultural OP exposure and PON1 L55M influence the rate of motor, cognitive, and mood-related symptom progression in PD.

METHODS
We followed a longitudinal cohort of 246 incident PD patients on average over 5years (7.5years after diagnosis), repeatedly measuring symptom progression with the Mini-Mental State Exam (MMSE), Unified Parkinson's Disease Rating Scale (UPDRS), and Geriatric Depressive Scale (GDS). OP exposures were generated with a geographic information system (GIS) based exposure assessment tool. We employed repeated-measures regression to assess associations between OP exposure and/or PON1 L55M genotype and progression.

RESULTS
High OP exposures were associated with faster progression of motor (UPDRS β=0.24, 95% CI=-0.01, 0.49) and cognitive scores (MMSE β=-0.06, 95% CI=-0.11, -0.01). PON1 55MM was associated with faster progression of motor (UPDRS β=0.28, 95% CI=0.08, 0.48) and depressive symptoms (GDS β=0.07; 95% CI=0.01, 0.13). We also found the PON1 L55M variant to interact with OP exposures in influencing MMSE cognitive scores (β=-1.26, 95% CI=-2.43, -0.09).

CONCLUSION
Our study provides preliminary support for the involvement of OP pesticides and PON1 in PD-related motor, cognitive, or depressive symptom progression. Future studies are needed to replicate findings and examine whether elderly populations generally are similarly impacted by pesticides or PON1 55M genotypes.

Paul|Kimberly C|KC|
Sinsheimer|Janet S|JS|
Cockburn|Myles|M|
Bronstein|Jeff M|JM|
Bordelon|Yvette|Y|
Ritz|Beate|B|

Organophosphates
PON1
Parkinson's disease
Progression
Cognitive decline


Redirection: an extension of career during retirement.

Abstract:
PURPOSE OF THE STUDY
This study explores (a) whether retirees' formal volunteer experiences represent an extension of their career in the paid workforce; and (b) how this integration of life roles affects career self-concept, as interpreted through Donald Super's life-span, life-space theory of career development.

DESIGN AND METHODS
A survey was conducted involving a Canadian sample of 214 individuals aged 55-75 years to examine retirees' volunteer activities and their sense of self.

RESULTS
The results demonstrate the need to further develop Super's theory with the addition of a new developmental stage, which I am labeling "Redirection" to better reflect postretirement experiences. During "Redirection," retirees develop a "new self."

IMPLICATIONS
This study indicates that retirees experienced a new stage of "Redirection" and found new meaning through volunteer work during retirement. The results will be of interest to professionals and researchers focused on career development, older workers, and retirement.

Retirement
Donald Super
Career development
Volunteerism and civic engagement
Work (after retirement
occupation)


Exploring the utility of the Threshold of Toxicological Concern (TTC) as a screening approach for complex substances.

Abstract: The Threshold of Toxicological Concern (TTC) has been applied to assess chemical safety for use, particularly in the food safety area. Although the TTC was developed for application to an individual chemical structure, more recently this concept has been suggested for the assessment of combined exposures to multiple chemicals. This study evaluated the potential for applying the TTC to a specific type of co-exposure, that of a complex substance of variable composition which contains multiple constituents, following the World Health Organization/International Programme on Chemical Safety framework for risk assessment of combined exposure to multiple chemicals. The results indicated that the TTC threshold was lower (i.e., more conservative) than regulatory thresholds derived for the same substance or even its most toxic constituent, providing assurance that the TTC could meet the requirements for a conservative screening process. This case study indicates that the TTC concept can be a useful tool to screen for potential risks from complex substances, with the consideration of additional aspects such as variability in chemical constituents and their relative proportions within the substance.

Zaleski|R|R|
Embry|M|M|
McKee|R|R|
Teuschler|L K|LK|

Threshold of toxicological concern
Complex substances
Combined exposures
Multiple chemicals
Chemical mixtures
Human health risk assessment
Screening of toxic chemicals


In Vitro Study of Receptor-Mediated Silica Nanoparticles Delivery across Blood-Brain Barrier.

Abstract: A brain drug delivery system has been demonstrated by attaching lactoferrin (Lf) on the silica nanoparticles (Si NPs). The nanoparticle surface was modified with polyethylene glycol to reduce protein adsorption. The transport efficiency of Lf attached Si NPs was studied using an in vitro blood-brain barrier (BBB) model consisting of three distinct types of cells: endocytes, pericytes, and astrocytes. Transfer of NPs from the apical side to the basolateral side is observed. The results indicated that Lf attached Si NPs demonstrated enhanced transport efficiency across the BBB with size-dependence compared to bare Si NPs. The maximum transport efficiency of lactoferrin conjugated silica nanoparticle was observed for 25 nm diameter particles. This receptor-mediated transcytosis of Si NPs across the cerebral endothelial cells can be employed to deliver drugs and imaging probes to the brain.

D001812:Blood-Brain Barrier
D001921:Brain
D016503:Drug Delivery Systems
D053758:Nanoparticles
D011092:Polyethylene Glycols
D012822:Silicon Dioxide

silica nanoparticles
lactoferrin
transcytosis
blood−brain barrier
receptor


N-Docosahexanoylethanolamine Reduces Microglial Activation and Improves Hippocampal Plasticity in a Murine Model of Neuroinflammation.

