Deep eutectic solvents: a structural point of view on the role of the cation

In this work we have developed an analytical procedure to identify metal ion coordination geometries in liquid media based on the calculation of Combined Distribution Functions (CDFs) starting from Molecular Dynamics (MD) simulations. CDFs provide a fingerprint which can be easily and unambiguously assigned to a reference polyhedron. The CDF analysis has been tested on five systems and has proven to reliably identify the correct geometries of several ion coordination complexes. This tool is simple and general and can be efficiently applied to different MD simulations of liquid systems

Total Hemi-overgrowth in Pigmentary Mosaicism of the (Hypomelanosis of) Ito Type: Eight Case Reports.

Pigmentary mosaicism of the (hypomelanosis of) Ito type is an umbrella term, which includes phenotypes characterized by mosaic hypopigmentation in the form of streaks, whorls, patchy, or more bizarre skin configurations (running along the lines of Blaschko): these cutaneous patterns can manifest as an isolated skin disorder (pigmentary mosaicism of the Ito type) or as a complex malformation syndrome in association with extracutaneous anomalies (most often of the musculoskeletal and/or nervous systems) (hypomelanosis of Ito). Affected individuals are anecdotally reported to have also partial or total body hemi-overgrowth (HOG), which often causes moderate to severe complications.We studied the occurrence and features of HOG in the 114 children and adults with mosaic pigmentary disorders of the Ito type diagnosed and followed up (from 2 to 22 years; average follow-up 16 years) at our Institutions.Eight patients (5 M, 3 F; aged 4 to 25 years; median age 16 years) out of the 114 analyzed (7%) fulfilled the criteria for unilateral HOG, with differences in diameter ranging from 0.4 to 4.0 cm (upper limbs) and 1.0 to 9.0 cm (lower limbs). Moreover, among these 8 patients, 5/8 filled in the 75th to 90th percentile for height; 6/8 had associated kyphoscoliosis; and 5/8 showed cognitive delays. No tumour complications were recorded. Overall, 6/8 HOG patients presented with additional (extracutaneous) syndromic manifestations, apart from the HOG (ie, with a clinical phenotype of hypomelanosis of Ito).The present study, which includes children and adults with the longest follow-up so far recorded, confirms the association between pigmentary mosaicism of the Ito type and HOG lowering previous estimates (7% vs 16%) for HOG in the context of mosaic hypopigmentation. A careful examination, looking at subtle to moderate asymmetries and associated complications within the spectrum of these mosaic pigmentary disorders, is recommended

Involvement of pro-inflammatory cytokines and growth factors in the pathogenesis of Dupuytren's contracture: a novel target for a possible future therapeutic strategy?

Dupuytren's contracture (DC) is a benign fibro-proliferative disease of the hand causing fibrotic nodules and fascial cords which determine debilitating contracture and deformities of fingers and hands. The present study was designed to characterize pro-inflammatory cytokines and growth factors involved in the pathogenesis, progression and recurrence of this disease, in order to find novel targets for alternative therapies and strategies in controlling DC. The expression of pro-inflammatory cytokines and of growth factors was detected by immunohistochemistry in fibrotic nodules and normal palmar fascia resected respectively from patients affected by DC and carpal tunnel syndrome (CTS; as negative controls). Reverse transcription (RT)-PCR analysis and immunofluorescence were performed to quantify the expression of transforming growth factor (TGF)-β1, interleukin (IL)-1β and vascular endothelial growth factor (VEGF) by primary cultures of myofibroblasts and fibroblasts isolated from Dupuytren's nodules. Histological analysis showed high cellularity and high proliferation rate in Dupuytren's tissue, together with the presence of myofibroblastic isotypes; immunohistochemical staining for macrophages was completely negative. In addition, a strong expression of TGF-β1, IL-1β and VEGF was evident in the extracellular matrix and in the cytoplasm of fibroblasts and myofibroblasts in Dupuytren's nodular tissues, as compared with control tissues. These results were confirmed by RT-PCR and by immunofluorescence in pathological and normal primary cell cultures. These preliminary observations suggest that TGF-β1, IL-1β and VEGF may be considered potential therapeutic targets in the treatment of Dupuytren's disease (DD)

One-step growth and shaping by a dual plasma reactor of diamond nanocones arrays for the assembling of stable cold cathodes

Arrays of conical-shaped nanodiamond structures are formed on silicon substrate by a single-step CVD process from CH4/H-2 mixtures. The formation of these nanocones has been found to depend on interplay between growing and etching during the CVD process carried out in a dual-mode MW/RF plasma reactor. Morphology and structure of the conical-like systems can be controlled by varying the process parameters, and have been investigated by scanning electron microscopy (SEM), reflection high energy electron diffraction (RHEED) and micro-Raman spectroscopy. The Field Emission (FE) properties of different diamond nanocones arrays have been investigated and compared with those of analogous systems in order to assess the feasibility of the present nano-materials as electron emitters for cold cathodes. The FE behavior is discussed taking into account the structure of the different diamond nanocones

