Introduction
Villa Ratti is a therapeutic community dedicated to the treatment of Personality Disorder with a particular focus on Borderline Personality Disorder (BPD), but this diagnosis may ...manifest in very different clinical conditions (Bayer & Parker, 2017; Scott, 2017).
Objectives
Since the second most common diagnosis we encounter from referring psychiatrists is Personality Disorder Not Otherwise Specified (PDNOS) (26,4%) and this diagnosis serves sometimes as a skeleton key for complex or unclear diagnostic scenarios (Verheul & Widiger, 2004), our main goal is to investigate how the variability within this category is reflected in terms of diagnostic accuracy, different development of the therapeutic and rehabilitative course, and of different outcomes at the end of the treatment.
Methods
To reach this goal, we collected data on all patients referred with a PDNOS diagnosis and compared their treatment program. scenarios.
Results
Our data showed how a PDNOS diagnosis hid in most cases complex personality disorders and comorbidities that reflected different specific difficulties and interventions during their treatment and, consequently, resulted in different outcomes.
Conclusions
Our experience led us to give additional attention to referred PDNOS diagnosis and to observe how much a clear diagnostic picture of a patient is crucial to correctly plan a treatment program and adapt local service interventions both for personality disorder and comorbidity
(1) Background: Andrographolide (AG) is a natural compound effective for the treatment of inflammation-mediated neurodegenerative disorders. The aim of this investigation was the preparation of ...liposomes to enhance the penetration into the brain of AG, by modifying the surface of the liposomes by adding Tween 80 (LPs-AG) alone or in combination with Didecyldimethylammonium bromide (DDAB) (CLPs-AG). (2) Methods: LPs-AG and CLPs-AG were physically and chemically characterized. The ability of liposomes to increase the permeability of AG was evaluated by artificial membranes (PAMPA) and hCMEC/D3 cells. (3) Results: Based on obtained results in terms of size, homogeneity, ζ-potential and EE%. both liposomes are suitable for parenteral administration. The systems showed excellent stability during a month of storage as suspensions or freeze-dried products. Glucose resulted the best cryoprotectant agent. PAMPA and hCMEC/D3 transport studies revealed that LPs-AG and CLPs-AG increased the permeability of AG, about an order of magnitude, compared to free AG without alterations in cell viability. The caveolae-mediated endocytosis resulted the main mechanism of up-take for both formulations. The presence of positive charge increased the cellular internalization of nanoparticles. (4) Conclusions: This study shows that developed liposomes might be ideal candidates for brain delivery of AG.
We have completed a new optical imaging and spectrophotometric survey of a 140 X 80 pc2 region of 30 Doradus centered on R136, covering key optical diagnostic emission lines including H Delta *a, H ...Delta *b, H Delta *g, O III Delta *l Delta *l4363, 4959, 5007, N II Delta *l Delta *l6548, 6584, S II Delta *l Delta *l6717, 6731 S III Delta *l6312, and in some locations S III Delta *l9069. We present maps of fluxes and intensity ratios for these lines, and catalogs of isolated ionizing stars, elephant-trunk pillars, and edge-on ionization fronts. The final science-quality spectroscopic data products are available to the public. Our analysis of the new data finds that, while stellar winds and supernovae undoubtedly produce shocks and are responsible for shaping the nebula, there are no global spectral signatures to indicate that shocks are currently an important source of ionization. We conclude that the considerable region covered by our survey is well described by photoionization from the central cluster where the ionizing continuum is dominated by the most massive O stars. We show that if 30 Dor were viewed at a cosmological distance, its integrated light would be dominated by its extensive regions of lower surface brightness rather than by the bright, eye-catching arcs.
Cannabis contains over 500 different compounds, including cannabinoids, terpenoids, and flavonoids. Cannabidiol (CBD) is a non-psychoactive constituent, whereas beta-caryophyllene (BCP) is one of ...most the well-known terpenoids of
. In recent years, there has been an emerging idea that the beneficial activities of these compounds are greater when they are combined. The aim of this study was to evaluate the anti-inflammatory effect of CBD and BCP using the in vitro model of lipopolysaccharide (LPS)-stimulated human keratinocytes (HaCaT) cells. The vitality of the cells was quantified using LDH and MTT assays. The levels of the following pro-inflammatory proteins and genes were quantified: IL-1β, COX-2, and phospho-NF-κB p65 (p-p65) through Western blotting (WB) and interleukin-1β (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor-α (TNFα) through quantitative real-time polymerase chain reaction (RT-qPCR). When present in the incubation medium, CBD and BCP reduced the increased levels of pro-inflammatory proteins (IL-1β, COX-2, and p-NF-kB) induced by LPS. The anti-inflammatory effects of CBD were blocked by a PPARγ antagonist, whereas a CB2 antagonist was able to revert the effects of BCP. Selected concentrations of CBD and BCP were able to revert the increases in the expression of pro-inflammatory genes (IL-1β, IL-6, and TNFα), and these effects were significant when the drugs were used in combination. Our results suggest that CBD and BCP work in concert to produce a major anti-inflammatory effect with good safety profiles.
