A non-synonymous SNP in exon 3 of the KIT gene is responsible for the classic grey phenotype in alpacas (Vicugna pacos).

The alpaca classic grey phenotype is of particular interest to the industry. Until now, there were only indirect data suggesting that the KIT gene was involved in the classic grey phenotype. All exons of KIT in three black and three classic silvergrey alpacas were sequenced. Five non-synonymous SNPs were observed. There was only one SNP found that was present only in the silvergrey alpacas, and this was also the only SNP predicted to be damaging. This variant results in a change of a glycine (Gly) to an arginine (Arg) at amino acid position 126 (c.376G>A), occurring in the second Ig-like domain of the extracellular domain of KIT. Basic protein modelling predicted that this variant is likely destabilising. Therefore, an additional 488 alpacas were genotyped for this SNP using the tetra-primer amplification refractory mutation system PCR (Tetra-primer ARMS-PCR). All classic grey alpacas were observed to be heterozygous, and 99.3% of non-grey dark base colour alpacas were found to be homozygous for the wildtype allele in this position. These results confirm that the classic grey phenotype in alpacas is the result of a c.376G>A (p.Gly126Arg) SNP in exon 3 of KIT. These data also support the hypothesis that the grey phenotype is autosomal dominant and that the mutation is most likely homozygous lethal.

[How to avoid overmedicalization of the elderly patient ?] / Comment éviter la surmédicalisation du patient âgé ?

Over-medicalization is a broad concept, which also concerns the elderly patient. It encompasses both over-diagnosis and over-treatment. An increasing awareness of this issue has emerged since 2013, with the first " Preventing Overdiagnosis " conference. Currently, Evidence-Based Medicine does not prevent over-diagnosis. Indeed, the presence of geriatric characteristics such as multiple comorbidities, polypharmacy and frailty can lead to misdiagnosis and to potentially deleterious treatment. Subclinical hypothyroidism and Alzheimer's disease are two examples of pitfalls in the interpretation of biological and para-clinical data that may lead to the administration of useless treatment. Different issues are discussed to identify the causes of over-medicalization and to better prevent it.

La surmédicalisation est un concept large, qui concerne également le patient âgé. Elle englobe à la fois le surdiagnostic et sa conséquence à savoir le surtraitement. Une sensibilisation à ce sujet a émergé depuis 2013, date du premier congrès " Preventing Overdiagnosis ". Actuellement, l'Evidence-Based Medicine ne permet pas d'éviter le surdiagnostic chez le patient âgé. En effet, la présence de caracté- ristiques gériatriques telles que les multiples comorbidités, la polymédication et la fragilité peut mener à l'élaboration d'un diagnostic erroné et à l'instauration d'un traitement potentiellement délétère. L'hypothyroïdie subclinique et la maladie d'Alzheimer sont deux exemples de pièges potentiels à l'interprétation de données biologiques et paracliniques pouvant mener à l'administration d'un traitement futile. Différentes pistes sont abordées pour identifier les causes de la surmédicalisation et mieux la prévenir.

Sutherlandia frutescens modulates adrenal hormone biosynthesis, acts as a selective glucocorticoid receptor agonist (SEGRA) and displays anti-mineralocorticoid properties.

ETHNOPHARMACOLOGICAL RELEVANCE: Sutherlandia frutescens is a traditional African medicinal plant used in the treatment of stress and anxiety, while also exhibiting anti-inflammatory properties. AIM OF STUDY: The study aimed at linking anti-stress and anti-inflammatory properties of S. frutescens to its influence on glucocorticoid biosynthesis and the inflammatory response via steroid receptor interaction. MATERIALS AND METHODS: The influence of S. frutescens extracts and sutherlandioside B (SUB),10 and 30µM, on key steroidogenic enzymes was assayed in COS-1 cells. Effects were also assayed on basal and stimulated hormone levels in the adrenal H295R cell model. Agonist activity for transactivation and transrepression of the extract and SUB with the glucocorticoid- (GR) and mineralocorticoid receptor (MR) was subsequently investigated. RESULTS: Inhibitory effects of the extract towards progesterone conversion by CYP17A1 and CYP21A2 were significant. SUB inhibited CYP17A1 and 3ß-HSD2, while not affecting CYP21A2. In H295R cells, SUB decreased cortisol and androgen precursors significantly. The extract decreased total steroid production (basal and stimulated) with cortisol and its precursor, deoxycortisol, together with mineralocorticoid metabolites significantly decreased under forskolin stimulated conditions. S. frutescens extracts and SUB repressed NF-κB-driven gene expression without activating GRE-driven gene expression and while neither activated MR mediated gene transcription, both antagonized the effects of aldosterone via the MR. CONCLUSION: Data provide evidence linking anti-stress, anti-inflammatory and anti-hypertensive properties of S. frutescens to inhibition of steroidogenic enzymes and modulation of adrenal hormone biosynthesis. Findings suggesting S. frutescens and SUB exhibit dissociated glucocorticoid characteristics underline potential therapeutic applications in the treatment of inflammation and hypertension.

