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  • 1
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    First Molecular Identification of Calicophoron daubneyi (Dinnik, 1962) and Paramphistomum leydeni (Nasmark, 1937) in Wild Ruminants from Romania
    MDPI AG ; 2023
    In:  Veterinary Sciences Vol. 10, No. 10 ( 2023-10-03), p. 603-
    Details
    In: Veterinary Sciences, MDPI AG, Vol. 10, No. 10 ( 2023-10-03), p. 603-
    Abstract: Rumen flukes are geographically widespread trematodes affecting wild and domestic ruminants. The juvenile forms, which are found in the small intestine, are more pathogenic compared to the adults. Severe diarrhoea and weight loss are the major clinical signs, and the disease might be fatal in severely infested individuals. In the last decade, paramphistomosis has been described as an emerging parasitic disease in Europe. This study aimed to identify the rumen fluke species in wild ruminants from western Romania. Fifty-two pre-stomachs obtained from roe deer (Capreolus capreolus) that were hunted on 14 hunting grounds from Timiș and Arad counties were examined for the presence of paramphistomes. Three (9.09%) out of 33 samples were positive in Timiș County, and one (5.26%) out of 19 samples was positive in Arad County. Subsequent PCR testing revealed that three samples were positive for Calicophoron daubneyi and one for Paramphistomum leydeni. The presence of C. daubneyi and P. leydeni in roe deer has not been previously reported in Romania. Two Paramphistomum species—C. daubneyi and P. leydeni—were revealed as the main species of rumen flukes in roe deer from forests in Romania.
    Type of Medium: Online Resource
    ISSN: 2306-7381
    URL: Article
    DOI: 10.3390/vetsci10100603
    Language: English
    Publisher: MDPI AG
    Publication Date: 2023
    detail.hit.zdb_id: 2768971-2
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  • 2
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    PET/MRI in the Presurgical Evaluation of Patients with Epilepsy: A Concordance Analysis
    MDPI AG ; 2022
    In:  Biomedicines Vol. 10, No. 5 ( 2022-04-20), p. 949-
    Details
    In: Biomedicines, MDPI AG, Vol. 10, No. 5 ( 2022-04-20), p. 949-
    Abstract: The aim of our prospective study was to evaluate the clinical impact of hybrid [18F]-fluorodeoxyglucose positron emission tomography/magnetic resonance imaging ([18F] -FDG PET/MRI) on the decision workflow of epileptic patients with discordant electroclinical and MRI data. A novel mathematical model was introduced for a clinical concordance calculation supporting the classification of our patients by subgroups of clinical decisions. Fifty-nine epileptic patients with discordant clinical and diagnostic results or MRI negativity were included in this study. The diagnostic value of the PET/MRI was compared to other modalities of presurgical evaluation (e.g., electroclinical data, PET, and MRI). The results of the population-level statistical analysis of the introduced data fusion technique and concordance analysis demonstrated that this model could be the basis for the development of a more accurate clinical decision support parameter in the future. Therefore, making the establishment of “invasive” (operable and implantable) and “not eligible for any further invasive procedures” groups could be much more exact. Our results confirmed the relevance of PET/MRI with the diagnostic algorithm of presurgical evaluation. The introduction of a concordance analysis could be of high importance in clinical and surgical decision-making in the management of epileptic patients. Our study corroborated previous findings regarding the advantages of hybrid PET/MRI technology over MRI and electroclinical data.
    Type of Medium: Online Resource
    ISSN: 2227-9059
    URL: Article
    DOI: 10.3390/biomedicines10050949
    Language: English
    Publisher: MDPI AG
    Publication Date: 2022
    detail.hit.zdb_id: 2720867-9
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  • 3
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    Canine Saliva as a Possible Source of Antimicrobial Resistance Genes
    MDPI AG ; 2022
    In:  Antibiotics Vol. 11, No. 11 ( 2022-10-27), p. 1490-
    Details
    In: Antibiotics, MDPI AG, Vol. 11, No. 11 ( 2022-10-27), p. 1490-
    Abstract: While the One Health issues of intensive animal farming are commonly discussed, keeping companion animals is less associated with the interspecies headway of antimicrobial resistance. With the constant advance in veterinary standards, antibiotics are regularly applied in companion animal medicine. Due to the close coexistence of dogs and humans, dog bites and other casual encounters with dog saliva (e.g., licking the owner) are common. According to our metagenome study, based on 26 new generation sequencing canine saliva datasets from 2020 and 2021 reposited in NCBI SRA by The 10,000 Dog Genome Consortium and the Broad Institute within Darwin’s Ark project, canine saliva is rich in bacteria with predictably transferable antimicrobial resistance genes (ARGs). In the genome of potentially pathogenic Bacteroides, Capnocytophaga, Corynebacterium, Fusobacterium, Pasteurella, Porphyromonas, Staphylococcus and Streptococcus species, which are some of the most relevant bacteria in dog bite infections, ARGs against aminoglycosides, carbapenems, cephalosporins, glycylcyclines, lincosamides, macrolides, oxazolidinone, penams, phenicols, pleuromutilins, streptogramins, sulfonamides and tetracyclines could be identified. Several ARGs, including ones against amoxicillin–clavulanate, the most commonly applied antimicrobial agent for dog bites, were predicted to be potentially transferable based on their association with mobile genetic elements (e.g., plasmids, prophages and integrated mobile genetic elements). According to our findings, canine saliva may be a source of transfer for ARG-rich bacteria that can either colonize the human body or transport ARGs to the host bacteriota, and thus can be considered as a risk in the spread of antimicrobial resistance.