Dry eye disease (DED) is a common ocular disorder characterized by an inadequate lubrication of the eye by tears leading to inflammation and the alteration of the ocular surface. Current treatments ...are often limited due to their side effects and ineffectiveness. Thymoquinone (TQ) is a natural compound present in the essential oil of
L., with anti-inflammatory and antioxidant activities. In this study, conventional and hyaluronic acid-coated liposomes were developed to improve TQ activity at ocular level. In the present study, the cytoprotective effects of TQ or TQ liposomes were assessed against oxidative and inflammatory processes in human corneal epithelial cells (HCE-2). Hyperosmolarity conditions (450 mOsm) were used as a model of DED. Interleukin-1β (IL-1β), Interleukin-6 (IL-6) and tumor necrosis factor (TNFα) were quantified by quantitative real-time polymerase chain reaction (RT-qPCR); COX-2 and Phospho-NF-κB p65 (p-p65) by Western blotting (WB). Moreover, the mitochondrial reactive oxygen species (mtROS) levels were measured by MitoSOX assay. The hyperosmotic treatment induced a significant increase of the proinflammatory genes and proteins expression that were significantly decreased in the liposomes-treated cells. The coincubation with hyaluronic acid-coated liposomes significantly reverted the increase of mtROS production, evidently stimulated by the hyperosmotic stress. Our data suggest that TQ-loaded liposomes have potential as a therapeutic agent in dry eye disease, improving the TQ efficacy.
(1) Background: Over the past 10 years, a number of scientific studies have demonstrated the therapeutic potential of cannabinoid compounds present in the Cannabis Sativa and Indica plants. However, ...their role in mechanisms leading to neurodegeneration following cerebral ischemia is yet unclear. (2) Methods: We investigated the effects of Cannabis extracts (Bedrocan, FM2) or selected cannabinoids (Δ9-tetrahydrocannabinol (THC), cannabidiol (CBD), and cannabigerol) in rat organotypic hippocampal slices exposed to oxygen-glucose deprivation (OGD), an in vitro model of forebrain global ischemia. Cell death in the CA1 subregion of slices was quantified by propidium iodide fluorescence, and morphological analysis and tissue organization were examined by immunohistochemistry and confocal microscopy. (3) Results: Incubation with the Bedrocan extract or THC exacerbated, whereas incubation with the FM2 extract or cannabidiol attenuated CA1 injury induced by OGD. Δ9-THC toxicity was prevented by CB1 receptor antagonists, the neuroprotective effect of cannabidiol was blocked by TRPV2, 5-HT1A, and PPARγ antagonists. Confocal microscopy confirmed that CBD, but not THC, had a significant protective effect toward neuronal damage and tissue disorganization caused by OGD in organotypic hippocampal slices. (4) Conclusions: Our results suggest that cannabinoids play different roles in the mechanisms of post-ischemic neuronal death. In particular, appropriate concentrations of CBD or CBD/THC ratios may represent a valid therapeutic intervention in the treatment of post-ischemic neuronal death.
BACKGROUND AND PURPOSES Thienyl‐isoquinolone (TIQ‐A) is a relatively potent PARP inhibitor able to reduce post‐ischaemic neuronal death in vitro. Here we have studied, in different stroke models in ...vivo, the neuroprotective properties of DAMTIQ and HYDAMTIQ, two TIQ‐A derivatives able to reach the brain and to inhibit PARP‐1 and PARP‐2.
EXPERIMENTAL APPROACH Studies were carried out in (i) transient (2 h) middle cerebral artery occlusion (tMCAO), (ii) permanent MCAO (pMCAO) and (iii) electrocoagulation of the distal portion of MCA in conjunction with transient (90 min) bilateral carotid occlusion (focal cortical ischaemia).
