Using milk mid-infrared spectroscopy to estimate cow-level nitrogen efficiency metrics.

Minimizing pollution from the dairy sector is paramount; one potential cause of such pollution is excess nitrogen. Nitrogen pollution contributes to a deterioration in water quality as well as an increase in both eutrophication and greenhouse gases. It is therefore essential to minimize the loss of nitrogen from the sector, including excretion from the cow. Breeding programs are one potential strategy to improve the efficiency with which nitrogen is used by dairy cows but relies on routine access to individual cow information on how efficiently each cows uses the nitrogen it ingests. A total of 3,497 test-day records for individual cow nitrogen efficiency metrics along with milk yield and the associated milk spectra were used to investigate the ability of milk infrared spectral data to predict these nitrogen traits; both traditional partial least squares regression and neural networks were used in the prediction process. The data originated from 4 farms across 11 years. The nitrogen traits investigated were nitrogen intake, nitrogen use efficiency, and nitrogen balance. Both nitrogen use efficiency and nitrogen balance were calculated considering nitrogen intake, nitrogen in milk, nitrogen in the conceptus, nitrogen used for the growth, nitrogen stored in the reserves, and nitrogen mobilized from the reserves. Irrespective of the nitrogen-related trait being investigated, the best prediction from 4-fold cross-validation were achieved using neural networks that considered both the morning and evening milk spectra along with milk yield, parity, and days in milk in the prediction process. The coefficient of determination in the cross-validation was 0.61, 0.74, and 0.58 for nitrogen intake, nitrogen use efficiency, and nitrogen balance, respectively. In a separate series of validation approaches, the calibration and validation was stratified by herd (n = 4) and separately by year. For these scenarios, partial least squares regression generated more accurate predictions compared with neural networks; the coefficient of determination was always lower than 0.29 and 0.60 when validation was stratified by herd and year, respectively. Therefore, if the variability of the data being predicted in the validation data sets is similar to that in the data used to develop the predictions, then nitrogen-related traits can be predicted with reasonable accuracy. In contrast, where the variability of the data that exists in the validation data set is poorly represented in the calibration data set, then poor predictions will ensue.

Genetic covariance components for measures of nitrogen utilization in grazing dairy cows.

Improved nitrogen utilization of dairy production systems should improve not only the economic output of the systems but also the environmental metrics. One strategy to improve efficiency is through breeding programs. Improving a trait through breeding is conditional on the presence of exploitable genetic variability. Using a database of 1,291 deeply phenotyped grazing dairy cows, the genetic variability for 2 definitions of nitrogen utilization was studied: nitrogen use efficiency (i.e., nitrogen output in milk and meat divided by nitrogen available) and nitrogen balance (i.e., nitrogen available less nitrogen output in milk and meat). Variance components for both variables were estimated using animal repeatability linear mixed models. Genetic variability was detected for both nitrogen utilization metrics, even though their heritability estimates were low (<0.10). Validation of genetic evaluations revealed that animals divergent for nitrogen use efficiency or nitrogen balance indeed differed phenotypically, further demonstrating that breeding for improved nitrogen efficiency should result in a shift in the population mean toward better efficiency. Nitrogen use efficiency and nitrogen balance were not genetically correlated with each other (<|0.28|), and neither metric was correlated with milk urea nitrogen (<|0.12|). Nitrogen balance was unfavorably correlated with milk yield, showing the importance of including the nitrogen utilization metrics in a breeding index to improve nitrogen utilization without negatively impacting milk yield. In conclusion, improvement of nitrogen utilization through breeding is possible, even if more nitrogen utilization phenotypic data need to be collected to improve the selection accuracy considering the low heritability estimates.

Cow-level factors associated with nitrogen utilization in grazing dairy cows using a cross-sectional analysis of a large database.