A practitioner's guide for exploring water quality patterns using principal components analysis and Procrustes.

To design sustainable water quality monitoring programs, practitioners must choose meaningful variables, justify the temporal and spatial extent of measurements, and demonstrate that program objectives are successfully achieved after implementation. Consequently, data must be analyzed across several variables and often from multiple sites and seasons. Multivariate techniques such as ordination are common throughout the water quality literature, but methods vary widely and could benefit from greater standardization. We have found little clear guidance and open source code for efficiently conducting ordination to explore water quality patterns. Practitioners unfamiliar with techniques such as principal components analysis (PCA) are faced with a steep learning curve to summarize expansive data sets in periodic reports and manuscripts. Here, we present a seven-step framework for conducting PCA and associated tests. The last step is dedicated to conducting Procrustes analysis, a valuable but rarely used test within the water quality field that describes the degree of concordance between separate multivariate data matrices and provides residual values for similar points across each matrix. We illustrate the utility of these tools using three increasingly complex water quality case studies in US parklands. The case studies demonstrate how PCA and Procrustes analysis answer common applied monitoring questions such as (1) do data from separate monitoring locations describe similar water quality regimes, and (2) what time periods exhibit the greatest water quality regime variability? We provide data sets and annotated R code for recreating case study results and as a base for crafting new code for similar monitoring applications.

Laryngeal chondrosarcoma: repeated laser and radiofrequency ablation in the palliative setting.

OBJECTIVE: The purpose of this article is to illustrate the use of radiofrequency and laser ablation in head and neck oncology and to describe the management of a case of laryngeal chondrosarcoma in a 90-year-old patient. CASE REPORT: A 90-year-old man, WHO performance status 3, with low-grade laryngeal chondrosarcoma was seen in the outpatients department at the end of 2008 for assessment of dysphonia. Total laryngectomy was considered to be too invasive and was consequently excluded. The patient was initially tracheotomized under local anaesthesia to relieve dyspnoea and was subsequently managed symptomatically by radiofrequency and laser ablation to ensure laryngeal disobstruction, allowing the patient to be extubated followed by speech therapy and oral feeding rehabilitation. DISCUSSION/CONCLUSION: This patient received symptomatic palliative treatment with a combination of radiofrequency and laser. Radiofrequency ablation can be applied in head and neck oncology as an alternative treatment to surgery allowing improvement of quality of life and survival.

Navigation in head and neck oncological surgery: an emerging concept.

Navigation surgery, initially applied in rhinology, neurosurgery and orthopaedic cases, has been developed over the last twenty years. Surgery based on computed tomography data has become increasingly important in the head and neck region. The technique for hardware fusion between RMI and computed tomography is also becoming more useful. We use such device since 2006 in head and neck carcinologic situation. Navigation allows control of the resection in order to avoid and protect the precise anatomical structures (vessels and nerves). It also guides biopsy and radiofrequency. Therefore, quality of life is much more increased and morbidity is decreased for these patients who undergo major and mutilating head and neck surgery. Here we report the results of 33 navigation procedures performed for 31 patients in our institution.

[Plasma selenium and peripartum cardiomyopathy in Bamako, Mali]. / Sélénium plasmatique et cardiomyopathie péripartum a Bamako (Mali).