KEY RESULTS In male rats with tMCAO, HYDAMTIQ (0.1–10 mg·kg−1) injected i.p. three times, starting 4 h after MCAO, reduced infarct volumes by up to 70%, reduced the loss of body weight by up to 60% and attenuated the neurological impairment by up to 40%. In age‐matched female rats, HYDAMTIQ also reduced brain damage. Protection, however, was less pronounced than in the male rats. In animals with pMCAO, HYDAMTIQ administered 30 min after MCAO reduced infarct volumes by approximately 40%. In animals with focal cortical ischaemia, HYDAMTIQ treatment decreased post‐ischaemic accumulation of PAR (the product of PARP activity) and the presence of OX42‐positive inflammatory cells in the ischaemic cortex. It also reduced sensorimotor deficits for up to 90 days after MCAO.
CONCLUSION AND IMPLICATIONS Our results show that HYDAMTIQ is a potent PARP inhibitor that conferred robust neuroprotection and long‐lasting improvement of post‐stroke neurological deficits.
Representing an important cause of long-term disability, term neonatal hypoxic-ischemic encephalopathy (HIE) urgently needs further research aimed at repurposing existing drug as well as developing ...new therapeutics. Since various experimental in vitro and in vivo models of HIE have been developed with distinct characteristics, it becomes important to select the appropriate preclinical screening cascade for testing the efficacy of novel pharmacological treatments. As therapeutic hypothermia is already a routine therapy for neonatal encephalopathy, it is essential that hypothermia be administered to the experimental model selected to allow translational testing of novel or repurposed drugs on top of the standard of care. Moreover, a translational approach requires that therapeutic interventions must be initiated after the induction of the insult, and the time window for intervention should be evaluated to translate to real world clinical practice. Hippocampal organotypic slice cultures, in particular, are an invaluable intermediate between simpler cell lines and in vivo models, as they largely maintain structural complexity of the original tissue and can be subjected to transient oxygen-glucose deprivation (OGD) and subsequent reoxygenation to simulate ischemic neuronal injury and reperfusion. Progressing to in vivo models, generally, rodent (mouse and rat) models could offer more flexibility and be more cost-effective for testing the efficacy of pharmacological agents with a dose-response approach. Large animal models, including piglets, sheep, and non-human primates, may be utilized as a third step for more focused and accurate translational studies, including also pharmacokinetic and safety pharmacology assessments. Thus, a preclinical proof of concept of efficacy of an emerging pharmacological treatment should be obtained firstly in vitro, including organotypic models, and, subsequently, in at least two different animal models, also in combination with hypothermia, before initiating clinical trials.
We present new Herschel observations of the (6,6) and (9,9) inversion transitions of the hydronium ion toward Sagittarius B2(N) and W31C. Observations of the same lines toward W31C, a line of sight ...that does not intersect the Central Molecular Zone but instead traces quiescent gas in the Galactic disk, also imply a high rotational temperature of ~380 K, well in excess of the kinetic temperature of the diffuse Galactic interstellar medium. We suggest instead that the highly excited states of the hydronium ion are populated mainly by exoergic chemical formation processes and the temperature describing the rotational level population does not represent the physical temperature of the medium. This offers a simple explanation of the long-standing puzzle of the presence of a pervasive, hot molecular gas component in the central region of the Milky Way. Moreover, our observations suggest that this is a universal process not limited to the active environments associated with galactic nuclei.
ABSTRACT
The H α and H β emission-line luminosities measured in a single integrated spectrum are affected in non-trivial ways by point-to-point variations in dust attenuation in a galaxy. This work ...investigates the impact of this variation when estimating global H α luminosities corrected for the presence of dust by a global Balmer decrement. Analytical arguments show that the dust-corrected H α luminosity is always underestimated when using the global H α/H β flux ratio to correct for dust attenuation. We measure this effect on 156 face-on star-forming galaxies from the Mapping Nearby Galaxies at APO (MaNGA) survey. At 1–2 kpc spatial resolution, the effect is small but systematic, with the integrated dust-corrected H α luminosity underestimated by 2–4 per cent (and typically not more than by 10 per cent), and depends on the specific star formation rate of the galaxy. Given the spatial resolution of MaNGA, these are lower limits for the effect. From Multi Unit Spectroscopic Explorer (MUSE) observations of NGC 628 with a resolution of 36 pc, we find the discrepancy between the globally and the point-by-point dust-corrected H α luminosity to be 14 ± 1 per cent, which may still underestimate the true effect. We use toy models and simulations to show that the true difference depends strongly on the spatial variance of the H α/H β flux ratio, and on the slope of the relation between H αluminosity and dust attenuation within a galaxy. Larger samples of higher spatial resolution observations are required to quantify the dependence of this effect as a function of galaxy properties.
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