Reducing nitrogen pollution while maintaining milk production is a major challenge of dairy production. One of the keys to delivering on this challenge is to improve the efficiency of how dairy cows use nitrogen. Thus, estimating the nitrogen utilization of lactating grazing dairy cows and exploring the association between animal factors and productivity with nitrogen utilization are the first steps to understanding the nitrogen utilization complex in dairy cows. Nitrogen utilization metrics were derived from milk and body weight records from 1,291 grazing dairy cows of multiple breeds and crossbreeds; all cows had sporadic information on nitrogen intake concurrent with information on nitrogen sinks (and other nitrogen sources, such as body tissue mobilization). Several nitrogen utilization metrics were investigated, including nitrogen use efficiency (nitrogen output as products such as milk and meat divided by nitrogen intake) and nitrogen excreted (nitrogen intake less the nitrogen output as products such as milk and meat). In the present study, a primiparous Holstein-Friesian used, on average, 20.6% of the nitrogen it ate, excreting the surplus as feces and urine, representing 402 g of nitrogen per day. Intercow variability existed, with a between-cow standard deviation of 0.0094 for nitrogen use efficiency and 24 g of nitrogen per day for nitrogen excretion. As lactation progressed, nitrogen use efficiency declined and nitrogen excretion increased. Nevertheless, nitrogen use efficiency improved (i.e., decreased) from first to second parity, even though it did not improve from second to third parity or greater. Furthermore, nitrogen excretion continued to increase from first to third parity or greater. Nitrogen use efficiency and nitrogen excretion were negatively correlated (-0.56 to -0.40), signifying that dairy cows who partition more of the ingested nitrogen into products such as milk and meat, on average, also excrete less nitrogen. Milk urea nitrogen was, at best, weakly correlated with nitrogen use efficiency and nitrogen excretion; the correlations were between -0.01 and 0.06. In conclusion, several cow-level factors such as parity, stage of lactation, and breed were associated with the range of different nitrogen efficiency metrics investigated; moreover, even after accounting for such effects, 4.8% to 6.3% of the remaining variation in the nitrogen use efficiency and nitrogen balance metrics were attributable to intercow differences.

Traditional healers or bonesetters ("rebouteux") in France: A survey of their practice, profile, and customers.

BACKGROUND: In France, many people consult "bonesetters" for several medical reasons. Little is known about them. We aimed to investigate the practices of traditional healers in France as well as their profile and that of their customers. METHODS: This was a survey carried out in Metropolitan France. A 33-item questionnaire developed by a multidisciplinary group was sent to a sample of 148 traditional healers found on the Internet and by word of mouth. RESULTS: Of the 148 questionnaires sent, 89 (60.1 %) were returned and 67 (45.3 %) were analyzed: 51.5 % (n = 34) of respondents were men, and the mean (±standard deviation) age was 51.6 ±â€¯11.6 years. The respondents considered that they had received a gift of healing and were mainly magnetic healers (68.2 %). They became aware of this gift at a mean age of 19.9 ±â€¯14.1 years. The traditional healers practiced mainly in rural areas (54.5 %), at home (59.1 %), and used their hands to transmit energy (95.5 %). They advertised their practice mainly by word of mouth (89.4 %) and had a predominantly female clientele (78.1 %). Various diseases were treated, with the most frequent being subjective complaints (pain, stress, fatigue, insomnia) and dermatological complaints (eczema, accidental and post-herpes-zoster burns, psoriasis, and warts). Most respondents considered their activities to be complementary to conventional medicine, and 10.9 % considered them more effective. Some indicated that they did not consider themselves "healers" but rather "providers of relief". DISCUSSION: The results of this survey provide a better understanding of this network of local care that revolves around medicine.

Clonal evolution of myelofibrosis treated with hematopoietic transplantation, using RUXOLITINIB for chronic GvHD: A case report.

Deciphering the mutational patterns and/or the biomarkers that might predict clinical response in patients with myelofibrosis is primordial to make treatment decisions. In this report, we discuss the clinical history, pathological evaluation, and genomics findings in a patient with JAK2-positive myelofibrosis who developed a secondary myelodysplasia after hematopoietic stem cell transplantation and JAK1/2 inhibitor treatment. Using next-generation sequencing, a paired comparison of relapse-specific versus primary tumour mutations highlighted the dynamic clonal evolution at relapse, showing concurrently the complete eradication of the JAK2-positive clone and the expansion of a second JAK2-negative clone with additional mutations. Importantly, another unexpected finding was that myelodysplasia was not secondary to allogeneic transplantation as relapse was driven by the overgrowth of a preexisting mutated clone, probably fostered by initial treatment options. This case underlines the fact that determining the genetic changes associated with the primary disease and its evolution is crucial to accurately correlate variants frequency to treatment decision and/or treatment response.

Transfusion-associated hazards: A revisit of their presentation.