Abstract: Chronic neuroinflammation is a common pathogenetic link in the development of various neurological and neurodegenerative diseases. Thus, a detailed study of neuroinflammation and the development of drugs that reduce or eliminate the negative effect of neuroinflammation on cognitive processes are among the top priorities of modern neurobiology. N-docosahexanoylethanolamine (DHEA, synaptamide) is an endogenous metabolite and structural analog of anandamide, an essential endocannabinoid produced from arachidonic acid. Our study aims to elucidate the pharmacological activity of synaptamide in lipopolysaccharide (LPS)-induced neuroinflammation. Memory deficits in animals were determined using behavioral tests. To study the effects of LPS (750 µg/kg/day, 7 days) and synaptamide (10 mg/kg/day, 7 days) on synaptic plasticity, long-term potentiation was examined in the CA1 area of acute hippocampal slices. The Golgi-Cox method allowed us to assess neuronal morphology. The production of inflammatory factors and receptors was assessed using ELISA and immunohistochemistry. During the study, functional, structural, and plastic changes within the hippocampus were identified. We found a beneficial effect of synaptamide on hippocampal synaptic plasticity and morphological characteristics of neurons. Synaptamide treatment recovered hippocampal neurogenesis, suppressed microglial activation, and significantly improved hippocampus-dependent memory. The basis of the phenomena described above is probably the powerful anti-inflammatory activity of synaptamide, as shown in our study and several previous works.

Tyrtyshnaia|Anna|A| Bondar|Anatoly|A| Konovalova|Sophia|S| Sultanov|Ruslan|R| Manzhulo|Igor|I|

N-docosahexanoylethanolamine
neuroinflammation
DHEA
synaptamide
long-term potentiation
neurogenesis
cytokines
dendrites
microglia


Co₃O₄/Al-ZnO Nano-composites: Gas Sensing Properties.

Abstract: In this paper, the gas sensing properties of metal oxide nano-powder composites are studied and modeled. The gas sensing properties of mixtures of two different metal oxide nanoparticles, prepared via low-cost routes, are investigated. The responses to both an oxidizing (NO₂) and a reducing gas (CO) are analyzed. The tested composites are obtained by mixing a different percentage of a p-type metal oxide, Co₃O₄, with moderate responses to NO₂ at about 200 °C and to CO at high temperature (above 260 °C), with n-type Al-doped ZnO, which is characterized by a large but unstable response towards NO₂ around 160 °C and a moderate response towards CO around 200 °C. In the oxides mixtures, p-n heterojunctions are formed by the juxtaposition of an n-type and a p-type grain in contact. Consequently, the electronic conductivity is modified and the obtained composite materials show novel characteristics with respect to the base materials. This indicates that predicting the behavior of the composites from those of their components is not possible and it suggests that the hetero-junction behavior has to be studied to understand the sensing properties of the composite materials. The obtained results indicate that the composites containing a significant amount of hetero-junctions exhibit a stable response to NO₂ at room temperature and significant responses towards CO at 160 °C.

Fort|Ada|A|
Panzardi|Enza|E|
Vignoli|Valerio|V|
Hjiri|Mokhtar|M|
Aida|Mohamed Salah|MS|
Mugnaini|Marco|M|
Addabbo|Tommaso|T|0000-0003-0168-9404

hetero-junctions
chemoresistors
gas sensors
metal oxides sensors
nano-materials


Are Occupational Complexity and Socioeconomic Position Related to Psychological Distress 20 Years Later?

Abstract:
OBJECTIVE
To assess occupational complexity in midlife in relation to psychological distress in older adulthood (69+ years) and explore the role of socioeconomic position.

METHOD
Baseline data from the Swedish Level of Living Survey and follow-up data from the Swedish Longitudinal Study of Living Conditions of the Oldest Old were combined, resulting in 20+ years of follow-up. Data were analyzed using ordered logistic regressions.

RESULTS
Higher occupational complexity was associated with less psychological distress 20 years later adjusted for age, sex, follow-up year, hours worked the year before baseline, and psychological distress at baseline. Higher socioeconomic position yielded the same pattern of results. Socioeconomic position partially accounted for the association between occupational complexity and psychological distress.

DISCUSSION
With social gradient not easily amenable to modification, efforts to increase engagement at work may offer a viable option to attenuate the influence of work environment on psychological distress later in life.

Darin-Mattsson|Alexander|A| Andel|Ross|R| Fors|Stefan|S| Kåreholt|Ingemar|I|

occupational complexity
socioeconomic position
psychological distress
old age
population based


Achyranthes japonica extracts supplementation to growing pigs positively influences growth performance, nutrient digestibility, fecal microbial shedding, and fecal gas emission.

Abstract:
OBJECTIVE
An experiment was conducted to investigate the effects of Achyranthes japonica extracts (AJE) on the growth performance, nutrient digestibility, fecal microbial shedding, and fecal gas emission of growing pigs.

METHODS
A total of 180 ([Landrace×Yorkshire]×Duroc) growing pigs with initial body weight (BW) of 23.94±1.54 kg were used in this study to investigate the effects of AJE as a feed additive. Dietary treatments included: i) CON (basal diet), ii) TRT1 (basal diet+0.05% AJE), and iii) TRT2 (basal diet+0.10% AJE).

RESULTS
As a result of the dietary supplementation of 0% to 0.10% AJE, a linear increase of BW (p<0.05) on d 21 and 42, a linear increase of average daily gain (ADG) (p<0.05) during d 21 to 42, a trend in linear increase of ADG (p<0.10) during d 0 to 21 and d 0 to 42, a linear increase of gain to feed ratio (G:F) (p<0.05) during d 0 to 42, and a tendency in the linear increase of G:F during d 21 to 42 were observed in this study. Additionally, dietary supplementation of 0% to 0.10% AJE had a linear increase (p<0.05) on the apparent total tract digestibility of dry matter (DM) and energy, a linear increase (p<0.05) on lactic acid bacteria counts, a tendency in reducing (linear effect, p<0.10) coliform bacteria counts, and a linear decrease (p<0.05) in excreta H2S emission content in growing pigs.

CONCLUSION
In conclusion, the results suggested that AJE had the potential to enhance growth performance, DM and energy digestibility, and fecal lactic acid bacteria counts, and decrease the fecal coliform bacteria counts and excreta H2S emission in growing pigs.

