ResearchPad - body-fluids https://www.researchpad.co Default RSS Feed en-us © 2020 Newgen KnowledgeWorks <![CDATA[Improvement of steatotic rat liver function with a defatting cocktail during <i>ex situ</i> normothermic machine perfusion is not directly related to liver fat content]]> https://www.researchpad.co/article/elastic_article_13803 There is a significant organ shortage in the field of liver transplantation, partly due to a high discard rate of steatotic livers from donors. These organs are known to function poorly if transplanted but make up a significant portion of the available pool of donated livers. This study demonstrates the ability to improve the function of steatotic rat livers using a combination of ex situ machine perfusion and a “defatting” drug cocktail. After 6 hours of perfusion, defatted livers demonstrated lower perfusate lactate levels and improved bile quality as demonstrated by higher bile bicarbonate and lower bile lactate. Furthermore, defatting was associated with decreased gene expression of pro-inflammatory cytokines and increased expression of enzymes involved in mitochondrial fatty acid oxidation. Rehabilitation of marginal or discarded steatotic livers using machine perfusion and tailored drug therapy can significantly increase the supply of donor livers for transplantation.

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<![CDATA[A prospective study of bloodstream infections among febrile adolescents and adults attending Yangon General Hospital, Yangon, Myanmar]]> https://www.researchpad.co/article/elastic_article_13833 Bloodstream infection (BSI) is common among persons seeking healthcare for severe febrile illness in low-and middle-income countries. Data on community-onset BSI are few for some countries in Asia, including Myanmar. Such data are needed to inform empiric antimicrobial treatment of patients and to monitor and control antimicrobial resistance. We performed a one year, prospective study collecting information and blood cultures from patients presenting with fever at a tertiary referral hospital in Yangon, Myanmar. We found that almost 10% of participants had a bloodstream infection, and that Salmonella enterica serovars Typhi and Paratyphi A were the most common pathogens. Typhoidal Salmonella were universally resistant to ciprofloxacin. More than half of Escherichia coli and Klebsiella pneumoniae were resistant to extended-spectrum cephalosporins and resistance to carbapenems was also identified in some isolates. We show that typhoid and paratyphoid fever are common, and fluoroquinolone resistance is widespread. Extended-spectrum cephalosporin resistance is common in E. coli and K. pneumoniae and carbapenem resistance is present. Our findings inform empiric antimicrobial management of severe febrile illness, underscore the value of routine use of blood cultures, indicate that measures to prevent and control enteric fever are warranted, and suggest a need to monitor and mitigate antimicrobial resistance among community-acquired pathogens.

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<![CDATA[Patients infected with <i>Mycobacterium africanum</i> versus <i>Mycobacterium tuberculosis</i> possess distinct intestinal microbiota]]> https://www.researchpad.co/article/elastic_article_13847 Mycobacterium africanum (MAF) is a hypovirulent mycobacterium species that is co-endemic with Mycobacterium tuberculosis (MTB) in West Africa and is selectively responsible for up to half the tuberculosis cases in this region. Why some individuals become infected with MAF versus MTB is unclear but has been suggested to be determined by differential host immune competency. Since the microbiome has now been implicated in numerous studies to generally influence host resistance to disease, we investigated whether differences in the intestinal microbiota might associate with MAF as compared with MTB infection. This report presents the first analysis of the intestinal microbiome of MAF-infected subjects as well as a comparison with the microbiota of co-endemic MTB patients and reveals that the microbiota of individuals with MAF infection display both decreased diversity and distinct differences in microbial taxa when compared to both MTB-infected and healthy controls. Furthermore, our data reveal for the first time in TB patients a correlation between the abundance of certain taxa and host blood transcriptional changes related to immune function. Our study also establishes that antibiotic treatment induces parallel changes in the gut microbiota of MAF- and MTB-infected patients. Although not directly addressed in the present study, the findings presented here raise the possibility that the microbiota or other host physiologic or immune factors closely associated with it may be a factor underlying the differential susceptibility of West Africans to MAF infection. In addition, the data identify certain commensal taxa that could be tested in future studies as specific determinants of this association.

