Aerosol precautions and airway complications: a national prospective multicentre cohort study.

The perceived risk of transmission of aerosolised viral particles from patients to airway practitioners during the COVID-19 pandemic led to the widespread use of aerosol precautions, including personal protective equipment and modifications to anaesthetic technique. The risk of these aerosol precautions on peri-operative airway complications has not been assessed outside of simulation studies. This prospective, national, multicentre cohort study aimed to quantify this risk. Adult patients undergoing general anaesthesia for elective or emergency procedures over a 96-hour period were included. Data collected included use of aerosol precautions by the airway practitioner, airway complications and potential confounding variables. Mixed-effects logistic regression was used to assess the risk of individual aerosol precautions on overall and specific airway complications. Data from 5905 patients from 70 hospital sites were included. The rate of airway complications was 10.0% (95%CI 9.2-10.8%). Use of filtering facepiece class 2 or class 3 respirators was associated with an increased risk of airway complications (odds ratio 1.38, 95%CI 1.04-1.83), predominantly due to an association with difficult facemask ventilation (odds ratio 1.68, 95%CI 1.09-2.61) and desaturation on pulse oximetry (odds ratio 2.39, 95%CI 1.26-4.54). Use of goggles, powered air-purifying respirators, long-sleeved gowns, double gloves and videolaryngoscopy were not associated with any alteration in the risk of airway complications. Overall, the use of filtering facepiece class 2 or class 3 respirators was associated with an increased risk of airway complications, but most aerosol precautions used during the COVID-19 pandemic were not.

Heart failure with preserved ejection fraction or non-cardiac dyspnea in paroxysmal atrial fibrillation: The role of left atrial strain.

BACKGROUND: Diagnosis of heart failure with preserved ejection fraction (HFpEF) in patients with dyspnea and paroxysmal atrial fibrillation (AF) is challenging. Speckle tracking-derived left atrial strain (LAS) provides an accurate estimate of left ventricular (LV) filling pressures and left atrial (LA) phasic function. However, data on clinical utility of LAS in patients with dyspnea and AF are scarce. OBJECTIVE: To assess relationship between the LAS and the probability of HFpEF in patients with dyspnea and paroxysmal AF. METHODS: The study included 205 consecutive patients (62 ± 10 years, 58% males) with dyspnea (NYHA≥II), paroxysmal AF and preserved LV ejection fraction (≥50%), who underwent speckle tracking echocardiography during sinus rhythm. Probability of HFpEF was estimated using H2FPEF and HFA-PEFF scores, which combine clinical characteristics, echocardiographic parameters and natriuretic peptides. RESULTS: Patients with high probability of HFpEF were significantly older, had higher body mass index, NT-proBNP, E/e', pulmonary artery pressure and larger LA volume index than patients in low-to-intermediate probability groups (all p < 0.05). All components of LAS and LA strain rate showed proportional impairment with increasing probability of HFpEF (all p < 0.05). Out of the speckle tracking-derived parameters, reservoir LAS showed the largest area under the curve (AUC = 0.78, p < 0.001) and the strongest independent predictive value (OR: 1.22, 95% CI 1.08-1.38) to identify patients with high probability of HFpEF. CONCLUSIONS: Reservoir LAS shows a high diagnostic performance to distinguish HFpEF from non-cardiac causes of dyspnea in symptomatic patients with paroxysmal AF.

Evaluating One Health: the role of team science in multisectoral collaboration.

In a review of the literature surrounding One Health, cross-boundary collaboration, the science of teams, and interdisciplinary health competencies, many individual disciplines, and in some cases multidisciplinary research teams, have looked at the scholarship of collaboration and arrived at remarkably similar conclusions as to which factors and competencies support effective collaboration. However, conclusions on how to effectively evaluate collaboration are consistently lacking across the literature reviewed. Although important advances have been made recently in the area of evaluating One Health operations and outcomes, there is an opportunity to develop process-based performance measures for One Health collaboration and teamwork. Synthesising work on collaborative performance evaluation across multiple disciplinary and sectoral lanes and levels of collaborative analysis, the authors argue that, in addition to outcome-based One Health evaluation, the evaluation of One Health processes needs to be further refined and 'team' effectiveness needs to be evaluated at all levels of the health system: individual, organisational and network.

