Maternal uniparental disomy for the entire chromosome 7 has so far been reported in three patients with intrauterine and postnatal growth retardation. Two were detected because they were homozygous for a cystic fibrosis mutation for which only the mother was heterozygous, and one because he was homozygous for a rare COL1A2 mutation. We investigated 35 patients with either the Silver-Russeli syndrome or primordial growth retardation and their parents with PCR markers to search for uniparental disomy 7. Four of 35 patients were found to have maternal disomy, including three with isodisomy and one with heterodisomy. The data confirm the hypothetical localization of a maternally imprinted gene (or more than one such gene) on chromosome 7. It is suggested to search for UPD 7 in families with an offspring with sporadic Silver-Russell syndrome or primordial growth retardation.

BackgroundThere is a growing concern regarding the increase of antimicrobial resistant bacteria in companion animals. Yet, there are no studies comparing the resistance levels of these organisms in European countries. The aim of this study was to investigate geographical and temporal trends of antimicrobial resistant bacteria causing urinary tract infection (UTI) in companion animals in Europe. The antimicrobial susceptibility of 22 256 bacteria isolated from dogs and cats with UTI was determined. Samples were collected between 2008 and 2013 from 16 laboratories of 14 European countries. The prevalence of antimicrobial resistance of the most common bacteria was determined for each country individually in the years 2012–2013 and temporal trends of bacteria resistance were established by logistic regression.ResultsThe aetiology of uropathogenic bacteria differed between dogs and cats. For all bacterial species, Southern countries generally presented higher levels of antimicrobial resistance compared to Northern countries. Multidrug-resistant Escherichia coli were found to be more prevalent in Southern countries. During the study period, the level of fluoroquinolone-resistant E. coli isolated in Belgium, Denmark, France and the Netherlands decreased significantly. A temporal increase in resistance to amoxicillin-clavulanate and gentamicin was observed among E. coli isolates from the Netherlands and Switzerland, respectively. Other country-specific temporal increases were observed for fluoroquinolone-resistant Proteus spp. isolated from companion animals from Belgium.ConclusionsThis work brings new insights into the current status of antimicrobial resistance in bacteria isolated from companion animals with UTI in Europe and reinforces the need for strategies aiming to reduce resistance.

SUMMARY. Blood flow in vasa recta capillaries of the exposed renal papilla of young antidiuretic rats (n = 18) was determined by an adaptation of the video-photometric technique of Intaglietta. The erythrocyte velocity and capillary diameter in vasa recta (« = 97) were measured at the same location by means of fluorescence video microscopy, with fluorescein-labeled bovine 7-globulin as a plasma marker. A factor relating erythrocyte velocity to mean cross-sectional blood velocity was determined in vitro to permit the calculation of single vasa recta blood flows from the measured indices, erythrocyte velocity and capillary diameter. Mean blood flow in descending vasa recta was 8.83 ± 0.96 (SE) nl/min, significantly greater than that in ascending vasa recta, 4.82 ± 0.34 nl/min. The total numbers of ascending and descending vasa recta at the base of the exposed papilla were also determined. Over 1500 vasa recta were identified as ascending vasa recta or descending vasa recta in electron micrographs of three papillas. At this level in the papilla (2 mm from the tip), there were four ascending vasa recta for each descending vas rectum. From the total numbers of ascending vasa recta and descending vas rectum, single vessel blood flows were converted to total blood flow. Total blood outflow in all ascending vasa recta, 11.3 /xl/min, substantially exceeded total blood inflow in all descending vasa recta, 5.2 fil/min. The difference between outflow and inflow (6.1 ^1/min) represents an estimate of water uptake by the papillary microcirculation, and is more than adequate to accommodate the known rate of water reabsorption from the collecting ducts of the exposed papilla. (Circ Res 53: 401-413, 1983)