Liu|Xiao|X|
Lee|Sang In|SI|
Kim|In Ho|IH|

Achyranthes japonica Extracts
Growing Pigs
Growth Performance
Nutrient Digestibility
Fecal Microbial Shedding
Fecal Gas Emissions


Changes in hepcidin and reticulocyte hemoglobin equivalent levels in response to continuous erythropoietin receptor activator administration in hemodialysis patients: a randomized study.

Abstract: Inadequate iron availability limits the response to erythropoiesis-stimulating agents (ESA) and hepcidin is a key regulator of iron metabolism. However, there is little information concerning time-dependent changes in hepcidin in response to the change of accelerated iron demand due to ESA-induced erythropoiesis. In this study, iron-related parameters, including hepcidin levels, were explored in comparison to patients receiving continuous erythropoietin receptor activator (CERA) and epoetin beta (EPO) treatment. Ninety-four patients were randomized to receive monthly CERA (N = 47) or EPO three times/week (N = 47). After the titration period, hemoglobin levels and iron-related parameters were examined. Data for 71 patients were evaluated (CERA, N = 34; EPO, N = 37). Compared with EPO treatment, CERA treatment caused significant decreases within 1 week in hepcidin (-93.5 ± 46.9 vs. -1.3 ± 38.3 ng/mL, P < 0.01), reticulocyte hemoglobin equivalent (Ret-He) (-4.03 ± 2.64 vs. -1.13 ± 1.41 pg, P < 0.01), ferritin (-58.9 ± 30.5 vs. -12.2 ± 23.8 ng/mL, P < 0.01) and transferrin saturation (-13.2 ± 9.1 vs. 1.0 ± 11.9%, P < 0.01) and significant increases within 2 weeks in the levels of hemoglobin (0.42 ± 0.38 vs. -0.02 ± 0.48 g/dL, P < 0.01). In conclusion, hepcidin, Ret-He, ferritin and transferrin saturation levels decreased within 1 week and hemoglobin increased within 2 weeks after CERA administration. Time course of iron-related parameters including hepcidin demonstrated accelerated iron utilization appropriately according to ESA-induced erythropoiesis.

Kakimoto-Shino|Midori|M| Toya|Yoshiyuki|Y| Kuji|Tadashi|T| Fujikawa|Tetsuya|T| Umemura|Satoshi|S|

Hepcidin
Hemodialysis
Anemia
Epoetin beta pegol
Erythropoiesis stimulating agents


Ultrathin Crystalline Covalent-Triazine-Framework Nanosheets with Electron Donor Groups for Synergistically Enhanced Photocatalytic Water Splitting.

Abstract: Ultrathin nanosheets have great potential for photocatalytic applications, however, suffer from enlarged band gap and narrowed visible-light-responsive range due to the quantum confinement effect. Herein, we report a novel redox strategy for efficient preparation of ultrathin crystalline amide-functionalized covalent-triazine-framework nanosheets (CTF NSs) with enhanced visible light absorption. The CTF NSs exhibited photocatalytic hydrogen (512.3 μmol h-1 ) and oxygen (12.37 μmol h-1 ) evolution rates much higher than that of pristine bulk CTF. Photocatalytic overall water splitting could be achieved with efficient stoichiometric H2 (5.13 μmol h-1 ) and O2 (2.53 μmol h-1 ) evolution rates under visible light irradiation. Experimental and theoretical analysis revealed that introduction of amide groups as electron donor optimized the band structure and improve its visible-light absorption, hydrophilicity and carrier separation efficiency, thus resulting in the enhanced photocatalytic performance. The well-dispersed CTF NSs could be easily cast onto a support as a thin film device and demonstrate excellent photocatalytic activity (25.7 mmol h-1  m-2 for hydrogen evolution).

photocatalytic water splitting
redox strategy
covalent triazine framework
electron donor effect
ultrathin crystalline nanosheets


Positive affect moderates the effect of negative affect on cardiovascular disease-related hospitalizations and all-cause mortality after cardiac rehabilitation.

Abstract:
BACKGROUND
Little is known as to whether negative emotions adversely impact the prognosis of patients who undergo cardiac rehabilitation. We prospectively investigated the predictive value of state negative affect (NA) assessed at discharge from cardiac rehabilitation for prognosis and the moderating role of positive affect (PA) on the effect of NA on outcomes.

METHODS
A total of 564 cardiac patients (62.49 ± 11.51) completed a comprehensive three-month outpatient cardiac rehabilitation program, filling in the Global Mood Scale (GMS) at discharge. The combined endpoint was cardiovascular disease (CVD)-related hospitalizations plus all-cause mortality at follow-up. Cox regression models estimated the predictive value of NA, as well as the moderating influence of PA on outcomes. Survival models were adjusted for sociodemographic factors, traditional cardiovascular risk factors, and severity of disease.

RESULTS
During a mean follow-up period of 3.4 years, 71 patients were hospitalized for a CVD-related event and 15 patients died. NA score (range 0-20) was a significant and independent predictor (hazard ratio (HR) 1.091, 95% confidence interval (CI) 1.012-1.175; p = 0.023) with a three-point higher level in NA increasing the relative risk by 9.1%. Furthermore, PA interacted significantly with NA (p < 0.001). The relative risk of poor prognosis with NA was increased in patients with low PA (p = 0.012) but remained unchanged in combination with high PA (p = 0.12).

CONCLUSION
The combination of NA with low PA was particularly predictive of poor prognosis. Whether reduction of NA and increase of PA, particularly in those with high NA, improves outcome needs to be tested.

