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1.
Environ Microbiol ; 24(1): 240-264, 2022 01.
Article in English | MEDLINE | ID: mdl-34811861

ABSTRACT

Cupriavidus necator UYPR2.512 is a rhizobial strain that belongs to the Beta-subclass of proteobacteria, able to establish successful symbiosis with Mimosoid legumes. The initial steps of rhizobium-legumes symbioses involve the reciprocal recognition by chemical signals, being luteolin one of the molecules involved. However, there is a lack of information on the effect of luteolin in beta-rhizobia. In this work, we used long-read sequencing to complete the genome of UYPR2.512 providing evidence for the existence of four closed circular replicons. We used an RNA-Seq approach to analyse the response of UYPR2.512 to luteolin. One hundred and forty-five genes were differentially expressed, with similar numbers of downregulated and upregulated genes. Most repressed genes were mapped to the main chromosome, while the upregulated genes were overrepresented among pCne512e, containing the symbiotic genes. Induced genes included the nod operon and genes implicated in exopolysaccharides and flagellar biosynthesis. We identified many genes involved in iron, copper and other heavy metals metabolism. Among repressed genes, we identified genes involved in basal carbon and nitrogen metabolism. Our results suggest that in response to luteolin, C. necator strain UYPR2.512 reshapes its metabolism in order to be prepared for the forthcoming symbiotic interaction.


Subject(s)
Cupriavidus necator , Cupriavidus , Fabaceae , Rhizobium , Cupriavidus/genetics , Cupriavidus necator/genetics , Fabaceae/microbiology , Genomics , Luteolin/metabolism , Luteolin/pharmacology , Nitrogen Fixation , Phylogeny , Rhizobium/genetics , Symbiosis/genetics , Transcriptome
2.
Microb Cell Fact ; 20(1): 41, 2021 Feb 10.
Article in English | MEDLINE | ID: mdl-33568151

ABSTRACT

BACKGROUND: Microbes are present in almost every environment on Earth, even in those with extreme environmental conditions such as Antarctica, where rocks may represent the main refuge for life. Lithobiontic communities are composed of microorganisms capable of colonizing rocks and, as it is a not so well studied bacterial community, they may represent a very interesting source of diversity and functional traits with potential for biotechnological applications. In this work we analyzed the ability of Antarctic lithobiontic bacterium to synthesize cadmium sulfide quantum dots (CdS QDs) and their potential application in solar cells. RESULTS: A basaltic andesite rock sample was collected from Fildes Peninsula, King George Island, Antarctica, and processed in order to isolate lithobiontic bacterial strains. Out of the 11 selected isolates, strain UYP1, identified as Pedobacter, was chosen for further characterization and analysis due to its high cadmium tolerance. A protocol for the biosynthesis of CdS QDs was developed and optimized for this strain. After 20 and 80 min of synthesis, yellow-green and orange-red fluorescent emissions were observed under UV light, respectively. QDs were characterized through spectroscopic techniques, dynamic light scattering analysis, high-resolution transmission electron microscopy and energy dispersive x-ray spectroscopy. Nanostructures of 3.07 nm, composed of 51.1% cadmium and 48.9% sulfide were obtained and further used as photosensitizer material in solar cells. These solar cells were able to conduct electrons and displayed an open circuit voltage of 162 mV, a short circuit current density of 0.0110 mA cm-2, and had an efficiency of conversion up to 0.0016%, which is comparable with data previously reported for solar cells sensitized with biologically produced quantum dots. CONCLUSIONS: We report a cheap, rapid and eco-friendly protocol for the production of CdS QDs by an Antarctic lithobiontic bacterium, Pedobacter, a genus that was not previously reported as a quantum dot producer. The application of the biosynthesized QDs as sensitizer material in solar cells was validated.


