Multiphase diets may improve feed efficiency in fattening crossbreed Holstein bulls: a retrospective simulation of the economic and environmental impact.

Beef industry needs alternative feeding strategies to enhance both economic and environmental sustainability. Among these strategies, adjusting the diet dynamically according to the change of nutritional requirements (multiphase diet) has demonstrated its economic and environmental benefits in pig production systems. Therefore, this retrospective study aims to assess, through simulation, the theoretical economic and environmental benefits of introducing a multiphase diet for crossbreed bulls feeding (one or more diet changes). For this, individual data of BW, BW gain, and daily intake were recorded from 342 bulls during the last fattening period (112 days). These data were used to estimate individual trajectory of energy and protein requirements, which were subsequently divided by individual intake to calculate the required dietary energy and protein concentrations. The area between two functions (i.e., ƒ1: constant protein concentration in the original diet during fattening and ƒ2: estimated protein concentration requirements) was minimised to identify the optimal moments to adjust the dietary concentration of energy and protein. The results indicated that both energy and protein intake exceeded requirements on average (+16% and +28% respectively, P < 0.001), justifying the adoption of a multiphase diet. Modelling the individual trajectories of required metabolisable protein (MP, g/kg DM) during the fattening period resulted in exponential decay model in relation to BW [32120 × exp(-0.026 × BW) + 59.9], while the dietary net energy concentration followed a slightly quadratic model [2.26-0.0026 × BW + 0.000003 × BW2]. Minimisation of the area between curves showed two optimal moments to adjust the diet: at 312 kg and 385 kg of BW, indicating three diet phases: (a) <312 kg, (b) 312-385 kg, and (c) 385-600 kg. For the second and third phases, the dietary energy and protein concentration should be 70 g MP/kg DM and 1.70 Mcal/kg DM and 61 g MP/kg DM and 1.65 Mcal/kg DM, respectively. These diet adjustments might improve economic profitability by 29 €/animal, reduce estimated nitrogen excretions by 16% (P < 0.001), and maintain similar weight gain (P > 0.16) compared to the commercial diet. However, the decrease in dietary energy concentration led to increased fibre concentration, which in turn increased the estimated CH4 emissions of animals with the multiphase diet (+44%, P < 0.001). Hence, multiphase diet could theoretically reduce feeding cost and nitrogen excretion from fattening cattle. Further in vivo studies should confirm these results and find optimal nutritional strategies to improve economic profitability and environmental impact.

Detection of blaCTX-M-15 in an integrative and conjugative element in four extensively drug-resistant Haemophilus parainfluenzae strains causing urethritis.

Haemophilus parainfluenzae is a commensal organism with rising numbers of multidrug-resistant (MDR) strains. This pathogen is of increasing clinical relevance in urogenital infection. The aim of this work was to identify and characterise the molecular mechanisms of resistance associated with four cephalosporin-resistant H. parainfluenzae strains collected from patients with urethritis. Antimicrobial resistance was determined by microdilution following European Committee on Antimicrobial Susceptibility Testing criteria. Strains were then analysed by whole-genome sequencing to determine clonal relationship and the molecular basis of antimicrobial resistance. Finally, a phylogenetic analysis was performed on all urogenital MDR strains of H. parainfluenzae previously isolated in our hospital. All strains were resistant to ß-lactams, macrolides, tetracycline, fluoroquinolones, chloramphenicol, cotrimoxazole, and aminoglycosides. The resistance profile was compatible with the presence of an extended-spectrum ß-lactamase (ESBL). Whole-genome sequencing detected blaCTX-M-15 that conferred high minimum inhibitory concentrations to cephalosporins in two novel integrative and conjugative elements (ICEHpaHUB6 and ICEHpaHUB7) that also harboured a blaTEM-1 ß-lactamase. This study shows a novel blaCTX-M-15 ESBL carried in an integrative conjugative element in four extensively drug-resistant H. parainfluenzae strains. This resistance determinant could be transmitted to other sexually transmitted pathogens and this is a cause for concern.

The effects of colostrum consumption and feed restriction during marketing and transportation of male dairy beef calves: Impact on pre-transport nutritional status and on farm recovery.

