What do they look for and what do they find? A coproduced qualitative study on young people's experiences of searching for mental health information online.

BACKGROUND: Many young people (YP) struggle with their mental health and look online for help. To capitalise on their digital presence, we need to better understand how and where they seek information online and what they think of what they find. METHOD: We recruited 24 YP (aged 13-18 years). Online interviews were co-conducted by research team members and trained young researchers. We presented a persona with depression symptoms and asked about potential sources of information/support they might seek. They were also asked to think aloud while searching online and reviewing mental health resources (NHS, Young Minds). We used reflexive thematic analysis. RESULTS: Analysis generated four themes: (1) the online help-seeking process, showcasing where YP look for information and why; (2) the mismatch between the information YP expected to find and the reality; (3) the strategies YP employed to determine a source's trust and credibility and (4) individual differences that can influence help-seeking. CONCLUSION: Participants initiated their online search by Googling symptoms. They trusted NHS websites for basic medical information, while charities provided detailed content. Despite scepticism about content, social media offered validation. Online resources should prioritise visual appeal, user-friendliness, age-appropriate and personalised content and peer insights. Codesign is imperative to ensure high-quality, impactful research.

Identification of A3 adenosine receptor agonists as novel non-narcotic analgesics.

Chronic pain negatively impacts the quality of life in a variety of patient populations. The current therapeutic repertoire is inadequate in managing patient pain and warrants the development of new therapeutics. Adenosine and its four cognate receptors (A1 , A2A , A2B and A3 ) have important roles in physiological and pathophysiological states, including chronic pain. Preclinical and clinical studies have revealed that while adenosine and agonists of the A1 and A2A receptors have antinociceptive properties, their therapeutic utility is limited by adverse cardiovascular side effects. In contrast, our understanding of the A3 receptor is only in its infancy, but exciting preclinical observations of A3 receptor antinociception, which have been bolstered by clinical trials of A3 receptor agonists in other disease states, suggest pain relief without cardiovascular side effects and with sufficient tolerability. Our goal herein is to briefly discuss adenosine and its receptors in the context of pathological pain and to consider the current data regarding A3 receptor-mediated antinociception. We will highlight recent findings regarding the impact of the A3 receptor on pain pathways and examine the current state of selective A3 receptor agonists used for these studies. The adenosine-to-A3 receptor pathway represents an important endogenous system that can be targeted to provide safe, effective pain relief from chronic pain.

Chitosan nanoparticles as delivery systems for doxorubicin.

The aim of this paper was to evaluate the potential of chitosan nanoparticles as carriers for the anthracycline drug, doxorubicin (DOX). The challenge was to entrap a cationic, hydrophilic molecule into nanoparticles formed by ionic gelation of the positively charged polysaccharide chitosan. To achieve this objective, we attempted to mask the positive charge of DOX by complexing it with the polyanion, dextran sulfate. This modification doubled DOX encapsulation efficiency relative to controls and enabled real loadings up to 4.0 wt.% DOX. Separately, we investigated the possibility of forming a complex between chitosan and DOX prior to the formation of the particles. Despite the low complexation efficiency, no dissociation of the complex was observed upon formation of the nanoparticles. Fluorimetric analysis of the drug released in vitro showed an initial release phase, the intensity of which was dependent on the association mode, followed by a very slow release. The evaluation of the activity of DOX-loaded nanoparticles in cell cultures indicated that those containing dextran sulfate were able to maintain cytostatic activity relative to free DOX, while DOX complexed to chitosan before nanoparticle formation showed slightly decreased activity. Additionally, confocal studies showed that DOX was not released in the cell culture medium but entered the cells while remaining associated to the nanoparticles. In conclusion, these preliminary studies showed the feasibility of chitosan nanoparticles to entrap the basic drug DOX and to deliver it into the cells in its active form.

Polysaccharide colloidal particles as delivery systems for macromolecules.

Mucosal delivery of complex molecules such as peptides, proteins, oligonucleotides, and plasmids is one of the most intensively studied subjects. The use of colloidal carriers made of hydrophilic polysaccharides, i.e. chitosan, has arisen as a promising alternative for improving the transport of such macromolecules across biological surfaces. This article reviews the approaches which have aimed to associate macromolecules to chitosan in the form of colloidal structures and analyzes the evidence of their efficacy in improving the transport of the associated molecule through mucosae and epithelia. Chitosan has been shown to form colloidal particles and entrap macromolecules through a number of mechanisms, including ionic crosslinking, desolvation, or ionic complexation, though some of these systems have been realized only in conjunction with DNA molecules. An alternative involving the chemical modification of chitosan has also been useful for the association of macromolecules to self-assemblies and vesicles. To date, the in vivo efficacy of these chitosan-based colloidal carriers has been reported for two different applications: while DNA-chitosan hybrid nanospheres were found to be acceptable transfection carriers, ionically crosslinked chitosan nanoparticles appeared to be efficient vehicles for the transport of peptides across the nasal mucosa. The potential applications and future prospects of these new systems for mucosal delivery of macromolecules are highlighted at the end of the chapter.

