A pH-sensitive stearoyl-PEG-poly(methacryloyl sulfadimethoxine)-decorated liposome system for protein delivery: an application for bladder cancer treatment

Stealth pH-responsive liposomes for the delivery of therapeutic proteins to the bladder epithelium were prepared using methoxy-poly(ethylene glycol)5kDa-1,2-distearoyl-sn-glycero-3-phosphoethanolamine (mPEG5kDa-DSPE) and stearoyl-poly(ethylene glycol)-poly(methacryloyl sulfadimethoxine) copolymer (stearoyl-PEG-polySDM), which possesses an apparent pKa of 7.2. Liposomes of 0.2:0.6:100, 0.5:1.5:100 and 1:3:100 mPEG5kDa-DSPE/stearoyl-PEG-polySDM/(soybean phosphatidylcholine + cholesterol) molar ratios were loaded with bovine serum albumin (BSA) as a protein model. The loading capacity was 1.3% w/w BSA/lipid. At pH 7.4, all liposome formulations displayed a negative zeta-potential and were stable for several days. By pH decrease or addition to mouse urine, the zeta potential strongly decreased, and the liposomes underwent a rapid size increase and aggregation. Photon correlation spectroscopy (PCS) and transmission electron microscopy (TEM) analyses showed that the extent of the aggregation depended on the stearoyl-PEG-polySDM/lipid molar ratio. Cytofluorimetric analysis and confocal microscopy showed that at pH 6.5, the incubation of MB49 mouse bladder cancer cells and macrophages with fluorescein isothiocyanate-labelled-BSA (FITC-BSA) loaded and N-(Lissamine Rhodamine B sulfonyl)-1, 2-dihexadecanoyl-sn-glycero-3-phosphoethanolamine triethylammonium salt (rhodamine-DHPE) labelled 1:3:100 mPEG5kDa-DSPE/stearoyl-PEG-polySDM/lipid molar ratio liposomes resulted in a time-dependent liposome association with the cells. At pH 7.4, the association of BSA-loaded liposomes with the MB49 cells and macrophages was remarkably lower than at pH 6.5. Confocal images of bladder sections revealed that 2 h after the instillation, liposomes at pH 7.4 and control non-responsive liposomes at pH 7.4 or 6.5 did not associate nor delivered FITC-BSA to the bladder epithelium. On the contrary, the pH-responsive liposome formulation set at pH 6.5 and soon administered to mice by bladder instillation showed that, 2 h after administration, the pH-responsive liposomes efficiently delivered the loaded FITC-BSA to the bladder epitheliu

Management of intracranial hypertension following traumatic brain injury: a best clinical practice adoption proposal for intracranial pressure monitoring and decompressive craniectomy. Joint statements by the Traumatic Brain Injury Section of the Italian Society of Neurosurgery (SINch) and the Neuroanesthesia and Neurocritical Care Study Group of the Italian Society of Anesthesia, Analgesia, Resuscitation and Intensive Care (SIAARTI)

No robust evidence is provided by literature regarding the management of intracranial hypertension following severe traumatic brain injury (TBI). This is mostly due to the lack of prospective randomized controlled trials (RCTs), the presence of studies containing extreme heterogeneously collected populations and controversial considerations about chosen outcome. A scientific society should provide guidelines for care management and scientific support for those areas for which evidence-based medicine has not been identified. However, RCTs in severe TBI have failed to establish intervention effectiveness, arising the need to make greater use of tools such as Consensus Conferences between experts, which have the advantage of providing recommendations based on experience, on the analysis of updated literature data and on the direct comparison of different logistic realities. The Italian scientific societies should provide guidelines following the national laws ruling the best medical practice. However, many limitations do not allow the collection of data supporting high levels of evidence for intracranial pressure (ICP) monitoring and decompressive craniectomy (DC) in patients with severe TBI. This intersociety document proposes best practice guidelines for this subsetting of patients to be adopted on a national Italian level, along with joint statements from "TBI Section" of the Italian Society of Neurosurgery (SINch) endorsed by the Neuroanesthesia and Neurocritical Care Study Group of the Italian Society of Anesthesia, Analgesia, Resuscitation and Intensive Care (SIAARTI). Presented here is a recap of recommendations on management of ICP and DC supported a high level of available evidence and rate of agreement expressed by the assemblies during the more recent consensus conferences, where members of both groups have had a role of active participants and supporters. The listed recommendations have been sent to a panel of experts consisting of the 107 members of the "TBI Section" of the SINch and the 111 members of the Neuroanesthesia and Neurocritical Care Study Group of the SIAARTI. The aim of the survey was to test a preliminary evaluation of the grade of predictable future adherence of the recommendations following this intersociety proposal. The following recommendations are suggested as representing best clinical practice, nevertheless, adoption of local multidisciplinary protocols regarding thresholds of ICP values, drug therapies, hemostasis management and perioperative care of decompressed patients is strongly recommended to improve treatment efficiency, to increase the quality of data collection and to provide more powerful evidence with future studies. Thus, for this future perspective a rapid overview of the role of the multimodal neuromonitoring in the optimal severe TBI management is also provided in this document. It is reasonable to assume that the recommendations reported in this paper will in future be updated by new observations arising from future trials. They are not binding, and this document should be offered as a guidance for clinical practice through an intersociety agreement, taking in consideration the low level of evidence