Subject(s)
Calcium Compounds/chemistry , Pedobacter/chemistry , Quantum Dots/chemistry , Solar Energy , Sulfides/chemistry , Antarctic Regions
3.
Gynecol Oncol ; 158(2): 323-330, 2020 08.
Article in English | MEDLINE | ID: mdl-32475773

ABSTRACT

OBJECTIVE: This study assessed outcomes of inoperable endometrial cancer (IEC) patients treated with definitive external beam radiation therapy (EBRT) followed by a 3D image-guided brachytherapy boost. METHODS: All consecutive patients treated with EBRT followed by 3D image-guided brachytherapy for IEC were retrospectively included. EBRT delivered a dose of 45Gy. Then, patients had an uterovaginal brachytherapy guided by 3D imaging. Clinical target volume (CTVBT) included the whole uterus and the initial disease extent. Gross tumour volume (GTVres) included the residual disease at time of brachytherapy. RESULTS: Twenty-seven patients were identified. Causes of inoperability were comorbidities (37%) or tumour loco regional extent (63%). Including EBRT and brachytherapy, the median D90 (minimal dose delivered to 90% of the volume) was 60.7 GyEQD2 (IQR = 56.4-64.2) for the CTVBT, and was 73.6 GyEQD2 (IQR = 64.1-83.7) for the GTVres. The median overall treatment time was 50 days (IQR = 46-54). The mean follow-up was 36.5 months (SD = 30.2). The cumulative incidence of local, pelvic and distant failures was 19% (n = 5), 7% (n = 2) and 26% (n = 7), respectively. Five-year overall survival was 63% (95% CI = 43-91). Late urinary and gastro intestinal toxicities ≥ grade 2 were reported in four (15%) and two patients (7%) respectively. No vaginal toxicity ≥ grade 2 was reported. CONCLUSIONS: EBRT followed by intracavitary brachytherapy seems to be an effective option for IEC. The implementation of 3D concepts at time of brachytherapy may contribute to high local control probability and low toxicity profile. Large scale retrospective or prospective data are needed to confirm these early data.


Subject(s)
Brachytherapy/methods , Endometrial Neoplasms/diagnostic imaging , Endometrial Neoplasms/radiotherapy , Radiotherapy, Image-Guided/methods , Aged , Case-Control Studies , Disease-Free Survival , Endometrial Neoplasms/pathology , Female , Humans , Imaging, Three-Dimensional/methods , Lymphatic Metastasis , Magnetic Resonance Imaging , Middle Aged , Neoplasm Staging , Radiotherapy Dosage , Radiotherapy Planning, Computer-Assisted/methods , Retrospective Studies , Tomography, X-Ray Computed
4.
PLoS One ; 19(4): e0302009, 2024.
Article in English | MEDLINE | ID: mdl-38620042

ABSTRACT

Phytoliths of biogenic silica play a vital role in the silicon biogeochemical cycle and occlude a fraction of organic carbon. The location, chemical speciation, and quantification of this carbon within phytoliths have remained elusive due to limited direct experimental evidence. In this work, phytoliths (bilobate morphotype) from the sugarcane stalk epidermis are sectioned with a focused ion beam to produce lamellas (≈10 × 10 µm2 size, <500 nm thickness) and probed by synchrotron scanning transmission X-ray microspectroscopy (≈100-200 nm pixel size; energies near the silicon and carbon K-absorption edges). Analysis of the spectral image stacks reveals the complementarity of the silica and carbon spatial distributions, with carbon found at the borders of the lamellas, in islands within the silica, and dispersed in extended regions that can be described as a mixed silica-carbonaceous matrix. Carbon spectra are assigned mainly to lignin-like compounds as well as to proteins. Carbon contents of 3-14 wt.% are estimated from the spectral maps of four distinct phytolith lamellas. The results provide unprecedented spatial and chemical information on the carbon in phytoliths obtained without interference from wet-chemical digestion.


