Transition cow clusters with distinctive antioxidant ability and their relation to performance and metabolic status in early lactation.

Metabolic and oxidative stress have been characterized as risk factors during the transition period from pregnancy to lactation. Although mutual relations between both types of stress have been suggested, they rarely have been studied concomitantly. For this, a total of 99 individual transition dairy cows (117 cases, 18 cows sampled during 2 consecutive lactations) were included in this experiment. Blood samples were taken at -7, 3, 6, 9, and 21 d relative to calving and concentrations of metabolic parameters (glucose, ß-hydroxybutyric acid (BHBA), nonesterified fatty acids, insulin, insulin-like growth factor 1, and fructosamine) were determined. In the blood samples of d 21, biochemical profiles related to liver function and parameters related to oxidative status were determined. First, cases were allocated to 2 different BHBA groups (ketotic vs. nonketotic, N:n = 20:33) consisting of animals with an average postpartum BHBA concentration and at least 2 out of 4 postpartum sampling points exceeding 1.2 mmol/L or remaining below 0.8 mmol/L, respectively. Second, oxidative parameters [proportion of oxidized glutathione to total glutathione in red blood cells (%)], activity of glutathione peroxidase, and of superoxide dismutase, concentrations of malondialdehyde and oxygen radical absorbance capacity were used to perform a fuzzy C-means clustering. From this, 2 groups were obtained [i.e., lower antioxidant ability (LAA80%, n = 31) and higher antioxidant ability (HAA80%, n = 19)], with 80% referring to the cutoff value for cluster membership. Increased concentrations of malondialdehyde, decreased superoxide dismutase activity, and impaired oxygen radical absorbance capacity were observed in the ketotic group compared with the nonketotic group, and inversely, the LAA80% group showed increased concentrations of BHBA. In addition, the concentration of aspartate transaminase was higher in the LAA80% group compared with the HAA80% group. Both the ketotic and LAA80% groups showed lower dry matter intake. However, a lower milk yield was observed in the LAA80% group but not in the ketotic group. Only 1 out of 19 (5.3%) and 3 out of 31 (9.7%) cases from the HAA80% and LAA80% clusters belong to the ketotic and nonketotic group, respectively. These findings suggested that dairy cows vary in oxidative status at the beginning of the lactation, and fuzzy C-means clustering allows to classify observations with distinctive oxidative status. Dairy cows with higher antioxidant capacity in early lactation rarely develop ketosis.

Subacute ruminal acidosis phenotypes in periparturient dairy cows differ in ruminal and salivary bacteria and in the in vitro fermentative activity of their ruminal microbiota.

Both ruminal microbial structure and functionality might play a role in inter-individual variation in susceptibility for subacute rumen acidosis (SARA) observed in dairy cows. The aims of this study were to determine whether differences between cows with distinct SARA susceptibility were reflected in distinct (1) ruminal microbial communities, (2) salivary bacterial communities, and (3) fermentative capacity of ruminal microbiota assessed in vitro. To test this hypothesis, rumen samples were collected via an esophageal tube on 21 d postpartum from 38 multiparous Holstein cows, which were classified into 4 groups differing in median and mean time of reticular pH below 6 as well as area under the curve of pH below 6.0. During the 21 d postpartum, all cows within a group fulfilled following criteria: susceptible (S, n = 10; mean or median ≥180 min/d), moderately susceptible (MS, n = 7; 60 min/d < mean time of pH below 6 < 180 min/d, and median time of pH below 6 <180 min/d), moderately unsusceptible (MU, n = 11; 10 min/d < mean < 60 min/d, and median time of pH below 6 ≤30 min/d), or unsusceptible (U, n = 10; median = 0 min/d, and mean <10 min/d). Groups did not differ in total daily dry matter intake nor in total, roughage, or concentrate intake during daily 6-h time intervals. Rumen bacterial α-diversity did not differ among groups, but ß-diversity varied and bacterial 16S rRNA gene copy numbers were lower in S compared with U cows. The relative abundance of genera Streptococcus, Sharpea, Prevotellaceae_YAB2003, Succinivibrionaceae_UCG-001, Ruminococcus, and Ruminococcaceae_UCG-001 were higher in S compared with U cows. In contrast, Lachnospiraceae_ND3007 and Oscillospiraceae_V9D2013 were more abundant in U cows. Although pH-associated, inter-animal differences were also observed in the salivary bacteria, common differences in ruminal and salivary bacterial genera were limited. The functionality of the rumen microbiota was evaluated in vitro through exposure of the microbial inoculum of S and U cows to an anaerobic buffer at pH 5.8 and 6.8, in the presence of sterile supernatant of their own and of dry cows' rumen fluid (2 × 2 design). Generally, the S inoculum produced more volatile fatty acids, except at low pH with dry cows' supernatant, where volatile fatty acid production was completely impaired and lactate accumulation was highest. Compared with the microbes of U cows, microbes of S cows showed less fermentative activity in situations with 2 stress factors (low pH and an unfamiliar environment, i.e., rumen fluid supernatant of dry cows).

