[The battery of tests for behavioral phenotyping of aging animals in the experiment].

The purpose of the study was to develop a battery of tests to study social and cognitive impairments for behavioral phenotyping of aging experimental animals with physiological neurodegeneration. Object of the study were outbred CD1 mice in the following groups: 1st group - 12-month old male mice (physiological aging); 2nd group - 2-month old male mice (control group). Social recognition test, elevated plus maze test (EPM), open field test, light-dark box test, and Fear conditioning protocol were used to estimate the neurological status of experimental animals. We found that aging male mice in a contrast to young ones have demonstrated lower social interest to female mice in the social recognition task. EPM and light-dark box tests showed increased level of anxiety in the group of aged mice comparing to the control group. Fear conditioning protocol revealed impairment of associative learning and memory in the group of aged mice, particularly, fear memory consolidation was dramatically suppressed. Analysis of behavioral factors, social interactions and anxiety level in the experimental mice has confirmed age-related neurodegeneration in the 1st group. We found that the most informative approach to identifying neurological impairments in aging mice (social interaction deficit, limitation of interests, increased level of anxiety) should be based on the open field test light-dark box test, and Fear conditioning protocol. Such combination allows obtaining new data on behavioral alterations in the age-associated of neurodegeneration and to develop novel therapeutic strategies for the treatment of age-related brain pathology.

Models of antimicrobial pressure on intestinal bacteria of the treated host populations.

Antimicrobial drugs are used to treat pathogenic bacterial infections in animals and humans. The by-stander enteric bacteria of the treated host's intestine can become exposed to the drug or its metabolites reaching the intestine in antimicrobially active form. We consider which processes and variables need to be accounted for to project the antimicrobial concentrations in the host's intestine. Those include: the drug's fraction (inclusive of any active metabolites) excreted in bile; the drug's fractions and intestinal segments of excretion via other mechanisms; the rates and intestinal segments of the drug's absorption and re-absorption; the rates and intestinal segments of the drug's abiotic and biotic degradation in the intestine; the digesta passage time through the intestinal segments; the rates, mechanisms, and reversibility of the drug's sorption to the digesta and enteric microbiome; and the volume of luminal contents in the intestinal segments. For certain antimicrobials, the antimicrobial activity can further depend on the aeration and chemical conditions in the intestine. Model forms that incorporate the inter-individual variation in those relevant variables can support projections of the intestinal antimicrobial concentrations in populations of treated host, such as food animals. To illustrate the proposed modeling framework, we develop two examples of treatments of bovine respiratory disease in beef steers by oral chlortetracycline and injectable third-generation cephalosporin ceftiofur. The host's diet influences the digesta passage time, volume, and digesta and microbiome composition, and may influence the antimicrobial loss due to degradation and sorption in the intestine. We consider two diet compositions in the illustrative simulations. The examples highlight the extent of current ignorance and need for empirical data on the variables influencing the selective pressures imposed by antimicrobial treatments on the host's intestinal bacteria.

Short history of regulations and approved indications of antimicrobial drugs for food animals in the USA.

We review historical availability and regulation, and recent indications of antimicrobial drugs for food animals in the USA. We summarize the timeline of introduction of individual antimicrobial drug classes from the 1930s to present, history of regulation of antimicrobial drugs from the 1930s to present and indications of antimicrobial drugs in 1996-2014 for food animals in the USA. The history of antimicrobial drug regulation demonstrates a historical precedent for harmonized regulations of antimicrobials 'for human and other animals' in the USA.

Evaluating targets for control of plasmid-mediated antimicrobial resistance in enteric commensals of beef cattle: a modelling approach.

Enteric commensal bacteria of food animals may serve as a reservoir of genes encoding antimicrobial resistance (AMR). The genes are often plasmidic. Different aspects of bacterial ecology can be targeted by interventions to control plasmid-mediated AMR. The field efficacy of interventions remains unclear. We developed a deterministic mathematical model of commensal Escherichia coli in its animate and non-animate habitats within a beef feedlot's pen, with some E. coli having plasmid-mediated resistance to the cephalosporin ceftiofur. We evaluated relative potential efficacy of within- or outside-host biological interventions delivered throughout rearing depending on the targeted parameter of bacterial ecology. Most instrumental in reducing the fraction of resistant enteric E. coli at steer slaughter age were interventions acting on the enteric E. coli and capable of either 'plasmid curing' E. coli, or lowering maximum E. coli numbers or the rate of plasmid transfer in this habitat. Also efficient was to increase the regular replacement of enteric E. coli. Lowering replication rate of resistant E. coli alone was not an efficient intervention target.

