bluuebunny/crossref_metadata_2025_split huggingface dataset:
Reduced neurobehavioral functioning in agricultural workers and rural inhabitants exposed to pesticides in northern Chile and its association with blood biomarkers inhibition
Authors: Ramírez-Santana Muriel , Zúñiga-Venegas Liliana , Corral Sebastián , Roeleveld Nel , Groenewoud Hans , Van der Velden Koos , Scheepers Paul T. J. , Pancetti Floria 
Published: July 2020

Abstract
Background
Previous biomonitoring studies have shown that people in the rural population of Coquimbo, the major agricultural area in northern Chile are being occupationally and environmentally exposed to organophosphate/carbamate (OP/CB) pesticides. Given their harmful effects, this study had two aims; first, to evaluate the effect of cumulative or chronic exposure to OP/CB pesticides on the neurobehavioral performance of agricultural workers and rural inhabitants; second, to determine if changes in the neurobehavioral performance are associated to changes in blood biomarkers of OP/CB pesticides during the spray season, when exposure is higher.

Methods
For the first aim, a cross sectional study of neurobehavioral performance in adult volunteers (men and women, 18–50 years-old, right-handed) was carried out in the pre-spray season. Sampling was done by convenience and a questionnaire was used to categorize participants depending on their level of chronic exposure, as either: occupationally exposed (OE, n = 87), environmentally exposed (EE, n = 81), or non-exposed controls or reference group (RG, n = 100). A neurobehavioral test battery consisting of 21 tests to measure cognitive, motor and emotional state was applied. For the second aim, neurobehavioral measures were taken a second time from EE and OE groups during the spray season, and their exposure corroborated by blood-based biomarker inhibition.

Results
Lower neurobehavioral performance was observed in the pre-spray evaluation of EE and OE groups compared to the non-exposed, OE being the worst performing group. Seasonal exposure impaired performance in both exposure groups on all tests except those on attention and mood. Data modeling of the basal (pre-spray) measurements showed that the level of exposure was the best predictor of performance. During spraying, inhibition of BChE activity in the EE group was the best predictor of low performance in tests measuring logical, auditory and visual memory, inhibitory control of cognitive interference, constructional and planning abilities, executive functions, and motor speed and coordination.

Conclusion
Long-term occupational or environmental exposure to pesticides caused impairment in neurobehavioral functioning, which worsened during the spraying season, mainly in EE. BChE inhibition was the best predictor for seasonal neurobehavioral changes in EE.
Opioid agonist therapy uptake among people who inject drugs: the findings of two consecutive bio-behavioral surveillance surveys in Iran
Authors: Nakhaeizadeh Mehran , Abdolahinia Zahra , Sharifi Hamid , Mirzazadeh Ali , Haghdoost Ali Akbar , Shokoohi Mostafa , Baral Stefan , Karamouzian Mohammad , Shahesmaeili Armita 
Published: July 2020

Abstract
Background
Opioid agonist therapy (OAT) uptake has been associated with multiple positive health outcomes among people who inject drugs (PWID). This study evaluated the pattern of OAT uptake among PWID in two consecutive national bio-behavioral surveillance surveys (2010 and 2014) in Iran.

Methods
Data were obtained from two national bio-behavioral surveillance surveys (N2010 = 1783 and N2014 = 2166) implemented using convenience sampling at the harm reduction facilities and street venues in 10 geographically diverse urban centers across Iran. Multivariable logistic regression models were built to determine the correlates of OAT uptake for the 2014 survey, and adjusted odds ratios (AORs) along with 95% confidence intervals (CI) were reported.

Results
The prevalence of OAT uptake decreased from 49.2% in 2010 to 45.8% in 2014 (P value = 0.033). OAT uptake varied across the studied cities ranging from 0.0 to 69.3% in the 2010 survey and 3.2 to 75.5% in the 2014 survey. Ever being married (AOR = 1.40; 95% CI 1.12, 1.75), having a history of incarceration (AOR = 1.56; 95% CI 1.16, 2.09), and human immunodeficiency virus (HIV) sero-positivity (AOR = 1.63; 95% CI 1.08, 2.50) were associated with OAT uptake. Conversely, PWID who reported using only non-opioid drugs (AOR = 0.43; 95% CI 0.26, 0.71) and those who reported concurrent use of opioid and non-opioid drugs (AOR = 0.66; 95% CI 0.51, 0.86) were less likely to uptake OAT.

