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Although liposomal nanoparticles are one of the most versatile class of drug delivery systems, stable liposomal formulation of small neutral drug molecules still constitutes a challenge due to the low drug retention of current lipid membrane technologies. In this study, we evaluate the encapsulation and retention of seven nucleoside analog-based drugs in liposomes made of archaea-inspired tetraether lipids, which are known to enhance packing and membrane robustness compared to conventional bilayer-forming lipids. Liposomes comprised of the pure tetraether lipid generally showed improved retention of drugs (up to 4-fold) compared with liposomes made from a commercially available diacyl lipid. Interestingly, we did not find a significant correlation between the liposomal leakage rates of the molecules with typical parameters used to assess lipophilicity of drugs (such logD or topological polar surface area), suggesting that specific structural elements of the drug molecules can have a dominant effect on leakage from liposomes over general lipophilic character.

BACKGROUND: Neurotrophic factors, such as Nerve Growth Factor (NGF), play a key role in the stimulation of sprouting, synaptic plasticity, and reorganization after spinal cord damage. AIM: The aim of this study was to investigate the expression of nerve growth factor (NGF) in the cerebrospinal fluid (CSF) of newborns with myelomeningocele (MMC) and to determine its correlation with this spinal malformation. PATIENTS AND METHODS: To measure the expression of NGF, we collected CSF samples of 14 newborns with MMC taken immediately before the neurosurgical correction of the spinal malformation and of 14 matched controls. Endogenous NGF levels were quantified using a two-site immuno-enzymatic assay. The statistical analysis was performed using the Mann-Whitney two-tailed two-sample test. RESULTS: In the CSF of patients with MMC, NGF levels showed a significant increase compared to the mean levels of the control group (63.05 ± 7.3 vs 18.32 ± 4.5 pg/mL; (p < 0.001). No correlation was found between NGF expression and different types of MMC malformation, such as the level of spinal lesion and the association with Chiari II syndrome. CONCLUSIONS: Our study shows an over-expression of NGF in the CSF of newborns with MMC. The observed pattern of NGF up-regulation in this subset of patients may stimulate axonal sprouting and synaptic reorganization of the damaged neural cells at the site of spinal cord injury, thereby representing an important biochemical marker of spinal cord damage in MMC patients.

Prospective study on local treatment of pressure sores using calcium alginate and foam dressings in spina bifida patients.Investigate if this sequential approach is valid and safe for selected patients with neurological impairments.Using European Pressure Ulcer Grading System, after clinical evaluation of local sore, selected patients of Spina Bifida Center of Rome were treated with sequential calcium alginate and foam dressings for 12 weeks. Pressure ulcere surfaces were measured monthly by ulcer tracing. The endpoints were the mean absolute areas surface reduction during every month and number of patients achieving a 50% or more during study.14 patients (7 males aged 12-24 years) with spina bifida and pressure sores were treated. Mean and standard deviation of mean surface area reduction were 12.5 ± 7.5 cm 2 at start of the study versus 3.7 ± 5.2 cm 2 after 12 weeks, p0.001. 75% of the patients reached mean surface area reduction of 50% during trial. Dressing tolerance was good in every patient.Calcium alginate and foam dressings are valid and safe approach in the treatment of pressure sores in selected patients with spina bifida. In fact, they protect the wound and create an environment favorable to healing.

Background: The aim of the study was to investigate Programmed cell Death protein 1 (PD-1) and Programmed Death-Ligand 1 (PD-L1) and their mRNA expression in thymic epithelial tumors (TETs). Research design and Methods: We analyzed 68 samples of formalin-fixed paraffin embedded tissue (63 thymomas and 5 thymic carcinomas). PD-1 and PD-L1 protein expression was evaluated by immunohistochemistry and mRNA expression was evaluated by Real Time-PCR. Results: M/F ratio was 33/35, and median age was 60.5 years. 20 patients had Myasthenia Gravis (MG). In the subgroup with large tumors (>5 cm), PD-L1 mRNA overexpression was significantly associated with worse prognosis vs. patients with no mRNA overexpression (p =0.0083) and simultaneous PD-L1 immunostaining (>1%); PD-L1 mRNA overexpression was significantly associated with worse prognosis, respect to patient with PD-L1 negative immunostaining and no PD-L1 mRNA overexpression (p = 0.0178). The elderly patients (> 60 years) with large tumors showed worse prognosis (p = 0.0395). PD-L1 immunostaining (>50%) resulted significantly associated with MG. Conclusions: Our data suggest the potential involvement of the PD-1 and PD-L1 pathway in TETs progression. According to our results, it may be helpful to design future trials with anti-PD-1 drugs to establish high-risk patients after surgery.

A theoretical pattern for Fe and As co-precipitation was tested directly in a groundwater natural system. Several monitoring wells were sampled to identify the different endmembers that govern the hydrodynamics of the Ferrarelle Groundwater System in the Riardo Plain (Southern Italy). In agreement with recent investigations, we found a mix of a deep and a shallow component in different proportions, resulting in a specific chemical composition of groundwater in each well depending on the percentages of each component. The shallow component was characterized by EC ~ 430 µS/cm, Eh ~ 300 mV, Fe ~ 0.06 µmol/L and As ~ 0.01–0.12 µmol/L, while the deep component was characterized by EC ~ 3400 µS/cm, Eh ~ 170 mV, Fe ~ 140 µmol/L and As ~ 0.59 µmol/L. A general attenuation of As and Fe concentration that was not due to a simple dilution effect was observed in the mixing process. The oxidation of Fe(II) to Fe(III) produces solid precipitates which adsorb As from solution and then co-precipitate. The reactions pattern of Fe(II) oxidation and As adsorption gave a linear function between [As] and [Fe], where the angular coefficient depends on the [O2]/[H+] ratio. Chemical data obtained from our samples showed a very good agreement with this theoretical relationship. The investigated geochemical dynamics represented a natural process of attenuation of Fe and As, two undesirable elements that usually affect groundwater quality in volcanic aquifers in central-southern Italy, which are exploited to supply drinking water. Graphic abstract