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<![CDATA[Amino acids serve as an important energy source for adult flukes of <i>Clonorchis sinensis</i>]]> https://www.researchpad.co/article/elastic_article_13829 Clonorchiasis, closely related to cholangiocarcinoma and hepatocellular carcinoma, has led to a negative socioeconomic impact in global areas especially some Asian endemic regions. Owing to the emergence of drug resistance and hypersensitivity reactions after the massive and repeated use of praziquantel as well as the lack of effective vaccines, searching for new strategies that prevent and treat clonorchiasis has become an urgent matter. Clonorchis sinensis, the causative agent of clonorchiasis, long-term inhabits the microaerobic and limited-glucose environment of the bile ducts. Adequate nutrients are essential for adult flukes to resist the adverse condition and survive in the crowed habitat. Studies on energy metabolism of adult flukes are beneficial for further exploring host-parasite interactions and developing novel anti-parasitic drugs. Our results suggest that gluconeogenesis probably plays a vital role in energy metabolism of Clonorchis sinensis and exogenous amino acids might be an essential energy source for adult flukes to successfully survive in the host. Our foundational study opens a new avenue for explaining energy metabolism of Clonorchis sinensis and provides a valuable strategy that the gluconeogenesis pathway will be a potential and novel target for the prevention and treatment of clonorchiasis.

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<![CDATA[Likely questionnaire-diagnosed food allergy in 78, 890 adults from the northern Netherlands]]> https://www.researchpad.co/article/elastic_article_13854 It is challenging to define likely food allergy (FA) in large populations which limited the number of large studies regarding risk factors for FA.ObjectiveWe studied the prevalence and characteristics of self-reported FA (s-rFA) in the large, population-based Dutch Lifelines cohort and identified associated risk factors.MethodsLikely food allergic cases (LikelyFA) were classified based on questionnaire reported characteristics consistent with FA. Subjects with atypical characteristics were classified as Indeterminate. We investigated 13 potential risk factors for LikelyFA such as birth mode and living on a farm and addressed health-related quality of life (H-RQOL).ResultsOf the 78, 890 subjects, 12.1% had s-rFA of which 4.0% and 8.1% were classified as LikelyFA and Indeterminate, respectively. Younger age, female sex, asthma, eczema and nasal allergy increased the risk of LikelyFA (p-value range <1.00*10−250–1.29*10−7). Living in a small city/large village or suburb during childhood was associated with a higher risk of LikelyFA than living on a farm (p-value = 7.81*10−4 and p = 4.84*10−4, respectively). Subjects classified as Indeterminate more often reported depression and burn-out compared to those without FA (p-value = 1.46*10−4 and p = 8.39*10−13, respectively). No association was found with ethnicity, (duration of) breastfeeding, birth mode and reported eating disorder. Mental and physical component scores measuring H-RQOL were lower in both those classified as LikelyFA and Indeterminate compared to those without FA.ConclusionThe prevalence of s-rFA among adults is considerable and one-third reports characteristics consistent with LikelyFA. Living on a farm decreased the risk of LikelyFA. The association of poorer H-RQOL as well as depression and burn-out with questionable self-perceived FA is striking and a priority for future study. ]]> <![CDATA[A modified arginine-depleting enzyme NEI-01 inhibits growth of pancreatic cancer cells]]> https://www.researchpad.co/article/elastic_article_11227 Arginine deprivation cancer therapy targets certain types of malignancies with positive result in many studies and clinical trials. NEI-01 was designed as a novel arginine-depleting enzyme comprising an albumin binding domain capable of binding to human serum albumin to lengthen its half-life. In the present work, NEI-01 is shown to bind to serum albumin from various species, including mice, rat and human. Single intraperitoneal administration of NEI-01 to mice reduced plasma arginine to undetectable level for at least 9 days. Treatment of NEI-01 specifically inhibited cell viability of MIA PaCa-2 and PANC-1 cancer cell lines, which were ASS1 negative. Using a human pancreatic mouse xenograft model, NEI-01 treatment significantly reduced tumor volume and weight. Our data provides proof of principle for a cancer treatment strategy using NEI-01.