As a therapy or a support to other therapies, despite being largely beneficial to patients in general, transfusion it is not devoid of some risks. In a moderate number of cases, patients may manifest adverse reactions, otherwise referred to as transfusion-associated hazards (TAHs). The latest French 2016 haemovigilance report indicates that 93% of TAHs are minor (grade 1), 5.5% are moderate (grade 2) and 1.6% are severe (grade 3), with only five deaths (grade 4) being attributed to transfusion with relative certainty (imputability of level [or grade] 1 to 3). Health-care providers need to be well aware of the benefits and potential risks (to best evaluate and discuss the benefit-risk ratio), how to prevent TAHs, the overall costs and the availability of alternative therapeutic options. In high-income countries, most blood establishments (BEs) and hospital blood banks (HBBs) have developed tools for reporting and analysing at least severe transfusion reactions. With nearly two decades of haemovigilance, transfusion reaction databases should be quite informative, though there are four main caveats that prevent it from being fully efficient: (ai) reporting is mainly declarative and is thus barely exhaustive even in countries where it is mandatory by law; (aii) it is often difficult to differentiate between the different complications related to transfusion, diseases, comorbidities and other types of therapies in patients suffering from debilitating conditions; (aiii) there is a lack of consistency in the definitions used to describe and report some transfusion reactions, their severity and their likelihood of being related to transfusion; and (aiv) it is difficult to assess the imputability of a particular BC given to a patient who has previously received many BCs over a relatively short period of time. When compiling all available information published so far, it appears that TAHs can be analysed using different approaches: (bi) their pathophysiological nature; (bii) their severity; (biii) the onset scheme; (biv) a quality assessment (preventable or non-preventable); (bv) their impact on ongoing therapy. Moreover, TAHs can be reported either in a non-integrative or in an integrative way; in the latter case, presentation may also differ when issued by a blood establishment or a treating ward. At some point, a recapitulative document would be useful to gain a better understanding of TAHs in order to decrease their occurrence and severity and allow decision makers to determine action plans: this is what this review attempts to make. This review attempts to merge the different aspects, with a focus on the hospital side, i.e., how the most frequent TAHs can be avoided or mitigated.

Sinusoidal obstruction syndrome/veno-occlusive disease complication in lymphoma patients treated with oxaliplatin-based regimen: A case series report.

AIM: SOS/VOD is a relevant clinical syndrome that usually appears early after hematopoietic stem cell transplantation. The purpose of this article was to report a case series of SOS/VOD in non-susceptible patients and draw physicians' attention to the plausible relationship between liver injury and oxaliplatin-based chemotherapy, preceding autologous transplantation. METHODS: In this study, we report a case series of SOS/VOD in 4 lymphoma patients following autologous transplantation. The data were collected between July 2013 and November 2015 by analyzing patient's characteristics and outcomes. RESULTS: We noticed 4 severe cases of SOS with unusual presentations in patients who did exhibit few classical risk factors. These patients received R-DHAO before transplantation. CONCLUSIONS: Physicians need to be aware that oxaliplatin-based regimen could contribute to SOS/VOD complications in hematological patients.

Acute lymphoblastic leukemia relapsing after first-line pediatric-inspired therapy: a retrospective GRAALL study.

The outcome of adult patients with Philadelphia chromosome-negative acute lymphoblastic leukemia (Ph- ALL) relapsing after pediatric-inspired front-line therapy is ill known. Here 229 relapsing Ph- ALL younger adults (18-63 years) treated within the Group for Research on Adult Acute Lymphoblastic Leukemia (GRAALL)-2003/-2005 trials were considered. Salvage regimens consisted of potentially curative therapies in 194 cases, low-intensity therapies in 21, allogeneic stem cell transplant (allo-SCT) in 6 and best supportive care in 8. Overall, 77 patients received allo-SCT after relapse. The median follow-up was 3.1 years. A second complete remission (CR2) was achieved in 121 patients (53%). In multivariate analysis, only younger age <45 years (P=0.008) and CR1 duration ⩾18 months (P=0.009) predicted CR2. Overall survival (OS) at 2 and 5 years was 19.3% (14-24%) and 13.3% (8-18%), respectively. In CR2 patients, disease-free survival (DFS) at 2 and 5 years was 29.0% (21-38%) and 25% (17-33%). In multivariate analysis, CR1 duration ⩾18 months and allo-SCT after relapse were associated with longer DFS (P<0.009 and P=0.004, respectively) and longer OS (P=0.004 and P<0.0001, respectively). In conclusion, although younger adults relapsing after pediatric-inspired ALL therapies retain a poor outcome, some of them may be cured if CR1 duration ⩾18 months and if allo-SCT can be performed in CR2. New therapies are definitely needed for these patients.

Heterogeneity in meta-analyses of treatment of acute postoperative pain: a review.