Chitosan-DNA nanoparticles as gene carriers: synthesis, characterization and transfection efficiency.

Chitosan-DNA nanoparticles were prepared using a complex coacervation process. The important parameters for the nanoparticle synthesis were investigated, including the concentrations of DNA, chitosan and sodium sulfate, temperature of the solutions, pH of the buffer, and molecular weights of chitosan and DNA. At an amino group to phosphate group ratio (N/P ratio) between 3 and 8 and a chitosan concentration of 100 microg/ml, the size of particles was optimized to approximately 100--250 nm with a narrow distribution, with a composition of 35.6 and 64.4% by weight for DNA and chitosan, respectively. The surface charge of these particles was slightly positive with a zeta potential of +12 to +18 mV at pH lower than 6.0, and became nearly neutral at pH 7.2. The chitosan-DNA nanoparticles could partially protect the encapsulated plasmid DNA from nuclease degradation as shown by electrophoretic mobility analysis. The transfection efficiency of chitosan-DNA nanoparticles was cell-type dependent. Typically, it was three to four orders of magnitude, in relative light units, higher than background level in HEK293 cells, and two to ten times lower than that achieved by LipofectAMINE-DNA complexes. The presence of 10% fetal bovine serum did not interfere with their transfection ability. Chloroquine could be co-encapsulated in the nanoparticles at 5.2%, but with negligible enhancement effect despite the fact that chitosan only showed limited buffering capacity compared with PEI. The present study also developed three different schemes to conjugate transferrin or KNOB protein to the nanoparticle surface. The transferrin conjugation only yielded a maximum of four-fold increase in their transfection efficiency in HEK293 cells and HeLa cells, whereas KNOB conjugated nanoparticles could improve gene expression level in HeLa cells by 130-fold. Conjugation of PEG on the nanoparticles allowed lyophilization without aggregation, and without loss of bioactivity for at least 1 month in storage. The clearance of the PEGylated nanoparticles in mice following intravenous administration was slower than unmodified nanoparticles at 15 min, and with higher depositions in kidney and liver. However, no difference was observed at the 1-h time point.

Results of a prospective multicenter trial evaluating the ePTFE peritoneal onlay laparoscopic inguinal hernioplasty.

A 2.8-year prospective multicenter trial was conducted to evaluate the ePTFE peritoneal onlay laparoscopic inguinal hernioplasty. A total of 441 inguinal hernias were repaired in 351 patients (326 male; 25 female). Two hundred twenty-six of the hernias were direct, 185 indirect, 4 femoral, 26 pantaloon, 90 bilateral, and 92 recurrent. Standardized data collection forms were used and submitted for centralized data analysis. For the hernioplasty, Cooper's ligament was exposed and an 8 cm x 12 cm x 1 mm GORE-TEX Soft Tissue Patch was stapled circumferentially to Cooper's ligament and the endoabdominal fascia. Patients were followed at 1 week, 6 months, 1 year, and then annually. Three-month intervals were used as needed. There was a mean follow-up of 447 days, with 21% of the total repairs followed for more than 2 years and 56% for more than a year. The overall follow-up rate was 95.5%. The operative and postoperative complication rates were 0.45% and 8%, respectively. There were 17 recurrent hernias (3.8%). The range of experience among the investigators was 13 to 168 hernioplasties. With the completion of 25 cases per investigator, the recurrence rate fell to 0.39%. Postoperative analgesia averaged a 24-hr supply of medication; 12.2% of patients required no analgesia. Convalescence averaged 5.4 days, and return to work averaged 7.7 days. This multicenter trial demonstrates that the ePTFE laparoscopic peritoneal onlay inguinal hernioplasty is a safe and dependable repair, especially after the initial learning curve is surmounted.

Alcoholic beverage server liability and the reduction of alcohol-involved problems.

