Possible case of hyperparathyroidism in a Roman period skeleton from the Dakhleh Oasis, Egypt, diagnosed using bone histomorphometry

A histomorphometric study of thin femoral head sections of a skeletal sample from the Dakhleh Oasis, Egypt, dated from circa 36 B.C. to 400 A.D., identified an adult female (Dk31-A1) in her mid-50s with a high percentage resorption surface with tunneling resorption as is typically found in hyperparathyroidism. Five static histomorphometric bone parameters were measured with the following results for this individual: 1) mean wall thickness, 41.94 micron, 2) trabecular bone volume, 18.54%, 3) surface volume, 4,070 mm2/cm3, 4) mean trabecular diameter, 132 microns, and 5) total resorption surface, 12.31%. The overall histomorphometric features and differential diagnosis support the diagnosis of hyperparathyroidism. We conclude that histomorphometry of dried bone, particularly in this case where preservation is ideal, is a valuable investigative technique for paleopathology.     

Fate of plant-derived secondary metabolites in three moth species (Syntomis mogadorensis,Syntomeida epilais,andCreatonotos transiens)

Summary Larvae of three moth species were compared with respect to strategies used to cope with secondary metabolites (allelochemicals) present in their diet.Syntomeida epilais is monophagous and accepted only oleander (which contains cardenolides, CG). CG were detected as stored products in the larvae and also in the faeces and exuviae. Pure CG (digoxin and gitoxin) which do not occur in oleander fed on oleander leaves were sequestered as the oleander CG.Syntomis mogadorensis is polyphagous: given a choice larvae avoided plants with a high load of allelochemicals. Upon shortage of preferred plants they ate a wide variety of plants which contain alkaloids, terpenes, or phenolics. Of these allelochemicals, alkaloids and CG were mainly recovered in the faeces and only minute fractions in the larvae.Creatonotos transiens larvae behaved similarly toSyntomis in terms of polyphagy and non-resorption. However, the larvae took up and stored pyrrolizidine alkaloids (PA) such as heliotrine selectively.Creatonotos is thus polyphagous (a generalist) but also a PA-specialist which exploits PA as defensive agents, as a morphogen for the male pheromone gland, and as a precursor for the male pheromone.Abbreviations CG cardiac glycosides - IG iridoid glycosides - PA pyrrolizidine alkaloids - GLC gas liquid chromatography - MS mass spectrometry     

Nutrient resorption from senescing leaves in two Stipa species native to central Argentina

Abstract Nutrient resorption from senescing leaves enables plants to conserve and reuse nutrients. As such, it could be expected that plant species adapted to infertile soils have a higher nutrient resorption efficiency (percentage reduction of nutrients between green and senesced leaves) and/or higher nutrient resorption proficiency (absolute reduction of nutrients in senesced leaves) than those adapted to fertile soils. Our objective was to compare nitrogen (N) and phosphorous (P) resorption of two congener grasses that successfully occupy uplands of relatively low fertility (Stipa gynerioides) or lowlands of relatively high fertility (Stipa brachychaeta) in natural grasslands of central Argentina. The two Stipa species did not differ in N and P resorption efficiency, but S. gynerioides had a higher N and P resorption proficiency than S. brachychaeta. As a consequence, leaf‐level N and P use efficiency were higher in the species adapted to low fertility conditions than in the species adapted to high fertility conditions. The higher nutrient resorption proficiency of S. gynerioides was also associated with relatively low leaf‐litter decomposition and nutrient release rates found in a previous study.     