    Type of Medium: Online Resource
    ISSN: 2079-6382
    URL: Article
    DOI: 10.3390/antibiotics11111490
    Language: English
    Publisher: MDPI AG
    Publication Date: 2022
    detail.hit.zdb_id: 2681345-2
    SSG: 15,3
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  • 4
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    Membrane Permeability and Aqueous Stability Study of Linear and Cyclic Diarylheptanoids from Corylus maxima
    MDPI AG ; 2022
    In:  Pharmaceutics Vol. 14, No. 6 ( 2022-06-12), p. 1250-
    Details
    In: Pharmaceutics, MDPI AG, Vol. 14, No. 6 ( 2022-06-12), p. 1250-
    Abstract: Seven diarylheptanoids were isolated from Corylus maxima by flash chromatography and semipreparative high-performance liquid chromatography (HPLC) and identified by Orbitrap® mass spectrometry (MS) and nuclear magnetic resonance (NMR) spectroscopy as linear diarylheptanoids: hirsutanonol-5-O-β-D-glucopyranoside (1), platyphyllonol-5-O-β-D-xylopyranoside (4), platyphyllenone (5); and cyclic derivatives: alnusonol-11-O-β-D-glucopyranoside (6), alnusone (7), giffonin F (8), carpinontriol B (9). Cyclic diarylheptanoids are reported in C. maxima for the first time. The aqueous stability of the isolated compounds and other characteristic constituents of C. maxima, oregonin (2), hirsutenone (3), quercitrin (10) and myricitrin (11) was evaluated at pH 1.2, 6.8 and 7.4. The passive diffusion of the constituents across biological membranes was investigated by parallel artificial membrane permeability assay for the gastrointestinal tract (PAMPA-GI) and the blood–brain barrier (PAMPA-BBB) methods. The cyclic diarylheptanoid aglycones and quercitrin were stable at all investigated pH values, while a pH-dependent degradation of the other compounds was observed. A validated ultrahigh-performance liquid chromatography-diode-array detection (UHPLC-DAD) method was utilized for the determination of compound concentrations. The structures of the degradation products were characterized by UHPLC-Orbitrap® MS. Platyphyllenone and alnusone possessed log Pe values greater than −5.0 and −6.0 in the PAMPA-GI and PAMPA-BBB studies, respectively, indicating their ability to cross the membranes via passive diffusion. However, only alnusone can be considered to have both good aqueous stability and satisfactory membrane penetration ability.