Meyer|Fiorenza Angela|FA|
von Känel|Roland|R|
Saner|Hugo|H|
Schmid|Jean-Paul|JP|
Stauber|Stefanie|S|

positive affect
negative affect
mortality
cardiac rehabilitation
Cardiovascular disease
prospective longitudinal study


Comprehensive Evaluation of Gene Expression in Negative and Positive Trigger-based Targeting Niosomes in HEK-293 Cell Line.

Abstract: An efficient gene delivery system has some critical factors that enhance the efficiency of nanocarrier. These factors are low production cost, high bioavailability, high encapsulation efficiency, controllable release, and targeting ability. Niosome (the nonionic surfactant vesicles) was considered as a promising gene delivery system. Niosome can increase stability and uptake of active agents. We used all mentioned factors in one optimized formulation entitled plasmid- loaded magnetic niosomes (PMN). To increase the bioavailability of niosomes, we used ergosterol (a natural lipid) instead of cholesterol in structure of niosome. Also, cetyl trimethyl ammonium bromide (CTAB) in different concentrations was used to improve encapsulation of plasmid and compared to niosomes that did not have CTAB (negative niosome). Afterward, magnetic nanoparticle (Fe3O4@SiO2) was synthesized and loaded into niosome to obtain targeting ability. Prepared formulations were evaluated regarding size, zeta potential, morphology, encapsulation of magnetic nanoparticles and plasmid (Pm-cherry-N1), release rate, and transfection efficiency. Results demonstrated that optimum formulation (Nio/CTAB3%/Fe/P) has a nanometric size (118 ± 2.31 nm, positive zeta potential (+25 ± 0.67 mV), high loading of plasmid (72%), and good gene expression (35%). Interestingly, after applying a magnetic field below the cell plate, we obtained ac increased gene expression from 35% to 42%. These results showed that this new formulation would have a promising future and also can be used for delivering the other drugs and active agents.

Barani|Mahmood|M|
Torkzadeh-Mahani|Masoud|M|
Mirzaei|Mohammad|M|
Nematollahi|Mohammad Hadi|MH|

Gene expression
Targeting
Niosome
Plasmid
Magnetic nano particle


Analysis of type 2 diabetes and obesity genetic variants in Mexican Pima Indians: Marked allelic differentiation among Amerindians at HLA.

Abstract: Prevalence of diabetes and obesity in Mexican Pima Indians is low, while prevalence in US Pima Indians is high. Although lifestyle likely accounts for much of the difference, the role of genetic factors is not well explored. To examine this, we genotyped 359 single nucleotide polymorphisms, including established type 2 diabetes and obesity variants from genome-wide association studies (GWAS) and 96 random markers, in 342 Mexican Pimas. A multimarker risk score of obesity variants was associated with body mass index (BMI; β = 0.81 kg/m2 per SD, P = 0.0066). The mean value of the score was lower in Mexican Pimas than in US Pimas (P = 4.3 × 10-11 ), and differences in allele frequencies at established loci could account for approximately 7% of the population difference in BMI; however, the difference in risk scores was consistent with evolutionary neutrality given genetic distance. To identify loci potentially under recent natural selection, allele frequencies at 283 variants were compared between US and Mexican Pimas, accounting for genetic distance. The largest differences were seen at HLA markers (e.g., rs9271720, difference = 0.75, P = 8.7 × 10-9 ); genetic distances at HLA were greater than at random markers (P = 1.6 × 10-46 ). Analyses of GWAS data in 937 US Pimas also showed sharing of alleles identical by descent at HLA that exceeds its genomic expectation (P = 7.0 × 10-10 ). These results suggest that, in addition to the widely recognized balancing selection at HLA, recent directional selection may also occur, resulting in marked allelic differentiation between closely related populations.

Obesity
HLA
American Indians
Type 2 Diabetes Mellitus


Invasion of rhizobial infection thread by non-rhizobia for colonization of Vigna radiata root nodules.

Abstract: Legumes develop symbiotic relationships with Rhizobium by a complex exchange of signals. Despite the high specificity between symbiotic partners, the presence of non-rhizobial bacteria in root nodules has been reported. To investigate how these rhizobacteria enter root nodules, fluorescently tagged Pseudomonas fluorescens and Klebsiella pneumoniae were co-inoculated with host-nodulating Ensifer adhaerens to Vigna radiata seedlings and root hair infection was monitored using confocal microscopy at 5 days post inoculation. Pseudomonas fluorescens and K. pneumoniae invaded the root hair only when co-inoculated with E. adhaerens. Recovery of inoculated tagged strains and confirmation through CLSM and 16S rRNA gene sequencing confirmed that the test rhizobacteria occupied nodules. We hereby report with the help of confocal microscopy that rhizobacteria migrate along the length of host-nodulating rhizobial strain and become localized in root nodules. We further report isolation of eight non-rhizobial bacterial genera, predominantly Bacillus spp. and Paenibacillus spp., from nodules of field-grown V. radiata.

Pandya|Maharshi|M|
Kumar|Gattupalli Naresh|GN|
Rajkumar|Shalini|S|

D004269:DNA, Bacterial
D004275:DNA, Ribosomal
D007887:Fabaceae
D007711:Klebsiella pneumoniae
D056265:Microbial Interactions
D018613:Microscopy, Confocal
D008969:Molecular Sequence Data
D011551:Pseudomonas fluorescens
D012336:RNA, Ribosomal, 16S
D012230:Rhizobiaceae
D053204:Root Nodules, Plant
D017422:Sequence Analysis, DNA

infection thread
Vigna radiata
fluorescent tagging
Rhizobium legume specificity
confocal laser scanning microscopy
root nodule endophytes


Exploiting teeth as a model to study basic features of signaling pathways.