Arx acts as a regional key selector gene in the ventral telencephalon mainly through its transcriptional repression activity

AbstractThe homeobox-containing gene Arx is expressed during ventral telencephalon development and required for correct GABAergic interneuron tangential migration from the ganglionic eminences to the olfactory bulbs, cerebral cortex and striatum. Its human ortholog is associated with a variety of neurological clinical manifestations whose symptoms are compatible with the loss of cortical interneurons and altered basal ganglia-related activities. Herein, we report the identification of a number of genes whose expression is consistently altered in Arx mutant ganglionic eminences. Our analyses revealed a striking ectopic expression in the ganglionic eminences of several of these genes normally at most marginally expressed in the ventral telencephalon. Among them, Ebf3 was functionally analyzed. Thus, its ectopic expression in ventral telencephalon was found to prevent neuronal tangential migration. Further, we showed that Arx is sufficient to repress Ebf3 endogenous expression and that its silencing in Arx mutant tissues partially rescues tangential cell movement. Together, these data provide new insights into the molecular pathways regulated by Arx during telencephalon development

Neurometabolic changes in a rat pup model of type C hepatic encephalopathy depend on age at liver disease onset.

Chronic liver disease (CLD) is a serious condition where various toxins present in the blood affect the brain leading to type C hepatic encephalopathy (HE). Both adults and children are impacted, while children may display unique vulnerabilities depending on the affected window of brain development.We aimed to use the advantages of high field proton Magnetic Resonance Spectroscopy ( <sup>1</sup> H MRS) to study longitudinally the neurometabolic and behavioural effects of Bile Duct Ligation (animal model of CLD-induced type C HE) on rats at post-natal day 15 (p15) to get closer to neonatal onset liver disease. Furthermore, we compared two sets of animals (p15 and p21-previously published) to evaluate whether the brain responds differently to CLD according to age onset.We showed for the first time that when CLD was acquired at p15, the rats presented the typical signs of CLD, i.e. rise in plasma bilirubin and ammonium, and developed the characteristic brain metabolic changes associated with type C HE (e.g. glutamine increase and osmolytes decrease). When compared to rats that acquired CLD at p21, p15 rats did not show any significant difference in plasma biochemistry, but displayed a delayed increase in brain glutamine and decrease in total-choline. The changes in neurotransmitters were milder than in p21 rats. Moreover, p15 rats showed an earlier increase in brain lactate and a different antioxidant response. These findings offer tentative pointers as to which neurodevelopmental processes may be impacted and raise the question of whether similar changes might exist in humans but are missed owing to <sup>1</sup> H MRS methodological limitations in field strength of clinical magnet

Self-selection effects in smokers attending lung cancer screening: a 9.5-year population-based cohort study in Varese, Italy.

BACKGROUND:: We hypothesize that mortality risk profile of participants and nonparticipants in nonrandomized lung cancer (LC) screening of smokers may be different. METHODS:: In 1997, a population-based cohort of 5815 smokers of Varese Province was invited to nonrandomized LC screening by annual chest x-ray examination for 4 years. LC risk factors and screening participation rate were recorded. Except for screening, the whole cohort received usual care. After 9.5-year observation, we compared mortality of participants versus nonparticipants by assessing age-standardized all-cause mortality rate ratio (MRR) and disease group-specific MRR with 95% confidence intervals (95% CI). RESULTS:: Self-selected screening participants were 21% of cohort. Participants were younger (p < 0.001), were more frequently current smokers (p = 0.019), had more pack-years of smoking (p < 0.0001), and had higher rate of LC family history (p < 0.0001) and of occupational LC risk (p < 0.0001) relative to nonparticipants. In logistic regression analysis familial LC, occupational risk and pack-years smoked were significant predictors of participation in screening and of developing LC. Participants displayed a healthy effect, as shown by all-cause MRR = 0.67 (95% CI, 0.53-0.84), all cancers except LC MRR = 0.61 (95% CI, 0.41-0.91), cardiovascular diseases MRR = 0.38 (95% CI, 0.22-0.63), and noncancer disease other than cardiovascular or respiratory MRR = 0.57 (95% CI, 0.34-0.92). The LC mortality (MRR = 1.40; 95% CI, 1.03-1.91) was higher in participants relative to nonparticipants (p = 0.031). CONCLUSION:: The selection effect in LC screening participants was dual: healthy effect and higher LC mortality. In assessing the overall effectiveness of LC screening on a population level, a higher LC mortality risk in participants should be considered

Amphiphilic drug interactions with model cellular membranes are influenced by lipid chain-melting temperature.

