Sterilization of lung matrices by supercritical carbon dioxide

Lung engineering is a potential alternative to transplantation for patients with end-stage pulmonary failure. Two challenges critical to the successful development of an engineered lung developed from a decellularized scaffold include (i) the suppression of resident infectious bioburden in the lung matrix, and (ii) the ability to sterilize decellularized tissues while preserving the essential biological and mechanical features intact. To date, the majority of lungs are sterilized using high concentrations of peracetic acid (PAA) resulting in extracellular matrix (ECM) depletion. These mechanically altered tissues have little to no storage potential. In this study, we report a sterilizing technique using supercritical carbon dioxide (ScCO(2)) that can achieve a sterility assurance level 10(−6) in decellularized lung matrix. The effects of ScCO(2) treatment on the histological, mechanical, and biochemical properties of the sterile decellularized lung were evaluated and compared with those of freshly decellularized lung matrix and with PAA-treated acellular lung. Exposure of the decellularized tissue to ScCO(2) did not significantly alter tissue architecture, ECM content or organization (glycosaminoglycans, elastin, collagen, and laminin), observations of cell engraftment, or mechanical integrity of the tissue. Furthermore, these attributes of lung matrix did not change after 6 months in sterile buffer following sterilization with ScCO(2), indicating that ScCO(2) produces a matrix that is stable during storage. The current study's results indicate that ScCO(2) can be used to sterilize acellular lung tissue while simultaneously preserving key biological components required for the function of the scaffold for regenerative medicine purposes

Suicide and suicides attempts in Italian prison epidemiological findings from the “Triveneto” area, 2010-2016

The aim of this observational study was to assess rates of suicide and suicide attempts, in relation to gender, age, place of birth and security levels, in north-eastern Italian prisons during 2010-2016, and investigate associations with prison overcrowding, offence type and prior self-harm and suicide attempts. The study was based on individual data on suicides and suicide attempts from 16 prisons, with an average yearly number of 3,900 inmates during the study period, for all prisons combined. Descriptive and binomial regression analyses were performed. Rates of suicide and suicide attempts in Triveneto prisons were 1and 15 per 1,000 inmates, respectively. More than 90% of suicides and suicide attempters were men aged between 21 and 49 years old, and most had committed violent offences. Only half the prisoners who died by suicide and 30% of those who made a suicide attempt in custody were Italians. ‘Cooperative witnesses’ had the highest mean suicide attempt rate (30/1,000 inmates). Fourteen per cent of suicides and 19% of attempters had a prior history of suicide attempts and self-injury. In binomial regression analyses, predictors of suicidal behaviour were being a male inmate in standard security conditions, with a mean age of 30 years. The study highlighted that there is a need for suicide prevention policies in Triveneto; these should take into account predictors of suicidal behaviours and individual characteristics of suicidal inmates. More research is warranted in order to both evaluate the effectiveness of prevention plans and better assess risk of suicide in specific groups, such as cooperative witnesses

Two-center experience of cannabidiol use in adults with Dravet syndrome

We describe real-world experience with cannabidiol (CBD) in adults with Dravet Syndrome (DS) via GW Pharma early access programme at two UK neurology centres. Adults with genetically-confirmed DS had CBD added to existing therapy, titrated up to 20 mg/kg, as tolerated. The primary outcome measure was percentage reduction in convulsive seizures. Secondary outcome measures included changes in myoclonic seizures, and in cognition and quality of life as assessed by the Caregiver Global Impression of Change (CGIC), and incidence of adverse events (AEs). 18 adults (7 female; median age 27.5 years; range 20–51) were included. Median follow-up was 176 days. In one, another antiseizure drug, clobazam, was introduced during the programme. 3/17 (17.6%) had >30% reduction in convulsive seizures (range: 87.5–100%). AEs occurred in all, the most common being transaminitis (52.9%). Behavioural AEs led to discontinuation in 3/18 (16.7%), including a seizure-free responder. In 7/18, CBD was stopped due to lack of effect. 8/18 continue on treatment. Improvements in CGIC were reported in 41.2% and 47.1% by physicians and families, respectively. 17.6% achieved sufficient reduction in convulsive seizure frequency to qualify for NHS funding. AEs led to withdrawal in only 16.7%. Close monitoring and dose adjustments of other antiseizure drugs were necessary

The in vivo effect of chelidonine on the stem cell system of planarians

The presence of adult pluripotent stem cells and the amazing regenerative capabilities make planarian flatworms an extraordinary experimental model to assess in vivo the effects of substances of both natural and synthetic origin on stem cell dynamics. This study focuses on the effects of chelidonine, an alkaloid obtained from Chelidonium majus. The expression levels of molecular markers specific for stem or differentiated cells were compared in chelidonine-treated and control planarians. The use of these markers demonstrates that chelidonine produces in vivo a significant anti-proliferative effect on planarian stem cells in a dosedependent fashion. In response to chelidonine treatment mitotic abnormalities were also observed and the number of cells able to proceed to anaphase/telophase appeared significantly reduced with respect to the controls. Our results support the possibility that chelidonine acts on cell cycle progression by inhibition of tubulin polymerization. These studies provide a basis for preclinical evaluation in vivo of the effects of chelidonine on physiologically proliferating stem cells