Abstract: Teeth constitute a classical model for the study of signaling pathways and their roles in mediating interactions between cells and tissues in organ development, homeostasis and regeneration. Rodent teeth are mostly used as experimental models. Rodent molars have proved fundamental in the study of epithelial-mesenchymal interactions and embryonic organ morphogenesis, as well as to faithfully model human diseases affecting dental tissues. The continuously growing rodent incisor is an excellent tool for the investigation of the mechanisms regulating stem cells dynamics in homeostasis and regeneration. In this review, we discuss the use of teeth as a model to investigate signaling pathways, providing an overview of the many unique experimental approaches offered by this organ. We discuss how complex networks of signaling pathways modulate the various aspects of tooth biology, and the models used to obtain this knowledge. Finally, we introduce new experimental approaches that allow the study of more complex interactions, such as the crosstalk between dental tissues, innervation and vascularization.

Pagella|Pierfrancesco|P|
Porcheri|Cristina|C|
Mitsiadis|Thimios A|TA|

signaling pathways
stem cells
tooth
developmental biology
epithelial–mesenchymal interactions
experimental embryology


The effects of previous statin treatment on plasma matrix metalloproteinase-9 level in Chinese stroke patients undergoing thrombolysis.

Abstract: It is unclear whether previous statin therapy influences the prognosis, hemorrhagic transformation, and plasma matrix metalloproteinases (MMP)-9 levels in Chinese stroke patients receiving intravenous thrombolysis. We conduct a prospective cohort study of 193 patients treated with intravenous thrombolysis. All the enrolled patients were divided into 2 groups (the control group and the statin group), according to the previous history of statin use. The plasma MMP-9 levels were detected before and at 6 hours, 12 hours, 24 hours, and 72 hours after intravenous thrombolysis. The clinical outcome of stroke was measured in terms of the functional outcome and occurrence of symptomatic intracerebral hemorrhage. The MMP-9 levels increased after thrombolysis in statin group and control group. No significant intergroup difference was found in the MMP-9 levels before and at 6 hours after thrombolysis, but the levels were significantly lower in the statin group than in the control group at 12, 24, and 72 hours (P < .001) after thrombolysis. Similarly, no significant intergroup difference was noted in the occurrence of symptomatic intracranial hemorrhage as was the case with the modified Rankin scale (assessed by the Mann-Whitney U test) at 7 days (P = .428) and 90 days (P = .419) after thrombolysis. Our results indicate that pretreatment with statin can inhibit the thrombolysis-induced increase in plasma MMP-9 levels but does not significantly affect the prognosis of acute ischemic stroke patients undergoing intravenous thrombolysis.

statin
matrix metalloproteinase-9
thrombolysis
prognosis
Ischemic stroke
prospective clinical cohort study


Brucellosis remains a neglected disease in the developing world: a call for interdisciplinary action.

Abstract:
BACKGROUND
Brucellosis is an endemic zoonotic disease in most of the developing world that causes devastating losses to the livestock industry and small-scale livestock holders. Infected animals exhibit clinical signs that are of economic significance to stakeholders and include reduced fertility, abortion, poor weight gain, lost draught power, and a substantial decline in milk production. In humans, brucellosis typically manifests as a variety of non-specific clinical signs. Chronicity and recurring febrile conditions, as well as devastating complications in pregnant women are common sequelae.

DISCUSSION
In regions where the disease is endemic, brucellosis has far-reaching and deleterious effects on humans and animals alike. Deeply entrenched social misconceptions and fear of government intervention contribute to this disease continuing to smolder unchecked in most of the developing world, thereby limiting economic growth and inhibiting access to international markets. The losses in livestock productivity compromise food security and lead to shifts in the cognitive competency of the working generation, influence the propagation of gender inequality, and cause profound emotional suffering in farmers whose herds are affected. The acute and chronic symptoms of the disease in humans can result in a significant loss of workdays and a decline in the socioeconomic status of infected persons and their families from the associated loss of income. The burden of the disease to society includes significant human healthcare costs for diagnosis and treatment, and non-healthcare costs such as public education efforts to reduce disease transmission.

CONCLUSION
Brucellosis places significant burdens on the human healthcare system and limits the economic growth of individuals, communities, and nations where such development is especially important to diminish the prevalence of poverty. The implementation of public policy focused on mitigating the socioeconomic effects of brucellosis in human and animal populations is desperately needed. When developing a plan to mitigate the associated consequences, it is vital to consider both the abstract and quantifiable effects. This requires an interdisciplinary and collaborative, or One Health, approach that consists of public education, the development of an infrastructure for disease surveillance and reporting in both veterinary and medical fields, and campaigns for control in livestock and wildlife species.

Franc|K A|KA|
Krecek|R C|RC|
Häsler|B N|BN|
Arenas-Gamboa|A M|AM|

Brucellosis
One health
Brucella
Global health (10 maximum)
Infectious disease
Zoonosis


Performance in adolescents of the two Japanese serum creatinine based estimated glomerular filtration rate equations, for adults and paediatric patients: A study of the Japan Renal Biopsy Registry and Japan Kidney Disease Registry from 2007 to 2013.

Abstract: There are two different Japanese serum creatinine-based equations for estimated glomerular filtration rate (eGFR), for adults and paediatric patients, with both equations deemed applicable to 18-year-old subjects. This study assessed the relative accuracy of the two equations in assessing eGFR in patients aged 18 years with chronic kidney disease. A total of 3042 patients (1679 males and 1363 females), aged 2-20 years, who were registered in the Japan Renal Biopsy Registry or the Japan Kidney Disease Registry between 2007 and 2013 were evaluated. eGFR values derived from formulas for children (Uemura's formula) and adults (the 3-variable Japanese formula) were calculated and compared, especially in patients aged 18 years. At all ages, but especially at younger ages, eGFR was significantly higher when calculated with the adult than the paediatric formula. This finding was also observed in 18-year-old adolescents with eGFR <90 mL/min per 1.73 m2 (P = 0.026). However, the mean difference between the two calculated eGFRs was only 2.79 mL/min per 1.73 m2 . These findings indicate that both creatinine-based equations used to calculate eGFR rate in Japanese children and adults with chronic kidney disease could be used to determine eGFR in 18-year-old subjects, with the difference between the two within permissible levels for clinical use.