BACKGROUND: Heterogeneity and its causes must be assessed using meta-analyses (meta-analysis). Especially in meta-analysis dealing with treatment of acute postoperative pain, the type of surgery is a source of heterogeneity. We aimed to assess whether the type of surgery is considered a source of heterogeneity in meta-analysis and how it is taken into account in meta-analysis evaluating the efficacy of treatment of acute postoperative pain. We further compared meta-analysis that pooled trials of surgeries with highly heterogeneous postoperative pain levels, the heterogeneous group, with meta-analysis that pooled trials involving surgeries with homogeneous pain levels, the homogenous group. METHODS: The meta-analysis reports available in Issue 3, 2011 of the electronic database of the Cochrane library and pooling results of randomized or quasi-randomized controlled trials that assessed the efficacy of treatment of acute postoperative pain alone were considered. A survey of experts established a rating of the postoperative pain levels for the type of surgery. For each meta-analysis, the different pain level ratings associated with the trials included in the meta-analysis were considered and the standard deviation (sd) of these ratings calculated. From the distribution of sd values, we defined the heterogeneous and homogeneous groups. RESULTS: Sixty-one meta-analyses were included; all assessed heterogeneity. Twenty-six meta-analyses considered the type of surgery as a subgroup (50% vs 38% in the homogeneous group vs heterogeneous group). Forty-four reports discussed the type of surgery as a source of clinical heterogeneity (85% vs 62% for the homogeneous vs heterogeneous group). Twenty-nine meta-analyses compared 'postoperative pain from dental surgery' to 'other type of surgery'. CONCLUSIONS: Meta-analyses evaluating treatment of postoperative pain should explore clinical heterogeneity associated with the type of surgery for better implications for practice.

Toxoplasmosis with hemophagocytic syndrome after bone marrow transplantation: diagnosis at autopsy.

Toxoplasmosis is a rare but well recognized opportunistic infection that can occur after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Besides encephalitis, other common presentations of Toxoplasma gondii infection are interstitial pneumonitis and myocarditis. Because of its non-specific clinical and biological signs and its lethal outcome, toxoplasmosis is often misdiagnosed and only revealed at autopsy. We report a case of a postmortem diagnosis of disseminated toxoplasmosis associated with hemophagocytic syndrome, which underlines the value of necropsy in cases of death after transplantation. We also discuss clinical presentations and risk factors that lead to toxoplasmosis in allo-HSCT recipients.

Outcome of treatment after first relapse in adults with acute lymphoblastic leukemia initially treated by the LALA-94 trial.

Fifty-four percent of adults with acute lymphoblastic leukemia (ALL) who entered the LALA-94 trial experienced a first relapse. We examined the outcome of these 421 adult patients. One hundred and eighty-seven patients (44%) achieved a second complete remission (CR). The median disease-free survival (DFS) was 5.2 months with a 5-year DFS at 12%. Factors predicting a better outcome after relapse were any transplant performed in second CR (P<0.0001), a first CR duration >1 year (P=0.04) and platelet level >100 x 10(9)/l at relapse (P=0.04). Risk groups defined at diagnosis and treatment received in first CR did not influence the outcome after relapse. The best results were obtained in a subset of patients who were eligible for allogeneic stem cell transplantation (SCT). Geno-identical allogeneic SCT was performed in 55 patients, and 3 patients received donor lymphocyte infusions. Forty-four transplantations were performed from an unrelated donor (of which four were cord blood). We conclude that most adult patients with recurring ALL could not be rescued using current available therapies, although allogeneic SCT remains the best therapeutic option.

[A case of hyperthyroidism due to functioning metastasis of differentiated thyroid carcinoma. Discussion and literature review]. / Un cas d'hyperthyroïdie par métastases sécrétantes de cancer thyroïdien différencié. Revue de la littérature.

We report on a very rare case of hyperthyroidism due to multiple autonomously functioning bone metastasis of papillary thyroid cancer in a 79-year-old woman. This situation remains extremely uncommon, as shown by our review of the literature; only 47 similar cases have been published from 1946 to 2005. The pathogenic mechanism remains largely unknown in spite of several hypotheses (conjunction in volume and differentiation, auto-antibodies). Hyperthyroidism can be severe, and often T3 levels are markedly more elevated than T4 levels. Apart from hyperthyroidism caused by the hormone-production, clinical features are similar to that of usual metastatic thyroid cancer, occurring in elderly women in most cases, and of follicular type on pathology. Metastases mostly occur in bones and lungs. Treatment relies mainly on radio-iodine ((131)I), which is efficient on hormonal disorders, and prognosis appears to be correlated with the ability of the metastatic sites to concentrate radio-iodine.

