Self-report of Cognition and Objective Test Performance in Posttraumatic Headache

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/74675/1/j.1526-4610.1996.3605300.x.pd

Liposomes characterization for market approval as pharmaceutical products: Analytical methods, guidelines and standardized protocols

Liposomes are nano-sized lipid-based vesicles widely studied for their drug delivery capabilities. Compared to standard carries they exhibit better properties such as improved site-targeting and drug release, protection of drugs from degradation and clearance, and lower toxic side effects. At present, scientific literature is rich of studies regarding liposomes-based systems, while 14 types of liposomal products have been authorized to the market by EMA and FDA and many others have been approved by national agencies. Although the interest in nanodevices and nanomedicine has steadily increased in the last two decades the development of documentation regulating and standardizing all the phases of their development and quality control still suffers from major inadequacy due to the intrinsic complexity of nano-systems characterization. Many generic documents (Type 1) discussing guidelines for the study of nano-systems (lipidic and not) have been proposed while there is a lack of robust and standardized methods (Type 2 documents). As a result, a widespread of different techniques, approaches and methodologies are being used, generating results of variable quality and hard to compare with each other. Additionally, such documents are often subject to updates and rewriting further complicating the topic. Within this context the aim of this work is focused on bridging the gap in liposome characterization: the most recent standardized methodologies suitable for liposomes characterization are here reported (with the corresponding Type 2 documents) and revised in a short and pragmatical way focused on providing the reader with a practical background of the state of the art. In particular, this paper will put the accent on the methodologies developed to evaluate the main critical quality attributes (CQAs) necessary for liposomes market approval

Exopolysaccharides from vaginal lactobacilli modulate microbial biofilms

Background: Exopolysaccharides (EPS) secreted by beneficial lactobacilli exert a plethora of positive activities, but little is known about their effects on biofilms of opportunistic vaginal pathogens and especially on biofilms of lactobacilli themselves. Here, the EPS produced by six vaginal lactobacilli, belonging to Lactobacillus crispatus (BC1, BC4, BC5) and Lactobacillus gasseri (BC9, BC12, BC14) species were isolated from cultural supernatants and lyophilized. Results: Lactobacillus EPS were chemically characterized in terms of monosaccharide composition by liquid chromatography (LC) analysis coupled to UV and mass spectrometry (MS) detection. Moreover, the ability of EPS (0.1, 0.5, 1 mg/mL) to stimulate the biofilm formation of lactobacilli and to inhibit the formation of pathogens’ biofilms was evaluated by crystal violet (CV) staining and 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay. Isolated EPS (yields 133–426 mg/L) were heteropolysaccharides mainly composed of d-mannose (40–52%) and d-glucose (11–30%). For the first time we demonstrated that Lactobacillus EPS were able to stimulate in a dose-dependent manner (p < 0.05) the formation of biofilms of ten strains belonging to L. crispatus, L. gasseri and Limosilactobacillus vaginalis species, in terms of cell viability (84–282% increase at 1 mg/mL) and especially biofilm biomass (40–195% increase at 1 mg/mL), quantified with MTT assay and CV staining, respectively. EPS released from L. crispatus and L. gasseri were found to better stimulate the biofilms of the same producer species rather than that of other species, including producing strains themselves and other strains. Conversely, the biofilm formation of bacterial (Escherichia coli, Staphylococcus spp., Enterococcus spp. and Streptococcus agalactiae) and fungal (Candida spp.) pathogens was inhibited. The anti-biofilm activity was dose-dependent and was more marked for L. gasseri-derived EPS (inhibition up to 86%, 70%, and 58% at 1 mg/mL, 0.5 mg/mL, and 0.1 mg/mL, respectively), whilst L. crispatus-derived EPS resulted overall less efficient (inhibition up to 58% at 1 mg/mL and 40% at 0.5 mg/mL) (p < 0.05). Conclusions: Lactobacilli-derived EPS favour the biofilm formation of lactobacilli preventing, at the same time, that of opportunistic pathogens. These results support the possible employment of EPS as postbiotics in medicine as a therapeutic/preventive strategy to counteract vaginal infections

Evaluation of the pharmacodynamic and pharmacokinetic interaction between pagoclone and ethanol

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/109936/1/cptclpt2003353.pd

Dairy bioactives and functional ingredients with skin health benefits

The potential of whey from Italian cheese productions to support skin health and anti-ageing mechanism was studied. The effect of whey on dermal and epidermal cells was evaluated. Whey inhibited the activity of elastase and tyrosinase enzymes by 60% and 32%, respectively. Whey cytotoxicity against tested skin cell lines, human fibroblasts (HDFa) and keratinocytes (HaCaT) was not observed. Moreover, the antioxidant activity of the samples was noted, after treatment with whey intracellular ROS level was decreased by 87% in comparison with the hydrogen peroxide-treated cells. Fibroblasts produced a significant amount of extracellular matrix molecules, collagen I, elastin and glycosaminoglycans as a result of treatment with tested whey. In addition, the ability of samples to improve the cell barrier integrity of keratinocytes was proven. The obtained results indicate that pure whey supports skin health and shows potential to be used by the cosmetic industry

First case of typhoid fever due to extensively drug-resistant Salmonella enterica serovar typhi in Italy