The Loss of Cbl-Phosphatidylinositol 3-Kinase Interaction Perturbs RANKL-mediated Signaling,Inhibiting Bone Resorption and Promoting Osteoclast Survival

Cbl is an adaptor protein and an E3 ligase that plays both positive and negative roles in several signaling pathways that affect various cellular functions. Tyrosine 737 is unique to Cbl and is phosphorylated by Syk and Src family kinases. Phosphorylated Cbl Tyr⁷³⁷ creates a binding site for the p85 regulatory subunit of PI3K, which also plays an important role in the regulation of bone resorption by osteoclasts. To investigate the role of Cbl-PI3K interaction in bone homeostasis, we examined the knock-in mice (Cbl^YF/YF) in which the PI3K binding site in Cbl is ablated due to the mutation in the regulatory tyrosine. We report that in Cbl^YF/YF mice, despite increased numbers of osteoclasts, bone volume is increased due to defective osteoclast function. Additionally, in ex vivo cultures, mature Cbl^YF/YF osteoclasts showed an increased ability to survive in the presence of RANKL due to delayed onset of apoptosis. RANKL-mediated signaling is perturbed in Cbl^YF/YF osteoclasts, and most interestingly, AKT phosphorylation is up-regulated, suggesting that the lack of PI3K sequestration by Cbl results in increased survival and decreased bone resorption. Cumulatively, these in vivo and in vitro results show that, on one hand, binding of Cbl to PI3K negatively regulates osteoclast differentiation, survival, and signaling events (e.g. AKT phosphorylation), whereas on the other hand it positively influences osteoclast function.     

An approach to integrated data assessment in a proficiency test on the enumeration of Escherichia coli

Aims: To develop appropriate statistical approaches to plan and evaluate proficiency tests for the enumeration of Escherichia coli, addressing, in particular, a possible but frequently unavoidable lack of test sample homogeneity. Methods and Results: Each of 50 laboratories analysed two samples of a stabilized suspension of E. coli in duplicate, using various media, inoculation methods, and incubation times and conditions. In parallel, the E. coli suspension was tested by the organiser for homogeneity and stability. Escherichia coli counts followed a log‐normal distribution. After eliminating, by Youden analysis, two data sets that were considered outliers and eight data sets for underperformance of the laboratories (substantial lack of repeatability), the standard deviation of the mean was about 0·06 log₁₀ units. There was no evidence of bimodality of the data. Lack of homogeneity of distribution of bacteria had a strong effect on measurement uncertainty, in addition to laboratory bias and method repeatability. The homogeneity decreases during storage of the individual test vials; this effect could be modelled by the known kinetics of inactivation of micro‐organisms. The results were confirmed by Monte Carlo simulations. Conclusions: By a tailored analysis of proficiency testing data, it is possible to distinguish the effect of lack of homogeneity, laboratory bias and method repeatability, on the measurement uncertainty. Significance and Impact of the Study: A statistic tool is provided to solve problems related to lack of stability of microbiological test material and to separate the effects of sample inhomogeneity from the performance of the individual laboratory.     

Alteration of the phenology of leaf senescence and fall in winter deciduous species by climate change: effects on nutrient proficiency

Leaf senescence in winter deciduous species signals the transition from the active to the dormant stage. The purpose of leaf senescence is the recovery of nutrients before the leaves fall. Photoperiod and temperature are the main cues controlling leaf senescence in winter deciduous species, with water stress imposing an additional influence. Photoperiod exerts a strict control on leaf senescence at latitudes where winters are severe and temperature gains importance in the regulation as winters become less severe. On average, climatic warming will delay and drought will advance leaf senescence, but at varying degrees depending on the species. Warming and drought thus have opposite effects on the phenology of leaf senescence, and the impact of climate change will therefore depend on the relative importance of each factor in specific regions. Warming is not expected to have a strong impact on nutrient proficiency although a slower speed of leaf senescence induced by warming could facilitate a more efficient nutrient resorption. Nutrient resorption is less efficient when the leaves senesce prematurely as a consequence of water stress. The overall effects of climate change on nutrient resorption will depend on the contrasting effects of warming and drought. Changes in nutrient resorption and proficiency will impact production in the following year, at least in early spring, because the construction of new foliage relies almost exclusively on nutrients resorbed from foliage during the preceding leaf fall. Changes in the phenology of leaf senescence will thus impact carbon uptake, but also ecosystem nutrient cycling, especially if the changes are consequence of water stress.     