The aim of this study was to evaluate the effects of colostrum consumption and feed restriction on biomarkers of stress, nutritional and health status, gut functionality, and behavior in male dairy beef calves being marketed and transported. A total of 82 male Holstein calves (42 ± 1.2 kg of body weight and 14 ± 0.9 d of age) were used to study the amount of colostrum given at birth at the dairy farm of origin, the degree of feed restriction suffered at an assembly center simulation (d -4 to d -1), and the effects of a 19 h transportation (d -1). Treatments were as follows: control calves (CTRL; n = 16) were fed 10 L of colostrum at the dairy farm of origin, milk replacer (MR) and concentrate at the assembly center, and were not transported; calves fed high colostrum and milk replacer (HCMR; n = 17) were given 10 L of colostrum at the dairy farm of origin, MR at the assembly center, and transported; calved fed high colostrum and rehydrating solution (HCRS; n = 16) were given 10 L of colostrum at the dairy farm of origin, a rehydrating solution (RS) at the assembly center, and transported; calves fed low colostrum and milk replacer (LCMR; n = 17) were given 2 L of colostrum at the dairy farm of origin, MR at the assembly center, and transported; and calves fed low colostrum and rehydrating solution (LCRS; n = 16) were given 2 L of colostrum at the dairy farm of origin, RS at the assembly center, and transported. Transported calves mimic a 19-h transportation. After transport, all calves were fed 2.5 L of MR twice daily and had ad libitum access to concentrate, straw, and water. Calves' recovery was followed for 7 d. Concentrate intake and health records were collected daily from d -4 until d 7 and body weight (BW) and blood samples were collected on d -4, -1, 0, 1, 2, and 7 of the study. Results showed that the feeding regimen provided at the assembly center reduced BW for the HCRS and LCRS calves compared with the CTRL, HCMR, and LCMR calves. Concentrate intake peaked on d 0 in the transported calves, followed by a reduction of intake on d 1 after transportation. Concentrate intake recovery was lower for the LCRS and LCMR calves. On d -1, nonesterified fatty acids and ß-hydroxybutyrate concentrations were greater for the HCRS and LCRS calves compared with the CTRL, HCMR, and HCRS calves. After transportation, serum Cr-EDTA concentration was greater for the HCRS and LCRS calves than the HCMR, LCMR, and CTRL calves. The LCRS calves had the lowest serum concentration of citrulline. Finally, health scores were greater for the LCRS calves from d 0 to 7. In summary, both the greatest degree of feed restriction during the assembly center and the low colostrum consumption at birth negatively affected the recovery of concentrate consumption and BW, gut functionality, health status, and behavior in calves after arrival at the rearing farm.

Feeding colostrum and transition milk facilitates digestive tract functionality recovery from feed restriction and fasting of dairy calves.

The objective of this study was to evaluate the digestive tract recovery and metabolism of feeding either bovine colostrum (BC), transition milk (TM), or milk replacer (MR) after an episode of feed restriction and fasting (FRF) in dairy calves. Thirty-five Holstein male calves (22 ± 4.8 d old) were involved in a 50-d study. After 3 d of feeding 2 L of rehydration solution twice daily and 19 h of fasting (d 1 of study), calves were randomly assigned to one of the 5 feeding treatments (n = 7): calves were offered either pooled BC during 4 (C4) or 10 (C10) days, pooled TM during 4 (TM4) or 10 (TM10) days, or MR for 10 d (CTRL) at the rate of 720 g/d DM content. Then, all calves were fed the same feeding program, gradually decreasing MR from 3 L twice daily to 2 L once daily at 12.5% DM until weaning (d 42), and concentrate feed, water, and straw were offered ad libitum until d 50. Citrulline, Cr-EDTA, ß-hydroxybutyrate (BHB), and nonesterified fatty acids (NEFA) in serum and complete blood count (CBC) were determined on d -3, 1, 2, 5, and 11 relative to FRF, except BHB and NEFA at d -3. Volatile fatty acids (VFA), lactoferrin (LTF), IgA, and microbiota (Firmicutes to Bacteroidetes ratio and Fecalis prausnitzii) were analyzed in feces on d 5 and 11 before the morning feeding. Health scores were recorded daily from d -3 to d 14 as well as d 23 and 30. Feed concentrate, MR, and straw intake were recorded daily, and body weight on d -3, 1, 2, 5, and 11 and weekly afterward. Calf performance, intake, serum Cr-EDTA, CBC, fecal LTF concentrations and microbiota parameters were similar among treatments throughout the study. Serum NEFA concentrations were greater in TM4, TM10 and C10 calves compared with the CTRL ones from d 2 to 11, and after the FRF, serum concentrations of BHB were lower in CTRL calves than in the other treatments, and on d 11, serum BHB concentrations in the long treatments (C10 and TM10) remained greater than those in the shorter ones (C4 and TM4) and CTRL. Serum citrulline concentrations were similar on d -3 and 1 in all treatments, but they were greater in C4, C10, TM4, and TM10 on d 2 and 5, and on d 11 they were only greater in C10 and TM10 than in CTRL calves. Fecal IgA concentrations tended to be greater in C10 than in CTRL, TM4, and TM10 calves, and in C4 and TM10 than in CTRL animals. Fecal propionate proportion was lesser in C10 than in CTRL, TM4, and TM10 calves, while butyrate was greater in C4 and C10 than in TM4 and CTRL calves. The proportion of non-normal fecal scores of C10 fed calves was greater than TM4 and TM10 calves. Results showed that TM and BC may help to recover intestinal functionality, provide gut immune protection, and increase liver fatty acid oxidation in calves after a FRF episode.

Evaluation of potential biomarkers to determine adequate colostrum provision in male dairy-beef calves upon arrival at the rearing facility beyond 14 days of age.