Uemura|Osamu|O| Yokoyama|Hitoshi|H| Ishikura|Kenji|K| Gotoh|Yoshimitsu|Y| Sato|Hiroshi|H| Sugiyama|Hitoshi|H| Honda|Masataka|M| Matsuo|Seiichi|S|

estimated glomerular filtration rate
creatinine-based equation
paediatric formula
Japanese adolescents
adult formula


Yin Yang 1 Orchestrates a Metabolic Program Required for Both Neural Crest Development and Melanoma Formation.

Abstract: Increasing evidence suggests that cancer cells highjack developmental programs for disease initiation and progression. Melanoma arises from melanocytes that originate during development from neural crest stem cells (NCSCs). Here, we identified the transcription factor Yin Yang 1 (Yy1) as an NCSCs regulator. Conditional deletion of Yy1 in NCSCs resulted in stage-dependent hypoplasia of all major neural crest derivatives due to decreased proliferation and increased cell death. Moreover, conditional ablation of one Yy1 allele in a melanoma mouse model prevented tumorigenesis, indicating a particular susceptibility of melanoma cells to reduced Yy1 levels. Combined RNA sequencing (RNA-seq), chromatin immunoprecipitation (ChIP)-seq, and untargeted metabolomics demonstrated that YY1 governs multiple metabolic pathways and protein synthesis in both NCSCs and melanoma. In addition to directly regulating a metabolic gene set, YY1 can act upstream of MITF/c-MYC as part of a gene regulatory network controlling metabolism. Thus, both NCSC development and melanoma formation depend on an intricate YY1-controlled metabolic program.

Varum|Sandra|S|
Baggiolini|Arianna|A|
Zurkirchen|Luis|L|
Atak|Zeynep Kalender|ZK|
Cantù|Claudio|C|
Marzorati|Elisa|E|
Bossart|Raphaël|R|
Wouters|Jasper|J|
Häusel|Jessica|J|
Tuncer|Eylül|E|
Zingg|Daniel|D|
Veen|Dominiek|D|
John|Nessy|N|
Balz|Marcel|M|
Levesque|Mitchell P|MP|
Basler|Konrad|K|
Aerts|Stein|S|
Zamboni|Nicola|N|
Dummer|Reinhard|R|
Sommer|Lukas|L|

metabolism
neural crest
development
melanoma
YY1
protein synthesis
tumor initiation


Interferon therapies in small animals.

Abstract: Interferons (IFNs) are cytokines that play an important role in the immune response of animals and humans. A number of studies reviewed here have evaluated the use of human, canine and feline IFNs as treatments for infectious, inflammatory and neoplastic disease in dogs and cats. Recombinant canine IFN-γ is deemed an efficacious therapy for canine atopic dermatitis. Recombinant feline IFN-ω is effective against canine parvoviral enteritis and has also been recommended for canine atopic dermatitis. Based on limited evidence, recombinant canine IFN-α could be a topical treatment option for dogs with gingivitis and keratoconjunctivitis sicca. Conclusive evidence is lacking for other diseases and large randomised controlled trials are needed before IFNs can be recommended for other indications.


Primary malignant myelomatous pleural effusion.

Abstract: Primary malignant myelomatous pleural effusion (PMMPE) occurs in less than 1% of patients with multiple myeloma and is diagnosed either by visualization of plasma cells on cytology or by positive flow cytometry. The presence of immature plasma cells characterized by high nucleus to cytoplasm ratio, visible nucleolus and presence of Mott cells and Russell bodies are independent poor prognostic factors. The clinician should differentiate PMMPE from secondary pleural effusion as it is associated with a significantly worse prognosis and poor overall survival.

Mangla|Ankit|A|0000-0002-6789-4315
Agarwal|Nikki|N|
Kim|George J|GJ|
Catchatourian|Rosalind|R|

pleural effusion
multiple myeloma
Mott cells
Russell bodies


The efficacy and toxicity of chemotherapy in the elderly with advanced pancreatic cancer.

Abstract:
OBJECTIVES
FOLFIRINOX (FFX) or abraxane plus gemcitabine (AG)-based chemotherapy is used widely as firstline treatment for patients with pancreatic cancer. However, their use in the elderly is discouraged because of adverse events. More clinical data about the therapeutic response and tolerability to FFX or AG in elderly patents (over 70 years old) are required.

METHODS
Patients with advanced pancreatic cancer (n = 203; 131 metastatic pancreatic cancer patients (MPC) and 72 locally advanced pancreatic cancer patients (LAPC)) were treated using modified-FFX (mFFX) or AG and mFFX sequentially. The patients were grouped according to their age, patients below 70 years old and patients above 70 years old. The objective response rate (ORR), disease control rate (DCR), progression free survival (PFS), overall survival (OS) and adverse events were compared between the groups.

RESULTS
The ORRs in the elderly and in patients below 70 were similar (30.0% versus 32.3%). The median OS and PFS were also similar between the groups (mOS 13.3 m vs 12.7 m, p = 0.729, HR 0.874 (95% CI 0.5310 to 1.438); mPFS mPFS 10.6 m vs 10.3 m, p = 0.363, HR 0.800 (95% CI 0.4954 to 1.293)). However, the elderly patients suffered a higher incidence of severe adverse events (50% vs. 28.3%).

CONCLUSIONS
These data could provide guidance for chemotherapy use in elderly patients with advanced pancreatic cancer. Age did not affect treatment outcome; however, supportive treatment is very important for elderly patients receiving chemotherapy.