Impact of changes in cattle movement regulations on the risks of bovine tuberculosis for Scottish farms.

Legislation requiring the pre- and post-movement testing of cattle imported to Scotland from regions with high bovine tuberculosis (bTB) incidence was phased in between September 2005 and May 2006 as part of efforts to maintain Officially Tuberculosis Free (OTF) status. In this analysis, we used centralized cattle movement records to investigate the influence of the legislative change on import movement patterns and the movement-based risk factors associated with new bTB herd breakdowns identified through routine testing or slaughter surveillance. The immediate reduction in the number of import movements from high incidence regions of England and Wales into Scotland suggests that pre- and post-movement testing legislation has had a strong deterrent effect on cattle import trade. Combined with the direct benefits of a more stringent testing regime, this likely explains the observed decrease in the odds of imported cattle subsequently being identified as reactors in herd breakdowns detected through routine surveillance compared to Scottish cattle. However, at the farm-level, herds that recently imported cattle from high incidence regions were still at increased risk of experiencing bTB breakdowns, which highlights the delay between the introduction of disease control measures and detectable changes in incidence. With the relative infrequency of routine herd tests and the insidious nature of clinical signs, past import movements were likely still important in determining the present farm-level risk for bTB breakdown. However, the possibility of low-level transmission between Scottish cattle herds cannot be ruled out given the known issues with test sensitivity, changes in import animal demographics, and the potential for on-farm transmission. Findings from this analysis emphasize the importance of considering how farmer behavioural change in response to policy interventions may influence disease transmission dynamics.

Evaluation of risks of foot-and-mouth disease in Scotland to assist with decision making during the 2007 outbreak in the UK.

An outbreak of foot-and-mouth disease (FMD) occurred in Surrey on August 3, 2007. A Great Britain-wide ban on livestock movements was implemented immediately. This coincided with the start of seasonal sheep movements off the hills in Scotland; the majority of these animals are sold via markets. The ban therefore posed severe economic and animal-welfare hardships if it was to last through September and beyond. The Scottish Government commissioned an analysis to assess the risk of re-opening markets given the uncertainty about whether FMD had entered Scotland. Tracing of livestock moved from within the risk zone in England between July 16 and August 3 identified contact chains to 12 Scottish premises; veterinary field inspections found a further three unrecorded movements. No signs of infection were found on these holdings. Under the conservative assumption that a single unknown Scottish holding was infected with FMD, an estimate of the time-dependent probability of Scotland being FMD free given no detection was made. Analyses indicated that if FMD was not detected by early to mid-September then it was highly probable that Scotland was FMD free. Risk maps were produced to visualise the potential spread of FMD across Scotland if it was to spread either locally or via market sales.

Risk factors associated with Salmonella status of broiler flocks delivered to grow-out farms.

In a prospective field observational study in the southeastern USA, we sampled gastrointestinal (GI) tracts from chicks of 65 broiler flocks delivered to conventional grow-out farms for rearing. The flocks were hatched at seven broiler hatcheries. The mean within-flock prevalence of Salmonella-positive samples was 6.5% and ranged from 0% to 86.7%. Of the 65 flocks studied, 25 (38.5%) had at least one Salmonella-positive sample. Accounting for confounding variability among the hatcheries and broiler companies, we tested whether the probability of detecting Salmonella in GI tracts of the chicks delivered was associated with certain characteristics of parent breeder flocks; hatchery production volume; hatchery ventilation system; hatchery egg-room conditions; egg incubation, candling, hatching, eggshell and bird separation, and bird-processing procedures; management of hatchery-to-farm transportation; day of week of hatch; weather conditions during transportation; or season of the hatch. Two risk factor models were adopted. The first model indicated that a greater number of parent flocks, manual separation of eggshell and bird, and a greater amount of fluff and feces on tray liners used during hatchery-to-farm transportation at delivery were associated with increased probability of detecting Salmonella in chick GI tracts, whereas a greater number of birds in the delivery vehicle was associated with decreased probability. The second model indicated that broiler flocks hatched on Tuesdays versus either Mondays or Thursdays (with no hatches on Wednesdays, Fridays or week-ends), increased average hatchability of the eggs from the parent flocks, and greater amounts of fluff and feces on the transport tray liners at delivery were all associated with increased probability of detecting Salmonella in chick GI tracts. The results of this study suggest potential management decisions to lessen Salmonella contamination of broilers supplied by commercial hatcheries and areas for further research.