Colostrum consumption is crucial for passive immunization and development of the newborn calf. However, the incidence on failed transfer of passive immunity in male calves destined to dairy-beef production remains high to date. In addition, the lack of an automated procedure to validate the immunization status upon arrival at rearing facilities in calves beyond 14 d of age impedes the identification of failed transfer of passive immunity, and therefore, of those calves at high risk of suffering diseases. For this study, 82 newborn male Holstein calves (43.3 ± 0.86 kg of body weight; mean ± standard error) from a commercial dairy farm were used to investigate potential serum biomarkers of colostrum provision. The potential biomarkers selected were IgG, IgG1, cholesterol, alkaline phosphatase, gamma-glutamyl transferase (GGT), and total protein (TP). Treatments were as follows: high-colostrum (HC; n = 49), in which calves received 4 L of colostrum within the first 2 h after birth and 2 L of colostrum in the next 3 feedings within the first 24 h after birth, for a total of 10 L of colostrum; and low-colostrum (LC; n = 33), in which calves received only 2 L of colostrum within the first 2 h after birth. After colostrum consumption, calves were allocated to individual hutches and fed 2 L of milk replacer twice daily at a concentration of 125 g/L as fed. Starter feed and water were offered ad libitum. At approximately 14 d of age (14.2 ± 0.81 d of age; mean ± standard error) calves were transported 2.5 h to a research unit at IRTA (Torre Marimon, Spain) simulating the arrival to a rearing facility. Blood samples were collected before feeding at birth, 48 h after birth, and at arrival to the rearing facility. Results on the serum concentrations of the potential biomarkers at arrival to the rearing facility showed that IgG, IgG1, GGT, and TP were greater for the HC calves compared with the LC calves. Serum concentrations of cholesterol and alkaline phosphatase did not show differences between treatment groups. Additionally, body weight losses from birth until arrival to the rearing facility were greater for the LC treatment compared with the HC. Because of their low cost, quickness, and ease of measurement, GGT and TP were good indicators of colostrum intake in calves arriving at rearing facilities beyond 14 d of age.

Drinking water chlorination in dairy beef fattening bulls: water quality, potential hazards, apparent total tract digestibility, and growth performance.

The first study aimed to evaluate the effect of drinking water disinfection (chlorination: NaClO 15%) and conditioning (acidification: H3PO4 diluted 1:5 in water) on water quality, water and feed consumption, apparent total tract digestibility, and its potential hazardous effects on Holstein bulls fed high-concentrate diets. Twenty-four animals (221 ±â€¯20.9 kg of BW, and 184 ±â€¯9.9 days of age) were individually assigned to one of four treatments according to a 2 × 2 factorial arrangement: conditioning (with or without acidification) and disinfection (with or without chlorination). The entire study lasted 210 days. Physicochemical and microbiological water quality, water and feed consumption, haematological and biochemical blood parameters, and apparent total tract digestibility were measured; data were analysed via a mixed-effects model. Chlorination and acidification increased (P = 0.02) free residual chlorine in water, and chlorination reduced (P = 0.01) total coliform and Clostridium perfringens counts in water. Treatment did not affect water consumption, total DM intake, or blood parameters. At the beginning of the study, NDF digestibility decreased (P = 0.04) with acidification, however, this was restored at the end of the study. The second study evaluated the potential benefit of drinking water chlorination and acidification on the performance of crossbred Holstein bulls fed high-concentrate diets under commercial conditions. Ninety-six animals (322 ±â€¯35.0 kg of BW, and 220 ±â€¯14.2 days of age) were allocated into six pens assigned to one of the two treatments: untreated drinking water or drinking water treated with chlorination and acidification for a total of 112 days. Physicochemical and microbiological water quality, water and concentrate consumption, eating behaviour, growth performance, and carcass quality were analysed via a mixed-effects model. Water conditioning and disinfection increased (P = 0.01) free residual chlorine concentration and reduced (P = 0.04) total coliform count in water. Although water consumption and eating behaviour were similar between treatments, water conditioning and disinfection increased average daily weight gain (P = 0.03), BW before slaughter (P = 0.01), and hot carcass weight (P = 0.01). In conclusion, drinking water chlorination and acidification in fattening dairy beef bulls is recommended as it improves growth performance without any detrimental side effects on health or nutrient digestibility.

Characterizing the diagnostic sensitivity and specificity of pain biomarkers in cattle using receiver operating characteristic curves.

