Solvates, salts, and cocrystals : a proposal for a feasible classification system

The design of pharmaceutical cocrystals has initiated widespread debate on the classification of cocrystals. Current attempts to classify multicomponent crystals suffer from ambiguity, which has led to inconsistent definitions for cocrystals and for multicomponent crystals in general. Inspired by the work of Aitipamula et al. (Cryst. Growth Des. 2012, 12, 2147-2152), we present a feasible classification system for all multicomponent crystals. The present classification enables us to analyze and classify multicomponent crystal structures present in the Cambridge Structural Database (CSD). This reveals that all seven classes proposed are relevant in terms of frequency of occurrence. Lists of CSD refcodes for all classes are provided. We identified over 5000 cocrystals in the CSD, as well as over 12 000 crystals with more than two components. This illustrates that the possibilities for alternative drug formulations can be increased significantly by considering more than two components in drug design

Activation and Inactivation Kinetics of Torpedo californica Acetylcholine Receptor in Reconstituted Membranes

P>Background: To date no studies have compared generic health-related quality of life (HRQL) of food allergic patients from childhood to adulthood with that of the general population or patients with other chronic diseases. The aim of this study was to compare generic HRQL of food allergic patients with the general population and other diseases. Methods: Generic HRQL questionnaires (CHQ-CF87 and RAND-36) were completed by 79 children, 74 adolescents and 72 adults with food allergy. The generic HRQL scores were compared with scores from published studies on the general population and patients with asthma, irritable bowel syndrome (IBS), diabetes mellitus (DM) and rheumatoid arthritis (RA). Results: Food allergic children and adolescents reported fewer limitations in school work due to behavioural problems (P <0.013), but food allergic adolescents and adults reported more pain (P = 0.020), poorer overall health (P <0.001), more limitations in social activities (P <0.001) and less vitality (P = 0.002) than individuals from the general population. Food allergic patients reported poorer generic HRQL than patients with DM, but better generic HRQL than patients with RA, asthma and IBS. Conclusion: HRQL is impaired in food allergic adolescents and adults, compared to the general population, and it is intermediate in magnitude between DM and RA, asthma and IBS. Children show the least impact on generic HRQL from food allergy

Reaching for the 'first 95': a cross-country analysis of HIV self-testing in nine countries in sub-Saharan Africa

OBJECTIVES: HIV self-testing (HIVST) offers a promising approach to increase HIV diagnosis and advance progress towards the UNAIDS 95-95-95 targets. We aimed to understand patterns of HIVST awareness and utilization in nine sub-Saharan African (SSA) countries, with the goal of identifying populations to target in disseminating this technology. DESIGN: A cross-sectional study. METHODS: We pooled individual-level population-based data from nine Demographic and Health Surveys (DHS) in SSA conducted 2015-2019 (Burundi, Cameroon, Guinea, Malawi, Senegal, Sierra Leone, South Africa, Zambia, Zimbabwe). Primary outcomes were HIVST awareness and utilization. We used logistic regression with survey fixed effects to explore the relationship between sociodemographic characteristics and these outcomes. Models were adjusted for sex, age, rural/urban residence, education, wealth, and marital status. We accounted for complex survey design. RESULTS: The study sample included 177 572 people (66.0% women, mean age 29 ± 10 years), of whom 86.6% [95% confidence interval (95% CI) 86.4-86.7] were unaware of HIVST, 11.7% (95% CI 11.6-11.9) were aware of but never used HIVST, and 1.7% (95% CI 1.6-1.8) had used HIVST. In adjusted models, women were less likely to be aware of HIVST [odds ratio (OR) 0.75, 95% CI 0.71-0.79], but more likely to have used HIVST (OR 1.17, 95% CI 1.03-1.32) compared with men. Rural residents, those who were least educated, and poorest were less likely to have heard of or used HIVST. CONCLUSION: HIVST awareness and uptake were low. Rural, less educated, and lower income populations were least likely to have heard of or used HIVST. Efforts to scale-up HIVST in these settings should aim to reach these less advantaged groups

