Dermatitis in community pharmacies: a survey on italian pharmacists’ management and implications on corticophobia

Community pharmacists represent an important resource for the promotion of a safer and more effective self-management of common skin diseases, as well as the provision of educational support on therapies prescribed by clinicians, ultimately improving patients’ adherence. In this study, a semi-structured survey was administered to 154 Italian community pharmacists, in order to acquire information on their counseling activity on dermatological disorders. Collected data provide an overview on the frequency and methodology of counseling offered in Italian community pharmacies, identifying knowledge gaps and misbeliefs. In particular, an overall negative opinion on topical corticosteroid therapy emerged among pharmacists, unveiling a phenomenon previously described as corticophobia. Starting from this observation, we discuss the risks for patients’ adherence, associated with corticophobia among pharmacists. Lastly, we briefly report on the main tools desired by pharmacists to improve their education on dermatology, envisioning their implementation with the aim of a more effective counseling

Adaptation of communication assessment tool for community pharmacists in medication adherence and minor diseases management

Aim: To develop two versions of the Communication Assessment Tool (CAT) skilled for the setting of community pharmacy and to pilot test it on a selected sample. Materials: Development of two versions of CAT-tool for community pharmacists. Validity and reliability assessments were required to determine the psychometric properties of developed tool versions. To investigate the construct validity of each adapted tool item, confirmatory factor analysis was performed. Reliability was assessed with the Cronbach’s Alpha evaluation, internal validity by submitting tool versions to patients of eleven pharmacies from North, Center, and South of Italy for pilot testing. Results: Two CAT versions were developed and tested: CAT-Pharm-community Adherence to therapy and Minor Disease Management versions. First to evaluate pharmacist-patient communication following the dispensing of a prescription drug, second a consultation for minor disease management. Conclusion: Communication tools are useful to implement optimal management of chronic diseases to minimize non-adherence and patients’ negative health outcomes

Modelling marine emissions and atmospheric distributions of halocarbons and dimethyl sulfide: the influence of prescribed water concentration vs. prescribed emissions

Marine-produced short-lived trace gases such as dibromomethane (CH2Br2), bromoform (CHBr3), methyliodide (CH3I) and dimethyl sulfide (DMS) significantly impact tropospheric and stratospheric chemistry. Describing their marine emissions in atmospheric chemistry models as accurately as possible is necessary to quantify their impact on ozone depletion and Earth's radiative budget. So far, marine emissions of trace gases have mainly been prescribed from emission climatologies, thus lacking the interaction between the actual state of the atmosphere and the ocean. Here we present simulations with the chemistry climate model EMAC (ECHAM5/MESSy Atmospheric Chemistry) with online calculation of emissions based on surface water concentrations, in contrast to directly prescribed emissions. Considering the actual state of the model atmosphere results in a concentration gradient consistent with model real-time conditions at the ocean surface and in the atmosphere, which determine the direction and magnitude of the computed flux. This method has a number of conceptual and practical benefits, as the modelled emission can respond consistently to changes in sea surface temperature, surface wind speed, sea ice cover and especially atmospheric mixing ratio. This online calculation could enhance, dampen or even invert the fluxes (i.e. deposition instead of emissions) of very short-lived substances (VSLS). We show that differences between prescribing emissions and prescribing concentrations (−28 % for CH2Br2 to +11 % for CHBr3) result mainly from consideration of the actual, time-varying state of the atmosphere. The absolute magnitude of the differences depends mainly on the surface ocean saturation of each particular gas. Comparison to observations from aircraft, ships and ground stations reveals that computing the air–sea flux interactively leads in most of the cases to more accurate atmospheric mixing ratios in the model compared to the computation from prescribed emissions. Calculating emissions online also enables effective testing of different air–sea transfer velocity (k) parameterizations, which was performed here for eight different parameterizations. The testing of these different k values is of special interest for DMS, as recently published parameterizations derived by direct flux measurements using eddy covariance measurements suggest decreasing k values at high wind speeds or a linear relationship with wind speed. Implementing these parameterizations reduces discrepancies in modelled DMS atmospheric mixing ratios and observations by a factor of 1.5 compared to parameterizations with a quadratic or cubic relationship to wind spee

Targeted Delivery of Adamantylated Peptidoglycan Immunomodulators in Lipid Nanocarriers: NMR Shows That Cargo Fragments are Available on the Surface