Intracerebral electrical stimulations of the temporal lobe: a stereo-electroencephalography study

The functional anatomy of the anteromesial portion of the temporal lobe and its involvement in epilepsy can be explored by means of intracerebral electrical stimulations. Here, we aimed to expand the knowledge of its physiological and pathophysiological symptoms by conducting the first large-sample systematic analysis of 1529 electrical stimulations of this anatomical region. We retrospectively analysed all clinical manifestations induced by intracerebral electrical stimulations in 173 patients with drug-resistant focal epilepsy with at least one electrode implanted in this area. We found that high-frequency stimulations were more likely to evoke electroclinical manifestations (p < .0001) and also provoked ‘false positive’ seizures. Multimodal symptoms were associated with EEG electrical modification (after discharge) (p < .0001). Visual symptoms were not associated with after discharge (p = .0002) and were mainly evoked by stimulation of the hippocampus (p = .009) and of the parahippocampal gyrus (p = .0212). ‘False positive seizures’ can be evoked by stimulation of the hippocampus, parahippocampal gyrus and amygdala, likely due to their intrinsic low epileptogenic threshold. Visual symptoms evoked in the hippocampus and parahippocampal gyrus, without EEG changes, are physiological symptoms and suggest involvement of these areas in the visual ventral stream. Our findings provide meaningful guidance in the interpretation of intracranial EEG studies of the temporal lobe

Neuroprotective effects of curcumin in methamphetamine-induced toxicity

Curcumin (CUR), a natural polyphenol extracted from rhizome of the Curcuma longa L, has received great attention for its multiple potential health benefits as well as disease prevention. For instance, CUR protects against toxic agents acting on the human body, including the nervous system. In detail, CUR possesses, among others, strong effects as an autophagy activator. The present study indicates that CUR counteracts methamphetamine (METH) toxicity. Such a drug of abuse is toxic by disturbing the autophagy machinery. We profited from an unbiased, low variable cell context by using rat pheochromocytoma PC12 cell line. In such a system, a strong protection was exerted by CUR against METH toxicity. This was associated with increased autophagy flux, merging of autophagosomes with lysosomes and replenishment of autophagy vacuoles with LC3, which instead is moved out from the vacuoles by METH. This is expected to enable the autophagy machinery. In fact, while in METH-treated cells the autophagy substrates α-synuclein accumulates in the cytosol, CUR speeds up α-synuclein clearance. Under the effects of CUR LC3 penetrate in autophagy vacuoles to commit them to cell clearance and promotes the autophagy flux. The present data provide evidence that CUR counteracts the neurotoxic effects induced by METH by promoting autophag

"A little theatrical but mostly athletic": The mutable erotics of Miranda July's The First Bad Man

By attending to the inherent flux of sexual fantasy, Miranda July’s first novel The First Bad Man reveals a mobile and mutable erotics capable of generating an enlarged range of self-identification and relational intimacy, far from any essentialist assumptions of stable or coherent sexual identity. July focuses specifically upon role-play as the means to unpack the normative categories of hetero/homosexuality, masculinity and femininity, celebrating rather than pathologising qualities like superficiality and inconsistency. The novel touches upon many polarising issues (for example, sexual violence, sadomasochism and assisted reproductive technology), deftly avoiding the conventional language which colours perception. Both erotic and humorous, The First Bad Man helps to redefine the often highly charged discourse around sex and sexuality

Salt stress in olive tree shapes resident endophytic microbiota

Olea europaea L. is a glycophyte representing one of the most important plants in the Mediterranean area, both from an economic and agricultural point of view. Its adaptability to different environmental conditions enables its cultivation in numerous agricultural scenarios, even on marginal areas, characterized by soils unsuitable for other crops. Salt stress represents one current major threats to crop production, including olive tree. In order to overcome this constraint, several cultivars have been evaluated over the years using biochemical and physiological methods to select the most suitable ones for cultivation in harsh environments. Thus the development of novel methodologies have provided useful tools for evaluating the adaptive capacity of cultivars, among which the evaluation of the plant-microbiota ratio, which is important for the maintenance of plant homeostasis. In the present study, four olive tree cultivars (two traditional and two for intensive cultivation) were subjected to saline stress using two concentrations of salt, 100 mM and 200 mM. The effects of stress on diverse cultivars were assessed by using biochemical analyses (i.e., proline, carotenoid and chlorophyll content), showing a cultivar-dependent response. Additionally, the olive tree response to stress was correlated with the leaf endophytic bacterial community. Results of the metabarcoding analyses showed a significant shift in the resident microbiome for plants subjected to moderate salt stress, which did not occur under extreme salt-stress conditions. In the whole, these results showed that the integration of stress markers and endophytic community represents a suitable approach to evaluate the adaptation of cultivars to environmental stresses