ObjectivesThis study aimed to identify and characterize extended-spectrum β-lactamase (ESBL) producing Enterobacteriaceae among clinical samples of companion animals.MethodsA total of 346 non-duplicate Enterobacteriaceae isolates were collected between 2012 and 2016 from diseased cats (n = 115) and dogs (n = 231). The presence of blaESBL, PMQR genes, and the azithromycin resistance gene mph(A) was confirmed by PCR and sequencing of bla genes. Isolates were further characterized by antimicrobial resistance profiling, multilocus sequence typing, phylogenetic grouping, identification of mutations in the QRDR of gyrA and parC, and screening for virulence-associated genes.ResultsAmong the 346 isolates, 72 (20.8%) were confirmed ESBL producers [58 Escherichia coli (E. coli), 11 Klebsiella pneumoniae (K. pneumoniae), and 3 Enterobacter cloacae]. The strains were cultured from urine (n = 45), skin and skin wounds (n = 8), abscesses (n = 6), surgical sites (n = 6), bile (n = 4), and other sites (n = 3). ESBL genes included blaCTX-M-1, 14, 15, 27, 55, and blaSHV-12, predominantly blaCTX-M-15 (54.8%, 40/73), and blaCTX-M-1 (24.7%, 18/73). Further genes included qnrB (4.2%, 3/72), qnrS (9.7%, 7/72), aac(6’)-Ib-cr (47.2%, 34/72), and mph(A) (38.9%, 28/72). Seventeen (23.6%) isolates belonged to the major lineages of human pathogenic K. pneumoniae ST11, ST15, and ST147 and E. coli ST131. The most prevalent ST was E. coli ST410 belonging to phylogenetic group C.ConclusionThe high prevalence of ESBL producing clinical Enterobacteriaceae from cats and dogs in Switzerland and the presence of highly virulent human-related K. pneumoniae and E. coli clones raises concern about transmission prevention as well as infection management and prevention in veterinary medicine.

Over the 5-year period ending in 2018, 16 countries with a combined birth cohort of over 6 million infants requiring life-saving immunizations are scheduled to transition (graduate) from outside financial and technical support for a number of their essential vaccines. This support has been provided over the past decade by the GAVI Alliance. Will these 16 countries be able to continue to sustain these vaccination efforts? To address this issue, GAVI and its partners are supporting transition planning, entailing country assessments of readiness to graduate and intensive dialogue with national officials to ensure a smooth transition process. This approach was piloted in Bhutan, Republic of Congo, Georgia, Moldova and Mongolia in 2012. The pilot showed that graduating countries are highly heterogeneous in their capacity to assume responsibility for their immunization programmes. Although all possess certain strengths, each country displayed weaknesses in some of the following areas: budgeting for vaccine purchase, national procurement practices, performance of national regulatory agencies, and technical capacity for vaccine planning and advocacy. The 2012 pilot experience further demonstrated the value of transition planning processes and tools. As a result, GAVI has decided to continue with transition planning in 2013 and beyond. As the graduation process advances, GAVI and graduating countries should continue to contribute to global collective thinking about how developing countries can successfully end their dependence on donor aid and achieve self-sufficiency.

Among 64 uropathogenic Escherichia coli (UPEC) isolated from 13 cats and 51 dogs, 35 were extended-spectrum beta-lactamase (ESBL) producers, and 29 were non-ESBL producers. Forty-six (71.9%) of the isolates were multidrug resistant (MDR). Among the ESBL producers, bla (n = 17/48.6% of the bla), bla (n = 10/28.6%), bla (n = 4/11.4%), bla (n = 3/8.6%), and bla (n = 1/2.9%) were identified. The plasmid-mediated fluoroquinolone resistance genes aac(6')-Ib-cr, qnrB and the azithromycin resistance gene mph(A) were detected in 17 (26.6% of all isolates), one (1.6%) and in 13 (20.3%) respectively. The most frequent phylogenetic groups were C (n = 19) and B2 (n = 15). Twenty-six different sequence types (STs) were identified, with two being novel. The most frequent STs were ST410 (n = 16/25%), ST131, and ST73 (both n = 5/7.8%), and ST361 (n = 4/6.3%). Ten (15.6%) of the STs have been associated with urinary tract infection (UTI) in humans, suggesting zoonotic potential. Among seven virulence-associated genes, fyuA was the most prevalent. The overall aggregate virulence factor (VF) score was highest for isolates belonging to phylogenetic group B2 (median aggregate VF score 6, mean score 5,5, range 3-7), and lowest for isolates belonging to phylogenetic group C (0/ 0.5/0-3). The most frequent ST in this study, ST410, harboured the lowest number of VF (0/0,3/0-2). VF scores were higher in NDR (4/3.8/3-4) than in MDR (1/1,9/0-7), and higher in non-ESBL producing isolates (3/3/0-7) than in ESBL producers (1/1,7/0-7). Our data advance our knowledge of the phenotypic and genotypic characteristics of UPEC in companion animals and their potential for infection, zoonotic transmission and dissemination of antimicrobial resistance determinants.

