Концепция создания гормонального контрацептивного средства с оптимальной фармакодинамикой

Приведены сведения о фундаментальных исследованиях стероидных соединений с гестагенной активностью, результатом которых стало создание дроспиренона. Представлены данные клинических исследований, доказывающие надежность контрацептивного эффекта нового препарата "Ярина(r)", содержащего дроспиренон и одновременно позволяющего получить ряд дополнительных преимуществ: повышение качества жизни, положительное влияние на общее самочувствие, хороший контроль цикла, уменьшение тяжести предменструальных симптомов, проявлений акне и себореи.The authors report about fundamental studies of steroid compounds with gestagenic activity, which stimulated Drospirenon production.The data of clinical investigations proving the reliability of contraceptive effect of a new drug Yarina(r) containing Drospirenon and allowing to obtain a number of additional advantages: improvement of the quality of life, positive influence on the general health, good control of the cycle, reduction of premenstrual signs severity, manifestations of acne and seborrhea are reported

Risk factors for persistence of livestock-associated MRSA and environmental exposure in veal calf farmers and their family members: an observational longitudinal study

Objectives: Livestock-associated methicillin-resistant Staphylococcus aureus (LA-MRSA) emergence is a major public health concern. This study was aimed at assessing risk factors for persistently carrying MRSA in veal calf farmers and their family members. We also evaluate the dynamics of MRSA environmental load during the veal-calf production cycle. Design: Observational, longitudinal, repeated cross-sectional study. Setting: 52 veal calf farms in the Netherlands. Participants: From the end of 2010 to the end of 2011, a total of 211 farmers, family members and employees were included in the study. Primary outcome and secondary outcome measures: Nasal swabs were taken from participants on days 0, 4, 7 and week 12. A persistent MRSA carrier was defined as a person positive for MRSA on days 0, 4 and 7. Participants filled in an extensive questionnaire to identify potential risk factors and confounders. For estimation of MRSA prevalence in calves and environmental contamination, animal nasal swabs and Electrostatic Dust Collectors were taken on day 0 and week 12. Results: The presence of potential animal reservoirs (free-ranging farm cats and sheep) and the level of contact with veal calves was positively associated with persistent MRSA carriage. Interestingly, at the end of the study (week 12), there was a twofold rise in animal prevalence and a significantly higher MRSA environmental load in the stables was found on farms with MRSA carriers. Conclusions: This study supports the hypothesis that environmental contamination with MRSA plays a role in the acquisition of MRSA in farmers and their household members and suggests that other animal species should also be targeted to implement effective control strategies

Estimating the day of highly pathogenic avian influenza (H7N7) virus introduction into a poultry flock based on mortality data

Despite continuing research efforts, knowledge of the transmission of the highly pathogenic avian influenza (HPAI) virus still has considerable gaps, which complicates epidemic control. The goal of this research was to develop a model to back-calculate the day HPAI virus is introduced into a flock, based on within-flock mortality data. The back-calculation method was based on a stochastic SEIR (susceptible (S) - latently infected (E) - infectious (I) - removed (= dead; R)) epidemic model. The latent and infectious period were assumed to be gamma distributed. Parameter values were based on experimental H7N7 within-flock transmission data. The model was used to estimate the day of virus introduction based on a defined within-flock mortality threshold (detection rule for determining AI). Our results indicate that approximately two weeks can elapse before a noticeable increase in mortality is observed after a single introduction into a flock. For example, it takes twelve (minimum 11 - maximum 15) days before AI is detected if the detection rule is fifty dead chickens on two consecutive days in a 10 000 chicken flock (current Dutch monitoring rule for notification). The results were robust for flock size and detection rule, but sensitive to the length of the latent and infectious periods. Furthermore, assuming multiple introductions on one day will result in a shorter estimated period between infection and detection. The implications of the model outcomes for detecting and tracing outbreaks of H7N7 HPAI virus are discussed