Subject(s)
Silicon Dioxide , Silicon , Silicon Dioxide/chemistry , X-Rays , Carbon/analysis , Synchrotrons
5.
Clin Neurophysiol ; 158: 35-42, 2024 02.
Article in English | MEDLINE | ID: mdl-38150916

ABSTRACT

OBJECTIVE: This longitudinal study aims at assessing the predictive value of facial nerve high-resolution ultrasound (HRUS) for incomplete clinical recovery in patients with Bell's palsy, the most common facial nerve disease. METHODS: We prospectively enrolled 34 consecutive patients with Bell's palsy. All patients underwent neurophysiological testing (including facial nerve conduction study) and HRUS evaluations 10-15 days (T1), one month (T2), and three months (T3) after the onset of Bell's palsy. Patients who did not experience complete recovery within three months were also evaluated after six months (T4). We have then compared the accuracy of HRUS with that of the facial nerve conduction study in predicting incomplete clinical recovery at three and six months. RESULTS: At T1, the facial nerve diameter, as assessed with HRUS, was larger on the affected side than on the normal side, particularly in patients with incomplete recovery at T2, T3 and T4. ROC curve analysis, however, showed that the facial nerve diameter at T1 had a lower predictive value than the facial nerve conduction study for an incomplete clinical recovery at three (T3) and six (T4) months. Still, the facial nerve diameter asymmetry, as assessed with HRUS, had a relatively high negative predictive value (thus indicating a strong association between normal HRUS examination and a good prognosis). CONCLUSIONS: Although HRUS shows abnormally increased facial nerve diameter in patients in the acute phase of Bell's palsy, the predictive value of this technique for incomplete clinical recovery at three and six months is lower than that of the nerve conduction study. SIGNIFICANCE: Nerve ultrasound has a low predictive value for incomplete clinical recovery in patients with Bell's Palsy.


Subject(s)
Bell Palsy , Facial Paralysis , Humans , Bell Palsy/diagnostic imaging , Facial Nerve/diagnostic imaging , Nerve Conduction Studies , Longitudinal Studies
6.
Nat Commun ; 15(1): 6375, 2024 Aug 14.
Article in English | MEDLINE | ID: mdl-39143069

ABSTRACT

Wisdom is the hallmark of social judgment, but how people across cultures recognize wisdom remains unclear-distinct philosophical traditions suggest different views of wisdom's cardinal features. We explore perception of wise minds across 16 socio-economically and culturally diverse convenience samples from 12 countries. Participants assessed wisdom exemplars, non-exemplars, and themselves on 19 socio-cognitive characteristics, subsequently rating targets' wisdom, knowledge, and understanding. Analyses reveal two positively related dimensions-Reflective Orientation and Socio-Emotional Awareness. These dimensions are consistent across the studied cultural regions and interact when informing wisdom ratings: wisest targets-as perceived by participants-score high on both dimensions, whereas the least wise are not reflective but moderately socio-emotional. Additionally, individuals view themselves as less reflective but more socio-emotionally aware than most wisdom exemplars. Our findings expand folk psychology and social judgment research beyond the Global North, showing how individuals perceive desirable cognitive and socio-emotional qualities, and contribute to an understanding of mind perception.


Subject(s)
Judgment , Humans , Female , Male , Adult , Young Adult , Emotions , Knowledge , Cross-Cultural Comparison , Cognition/physiology , Middle Aged , Social Perception , Adolescent , Perception
7.
J Chem Phys ; 138(12): 124112, 2013 Mar 28.
Article in English | MEDLINE | ID: mdl-23556714

ABSTRACT

We apply the frozen density embedding method, using a full relaxation of embedded densities through a freeze-and-thaw procedure, to study the electronic structure of several benchmark ground-state charge-transfer complexes, in order to assess the merits and limitations of the approach for this class of systems. The calculations are performed using both semilocal and hybrid exchange-correlation (XC) functionals. The results show that embedding calculations using semilocal XC functionals yield rather large deviations with respect to the corresponding supermolecular calculations. Due to a large error cancellation effect, however, they can often provide a relatively good description of the electronic structure of charge-transfer complexes, in contrast to supermolecular calculations performed at the same level of theory. On the contrary, when hybrid XC functionals are employed, both embedding and supermolecular calculations agree very well with each other and with the reference benchmark results. In conclusion, for the study of ground-state charge-transfer complexes via embedding calculations hybrid XC functionals are the method of choice due to their higher reliability and superior performance.