Li|Xiang|X| Huang|Da-Bing|DB| Zhang|Qi|Q| Guo|Cheng-Xiang|CX| Fu|Qi-Han|QH| Zhang|Xiao-Chen|XC| Tang|Tian-Yu|TY| Su|Wei|W| Chen|Yi-Wen|YW| Chen|Wei|W| Ma|Tao|T| Gao|Shun-Liang|SL| Que|Ri-Sheng|RS| Bai|Xue-Li|XL| Liang|Ting-Bo|TB|

D000971:Antineoplastic Combined Chemotherapy Protocols

Chemotherapy
Elderly
Abraxane plus gemcitabine
Tolerability
Modified-FOLFIRINOX


Programmed death-1 expression in cutaneous B-cell lymphoma.

Abstract:
BACKGROUND
Numbers of programmed death-1 (PD-1) positive T cells have prognostic significance in some types of nodal B-cell lymphomas, but data on PD-1 expression in cutaneous B-cell lymphoma (CBCL) are few. In this study we determined the expression and distribution of PD-1 on neoplastic B cells and reactive T cells in skin sections from primary CBCLs.

METHODS
By means of immunohistochemical staining, PD-1 expression was investigated in skin biopsies from 10 patients with primary cutaneous marginal zone lymphoma (PCMZL), 18 patients with primary cutaneous follicle center lymphoma (PCFCL) and 12 patients with primary cutaneous diffuse large B-cell lymphoma-leg type (PCDLBCL-LT).

RESULTS
Neoplastic B cells were negative for PD-1 in all cases, except for two cases of PCDLBCL-LT. The frequency of PD-1(+) T cells was significantly higher in PCFCL than in PCMZL and PCDLBCL-LT, accounting for 20, 10 and 3% of the total number of infiltrating cells, and 60, 20 and 15% of the total number of CD3(+) T cells, respectively.

CONCLUSIONS
PD-1 is rarely expressed by the neoplastic B cells in CBCL. High percentages of PD-1(+) T cells, particularly if found outside germinal centers, support a diagnosis of PCFCL.

Çetinözman|Fatma|F|
Koens|Lianne|L|
Jansen|Patty M|PM|
Willemze|Rein|R|

D061026:Programmed Cell Death 1 Receptor

cutaneous B-cell lymphoma
PD-1
follicular helper T cell
non-Hodgkin lymphoma


Fucoidan--a α-D-glucosidase inhibitor from Sargassum wightii with relevance to type 2 diabetes mellitus therapy.

Abstract: The present study was conducted to screen the α-d-glucosidase inhibitory activity of fucoidan extracted from Sargassum wightii collected at Mandapam coastal area, Tamil Nadu, India. Fucoidan was extracted from the sporophyll of S. wightii using ethanol, acetone and CaCl2 precipitation. The average yield was 1.8 ± 0.16% and the extracted fucoidan was found to contain 53 ± 0.52% of fucose and 36 ± 0.60% of sulphate. FT-IR, NMR and in vitro α-d-glucosidase activity of purified fucoidan were performed. Fucoidan at the concentration of 31.25, 62.5, 125 and 250 μg exhibited 19, 31, 38 and 71% inhibition against α-d-glucosidase respectively in a dose dependent manner. The IC50 value against α-D-glucosidase of fucoidan is found to be 132.9 μg which is more effective than that of acarbose (1mg). The diverse biological activities of Fucoidan include anticancer, anti inflammatory and antimicrobial but the α-d-glucosidase inhibitory activity of native fucoidan from S. wightii for type 2 diabetes therapy is first of its kind.

Vinoth Kumar|T|T|
Lakshmanasenthil|S|S|
Geetharamani|D|D|
Marudhupandi|T|T|
Suja|G|G|
Suganya|P|P|

D017550:Spectroscopy, Fourier Transform Infrared


Irradiation of pyrimidine in pure H2O ice with high-energy ultraviolet photons.

Abstract: The detection of nucleobases, the informational subunits of DNA and RNA, in several meteorites suggests that these compounds of biological interest were formed via astrophysical, abiotic processes. This hypothesis is in agreement with recent laboratory studies of irradiation of pyrimidine in H2O-rich ices with vacuum UV photons emitted by an H2-discharge lamp in the 6.9-11.3 eV (110-180 nm) range at low temperature, shown to lead to the abiotic formation of several compounds including the nucleobases uracil, cytosine, and thymine. In this work, we irradiated H2O:pyrimidine ice mixtures under astrophysically relevant conditions (14 K, ≤10(-9) torr) with high-energy UV photons provided by a synchrotron source in three different ranges: the 0(th) order light (4.1-49.6 eV, 25-300 nm), the He i line (21.2 eV, 58.4 nm), and the He ii line (40.8 eV, 30.4 nm). The photodestruction of pyrimidine was monitored with IR spectroscopy, and the samples recovered at room temperature were analyzed with liquid and gas chromatographies. Uracil and its precursor 4(3H)-pyrimidone were found in all samples, with absolute and relative abundances varying significantly from one sample to another. These results support a scenario in which compounds of biological interest can be formed and survive in environments subjected to high-energy UV radiation fields.

Nuevo|Michel|M|
Chen|Yu-Jung|YJ|
Hu|Wei-Jie|WJ|
Qiu|Jun-Ming|JM|
Wu|Shang-Ruei|SR|
Fung|Hok-Sum|HS|
Chu|Ching-Chi|CC|
Yih|Tai-Sone|TS|
Ip|Wing-Huen|WH|
Wu|C-Y Robert|CY|

Pyrimidine-Nucleobases-Interstellar ices-Cometary ices-High-energy photons-Molecular processes-Prebiotic chemistry.


