Automated Potentiometric Titrations in KCl/Water-Saturated Octanol: Method for Quantifying Factors Influencing Ion-Pair Partitioning

The knowledge base of factors influencing ion pair partitioning is very sparse, primarily because of the difficulty in determining accurate log PI values of desirable low molecular weight (MW) reference compounds. We have developed a potentiometric titration procedure in KCl/water-saturated octanol that provides a link to log PI through the thermodynamic cycle of ionization and partitioning. These titrations have the advantage of being independent of the magnitude of log P, while maintaining a reproducibility of a few hundredths of a log P in the calculated difference between log P neutral and log P ion pair (diff (log PN − I)). Simple model compounds can be used. The titration procedure is described in detail, along with a program for calculating pKa′′ values incorporating the ionization of water in octanol. Hydrogen bonding and steric factors have a greater influence on ion pairs than they do on neutral species, yet these factors are missing from current programs used to calculate log PI and log D. In contrast to the common assumption that diff (log PN − I) is the same for all amines, they can actually vary more than 3 log units, as in our examples. A major factor affecting log PI is the ability of water and the counterion to approach the charge center. Bulky substituents near the charge center have a negative influence on log PI. On the other hand, hydrogen bonding groups near the charge center have the opposite effect by lowering the free energy of the ion pair. The use of this titration method to determine substituent ion pair stabilization values (IPS) should bring about more accurate log D calculations and encourage species-specific QSAR involving log DN and log DI. This work also brings attention to the fascinating world of nature’s highly stabilized ion pairs

Molecular and epidemiologic analysis of a county-wide outbreak caused by Salmonella enterica subsp. enterica serovar Enteritidis traced to a bakery

BACKGROUND: An increase in the number of attendees due to acute gastroenteritis and fever was noted at one hospital emergency room in Taiwan over a seven-day period from July to August, 2001. Molecular and epidemiological surveys were performed to trace the possible source of infection. METHODS: An epidemiological investigation was undertaken to determine the cause of the outbreak. Stool and blood samples were collected according to standard protocols per Center for Disease Control, Taiwan. Typing of the Salmonella isolates from stool, blood, and food samples was performed with serotyping, antibiotypes, and pulsed field gel electrophoresis (PFGE) following XbaI restriction enzyme digestion. RESULTS: Comparison of the number of patients with and without acute gastroenteritis (506 and 4467, respectively) during the six weeks before the outbreak week revealed a significant increase in the number of patients during the outbreak week (162 and 942, respectively) (relative risk (RR): 1.44, 95% confidence interval (CI): 1.22–1.70, P value < 0.001). During the week of the outbreak, 34 of 162 patients with gastroenteritis were positive for Salmonella, and 28 of these 34 cases reported eating the same kind of bread. In total, 28 of 34 patients who ate this bread were positive for salmonella compared to only 6 of 128 people who did not eat this bread (RR: 17.6, 95%CI 7.9–39.0, P < 0.001). These breads were produced by the same bakery and were distributed to six different traditional Chinese markets., Salmonella enterica subsp. enterica serovar Enteritidis (S. Enteritidis) was isolated from the stool samples of 28 of 32 individuals and from a recalled bread sample. All S. Enteritidis isolates were of the same antibiogram. PFGE typing revealed that all except two of the clinical isolates and the bread isolates were of the same DNA macrorestriction pattern. CONCLUSIONS: The egg-covered bread contaminated with S. Enteritidis was confirmed as the vehicle of infection. Alertness in the emergency room, surveillance by the microbiology laboratory, prompt and thorough investigation to trace the source of outbreaks, and institution of appropriate control measures provide effective control of community outbreaks

Challenges to the surveillance of non-communicable diseases – a review of selected approaches

Background: The rising global burden of non-communicable diseases (NCDs) necessitates the institutionalization of surveillance systems to track trends and evaluate interventions. However, NCD surveillance capacities vary across high- and low- and middle-income countries. The objective of the review was to analyse existing literature with respect to structures of health facility-based NCD surveillance systems and the lessons low- and middle-income countries can learn in setting up and running these systems. Methods: A literature review was conducted using Pub Med, Web of Knowledge and WHOLIS databases to identify citations published in English language between 1993 and 2013. In total, 20 manuscripts met inclusion criteria: 12 studies were analysed in respect to the surveillance approach, eight supporting documents in respect to general and regional challenges in NCD surveillance. Results: Eleven of the 12 studies identified were conducted in high-income countries. Five studies had a single disease focus, three a multiple NCD focus and three covered communicable as well as non-communicable diseases. Nine studies were passive assisted sentinel surveillance systems, of which six focused on the primary care level and three had additional active surveillance components, i.e., population-based surveys. The supporting documents reveal that NCD surveillance is rather limited in most low- and middle-income countries despite the increasing disease burden and its socioeconomic impact. Major barriers include institutional surveillance capacities and hence data availability. Conclusions: The review suggests that given the complex system requirements, multiple surveillance approaches are necessary to collect comprehensive information for effective NCD surveillance. Sentinel augmented facility-based surveillance, preferably supported by population-based surveys, can provide improved evidence and help budget scarce resources. Electronic supplementary material: The online version of this article (doi:10.1186/s12889-015-2570-z) contains supplementary material, which is available to authorized users