We present an in-depth investigation of the membrane interactions of peptidoglycan (PGN)-based immune adjuvants designed for lipid-based delivery systems using NMR spectroscopy. The derivatives contain a cargo peptidoglycan (PGN) dipeptide fragment and an adamantyl group, which serves as an anchor to the lipid bilayer. Furthermore, derivatives with a mannose group that can actively target cell surface receptors on immune cells are also studied. We showed that the targeting mannose group and the cargo PGN fragment are both available on the lipid bilayer surface, thereby enabling interactions with cognate receptors. We found that the nonmannosylated compounds are incorporated stronger into the lipid assemblies than the mannosylated ones, but the latter compounds penetrate deeper in the bilayer. This might be explained by stronger electrostatic interactions available for zwitterionic nonmannosylated derivatives as opposed to the compounds in which the charged N-terminus is capped by mannose groups. The higher incorporation efficiency of the nonmannosylated compounds correlated with a larger relative enhancement in immune stimulation activities upon lipid incorporation compared to that of the derivatives with the mannose group. The chirality of the adamantyl group also influenced the incorporation efficiency, which in turn correlated with membrane-associated conformations that affect possible intermolecular interactions with lipid molecules. These findings will help in improving the development of PGN-based immune adjuvants suitable for delivery in lipid nanoparticles

Validation of the Italian Version of the Test of Adherence to Inhalers

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Globular domain of the prion protein needs to be unlocked by domain swapping to support prion protein conversion

Prion diseases are fatal transmissible neurodegenerative diseases affecting many mammalian species. The normal prion protein (PrP) converts into a pathological aggregated form, PrPSc, which is enriched in the β-sheet structure. While the high resolution structure of the normal PrP was determined, the structure of the converted form of PrP remains inaccessible to high resolution techniques. In order to map the PrP conversion process we introduced disulfide bridges into different positions within the globular domain of PrP, tethering selected secondary structure elements. The majority of tethered PrP mutants exhibited increased thermodynamic stability, nevertheless they converted efficiently. Only the disulfides which tether subdomain B1-H1-B2 to subdomain H2-H3 prevented PrP conversion in vitro and in prion infected cell cultures. Reduction of disulfides recovered the ability of these mutants to convert, demonstrating that the separation of subdomains is an essential step in conversion. Formation of disulfide-linked proteinase K-resistant dimers in fibrils composed of a pair of single cysteine mutants supports the model based on domain-swapped dimers as the building blocks of prion fibrils. In contrast to previously proposed structural models of PrPSc suggesting conversion of large secondary structure segments, we provide evidence for the conservation of secondary structure elements of the globular domain upon PrP conversion. Previous studies already showed that dimerization is the rate-limiting step in PrP conversion. We show that separation and swapping of subdomains of the globular domain is necessary for conversion. Therefore, we propose that domain-swapped dimer of PrP precedes amyloid formation and represents a potential target for therapeutic intervention

Medicinali equivalenti in Italia: le ragioni della diffidenza di medici e farmacisti = Equivalent medicinal products in Italy: the reasons for the prudence of physicians and pharmacists

Despite the regulatory framework favourable to the use of equivalent medicines in Italy, it remains below the European average. Although the causes are not fully clarified, several factors can concur to the patient reluctance to take generic medicines. In this context, the influence of health professionals (e.g., physicians, pharmacists) could play an important role. The aim of this work is to investigate the reasons behind the reticence of doctors and pharmacists to prescribe/ recommend equivalent medicines by means of a survey sent to 308 health professionals. The results confirmed a lack of confidence in 43% of the interviewees. Based on such results, another survey was conducted on the same sub-group of health professionals to better identify the causes of their reluctance. Among the main causes of distrust towards equivalent medicines remains the erroneous belief that the quality, safety and efficacy profile is not comparable with the originator. Physicians and pharmacists were particularly sceptics towards the equivalent drugs of the therapeutic classes most frequently used to treat chronic diseases (e.g., hypertension, arrhythmias, cardiopathies, diabetes mellitus). Such results highlighted that there is room for improving the preparation of the health professionals towards a better patient education about equivalent medicines. On the other side, the results highlighted the caution of both physicians and pharmacists with respect to uncontrolled switching of medicines and their propensity to promote a linear therapeutic choice so that the patient takes the same medicine throughout the therapy

Capping protein-controlled actin polymerization shapes lipid membranes

Arp2/3 complex-mediated actin assembly at cell membranes drives the formation of protrusions or endocytic vesicles. To identify the mechanism by which different membrane deformations can be achieved, we reconstitute the basic membrane deformation modes of inward and outward bending in a confined geometry by encapsulating a minimal set of cytoskeletal proteins into giant unilamellar vesicles. Formation of membrane protrusions is favoured at low capping protein (CP) concentrations, whereas the formation of negatively bent domains is promoted at high CP concentrations. Addition of non-muscle myosin II results in full fission events in the vesicle system. The different deformation modes are rationalized by simulations of the underlying transient nature of the reaction kinetics. The relevance of the regulatory mechanism is supported by CP overexpression in mouse melanoma B16-F1 cells and therefore demonstrates the importance of the quantitative understanding of microscopic kinetic balances to address the diverse functionality of the cytoskeleton