The students' intentions and satisfaction with the field of study and university.

Abstract:
INTRODUCTION
The present study aimed to find an appropriate method to inform senior high school students to correctly select their academic field of study and their intentions.

METHODS
This is a descriptive-analytic and cross-sectional study. A verified questionnaire was given to a total of 2600 students selected by stratified random sampling method (ten different colleges and entrance year from the 1(st) to 4(th) are considered as the strata). The position of the present field of study (major) among the list of the fields in the entrance exam was asked. The students' methods of familiarity with different fields of study in Shiraz University of Medical Sciences (SUMS), the reasons for their selection, the students' motivation and insistence on studying in the same field and university were asked in the questionnaire. Data were analyzed using independent two samples t-test, Analysis of Variance (ANOVA) and Chi-Square test.

RESULTS
The most significant references for university field selection were high school teachers, the students' parents and the adjacency of university to one's living place. Also, the results revealed the good reputation of SUMS in the first year and its downward trend during the following years. 59.4% of the 1(st) year students were satisfied with their field of study and SUMS. 31.8% were satisfied with the university but not with their fields of study. 6.4% were dissatisfied with the university but not with their fields of study. 2% of the students were dissatisfied with both their fields of study and university. Dissatisfaction with SUMS and field of study increased little by little so that the results obtained among the students who had entered the university earlier (in the 4(th) year of their study) showed nearly 16.3% dissatisfaction with both the university and the study fields.

CONCLUSION
The methods for introducing the university are recommended to be revised.

Noorafshan|Ali|A|
Pourahmad|Saeedeh|S|
Sagheb|Mohammad Mahdi|MM|
Dehghani Nazhvani|Ali|A|
Dehshahri|Ali|A|
Abdollahi|Manijeh|M|
Mohebbi|Zeynab|Z|
Keshtkaran|Zahra|Z|
Ahmadi|Afsaneh|A|
Kavousipour|Somayeh|S|
Farahmand|Fariba|F|
Khorrami|Hamid Reza|HR|
Soltani|Robabeh|R|
Karbalay Doust|Saied|S|


Context-Dependent Functions of NANOG Phosphorylation in Pluripotency and Reprogramming.

Abstract: The core pluripotency transcription factor NANOG is critical for embryonic stem cell (ESC) self-renewal and somatic cell reprogramming. Although NANOG is phosphorylated at multiple residues, the role of NANOG phosphorylation in ESC self-renewal is incompletely understood, and no information exists regarding its functions during reprogramming. Here we report our findings that NANOG phosphorylation is beneficial, although nonessential, for ESC self-renewal, and that loss of phosphorylation enhances NANOG activity in reprogramming. Mutation of serine 65 in NANOG to alanine (S65A) alone has the most significant impact on increasing NANOG reprogramming capacity. Mechanistically, we find that pluripotency regulators (ESRRB, OCT4, SALL4, DAX1, and TET1) are transcriptionally primed and preferentially associated with NANOG S65A at the protein level due to presumed structural alterations in the N-terminal domain of NANOG. These results demonstrate that a single phosphorylation site serves as a critical interface for controlling context-dependent NANOG functions in pluripotency and reprogramming.

Saunders|Arven|A| Li|Dan|D| Faiola|Francesco|F| Huang|Xin|X| Fidalgo|Miguel|M| Guallar|Diana|D| Ding|Junjun|J| Yang|Fan|F| Xu|Yang|Y| Zhou|Hongwei|H| Wang|Jianlong|J|

pluripotency
reprogramming
self-renewal
iPSC
phospho-NANOG
post-translational modification
serine to alanine mutation


Influence of environmental and biological macromolecules on aggregation kinetics of nanoplastics in aquatic systems.

Abstract: Nanoplastics derived from degradation of micro- or macroplastics are emerging contaminants in aquatic environments, where their fate and transport as well as toxicity are affected by aggregation. This study employed time-resolved dynamic light scattering to investigate the aggregation kinetics of polystyrene nanoplastics (PSNPs) in the presence of four macromolecules (sodium alginate (SA), bovine serum albumin (BSA), extracellular polymeric substance (EPS), and Suwannee River humic acid (HA)) in solutions containing monovalent (NaCl) and divalent (CaCl2) salts at different pH. Our results showed that the macromolecules enhanced PSNP stability in NaCl solutions but destabilized PSNPs in CaCl2 solutions at pH 6. In NaCl solutions, macromolecules inhibited PSNP aggregation due to steric hindrance originated from macromolecular layer adsorbed on PSNPs. The strongest stabilization effect was observed for BSA having the greatest hydrodynamic adsorption layer thickness of 21.9 nm, followed by HA, EPS, and SA. In CaCl2 solutions, SA significantly destabilized PSNPs via alginate bridging with Ca2+, which enhanced with concentrations of SA and CaCl2. The destabilization effects of other three macromolecules in CaCl2 solutions were governed by the interplay among molecular bridging, charge screening, and steric hindrance. An increased pH in NaCl or CaCl2 solutions containing macromolecules all stabilized PSNPs due to elevated electrostatic repulsion, except that SA destabilized PSNPs in CaCl2 solutions via enhanced molecular bridging. The stabilization effect of macromolecules may also compete with the destabilization effect under seawater condition. This study suggested that PSNP aggregation in aquatic environments could be strongly affected by macromolecules and solution chemistry.

Liu|Yanjun|Y| Huang|Ziqing|Z| Zhou|Jini|J| Tang|Jie|J| Yang|Chen|C| Chen|Chengyu|C| Huang|Weilin|W| Dang|Zhi|Z|

D000077317:Extracellular Polymeric Substance Matrix

Steric hindrance
Adsorption
Molecular bridging
Colloidal stability
Electrical double layer compression
Nanoparticles