Typhoid fever is a potentially severe and occasionally life-threatening bacteraemic illness caused by Salmonella enterica serovar Typhi (S. Typhi). In Pakistan, an outbreak of extensively drug-resistant (XDR) S. Typhi cases began in November 2016. We report on a five-year-old boy who contracted enteric fever while travelling in Pakistan and was diagnosed after returning to Italy in September 2019. Blood culture isolated Salmonella enterica serovar Typhi that was XDR to all first-line antibiotics, including ceftriaxone and fluoroquinolones. Empiric therapy was switched to meropenem, and the patient recovered completely. Whole-genome sequencing showed that this isolate was of haplotype H58. The XDR S. Typhi clone encoded a chromosomally located resistance region and harbored a plasmid encoding additional resistance elements, including the blaCTX-M-15 extended-spectrum β-lactamase and the qnrS fluoroquinolone resistance gene. This is the first case of typhoid fever due to XDR S. Typhi detected in Italy and one of the first paediatric cases reported outside Pakistan, highlighting the need to be vigilant for future cases. While new vaccines against typhoid are in development, clinicians should consider adapting their empiric approach for patients returning from regions at risk of XDR S. Typhi outbreak with typhoid symptoms

FFF-based high-throughput sequence shortlisting to support the development of aptamer-based analytical strategies

Aptamers are biomimetic receptors that are increasingly exploited for the development of optical and electrochemical aptasensors. They are selected in vitro by the SELEX (Systematic Evolution of Ligands by Exponential Enrichment) procedure, but although they are promising recognition elements, for their reliable applicability for analytical purposes, one cannot ignore sample components that cause matrix effects. This particularly applies when different SELEX-selected aptamers and related truncated sequences are available for a certain target, and the choice of the aptamer should be driven by the specific downstream application. In this context, the present work aimed at investigating the potentialities of asymmetrical flow field-flow fractionation (AF4) with UV detection for the development of a screening method of a large number of anti-lysozyme aptamers towards lysozyme, including randomized sequences and an interfering agent (serum albumin). The possibility to work in native conditions and selectively monitor the evolution of untagged aptamer signal as a result of aptamer-protein binding makes the devised method effective as a strategy for shortlisting the most promising aptamers both in terms of affinity and in terms of selectivity, to support subsequent development of aptamer-based analytical devices. Graphical abstract: [Figure not available: see fulltext.

Variations of neck structures after supracricoid partial laryngectomy: a multislice computed tomography evaluation

Background: Surgery of laryngeal cancer used to profoundly alter the anatomy of the cervical region. Accurate anatomo-embryologic studies and repeated surgical trials allowed recognition of the cricoarytenoid complex as the smallest anatomofunctional unit able to maintain all the laryngeal functions. Objectives: The aim of this study was to determine whether significant variations of neck anatomical parameters exist after partial laryngectomy, and to analyze whether some of these parameters are associated with a positive functional outcome. Methods: Out of 48 patients treated with a surgical technique according to Mayer-Piquet (cricohyoidoepiglottopexy, CHEP) over a 6-year period, 18 patients were enrolled in the study. Patients were all males with a mean age of 60 years. Cervical structures and their relationships were measured by computed tomography, and the measurements before and after surgery were compared. Results: Our data showed that hyoid bone is modified, both in morphology and position during CHEP. More specifically the relation of the hyoid bone to other neck structures ( identified by the alpha-angle) is modified. The neolarynx and trachea undergo a caudocranial shift. All diameters of the cricoid cartilage remain unchanged after surgery. The position of the epiglottis after CHEP, in particular its relation with the arytenoid cartilage, is closely related to swallowing function outcome and recovery time. Conclusions: Our study showed that these structures, and more specifically the relations among them, undergo significant variations after CHEP. Our results identify some parameters, i.e. the alpha-angle, width of the hyoid bone and position of the epiglottis, that may predispose to a positive functional outcome after surgery

Emerging Microfluidic Tools for Simultaneous Exosomes and Cargo Biosensing in Liquid Biopsy: New Integrated Miniaturized FFF-Assisted Approach for Colon Cancer Diagnosis

The early-stage diagnosis of cancer is a crucial clinical need. The inadequacies of surgery tissue biopsy have prompted a transition to a less invasive profiling of molecular biomarkers from biofluids, known as liquid biopsy. Exosomes are phospholipid bilayer vesicles present in many biofluids with a biologically active cargo, being responsible for cell-to-cell communication in biological systems. An increase in their excretion and changes in their cargo are potential diagnostic biomarkers for an array of diseases, including cancer, and they constitute a promising analyte for liquid biopsy. The number of exosomes released, the morphological properties, the membrane composition, and their content are highly related to the physiological and pathological states. The main analytical challenge to establishing liquid biopsy in clinical practice is the development of biosensors able to detect intact exosomes concentration and simultaneously analyze specific membrane biomarkers and those contained in their cargo. Before analysis, exosomes also need to be isolated from biological fluids. Microfluidic systems can address several issues present in conventional methods (i.e., ultracentrifugation, size-exclusion chromatography, ultrafiltration, and immunoaffinity capture), which are time-consuming and require a relatively high amount of sample; in addition, they can be easily integrated with biosensing systems. A critical review of emerging microfluidic-based devices for integrated biosensing approaches and following the major analytical need for accurate diagnostics is presented here. The design of a new miniaturized biosensing system is also reported. A device based on hollow-fiber flow field-flow fractionation followed by luminescence-based immunoassay is applied to isolate intact exosomes and characterize their cargo as a proof of concept for colon cancer diagnosis