    Type of Medium: Online Resource
    ISSN: 1999-4923
    URL: Article
    DOI: 10.3390/pharmaceutics14061250
    Language: English
    Publisher: MDPI AG
    Publication Date: 2022
    detail.hit.zdb_id: 2527217-2
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  • 5
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    A New Oxygen Containing Pyclen-Type Ligand as a Manganese(II) Binder for MRI and 52Mn PET Applications: Equilibrium, Kinetic, Relaxometric, Structural and Radiochemical Studies
    MDPI AG ; 2022
    In:  Molecules Vol. 27, No. 2 ( 2022-01-07), p. 371-
    Details
    In: Molecules, MDPI AG, Vol. 27, No. 2 ( 2022-01-07), p. 371-
    Abstract: A new pyclen-3,9-diacetate derivative ligand (H23,9-OPC2A) was synthesized possessing an etheric O-atom opposite to the pyridine ring, to improve the dissociation kinetics of its Mn(II) complex (pyclen = 3,6,9,15-tetraazabicyclo(9.3.1)pentadeca-1(15),11,13-triene). The new ligand is less basic than the N-containing analogue (H23,9-PC2A) due to the non-protonable O-atom. In spite of its lower basicity, the conditional stability of the [Mn(3,9-OPC2A)] (pMn = −log(Mn(II)), cL = cMn(II) = 0.01 mM. pH = 7.4) remains unaffected (pMn = 8.69), compared to the [Mn(3,9-PC2A)] (pMn = 8.64). The [Mn(3,9-OPC2A)] possesses one water molecule, having a lower exchange rate with bulk solvents (kex298 = 5.3 ± 0.4 × 107 s−1) than [Mn(3,9-PC2A)] (kex298 = 1.26 × 108 s−1). These mild differences are rationalized by density-functional theory (DFT) calculations. The acid assisted dissociation of [Mn(3,9-OPC2A)] is considerably slower (k1 = 2.81 ± 0.07 M−1 s−1) than that of the complexes of diacetates or bisamides of various 12-membered macrocycles and the parent H23,9-PC2A. The [Mn(3,9-OPC2A)] is inert in rat/human serum as confirmed by 52Mn labeling (nM range), as well as by relaxometry (mM range). However, a 600-fold excess of EDTA (pH = 7.4) or a mixture of essential metal ions, propagated some transchelation/transmetalation in 7 days. The H23,9-OPC2A is labeled efficiently with 52Mn at elevated temperatures, yet at 37 °C the parent H23,9-PC2A performs slightly better. Ultimately, the H23,9-OPC2A shows advantageous features for further ligand designs for bifunctional chelators.
    Type of Medium: Online Resource
    ISSN: 1420-3049
    URL: Article
    DOI: 10.3390/molecules27020371
    Language: English
    Publisher: MDPI AG
    Publication Date: 2022
    detail.hit.zdb_id: 2008644-1
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  • 6
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    Droplet Digital PCR Is a Novel Screening Method Identifying Potential Cardiac G-Protein-Coupled Receptors as Candidate Pharmacological Targets in a Rat Model of Pressure-Overload-Induced Cardiac Dysfunction
    MDPI AG ; 2023
    In:  International Journal of Molecular Sciences Vol. 24, No. 18 ( 2023-09-07), p. 13826-
    Details
    In: International Journal of Molecular Sciences, MDPI AG, Vol. 24, No. 18 ( 2023-09-07), p. 13826-
    Abstract: The identification of novel drug targets is needed to improve the outcomes of heart failure (HF). G-protein-coupled receptors (GPCRs) represent the largest family of targets for already approved drugs, thus providing an opportunity for drug repurposing. Here, we aimed (i) to investigate the differential expressions of 288 cardiac GPCRs via droplet digital PCR (ddPCR) and bulk RNA sequencing (RNAseq) in a rat model of left ventricular pressure-overload; (ii) to compare RNAseq findings with those of ddPCR; and (iii) to screen and test for novel, translatable GPCR drug targets in HF. Male Wistar rats subjected to transverse aortic constriction (TAC, n = 5) showed significant systolic dysfunction vs. sham operated animals (SHAM, n = 5) via echocardiography. In TAC vs. SHAM hearts, RNAseq identified 69, and ddPCR identified 27 significantly differentially expressed GPCR mRNAs, 8 of which were identified using both methods, thus showing a correlation between the two methods. Of these, Prostaglandin-F2α-receptor (Ptgfr) was further investigated and localized on cardiomyocytes and fibroblasts in murine hearts via RNA-Scope. Antagonizing Ptgfr via AL-8810 reverted angiotensin-II-induced cardiomyocyte hypertrophy in vitro. In conclusion, using ddPCR as a novel screening method, we were able to identify GPCR targets in HF. We also show that the antagonism of Ptgfr could be a novel target in HF by alleviating cardiomyocyte hypertrophy.
