Microplastics (MPs) have become a global issue as they are omnipresent in the ocean. Fish ingesting MPs through feed could be affected in their physiological function, e.g., disrupted enzyme ...production and function, reduction of feeding and reproductive failure. This study assessed the effects of feed containing naturally weathered MPs from the Oslofjord (Norway) on the reproductive physiology of Atlantic cod (Gadus morhua). Farmed cod broodstock were fed either control (C-diet) or feeds containing 1% microplastic (MP-diet) starting nine months prior to spawning, from June until May. No major differences were found between diet groups in overall biometrics or gonad histology. Sex steroid levels (testosterone, 11-ketotestosterone and 17β-estradiol) resulted in expected profiles increasing over time without any significant differences between treatments. Gene expression levels of the steroidogenic enzyme 20β-hydroxysteroid dehydrogenase (20β-hsd) and vitellogenin1 (vtg1) showed significant differences between dietary treatments with lower expression in the control group. This can be a direct effect of MPs, but endocrine disrupting effects of potentially leachable plastic additives cannot be completely ruled out. Thus, these enzymes could be indicators of exposure to contaminants that disrupt sexual maturation by affecting the production of primarily maturation-inducing steroid. Although the concentration of MPs employed in this study may not be high enough to elicit any observable short-term biological effects, the observed gene expression suggests that long-term consequences should be considered caused by an expected increase of MPs in marine environments.
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•Dietary inclusion of 1% weathered PE had no effect on digestion or fish biometrics.•No dietary effect on gonadal development, fecundity or on egg quality were observed.•Gene expression through the BPG-axis and plasma steroid analysis was normal.•Gonadal and liver gene expressions of 20β-hsd and vtg1 differed between the groups.
The major allergen is the benzylpenicilloyl determinant; however, minor determinants have also been reported.1 Adverse reactions to penicillin occur in up to 10% of the patients and anaphylaxis in ...0.015% to 0.04%.2 Correct diagnosis of allergy to antibiotics is of great importance because false-negative reports can lead to severe adverse reactions and false-positive reports to limited administration of the drugs or change to more expensive alternatives when they are indicated strongly.3 The diagnosis is based on case history, skin prick test (SPT), which has a good negative predictive value,4 and serum IgE antibodies (IgE-ab), for example, measured by ImmunoCAP (IDD Thermo Fisher Science, Uppsala, Sweden) sometimes followed up with intradermal and provocation testing. The result is in contrast to Patent Blue V-induced anaphylaxis where only basophils in the patient's plasma are positive in CD-sens, indicating that the allergenic epitope is dependent on a carrier-hapten complex, the carrier being present in the plasma.8 There is a good correlation of CD-sens with allergen sensitivity in allergic rhinitis7 and asthma9 and thus the negative CD-sens to penicillin excludes clinical relevance of the detected IgE-ab.
Antibiotic-tolerant persister bacteria involve frequent treatment failures, relapsing infections and the need for extended antibiotic treatment. The virulence of an intracellular human pathogen
is ...tightly linked to its propensity for persistence and means for its chemosensitization are urgently needed. In the current work, persistence of
clinical isolate CV6 was studied in THP-1 macrophages using quantitative PCR and quantitative culture. A dibenzocyclooctadiene lignan schisandrin reverted
persistence and promoted productive infection. The concomitant administration of schisandrin and azithromycin resulted in significantly improved bacterial eradication compared to sole azithromycin treatment. In addition, the closely related lignan schisandrin C was superior to azithromycin in eradicating the
infection from the macrophages. The observed chemosensitization of
was associated with the suppression of cellular glutathione pools by the lignans, implying to a previously unknown aspect of chlamydia-host interactions. These data indicate that schisandrin lignans induce a phenotypic switch in
, promoting the productive and antibiotic-susceptible phenotype instead of persistence. By this means, these medicinal plant -derived compounds show potential as adjuvant therapies for intracellular bacteria resuscitation.
Recently the clinical importance of human organic cation transporters 1 (hOCT1/SLC22A1) and 2 (hOCT2/SLC22A2) in drug disposition, for example, clearance, toxicity, and drug–drug interactions, have ...been highlighted Annu. Rev. Pharmacol. Toxicol. 2012, 52, 249−273 ; Nat. Rev. Drug Discovery 2010, 9 (3), 215–236 . Consequently, there is an extensive need for experimental assessment of structure–transport relationships as well as tools to predict drug uptake by these transporters in ADMET (absorption, distribution, metabolism, excretion, toxicity) investigations. In the present study, we developed a robust assay for screening unlabeled compound uptake by hOCT1 and hOCT2 using transfected HEK293 cells. For the first time, an extensive data set comprising uptake of 354 compounds is presented. As expected, there was a large overlap in substrate specificity between the two organic cation transporters. However, several compounds selectively taken up by either hOCT1 or hOCT2 were identified. In particular, a chemical series of phenylthiophenecarboxamide ureas was identified as selective hOCT1 substrates. Moreover, the drivers for transport differed: molecular volume was the most important determinant of hOCT1 substrates, whereas H-bonding parameters like polar surface area (PSA) dominated for hOCT2.
Cognitive deficits have been documented in patients with bipolar disorder. Further, it has been suggested that the degree and type of cognitive impairment differ between bipolar I and bipolar II ...disorder, but data is conflicting and remains inconclusive. This study aimed to clarify the suggested differences in cognitive impairment between patients with bipolar I and II disorder in a relatively large, clinically stable sample while controlling for potential confounders.