Peripartum heart failure due to unexplained dilated cardiomyopathy is a common disorder as Savannak-Sahelian Africa. One of the many suspected risk factors identified is selenium deficiency. The purpose of this study was to measure plasma selenium levels in patients with peripartum heart failure due to cardiomyopathy in Bamako, Republic of Mali and compare data with healthy Sahalian women with the same obstetrical status. Plasma selenium was measured in a patient group consisting of 28 Malian women presenting peripartum heart failure and in a control group of 28 healthy breast-feeding Nigerien women of comparable age. The criteria for matching the two groups was parity (similar number of deliveries) since multiparity is a risk factor for peripartum cardiomyopathy. The Wilcoxon test (nonparametric) was used to compare the 2 groups considering up value < 0.05 as significant. Plasma selenium was significantly lower in patients from Mali than in controls from Niger (65 +/- 17 ng/ml vs. 78 +/- 17 ng/ml, p = 0.01). The results of this study showing lower plasma selenium in Bamako patients with peripartum cardiomyopathy than in a matching healthy control population confirms the previous data from the Niamey study.

Sélénium plasmatique et cardiomyopathie péripartum à Bamako (Mali)

L'insuffisance cardiaque péripartum, fréquente en Afrique soudano-sahélienne,est une cardiomyopathie dilatée de cause inconnue. Parmi les facteurs de risque identifiés une carence alimentaire en sélénium est discutée. Le but de ce travail est de définir le sélénium plasmatique de patientes en insuffisance cardiaque par cardiomyopathie péripartum à Bamako (République du Mali) et de le comparer à celui de sahéliennes en bonne santé à statut obstétrical identique. Afin de préciser le statut en sélénium à Bamako (République du Mali) les auteurs ont dosé le sélénium plasmatique chez 28 Maliennes atteintes de cardiomyopathie dilatée péripartum. Elles ont été appariées à 28 Nigériennes en bonne santé, d'âge comparable et allaitantes, constituant le groupe témoins. Le critère d'appariement a été la parité des malades et des témoins (nombre identique ou proche d'accouchements). Le test de Wilcoxon (test non paramétrique) a été appliqué pour comparer les 2 groupes, une valeur de p < 0,05 étant significative. Le sélénium plasmatique des patientes de Bamako (65 ± 17 ng/ml) est significativement plus bas que celui des Nigériennes en bonne santé de Niamey (78 ± 17 ng/ml, p = 0,01). Conclusion. La sélénémie des malades avec cardiomyopathie dilatée péripartum à Bamako est plus basse que dans la population témoin appariée,en accord avec les faits constatés antérieurement à Niamey

Technetium species induced in maize as measured by phosphorimager.

Leaves of plants have the ability to accumulate the long-lived fission product (99)Tc. In the present work, an attempt was made to separate and characterize technetium species formed in maize grown on soil contaminated with Tc(VII)O(4)(-) solution. Data obtained from selective extraction, a Phosphorimager and liquid scintillation were employed.

Iron, ferritin, transferrin, and transferrin receptor in the adult rat retina.

PURPOSE: The retina and other tissues need iron to survive. However, the normal iron metabolism in rodent retinas had not been characterized. This study was intended to investigate iron and iron homeostasis protein (ferritin, transferrin [Tf] and transferrin receptor [Tf-R]) distribution in 20- to 55-day-old rat retinas. METHODS: Iron was revealed on retinal sections directly by proton-induced x-ray emission (PIXE) and indirectly by electron microscopy (EM). Ferritin, Tf, and Tf-R proteins were localized by immunohistochemistry. Transferrin expression was localized by in situ hybridization (ISH). Transferrin and ferritin proteins and mRNA were analyzed by Western blot analysis and reverse transcription-polymerase chain reaction (RT-PCR), respectively. RESULTS: Iron is widely and unevenly distributed throughout the adult rat retina. The highest concentration was observed by PIXE in the choroid and the retinal pigmented epithelial cell (RPE) layer, and in inner segments of photoreceptors (IS). Outer segments of photoreceptors (OS) also contain iron. EM studies suggested the presence of iron inclusions inside the photoreceptor discs. Choroid, RPE, and IS showed a strong immunoreactivity for ferritin. Transferrin accumulated mainly in the IS and OS areas and in RPE cells but can also be detected slightly in retinal capillaries. Western blot analysis for Tf and ferritin confirmed their presence in the adult neural retina. By RT-PCR, H- and L-chains of ferritin and Tf mRNAs were expressed in neural retina, but the main sites of Tf synthesis observed by ISH were the RPE and choroid cell layers. Tf-R immunoreactivity was detected in the ganglion cell layer, inner nuclear layer, outer plexiform layer, IS, RPE, and choroid. These results were similar for all stages studied. CONCLUSIONS: For the first time, the present study characterized both iron and iron homeostasis proteins in rodent retinas. In the outer retina, iron and ferritin shared the same distribution patterns. In contrast, Tf, mainly synthesized by RPE cells and detected in OS and IS areas, probably helps to transport iron to photoreceptors through their Tf-R. This is a likely pathway for filling iron needs in the outer retina.