Antimicrobial resistance has become an important concern in veterinary medicine. The aim of this study was to describe the rate of antimicrobial resistance in common equine pathogens and to determine the occurrence of multidrug-resistant isolates. A retrospective analysis of all susceptibility testing results from bacterial pathogens cultured from horses at the University of Zurich Equine Hospital (2012-2015) was performed. Strains exhibiting resistance to 3 or more antimicrobial categories were defined as multidrug-resistant. Susceptibility results from 303 bacterial pathogens were analyzed, most commonly Escherichia coli (60/303, 20%) and Staphylococcus aureus (40/303, 13%). High rates of acquired resistance against commonly used antimicrobials were found in most of the frequently isolated equine pathogens. The highest rate of multidrug resistance was found in isolates of Acinetobacter baumannii (23/24, 96%), followed by Enterobacter cloacae complex (24/28, 86%) and Escherichia coli (48/60, 80%). Overall, 60% of Escherichia coli isolates were phenotypically ESBL-producing and 68% of Staphylococcus spp. were phenotypically methicillin-resistant. High rates of acquired antimicrobial resistance towards commonly used antibiotics are concerning and underline the importance of individual bacteriological and anti microbial susceptibility testing to guide antimicrobial therapy. Minimizing and optimizing antimicrobial therapy in horses is needed. Keywords: horse, multidrug-resistant (MDR) bacteria, methicillin-resistant staphylococci (MRS), ESBL-producing

BackgroundMedicine price information mechanisms provide an essential tool to countries that seek a better understanding of product availability, market prices and price compositions of individual medicines. To be effective and contribute to cost savings, these mechanisms need to consider prices in their particular contexts when comparing between countries. This article discusses in what ways medicine price information mechanisms can contribute to increased price transparency and how this may affect access to medicines for developing countries.MethodsWe used data collected during the course of a WHO project focusing on the development of a vaccine price and procurement information mechanism. The project collected information from six medicine price information mechanisms and interviewed data managers and technical experts on key aspects as well as observed market effects of these mechanisms.The reviewed mechanisms were broken down into categories including objective and target audience, as well as the sources, types and volumes of data included. Information provided by the mechanisms was reviewed according to data available on medicine prices, product characteristics, and procurement modalities.ResultsWe found indications of positive effects on access to medicines resulting from the utilization of the reviewed mechanisms. These include the uptake of higher quality medicines, more favorable results from contract negotiations, changes in national pricing policies, and the decrease of prices in certain segments for countries participating in or deriving data from the various mechanisms.ConclusionThe reviewed mechanisms avoid the methodological challenges observed for medicine price comparisons that only use national price databases. They work with high quality data and display prices in the appropriate context of procurement modalities as well as the peculiarities of purchasing countries. Medicine price information mechanisms respond to the need for increased medicine price transparency and have the potential to contribute to improved access to medicines in developing countries.Additional research is required to explore more specific aspects. These include the market effects of dedicated donor funds for certain medicines to explain the driving force of user demands, and the effects of increased price transparency on different groups of medicines in context of the maturity of their markets.