Early relapse after non myeloablative allogeneic stem cell transplantation in a patient with acute promyelocytic leukemia in complete molecular remission.

We described a 41-year-old patient with acute promyelocytic leukemia (APL) who experienced two successive relapses: one after all-trans retinoic acid (ATRA) treatment and chemotherapy, and another after ATRA treatment and chemotherapy, followed by autologous peripheral blood stem cell transplantation. A third complete remission (CR) was achieved with arsenic trioxide (As2O3) therapy. Mini-transplantation was performed as consolidation therapy. While the patient was in molecular remission at the beginning of conditioning regimen, a new relapse arose after transplantation at time of cell recovery. This raises a potential relationship between relapse and the severe immunosuppression induced by mini-transplantation. To our knowledge, this is the first description of a mini-allograft in an APL patient achieving molecular remission after As2O3 therapy.

Early Events Induced by the Elicitor Cryptogein in Tobacco Cells: Involvement of a Plasma Membrane NADPH Oxidase and Activation of Glycolysis and the Pentose Phosphate Pathway.

Application of the elicitor cryptogein to tobacco (cv Xanthi) is known to evoke external medium alkalinization, active oxygen species production, and phytoalexin synthesis. These are all dependent on an influx of calcium. We show here that cryptogein also induces calcium-dependent plasma membrane depolarization, chloride efflux, cytoplasm acidification, and NADPH oxidation without changes in NAD+ and ATP levels, indicating that the elicitor-activated redox system, responsible for active oxygen species production, uses NADPH in vivo. NADPH oxidation activates the functioning of the pentose phosphate pathway, leading to a decrease in glucose 6-phosphate and to the accumulation of glyceraldehyde 3-phosphate, 3- and 2-phosphoglyceric acid, and phosphoenolpyruvate. By inhibiting the pentose phosphate pathway, we demonstrate that the activation of the plasma membrane NADPH oxidase is responsible for active oxygen species production, external alkalinization, and acidification of the cytoplasm. A model is proposed for the organization of the cryptogein responses measured to date.

Involvement of Free Calcium in Action of Cryptogein, a Proteinaceous Elicitor of Hypersensitive Reaction in Tobacco Cells.

Treatment of suspension-cultured tobacco (Nicotiana tabacum var Xanthi) cells with cryptogein, a proteinaceous elicitor from Phytophthora cryptogea, induced a great stimulation of Ca2+ influx within the first minutes. Ca2+ influx is essential for the initiation of cryptogein-induced responses, since ethyleneglycol-bis([beta]-amino-ethyl ether)-N,N[prime]-tetraacetic acid or La3+, which block Ca2+ entrance, suppress cryptogein-induced responses such as extracellular alkalinization, active oxygen species, and phytoalexin production. Moreover, once initiated, these responses require sustained Ca2+ influx within the 1st h. A Ca2+ ionophore (A23187) was able to trigger an extracellular alkalinization but not the formation of active oxygen species and phytoalexins, even in the presence of cryptogein. Staurosporine, a protein kinase inhibitor that was recently reported to suppress cryptogein-induced responses (M.-P. Viard, F. Martin, A. Pugin, P. Ricci, J.-P. Blein [1994] Plant Physiol 104: 1245-1249), inhibited Ca2+ influx induced by cryptogein in a dose-dependent manner. These results suggest that protein phosphorylation followed by Ca2+ influx might be involved in the initial steps of cryptogein signal transduction.

Phospholipase activities associated with the tonoplast from Acer pseudoplatanus cells: identification of a phospholipase A1 activity.

The study of phospholipase activities associated with the tonoplast of Acer pseudoplatanus was performed in vitro with sn-2-[14C]acylphosphatidylcholine (PC) as a substrate. The hydrolysis of radiolabelled PC into [14C]phosphatidic acid and [14C]lyso-PC demonstrated the presence of phospholipase D and A1 activities, respectively, associated with the tonoplast of Acer pseudoplatanus. The vacuolar sap did not show any significant phospholipase activity. In a second step, the properties of the phospholipase A1 activity was studied using tonoplast endogenous PC labelled in vivo with [14C]choline as a substrate. The phospholipase A1 showed an optimal activity at pH about 6-6.5, did not necessarily require divalent cations, but was stimulated by Mg2+ and particularly by Ca2+. This work presents the first evidence for the presence of phospholipases A1 in plant cells.