67 patients with bipolar I disorder, 43 with bipolar II disorder, and 86 randomly selected population-based healthy controls were compared. A number of neuropsychological tests were administered, assessing verbal and visual memory and executive functions. Patients were in a stable phase during testing.
Patients with bipolar type I and type II were cognitively impaired compared to healthy controls, but there were no statistically significant differences between the two subtypes. The strongest predictor of cognitive impairment within the patient group was current antipsychotic treatment.
The present study suggests that the type and degree of cognitive dysfunction is similar in bipolar I and II patients. Notably, treatment with antipsychotics - but not a history of psychosis - was associated with more severe cognitive impairment. Given that patients with bipolar I disorder are more likely to be on antipsychotic drugs, this might explain why some previous studies have found that patients with type I bipolar disorder are more cognitively impaired than those with type II.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Bipolar disorder is a psychiatric disorder characterized by recurrent episodes of mania/hypomania and depression. Progressive cognitive dysfunction such as impairments in executive function and ...verbal memory is common in euthymic bipolar patients. The cerebrospinal fluid has previously been used to study neurodegenerative processes in Alzheimer's disease, from which changes in three core biomarkers have emerged as indicative of degeneration: amyloid β, total tau, and hyperphosphorylated tau. Here, neurodegeneration in bipolar disorder was investigated by assessing the association between bipolar disorder and cerebrospinal fluid biomarkers for neurodegenerative processes. Cerebrospinal fluid was obtained from 139 bipolar disorder patients and 71 healthy controls. Concentrations of total and phosphorylated tau, amyloid β1-42, amyloid β38/β40/β42, and the soluble forms of amyloid precursor protein were measured in patients vs controls. The concentrations of the soluble forms of amyloid precursor protein were significantly lower in bipolar patients compared with controls. The amyloid β42/amyloid β38 and the amyloid β42/amyloid β40 ratios were higher in bipolar patients than controls. There were no discernible differences in the concentrations of total/phosphorylated tau, amyloid β1-42, or amyloid β38/β40/β42. The concentrations of the biomarkers within the bipolar patient group were further associated with different ongoing medical treatments and diagnostic subgroups. The findings suggest that the amyloid precursor protein metabolism is altered in bipolar disorder. The results may have implications for the understanding of the pathophysiology of bipolar disorder and for the development of treatment strategies. Importantly, there were no signs of an Alzheimer-like neurodegenerative process among bipolar patients.
Summary
Background
IgE sensitization to hazelnut is common, especially in birch endemic areas. However, its clinical significance often needs to be confirmed by a food challenge.
Objective
To ...evaluate the clinical significance of IgE antibodies to hazelnut components and basophil allergen threshold sensitivity (CD‐sens) to hazelnut, in relation to double‐blind placebo‐controlled food challenge (DBPCFC) in children with a suspected hazelnut allergy.
Methods
Forty children underwent a DBPCFC. CD‐sens to hazelnut as well as IgE antibodies to hazelnut and its components Cor a 1, Cor a 8, Cor a 9 and Cor a 14 were analysed. Serum tryptase was measured before, during and after DBPCFC.
Results
Eight children had a positive DBPCFC, and all of them had a high CD‐sens value to hazelnut. Of the 32 children that passed the DBPCFC, 31 were very low or negative in CD‐sens. A positive DBPCFC corresponded with significantly higher CD‐sens values (median 8.9, range 3.3–281) compared to children negative in challenge (median 0.05, range 0–34.7, P < 0.0001). Children positive in challenge also had higher levels of IgE‐ab to Cor a 9 and Cor a 14 (P < 0.01 and P < 0.001, respectively) compared with those with a negative challenge. In relation to the results from DBPCFC, the sensitivity of CD‐sens and IgE‐ab to Cor a 14 was excellent (100%) and the specificity was very high (> 97% and > 94%, respectively). Five of the eight patients positive at challenge showed an increase in tryptase > 20% compared to tryptase baseline levels.
Conclusions and Clinical Relevance
CD‐sens and component‐resolved diagnostics to hazelnut, used separately or in combination, may improve the diagnostic accuracy and safety and reduce overdiagnosis of hazelnut allergy.
In order to apply all ideas from quantum optics to the field of quantum circuits, one of the missing ingredients is a high-efficiency single-photon detector. In this work we propose a design for such ...a device which successfully reaches 100% efficiency with only one absorber. Our photon detector consists of a three-level system (a phase qubit) coupled to a semi-infinite one-dimensional waveguide (a microwave transmission line) which performs highly efficient photodetection in a simplified manner as compared to previous proposals. Using the tools of quantum optics we extensively study the scattering properties of realistic wave packets against this device, thereby computing the efficiency of the detector. We find that the detector has many operating modes, can detect detuned photons, is robust against design imperfections, and can be made broadband by using more than one absorbing element in the design. Many of these ideas could be translated to other single-mode photonic or plasmonic waveguides interacting with three-level atoms or quantum dots.
This book explores the life and times of Jón Halldórsson, bishop of Skálholt (1322-39), a Dominican who had studied the liberal arts and canon law in Paris and Bologna, and provides a snapshot with ...wider implications for understanding of medieval literacy.
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