Biomarkers are used to assess pain and analgesic drug efficacy in livestock. However, often the diagnostic sensitivity and specificity of these biomarkers for different painful conditions over time have not been described. Receiver operating characteristic (ROC) curves are graphical plots that illustrate the diagnostic ability of a test as its discrimination threshold is varied. The objective of this analysis was to use area under the curve (AUC) values derived from ROC analysis to characterize the predictive value of potential pain biomarkers at specific time points following a painful stimulus. The biomarkers included in the analysis were plasma cortisol, salivary cortisol, hair cortisol, infrared thermography (IRT), mechanical nociceptive threshold (MNT), substance P, kinematic gait analysis, and a visual analog scale for pain. A total of 7,992 biomarker outcomes collected from 7 pain studies involving pain associated with castration, dehorning, lameness, and abdominal surgery were included in the analysis. Each study consisted of 3 treatments: uncontrolled pain (tissue damage), no pain (handled controls), and analgesic use (tissue damage, administered a nonsteroidal anti-inflammatory drug). Results comparing analgesic effects to uncontrolled pain consistently yielded AUC values >0.7 (95% confidence interval: 0.40 to 0.99) for plasma cortisol (time points: 1.5, 2, 3, 4, 6, and 8 h), hair cortisol (time point: 62 d), and IRT (time point: 72 h). Results comparing analgesic effects to uncontrolled pain consistently yielded AUC values <0.7 (95% confidence interval: 0.28 to 0.90) for salivary cortisol (6, 13, 20, 34, 48, and 62 d); MNT (6, 25, and 49 h); substance P (1, 2, 3, 4, 6, 8, 12, 18, 24, 48, 72, 96, 120, 144, 312, 480, 816, 1,152, and 1,488 h); kinematic gait analysis including area (8, 16, 48, 72, 96, and 120 h), force (8, 16, 24, 48, 72, 96, and 120 h), and pressure (8, 16, 24, 48, 72, 96, and 120 h); and a visual analog scale for pain (1, 2, 3, 4, 5, and 6 d). These results indicate that ROC analysis can be used to characterize the predictive value of pain biomarkers and provide new knowledge on the diagnostic accuracy of pain biomarkers within this data set. This analysis, using data from 7 studies, was a preliminary approach to identify biomarkers and collection time points that could inform additional analytical approaches or meta-analyses with larger sample sizes, which are needed to further validate these hypotheses and conclusions.

Simulation of feed restriction and fasting: Effects on animal recovery and gastrointestinal permeability in unweaned Angus-Holstein calves.

Feed restriction and fasting experienced during commercial production negatively affect unweaned calves' behavior and health status. Transportation and stays at assembly centers are the main factors generating these disorders. For this study, 20 unweaned Angus-Holstein bull calves [44.1 ± 2.04 kg of body weight (BW) and 14.7 ± 0.63 d of age (± standard error)] were used to evaluate the effects of feed restriction and fasting on performance, energy status [serum concentration of glucose, ß-hydroxybutyrate (BHB), and nonesterified fatty acids], and gastrointestinal permeability [serum concentration of citrulline, chromium (Cr)-EDTA, lactulose, and d-mannitol]. Calves were randomly assigned to 1 of 4 treatments that simulated the feed restrictions of an assembly center situation on one hand, and the fasting hours during transportation on the other. Treatments were as follows. Control (CT): from d -4 to -1, calves were fed 2.5 L of milk replacer (MR) twice daily; concentrate and straw were offered ad libitum. Mild (MD): calves were fed only MR (d -4 to -1) as described for CT, and on d -1 calves were subjected to a 9-h feed withdrawal. Moderate (MO): calves were fed only MR (d -4 to -1) as described for CT and on d -1 subjected to a 19-h feed withdrawal. Severe (SV): calves were fed only 2.5 L of a rehydrating solution twice daily (d -4 to -1) and on d -1 subjected to a 19-h feed withdrawal. From d 0 to d 42 (weaning) all calves were fed the same feeding program (MR, concentrate, and straw ad libitum). Results showed that BW was greater for the CT treatment compared with the others from d 0 to d 7, whereas BW of SV was lesser compared with the others from d -1 to d 7. No differences among treatments were observed at weaning. At d 2 concentrate intakes of MD, MO, and SV were lesser compared with CT. By d 4, concentrate intake of SV was similar to that for CT and greater than MD and MO. Similarly to BW, no differences in concentrate intake among treatments were observed at weaning on d 42 of the study. At d -1 for SV and d 0 in all restricted calves, serum glucose concentration was lesser compared with CT. At d -1 and 0, nonesterified fatty acids and BHB serum concentrations were greater in the SV calves compared with the other treatments. By d 2, serum concentrations of nonesterified fatty acids, BHB, and glucose were restored to CT levels. At d -1 serum citrulline concentration was lesser in SV and greater in MD calves. The CT calves had lower serum concentrations of Cr-EDTA (d -1 and d 0), lactulose (d 0), and d-mannitol (d 0) compared with the other restricted calves. Results showed that degree of dietary restriction, type of liquid diet (MR or rehydrating solution), and fasting hours (9 vs. 19 h) affected calves' BW, concentrate intake, and serum concentration of markers indicative of energy status and gastrointestinal permeability.

One-year prognosis of non-traumatic cortical subarachnoid haemorrhage: A prospective series of 34 patients. / Pronóstico al año de la hemorragia subaracnoidea cortical no traumática: Serie prospectiva de 34 pacientes.