The Riardo basin hosts groundwater exploited for the production of high quality, naturally sparkling, bottled water (e.g., Ferrarelle water), and circulating in a system constituted by highly fractured Mesozoic carbonates, overlain by more impervious volcanic rocks of the Roccamonfina complex. The two formations are locally in hydraulic connection and dislocated by deep-rooted faults. The study aimed at elucidating groundwater origin and circulation, using isotopic tracers (δ18O, δ2H, δ11B and 87Sr/86Sr) coupled to groundwater dating (Tritium, CFCs and SF6). Besides recharge by local precipitation over the Riardo hydrogeological basin, stable isotope ratios in water indicated an extra-basin recharge, likely from the elevated surrounding carbonate reliefs (e.g., Maggiore and Matese Mts.). The mineralization process, promoted by the deep CO2 flux, controls the B and Sr contents. However, their isotopic ratios did not allow discriminating between circulation in the volcanic and in the carbonate aquifers, as in the latter the isotopic composition differed from the original marine signature. Groundwater model ages ranged from ~ 30 years for the volcanic endmember to > 70 years for the deep, mineralized end-member, with longer circuits recharged at higher elevations. Overall, the results of this study were particularly relevant for mineral water exploitation. A recharge from outside the hydrogeological basin could be evidenced, especially for the more mineralized and valuable groundwater, and an active recent recharge was detected for the whole Riardo system. Both findings will contribute to the refinement of the hydrogeological model and water budget, and to a sustainable development of the resource.

The successful management of carbon in the Earth's crust is critical for mitigating the increase of anthropogenic CO2 in the atmosphere. Carbon Capture and Storage (CCS) requires an understanding of the behavior of carbon in the crust and the development of robust monitoring techniques to constrain the movement, mechanisms, and pathways for any potential CO2 leakage. Here, we examine an aquifer from the Riardo Plain (Campania Region, southern Italy), which serves as a suitable natural analogue for CO2 migration to the critical zone (i.e., shallow crust and aquifers) and as a case study to evaluate the geochemical processes that occur when CO2-saturated fluids mix with freshwater in shallow aquifers. We investigate the behavior of various geochemical constituents (major and trace elements, δ18O–H2O, δ13C-DIC, and Rn content). Water from this area has a high degree of mineralization (EC 2500–3000 μS/cm), high HCO3- (~2.5 g/L), is saturated with respect to CaCO3, and is enriched in alkali ions (e.g., Na+ + K+). The high degree of mineralization occurs in groundwater that discharges from the basal aquifer of the Roccamonfina volcanic edifice (~6 km NW), with vast CO2 inputs that promote host rock leaching. Superficial volcanic aquifers are recharged by fresh meteoric precipitation when groundwater flows from carbonates at the edge of the plain to aquifers hosted in the southeastern slope of the Roccamonfina volcano. The presence of normal faults in this area permits natural upwelling of CO2-rich groundwater, which locally mixes with shallow freshwater present within the upper volcanic succession. Significant (R > 0.8) linear correlations between conservative elements suggest that groundwater geochemistry is dominated by a mixture of two main endmembers: (i) deep/mineralized waters and (ii) shallow/diluted waters. The intrusion of freshwater to volcanic aquifers induces oxidation, leading to adsorption of select elements (e.g., As and Ba) onto Fe-oxyhydroxide precipitates within these aquifers. Geochemical modeling suggests that CO2 saturation approaches 3 g/L, which agrees with direct measurements of CO2 flux. We conclude that our conceptual geochemical model helps to constrain mixing of CO2 with freshwater and to diagnose the secondary geochemical processes that influence aqueous geochemistry within CO2-influenced groundwater.

Introduction Issues in ventral hernia repair are represented by the need for mesh fixation and how to assure a sufficient mesh overlap of the defect. Aiming to resolve these problems, this study describes a modified technique for ventral and incisional hernia repair based upon a newly developed mesh with a special design. This new type of implant allows broader coverage of the abdominal wall and results in tension- and fixation-free repair. Materials and methods A unique geometrically shaped mesh consisting of a large central body and radiating arms was used to repair ventral or incisional hernia. The mesh was intended not to be point-fixated. The friction of the straps passing through the tissues was hypothesized to be adequate to maintain the mesh firmly fastened in the abdominal wall, ensuring a wide coverage far from the hernia border. The newly designed mesh was placed in the preperitoneal sublay in 22 patients with ventral or incisional hernia. All straps were passed laterally through the transverse and oblique muscles. In all patients, a defect overlap of at least 8–12 cm was achieved. Results In a midterm follow-up of 18–24 (mean 22) months, three seromas and one infection occurred, which were successfully managed without mesh removal. No hematoma, chronic pain, or recurrence has been reported to date. Conclusions The described arm system of the implant allowed for a much smaller incision and eliminated the complicated maneuvers associated with suturing the mesh. The fixation arms seemed to have ensured the mesh stayed orientated in all patients. A very wide lateral mesh placement was accomplished, assuring sufficient defect overlap when shrinkage occurs.