Small-molecule amphiphilic species such as many drug molecules frequently exhibit low-to-negligible aqueous solubility, and generally have no identified transport proteins assisting their distribution, yet are able to rapidly penetrate significant distances into patient tissue and even cross the blood-brain barrier. Previous work has identified a mechanism of translocation driven by acid-catalysed lipid hydrolysis of biological membranes, a process which is catalysed by the presence of cationic amphiphilic drug molecules. In this study, the interactions of raclopride, a model amphiphilic drug, were investigated with mixtures of biologically relevant lipids across a range of compositions, revealing the influence of the chain-melting temperature of the lipids upon the rate of acyl hydrolysis

Anaphylactic death: A new forensic workflow for diagnosis

Anaphylaxis is a life-threatening or fatal clinical emergency characterized by rapid onset, and death may be sudden. The margin of certainty about the diagnosis of anaphylactic death is not well established. The application of immunohistochemical techniques combined with the evaluation of blood tryptase concentrations opened up a new field of investigation into anaphylactic death. The present study investigated eleven autopsy cases of anaphylactic death, carried out between 2005 and 2017, by the Departments of Forensic Pathology of the Universities of Foggia and Catania (Italy). An analysis of the medical records was carried out in all autopsies. Seven autopsies were carried out on males and four on females. Of the eleven cases, one showed a history of asthma, one of food ingestion, two of oral administration of medications, six did not refer any allergy history, and one subject was unknown. All cases (100%) showed pulmonary congestion and edema; 7/11 (64%) of the cases had pharyngeal/laryngeal edema and mucus plugging in the airway; only one case (9%) had a skin reaction that was found during external examination. Serum tryptase concentration was measured in ten cases, and the mean value was 133.5 µg/L ± 177.9. The immunohistochemical examination using an anti-tryptase antibody on samples from the lungs, pharynx/larynx, and skin site of medication injection showed that all cases (100%) were strongly immunopositive for anti-tryptase antibody staining on lung samples; three cases (30%) were strongly immunopositive for anti-tryptase antibody staining on pharyngeal/laryngeal samples; and eight cases (80%) were strongly immunopositive for anti-tryptase antibody staining on skin samples. We conclude that a typical clinical history, blood tryptase level >40 µg/L, and strongly positive anti-tryptase antibody staining in the immunohistochemical investigation may represent reliable parameters in the determination of anaphylactic death with the accuracy needed for forensic purposes

Treatment of ovarian cancer with surgery, short-course chemotherapy and whole abdominal radiation

Background The primary aim was to induce a high number of pCR in early (FIGO IC, JIB + C)-and advanced (FIGO ffl—IV)—stage ovarian cancer with a surgery plus 4 cycles of cisplatin and meiphalan (PAMP) regimen. The second objective was to prevent relapse with WAR in patients in remission after chemotherapy. Patients and methods 218 eligible patients were treated after staging laparotomy with cisplatin 80 mg/sqm iv. on day 1 and melphalan 12 mg/sqm i.v. on day 2 q 4 weeks. Response was verified by second-look laparotomy. WAR was carried out with the open field technique on a linear accele rator (daily dose: 1.3 Gy, total dose: 29.9 Gy) in patients with pathological or clinicaJ CR or pathological PR with microscopical residual disease. Results 146/218 patients (67%, 95% CI: 61%-73%) responded to PAMIP: 56 (26%) achieved pCR, 24 (11%), cCR, 56 (26%) pPR and 10 (5%) cPR (c=clinical, p=pathological). Multivariate analyses revealed that in advanced stages (92 cases in remission), the achievement of pCR was the most important factor for longer time to failure (TIF) and survival. Only 5 1/118 (43%) patients in remission received WAR Early-stage patients <=55 years were more likely to have WAR than patients older than 55 years (77% vs. 23%; p= 0.02). Advanced-stage patients with cCR were less likely to be irradiated than patients with pCR or pPR (10% vs. 51%; p= 0.003). Toxicity of PAMP was acceptable with 10% of WHO grade 4 hematologic toxicity. Acute hematological toxicity of WAR caused interruption (3 3%) or incompleteness (3 3%) of irradiation in the majority of patients. Conclusions PAMP is an effective treatment for advanced ovarian cancer with a 67% response rate after 4 cycles. For the majority of patients in remission, WAR as a consolidation treatment was hardly feasible. For these patients new treatment modalities to consolidate remission are neede