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<![CDATA[Methamphetamine administration increases hepatic CYP1A2 but not CYP3A activity in female guinea pigs]]> https://www.researchpad.co/article/elastic_article_7848 Methamphetamine use has increased over the past decade and the first use of methamphetamine is most often when women are of reproductive age. Methamphetamine accumulates in the liver; however, little is known about the effect of methamphetamine use on hepatic drug metabolism. Methamphetamine was administered on 3 occassions to female Dunkin Hartley guinea pigs of reproductive age, mimicking recreational drug use. Low doses of test drugs caffeine and midazolam were administered after the third dose of methamphetamine to assess the functional activity of cytochrome P450 1A2 and 3A, respectively. Real-time quantitative polymerase chain reaction was used to quantify the mRNA expression of factors involved in glucocorticoid signalling, inflammation, oxidative stress and drug transporters. This study showed that methamphetamine administration decreased hepatic CYP1A2 mRNA expression, but increased CYP1A2 enzyme activity. Methamphetamine had no effect on CYP3A enzyme activity. In addition, we found that methamphetamine may also result in changes in glucocorticoid bioavailability, as we found a decrease in 11β-hydroxysteroid dehydrogenase 1 mRNA expression, which converts inactive cortisone into active cortisol. This study has shown that methamphetamine administration has the potential to alter drug metabolism via the CYP1A2 metabolic pathway in female guinea pigs. This may have clinical implications for drug dosing in female methamphetamine users of reproductive age.

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<![CDATA[Potency and breadth of human primary ZIKV immune sera shows that Zika viruses cluster antigenically as a single serotype]]> https://www.researchpad.co/article/elastic_article_7747 The recent emergence of Zika virus as an important human pathogen has raised questions about the durability and breadth of Zika virus immunity following natural infection in humans. While global epidemic patterns suggest that Zika infection elicits a protective immune response that is likely to offer long-term protection against repeat infection by other Zika viruses, only one study to date has formally examined the ability of human Zika immune sera to neutralize different Zika viruses. That study was limited because it evaluated human immune sera no more than 13 weeks after Zika virus infection and tested a relatively small number of Zika viruses. In this study, we examine twelve human Zika immune sera as far as 3 years after infection and test the sera against a total of eleven Zika virus isolates. Our results confirm the earlier study and epidemic patterns that suggest Zika virus exists in nature as a single serotype, and infection with one Zika virus can be expected to elicit protective immunity against repeat infection by any Zika virus for years to decades after the first infection.

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<![CDATA[Digestibility of black soldier fly larvae (<i>Hermetia illucens</i>) fed to leopard geckos (<i>Eublepharis macularius</i>)]]> https://www.researchpad.co/article/elastic_article_7714 Black soldier fly (BSF) larvae have been marketed as an excellent choice for providing calcium to reptiles without the need of dusting or gut loading. However, previous studies have indicated that they have limited calcium digestibility and are deficient in fat soluble vitamins (A, D3, and E). In this feeding and digestibility trial, 24 adult male leopard geckos were fed one of three diets for 4 months: 1) whole, vitamin A gut loaded larvae; 2) needle pierced, vitamin A gut loaded larvae; or 3) whole, non-gut loaded larvae. Fecal output from the geckos was collected daily and apparent digestibility was calculated for dry matter, protein, fat, and minerals. There were no differences in digestibility coefficients among groups. Most nutrients were well digested by the leopard geckos when compared to previous studies, with the exception of calcium (digestibility co-efficient 43%), as the calcium-rich exoskeleton usually remained intact after passage through the GI tract. Biochemistry profiles revealed possible deficits occurring over time for calcium, sodium, and total protein. In regards to vitamin A digestibility, plasma and liver vitamin A concentrations were significantly higher in the supplemented groups (plasma- gut loaded groups: 33.38 ± 7.11 ng/ml, control group: 25.8 ± 6.72 ng/ml, t = 1.906, p = 0.04; liver- gut loaded groups: 28.67 ± 18.90 μg/g, control group: 14.13 ± 7.41 μg/g, t = 1.951, p = 0.03). While leopard geckos are able to digest most of the nutrients provided by BSF larvae, including those that have been gut loaded, more research needs to be performed to assess whether or not they provide adequate calcium in their non-supplemented form.