INTRODUCTION: Cortical subarachnoid haemorrhage (cSAH) has multiple aetiologies. No prospective study has reported the long-term progression of the condition. The objective of this study is to describe the clinical and aetiological characteristics of patients with cSAH and to gain insight into prognosis. METHODS: We performed a prospective, observational, multi-centre study. Data on clinical and radiological variables were collected; during a one-year follow-up period, we recorded data on mortality, dependence, rebleeding, and the appearance of dementia. RESULTS: The study included 34 patients (mean age, 68.3 years; range, 27-89). The most frequent symptoms were headache and focal neurological deficits, which were frequently transient and recurrent. CT scans returned pathological findings in 28 patients (85%). Brain MRI scans were performed in 30 patients (88%), revealing acute ischaemia in 10 (29%), old haemorrhage in 7 (21%), and superficial siderosis in 2 (6%). Aetiology was identified in 26 patients (76.5%): causes were cerebral amyloid angiopathy in 8, ischaemic stroke in 5, vasculitis in 4, reversible posterior encephalopathy in 2, venous thrombosis in 2, reversible cerebral vasoconstriction syndrome in 2, carotid occlusion in 1, Marfan syndrome in 1, and meningeal carcinomatosis in 1. Three patients died during follow-up (2 due to causes related to the cause of cSAH). Three patients developed dementia, 3 had lobar haemorrhages, and one had a second cSAH. CONCLUSIONS: The most frequent causes of cSAH in our series were cerebral amyloid angiopathy, ischaemic stroke, and vasculitis. This type of haemorrhage has a worse prognosis than other non-aneurysmal cSAH. There are numerous possible causes, and prognosis depends on the aetiology. In elderly patients, intracranial haemorrhage is frequently associated with cognitive impairment.

Biotic and abiotic factors influencing haplosporidian species distribution in the cockle Cerastoderma edule in Ireland.

The Phylum Haplosporidia consists of four genera (Minchinia, Haplosporidium, Urosporidium and Bonamia) that are endoparasitic protists of a wide range of marine invertebrates including commercial bivalve species. Characterization of haplosporidian species remains a challenge due to their patchy spatial and temporal distributions, host-restricted occurrence, and poorly known life cycles. However, they are commonly associated with significant mortality events in bivalves. Due to the recent sporadic mortality events that have occurred in cockles in Europe, the objectives of this study were to determine the diversity, distribution and seasonality of haplosporidian species in Cerastoderma edule populations at several Irish sites. The role of abiotic (temperature, salinity and dissolved oxygen in water) and biotic (cockle size and age) factors as drivers or inhibitors of haplosporidian infection were also assessed. Cockles (n = 998) from the intertidal were sampled from April/July 2018 to April 2019 at three sites with no commercial fishing activity on the south coast (Celtic Sea) and one site on the northeast coast (Irish Sea) with an active commercial fishery. Screening of the cockles by molecular techniques (PCR, Sanger sequencing) and by histopathology was carried out. Two species were identified and confirmed in Irish C. edule for the first time, Minchinia mercenariae -like (14.8%) and Minchinia tapetis (29.6%). Similar to other haplosporidian parasites, the Minchinia spp. detected in our study were present year-round at all sites, except for M. tapetis in Youghal Bay (Celtic Sea). Coinfection of both Minchinia species was only observed in Cork Harbour (Celtic Sea) and Dundalk Bay (Irish Sea), where Minchinia spp. showed a higher presence compared to Youghal Bay and Dungarvan Harbour (Celtic Sea). Moreover, haplosporidians detected with generic primers, were present at all of the sample sites throughout the year but had a higher occurrence during the winter months and were positively correlated with dissolved oxygen. Likewise, smaller and older C.edule seemed to be more vulnerable to the haplosporidian infection. Furthermore, haplosporidian distribution displayed spatial variability between and within sample sites, with the highest presence being observed in cockles at one of the commercially fished Dundalk beds, while the lowest presence was observed in cockles at the second Dundalk bed that was more influenced by freshwater runoff when the tide was out. Findings from this study provide additional information on the distribution and seasonal presence of novel haplosporidian species and their potential abiotic and biotic drivers/inhibitors of infection.

Darolutamide for treatment of castration-resistant prostate cancer.

Darolutamide is a novel, nonsteroidal androgen receptor (AR)-signaling inhibitor. It serves as a second-generation antiandrogen and is currently indicated for the treatment of patients with nonmetastatic castration-resistant prostate cancer (nmCRPC). The product was approved by the United States Food and Drug Administration (FDA) in July 2019 and by the Japanese Ministry of Health, Labour and Welfare (MHLW) in January 2020 for the treatment of men with nmCRPC, and is awaiting approval in the E.U. for the same indication. This review will cover the background, preclinical development, safety, pharmacokinetics, pharmacodynamics and clinical studies that led to the approval of darolutamide. The key clinical data, ongoing trials and future directions for darolutamide are also discussed herein.

Assessment of trimethoprim-sulfamethoxazole susceptibility testing methods for fastidious Haemophilus spp.

