DiMaria delves into how playwrights not only brought inventive new dramaturgical methods to the genre, but also incorporated significant aspects of the morals and aesthetic preferences familiar to ...contemporary spectators into their works.
While several behavioral and neuroscience studies have explored visual, auditory, and cross-modal illusions, information about the phenomenology and neural correlates of somatosensory illusions is ...meager. By combining psychophysics and somatosensory evoked potentials, we explored in healthy humans the neural correlates of 2 compelling tactuo-proprioceptive illusions, namely Aristotle (1 object touching the contact area between 2 crossed fingers is perceived as 2 lateral objects) and Reverse illusions (2 lateral objects are perceived as 1 between crossed-fingers object). These illusions likely occur because of the tactuo-proprioceptive conflict induced by fingers being crossed in a non-natural posture. We found that different regions in the somatosensory stream exhibit different proneness to the illusions. Early electroencephalographic somatosensory activity (at 20 ms) originating in the primary somatosensory cortex (S1) reflects the phenomenal rather than the physical properties of the stimuli. Notably, later activity (around 200 ms) originating in the posterior parietal cortex is higher when subjects resist the illusions. Thus, while S1 activity is related to illusory perception, PPC acts as a conflict resolver that recodes tactile events from somatotopic to spatiotopic frames of reference and ultimately enables veridical perception.
An undescribed 5,6-dihydropyran-2-one, namely diplopyrone C, was isolated and characterized from the cultures of an isolate of the fungus
recovered from
in Algeria. The structure and relative ...stereostructure of (5
,6S,7
,9
,10
)-5-hydroxy-6-(2-(3-methyloxiran-2-yl)vinyl)-5,6-dihydro-2H-pyran-2-one were assigned essentially based on NMR and MS data. Furthermore, ten known compounds were isolated and identified in the same cultures. The most abundant product, the tetracyclic pimarane diterpene sphaeropsidin A, was tested for insecticidal effects against the model sucking aphid,
. Results showed a toxic dose-dependent oral activity of sphaeropsidin A, with an LC
of 9.64 mM.
A new family of
Tc(I)- tricarbonyl complexes and
I-heteroaromatic compounds bearing an acridine orange (AO) DNA targeting unit was evaluated for Auger therapy. Characterization of the DNA ...interaction, performed with the non-radioactive Re and
I congeners, confirmed that all compounds act as DNA intercalators. Both classes of compounds induce double strand breaks (DSB) in plasmid DNA but the extent of DNA damage is strongly dependent on the linker between the Auger emitter (
Tc or
I) and the AO moiety. The in vitro evaluation was complemented with molecular docking studies and Monte Carlo simulations of the energy deposited at the nanometric scale, which corroborated the experimental data. Two of the tested compounds,
I-C
and
Tc-C
, place the corresponding radionuclide at similar distances to DNA and produce comparable DSB yields in plasmid and cellular DNA. These results provide the first evidence that
Tc can induce DNA damage with similar efficiency to that of
I, when both are positioned at comparable distances to the double helix. Furthermore, the high nuclear retention of
Tc-C
in tumoral cells suggests that
Tc-labelled AO derivatives are more promising for the design of Auger-emitting radiopharmaceuticals than the
I-labelled congeners.
Despite some progress, the overall survival of patients with glioblastoma (GBM) remains extremely poor. In this context, there is a pressing need to develop innovative therapy strategies for GBM, ...namely those based on nanomedicine approaches. Towards this goal, we have focused on nanoparticles (AuNP-SP and AuNP-SPTyr8) with a small gold core (ca. 4 nm), carrying DOTA chelators and substance P (SP) peptides. These new SP-containing AuNPs were characterized by a variety of analytical techniques, including TEM and DLS measurements and UV-vis and CD spectroscopy, which proved their high in vitro stability and poor tendency to interact with plasma proteins. Their labeling with diagnostic and therapeutic radionuclides was efficiently performed by DOTA complexation with the trivalent radiometals
Ga and
Lu or by electrophilic radioiodination with
I of the tyrosyl residue in AuNP-SPTyr8. Cellular studies of the resulting radiolabeled AuNPs in NKR1-positive GBM cells (U87, T98G and U373) have shown that the presence of the SP peptides has a crucial and positive impact on their internalization by the tumor cells. Consistently,
Lu-AuNP-SPTyr8 showed more pronounced radiobiological effects in U373 cells when compared with the non-targeted congener
Lu-AuNP-TDOTA, as assessed by cell viability and clonogenic assays and corroborated by Monte Carlo microdosimetry simulations.