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<![CDATA[Plasma Galectin-3 predicts deleterious vascular dysfunction affecting post-myocardial infarction patients: An explanatory study]]> https://www.researchpad.co/article/elastic_article_7712 In a previous analysis of a post-myocardial infarction (MI) cohort, abnormally high systemic vascular resistances (SVR) were shown to be frequently revealed by MRI during the healing period, independently of MI severity, giving evidence of vascular dysfunction and limiting further recovery of cardiac function. The present ancillary and exploratory analysis of the same cohort was aimed at characterizing those patients suffering from high SVR remotely from MI with a large a panel of cardiovascular MRI parameters and blood biomarkers.MethodsMRI and blood sampling were performed 2–4 days after a reperfused MI and 6 months thereafter in 121 patients. SVR were monitored with a phase-contrast MRI sequence and patients with abnormally high SVR at 6-months were characterized through MRI parameters and blood biomarkers, including Galectin-3, an indicator of cardiovascular inflammation and fibrosis after MI. SVR were normal at 6-months in 90 patients (SVR-) and abnormally high in 31 among whom 21 already had high SVR at the acute phase (SVR++) while 10 did not (SVR+).ResultsWhen compared with SVR-, both SVR+ and SVR++ exhibited lower recovery in cardiac function from baseline to 6-months, while baseline levels of Galectin-3 were significantly different in both SVR+ (median: 14.4 (interquartile range: 12.3–16.7) ng.mL-1) and SVR++ (13.0 (11.7–19.4) ng.mL-1) compared to SVR- (11.7 (9.8–13.5) ng.mL-1, both p < 0.05). Plasma Galectin-3 was an independent baseline predictor of high SVR at 6-months (p = 0.002), together with the baseline levels of SVR and left ventricular end-diastolic volume, whereas indices of MI severity and left ventricular function were not. In conclusion, plasma Galectin-3 predicts a deleterious vascular dysfunction affecting post-MI patients, an observation that could lead to consider new therapeutic targets if confirmed through dedicated prospective studies. ]]> <![CDATA[The adipokine vaspin is associated with decreased coronary in-stent restenosis <i>in vivo</i> and inhibits migration of human coronary smooth muscle cells <i>in vitro</i>]]> https://www.researchpad.co/article/elastic_article_7692 Percutaneous coronary intervention represents the most important treatment modality of coronary artery stenosis. In-stent restenosis (ISR) is still a limitation for the long-term outcome despite the introduction of drug eluting stents. It has been shown that adipokines directly influence vessel wall homeostasis by influencing the function of endothelial cells and arterial smooth muscle cells. Visceral adipose tissue-derived serpin vaspin was recently identified as a member of serine protease inhibitor family and serveral studies could demonstrate a relation to metabolic diseases. The aim of this study was to investigate a role of vaspin in the development of in-stent restenosis in vivo and on migration of smooth muscle cells and endothelial cells in vitro.MethodsWe studied 85 patients with stable coronary artery disease who underwent elective and successful PCI with implatation of drug eluting stents. Blood samples were taken directly before PCI. Vaspin plasma levels were measured by specific ELISA. ISR was evaluated eight months later by coronary angiography. Human coronary artery smooth muscle cells (HCASMC) and human umbilical vein endothelial cells (HUVEC) migration was analyzed by an in-vitro migration assay with different concentrations (0.004ng/mL up to 40ng/mL) of vaspin as well as by an scratch assay. For proliferation an impedance measurement with specialiced E-Plates was performed.ResultsDuring the follow up period, 14 patients developed ISR. Patients with ISR had significantly lower vaspin plasma levels compared to patients without ISR (0.213 ng/ml vs 0.382 ng/ml; p = 0.001). In patients with plasma vaspin levels above 1.35 ng/ml we could not observe any restenosis. There was also a significant correlation of plasma vaspin levels and late lumen loss in the stented coronary segments. Further we could demonstrate that vaspin nearly abolishes serum induced migration of HCASMC (100% vs. 9%; p<0.001) in a biphasic manner but not migration of HUVEC. Proliferation of HCASMC and HUVEC was not modulated by vaspin treatment.ConclusionWe were able to show that the adipokine vaspin selectively inhibits human coronary SMC migration in vitro and has no effect on HUVEC migration. Vaspin had no effect on proliferation of HUVEC which is an important process of the healing of the stented vessel. In addition, the occurrence of ISR after PCI with implantation of drug eluting stents was significantly associated with low vaspin plasma levels before intervention. Determination of vaspin plasma levels before PCI might be helpful in the identification of patients with high risk for development of ISR after stent implantation. In addition, the selective effects of vaspin on smooth muscle cell migration could potentially be used to reduce ISR without inhibition of re-endothelialization of the stented segment. ]]> <![CDATA[Identification of miRNA signatures associated with radiation-induced late lung injury in mice]]> https://www.researchpad.co/article/elastic_article_7641 Acute radiation exposure of the thorax can lead to late serious, and even life-threatening, pulmonary and cardiac damage. Sporadic in nature, late complications tend to be difficult to predict, which prompted this investigation into identifying non-invasive, tissue-specific biomarkers for the early detection of late radiation injury. Levels of circulating microRNA (miRNA) were measured in C3H and C57Bl/6 mice after whole thorax irradiation at doses yielding approximately 70% mortality in 120 or 180 days, respectively (LD70/120 or 180). Within the first two weeks after exposure, weight gain slowed compared to sham treated mice along with a temporary drop in white blood cell counts. 52% of C3H (33 of 64) and 72% of C57Bl/6 (46 of 64) irradiated mice died due to late radiation injury. Lung and heart damage, as assessed by computed tomography (CT) and histology at 150 (C3H mice) and 180 (C57Bl/6 mice) days, correlated well with the appearance of a local, miRNA signature in the lung and heart tissue of irradiated animals, consistent with inherent differences in the C3H and C57Bl/6 strains in their propensity for developing radiation-induced pneumonitis or fibrosis, respectively. Radiation-induced changes in the circulating miRNA profile were most prominent within the first 30 days after exposure and included miRNA known to regulate inflammation and fibrosis. Importantly, early changes in plasma miRNA expression predicted survival with reasonable accuracy (88–92%). The miRNA signature that predicted survival in C3H mice, including miR-34a-5p, -100-5p, and -150-5p, were associated with pro-inflammatory NF-κB-mediated signaling pathways, whereas the signature identified in C57Bl/6 mice (miR-34b-3p, -96-5p, and -802-5p) was associated with TGF-β/SMAD signaling. This study supports the hypothesis that plasma miRNA profiles could be used to identify individuals at high risk of organ-specific late radiation damage, with applications for radiation oncology clinical practice or in the context of a radiological incident.

