The use of new psychoactive substances (NPS) in young people and their role in mental health care: a systematic review

© 2019 Informa UK Limited, trading as Taylor & Francis Group. Accepted for publication in Expert Review of Neurotherapeutics, 09/09/2019.Introduction: Over the past 10 years, a large number of New Psychoactive Substances (NPS) have entered the recreational drug scenario. NPS intake has been associated with health-related risks, and especially so for vulnerable populations such as the youngsters. Currently, most knowledge on the NPS health effects is learnt from both a range of users’ reports, made available through the psychonauts’ web fora, and from the few published, related toxicity, clinical observations. Areas covered: This paper aims at providing an overview of NPS effects on youngsters’ mental health, whilst performing a systematic review of the current related knowledge. Expert opinion: NPS consumption poses serious health risks, due to both a range of unpredictable clinical pharmacological properties and the typical concomitant use of other psychoactive molecules; overall, this can lead to near misses and fatalities. In comparison with adults, the central nervous system of children/adolescents may be more vulnerable to the activity of these molecules, hence raising even further the levels of health-related concerns. More research is needed to provide evidence of both short- and long-term effects of NPS, related health risks, and their addiction potential.Peer reviewedFinal Accepted Versio

Rhinocerebral mucormycosis treated with 32 gram liposomal amphotericin B and incomplete surgery: a case report

BACKGROUND: Mucormycosis (or zygomycosis) is the term for infection caused by fungi of the order Mucorales. Mucoraceae may produce severe disease in susceptible individuals, notably patients with diabetes and leukemia. Rhinocerebral mucormycosis most commonly manifests itself in the setting of poorly controlled diabetes, especially with ketoacidosis. CASE PRESENTATION: A 31-year-old diabetic man presented to the outpatient clinic with the following signs and symptoms: headache, periorbital pain, swelling and loss of vision in the right eye. On physical examination his right eye was red and swollen. There was periorbital cellulitis and the conjunctiva was edematous. KOH preparation of purulent discharge showed broad, ribbonlike, aseptate hyphae when examined under a fluorescence microscope. Cranial MRI showed involvement of the right orbit, thrombosis in cavernous sinus and infiltrates at ethmoid and maxillary sinuses. Mucormycosis was diagnosed based on these findings. Amphotericin B (AmBisome(®); 2 mg/kg.d) was initiated after the test doses. Right orbitectomy and right partial maxillectomy were performed; the lesions in ethmoid and maxillary sinuses were removed. The duration of the liposomal amphotericin B therapy was approximately 6 months and the total dose of liposomal amphotericin B used was 32 grams. Liposomal amphotericin B therapy was stopped six months later and oral fluconazole was started. CONCLUSIONS: Although a total surgical debridement of the lesions could not be performed, it is remarkable that regression of the disease could be achieved with medical therapy alone

Halo Excitation of 6^6He in Inelastic and Charge-Exchange Reactions

Four-body distorted wave theory appropriate for nucleon-nucleus reactions leading to 3-body continuum excitations of two-neutron Borromean halo nuclei is developed. The peculiarities of the halo bound state and 3-body continuum are fully taken into account by using the method of hyperspherical harmonics. The procedure is applied for A=6 test-bench nuclei; thus we report detailed studies of inclusive cross sections for inelastic $^6$He(p,p')$^6$He$^*$ and charge-exchange $^6$Li(n,p)$^6$He$^*$ reactions at nucleon energy 50 MeV. The theoretical low-energy spectra exhibit two resonance-like structures. The first (narrow) is the excitation of the well-known $2^+$ three-body resonance. The second (broad) bump is a composition of overlapping soft modes of multipolarities $1^-, 2^+, 1^+, 0^+$ whose relative weights depend on transferred momentum and reaction type. Inelastic scattering is the most selective tool for studying the soft dipole excitation mode.Comment: Submitted to Phys. Rev. C., 11 figures using eps

Tumor-infiltrating macrophages and dendritic cells in human colorectal cancer: relation to local regulatory T cells, systemic T-cell response against tumor-associated antigens and survival