OBJECTIVES: To compare the determinants of trimethoprim-sulfamethoxazole resistance with established susceptibility values for fastidious Haemophilus spp., to provide recommendations for optimal trimethoprim-sulfamethoxazole measurement. METHODS: We collected 50 strains each of Haemophilus influenzae and Haemophilus parainfluenzae at Bellvitge University Hospital. Trimethoprim-sulfamethoxazole susceptibility was tested by microdilution, E-test and disc diffusion using both Mueller-Hinton fastidious (MH-F) medium and Haemophilus test medium (HTM) following EUCAST and CLSI criteria, respectively. Mutations in folA, folP and additional determinants of resistance were identified in whole-genome-sequenced isolates. RESULTS: Strains presented generally higher rates of trimethoprim-sulfamethoxazole resistance when grown on HTM than on MH-F, independent of the methodology used (average MIC 2.6-fold higher in H. influenzae and 1.2-fold higher in H. parainfluenzae). The main resistance-related determinants were as follows: I95L and F154S/V in folA; 3- and 15-bp insertions and substitutions in folP; acquisition of sul genes; and FolA overproduction potentially linked to mutations in -35 and -10 promoter motifs. Of note, 2 of 19 H. influenzae strains (10.5%) and 9 of 33 H. parainfluenzae strains (27.3%) with mutations and assigned as resistant by microdilution were inaccurately considered susceptible by disc diffusion. This misinterpretation was resolved by raising the clinical resistance breakpoint of the EUCAST guidelines to ≤30 mm. CONCLUSIONS: Given the routine use of disc diffusion, a significant number of strains could potentially be miscategorized as susceptible to trimethoprim-sulfamethoxazole despite having resistance-related mutations. A simple modification to the current clinical resistance breakpoint given by the EUCAST guideline for MH-F ensures correct interpretation and correlation with the reference standard method of microdilution.

Impact assessment of the incorporation of the rotavirus vaccine in the province of San Luis - Argentina.

Rotavirus (RV) is the main cause of acute gastroenteritis (AGE) in young children. The San Luis province of Argentina introduced RV vaccination in May 2013. We estimate vaccine impact (RVI) using real-world data. Data on all-cause AGE cases and AGE-related hospitalisations for San Luis and the adjacent Mendoza province (control group) were obtained and analysed by interrupted time-series methods. Regardless of the model used for counterfactual predictions, we estimated a reduction in the number of all-cause AGE cases of 20-25% and a reduction in AGE-related hospitalisations of 55-60%. The vaccine impact was similar for each age group considered (<1 year, <2 years and <5 years). RV vaccination was estimated to have reduced direct medical costs in the province by about 4.5 million pesos from May 2013 to December 2014. Similar to previous studies, we found a higher impact of RV vaccination in preventing severe all-cause AGE cases requiring hospitalisation than in preventing all-cases AGE cases presenting for medical care. An assessment of the economic value of RV vaccination could take other benefits into account in addition to the avoided medical costs and the costs of vaccination.

Insights into the population structure and pan-genome of Haemophilus influenzae.

The human-restricted bacterium Haemophilus influenzae is responsible for respiratory infections in both children and adults. While colonization begins in the upper airways, it can spread throughout the respiratory tract potentially leading to invasive infections. Although the spread of H. influenzae serotype b (Hib) has been prevented by vaccination, the emergence of infections by other serotypes as well as by non-typeable isolates (NTHi) have been observed, prompting the need for novel prevention strategies. Here, we aimed to study the population structure of H. influenzae and to get some insights into its pan-genome. We studied 305H. influenzae strains, enrolling 217 publicly available genomes, as well as 88 newly sequenced H. influenzae invasive strains isolated in Portugal, spanning a 24-year period. NTHi isolates presented a core-SNP-based genetic diversity about 10-fold higher than the one observed for Hib. The analysis of key factors involved in pathogenesis, such as lipooligosaccharides, hemagglutinating pili and High Molecular Weight-adhesins, suggests that NTHi shape its virulence repertoire, either by acquisition and loss of genes or by SNP-based diversification, likely towards host immune evasion and persistence. Discreet NTHi subpopulations structures are proposed based on core-genome supported with 17 candidate genetic markers identified in the accessory genome. Additionally, this study provides two bioinformatics tools for in silico rapid identification of H. influenzae serotypes and NTHi clades previously proposed, obviating laboratory-based demanding procedures. The present study constitutes an important genomic framework that could lay way for future studies on the genetic determinants underlying invasiveness and disease and population structure of H. influenzae.

Effect of a single dose of meloxicam prior to band or knife castration in 1-wk-old beef calves: I. Acute pain.