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<![CDATA[Role of intraoperative oliguria in risk stratification for postoperative acute kidney injury in patients undergoing colorectal surgery with an enhanced recovery protocol: A propensity score matching analysis]]> https://www.researchpad.co/article/N90678846-11a4-456d-84dc-7e3677d2f27e

Background

The enhanced recovery after surgery (ERAS) protocol for colorectal cancer resection recommends balanced perioperative fluid therapy. According to recent guidelines, zero-balance fluid therapy is recommended in low-risk patients, and immediate correction of low urine output during surgery is discouraged. However, several reports have indicated an association of intraoperative oliguria with postoperative acute kidney injury (AKI). We investigated the impact of intraoperative oliguria in the colorectal ERAS setting on the incidence of postoperative AKI.

Patients and methods

From January 2017 to August 2019, a total of 453 patients underwent laparoscopic colorectal cancer resection with the ERAS protocol. Among them, 125 patients met the criteria for oliguria and were propensity score (PS) matched to 328 patients without intraoperative oliguria. After PS matching had been performed, 125 patients from each group were selected and the incidences of AKI were compared between the two groups. Postoperative kidney function and surgical outcomes were also evaluated.

Results

The incidence of AKI was significantly higher in the intraoperative oliguria group than in the non-intraoperative oliguria group (26.4% vs. 11.2%, respectively, P = 0.002). Also, the eGFR reduction on postoperative day 0 was significantly greater in the intraoperative oliguria than non-intraoperative oliguria group (−9.02 vs. −1.24 mL/min/1.73 m2 respectively, P < 0.001). In addition, the surgical complication rate was higher in the intraoperative oliguria group than in the non-intraoperative oliguria group (18.4% vs. 9.6%, respectively, P = 0.045).