Conclusions
Although OAT uptake among PWID in Iran is above the 40% threshold defined by the World Health Organization, there remain significant disparities across urban settings in Iran. Importantly, the OAT services appear to be serving high-risk PWID including those living with HIV and those with a history of incarceration. Evaluating service integration including mental health, HIV and hepatitis C virus care, and other harm reduction services may support the optimization of health outcomes associated with OAT across Iran.
Histamine 2/3 receptor agonists alleviate perioperative neurocognitive disorders by inhibiting microglia activation through the PI3K/AKT/FoxO1 pathway in aged rats
Authors: Chen Yi-Nan , Sha Huan-Huan , Wang Yi-Wei , Zhou Qin , Bhuiyan Piplu , Li Na-Na , Qian Yan-Ning , Dong Hong-Quan 
Published: July 2020

AbstractBackgroundMicroglia, the principal sentinel immune cells of the central nervous system (CNS), play an extensively vital role in neuroinflammation and perioperative neurocognitive disorders (PND). Histamine, a potent mediator of inflammation, can both promote and prevent microglia-related neuroinflammation by activating different histamine receptors. Rat microglia express four histamine receptors (H1R, H2R, H3R, and H4R), among which the histamine 1 and 4 receptors can promote microglia activation, whereas the role and cellular mechanism of the histamine 2 and 3 receptors have not been elucidated. Therefore, we evaluated the effects and potential cellular mechanisms of histamine 2/3 receptors in microglia-mediated inflammation and PND.MethodsThis study investigated the role of histamine 2/3 receptors in microglia-induced inflammation and PND both in vivo and in vitro. In the in vivo experiments, rats were injected with histamine 2/3 receptor agonists in the right lateral ventricle and were then subjected to exploratory laparotomy. In the in vitro experiments, primary microglia were pretreated with histamine 2/3 receptor agonists before stimulation with lipopolysaccharide (LPS). Cognitive function, microglia activation, proinflammatory cytokine production, NF-κb expression, M1/M2 phenotypes, cell migration, and Toll-like receptor-4 (TLR4) expression were assessed.ResultsIn our study, the histamine 2/3 receptor agonists inhibited exploratory laparotomy- or LPS-induced cognitive decline, microglia activation, proinflammatory cytokine production, NF-κb expression, M1/M2 phenotype transformation, cell migration, and TLR4 expression through the PI3K/AKT/FoxO1 pathway.ConclusionBased on our findings, we conclude that histamine 2/3 receptors ameliorate PND by inhibiting microglia activation through the PI3K/AKT/FoxO1 pathway. Our results highlight histamine 2/3 receptors as potential therapeutic targets to treat neurological conditions associated with PND.
Muramyl dipeptide-mediated immunomodulation on monocyte subsets exerts therapeutic effects in a mouse model of Alzheimer’s disease
Authors: Fani Maleki Adham , Cisbani Giulia , Plante Marie-Michèle , Préfontaine Paul , Laflamme Nataly , Gosselin Jean , Rivest Serge 
Published: July 2020

Abstract
Background
Muramyl dipeptide (MDP) is a component derived from minimal peptidoglycan motif from bacteria, and it is a ligand for the NOD2 receptor. Peripheral administration of MDP converts Ly6Chigh into Ly6Clow monocytes. Previously, we have shown that Ly6Clow monocytes play crucial roles in the pathology of a mouse model of Alzheimer’s disease (AD). However, medications with mild immunomodulatory effects that solely target specific monocyte subsets, without triggering microglial activation, are rare.

Methods
Three months old APPswe/PS1 transgenic male mice and age-matched C57BL/6 J mice were used for high frequency (2 times/week) over 6 months and low frequency (once a week) over 3 months of intraperitoneally MDP (10 mg/kg) administrations. Flow cytometry analysis of monocyte subsets in blood, and behavioral and postmortem analyses were performed.

Results
Memory tests showed mild to a strong improvement in memory function, increased expression levels of postsynaptic density protein 95 (PSD95), and low-density lipoprotein receptor-related protein 1 (LRP1), which are involved in synaptic plasticity and amyloid-beta (Aβ) elimination, respectively. In addition, we found monocyte chemoattractant protein-1(MCP-1) levels significantly increased, whereas intercellular adhesion molecule-1(ICAM-1) significantly decreased, and microglial marker (Iba1) did not change in the treatment group compared to the control. In parallel, we discovered elevated cyclooxygenase-2 (COX2) expression levels in the treated group, which might be a positive factor for synaptic activity.