    Type of Medium: Online Resource
    ISSN: 1422-0067
    URL: Article
    DOI: 10.3390/ijms241813826
    Language: English
    Publisher: MDPI AG
    Publication Date: 2023
    detail.hit.zdb_id: 2019364-6
    SSG: 12
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  • 7
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    Rescue of Vasopressin Synthesis in Magnocellular Neurons of the Supraoptic Nucleus Normalises Acute Stress-Induced Adrenocorticotropin Secretion and Unmasks an Effect on Social Behaviour in Male Vasopressin-Deficient Brattleboro Rats
    MDPI AG ; 2022
    In:  International Journal of Molecular Sciences Vol. 23, No. 3 ( 2022-01-25), p. 1357-
    Details
    In: International Journal of Molecular Sciences, MDPI AG, Vol. 23, No. 3 ( 2022-01-25), p. 1357-
    Abstract: The relevance of vasopressin (AVP) of magnocellular origin to the regulation of the endocrine stress axis and related behaviour is still under discussion. We aimed to obtain deeper insight into this process. To rescue magnocellular AVP synthesis, a vasopressin-containing adeno-associated virus vector (AVP-AAV) was injected into the supraoptic nucleus (SON) of AVP-deficient Brattleboro rats (di/di). We compared +/+, di/di, and AVP-AAV treated di/di male rats. The AVP-AAV treatment rescued the AVP synthesis in the SON both morphologically and functionally. It also rescued the peak of adrenocorticotropin release triggered by immune and metabolic challenges without affecting corticosterone levels. The elevated corticotropin-releasing hormone receptor 1 mRNA levels in the anterior pituitary of di/di-rats were diminished by the AVP-AAV-treatment. The altered c-Fos synthesis in di/di-rats in response to a metabolic stressor was normalised by AVP-AAV in both the SON and medial amygdala (MeA), but not in the central and basolateral amygdala or lateral hypothalamus. In vitro electrophysiological recordings showed an AVP-induced inhibition of MeA neurons that was prevented by picrotoxin administration, supporting the possible regulatory role of AVP originating in the SON. A memory deficit in the novel object recognition test seen in di/di animals remained unaffected by AVP-AAV treatment. Interestingly, although di/di rats show intact social investigation and aggression, the SON AVP-AAV treatment resulted in an alteration of these social behaviours. AVP released from the magnocellular SON neurons may stimulate adrenocorticotropin secretion in response to defined stressors and might participate in the fine-tuning of social behaviour with a possible contribution from the MeA.
    Type of Medium: Online Resource
    ISSN: 1422-0067
    URL: Article
    DOI: 10.3390/ijms23031357
    Language: English
    Publisher: MDPI AG
    Publication Date: 2022
    detail.hit.zdb_id: 2019364-6
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  • 8
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    Insights Gained in the Aftermath of the COVID-19 Pandemic: A Follow-Up Survey of a Recreational Training Program, Focusing on Sense of Coherence and Sleep Quality
    MDPI AG ; 2020
    In:  International Journal of Environmental Research and Public Health Vol. 17, No. 24 ( 2020-12-09), p. 9201-
    Details
    In: International Journal of Environmental Research and Public Health, MDPI AG, Vol. 17, No. 24 ( 2020-12-09), p. 9201-
    Abstract: The original aim of this study was a follow-up assessment of a recreational program running for six months (September 2019–February 2020) within controlled conditions. Following the arrival of the COVID-19 pandemic, the survey acquired a new goal: how do the subjects of the follow-up sampling experience this severe stress situation, and in this experience, what role does physical activity and a salutogenetic sense of coherence play. Austrian women (N = 53) took part in the training program, whose physical condition was assessed before the start of the program, then reassessed after three months and after six months; the organizers also had them fill out the sense of coherence questionnaire (SOC) as well as the Regensburger insomnia scale. After the lifting of the lockdown introduced due to the pandemic, participants completed an online survey relating to their changed life conditions, physical activities, sense of coherence and sleep quality. Results: After the first three months of the training, no significant changes were detected. After six months, the participants SOC and sleep quality improved (Friedman test: p = 0.005 and p 〈 0.001). During the lockdown, sleep quality generally deteriorated (W-rank test: p = 0.001), while SOC did not change. The women in possession of a relatively stronger SOC continued the training (OR = 3.6, CI 95% = 1.2–12.2), and their sleep quality deteriorated to a lesser degree. (OR = 1.7, CI 95% = 1.1–2.8). Conclusion: The data reinforce the interdependency between physical exercise (PE) and SOC; furthermore, the personal training that the authors formulated for middle-aged women proved to be successful in strengthening their sense of coherence, and it also reduced the deterioration in sleep quality due to stress.