Legal liability of alcoholic beverage servers has been suggested as a means to stimulate preventive serving practices and thus reduce alcohol-involved problems. A number of variables contribute (both negatively and positively) to the potential of such liability and a conceptual model that links these variables was developed. In this project, an expert legal panel was used to identify and rate the major legal factors contributing to server liability. As a result each state was ranked according to its relative level of liability exposure. States that ranked highest in server liability were found to have more publicity about such liability, greater awareness and higher concern among licensed establishment owners/managers and different serving practices compared to states with lowest liability exposure. As a result we conclude that server liability has a real potential for reducing alcohol-involved problems but additional research is needed.

Alcohol availability and the formal power and resources of state alcohol beverage control agencies.

The formal powers and resources of state alcohol beverage control agencies place them in a position to regulate access to alcoholic beverages through restrictions on retail distribution and sales. For example, monopoly states restrict access to spirits, and sometimes wine, by allowing retail sales only through state stores. On the other hand, license and monopoly states share in restricting sales through the use of price posting and fixing provisions. The degree to which these powers are realized in restrictions on alcohol outlets (e.g., licenses) and subsequent alcohol consumption (e.g., sales) was investigated in the current study. In a cross-sectional analysis of data available from 44 alcohol beverage control (ABC) jurisdictions in the United States, it was shown that states with greater restrictions on retail sales had greater resources for the conduct of ABC activities and lower densities of spirit outlets. These states, however, had greater densities of wine and beer outlets. States with greater marketplace restrictions had more resources for ABC enforcement activities and lower outlet densities across all beverage types. Further, supporting the suggestion that availability and demand may be simultaneously related, greater outlet densities were related to greater alcohol consumption (for beer) and greater levels of consumption were related to greater outlet densities (for wine).

The role of formal law in alcohol control systems: a comparison among states.

Formal laws and regulations governing activities of state alcohol beverage control agencies in the United States were classified into 10 categories of physical availability and four categories of economic availability. These categories were subjected to similarity analysis to determine variation among states. Kruskal's stress-one measure revealed three major dimensions of alcohol control laws: forms of retail sales, administrative penalties for violations of alcohol control laws, and price restrictions. This finding suggests that the license/monopoly distinction frequently used to categorize state alcohol control systems is inadequate to characterize the variations in control systems.

Clinical experience with zidovudine for patients with acquired immune deficiency syndrome and acquired immune deficiency syndrome-related complex.

We have treated 113 patients with zidovudine since its licensure, 80 with acquired immunodeficiency syndrome and 33 with acquired immunodeficiency syndrome-related complex. This paper reports on the efficacy and toxicity observed in these patients. Improved well-being, reduced frequency and severity of opportunist infections were notable in the first year of follow-up. More rapid improvement in pulmonary physiological tests during recovery from Pneumocystis carinii pneumonia was also observed in treated patients. Patients with lower initial platelet counts showed early increases in platelet counts. There was a consistent fall in human immunodeficiency virus (HIV) p24 antigen during treatment, although not always to undetectable levels. CD4 cell counts showed a rise in the first months of treatment but these were not sustained, despite continuing clinical benefit. Neuropsychological and clinical evidence of benefit in HIV encephalopathy are described. We have analysed the factors influencing marrow toxicity and have found that low CD4 count and the intercurrent use of ganciclovir and dapsone increase myelotoxicity. We describe the clinical and biochemical features of the myopathy associated with long-term use of zidovudine and summarise our findings on dose-reduction associated meningo-encephalitis.

[The effect of selected preparations for the protection of draft horses against dipterous blood-sucking insects]. / Ucinnost vybraných preparátu k ochrane tazných koní pred dvoukrídlým hmyzem sajícím krev.

Dipterous blood-sucking insects (horseflies, black flies, gnats, midges) have negative impacts on the performance of draught horses in forest enterprises. For the protection of these animals, the following preparations were applied at the interval of 24 hours: diethyltoluamide, Oxamat (N,N-diethyloxamine acid, USSR) and Stomoxin (synthetic pyrethroid, product of the firm Wellcome, England). In the course of 66 working days, the performance of test animals treated with 10% water emulsion of diethyltoluamide increased by 49.25 cu. m. of skidded wood, i.e. by 0.74 cu. m. wood per horse/day (21.65%), as compared with the control group. The daily savings of prime costs per test horse/day made 16.99 Kcs (Czechoslovak crowns). In comparison with the control group, the performance of horses treated with 5% water emulsion of Oxamat increased by 85.50 cu. m. wood, i.e. by 1.29 cu. m. wood per horse/day (38.00%). Stomoxin at the concentration of 0.05% acted as a good insecticide but had no marked repellent effect. The results of this study document that the production of effective repellents should be introduced in the Czechoslovak Socialist Republic.