Erector Spinae Plane Block and Chronic Pain: An Updated Review and Possible Future Directions

: Chronic pain is a common, pervasive, and often disabling medical condition that affects millions of people worldwide. According to the Global Burden of Disease survey, painful chronic conditions are causing the largest numbers of years lived with disability worldwide. In America, more than one in five adults experiences chronic pain. Erector spinae plane block is a novel regional anesthesia technique used to provide analgesia with multiple possible uses and a relatively low learning curve and complication rate. Here, we review the erector spinae plane block rationale, mechanism of action and possible complications, and discuss its potential use for chronic pain with possible future directions for research

Optical Photometry of the Type Ia SN 1999ee and the Type Ib/c SN 1999ex in IC 5179

We present UBVRIz lightcurves of the Type Ia SN 1999ee and the Type Ib/c SN 1999ex, both located in the galaxy IC 5179. SN 1999ee has an extremely well sampled lightcurve spanning from 10 days before Bmax through 53 days after peak. Near maximum we find systematic differences ~0.05 mag in photometry measured with two different telescopes, even though the photometry is reduced to the same local standards around the supernova using the specific color terms for each instrumental system. We use models for our bandpasses and spectrophotometry of SN 1999ee to derive magnitude corrections (S-corrections) and remedy this problem. This exercise demonstrates the need of accurately characterizing the instrumental system before great photometric accuracies of Type Ia supernovae can be claimed. It also shows that this effect can have important astrophysical consequences since a small systematic shift of 0.02 mag in the B-V color can introduce a 0.08 mag error in the extinction corrected peak B magnitudes of a supernova and thus lead to biased cosmological parameters. The data for the Type Ib/c SN 1999ex present us with the first ever observed shock breakout of a supernova of this class. These observations show that shock breakout occurred 18 days before Bmax and support the idea that Type Ib/c supernovae are due to core collapse of massive stars rather than thermonuclear disruption of white dwarfs.Comment: 55 pages, 15 figures, accepted by the Astronomical Journa

Anatomical iconography in the thirties in Padova: Mario Alfonsi and cardboard, ink and watercolour

The image in Anatomy has a pivotal role, due to the need of the student to learn on images the anatomical structures. This need is unchanged from the past to nowadays. In the last century Mario Alfonsi, a fine illustrator, was the official designer at the Anatomical Institute of Padova, working closely with Professor Tullio Terni. Terni was removed from teaching because of the racial laws and was rejected by the Jewish community and expelled from the Academy of the Lincei. The removal of Terni is the principal reason why the school of anatomical drawing was not founded in Padova. Mario Alfonsi is author of about 300 illustrative plates of Anatomy and the major part of his collection is kept in the archives of the institute of Human Anatomy of Padova. The tables are large (100 x 200 cm), illustrating the systems and organs of the human body, and were used as a teaching tool for lessons to students of Medicine till 1970. They are made of cardboard supported by a rod wood which allowed their exposure in the Falloppio Classroom. The drawings are made with ink and coloured with watercolour or tempera and date back to the thirties. They are signed and report the date expressed in the fascist calendar. They are in good condition, classified and stored in special cabinets. Alfonsi in his career also made drawings for texts of Anatomy and Surgery. In fact, he worked also with surgeons, illustrating step by step innovative surgical procedures