À l'occasion d'une revue de la littérature scientifique consacrée à Une seule santé, à la collaboration transversale, à la science des équipes et aux compétences interdisciplinaires en matière de santé, plusieurs équipes de chercheurs, pour la plupart spécialisées dans une seule discipline mais aussi, pour certaines, multidisciplinaires, ont étudié la science du travail en collaboration et sont parvenues à des conclusions étonnamment similaires quant aux facteurs et aux compétences qui soutiennent une collaboration efficace. En revanche, il ressort de cet examen de la littérature qu'aucune conclusion n'y apparaît sur la manière d'évaluer efficacement une telle collaboration. Si des avancées importantes ont été enregistrées dans le domaine de l'évaluation des interventions et des résultats Une seule santé, il y a encore matière à développer des méthodes de mesure des performances basées sur les procédures. Cette synthèse des travaux sur l'évaluation collaborative des performances, qui recouvre de multiples voies disciplinaires et sectorielles et différents niveaux d'analyse collaborative permet aux auteurs de soutenir que les évaluations des processus Une seule santé doivent être élaborées plus finement afin de compléter les évaluations basées sur les résultats, et que l'efficacité des « équipe ¼ doit être évaluée à tous les niveaux du système de santé : individus, organisations et réseaux.

Los autores exponen un estudio recapitulativo de la bibliografía relativa a temas como la noción de Una sola salud, la colaboración transfronteriza, la ciencia del trabajo en equipo o las competencias interdisciplinares en temas de salud, señalando a partir de ahí que buen número de disciplinas y, en ciertos casos, equipos pluridisciplinares de investigación, tras examinar cuanto saben los estudiosos en cuestiones de colaboración, llegaron a conclusiones notablemente similares acerca de la suma de factores y competencias que propician una colaboración eficaz. En la bibliografía examinada, sin embargo, brillan por su ausencia las pistas sobre el modo de evaluar eficazmente la colaboración. Aunque últimamente ha habido avances importantes en cuanto a la evaluación de las actividades emprendidas en clave de Una sola salud y sus resultados, existe la posibilidad de establecer parámetros que midan la eficacia de los procesos de colaboración y de trabajo en equipo encuadrados en la filosofía de Una sola salud. Sintetizando los estudios de evaluación de la eficacia de la colaboración que se han realizado desde múltiples ángulos disciplinares y sectoriales y niveles de análisis colectivo, los autores postulan que, además de la evaluación de los resultados, es preciso perfeccionar aún más la evaluación de los procesos de Una sola salud y evaluar asimismo la eficacia de los «equipos¼ en todos los niveles que configuran un sistema de salud: el individual, el institucional y el de las redes de trabajo.

Short communication: Increased somatic cell count is associated with milk loss and reduced feed efficiency in lactating dairy cows.

The objective was to evaluate the relationship of somatic cell count (SCC; cells/mL) with milk yield, energy-corrected milk yield (ECM; kg/d), dry matter intake (DMI; kg/d), feed efficiency for milk (FEMY; kg of milk/kg of DMI), and feed efficiency for ECM (FEECM; kg of ECM/kg of DMI) in lactating dairy cows. We analyzed an SCC database consisting of 7 experiments, which were conducted at The Pennsylvania State University's Dairy Teaching and Research Center between 2009 and 2015. The experiments included in the SCC database were randomized block designs and investigated dietary effects on cow performance over 6 to 11 wk. Each experiment took repeated measurements of SCC, milk yield, milk composition, and DMI. After exclusion of records from cows without lactation number, days in milk, and only 1 measurement, the database comprised 1,094 observations of 254 cows for estimating the effect of SCC on milk yield, DMI, and FEMY and 1,079 observations of 250 cows for estimating the effect of SCC on ECM and FEECM. Data were analyzed in R using a linear mixed model with natural logarithm of SCC, lactation number (1, 2, and ≥3), days in milk, and the interactions of the linear predictors as fixed effects and cow within block and experiment as random effect. Natural logarithm of SCC was negatively correlated with milk yield, ECM, DMI, FEMY, and FEECM. Our results suggest that a cow with relatively high SCC (250,000 cells/mL) compared with a cow with a relatively low SCC (50,000 cells/mL) produces, on average, 1.6 kg/d less milk, consumes 0.3 kg/d less DMI, produces 0.04 kg less milk per kg of DMI, and produces 0.03 less ECM per kg of DMI. The observed decrease of feed efficiency with increased SCC adds to previously known economic losses and environmental impacts associated with mastitis, which should provide a further incentive to control mastitis in dairy cows.