Subject(s)
Quantum Theory
8.
Cancer Radiother ; 27(4): 328-336, 2023 Jun.
Article in English | MEDLINE | ID: mdl-36759241

ABSTRACT

Adenoid cystic carcinoma of the Bartholin's gland (ACCBG) is a rare, slowly but aggressive malignancy. We reported the case of a 31-year-old woman who was treated by local excision and then hemi-vulvectomy, with positive margins and perineural invasion. Radiation therapy (RT) was then performed delivering 45Gy in 25 fractions in bilateral inguinal lymph nodes and 64.8Gy in 36 fractions on the vulvar area. After 30 months, there was no local relapse (LR) but the patient presented a histologically documented lung recurrence. Genomic profiling of the tumor showed a MYB-NFIB fusion transcript and a somatic mutation of PLCG1. A treatment by Lenvatinib was started. We conducted a literature review of 100 published cases. Patients were mainly treated by radical vulvectomy (30%), hemi-vulvectomy (17%), wide or local excision (21% and 24%, respectively) or other. Forty-four percent of patients received postoperative RT, more frequently in case of positive margin (71.9% versus 29.5%). RT may reduce the risk of LR regardless of margin status, with 15.4% vs. 41.9% of LR with or without RT, respectively, in patients with negative margins, and 13% vs. 33.3% of LR with or without RT, respectively, in patients with positive margins. The risk of relapse of any type was 40.9% in patients who received adjuvant RT vs. 48.2% in patients who did not. Median time to relapse was 24 months (range 6-156 months). The most frequent metastatic sites were lung (76.7%) and bone (26.7%). Optimal treatment for ACCBG is still not clearly defined but pooling the data from published case report help us better understand this rare disease and help in the therapeutic decision.


Subject(s)
Bartholin's Glands , Carcinoma, Adenoid Cystic , Vulvar Neoplasms , Female , Humans , Adult , Carcinoma, Adenoid Cystic/genetics , Carcinoma, Adenoid Cystic/therapy , Bartholin's Glands/pathology , Vulvar Neoplasms/genetics , Vulvar Neoplasms/therapy , Genomics , Recurrence
9.
J Chem Phys ; 137(1): 014102, 2012 Jul 07.
Article in English | MEDLINE | ID: mdl-22779632

ABSTRACT

We analyze the accuracy of the frozen density embedding (FDE) method, with hybrid and orbital-dependent exchange-correlation functionals, for the calculation of the total interaction energies of weakly interacting systems. Our investigation is motivated by the fact that these approaches require, in addition to the non-additive kinetic energy approximation, also approximate non-additive exact-exchange energies. Despite this further approximation, we find that the hybrid/orbital-dependent FDE approaches can reproduce the total energies with the same accuracy (about 1 mHa) as the one of conventional semi-local functionals. In many cases, thanks to error cancellation effects, hybrid/orbital-dependent approaches yield even the smallest error. A detailed energy-decomposition investigation is presented. Finally, the Becke-exchange functional is found to reproduce accurately the non-additive exact-exchange energies also for non-equilibrium geometries. These performances are rationalized in terms of a reduced-gradient decomposition of the non-additive exchange energy.


Subject(s)
Quantum Theory , Kinetics , Thermodynamics
10.
J Chem Phys ; 137(13): 134702, 2012 Oct 07.
Article in English | MEDLINE | ID: mdl-23039605

ABSTRACT

We present an extension of the charge-dipole model for the description of periodic systems. This periodic charge-dipole electrostatic model (PCDEM) allows one to describe the linear response of periodic structures in terms of charge- and dipole-type gaussian basis functions. The long-range electrostatic interaction is efficiently described by means of the continuous fast multipole method. As a first application, the PCDEM method is applied to describe the polarizability of silver slabs. We find that for a correct description of the polarizability of the slabs both charges and dipoles are required. However a continuum set of parametrizations, i.e., different values of the width of charge- and dipole-type gaussians, leads to an equivalent and accurate description of the slabs polarizability but a completely unphysical description of induced charge-density inside the slab. We introduced the integral squared density measure which allows one to obtain a unique parametrization which accurately describes both the polarizability and the induced density profile inside the slab. Finally the limits of the electrostatic approximations are also pointed out.