    Type of Medium: Online Resource
    ISSN: 1660-4601
    URL: Article
    DOI: 10.3390/ijerph17249201
    Language: English
    Publisher: MDPI AG
    Publication Date: 2020
    detail.hit.zdb_id: 2175195-X
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  • 9
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    Complexes of Bifunctional DO3A-N-(α-amino)propinate Ligands with Mg(II), Ca(II), Cu(II), Zn(II), and Lanthanide(III) Ions: Thermodynamic Stability, Formation and Dissociation Kinetics, and Solution Dynamic NMR Studies
    MDPI AG ; 2021
    In:  Molecules Vol. 26, No. 16 ( 2021-08-16), p. 4956-
    Details
    In: Molecules, MDPI AG, Vol. 26, No. 16 ( 2021-08-16), p. 4956-
    Abstract: The thermodynamic, kinetic, and structural properties of Ln3+ complexes with the bifunctional DO3A-ACE4− ligand and its amide derivative DO3A-BACE4− (modelling the case where DO3A-ACE4− ligand binds to vector molecules) have been studied in order to confirm the usefulness of the corresponding Gd3+ complexes as relaxation labels of targeted MRI contrast agents. The stability constants of the Mg2+ and Ca2+ complexes of DO3A-ACE4− and DO3A-BACE4− complexes are lower than for DOTA4− and DO3A3−, while the Zn2+ and Cu2+ complexes have similar and higher stability than for DOTA4− and DO3A3− complexes. The stability constants of the Ln(DO3A-BACE)− complexes increase from Ce3+ to Gd3+ but remain practically constant for the late Ln3+ ions (represented by Yb3+). The stability constants of the Ln(DO3A-ACE)4− and Ln(DO3A-BACE)4− complexes are several orders of magnitude lower than those of the corresponding DOTA4− and DO3A3− complexes. The formation rate of Eu(DO3A-ACE)− is one order of magnitude slower than for Eu(DOTA)−, due to the presence of the protonated amine group, which destabilizes the protonated intermediate complex. This protonated group causes the Ln(DO3A-ACE)− complexes to dissociate several orders of magnitude faster than Ln(DOTA)− and its absence in the Ln(DO3A-BACE)− complexes results in inertness similar to Ln(DOTA)− (as judged by the rate constants of acid assisted dissociation). The 1H NMR spectra of the diamagnetic Y(DO3A-ACE)− and Y(DO3A-BACE)− reflect the slow dynamics at low temperatures of the intramolecular isomerization process between the SA pair of enantiomers, R-Λ(λλλλ) and S-Δ(δδδδ). The conformation of the Cα-substituted pendant arm is different in the two complexes, where the bulky substituent is further away from the macrocyclic ring in Y(DO3A-BACE)− than the amino group in Y(DO3A-ACE)− to minimize steric hindrance. The temperature dependence of the spectra reflects slower ring motions than pendant arms rearrangements in both complexes. Although losing some thermodynamic stability relative to Gd(DOTA)−, Gd(DO3A-BACE)− is still quite inert, indicating the usefulness of the bifunctional DO3A-ACE4− in the design of GBCAs and Ln3+-based tags for protein structural NMR analysis.
    Type of Medium: Online Resource
    ISSN: 1420-3049
    URL: Article
    DOI: 10.3390/molecules26164956
    Language: English
    Publisher: MDPI AG
    Publication Date: 2021
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  • 10
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    How Equine-Assisted Activities Affect the Prosocial Behavior of Adolescents
    MDPI AG ; 2020
    In:  International Journal of Environmental Research and Public Health Vol. 17, No. 8 ( 2020-04-24), p. 2967-
    Details
    In: International Journal of Environmental Research and Public Health, MDPI AG, Vol. 17, No. 8 ( 2020-04-24), p. 2967-
    Abstract: Multiple studies have investigated the positive effects of human–animal interactions and showed that animal-assisted activities can be successfully used to better human physical and mental health. Equine-assisted activities have also raised considerable attention within the field. Our research focuses on healthy students (aged 14–18) without deviations or special educational needs. We analyze the occurrence of behavior problems and prosocial behavior among adolescents who regularly have interactions with horses, and those who have no connection to horses at all. The subjects of our investigation completed the strengths and difficulties questionnaire (SDQ), and we use a ‘quasi’ 2 × 2 before-after control-impact design to analyze the data. Students studying equine-related vocations and students of other vocations are compared, at the beginning and at the end of their studies. Our results indicate that students of equine-related vocations are more helpful and empathetic, and have fewer behavior problems, than those studying other vocations. There is a negative correlation between prosocial behavior and behavior problems. The development of the prosocial behaviors of students with regular horse–human interactions is more remarkable than of those who have no connection to horses. With these results, we are going to confirm the hypothesis that equine-assisted activities correlate with positive behavioral traits among healthy adolescents.
    Type of Medium: Online Resource
    ISSN: 1660-4601
    URL: Article
    DOI: 10.3390/ijerph17082967
    Language: English
    Publisher: MDPI AG
    Publication Date: 2020
    detail.hit.zdb_id: 2175195-X
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