Charged cyclic hexapeptides: Updating molecular descriptors for permeability purposes.

Three polar cyclic hexapeptides differently charged at physiological pH (1 = neutral, 2 = anionic, 3 = cationic) were synthesized and their cell permeability measured. Lipophilicity in octanol/water didn't account for the higher permeability of the cationic derivative but three chromatographic indexes (log KwIAM, log k' HILIC and log k' c-HILIC) were more efficient to this respect. NMR amide chemical shift temperature coefficients (ΔδNH/ΔT) were used to explore the IMHB network of the backbone. MD simulations in different environments (water, chloroform and DMPC lipid bilayer) highlighted that the charged amino group of the lysine moiety of 3 is not involved in the formation of any IMHB in water whereas a different behavior is registered in chloroform and DMPC lipid bilayer. Overall this paper highlights how a combination of experimental and computational approaches could help in comparing permeability and physicochemical properties of neutral and charged cyclic peptides.

Pharmacokinetic-pharmacodynamic integration and modelling of oxytetracycline for the calf pathogens Mannheimia haemolytica and Pasteurella multocida.

A calf tissue cage model was used to study the pharmacokinetics (PK) and pharmacodynamics (PD) of oxytetracycline in serum, inflamed (exudate) and noninflamed (transudate) tissue cage fluids. After intramuscular administration, the PK was characterized by a long mean residence time of 28.3 hr. Based on minimum inhibitory concentrations (MICs) for six isolates each of Mannheimia haemolytica and Pasteurella multocida, measured in serum, integration of in vivo PK and in vitro PD data established area under serum concentration-time curve (AUC0-∞ )/MIC ratios of 30.0 and 24.3 hr for M. haemolytica and P. multocida, respectively. Corresponding AUC0-∞ /MIC ratios based on MICs in broth were 656 and 745 hr, respectively. PK-PD modelling of in vitro bacterial time-kill curves for oxytetracycline in serum established mean AUC0-24 hr /MIC ratios for 3log10 decrease in bacterial count of 27.5 hr (M. haemolytica) and 60.9 hr (P. multocida). Monte Carlo simulations predicted target attainment rate (TAR) dosages. Based on the potency of oxytetracycline in serum, the predicted 50% TAR single doses required to achieve a bacteriostatic action covering 48-hr periods were 197 mg/kg (M. haemolytica) and 314 mg/kg (P. multocida), respectively, against susceptible populations. Dosages based on the potency of oxytetracycline in broth were 25- and 27-fold lower (7.8 and 11.5 mg/kg) for M. haemolytica and P. multocida, respectively.

Detection of genetic incompatibilities in non-model systems using simple genetic markers: hybrid breakdown in the haplodiploid spider mite Tetranychus evansi.

When two related species interbreed, their hybrid offspring frequently suffer from reduced fitness. The genetics of hybrid incompatibility are described by the Bateson-Dobzhansky-Muller (BDM) model, where fitness is reduced by epistatic interactions between alleles of heterospecific origin. Unfortunately, most empirical evidence for the BDM model comes from a few well-studied model organisms, restricting our genetic understanding of hybrid incompatibilities to limited taxa. These systems are predominantly diploid and incompatibility is often complete, which complicates the detection of recessive allelic interactions and excludes the possibility to study viable or intermediate stages. Here, we advocate research into non-model organisms with haploid or haplodiploid reproductive systems and incomplete hybrid incompatibility because (1) dominance is absent in haploids and (2) incomplete incompatibility allows comparing affected with unaffected individuals. We describe a novel two-locus statistic specifying the frequency of individuals for which two alleles co-occur. This approach to studying BDM incompatibilities requires genotypic characterization of hybrid individuals, but not genetic mapping or genome sequencing. To illustrate our approach, we investigated genetic causes for hybrid incompatibility between differentiated lineages of the haplodiploid spider mite Tetranychus evansi, and show that strong, but incomplete, hybrid breakdown occurs. In addition, by comparing the genotypes of viable hybrid males and inviable hybrid male eggs for eight microsatellite loci, we show that nuclear and cytonuclear BDM interactions constitute the basis of hybrid incompatibility in this species. Our approach opens up possibilities to study BDM interactions in non-model taxa, and may give further insight into the genetic mechanisms behind hybrid incompatibility.