Hyperthyroidism related to Graves' disease is associated with a suppression of TSH values which may persist after surgery in spite of a LT
replacement therapy at non-TSH-suppressing doses. The aim of ...this retrospective study was to evaluate the time to TSH normalization in a group of patients who underwent total thyroidectomy for Graves' disease receiving a LT
therapy dose regimen based on a previously published nomogram, and to identify possible correlations between the time to normalization of post-operative TSH values and preoperative clinical and biochemical parameters. 276 patients affected by Graves' disease who underwent surgery between 2010 and 2015, were retrospectively evaluated for clinical and biochemical parameters as well as post-surgical LT4 treatment regimen. Of the 276 subjects, 174 had initiated LT4 dosage corresponding to a previously published nomogram. 59 patients were excluded because their LT4 requirement (in mcg/kg/day) changed and deviated from the nomogram during the follow-up period, 15 patients were excluded because their TSH level was >4 mcU/ml during the first biochemical evaluation and 2 patients were excluded because they had low TSH levels potentially related to central hypothyroidism due to concomitant hypopituitarism. Therefore, 98 patients were included in our statistical analysis. TSH and FT4 were evaluated at the first post-operative assessment and during follow up until the normalization of TSH values was achieved, and then included in the analysis. During the first post-operative evaluation 2 months after surgery, 59/98 patients had TSH values in the normal range (0.4 to 4.0 mcU/ml), while 39/98 patients had a TSH value < 0.4 mcU/mL. The persistence of post-operative TSH levels < 0.4 mcU/ml was significantly correlated (
= 0.022) with longer duration of the disease. The value of anti-TSH receptor autoantibodies (TrAb) at the diagnosis of hyperthyroidism, significantly correlated (
= 0.002) with the time to TSH normalization in the group of patients with TSH < 0.4 mcU/ml at first control. This retrospective analysis confirms that in subjects who have undergone thyroidectomy for Graves' disease, time to normalization of TSH may be prolonged. Hence, the role of TSH as the "gold standard" to assess the appropriate LT
replacement therapy regimen during the initial months following surgery may need to be reconsidered.
Background
Recently, a new family of
99m
Tc(I)-tricarbonyl complexes bearing an acridine orange (AO) DNA targeting unit and different linkers between the Auger emitter (
99m
Tc) and the AO moiety was ...evaluated for Auger therapy. Among them,
99m
Tc-C
3
places the corresponding radionuclide at a shortest distance to DNA and produces important double strand breaks (DSB) yields in plasmid DNA providing the first evidence that
99m
Tc can efficiently induce DNA damage when well positioned to the double helix. Here in, we have extended the studies to human prostate cancer PC3 cells using the
99m
Tc-C
3
and
99m
Tc-C
5
complexes, aiming to assess how the distance to DNA influences the radiation-induced biological effects in this tumoral cell line, namely, in which concerns early and late damage effects.
Results
Our results highlight the limited biological effectiveness of Auger electrons, as short path length radiation, with increasing distances to DNA. The evaluation of the radiation-induced biological effects was complemented with a comparative microdosimetric study based on intracellular dose values. The comparative study, between MIRD and Monte Carlo (MC) methods used to assess the cellular doses, revealed that efforts should be made in order to standardize the bioeffects modeling for DNA-incorporated Auger electron emitters.
Conclusions
99m
Tc might not be the ideal radionuclide for Auger therapy but can be useful to validate the design of new classes of Auger-electron emitting radioconjugates. In this context, our results highlight the crucial importance of the distance of Auger electron emitters to the target DNA and encourage the development of strategies for the fine tuning of the distance to DNA for other medical radionuclides (e.g.,
111
In or
161
Tb) in order to enhance their radiotherapeutic effects within the Auger therapy of cancer.