In Western Canada, approximately half of the calves produced are castrated before 1 wk of age. Therefore, it is important to identify effective analgesic drugs to mitigate pain associated with castration and consequently improve animal welfare. The aim of this study was to assess the efficacy of a single s.c. dose of meloxicam at mitigating pain associated with knife and band castration in 1-wk-old calves. Seventy-two Angus crossbred bull calves (47.3 ± 6.70 kg of body weight (BW), 1 wk old) were used in a 3 × 2 factorial design where main factors included castration method-sham (CT), band (BA) or knife (KN) castration- and medication-lactate ringer (NM) or 0.5 mg/kg BW of meloxicam (M). Measurements included different physiological and behavioral parameters. Samples were collected on day -1, immediately before castration (T0); and 60, 90, and 120 min and 1, 2, 3, and 7 d after castration except for visual analog scale (VAS) which was collected at the time of castration. The salivary cortisol concentrations were greater (P = 0.04) in KN and BA calves than CT calves 60 min after castration, while 90 min after castration BA had greater concentrations than CT calves. Substance P concentrations were greater (P = 0.04) in NM calves than M calves on d 3 and 7 after castration. The serum amyloid-A (SAA) concentrations were greater (P = 0.05) in KN calves than BA and CT calves on days 0, 2, and 3, while BA calves had greater SAA concentrations on day 7 than KN and CT calves. The visual analog scores were greater (P < 0.01) in KN calves than BA, and in BA compared to CT calves. The KN calves tail flicked more (P < 0.01) than BA and CT calves, and NM calves tail flicked more (P = 0.03) than M calves. No castration or medication effect (P > 0.10) was observed for stride length, walking, standing, lying ventral, eating, foot stamping, head turning, lying and standing percentage, performance, platelets, or body temperature. Overall, knife castrated calves exhibited a greater acute pain response than band castrated calves. Meloxicam was able to reduce substance P concentrations, white blood cell counts and number of tail flicks after castration, suggesting that the drug was able to mitigate acute pain to some extent. However, meloxicam did not have an effect on the other physiological and behavioral parameters assessed.

Effect of band and knife castration of beef calves on welfare indicators of pain at three relevant industry ages: II. Chronic pain.

Three experiments were conducted to evaluate the effects of band and knife castration on behavioral and physiological indicators of chronic pain in beef calves at 3 different ages (36 calves/age group): 1 wk of age (Exp. 1, 4 ± 1.1 d of age, 43 ± 1.1 kg BW), 2 mo of age (Exp. 2, 63 ± 2.3 d of age, 92 ± 1.7 kg BW), and 4 mo of age (Exp. 3, 125 ± 4.6 d of age, 160 ± 3.4 kg BW). In each experiment calves were randomly assigned to either sham (CT), band (BA) or knife (KN) castration. Experiments 1, 2, and 3 ended when the testicles of banded calves had sloughed off (68, 49, and 42 d, respectively). Animal BW and rectal temperature were recorded weekly over the experimental period. Salivary cortisol, substance P, haptoglobin, scrotal area temperature using infrared thermography, visual evaluation of swelling (5-point scale), and gait stride length were collected on d -1 and immediately before castration and weekly thereafter until the end of the study. Hair samples were collected 1 d prior to and 28 d after castration and at the end of the study for cortisol concentration. Standing and lying behaviors were recorded over a 28-d period immediately after castration. No differences ( > 0.10) were observed in salivary cortisol, substance P, haptoglobin, or hair cortisol among castration methods for any of the 3 ages. No changes in behavior were observed in calves castrated at 1 wk or 2 mo of age. In 4 mo-old-calves, BA spent less time lying ( < 0.01) than CT and KN calves. Also, the average duration of lying time for BA calves was greater ( < 0.05) than for CT calves. Both, 1-wk- and 2-mo-old calves had inflammation in the scrotal area lasting 7 d after KN castration, whereas inflammation was observed for up to 14 d in 4-mo-old calves. Swelling in BA calves lasted for 21 to 28 d in the 2 younger groups of calves, whereas in 4-mo-old calves swelling was observed until d 35 postcastration. Knife- and band-castrated calves did not exhibit indicators of chronic pain or distress when the procedures were performed in calves younger than 2 mo of age. Therefore, pain mitigation should be used when castrating to improve animal welfare, especially when castrations are performed in calves older than 2 mo of age independent of the method of castration.

Effect of band and knife castration of beef calves on welfare indicators of pain at three relevant industry ages: I. Acute pain.

