correction moulding calixarenes for biomacromolecule targeting

Correction for 'Moulding calixarenes for biomacromolecule targeting' by Marta Giuliani et al., Chem. Commun., 2015, 51, 14140–14159

RAPID-PROTOTYPING OF PDMS-BASED MICROFLUIDIC DEVICES

Microfluidics uses the manipulation of fluids in microchannels to accomplish innumerous goals, and is attractive to analytical chemistry because it can reduce the scale of larger analytical processes. The benefits of the use of microfluidic systems, in comparison with conventional processes, include efficient sample and reagent consumption, low power usage and portability. Most microfluidic applications require a development process based on iterative design and testing of multiple prototype microdevices. Typical microfabrication protocols, however, can require over a week of specialist time in high-maintenance cleanroom facilities, making the iterative process resource-intensive and prohibitive in many locations. Rapid prototyping techniques can alleviate these issues, enabling faster development of microfluidic structures at lower costs. Print-and-peel techniques (PAP), including wax printing and xurography, are low-cost fast-prototyping tools used to create master molds for polydimethylsiloxane (PDMS) miniaturized systems. In this work, three different methods were created to improve the rapid-prototyping of PDMS-based microfluidic devices. Using the wax printing method, PDMS microdevices can now be fabricated from design to testing in less than 1 hour, at the cost of $0.01 per mold, being one of the fastest and cheapest methods to date. If extensive fluidic manipulation is required, xurography becomes the method of choice. The xurography technique presented here is the most rapid tool to fabricate PDMS-based microdevices to date, presenting turnaround times as fast as 5 minutes. The first hybrid technique that can be used either as a PAP or a scaffolding method is also presented here, using the same materials and fabrication process. The green, low-cost, user-friendly elastomeric (GLUE) rapid prototyping method to fabricate PDMS-based devices uses white glue as the patterning material, and is capable of fabricating multi-height molds in a single step, improving even further the development of PDMS microfluidic devices. Device fabrication is only one of the steps in the iterative process of designing a fully-functional microfluidic tool. The design of the microdevice itself plays a crucial role in its performance, which directly impacts processes conducted in miniaturized devices. In this work, the influence of hydrodynamic resistance in sample dispersion on a microfluidic multiplexer was studied using paper-based analytical microfluidic devices (µPADs) as the testbed. When microfluidic devices are not rationally designed, and when the influence of fluidic resistance is not taken into account, sample dispersion can be biased. A bias can influence the output of colorimetric enzymatic assays supported on these microstructures, which are the most common applications of µPADs, demonstrating the need for rational design of microdevices. The third essential component of developing microfluidic devices is their effective testing, especially when incorporating active pumping elements on-chip. To overcome issues in the manual operation or coding for operation of microvalves, a program that can automatically generate sequences for fluidic manipulation in microfluidic processors was written in Python, with the only inputs required from the user being reservoir positions, mixing ratio and the desired input and output reservoirs. To further improve testing and avoid the use of fixed mounts, a modular system was created to aid the testing of devices with different designs, another advance in the area. This research enables better design and testing of microfluidic devices in shorter times and at lower costs, enabling improvements in the interfacing between different unit operations on-chip, a challenge in the microfluidics area. More than that, it also makes this area, traditionally confined into expensive cleanroom facilities, available to more research groups worldwide.Ph.D

Sexual functioning and opioid maintenance treatment in women. Results from a large multicentre study

Opioid maintenance treatment (OMT) is the most widespread therapy for both females and males opioid addicts. While many studies have evaluated the OMT impact on men’s sexuality, the data collected about the change in women’s sexual functioning is still limited despite the fact that it is now well-known that opioids-both endogenous and exogenous-affect the endocrine system and play an important role in sexual functioning. The present study aims to determine how OMT with buprenorphine (BUP) or methadone (MTD) affects sexual health in women; examining also any possible emerging correlation between sexual dysfunction (SD), type of opioid and patients’ mental health. This multi-center study case recruited 258 female volunteers attending Italian public Addiction Outpatients Centers that were stabilized with OMT for at least 3 months. SD was assessed with the Arizona Sexual Experience Scale. The twelve-item General Health Questionnaire was used to assess participants’ mental health conditions. The results show that 56.6% of women receiving OMT for at least 3 months presented SD without significant differences between MTD e BUP groups. The majority of the subjects with SD have a poorer quality of intimate relationships and worse mental health than the average. To the best of our knowledge, the present study is the largest report on the presence of SDs in women as a side effects of MTD and BUP used in OMT. Since SDs cause difficulties in intimate relationships, lower patients’ quality of life and interfere with OMT beneficial outcomes, we recommend that women undertaking an opioid therapy have routine screening for SD and we highlight the importance to better examine opioid-endocrine interactions in future studies in order to provide alternative potential treatments such as the choice of opioid, opioid dose reduction and hormone supplementation

Calixarene-decorated liposomes for intracellular cargo delivery

Amphiphilic calix[4]arenes, functionalized with guanidinium groups, are used to decorate the outer surface of liposomes and significantly improve the cellular uptake of a cargo compared to plain liposomes. The improved uptake is elicited and mediated by the interaction between the cationic polar heads of the macrocycle units embedded in the liposome bilayer and anionic heparan-sulfate proteoglycans surrounding the exterior of cells

Optic Nerve Degeneration and Reduced Contrast Sensitivity Due to Folic Acid Deficiency: A Behavioral and Electrophysiological Study in Rhesus Monkeys

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Calixarene-decorated liposomes for intracellular cargo delivery