Conclusions

Despite the proven benefits of perioperative care with the ERAS protocol, caution is required in patients with intraoperative oliguria to prevent postoperative AKI. Further studies regarding appropriate management of intraoperative oliguria in association with long-term prognosis are needed in the colorectal ERAS setting.

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<![CDATA[Baloxavir treatment of ferrets infected with influenza A(H1N1)pdm09 virus reduces onward transmission]]> https://www.researchpad.co/article/Nca8f7add-a1d9-4373-9c77-344aec55ea94

Influenza viruses cause seasonal outbreaks and pose a continuous pandemic threat. Although vaccines are available for influenza control, their efficacy varies each season and a vaccine for a novel pandemic virus manufactured using current technology will not be available fast enough to mitigate the effect of the first pandemic wave. Antivirals can be effective against many different influenza viruses but have not thus far been used extensively for outbreak control. Baloxavir, a recently licensed antiviral drug that targets the influenza virus endonuclease, has been shown to reduce virus shedding more effectively than oseltamivir, a widely used neuraminidase inhibitor drug. Thus it is possible that treatment with baloxavir might also interrupt onward virus transmission. To test this, we utilized the ferret model, which is the most commonly used animal model to study influenza virus transmission. We established a subcutaneous baloxavir administration method in ferrets which achieved similar pharmacokinetics to the approved human oral dose. Transmission studies were then conducted in two different locations with different experimental setups to compare the onward transmission of A(H1N1)pdm09 virus from infected ferrets treated with baloxavir, oseltamivir or placebo to naïve sentinel ferrets exposed either indirectly in adjacent cages or directly by co-housing. We found that baloxavir treatment reduced infectious viral shedding in the upper respiratory tract of ferrets compared to placebo, and reduced the frequency of transmission amongst sentinels in both experimental setups, even when treatment was delayed until 2 days post-infection. In contrast, oseltamivir treatment did not substantially affect viral shedding or transmission compared to placebo. We did not detect the emergence of baloxavir-resistant variants in treated animals or in untreated sentinels. Our results support the concept that antivirals which decrease viral shedding could also reduce influenza transmission in the community.

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<![CDATA[Investigation of synovial fluid induced Staphylococcus aureus aggregate development and its impact on surface attachment and biofilm formation]]> https://www.researchpad.co/article/Nf13f73b5-5132-41b9-b894-3d4dd0a113b1

Periprosthetic joint infections (PJIs) are a devastating complication that occurs in 2% of patients following joint replacement. These infections are costly and difficult to treat, often requiring multiple corrective surgeries and prolonged antimicrobial treatments. The Gram-positive bacterium Staphylococcus aureus is one of the most common causes of PJIs, and it is often resistant to a number of commonly used antimicrobials. This tolerance can be partially attributed to the ability of S. aureus to form biofilms. Biofilms associated with the surface of indwelling medical devices have been observed on components removed during chronic infection, however, the development and localization of biofilms during PJIs remains unclear. Prior studies have demonstrated that synovial fluid, in the joint cavity, promotes the development of bacterial aggregates with many biofilm-like properties, including antibiotic resistance. We anticipate these aggregates have an important role in biofilm formation and antibiotic tolerance during PJIs. Therefore, we sought to determine specifically how synovial fluid promotes aggregate formation and the impact of this process on surface attachment. Using flow cytometry and microscopy, we quantified the aggregation of various clinical S. aureus strains following exposure to purified synovial fluid components. We determined that fibrinogen and fibronectin promoted bacterial aggregation, while cell free DNA, serum albumin, and hyaluronic acid had minimal effect. To determine how synovial fluid mediated aggregation affects surface attachment, we utilized microscopy to measure bacterial attachment. Surprisingly, we found that synovial fluid significantly impeded bacterial surface attachment to a variety of materials. We conclude from this study that fibrinogen and fibronectin in synovial fluid have a crucial role in promoting bacterial aggregation and inhibiting surface adhesion during PJI. Collectively, we propose that synovial fluid may have conflicting protective roles for the host by preventing adhesion to surfaces, but by promoting bacterial aggregation is also contributing to the development of antibiotic tolerance.