Conclusions
Our results demonstrate that MDP is beneficial in both the early phase and, to some extent, later phases of the pathology in the mouse model of AD. These data open the way for potential MDP-based medications for AD.
Differential expression of receptors mediating receptor-mediated transcytosis (RMT) in brain microvessels, brain parenchyma and peripheral tissues of the mouse and the human
Authors: Zhang Wandong , Liu Qing Yan , Haqqani Arsalan S. , Leclerc Sonia , Liu Ziying , Fauteux François , Baumann Ewa , Delaney Christie E. , Ly Dao , Star Alexandra T. , Brunette Eric , Sodja Caroline , Hewitt Melissa , Sandhu Jagdeep K. , Stanimirovic Danica B. 
Published: July 2020

AbstractReceptor-mediated transcytosis (RMT) is a principal pathway for transport of macromolecules essential for brain function across the blood–brain barrier (BBB). Antibodies or peptide ligands which bind RMT receptors are often co-opted for brain delivery of biotherapeutics. Constitutively recycling transferrin receptor (TfR) is a prototype receptor utilized to shuttle therapeutic cargos across the BBB. Several other BBB-expressed receptors have been shown to mediate transcytosis of antibodies or protein ligands including insulin receptor (INSR) and insulin-like growth factor-1 receptor (IGF1R), lipid transporters LRP1, LDLR, LRP8 and TMEM30A, solute carrier family transporter SLC3A2/CD98hc and leptin receptor (LEPR). In this study, we analyzed expression patterns of genes encoding RMT receptors in isolated brain microvessels, brain parenchyma and peripheral organs of the mouse and the human using RNA-seq approach. IGF1R, INSR and LRP8 were highly enriched in mouse brain microvessels compared to peripheral tissues. In human brain microvessels only INSR was enriched compared to either the brain or the lung. The expression levels of SLC2A1, LRP1, IGF1R, LRP8 and TFRC were significantly higher in the mouse compared to human brain microvessels. The protein expression of these receptors analyzed by Western blot and immunofluorescent staining of the brain microvessels correlated with their transcript abundance. This study provides a molecular transcriptomics map of key RMT receptors in mouse and human brain microvessels and peripheral tissues, important to translational studies of biodistribution, efficacy and safety of antibodies developed against these receptors.
Temperature and flow rate limit the optimal ex-vivo perfusion of the heart - an experimental study
Authors: Quader Mohammed , Torrado Juan Francisco , Mangino Martin J. , Toldo Stefano 
Published: July 2020

Abstract
Background
Ex-vivo heart perfusion can be utilized to study a variety of physiologic and molecular pathways in a controlled system outside of the body. It can also be used in clinical settings such as for organ preservation before transplantation. Myocardial oxygen consumption (MVO2) correlates with energy production in the myocardium and can also be used to determine the balance between the oxygen supply and demand of the perfused heart. This study sought to determine an ex-vivo perfusion rate that matches the metabolic demands of the heart according to different temperatures and solution compositions (with and without the addition of erythrocytes), a flow below which the supply of oxygen is not sufficient to maintain an aerobic state of the perfused heart (“DCRIT”).

Methods
Under general anesthesia, rat hearts were procured and preserved by perfusing with the University of Wisconsin Belzer machine perfusion system (UW Belzer MPS) solution saturated with 100% O2. The key elements of this solution include supraphysiological potassium (to stop the heartbeat and reduce the cellular metabolic demand), starch, gluconate and mannitol (to maintain cell wall integrity), glucose (to sustain basal metabolism), and glutathione (to scavenge free radicals). Three groups of rat hearts (n = 7) were randomly allocated to be perfused at 15 °C, 22 °C or 37 °C, at a varying flow index (FI) starting from a minimum of 380 mL/min/100 g to less than 50 mL/min/100 g, decreasing by 50 mL/min/100 g at 10 min intervals while measuring the MVO2 at each FI. Lactate was measured from coronary sinus samples to determine the onset of tissue hypoxia/anaerobic state.

Results
The DCRIT at 15 °C was 99.9 ± 4.9 mL/min/100 g; however, at 22 °C and 37 °C we could not reach a DCRIT. The myocardial oxygen demand could not be met at 22 °C and 37 °C with the maximum FI above 380 mL/min/100 g even when erythrocytes (10% V/V) were added to the solution. At 15 °C, the production of lactate was evident only below the DCRIT, while at 22 °C lactate production was present at all flow indices.