<p>Abstract</p> <p>Introduction</p> <p>Although systemic T-cell responses against tumor antigens and tumor infiltration by T cells have been investigated in colorectal cancer (CRC), the initiation of spontaneous immune responses <it>in situ </it>is not well understood. Macrophages and dendritic cells (DC) play an important role as a link between innate and adaptive immune response. The aim of the present study was to analyze macrophage and DC infiltration in CRC and to investigate whether there is a correlation to systemic T-cell response, regulatory T cell (Treg) infiltration, and survival.</p> <p>Methods</p> <p>Immunohistological staining was performed with nine markers for macrophages and DC (CD68, CD163, S100, CD11c, CD208, CD209, CD123, CD1a, Langerin) in 40 colorectal cancer samples from patients, in whom the state of systemic T-cell responses against tumor-associated antigens (TAA) and Treg infiltration had previously been determined.</p> <p>Results</p> <p>All specimens contained cells positive for CD68, CD163, S100 and CD1a in epithelial tumor tissue and tumor stroma. Only a very few (less than median 3/HPF) CD123+, CD1a+, CD11c+, CD 208+, CD209+, or Langerin+ cells were detected in the specimens. Overall, we found a trend towards increased infiltration by S100-positive DC and a significantly increased number of stromal S100-positive DC in patients without T-cell response. There was an increase of stromal S100 DC and CD163 macrophages in limited disease (S100: 11.1/HPF vs. 7.3/HPF, p = 0.046; CD163: 11.0/HPF vs. 8.1/HPF, p = 0.06). We found a significant, positive correlation between S100-positive DC and FOXP3-positive Tregs. Survival in patients with high DC infiltration was significantly better than that in those with low DC infiltration (p < 0.05). Furthermore, we found a trend towards better survival for increased infiltration with CD163-positive macrophages (p = 0.07).</p> <p>Conclusion</p> <p>The present <it>in situ </it>study adds new data to the discussion on the interaction between the innate and adoptive immune system. Our data strongly support the hypothesis that tumor-infiltrating DC are a key factor at the interface between innate and adaptive immune response in malignant disease. Tumor infiltrating S100-positive DC show an inverse relationship with the systemic antigen-specific T-cell response, a positive correlation with regulatory T cells, and a positive association with survival in CRC. These data put tumor-infiltrating DC at the center of the relevant immune response in CRC.</p

Design of experiments to study the impact of process parameters on droplet size and development of non-invasive imaging techniques in tablet coating

Atomisation of an aqueous solution for tablet film coating is a complex process with multiple factors determining droplet formation and properties. The importance of droplet size for an efficient process and a high quality final product has been noted in the literature, with smaller droplets reported to produce smoother, more homogenous coatings whilst simultaneously avoiding the risk of damage through over-wetting of the tablet core. In this work the effect of droplet size on tablet film coat characteristics was investigated using X-ray microcomputed tomography (XμCT) and confocal laser scanning microscopy (CLSM). A quality by design approach utilising design of experiments (DOE) was used to optimise the conditions necessary for production of droplets at a small (20 μm) and large (70 μm) droplet size. Droplet size distribution was measured using real-time laser diffraction and the volume median diameter taken as a response. DOE yielded information on the relationship three critical process parameters: pump rate, atomisation pressure and coating-polymer concentration, had upon droplet size. The model generated was robust, scoring highly for model fit (R2 = 0.977), predictability (Q2 = 0.837), validity and reproducibility. Modelling confirmed that all parameters had either a linear or quadratic effect on droplet size and revealed an interaction between pump rate and atomisation pressure. Fluidised bed coating of tablet cores was performed with either small or large droplets followed by CLSM and XμCT imaging. Addition of commonly used contrast materials to the coating solution improved visualisation of the coating by XμCT, showing the coat as a discrete section of the overall tablet. Imaging provided qualitative and quantitative evidence revealing that smaller droplets formed thinner, more uniform and less porous film coats