Subject(s)
Quantum Theory , Silver/chemistry , Static Electricity
12.
Phys Rev Lett ; 106(18): 186406, 2011 May 06.
Article in English | MEDLINE | ID: mdl-21635112

ABSTRACT

We use the asymptotic expansions of the semiclassical neutral atom as a reference system in density functional theory to construct accurate generalized gradient approximations (GGAs) for the exchange-correlation and kinetic energies without any empiricism. These asymptotic functionals are among the most accurate GGAs for molecular systems, perform well for solid state, and overcome current GGA state of the art in frozen density embedding calculations. Our results also provide evidence for the conjointness conjecture between exchange and kinetic energies of atomic systems.

13.
J Chem Phys ; 134(19): 194112, 2011 May 21.
Article in English | MEDLINE | ID: mdl-21599049

ABSTRACT

We compare the performance of different exchange-correlation functionals, based on the Perdew-Burke-Ernzerhof (PBE) generalized gradient approximation, for the structural and electronic properties of gold nanostructures. In particular we consider PBEsol (constructed to correctly describe solid-state systems) and PBEint [Phys. Rev. B 82, 113104 (2010)] which was recently introduced for hybrid interfaces and preserves the correct second-order gradient expansion of exchange energy (as in PBEsol) providing as well a significant nonlocality for higher density variation (as in PBE). We find that the PBEint functional gives a well balanced description of atomization energies, structural properties, energy differences between isomers, and bulk properties. Results indicate that PBEint is expected to be the most accurate functional for medium and large size gold clusters of different shapes.


Subject(s)
Algorithms , Chemistry, Physical/methods , Gold/chemistry , Models, Chemical , Nanostructures/chemistry , Computer Simulation , Surface Properties , Thermodynamics
14.
Cancer Radiother ; 25(8): 771-778, 2021 Dec.
Article in French | MEDLINE | ID: mdl-34175226

ABSTRACT

PURPOSE: The purpose of this study was to assess the efficacy in terms of neck failure of an initial neck dissection before definitive chemoradiotherapy in N2-3 oropharyngeal squamous cell carcinomas, as well as the dosimetric impact and the acute and delayed morbidity of this approach. MATERIALS AND METHODS: All patients consecutively treated between 2009 and 2018 with definitive chemoradiotherapy using intensity-modulated conformal radiotherapy (IMRT) for a histologically proven N2-3 oropharyngeal squamous cell carcinomas were retrospectively included. The therapeutic approach consisted of induction chemotherapy, followed by cisplatine-based chemoradiotherapy preceded or not by neck dissection. Neck dissection was discussed on a case-by-case basis in a dedicated multidisciplinary tumour board for patients with a dissociated response to induction chemotherapy, defined as a better response on the primary than on the node. Chemoradiotherapy without neck dissection was systematically performed in case of a major lymph node response to induction chemotherapy (decrease in size of 90% or more). Intensity-modulated radiotherapy using a simultaneous-integrated boost delivered 70Gy in 35 fractions on macroscopic tumour volumes, 63Gy on intermediate-risk levels or extra-nodal extension and 54Gy on prophylactic lymph node areas. RESULTS: Two groups were constituted: 47 patients without an initial neck dissection (62.7%), and 28 patients with a neck dissection prior to definitive chemoradiotherapy (37.3%). Initial patient characteristics were not statistically different between the two groups. The median follow-up was 60.1months (range: 3.2-119months). Incidence of neck failure was higher in patients without neck dissection (P=0.015). The neck failure rate at 5years was 19.8% (95% confidence interval: 7.4-30.6%; P=0.015) without neck dissection versus 0% following neck dissection. All lymph node failures occurred in the planned target volume at 70Gy. Upfront neck dissection suggested a decrease in the mean dose received by the homolateral parotid gland (P=0.01), mandible (P=0.02), and thyroid gland (P=0.02). Acute toxicity of chemoradiotherapy after neck dissection suggested a reduction in grade≥3 adverse events (P=0.04), early discontinuation of concomitant chemotherapy (P=0.009) and feeding tube-dependence (P=0.008) in univariate analysis. During follow-up, there was no difference between the two groups in terms of xerostomia, dysgeusia, dysphagia or gastrostomy dependence in univariate analysis. CONCLUSION: Neck dissection prior to definitive chemoradiotherapy in N2-3 oropharyngeal squamous cell carcinoma was associated with high neck control without additional mid and long-term morbidity.