Promising perspectives for ruminal protection of polyunsaturated fatty acids through polyphenol-oxidase-mediated crosslinking of interfacial protein in emulsions.

Previously, polyunsaturated fatty acids (PUFA) from linseed oil were effectively protected (>80%) against biohydrogenation through polyphenol-oxidase-mediated protein crosslinking of an emulsion, prepared with polyphenol oxidase (PPO) extract from potato tuber peelings. However, until now, emulsions of only 2 wt% oil have been successfully protected, which implies serious limitations both from a research perspective (e.g. in vivo trials) as well as for further upscaling toward practical applications. Therefore, the aim of this study was to increase the oil/PPO ratio. In the original protocol, the PPO extract served both an emulsifying function as well as a crosslinking function. Here, it was first evaluated whether alternative protein sources could replace the emulsifying function of the PPO extract, with addition of PPO extract and 4-methylcatechol (4MC) to induce crosslinking after emulsion preparation. This approach was then further used to evaluate protection of emulsions with higher oil content. Five candidate emulsifiers (soy glycinin, gelatin, whey protein isolate (WPI), bovine serum albumin and sodium caseinate) were used to prepare 10 wt% oil emulsions, which were diluted five times (w/w) with PPO extract (experiment 1). As a positive control, 2 wt% oil emulsions were prepared directly with PPO extract according to the original protocol. Further, emulsions of 2, 4, 6, 8 and 10 wt% oil were prepared, with 80 wt% PPO extract (experiment 2), or with 90, 80, 70, 60 and 50 wt% PPO extract, respectively (experiment 3) starting from WPI-stabilized emulsions. Enzymatic crosslinking was induced by 24-h incubation with 4MC. Ruminal protection efficiency was evaluated by 24-h in vitro batch simulation of the rumen metabolism. In experiment 1, protection efficiencies were equal or higher than the control (85.5% to 92.5% v. 81.3%). In both experiments 2 and 3, high protection efficiencies (>80%) were achieved, except for emulsions containing 10 wt% oil emulsions (<50% protection), which showed oiling-off after enzymatic crosslinking. This study demonstrated that alternative emulsifier proteins can be used in combination with PPO extract to protect emulsified PUFA-rich oils against ruminal biohydrogenation. By applying the new protocol, 6.5 times less PPO extract was required.

[How molecular biology can improve the clinical diagnosis of gliomas?] / Comment la biologie moléculaire améliore le diagnostic clinique des gliomes?