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<![CDATA[Opposing effects of HNP1 (α-defensin-1) on plasma cholesterol and atherogenesis]]> https://www.researchpad.co/article/Ndf7081dd-c312-4392-aa9c-ddf6cf67dfa0

Atherosclerosis, the predominant cause of death in well-resourced countries, may develop in the presence of plasma lipid levels within the normal range. Inflammation may contribute to lesion development in these individuals, but the underlying mechanisms are not well understood. Transgenic mice expressing α-def-1 released from activated neutrophils develop larger lipid and macrophage-rich lesions in the proximal aortae notwithstanding hypocholesterolemia caused by accelerated clearance of α-def-1/low-density lipoprotein (LDL) complexes from the plasma. The phenotype does not develop when the release of α-def-1 is prevented with colchicine. However, ApoE-/- mice crossed with α-def-1 mice or given exogenous α-def-1 develop smaller aortic lesions associated with reduced plasma cholesterol, suggesting a protective effect of accelerated LDL clearance. Experiments were performed to address this seeming paradox and to determine if α-def-1 might provide a means to lower cholesterol and thereby attenuate atherogenesis. We confirmed that exposing ApoE-/- mice to α-def-1 lowers total plasma cholesterol and decreases lesion size. However, lesion size was larger than in mice with total plasma cholesterol lowered to the same extent by inhibiting its adsorption or by ingesting a low-fat diet. Furthermore, α-def-1 levels correlated independently with lesion size in ApoE-/- mice. These studies show that α-def-1 has competing effects on atherogenesis. Although α-def-1 accelerates LDL clearance from plasma, it also stimulates deposition and retention of LDL in the vasculature, which may contribute to development of atherosclerosis in individuals with normal or even low plasma levels of cholesterol. Inhibiting α-def-1 may attenuate the impact of chronic inflammation on atherosclerotic vascular disease.

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<![CDATA[Changes in human health parameters associated with an immersive exhibit experience at a zoological institution]]> https://www.researchpad.co/article/N69289aa2-a5fc-4464-abf6-42bfa80ae1ee

Zoological institutions often use immersive, naturalistic exhibits to create an inclusive atmosphere that is inviting for visitors while providing for the welfare of animals in their collections. In this study, we investigated physiological changes in salivary cortisol and blood pressure, as well as psychological changes among visitors before and after a walk through the River’s Edge, an immersive, naturalistic exhibit at the Saint Louis Zoo. Study participants had a significant reduction in salivary cortisol and blood pressure after walking through the exhibit. Psychological assessments of mood found that most visitors felt happier, more energized, and less tense after the visit. Additionally, participants who spent more time in River’s Edge, had visited River’s Edge prior to the study, and had seen more exhibits at the Zoo prior to entering River’s Edge experienced greater psychological and/or physiological benefits. We conclude that immersive, naturalistic exhibits in zoos can elicit positive changes in physiological and psychological measures of health and well-being and argue for a greater scientific focus on the role of zoos and other green spaces in human health.

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<![CDATA[Effects of amotosalen treatment on human platelet lysate bioactivity: A proof-of-concept study]]> https://www.researchpad.co/article/Ne8e94533-b9bd-43e3-83be-324d5eb7ad87

Background

Clinical application of mesenchymal stromal cells (MSCs) usually requires an in vitro expansion step to reach clinically relevant numbers. In vitro cell expansion necessitates supplementation of basal mammalian cell culture medium with growth factors. To avoid using supplements containing animal substances, human platelet lysates (hPL) produced from expired and pathogen inactivated platelet concentrates can be used in place of fetal bovine serum. However, globally, most transfusion units are currently not pathogen inactivated. As blood banks are the sole source of platelet concentrates for hPL production, it is important to ensure product safety and standardized production methods. In this proof-of-concept study we assessed the feasibility of producing hPL from expired platelet concentrates with pathogen inactivation applied after platelet lysis by evaluating the retention of growth factors, cytokines, and the ability to support MSC proliferation and tri-lineage differentiation.