Associations between vaccinations against protozoal and viral infections and Salmonella in broiler flocks.

Reducing the burden of Salmonella in broiler flocks presents a challenge for public health. Worldwide, grow-out broilers are routinely vaccinated to prevent or lessen clinical manifestation of other infections. In this exploratory analysis we tested if details of a routine vaccination programme delivered to conventional grow-out broilers were associated with the burden of Salmonella in the flock as it progressed through its production cycle. None of the flocks studied were vaccinated against Salmonella or received a competitive exclusion product. The flocks were reared on conventional grow-out farms in southeastern USA, and sampled in a prospective field observational study. We observed significant associations between the content and design of a grow-out vaccination programme targeting other infections and the probability of detecting Salmonella in the broiler flock at different time points throughout the production cycle. To the best of the authors' knowledge, this is the first field report of such associations.

Risk factors associated with detection of Salmonella in broiler litter at the time of new flock placement.

In this study, we investigated risk factors associated with the probability to detect Salmonella in samples of litter collected within 2 h prior to new flock placement in 76 grow-out houses on 38 conventional broiler farms located in the US states of Mississippi, Alabama and Texas. We evaluated characteristics of location and layout of the farm; area adjacent to and surrounding the house; house construction; condition and type of equipment in the house; litter management and other production, sanitation, visitation and biosecurity practices; non-broiler animal species on the farm; and weather conditions on the 3 days leading up to flock placement. Logistic regression was used to model the relationships between probability to detect Salmonella in litter and potential risk factors. In the screening process, each risk factor was evaluated as a single fixed effects factor in a multilevel model that accounted for variability among the sampled farms and their production complexes and companies. Of almost 370 risk factors screened, 24 were associated with the probability to detect Salmonella in litter. These were characteristics of the surroundings of the house, house construction and conditions, litter management, length of downtimes between flocks in the house, biosecurity and farm location. After investigation of collinearity between these variables and building of models for important risk factor categories, the list of candidate variables for the final model was refined to eight factors. The final model demonstrated that a higher probability of detecting Salmonella in litter was strongly associated with the use of wood to construct the base of the walls or to cover the inside of the broiler house foundation, and with the use of fresh wood shavings to top-dress or completely replace the litter between flocks.

Potential for transmission of infections in networks of cattle farms.

The aim of this analysis is to evaluate how generic properties of networks of livestock farms connected by movements of cattle impact on the potential for spread of infectious diseases. We focus on endemic diseases with long infectious periods in affected cattle, such as bovine tuberculosis. Livestock farm networks provide a rare example of large but fully specified directed contact networks, allowing investigations into how properties of such networks impact the potential for spread of infections within them. Here we quantify the latter in terms of the basic reproduction number, R0, and partition the contributions to R0 from first order moments (mean contact rates) and second order moments (variances and covariances of contact rates) of the farm contact matrices. We find that the second order properties make a substantial contribution to the magnitude of R0 similarly to that reported for other populations. Importantly, however, we find that the magnitude of these effects depends on exactly how the contacts between farms are defined or weighted. We note that the second order properties of a directed contact network may vary through time even with little change in the mean contact rates or in overall connectedness of the network.

Inter-relationships of Salmonella status of flock and grow-out environment at sequential segments in broiler production and processing.