This paper summarizes the results of an intercomparison on the use of the ICRP Reference Computational Phantoms with radiation transport codes, which was organized by EURADOS working group 6. Three ...exercises are described: exposure to an anterior-posterior (AP) photon point source, exposure to an AP neutron point source, and exposure to two typical medical X-ray examinations. The three exercises received 17, 8 and 8 solutions, respectively. Participants originated from fifteen different countries, and used a wide range of Monte Carlo codes. Due to difficulties in defining the precise source location unambiguously in the exercise description, agreement to within ∼10% of the reference solution was considered satisfactory for a given participant's results. Although some participants provided initial solutions in good agreement with the reference solutions, differences of several tens of percent, or even several orders of magnitude, were exhibited for many of the others. Following feedback and suggestions from the organizers, revised solutions were submitted by some of the participants for the photon exercises; in general, agreement was improved. The overall observations from these three intercomparison exercises are summarized and discussed.
•Intercomparison on use of ICRP Reference Computational Phantoms with radiation transport codes.•Deviations from reference solution of up to several orders of magnitude for many participants.•The general trends and common errors made by the participants are discussed.
Ovarian leiomyomas are very rare in domestic cats and occasionally mentioned in studies reporting general pathological findings and neoplasm occurrence in non-domestic large felids. This report ...describes a case of ovarian leiomyoma in a 22-year-old white tiger (Panthera tiger), treated with deslorelin implants, detailing pathological and immunohistochemical characteristics. Gross examination revealed a markedly enlarged, firm, whitish right ovary with a multinodular appearance. On a cut surface, multiple brown-fluid-filled cysts interspersed with solid grey-to-white areas were observed. On histopathological examination, the ovary was enlarged and replaced by a densely cellular neoplasm composed of spindle cells arranged in fascicles, or occasionally in a herringbone pattern, embedded in a large stroma of collagenous connective tissue. Neoplastic cells showed mild nuclear atypia and pleomorphism and low mitotic rate. Immunohistochemistry confirmed smooth muscle origin of the neoplasm, and cells were positive for vimentin, alpha-smooth muscle actin, desmin, and caldesmon. A low rate (<1%) of Ki-67-positive cells was observed. Although rare, ovarian leiomyoma should be considered when a mass is present in the ovary of a tiger with reproductive failure. Because cancer of the reproductive system impacts on species conservation by affecting reproduction, regular health monitoring is warranted to support wildlife conservation. Finally, the adverse effects associated with long-term treatment with synthetic GnRH analogues as contraceptives in non-domestic felids are worthy of future investigation.
Cone-beam computed tomography (CBCT) is widely used for pre-treatment verification and patient setup in image-guided radiation therapy (IGRT). CBCT imaging is employed daily and several times per ...patient, resulting in potentially high cumulative imaging doses to healthy tissues that surround exposed target organs. Computed tomography dose index (CTDI) is the parameter used by CBCT equipment as indication of the radiation output to patients. This study aimed to increase the knowledge on the relation between CBCT organ doses and weighted CTDI (CTDI
W
) for a thorax scanning protocol. A CBCT system was modelled using the Monte Carlo (MC) radiation transport program MCNPX2.7.0. Simulation results were validated against half-value layer (HVL), axial beam profile, patient skin dose (PSD) and CTDI measurements. For organ dose calculations, a male voxel phantom (“Golem”) was implemented with the CBCT scanner computational model. After a successful MC model validation with measurements, a systematic comparison was performed between organ doses (and their distribution) and CTDI dosimetry concepts CTDI
W
and cumulative dose quantities
f
100
(150) and
CTD
I
∞
. The results obtained show that CBCT organ doses vary between 1.2 ± 0.1 mGy and 3.3 ± 0.2 mGy for organs located within the primary beam. It was also verified that CTDI
W
allows prediction of absorbed doses to tissues at distances of about 5 cm from the isocentre of the CBCT system, whereas
f
100
(150) allows prediction of organ doses at distances of about 10 cm from the isocentre, independently from its location. This study demonstrates that these dosimetric concepts are suitable methods that easily allow a good approximation of the additional CBCT imaging doses during a typical lung cancer IGRT treatment.
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