A large potentiation effect of serum on the in vitro potency of tulathromycin against Mannheimia haemolytica and Pasteurella multocida.

The antimicrobial properties of tulathromycin were investigated for M. haemolytica and P. multocida. Three in vitro indices of antimicrobial activity, minimum inhibitory concentration (MIC), minimum bactericidal concentration (MBC) and time-kill curves, were established for six isolates of each organism. Each index was measured in two growth media: Mueller-Hinton broth (MHB) and calf serum. It was shown that MICs and MBCs were markedly lower in serum than in MHB. MHB:serum ratios for MIC were 47:1 (M. haemolytica) and 53:1 (P. multocida). For both serum and MHB, adjustment of pH led to greater potency at alkaline compared to acid pH. Tulathromycin MIC was influenced by size of inoculum count, being 4.0- to 7.7-fold greater for high compared to low initial counts. It was concluded that for the purpose of determining dosages for therapeutic use, pharmacodynamic data for tulathromycin should be derived in biological fluids such as serum. It is hypothesized that in vitro measurement of MIC in broth, conducted according to internationally recommended standards, may be misleading as a basis for estimating the in vivo potency of tulathromycin.

Standard PK/PD concepts can be applied to determine a dosage regimen for a macrolide: the case of tulathromycin in the calf.

The pharmacokinetic (PK) profile of tulathromycin, administered to calves subcutaneously at the dosage of 2.5 mg/kg, was established in serum, inflamed (exudate), and noninflamed (transudate) fluids in a tissue cage model. The PK profile of tulathromycin was also established in pneumonic calves. For Mannheimia haemolytica and Pasteurella multocida, tulathromycin minimum inhibitory concentrations (MIC) were approximately 50 times lower in calf serum than in Mueller-Hinton broth. The breakpoint value of the PK/pharmacodynamic (PD) index (AUC(0-24 h) /MIC) to achieve a bactericidal effect was estimated from in vitro time-kill studies to be approximately 24 h for M. haemolytica and P. multocida. A population model was developed from healthy and pneumonic calves and, using Monte Carlo simulations, PK/PD cutoffs required for the development of antimicrobial susceptibility testing (AST) were determined. The population distributions of tulathromycin doses were established by Monte Carlo computation (MCC). The computation predicted a target attainment rate (TAR) for a tulathromycin dosage of 2.5 mg/kg of 66% for M. haemolytica and 87% for P. multocida. The findings indicate that free tulathromycin concentrations in serum suffice to explain the efficacy of single-dose tulathromycin in clinical use, and that a dosage regimen can be computed for tulathromycin using classical PK/PD concepts.

Effects of in ovo supplementation of probiotics on performance and immunocompetence of broiler chicks to an Eimeria challenge.

Coccidiosis is regarded as the parasitic disease with the greatest economic impact on the poultry industry due to reduced performance and increased mortality. A study was conducted to investigate the effects of in ovo administration of probiotics on hatchability, performance, immune organ weights, and lesion scores in broiler chicks during a mixed Eimeria infection. At embryonic day 18, 210 eggs were injected with either sterile water or 1×106 cfu probiotic bacteria. On day 3 post-hatch, half of the chicks from each treatment group were challenged with a mixed inoculum of Eimeria acervulina, Eimeria maxima and Eimeria tenella. Measurements and tissue samples were taken on day of hatch (DOH) and days 3, 9 and 15. On day 9, 24 birds per treatment were scored for intestinal Eimeria lesions. No differences were seen among groups for hatchability as well as for body weight (BW), BW gain (BWG), or immune organ weights prior to the Eimeria challenge. On day 9, the non-challenged birds with probiotic supplementation had higher BW and BWG than the non-supplemented controls while no differences were seen among the challenged groups. On day 15, probiotic supplemented birds had improved BW compared to the non-supplemented birds as well as increased BWG from day 9 to 15. Bursa weight was not affected by treatment at any time point while spleen weight was greater in supplemented birds on day 15. Birds receiving the probiotic had significantly lower mortality than non-treated birds. Additionally, gross lesion severity was reduced due to probiotic supplementation in all intestinal segments evaluated. These results suggest that in ovo supplementation of probiotics may improve early performance and provide protection against a mixed Eimeria infection.