Conclusions
Determining the DCRIT for optimal ex-vivo perfusion of the heart is necessary to ensure adequate tissue oxygenation and limit anaerobic state. Temperatures employed above 15 °C limit the efficient ex-vivo perfusion preservation of heart with the UW Belzer MPS solution.
Bovine Leukemia virus (BLV) and risk of breast cancer: a systematic review and meta-analysis of case-control studies
Authors: Khatami Alireza , Pormohammad Ali , Farzi Rana , Saadati Hassan , Mehrabi Maryam , Kiani Seyed Jalal , Ghorbani Saied 
Published: July 2020

Abstract
Background
Breast cancer is reported as one of the most common cancers among females worldwide. Infectious agents especially viruses have been considered as role players in the development of breast cancer. Although some investigations suggest an association between bovine leukemia virus (BLV) and breast cancer, the involvement of this virus as a risk factor remains controversial. The present study aimed to find out any possible association between BLV and breast cancer through conducting a systematic review and meta-analysis.

Methods
Systematic literature search was performed by finding related case-control articles from the PubMed, Google Scholar, Web of Science, Scopus, and EMBASE databases. The heterogeneity and the multivariable-adjusted OR and corresponding 95% CI were applied by meta-analysis and forest plot across studies. All statistical analyses were performed using Stata 14.1.

Result
Based on a comprehensive literature search, 9 case-control studies were included for meta-analysis. The combination of all included studies showed that BLV infection is associated with an increased risk of breast cancer [summary OR (95% CI) 2.57 (1.45, 4.56)].

Conclusion
This is the first meta-analysis to analyze a potential association between BLV infection and the risk of breast cancer. Control of the infection in cattle herds and screening of the milk and dairy products may help to reduce the transmission of the virus to humans.
First molecular subtyping and phylogeny of Blastocystis sp. isolated from domestic and synanthropic animals (dogs, cats and brown rats) in southern Iran
Authors: Mohammadpour Iraj , Bozorg-Ghalati Farzaneh , Gazzonis Alessia Libera , Manfredi Maria Teresa , Motazedian Mohammad Hossein , Mohammadpour Niloofar 
Published: July 2020

Abstract
Background
Blastocystis sp. is a common intestinal protist that infects humans and many animals globally. Thus far, 22 subtypes (STs) have been identified in mammalian and avian hosts. Since various STs are common to humans and animals, it was suggested that some human infections might arise from zoonotic transmission. Therefore, the aim of this study was to assess the presence of Blastocystis sp. in domestic (dogs and cats) and synanthropic animals (rats) of Fars Province, Iran, and to genetically characterize the samples.

Methods
A total of 400 fresh faecal samples from 154 dogs, 119 cats, and 127 rats were inspected by direct microscopy, Wheatley’s trichrome staining, in vitro culture, and 18S rRNA gene nested-PCR. Finally, sequencing and phylogenetic analyses were performed.

Results
Out of 400 samples, 47 (11.8%) and 61 (15.3%) samples were detected as positive by direct wet mount and culture, respectively. Molecular analysis detected a larger number of positive samples (n = 70, 17.5%): nested-PCR showed that 29 (18.8%) dogs, 21 (17.7%) cats, and 20 (15.8%) rats were infected by Blastocystis sp. Sequence analysis of positive samples indicated the presence of zoonotic STs in all investigated host species. Specifically, ST2 (allele 9), ST3 (allele 34), ST4 (allele 94), ST7 (allele 99), ST8 (allele 21), and ST10 (allele 152) were detected in dogs; ST1 (allele 2), ST3 (allele 34), ST4 (allele 94), ST10 (allele 152), and ST14 (allele 159) were detected in cats; and ST1 (allele 2), ST3 (allele 34), and ST4 (allele 92) were detected in rats.

Conclusions
Our data suggest that domestic dogs and cats can serve as possible reservoirs for in-contact humans, especially those who handle shelter-resident and client-owned animals. Moreover, rats as synanthropic animals can function as a potential source of human infections. Conversely, humans can act as a source of infections to animals. These results should be reinforced in future molecular epidemiological studies.
The role of the Acanthamoeba castellanii Sir2-like protein in the growth and encystation of Acanthamoeba
Authors: Joo So-Young , Aung Ja Moon , Shin Minsang , Moon Eun-Kyung , Kong Hyun-Hee , Goo Youn-Kyoung , Chung Dong-Il , Hong Yeonchul 
Published: July 2020

Abstract
Background
The encystation of Acanthamoeba leads to the development of resilient cysts from vegetative trophozoites. This process is essential for the survival of parasites under unfavorable conditions. Previous studies have reported that, during the encystation of A. castellanii, the expression levels of encystation-related factors are upregulated. However, the regulatory mechanisms for their expression during the encystation process remains unknown. Proteins in the sirtuin family, which consists of nicotinamide adenine dinucleotide-dependent deacetylases, are known to play an important role in various cellular functions. In the present study, we identified the Acanthamoeba silent-information regulator 2-like protein (AcSir2) and examined its role in the growth and encystation of Acanthamoeba.