Modeling Vesicle Traffic Reveals Unexpected Consequences for Cdc42p-Mediated Polarity Establishment

SummaryBackgroundPolarization in yeast has been proposed to involve a positive feedback loop whereby the polarity regulator Cdc42p orients actin cables, which deliver vesicles carrying Cdc42p to the polarization site. Previous mathematical models treating Cdc42p traffic as a membrane-free flux suggested that directed traffic would polarize Cdc42p, but it remained unclear whether Cdc42p would become polarized without the membrane-free simplifying assumption.ResultsWe present mathematical models that explicitly consider stochastic vesicle traffic via exocytosis and endocytosis, providing several new insights. Our findings suggest that endocytic cargo influences the timing of vesicle internalization in yeast. Moreover, our models provide quantitative support for the view that integral membrane cargo proteins would become polarized by directed vesicle traffic given the experimentally determined rates of vesicle traffic and diffusion. However, such traffic cannot effectively polarize the more rapidly diffusing Cdc42p in the model without making additional assumptions that seem implausible and lack experimental support.ConclusionsOur findings suggest that actin-directed vesicle traffic would perturb, rather than reinforce, polarization in yeast

Multicentre Double-Blind Placebo-Controlled Food Challenge Study in Children Sensitised to Cashew Nut

Few studies with a limited number of patients have provided indications that cashew-allergic patients may experience severe allergic reactions to minimal amounts of cashew nut. The objectives of this multicentre study were to assess the clinical relevance of cashew nut sensitisation, to study the clinical reaction patterns in double-blind placebo-controlled food challenge tests and to establish the amount of cashew nuts that can elicit an allergic reaction.A total of 179 children were included (median age 9.0 years; range 2-17 years) with cashew nut sensitisation and a clinical history of reactions to cashew nuts or unknown exposure. Sensitised children who could tolerate cashew nuts were excluded. The study included three clinical visits and a telephone consultation. During the first visit, the medical history was evaluated, physical examinations were conducted, blood samples were drawn and skin prick tests were performed. The children underwent a double-blind placebo-controlled food challenge test with cashew nut during the second and third visits. The study showed that 137 (76.5%) of the sensitised children suspected of allergy to cashew nut had a positive double-blind placebo-controlled food challenge test, with 46% (63) manifesting subjective symptoms to the lowest dose of 1 mg cashew nut protein and 11% (15) developing objective symptoms to the lowest dose. Children most frequently had gastro-intestinal symptoms, followed by oral allergy and skin symptoms. A total of 36% (49/137) of the children experienced an anaphylactic reaction and 6% (8/137) of the children were treated with epinephrine.This prospective study demonstrated a strikingly high percentage of clinical reactions to cashew nut in this third line population. Severe allergic reactions, including anaphylaxis requiring epinephrine, were observed. These reactions were to minimal amounts of cashew nut, demonstrated the high potency of this allergens.www.ncbi.nlm.nih.gov/pubmed NTR3572

CoPub update: CoPub 5.0 a text mining system to answer biological questions

In this article, we present CoPub 5.0, a publicly available text mining system, which uses Medline abstracts to calculate robust statistics for keyword co-occurrences. CoPub was initially developed for the analysis of microarray data, but we broadened the scope by implementing new technology and new thesauri. In CoPub 5.0, we integrated existing CoPub technology with new features, and provided a new advanced interface, which can be used to answer a variety of biological questions. CoPub 5.0 allows searching for keywords of interest and its relations to curated thesauri and provides highlighting and sorting mechanisms, using its statistics, to retrieve the most important abstracts in which the terms co-occur. It also provides a way to search for indirect relations between genes, drugs, pathways and diseases, following an ABC principle, in which A and C have no direct connection but are connected via shared B intermediates. With CoPub 5.0, it is possible to create, annotate and analyze networks using the layout and highlight options of Cytoscape web, allowing for literature based systems biology. Finally, operations of the CoPub 5.0 Web service enable to implement the CoPub technology in bioinformatics workflows. CoPub 5.0 can be accessed through the CoPub portal http://www.copub.org