VT Recurrence After Ablation: Incomplete Ablation or Disease Progression? A Multicentric European Study.

AIM: To determine whether ventricular tachycardia (VT) recurrences in arrhythmogenic RV cardiomyopathy (ARVC) and nonischemic cardiomyopathy (NICM) are related to incomplete ablation or disease progression. METHODS: ARVC and NICM patients with two substrate maps of the same diseased ventricle with an interprocedural delay of ≥12 months were included. Disease progression was defined as ≥1 factor: scar area progression (PROG, +5%), ventricular remodeling (dilatation [+25 mL] or decreased ejection fraction [-5%EF]). Incomplete ablation was defined as index VT recurrence or ablation in previously unablated regions inside index scar without PROG. RESULTS: Twenty patients from nine centers were included (80% male 55 ± 16 years, 7 ARVC and 13 NICM, LVEF 43 ± 14%). Mean delay was 28 ± 18 months. Disease progression occurred in 75% with ventricular remodeling in 70%: ventricular dilation in 45% (ARVC [71%]; NICM [38%]), decreased EF in 60% [RVEF in ARVC (71%); LVEF in NICM (54%)], and scar progression in 50% (in ARVC [57%] and NICM [46%]). Index VT recurrence was observed in 40%. Redo ablation sites were located in previously unablated regions inside the index scar in 70% of patients. VT recurrence following the second procedure was seen in 25%. Fifteen percent died during a follow-up of 17 ± 17 months. CONCLUSION: Disease progression is the rule in ARVC and NICM while scar progression occurs in half. However, even if disease progression is frequently observed, incomplete index ablation is the most common finding, strongly suggesting the need for more extensive ablation.

Pharmacokinetic/pharmacodynamic integration and modelling of amoxicillin for the calf pathogens Mannheimia haemolytica and Pasteurella multocida.

The antimicrobial properties of amoxicillin were determined for the bovine respiratory tract pathogens, Mannheima haemolytica and Pasteurella multocida. Minimum inhibitory concentration (MIC), minimum bactericidal concentration (MBC) and time-kill curves were established. Pharmacokinetic (PK)/pharmacodynamic (PD) modelling of the time-kill data, based on the sigmoidal Emax equation, generated parameters for three levels of efficacy, namely bacteriostatic, bactericidal (3log10 reduction) and 4log10 reduction in bacterial counts. For these levels, mean AUC(0-24 h) /MIC serum values for M. haemolytica were 29.1, 57.3 and 71.5 h, respectively, and corresponding values for P. multocida were 28.1, 44.9 and 59.5 h. Amoxicillin PK was determined in calf serum, inflamed (exudate) and noninflamed (transudate) tissue cage fluids, after intramuscular administration of a depot formulation at a dosage of 15 mg/kg. Mean residence times were 16.5 (serum), 29.6 (exudate) and 29.0 h (transudate). Based on serum MICs, integration of in vivo PK and in vitro PD data established maximum concentration (Cmax )/MIC ratios of 13.9:1 and 25.2:1, area under concentration-time curve (AUC0-∞ )/MIC ratios of 179 and 325 h and T>MIC of 40.3 and 57.6 h for P. multocida and M. haemolytica, respectively. Monte Carlo simulations for a 90% target attainment rate predicted single dose to achieve bacteriostatic and bactericidal actions over 48 h of 17.7 and 28.3 mg/kg (M. haemolytica) and 17.7 and 34.9 mg/kg (P. multocida).

Pharmacokinetic-pharmacodynamic integration and modelling of florfenicol in calves.