In this study, we investigated how the likelihoods of Salmonella presence in various samples from broilers and their grow-out environment throughout one production cycle were related. Sixty-four broiler flocks from 10 complexes of two companies in the southern United States were included in the study. Samples from the gastrointestinal tracts of chicks, transport tray pads and litter and drag swabs from the house were collected on the day of placement of each flock. Approximately, 1 week before harvest, whole bird carcass rinses, caecum and crop samples were collected from birds from these same flocks. On the day of harvest, litter and drag swab samples were also taken from the house after the birds were removed. Upon arrival of the flocks at the processing plant, whole carcass rinses, caecum and crop samples were collected. As the flocks were processed, carcass rinses were collected just before the carcasses entered the immersion chill tank and as they exited the chill tank. Logistic regression was used to model the relationships between the likelihood of Salmonella in samples of each type collected at each sampling point and Salmonella frequencies in all the samples taken from the flock and grow-out environment at preceding production stages. The analysis demonstrated that increased likelihood of Salmonella contaminated carcasses entering the immersion chill tank was associated with higher contamination of the exteriors and crops of birds at arrival for processing as well as house environmental samples at the time of harvest and prior to placement. The best predictors of post-chill broiler carcass Salmonella status were the frequencies of Salmonella in the litter on the day of harvest and prior to placement. The immersion chilling appeared to disrupt some of the relationships between the processing plant and pre-harvest samples.

[Dirithromycin, a new antibiotic in the treatment of pharyngeal inflammation]. / Diritromitsin--novyi antibiotik dlia lecheniia vospalitel'nykh zabolevanii glotki.

The trial of a new antibiotic dirithromycin against acute pharyngitis and tonsillitis for safety and efficacy included 28 patients with acute tonsillitis and pharyngitis. Microbiological, biochemical, clinical and laboratory tests were conducted throughout the treatment and 2-3 weeks after the end of dirithromycin administration. The results support dirithromycin clinical potential in acute, chronic pharyngeal inflammation due to its high selective activity in relation to beta-hemolytic streptococcus A and the absence of side effects.

[The nervous system function of patients with periodontitis]. / Funktsional'noe sostoianie nervnoi sistemy u bol'nykh parodontitom.

Analysis of the function of the nervous system, based on clinical, neurological, and psychological studies in 78 patients with generalized periodontitis, revealed central regulation disorders without signs of organic lesions of the brain in 76% patients. The authors claim that stress and a high level of personal anxiety may be responsible for the development of these disorders, which was confirmed by the results of psychological testing.

[Cytological and immunological aspects of the antitumor action of polyhexamethylene guanidine in BALB/c mice]. / Tsitologicheskii i immunologicheskii aspekty protivoopukholevogo deistviia poligeksametilenguanidina u myshei linii BALB/c.

Repeated intraperitoneal and intratumor administration of polyhexamethylene guanidine (PMG) in 3 and 5 mg/kg doses to sarcoma 180 bearing mice caused a significant reduction in tumour mass accompanied by increased incidence of diploid and hypodiploid cells. PMG brings about an increase in the number of activated macrophages in the spleen, whereas the response of antibody-producing cells (APC) varies with the dose. A single injection of PMG (1 mg/kg) caused stimulation, but under repeated administration and at higher doses the drug suppressed APC proliferation. The dose-dependent effects of PMG on humoral immunity was due to its specific influence on the spleen L-ornithine decarboxylase activity.

[Viral-microbial associations and the function of humoral factors of natural immunity in acute pneumonia patients]. / Virusno-mikrobnye assotsiatsii i sostoianie gumoral'nykh faktorov estestvennogo immuniteta u bol'nykh ostroi pnevmoniei.

A total of 359 patients with acute pneumonia and 152 practically healthy subjects comprising the control group were examined. Immunofluorescence was used to investigate nasopharyngeal washings for detecting antigens of influenza and parainfluenza viruses, respiratory-syncytial virus, adenoviruses, whereas serological studies according to the hemagglutination delay test with diagnostic agents for detecting influenza A1, A2, B, types 1, 2 and 3 parainfluenza, and the complement fixation test were made to detect antibodies against adenoviruses. Serological (65%) and immunofluorescence (63%) studies revealed associations of different viruses: type 3 and 1 parainfluenza, respiratory-syncytial virus (73%) with adenoviruses, influenza B, A2, type 2 parainfluenza. Association of different bacteria was observed in 67% of patients: hemolytic staphylococcus (65%), hemolytic streptococcus (50%), pneumococci (45%), P. aeruginosa (40%), P. mirabilis (35%), E. coli (30%), enterococci (25%). Associations of 3-2 causative agents were predominant (53%). Marked decrease in the content of complement and beta-lysins, elevation of the level of lysozyme were observed in patients with viral-bacterial and viral pneumonias as compared to the same characteristics in patients with bacterial pneumonia and in control group subjects.