Subject(s)
Chemoradiotherapy/methods , Neck Dissection , Oropharyngeal Neoplasms/therapy , Radiotherapy, Intensity-Modulated , Squamous Cell Carcinoma of Head and Neck/therapy , Adult , Aged , Aged, 80 and over , Chemoradiotherapy/adverse effects , Cisplatin/therapeutic use , Combined Modality Therapy/methods , Deglutition Disorders/epidemiology , Dose Fractionation, Radiation , Dysgeusia/epidemiology , Female , Follow-Up Studies , Humans , Induction Chemotherapy , Lymphatic Metastasis , Male , Mandible/radiation effects , Middle Aged , Neck Dissection/adverse effects , Organs at Risk/radiation effects , Oropharyngeal Neoplasms/mortality , Oropharyngeal Neoplasms/pathology , Parotid Gland/radiation effects , Radiotherapy Dosage , Radiotherapy, Intensity-Modulated/adverse effects , Retrospective Studies , Squamous Cell Carcinoma of Head and Neck/mortality , Squamous Cell Carcinoma of Head and Neck/pathology , Thyroid Gland/radiation effects , Xerostomia/epidemiology
15.
Clin Sci (Lond) ; 119(7): 283-92, 2010 Jun 25.
Article in English | MEDLINE | ID: mdl-20459396

ABSTRACT

Our present study examines, in mesenteric resistance arteries, possible vasodilation alterations, and the role of NO and COX (cyclo-oxygenase) derivatives, in cirrhosis. The vasodilator response to acetylcholine was analysed in segments from control and cirrhotic rats. The effects of the non-specific COX inhibitor indomethacin, the specific COX-1 inhibitor SC-560 and the specific COX-2 inhibitor NS-398 were analysed in segments from both groups of rats. NO release was measured, and eNOS [endothelial NOS (NO synthase)], phospho-eNOS, iNOS (inducible NOS), COX-1 and COX-2 protein expression was also analysed. The effects of the TP receptor [TXA2 (thromboxane A(2)) receptor] antagonist SQ 29548, the TXA(2) synthesis inhibitor furegrelate, the PGI(2) (prostaglandin I(2)) synthesis inhibitor TCP (tranylcypromine) or TCP+furegrelate were only determined in segments from cirrhotic rats. The vasodilator response to acetylcholine was higher in segments from cirrhotic rats. Indomethacin, SC-560 and NS-398 did not modify the vasodilator response in control rats; however, indomethacin, NS-398 and TCP+furegrelate increased, whereas SC-560 did not modify and SQ 29548, furegrelate or TCP decreased, the vasodilator response to acetylcholine in cirrhotic rats. NO release was higher in cirrhotic rats. Furegrelate decreased, whereas TCP+furegrelate increased, the NO release in segments from cirrhotic rats. eNOS and COX-1 protein expression was not modified, whereas phosho-eNOS, iNOS and COX-2 protein expression was higher in cirrhotic rats. Therefore the increase in iNOS expression and eNOS activity may mediate increases in endothelial NO release. The COX-2 derivatives TXA(2) and PGI(2) may act simultaneously, producing a compensatory effect that reduces NO release and may limit the hyperdynamic circulation.


Subject(s)
Liver Cirrhosis, Experimental/metabolism , Mesenteric Arteries/metabolism , Nitric Oxide/metabolism , Prostaglandins A/physiology , Thromboxane A2/physiology , Animals , Blood Pressure/physiology , Body Weight/physiology , C-Reactive Protein/metabolism , Lipid Metabolism/physiology , Liver/pathology , Liver Cirrhosis, Experimental/physiopathology , Male , Organ Size/physiology , Prostaglandins/metabolism , Prostaglandins A/biosynthesis , Rats , Rats, Sprague-Dawley , Spleen/pathology , Superoxides/metabolism , Thromboxane A2/biosynthesis , Vasodilation/physiology
16.
J Chem Phys ; 133(16): 164111, 2010 Oct 28.
Article in English | MEDLINE | ID: mdl-21033779