Transmission of highly pathogenic avian influenza H7 virus

Knowledge of the transmission of highly pathogenic avian influenza (HPAI) virus still has gaps, complicating epidemic control. A model was developed to back-calculate the day HPAI virus was introduced into a flock, based on within-flock mortality data of the Dutch HPAI H7N7 epidemic (2003). The method was based on a stochastic epidemic model in which birds move from being susceptible, latently infected and infectious, to death. Our results indicated that two weeks can elapse before a noticeable increase in mortality is observed after a single introduction into a flock. Furthermore, field data were used to estimate the transmission rate parameter beta and the influence of risk factors on within-flock transmission. Daily mortality data again were back-calculated to fit a susceptible – infectious – dead format. The method took into account the uncertainty of the length of the latent period, the survival of an infection by some birds and the influence of farm characteristics. The beta was estimated at 4.50 per chicken per day (95% CI: 2.68 – 7.57) with a bird-infectious period of four days. In contrast to general belief, none of the studied risk factors (housing system, flock size, species, age of the birds and date of depopulation) had significant influence on the estimated beta. The same method was used on field data of the HPAI H7N1 epidemic in Italy in 1999-2000. The bird-infectious period was assumed to be two days, and all birds were assumed to die after this infectious period. The estimated beta for HPAI H7N1 virus transmission in turkeys was 1.43 (95% CI: 1.17 – 1.74). Farm risk factors such as flock size and age of the turkeys again did not influence beta. The effect of vaccination on HPAI H7N7 transmission in turkeys was estimated by means of a transmission experiment. Cloacal and tracheal swabs (for real-time RT-PCR) and serum samples (for hemagglutination inhibition test) were taken to monitor the infection both in inoculated and in susceptible contact turkeys, which were all either unvaccinated, vaccinated once or vaccinated twice with H7N1. Unvaccinated contact birds had a mean infectious period of 6.2 days, and an estimated beta of 1.26 per infectious bird per day. However, no virus shedding was found in inoculated vaccinated turkeys and thus we concluded that vaccination with H7N1 protected against challenge with HPAI H7N7 virus. During the Dutch epidemic a large number of human infections were reported. We estimated infection probabilities for persons involved in disease control on infected farms. Case definition was based on self-reported conjunctivitis and positive hemagglutination inhibition test. A high infection probability during a farm-visit was associated with clinical inspection of poultry in the area surrounding infected flocks (7.6%, 95% CI: 1.4 – 18.9%) and active culling during depopulation (6.2%, 95% CI: 3.7 – 9.6%). Low probabilities were estimated for managing biosecurity (0.0%, 95% CI: 0.0 – 1.0%) and cleaning assistance during depopulation (0.0%, 95% CI: 0.0 – 9.2%). No significant association was observed between the probability of infection and some exposure variables (number of birds present, housing type, poultry type, depopulation method, period during epidemic)

Transmission of highly pathogenic avian influenza H7 virus

Knowledge of the transmission of highly pathogenic avian influenza (HPAI) virus still has gaps, complicating epidemic control. A model was developed to back-calculate the day HPAI virus was introduced into a flock, based on within-flock mortality data of the Dutch HPAI H7N7 epidemic (2003). The method was based on a stochastic epidemic model in which birds move from being susceptible, latently infected and infectious, to death. Our results indicated that two weeks can elapse before a noticeable increase in mortality is observed after a single introduction into a flock. Furthermore, field data were used to estimate the transmission rate parameter beta and the influence of risk factors on within-flock transmission. Daily mortality data again were back-calculated to fit a susceptible – infectious – dead format. The method took into account the uncertainty of the length of the latent period, the survival of an infection by some birds and the influence of farm characteristics. The beta was estimated at 4.50 per chicken per day (95% CI: 2.68 – 7.57) with a bird-infectious period of four days. In contrast to general belief, none of the studied risk factors (housing system, flock size, species, age of the birds and date of depopulation) had significant influence on the estimated beta. The same method was used on field data of the HPAI H7N1 epidemic in Italy in 1999-2000. The bird-infectious period was assumed to be two days, and all birds were assumed to die after this infectious period. The estimated beta for HPAI H7N1 virus transmission in turkeys was 1.43 (95% CI: 1.17 – 1.74). Farm risk factors such as flock size and age of the turkeys again did not influence beta. The effect of vaccination on HPAI H7N7 transmission in turkeys was estimated by means of a transmission experiment. Cloacal and tracheal swabs (for real-time RT-PCR) and serum samples (for hemagglutination inhibition test) were taken to monitor the infection both in inoculated and in susceptible contact turkeys, which were all either unvaccinated, vaccinated once or vaccinated twice with H7N1. Unvaccinated contact birds had a mean infectious period of 6.2 days, and an estimated beta of 1.26 per infectious bird per day. However, no virus shedding was found in inoculated vaccinated turkeys and thus we concluded that vaccination with H7N1 protected against challenge with HPAI H7N7 virus. During the Dutch epidemic a large number of human infections were reported. We estimated infection probabilities for persons involved in disease control on infected farms. Case definition was based on self-reported conjunctivitis and positive hemagglutination inhibition test. A high infection probability during a farm-visit was associated with clinical inspection of poultry in the area surrounding infected flocks (7.6%, 95% CI: 1.4 – 18.9%) and active culling during depopulation (6.2%, 95% CI: 3.7 – 9.6%). Low probabilities were estimated for managing biosecurity (0.0%, 95% CI: 0.0 – 1.0%) and cleaning assistance during depopulation (0.0%, 95% CI: 0.0 – 9.2%). No significant association was observed between the probability of infection and some exposure variables (number of birds present, housing type, poultry type, depopulation method, period during epidemic)