Methods
We obtained the full-length sequence for AcSir2 using reverse-transcription polymerase chain reaction. In Acanthamoeba transfectants that constitutively overexpress AcSir2 protein, SIRT deacetylase activity was measured, and the intracellular localization of AcSir2 and the effects on the growth and encystation of trophozoites were examined. In addition, the sirtuin inhibitor salermide was used to determine whether these effects were caused by AcSir2 overexpression

Results
AcSir2 was classified as a class-IV sirtuin. AcSir2 exhibited functional SIRT deacetylase activity, localized mainly in the nucleus, and its transcription was upregulated during encystation. In trophozoites, AcSir2 overexpression led to greater cell growth, and this growth was inhibited by treatment with salermide, a sirtuin inhibitor. When AcSir2 was overexpressed in the cysts, the encystation rate was significantly higher; this was also reversed with salermide treatment. In AcSir2-overexpressing encysting cells, the transcription of cellulose synthase was highly upregulated compared with that of control cells, and this upregulation was abolished with salermide treatment. Transmission electron microscope-based ultrastructural analysis of salermide-treated encysting cells showed that the structure of the exocyst wall and intercyst space was impaired and that the endocyst wall had not formed.

Conclusions
These results indicate that AcSir2 is a SIRT deacetylase that plays an essential role as a regulator of a variety of cellular processes and that the regulation of AcSir2 expression is important for the growth and encystation of A. castellanii.
Identification and antigenicity of the Babesia caballi spherical body protein 4 (SBP4)
Authors: Mahmoud Mona S. , Kandil Omnia M. , Abu El-Ezz Nadia T. , Hendawy Seham H. M. , Elsawy Bassma S. M. , Knowles Donald P. , Bastos Reginaldo G. , Kappmeyer Lowell S. , Laughery Jacob M. , Alzan Heba F. , Suarez Carlos E. 
Published: July 2020

Abstract
Background
The tick-borne intra-erythrocytic apicomplexan Babesia caballi is one of the etiological agents of equine babesiosis, an economically important disease of equids in most tropical and subtropical areas of the world. Discovering candidate antigens for improved diagnostic tools and vaccines remains needed for controlling equine babesiosis. This study describes the B. caballi sbp4 (Bcsbp4) gene and protein (BcSBP4) and analyzes its antigenicity in infected equids.

Methods
BLAST searches of an uncurated B. caballi assembly genome using the B. bovis SBP4 as a query were carried out, followed by PCR amplification and sequencing of a newly identified BcSBP4. Characterization of this novel gene and protein was performed by bioinformatics analysis, western blots, immunofluorescence (IFA) and an in vitro neutralization test using anti SBP4 peptide antibodies. Antigenicity of recombinant BcSBP4 (rBcSBP4) was tested with sera from field animals (n = 18) using an indirect ELISA (iELISA).

Results
Babesia caballi genome searches using B. bovis SBP4 as a query allowed identification of a novel gene termed Bcsbp4. The Bcsbp4 gene encodes for a protein of 30.58 kDa, which is fully conserved among B. caballi isolates from USA and Egypt. Bioinformatics analysis indicates that BcSBP4 contains a signal peptide and lacks additional transmembrane domains. Expression of BcSBP4 in blood stages of B. caballi was confirmed by western blot and IFA using antibodies against synthetic peptides representing putative B-cell epitopes of BcSBP4 predicted by in silico analysis. In vitro neutralization tests using anti-BcSBP4 peptide antibodies showed a marginal, but statistically significant inhibitory effect on the infectivity of B. caballi merozoites in horse red blood cells. Sera from eight B. caballi-infected equids, but none out of ten negative equid control sera, gave a positive signal in an rBcSBP4 based iELISA.

Conclusions
The Bcsbp4 gene is expressed in B. caballi blood stages. The BcSBP4 protein is a potential candidate for developing a novel serological test that could detect B. caballi infection in equids in tropical and subtropical countries worldwide.