ABSTRACT

The Kohn-Sham equations with constrained electron density are extended to hybrid exchange-correlation (XC) functionals. We derive the frozen density embedding generalized Kohn-Sham (FDE-GKS) scheme which allows to treat the nonlocal exact-exchange in the subsystems. For practical calculations we propose an approximated version of the FDE-GKS in which the nonadditive exchange potential is computed at a semilocal level. The proposed method is applied to compute the ground-state electronic properties of small test systems and selected DNA base pairs. The results of calculations employing the hierarchy of XC functionals BLYP/B3LYP/BHLYP and PBE/PBE0 are presented, in order to analyze the effect of nonlocal exchange contributions, and compared with reference coupled-cluster singles and doubles results. We find that the use of hybrid functionals leads to a significant improvement in the description of ground-state electronic properties of the investigated systems. The semilocal version of the FDE-GKS correctly reproduces the dipole and the electron density distribution of the exact GKS supramolecular system, with errors smaller than the ones obtained using conventional semilocal XC functionals.


Subject(s)
Base Pairing , DNA/chemistry , Quantum Theory , Models, Molecular
17.
J Physiol Biochem ; 66(4): 301-9, 2010 Dec.
Article in English | MEDLINE | ID: mdl-20865358

ABSTRACT

Spontaneously hypertensive rat (SHR) offspring from L-arginine- and antioxidant-supplemented SHR dams had persistent lower blood pressure in adulthood. We investigated the influence of vascular mechanism in this effect. We analyzed response to acetylcholine and phenylephrine in aorta and superior mesenteric arteries from Wistar-Kyoto (WKY), SHR, and SHR perinatally supplemented with L-arginine and 4-hydroxy-2,2,6,6-tetramethylpiperidinoxyl (TEMPOL; SHR-suppl). Supplements reduced blood pressure persistently in SHR. Relaxation to acetylcholine was greater in WKY than SHR and remained unmodified in SHR-suppl compared with SHR. Acute TEMPOL did not alter relaxation to acetylcholine in WKY but increased it similarly in SHR and SHR-suppl. Phenylephrine contraction was increased in SHR compared to WKY. In SHR-suppl, this response was similar to SHR. Endothelium removal or N-nitro-L-arginine methyl ester (L-NAME) increased contraction to phenylephrine more in WKY than SHR. In SHR-suppl, this was similar to SHR. In both SHR and SHR-suppl, TEMPOL similarly reduced phenylephrine response. This effect was prevented by L-NAME. Results exposed reinforce the concept that oxidative stress during perinatal period is a contributing factor to the development of hypertension in SHR. Results also reveal that the beneficial effect of this supplementation does not appear to be related to improved endothelial function, suggesting that other regulatory mechanisms of blood pressure may be involved.


Subject(s)
Antioxidants/metabolism , Arginine/metabolism , Acetylcholine/chemistry , Animals , Animals, Newborn , Antioxidants/chemistry , Blood Pressure , Cyclic N-Oxides/chemistry , Cyclic N-Oxides/pharmacology , Dose-Response Relationship, Drug , Hypertension/drug therapy , Hypertension/pathology , NG-Nitroarginine Methyl Ester/metabolism , Nitric Oxide/chemistry , Oxidative Stress , Phenylephrine/chemistry , Rats , Rats, Inbred SHR , Rats, Inbred WKY , Spin Labels
18.
Acta Physiol (Oxf) ; 230(1): e13484, 2020 09.
Article in English | MEDLINE | ID: mdl-32336027