Liposomes equipped at the outer membrane with positively charged calixarenes show improved efficiency in cargo delivery. This is facilitated by the interaction between the macrocycle units and heparan sulfate proteoglycans surrounding the cell

Detoxification improves multidomain cognitive dysfunction in high-dose benzodiazepine abusers

Purpose: High-dose benzodiazepines (BZDs) abuse has been documented to cause multidomain cognitive dysfunction. We explored whether cognitive abnormalities to high-dose BZD abuse might be reversed by detoxification with slow subcutaneous infusion of flumazenil. Methods: We recruited 96 patients consecutively admitted to the Department of Internal Medicine, Addiction Medicine Unit, Verona University Hospital, Italy for detoxification from high-dose BZD dependence. After selection for inclusion and exclusion criteria, 50 patients (23 men, 27 women; age 42.7 \ub1 10.3 years) were included. They underwent a comprehensive neuropsychological battery to explore verbal memory, visuospatial memory, working memory, attention, and executive functions 28-30 days prior to admission for detoxification (T0) and at the end of detoxification, i.e., 7 days after admission (T1). A group of 50 healthy adults (24 men, 26 women; mean age 44.5 \ub1 12.8 years) matched for age, sex, and education served as controls. Results: At T0, patients scored significantly worse than healthy controls in all the neuropsychological tests. Depression and anxiety scores were associated with impaired verbal memory at T0 in patients. T1-T0 comparison showed improved performances in all neuropsychological tests after the end of detoxification in patients. Conclusion: We confirmed that all neuropsychological domains were significantly and profoundly impaired by high-dose BZD abuse and documented that cognitive abnormalities improved after detoxification with slow subcutaneous infusion of flumazenil

The biocompatibility of porous vs non-porous bone cements: a new methodological approach.

Composite cements have been shown to be biocompatible, bioactive, with good mechanical properties and capability to bind to the bone. Despite these interesting characteristic, in vivo studies on animal models are still incomplete and ultrastructural data are lacking. The acquisition of new ultrastructural data is hampered by uncertainties in the methods of preparation of histological samples due to the use of resins that melt methacrylate present in bone cement composition. A new porous acrylic cement composed of polymethyl-metacrylate (PMMA) and β-tricalcium-phosphate (p-TCP) was developed and tested on an animal model. The cement was implanted in femurs of 8 New Zealand White rabbits, which were observed for 8 weeks before their sacrifice. Histological samples were prepared with an infiltration process of LR white resin and then the specimens were studied by X-rays, histology and scanning electron microscopy (SEM). As a control, an acrylic standard cement, commonly used in clinical procedures, was chosen. Radiographic ultrastructural and histological exams have allowed finding an excellent biocompatibility of the new porous cement. The high degree of osteointegration was demonstrated by growth of neo-created bone tissue inside the cement sample. Local or systemic toxicity signs were not detected. The present work shows that the proposed procedure for the evaluation of biocompatibility, based on the use of LR white resin allows to make a thorough and objective assessment of the biocompatibility of porous and non-porous bone cements

The biocompatibility of porous vs non-porous bone cements: a new methodological approach.

Composite cements have been shown to be biocompatible, bioactive, with good mechanical properties and capability to bind to the bone. Despite these interesting characteristic, in vivo studies on animal models are still incomplete and ultrastructural data are lacking. The acquisition of new ultrastructural data is hampered by uncertainties in the methods of preparation of histological samples due to the use of resins that melt methacrylate present in bone cement composition. A new porous acrylic cement composed of polymethyl-metacrylate (PMMA) and \u3b2-tricalcium-phosphate (p-TCP) was developed and tested on an animal model. The cement was implanted in femurs of 8 New Zealand White rabbits, which were observed for 8 weeks before their sacrifice. Histological samples were prepared with an infiltration process of LR white resin and then the specimens were studied by X-rays, histology and scanning electron microscopy (SEM). As a control, an acrylic standard cement, commonly used in clinical procedures, was chosen. Radiographic ultrastructural and histological exams have allowed finding an excellent biocompatibility of the new porous cement. The high degree of osteointegration was demonstrated by growth of neo-created bone tissue inside the cement sample. Local or systemic toxicity signs were not detected. The present work shows that the proposed procedure for the evaluation of biocompatibility, based on the use of LR white resin allows to make a thorough and objective assessment of the biocompatibility of porous and non-porous bone cements

The biocompatibility of bone cements: progress in methodological approach

The ideal bone graft substitute should have certain properties and there are many studies dealing with mixture of polymethylmetacrilate (PMMA) and β-tricalciumphospate (β-TCP) presenting the best characteristics of both. Scanning Electron Microscopy (SEM), for ultra-structural data, resulted a very reliable in vivo model to better understand the bioactivity of a cement and to properly evaluate its suitability for a particular purpose. The present study aims to further improve the knowledge on osteointegration development, using both parameters obtained with the Environmental Scanning Electron Microscopy (ESEM) and focused histological examination. Two hybrid bone graft substitute were designed among ceramic and polymer-based bone graft substitutes. Based on β-TCP granules sizes, they were created with theoretical different osteoconductive properties. An acrylic standard cement was chosen as control. Cements were implanted in twelve New Zealand White (NZW) rabbits, which were sacrificed at 1, 2, 3, 6, 9 and 12 months after cement implantation. Histological samples were prepared with an infiltration process of LR white resin and then specimens were studied by X-rays, histology and Environmental Scanning Electron Microscopy (ESEM). Comparing the resulting data, it was possible to follow osteointegration's various developments resulting from different sizes of β-TCP granules. In this paper, we show that this evaluation process, together with ESEM, provides further important information that allows to follow any osteointegration at every stage of develop