Livestock-associated MRSA prevalence in veal calf production is associated with farm hygiene, use of antimicrobials, and age of the calves

Livestock-associated methicillin-resistant Staphylococcus aureus (LA-MRSA) is highly prevalent in pork and veal production chains. In this study, we used data from a crosssectional survey on 2151 calves from 102 veal calf farms to identify potential risk factors, with the goal of reducing MRSA prevalence by developing intervention strategies. Overall, calves from rose veal farms had a lower risk of LA-MRSA carriage than calves from white veal farms. Data were analysed separately for white and rose veal calves, because management systems of the two production chains were largely different. Group treatment with antimicrobials appeared to be a risk factor for MRSA carriage in white veal calves in univariate analyses, but was not included in the final multiple regression model that included age of the calves and rodent control. Number of start treatment days was positively associated with LA-MRSA carriage in rose veal calves, and was the only risk factor selected for the final multiple regression model for this group. Interpretation of the results from this cross-sectional study is complicated by the strong correlation between antimicrobial use, LA-MRSA carriage and age of the calves. Other age-related factors may be more influential. However, taken together these findings emphasize the need for prudent use of antimicrobials, and point to improvement of farm hygiene as a control measure

Effect of H7N1 vaccination on highly pathogenic avian influenza H7N7 virus transmission in turkeys

This study describes the results of a transmission experiment with highly pathogenic avian influenza (HPAI) H7N7 virus in 12-week-old turkeys. Cloacal and tracheal swabs as well as serum samples were taken to monitor the infection both in inoculated and in susceptible contact turkeys, which were all either unvaccinated, vaccinated once or vaccinated twice with H7N1. Swabs were tested by real-time RT-PCR and serum samples with hemagglutination inhibition test (HI). Unvaccinated contact birds had a mean infectious period of 6.2 days, and an estimated transmission rate parameter of 1.26 per infectious bird per day. However, no virus shedding was found in inoculated vaccinated turkeys and thus we concluded that vaccination with H7N1 protected against challenge with HPAI H7N7 virus

Can short-term frustration facilitate feather pecking in laying hens?

Feather pecking is a major problem in laying hens. Frustration, i.e. the omission of expected reward, may play a role in the development of feather pecking. In two experiments, we studied if feather pecking could be facilitated by short-term frustration in birds with a high feather pecking phenotype and victims of feather pecking (experiment 1), and in birds with a high or low feather pecking genotype (experiment 2). Furthermore, the motivation to peck a key for a food reward was assessed in birds with a high or low feather pecking genotype in experiment 3, as birds that have a stronger motivation may also react stronger to the omission of a reward. We trained birds to peck a key for a food reward in an automated Skinnerbox and tested them in control and frustration sessions. During frustration, the feeder was covered with Perspex. Frustration did not facilitate feather pecking in either experiment. In experiment 1, birds with a high feather pecking phenotype did show more gentle feather pecking and aggressive pecking than victims of feather pecking during some of the control sessions. Furthermore, victims of feather pecking vocalised more than birds with a high feather pecking phenotype. In experiment 2, birds with a high feather pecking genotype scratched more than birds with a low feather pecking genotype, indicating differences in motivation for foraging or dust-bathing behaviour, which shows a relation to feather pecking. Birds with a low feather pecking genotype also had a stronger motivation to peck at a key for a food reward than birds with a high feather pecking genotype. No evidence was found that feather pecking could be facilitated by short-term frustration in a Skinnerbox. However, differences in reaction to frustration and in motivation to peck a key for a food reward in birds with a high or low feather pecking phenotype or genotype indicate that frustration may still play a role in the development of feather pecking