Three experiments evaluated the effect of band and knife castration on acute pain for the first 7 d after the procedure on 1-wk-, 2-mo-, and 4-mo-old calves. All calves were blocked by age and weight and randomly assigned to 1 of 3 treatments: sham castration (control, CT), band castration (BA), and knife castration (KN). Experiment 1 evaluated 1-wk-old Angus bull calves ( = 34; 43.0 ± 6.61 kg BW), Exp. 2 evaluated 2-mo-old Angus bull calves ( = 34; 91.5 ± 11.93 kg BW), and Exp. 3 evaluated 4-mo-old Angus bull calves ( = 35; 157.6 ± 22.52 kg BW). For all experiments, physiological and behavioral parameters were collected before (d -1 and immediately before castration [T0]) and after (60 and 120 min and on d 7) castration to assess acute pain. Physiological measures included complete blood cell count, cortisol, substance P, and scrotal temperature. Behavioral measures consisted of a visual analog scale, stride length, and time and frequency budgets for walking, standing, lying, tail flicking, foot stamping, and head turning. Performance parameters included initial and final BW and ADG. In Exp. 1, tail flicking was greater ( = 0.02) in KN calves compared to BA calves 2 to 4 h after castration, although no differences were seen between BA and KN compared to CT calves. In Exp. 2, a treatment × time interaction ( = 0.02) was observed for cortisol, where KN calves had greater cortisol concentrations 120 min after castration compared to BA and CT calves; KN calves also lay down and ate less ( < 0.01; = 0.02) and stood and walked more ( < 0.01; = 0.05) compared to BA and CT calves 2 to 4 h after castration. In Exp. 3, a treatment × time interaction ( < 0.01) was observed for cortisol concentrations in which all treatments were different from one another at 60 and 120 min, with BA calves having the greatest concentrations, KN calves being intermediate, and CT having the lowest concentrations. Overall, KN and BA castrated calves presented physiological and behavioral changes associated with acute pain; however, 2-mo-old BA calves presented the fewest behavioral changes and no physiological changes associated with acute pain compared to CT calves.

Vacuna tetravalente CYD-TDV contra el Dengue / Quadrivalent vaccine CYD-TDV against Dengue

CONTEXTO CLÍNICO: El dengue es una enfermedad viral transmitida por la picadura del mosquito Aedes aegypti, vector de la enfermedad. El virus pertenece a la familia Flaviviridae, y existen cuatro variantes: los serotipos DEN1, DEN2, DEN3 y DEN4. El número de casos de dengue notificados anualmente a la Organización Mundial de la Salud há aumentado de 0,4 a 1,3 millones entre 1996-2005, llegando a 2,2 millones en el 2010 y 3,2 millones en el 2015. La Organización Mundial de la Salud (OMS) estima que alrededor de 50 a 100 millones de casos sintomáticos en los últimos años, predominantemente en Asia, seguida por América Latina y África. Los casos de infección que presentan síntomas probablemente representen alrededor del 25% de todas las infecciones por el virus. La incidencia reportada promedio entre 1995 y 2009 en Argentina fue de 1,6 casos por cada 100.000 habitantes, mientras que en países como Brasil, Paraguay y Bolivia es de 196, 107, y 108 casos cada 100.000 habitantes, respectivamente. TECNOLOGÍA: La vacuna CYD-TDV (Dengvaxia®) es una vacuna recombinante a virus atenuado de los cuatro serotipos virales (DEN1, DEN2, DEN3, DEN4) insertados en el esqueleto de la vacuna de la fiebre amarilla. Es um producto liofilizado para ser reconstituido antes de la inyección y aplicado en una dosis de 0,5 ml em por vía subcutánea. Se indica a pacientes de 9 a 60 años y debe administrarse en tres dosis a los 0, 6 y 12 meses. La vacuna está contraindicada en individuos con un historial de reacción alérgica a cualquier componente de la vacuna de dengue; individuos con inmunodeficiencia celular congénita o adquirida; personas con infección por VIH sintomática o con infección asintomática por VIH cuando se acompanha de evidencia de deterioro de la función inmune; mujeres embarazadas o mujeres en lactancia; además la aplicación debería ser pospuesta en personas con síndrome febril. OBJETIVO: El objetivo del presente informe es evaluar la evidencia disponible acerca de la eficacia, seguridad y aspectos relacionados a las políticas de cobertura del uso de la vacuna tetravalente CYD-TDV contra el dengue. MÉTODOS: Se realizó una búsqueda en las principales bases de datos bibliográficas, en buscadores genéricos de internet, y financiadores de salud. Se priorizó la inclusión de revisiones sistemáticas (RS), ensayos clínicos controlados aleatorizados (ECAs), evaluaciones de tecnologías sanitarias (ETS), evaluaciones económicas, guías de práctica clínica (GPC) y políticas de cobertura de diferentes sistemas de salud. RESULTADOS: Se incluyeron dos RS, una GPC, una evaluación económica, y cuatro informes de políticas de cobertura. CONCLUSIONES: Evidencia de alta calidad demuestra que la vacuna tetravalente contra el dengue (CYD-TDV) es efectiva para prevenir la enfermedad sintomática, al comparar la incidencia de la misma en indivíduos vacunados versus no vacunados. El análisis de efectividad por subgrupos, demuestra que la misma es mayor en aquellos pacientes que han sido previamente sensibilizados de manera natural. Una guía de la Organización Mundial de la Salud (OMS) recomienda su aplicación en poblaciones que presentan una seroprevalencia mayor al 70%. En aquellas poblaciones con una seroprevalencia entre el 50 y 70%, refiere que su uso también sería aceptable, pero el impacto del programa sería menor. No recomienda su aplicación en poblaciones con una seroprevalencia menor al 50%. No se cuenta con información acerca de la seroprevalencia en Argentina, pero se estima que sería muy baja, en base a estudios de incidencia.