[Dilated cardiomyopathy and selenium deficiency in AIDS. Apropos of a case]. / Cardiomyopathie dilatée et déficit en sélénium au cours du SIDA. A propos d'un cas.

Cardiac-related death of HIV-positive patients is not rare. The etiology of AIDS-associated dilated cardiomyopathies often remains unknown, even at autopsy. We report an observation associated to a severe deficit in selenium. The patient had been diagnosed as HIV-positive 2 years before. He presented Pneumocystis carinii pneumonia then Cryptococcus meningitis. Two months later he was hospitalized for pancreatitis and cachexia. He presented global heart failure that lead to death. No microorganism was found in myocardium at autopsy but plasma selenium was dramatically decreased (24 micrograms/L). The deficit in selenium has been associated to a dilated cardiomyopathy in non-AIDS patients. HIV-positive patients have an early decrease in plasma selenium, this concentration is dramatically decreased in malnourished patients. Selenium deficit might be the cause of some of the AIDS-related dilated cardiomyopathies and selenium supplementation might be useful in these patients.

The enzymatic antioxidant system in blood and glutathione status in human immunodeficiency virus (HIV)-infected patients: effects of supplementation with selenium or beta-carotene.

To investigate the effects of selenium or beta-carotene supplementation in human immunodeficiency virus (HIV)-infected patients, who are known to have deficiencies of selenium and vitamin A, we evaluated the blood enzymatic antioxidant system, including superoxide dismutase (SOD), selenodependent glutathione peroxidase (GPX), and catalase (Cat); glutathione (GSH) status; and plasma selenium concentration. The placebo group consisted of 18 HIV-infected patients with no supplementation, the selenium group was composed of 14 patients receiving oral selenium treatment, and the beta-carotene group comprised 13 patients receiving oral beta-carotene supplementation. All groups were studied for 1 y. At the beginning of the study, a significantly higher SOD activity (P < 0.001) was observed in all HIV-infected patients compared with uninfected control subjects, and GPX activity at baseline was higher in the placebo (P < 0.004) and selenium (P < 0.014) groups than in the control subjects. These higher enzyme activities could be related to an increased synthesis of these enzymes in erythrocyte precursors under oxidative stress. Moreover, we observed significantly lower GSH values in all HIV-infected patients than in control subjects at the beginning of the study (P < 0.001). After selenium or beta-carotene supplementation, no significant difference was observed for SOD activity compared with baseline. On the contrary, GPX activity increased significantly after selenium treatment (P < 0.04 between 3 and 6 mo), whereas a slight increase was found after beta-carotene treatment. Similarly, a significant increase in GSH values was observed at 12 mo compared with baseline both after selenium supplementation (P < 0.001) and beta-carotene supplementation (P < 0.01). Because GPX and GSH play an important role in the natural enzymatic defense system in detoxifying hydrogen peroxide in water, selenium supplementation could be of great interest in protecting cells against oxidative stress. The lower efficiency of beta-carotene could be attributed to the seriousness of the pathology at the time of recruitment into the beta-carotene group.

Fatty acids and plasma antioxidants in HIV-positive patients: correlation with nutritional and immunological status.

OBJECTIVE: To investigate red blood cell (RBC) and plasma fatty acids (FA) in HIV-positive patients in relation to oxidative stress and nutritional or immunological status. DESIGN AND METHODS: FA, plasma selenium, vitamins A and E were measured in 95 patients divided into four groups according to CD4 cells. RESULTS: Poly- and di-unsaturated FA (PUFA, DUFA) decreased and saturated FA (SFA) increased in RBC in the patients below 400/mm3 and in plasma in the patients below 50/mm3. RBC SFA correlated to CD4 cells, PUFA to MDA. Unlike vitamin E, plasma vitamin A and selenium decreased in most groups. Plasma SFA and MUFA correlated negatively to selenium and PUFA and DUFA to vitamin E. No correlation was found between PUFA and nutritional markers. CONCLUSION: FA seem to be modified during HIV infection by oxidative stress and disease evolution, but not by denutrition.