Methodology/Principal findings

Bone marrow-derived MSCs (BM-MSCs) were expanded and differentiated using hPL derived from pathogen inactivated platelet lysates (hPL-PIPL), with pathogen inactivation by amotosalen/ultraviolet A treatment applied after lysis of expired platelets. Results were compared to those using hPL produced from conventional expired pathogen inactivated platelet concentrates (hPL-PIPC), with pathogen inactivation applied after blood donation. hPL-PIPL treatment had lower concentrations of soluble growth factors and cytokines than hPL-PIPC treatment. When used as supplementation in cell culture, BM-MSCs proliferated at a reduced rate, but more consistently, in hPL-PIPL than in hPL-PIPC. The ability to support tri-lineage differentiation was comparable between lysates.

Conclusion/Significance

These results suggest that functional hPL can be produced from expired and untreated platelet lysates by applying pathogen inactivation after platelet lysis. When carried out post-expiration, pathogen inactivation may provide a valuable solution for further standardizing global hPL production methods, increasing the pool of starting material, and meeting future demand for animal-free supplements in human cell culturing.

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<![CDATA[Severe hyperbilirubinemia is associated with higher risk of contrast-related acute kidney injury following contrast-enhanced computed tomography]]> https://www.researchpad.co/article/N624c57d4-8983-4ece-aecc-e0e7860066cf

Introduction

Contrast-induced acute kidney injury (CI-AKI) is associated with high risks of morbidity and mortality. Hyperbilirubinemia might have some renal protection but with no clear cutoff value for protection. Related studies are typically on limited numbers of patients and only in conditions of vascular intervention.

Methods

We performed this study to elucidate CI-AKI in patients after contrast-enhanced computed tomography (CCT). The outcomes were CI-AKI, dialysis and mortality. Patients were divided to three groups based on their serum levels of total bilirubin: ≤1.2 mg/dl, 1.3–2.0 mg/dl, and >2.0 mg/dl.

Results

We enrolled a total of 9,496 patients who had received CCT. Patients with serum total bilirubin >2.0 mg/dl were associated with CI-AKI. Those undergoing dialysis had the highest incidence of PC-AKI (p<0.001). No difference was found between the two groups of total bilirubin ≤1.2 and 1.3–2.0 mg/dl. Patients with total bilirubin >2mg/dl were associated with CI-AKI (OR = 1.89, 1.53–2.33 of 95% CI), dialysis (OR = 1.40, 1.01–1.95 of 95% CI) and mortality (OR = 1.63, 1.38–1.93 of 95% CI) after adjusting for laboratory data and all comorbidities (i.e., cerebrovascular disease, coronary artery disease, peripheral arterial disease, and acute myocardial infarction, diabetes mellitus, hypertension, gastrointestinal bleeding, cirrhosis, peritonitis, ascites, hepatoma, shock lung and colon cancer). We concluded that total bilirubin level >2 mg/dl is an independent risk factor for CI-AKI, dialysis and mortality after CCT. These patients also had high risks for cirrhosis or hepatoma.

Conclusion

This is the first study providing evidence that hyperbilirubinemia (total bilirubin >2.0 mg/dl) being an independent risk factor for CI-AKI, dialysis and mortality after receiving CCT. Most patients with total bilirubin >2.0mg/dl had cirrhosis or hepatoma.

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<![CDATA[Beware of vested interests: Epistemic vigilance improves reasoning about scientific evidence (for some people)]]> https://www.researchpad.co/article/Na4c1a7a8-d330-434e-b120-e60e98785391

In public disputes, stakeholders sometimes misrepresent statistics or other types of scientific evidence to support their claims. One of the reasons this is problematic is that citizens often do not have the motivation nor the cognitive skills to accurately judge the meaning of statistics and thus run the risk of being misinformed. This study reports an experiment investigating the conditions under which people become vigilant towards a source’s claim and thus reason more carefully about the supporting evidence. For this, participants were presented with a claim by a vested-interest or a neutral source and with statistical evidence which was cited by the source as being in support of the claim. However, this statistical evidence actually contradicted the source’s claim but was presented as a contingency table, which are typically difficult for people to interpret correctly. When the source was a lobbyist arguing for his company’s product people were better at interpreting the evidence compared to when the same source argued against the product. This was not the case for a different vested-interests source nor for the neutral source. Further, while all sources were rated as less trustworthy when participants realized that the source had misrepresented the evidence, only for the lobbyist source was this seen as a deliberate attempt at deception. Implications for research on epistemic trust, source credibility effects and science communication are discussed.

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