Florfenicol was administered subcutaneously to 10 calves at a dose of 40 mg/kg. Pharmacokinetic-pharmacodynamic (PK-PD) integration and modelling of the data were undertaken using a tissue cage model, which allowed comparison of microbial growth inhibition profiles in three fluids, serum, exudate and transudate. Terminal half-lives were relatively long, so that florfenicol concentrations were well maintained in all three fluids. Minimum inhibitory concentration (MIC) and minimum bactericidal concentration were determined in vitro for six strains each of the calf pneumonia pathogens, Mannhemia haemolytica and Pasteurella multocida. An PK-PD integration for three serum indices provided mean values for P. multocida and M. haemolytica, respectively, of 12.6 and 10.4 for Cmax /MIC, 183 and 152 h for AUC0-24 h /MIC and 78 and 76 h for T>MIC. Average florfenicol concentrations in serum exceeded 4 × MIC and 1.5 × MIC for the periods 0-24 and 48-72 h, respectively. Ex vivo growth inhibition curves for M. haemolytica and P. multocida demonstrated a rapid (with 8 h of exposure) and marked (6 log10 reduction in bacterial count or greater) killing response, suggesting a concentration-dependent killing action. During 24-h incubation periods, inhibition of growth to a bacteriostatic level or greater was maintained in serum samples collected up to 96 h and in transudate and exudate samples harvested up to 120 h. Based on the sigmoidal Emax relationship, PK-PD modelling of the ex vivo time-kill data provided AUC0-24 h /MIC serum values for three levels of growth inhibition, bacteriostatic, bactericidal and 4 log10 decrease in bacterial count; mean values were, respectively, 8.2, 26.6 and 39.0 h for M. haemolytica and 7.6, 18.1 and 25.0 h for P. multocida. Similar values were obtained for transudate and exudate. Based on pharmacokinetic and PK-PD modelled data obtained in this study and scientific literature values for MIC distributions, Monte Carlo simulations over 100 000 trials were undertaken to predict once daily dosages of florfenicol required to provide 50% and 90% target attainment rates for three levels of growth inhibition, namely, bacteriostasis, bactericidal action and 4 log10 reduction in bacterial count.

Pharmacodynamics of florfenicol for calf pneumonia pathogens.

The antimicrobial properties of florfenicol were investigated for the bovine respiratory tract pathogens, Mannheimia haemolytica and Pasteurella multocida. Three in vitro indices of efficacy and potency were determined; minimum inhibitory concentration (MIC), minimum bactericidal concentration (MBC) and in vitro time-kill curves for six pathogenic strains of each organism. Each was monitored in two matrices, Mueller Hinton broth (MHB) and calf serum. MBC:MIC ratios were low, 1.8 : 1 for M haemolytica in both MHB and serum and 2.4 : 1 and 2.1 : 1 for P multocida in MHB and serum, respectively. The killing action of florfenicol had the characteristics of concentration dependency against M haemolytica and codependency (on time and concentration) against P multocida. Modelling of the time-kill data after 24 hours exposure was undertaken to quantify three levels of activity for the ratio, area under concentration-time curve over 24 hours (AUC24h)/MIC; bacteriostatic action (no change in bacterial count), 3log10 reduction and 4log10 reduction in bacterial count. Mean AUC24h/MIC values for P multocida in MHB (and serum) were 22.0 (23.3) hour, 34.5 (39.9) hour and 45.8 (50.4) hour, respectively. Similar numerical values were obtained for M haemolytica. For both bacterial species, interstrain variability was low; coefficients of variation ( per cent) in serum for 3log10 and 4log10 reductions in count were, respectively, 14.3 and 24.1 for P multocida and 7.8 and 11.4 for M haemolytica. These data form a rational basis for dosage selection for treatment of calf pneumonia caused by M haemolytica or P multocida.

Aerobic training-induced improvements in arterial stiffness are not sustained in older adults with multiple cardiovascular risk factors.