Significant Reduction of Antibiotic Use in the Community after a Nationwide Campaign in France, 2002–2007

Didier Guillemot and colleagues describe the evaluation of a nationwide programme in France aimed at decreasing unnecessary outpatient prescriptions for antibiotics. The campaign was successful, particularly in reducing prescriptions for children

The effect of using an interactive booklet on childhood respiratory tract infections in consultations: Study protocol for a cluster randomised controlled trial in primary care

Background: Respiratory tract infections in children result in more primary care consultations than any other acute condition, and are the most common reason for prescribing antibiotics (which are largely unnecessary). About a fifth of children consult again for the same illness episode. Providing parents with written information on respiratory tract infections may result in a reduction in re-consultation rates and antibiotic prescribing for these illnesses. Asking clinicians to provide and discuss the information during the consultation may enhance effectiveness. This paper outlines the protocol for a study designed to evaluate the use of a booklet on respiratory tract infections in children within primary care consultations. Methods/Design: This will be a cluster randomised controlled trial. General practices will be randomised to provide parents consulting because their child has an acute respiratory tract infection with either an interactive booklet, or usual care. The booklet provides information on the expected duration of their child's illness, the likely benefits of various treatment options, signs and symptoms that should prompt re-consultation, and symptomatic treatment advice. It has been designed for use within the consultation and aims to enhance communication through the use of specific prompts. Clinicians randomised to using the interactive booklet will receive online training in its use. Outcomes will be assessed via a telephone interview with the parent two weeks after first consulting. The primary outcome will be the proportion of children who re-consult for the same illness episode. Secondary outcomes include: antibiotic use, parental satisfaction and enablement, and illness costs. Consultation rates for respiratory tract infections for the subsequent year will be assessed by a review of practice notes. Discussion: Previous studies in adults and children have shown that educational interventions can result in reductions in re-consultation rates and use of antibiotics for respiratory tract infections. This will be the first study to determine whether providing parents with a booklet on respiratory tract infections in children, and discussing it with them during the consultation, reduces re-consultations and antibiotic use for the same illness without reducing satisfaction with care. Trial registration: Current Controlled Trials ISRCTN46104365 </p

Allergotoxicology: Research of Pollutant Influence on the Development of Allergic Reactions

Alergotoksikologija je znanstvenoistraživačko područje koje se bavi ispitivanjem utjecaja polutanata (onečišćivača zraka) na nastanak alergijskih reakcija i bolesti. Ispitivanja su prvobitno bila usmjerena na polutante vanjskih prostora, a u novije vrijeme sve više na polutante unutarnjih prostora u kojima ljudi provode većinu vremena. Polutanti po svojoj prirodi mogu biti krute, tekuće ili plinovite čestice, koje se razlikuju s obzirom na veličinu, sastav i izvor iz kojeg nastaju. S obzirom na izvor mogu biti biološkog i nebiološkog podrijetla. Polutanti koji su predmet suvremenih istraživanja s gledišta nastanka alergijskih bolesti su respirabilne krute čestice, ozon, dušični oksidi i bioaerosoli. Mehanizam djelovanja polutanata ovisi o veličini čestica, njihovoj topljivosti i mjestu ulaska u organizam. Dosadašnja ispitivanja su pokazala da različite čestice uvjetuju različite imunosne i neimunosne odgovore u organizmu. Interakcija polutanata i alergena može se zbivati izvan eksponirane osobe, tj. sa samim alergenom ili u eksponiranoj osobi na sluznicama i koži. Polutanti mogu biti nosioci alergena i mogu interferirati na različitim nivoima u nastanku alergijske reakcije. U ovom prikazu razma raju se dosadašnja saznanja o mehanizmima djelovanja polutanata na alergene, na imunosni sustav izloženih osoba na osnovi epidemioloških populacijskih istraživanja, kliničkih studija ekspozcije u kontroliranim uvjetima i eksperimentalnih testnih sistema in vivo i in vitro.Allergotoxicology studies the infl uence of pollutants on the development of allergic reactions and diseases. At the beginning, the research was focused on outdoor air pollutants, while recently it turns to the indoor environment, mainly because people this is where people spend most of their time. Air pollutants may be solid, soluble, or gaseous particles in nature, and they can differ in size, structure, and sources. Pollutants can be of biological or nonbiological origin. Currently interesting air pollutants include particulate matter, ozone, nitrogen oxides, and bioaerosols. The mechanisms of pollutant activity depend on the particle size, solubility, site of deposition, and specifi c chemical properties. Recent studies have shown that different pollutants provoke different immunological and nonimmunological responses in exposed persons. Interaction between air pollutants and allergens can take place outside the exposed person i.e. with allergen itself, or inside the organism on mucous membranes and skin. Pollutants may be the carriers of allergens and may exacerbate allergic reactions and diseases. This review presents recent views about the mechanisms of pollutant activity on allergens and immune system response in exposed persons, based on epidemiological population studies, clinical studies of exposure under controlled conditions, and experimental tests in vitro and in vivo