ABSTRACT

For a long time, the vascular tone was considered to be regulated exclusively by tonic innervation of vasoconstrictor adrenergic nerves. However, accumulating experimental evidence has revealed the existence of nerves mediating vasodilatation, including perivascular nitrergic nerves (PNN), in a wide variety of mammalian species. Functioning of nitrergic vasodilator nerves is evidenced in several territories, including cerebral, mesenteric, pulmonary, renal, penile, uterine and cutaneous arteries. Nitric oxide (NO) is the main neurogenic vasodilator in cerebral arteries and acts as a counter-regulatory mechanism for adrenergic vasoconstriction in other vascular territories. In the penis, NO relaxes the vascular and cavernous smooth muscles leading to penile erection. Furthermore, when interacting with other perivascular nerves, NO can act as a neuromodulator. PNN dysfunction is involved in the genesis and maintenance of vascular disorders associated with arterial and portal hypertension, diabetes, ageing, obesity, cirrhosis and hormonal changes. For example defective nitrergic function contributes to enhanced sympathetic neurotransmission, vasoconstriction and blood pressure in some animal models of hypertension. In diabetic animals and humans, dysfunctional nitrergic neurotransmission in the corpus cavernosum is associated with erectile dysfunction. However, in some vascular beds of hypertensive and diabetic animals, an increased PNN function has been described as a compensatory mechanism to the increased vascular resistance. The present review summarizes current understanding on the role of PNN in control of vascular tone, its alterations under different conditions and the associated mechanisms. The knowledge of these changes can serve to better understand the mechanisms involved in these disorders and help in planning new treatments.


Subject(s)
Arteries/innervation , Vasoconstriction , Vasodilation , Animals , Humans , Male , Nitric Oxide , Penis/innervation
19.
Curr Pharm Des ; 26(30): 3633-3651, 2020.
Article in English | MEDLINE | ID: mdl-32242780

ABSTRACT

Cardiovascular diseases (CVD) are considered a major health problem worldwide, being the main cause of mortality in developing and developed countries. Endothelial dysfunction, characterized by a decline in nitric oxide production and/or bioavailability, increased oxidative stress, decreased prostacyclin levels, and a reduction of endothelium-derived hyperpolarizing factor is considered an important prognostic indicator of various CVD. Changes in cyclic nucleotides production and/ or signalling, such as guanosine 3', 5'-monophosphate (cGMP) and adenosine 3', 5'-monophosphate (cAMP), also accompany many vascular disorders that course with altered endothelial function. Phosphodiesterases (PDE) are metallophosphohydrolases that catalyse cAMP and cGMP hydrolysis, thereby terminating the cyclic nucleotide-dependent signalling. The development of drugs that selectively block the activity of specific PDE families remains of great interest to the research, clinical and pharmaceutical industries. In the present review, we will discuss the effects of PDE inhibitors on CVD related to altered endothelial function, such as atherosclerosis, diabetes mellitus, arterial hypertension, stroke, aging and cirrhosis. Multiple evidences suggest that PDEs inhibition represents an attractive medical approach for the treatment of endothelial dysfunction-related diseases. Selective PDE inhibitors, especially PDE3 and PDE5 inhibitors are proposed to increase vascular NO levels by increasing antioxidant status or endothelial nitric oxide synthase expression and activation and to improve the morphological architecture of the endothelial surface. Thereby, selective PDE inhibitors can improve the endothelial function in various CVD, increasing the evidence that these drugs are potential treatment strategies for vascular dysfunction and reinforcing their potential role as an adjuvant in the pharmacotherapy of CVD.


Subject(s)
Cyclic GMP , Phosphoric Diester Hydrolases , Biological Factors , Humans , Nitric Oxide , Nucleotides, Cyclic
20.
Cancer Radiother ; 24(6-7): 751-754, 2020 Oct.
Article in French | MEDLINE | ID: mdl-32753236

ABSTRACT

New concepts of medical consultations are currently disrupting the practice of medicine. The use of standardized questionnaires, or patient-reported outcome (PRO and ePRO) has already significantly changed the relationship between the physician and the patient. Telemedicine, or even automatic conversational agents, such as chatbots, are also providing more convenient access to care and medical information for many patients. These tools have a major impact in oncology, precisely because of the rising chronicity of the diseases the radiation oncologists treat. In this article, we provide a detailed analysis of these new concepts.


Subject(s)
Neoplasms/radiotherapy , Radiation Oncology/methods , Remote Consultation , Humans , Patient Reported Outcome Measures , Surveys and Questionnaires
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