There is a well-established relationship between increased arterial stiffness and cardiovascular mortality. We examined whether a long-term aerobic exercise intervention (6 months) would increase arterial compliance in older adults with hypertension complicated by Type 2 diabetes (T2DM) and hyperlipidemia. A total of 52 older adults (mean age 69.3±0.6 years, 30 males and 22 females) with diet/oral hypoglycemic-controlled T2DM, hypertension and hypercholesterolemia were recruited. Subjects were randomly assigned to one of two groups: an aerobic group (6 months vigorous aerobic exercise, AT group) and a non-aerobic group (6 months of no aerobic exercise, NA group). Arterial stiffness was measured as pulse-wave velocity (PWV) using the Complior device. Aerobic training decreased arterial stiffness as measured by both radial (P=0.001, 2-way analysis of variance with repeated measures) and femoral (P=0.002) PWV. This was due to a decrease in arterial stiffness in the AT group after 3 months of training, which was not maintained after 6-month training for either radial (P=0.707) or femoral (P=0.680) PWV. Our findings indicate that in older adults with multiple cardiovascular risk factors, short-term improvements in arterial stiffness became attenuated over the long term.

Pharmacokinetic and pharmacodynamic integration and modelling of marbofloxacin in calves for Mannheimia haemolytica and Pasteurella multocida.

The pharmacokinetics (PK) and pharmacodynamics (PD) of marbofloxacin were established in calves for six strains of each of the pneumonia pathogens Mannheimia haemolytica and Pasteurella multocida. The distribution of marbofloxacin into inflamed (exudate) and non-inflamed (transudate) tissue cage fluids allowed comparison with the serum concentration-time profile. To establish the PD profile, minimum inhibitory concentration (MIC) was determined in Mueller-Hinton broth (MHB) and calf serum. Moderately higher MICs were obtained for serum compared to MHB. An initial integration of PK-PD data established C(max)/MIC ratios of 45.0 and AUC(24h)/MIC values of 174.7 h, based on serum MICs, for both bacterial species. Using bacterial time-kill curves, generated ex vivo for serum marbofloxacin concentrations, PK-PD modelling established three levels of growth inhibition: AUC(24 h)/MIC ratios for no reduction, 3 log(10) and 4 log(10) reductions in bacterial count from the initial inoculum count were 41.9, 59.5 and 68.0 h for M. haemolytica and 48.6, 64.9 and 74.8 h for P. multocida, on average respectively. Inter-strain variability for 3 log(10) and 4 log(10) reductions in bacterial count was smaller for P. multocida than for M. haemolytica. In conjunction with literature data on MIC(90) values, the present results allowed prediction of dosages for efficacy for each organism for the three levels of growth inhibition.

Elements in human placentae in Jamaica / Elementos en las placentas humanas en Jamaica

AIM: To investigate the relationships, if any, between elemental content of the placenta with age of mother, birthweight and the Apgar scores of a neonate. METHODS: Placental samples were collected, stored at -20ºC and then dried and analysed using neutron activation with the SLOWPOKE II reactor at the International Centre for Environmental and Nuclear Sciences (ICENS). A questionnaire was administered at the time of delivery to determine the level of fish consumption, numbers of dental amalgam fillings and use of cough syrups. Placental concentrations of bromine, calcium, chlorine, iron, mercury, potassium, rubidium, selenium, sodium and zinc were determined. RESULTS: The placentae of 52 Jamaican mothers with a mean age 29 years (range 18-42 years) delivering singleton neonates with a mean birthweight of 3.1 kg (1.3 - 5.5 kg) at term were collected. With the exception of iron and bromine, all results for elemental determinations are very similar to those found elsewhere. Correlation was observed for Apgar 2 (5 minutes), calcium and zinc with birthweight, with p-values of 0.002, 0.007 and 0.07, respectively. Negative correlation was observed for the Apgar 2 and potassium (p = 0.056) and age of mother at birth and bromine (p = 0.02). The mercury concentration in the measured placentae (7.29 ±9.1 µg/kg w/w) was slightly lower than the mean concentration found in the literature (8 µg/kg w/w). Approximately 93% of the measured placentae in this study are below the derived placentae upper limit of 22 µg/kg. Of the 7% above the upper limit none exceeded the conservative estimated limit of 115 /µg/kg at which neural developmental problems start. CONCLUSION: The significant associations noted are of unknown clinical relevance and need further study.