Gliomas are the most common primary brain tumors and include different diagnoses associated with a different prognosis. Histology remains the gold standard for the diagnosis of these tumors. However, pathologists may encounter diagnostic difficulties due to tumor heterogeneity or to the small size of the samples. Recently, major advances in discovery of molecular alterations of these cancers have led to the development of new molecular markers, some with a diagnostic role, others with a prognostic impact and / or predictive of therapeutic response. The testing of different molecular alterations such as 1p / 19q codeletion, mutations of IDH genes, p16 deletion, EGFR amplification or MGMT promoter methylation has been included in the daily practice in order to confirm the diagnosis, assess the patient prognosis and guide treatment choices.

Les gliomes représentent les tumeurs cérébrales primitives les plus fréquentes et regroupent différentes entités au pronostic très différent. L'examen anatomopathologique est le gold standard pour le diagnostic de ces tumeurs. Cependant, les pathologistes peuvent rencontrer des difficultés diagnostiques dues, entre autres, à l'hétérogénéité tumorale ou à la petite taille des prélèvements. Nous avons assisté, ces dernières années, à des avancées majeures dans la découverte des altérations moléculaires de ces cancers, ce qui a mené au développement de nouveaux marqueurs moléculaires, certains avec un rôle diagnostique, d'autres avec un impact pronostique et/ou prédictif de la réponse thérapeutique. Dans la pratique quotidienne, il est donc devenu utile de tester la présence de différentes altérations moléculaires telles que la codélétion 1p/19q, les mutations des gènes IDH, la délétion du gène CDKN2A/p16, l'amplification du gène EGFR ou la méthylation du promoteur du gène MGMT, afin de confirmer le diagnostic, d'évaluer le pronostic des patients ainsi que d'orienter les choix thérapeutiques.

[Next generation sequencing]. / Une nouvelle technologie pour améliorer le diagnostic des cancers thyroïdiens.

Fine needle aspiration is the gold standard method to differentiate benign thyroid nodules from malignant. However, for 15 to 30% of the cases the cytological diagnosis is indeterminate, leading to surgery. Integration of new molecular markers is opening new perspectives in order to increase the diagnostic precision of thyroid nodules with an indeterminate cytology.

La méthode diagnostique de référence pour différencier les nodules thyroïdiens bénins des nodules malins est la ponction écho-guidée à l'aiguille fine. Cependant dans 15 à 30 % des cas le diagnostic cytologique est indéterminé, menant à une intervention chirurgicale. L'intégration de nouveaux marqueurs moléculaires nous ouvrent de nouvelles perspectives pour augmenter la précision diagnostique des nodules thyroïdiens de diagnostic cytologique indéterminé.

Aminoglycosides for life-threatening infections: a plea for an individualized approach using intensive therapeutic drug monitoring.

Aminoglycosides are potent antibiotics with a renewed interest due to the increase in multidrug resistant infections. Their use in life-threatening infections ­ in combination with other antibiotics ­ has been debated due to the lack of clear outcome benefits. However, based on recent pharmacokinetic-pharmacodynamic studies, conventional dosing may be inefficient in a considerable number of patients, which could preclude the efficiency of this potent drug class. Toxicity on the other hand remains a concern, with nephrotoxicity as the most relevant negative effect in the critically ill. Short term, intensively monitored treatment strategies - with monitoring both peak and trough levels - may increase efficacy as well as reduce toxicity in the critically ill patient.

Aspiration pneumonia: an underestimated cause of severe respiratory failure in patients with haematological malignancies and severe oral mucositis?

Aspiration pneumonia is rarely considered in the differential diagnosis of respiratory failure in patients suffering from haematologic malignancies in daily practice. We describe four patients who were admitted with severe respiratory failure in the ICU over a one-year-period prospective survey (a total of 72 patients with haematological malignancies of which 34 presented with respiratory failure). All of these patients had chemotherapy-induced severe oral mucositis (WHO grade ILL-IV) for which three of them received opioids. All had a history of cough after oral rinsing and two of them experienced sudden brief desaturation in the days before ICU referral. Two of these patients, both in allogeneic bone marrow transplant setting, died. With this data, we want to draw the attention to the diagnosis of aspiration pneumonia in this group of patients.