OBJETIVO: Investigar las relaciones que pudieran existir entre el contenido elemental de la placenta y la edad de la madre, el peso al nacer, y la puntuación Apgar del neonato. MÉTODOS: Muestras de placenta fueron recogidas, almacenadas a -20ºC y entonces secadas y analizadas usando la activación neutrónica con el reactor SLOWPOKE II del Centro Internacional de Ciencias Medioambientales y Nucleares (ICENS). A la hora del parto se aplicó una encuesta para determinar el nivel de consumo de pescado, el número de amalgamas dentales y el uso de jarabes para la tos. Se determinaron las concentraciones placentales de bromo, calcio, cloro, hierro, mercurio, potasio, rubidio, selenio, sodio y cinc. RESULTADOS: Se recogieron las placentas de 52 madres jamaicanas con una edad promedio de 29 años (rango 18-42 años) que parieron neonatos únicos con un peso promedio de 3.1 kg (1.3-5.5 kg) a término. Con la excepción del hierro y el bromo, todos los resultados para las determinaciones elementales son muy similares a los hallados en otras partes. Se observó una correlación de Apgar 2 (5 minutos), el calcio y el cinc con el peso al nacer, los valores p de 0.002, 0.007 y 0.07 respectivamente. Se observó una correlación negativa de Apgar 2 y el potasio (p = 0.056) y la edad de la madre a la hora del alumbramiento, con el bromo (p = 0.02). La concentración de mercurio en las placentas medidas (7.29 ± 9.1 w/w de µg/kg) fue ligeramente más baja que la concentración promedio hallada en la literatura (8 µg/kg w/w). Aproximadamente 93% de las placentas evaluadas en este estudio están por debajo del límite superior de 22 µg/kg. Del 7% por encima del límite superior, ninguna excedió el límite conservador estimado de 115 µg/kg en el cual comienzan los problemas del desarrollo neural. CONCLUSIÓN: Se desconoce la importancia clínica de las asociaciones significativas observadas y se requiere más estudio.

Global and right ventricular end-diastolic volumes correlate better with preload after correction for ejection fraction.

BACKGROUND: Volumetric monitoring with right ventricular end-diastolic volume indexed (RVEDVi) and global end-diastolic volume indexed (GEDVi) is increasingly being suggested as a superior preload indicator compared with the filling pressures central venous pressure (CVP) or the pulmonary capillary wedge pressure (PCWP). However, static monitoring of these volumetric parameters has not consistently been shown to be able to predict changes in cardiac index (CI). The aim of this study was to evaluate whether a correction of RVEDVi and GEDVi with a measure of the individual contractile reserve, assessed by right ventricular ejection fraction (RVEF) and global ejection fraction, improves the ability of RVEDVi and GEDVi to monitor changes in preload over time in critically ill patients. METHODS: Hemodynamic measurements, both by pulmonary artery and by transcardiopulmonary thermodilution, were performed in 11 mechanically ventilated medical ICU patients. Correction of volumes was achieved by normalization to EF deviation from normal EF values in an exponential fashion. Data before and after fluid administration were obtained in eight patients, while data before and after diuretics were obtained in seven patients. RESULTS: No correlation was found between the change in cardiac filling pressures (DeltaCVP, DeltaPCWP) and DeltaCI (R(2) 0.01 and 0.00, respectively). Further, no correlation was found between DeltaRVEDVi or DeltaGEDVi and DeltaCI (R(2) 0.10 and 0.13, respectively). In contrast, a significant correlation was found between DeltaRVEDVi corrected to RVEF (DeltacRVEDVi) and DeltaCI (R(2) 0.64), as well as between DeltacGEDVi and DeltaCI (R(2) 0.59). An increase in the net fluid balance with +844 + or - 495 ml/m(2) resulted in a significant increase in CI of 0.5 + or - 0.3 l/min/m(2); however, only DeltacRVEDVi (R(2) 0.58) and DeltacGEDVi (R(2) 0.36) correlated significantly with DeltaCI. Administration of diuretics resulting in a net fluid balance of -942 + or - 658 ml/m(2) caused a significant decrease in CI with 0.7 + or - 0.5 l/min/m(2); however, only DeltacRVEDVi (R(2) 0.80) and DeltacGEDVi (R(2) 0.61) correlated significantly with DeltaCI. CONCLUSION: Correction of volumetric preload parameters by measures of ejection fraction improved the ability of these parameters to assess changes in preload over time in this heterogeneous group of critically ill patients.