Evaluation of proficiency testing as a method of assessing competence to screen cervical smears

Evaluation of proficiency testing as a method of assessing competence to screen cervical smears Regular proficiency testing of pathologists and cytotechnologists who undertake the analysis of cervical smears has been carried out in cytology laboratories in the North Thames (West) Region since 1989. The protocol followed is one that has been adopted nationally. Since the scheme started, laboratory personnel from 17 cytology laboratories in the Region have participated and seven rounds of testing have been completed. Nine hundred and seventy-one tests were carried out and a pass rate of 96.4% was recorded. Two hundred and forty-seven cytologists took the test on at least one occasion and 63 cytologists took part in all seven rounds. Our results indicate that proficiency testing is capable of detecting cytologists who consistently perform below an acceptable standard and require retraining. They also show that even the most competent screeners can miss an abnormal smear. Seven cytologists who had proved their competence to screen on six occasions, missed an abnormal smear on the seventh, despite the fact that they were screening under test conditions when their vigilance should have been at its peak. Our findings indicate that false-negative reporting will inevitably occur during manual screening, and emphasize the need for further research into the causes and prevention of screening error. Evaluation des tests d'aptitude comme méthode d'appréciation de la compétence à lire les frottis cervico-utérins de dépistage Le passage régulier de tests d'aptitude pour les pathologistes et les cytotechniciens qui prennent en charge l'analyse de frottis cervico-utérins est utilisé dans les laboratoires de cytologie de la région North Thames (West) depuis 1989. Le protocole choisi est l'un de ceux qui ont été adoptés au niveau national. Depuis le début de ce programme, 7 sessions de tests ont été organisées et le personnel de 17 laboratoires de cytologie de la région a participé. Neuf cent soixante et onze tests ont été pratiqués et le taux de participation enregistré est de 96,4%. Deux cent quarante sept cytologistes ont fait le test au moins une fois et 63 cytologistes ont passé les 7 sessions de tests. Nos résultats indiquent que les tests d'apitude sont capables d'identifier les cytologistes qui ont besoin d'une formation car leur résultats aux tests sont régulièrement en dessous des standards acceptables. Ils montrent également que même les “screeners” les plus compétents peuvent passer à côté d'un frottis anormal. Sept cytologistes ayant montré leur compétence pour la lecture des frottis de dépistage sur 6 tests n'ont pas été capable de détecter un frottis anormal sur le septième test, bien que cette lecture ait été faite dans des conditions de test où leur vigilance aurait dû être à son maximum. Ces résultats indiquent qu'il est impossible d‘éviter les faux négatifs au cours du “screening manuel” et confirment la n?essité de poursuivre les recherches sur les causes des erreurs de lecture et sur leur prévention. Die Ergebnisse der Laistungstests als Grundlage für die Fähigkeit gynäkologische Abstriche auszuwerten Regelmässige Leistungstests von Zytopathologen und Zytotechnikerinnen beim Auswerten gynäkologischer Abstriche wurden seit 1989 in den Labors der Nord-Themse Region durchgeführt. Das Testprotokoll entspricht dem landesweit angewandten. Inzwischen nahmen 17 Labors an insgesamt 7 Testrunden teil. Die Gesamtzahl der Tests beträgt 971 wobei 96,4% der Teilnehmer die Tests bestanden. 247 Teilnehmer nahmen an zumindest einem Test, 63 an allen sieben teil. Die Auswertungen ergaben, dass auf diese Weise Zytologen mit unterdurch schnittlicher Leistung identifiziert und einem Zusatztraining zugeführt werden können. Sie zeigen aber auch, dass selbst die Erfahrendsten gelegentlich positive Befunde übersehen. Sieben Teilnehmer begingen diesen Fehler nach sechs fehlerfreien Durchgängen beim siebten Test trotz der bekannten Testsituation. Dies bedeutet, dass Fehler bei nichtautomatischer Auswertung unvermeidbar sind. Die Ursachenforschung muss weitergeführt werden.     

The effects of short-term fluoride ingestion on bone formation and resorption in the rat femur

Summary The femurs from rats given 120 ppm fluoride in their drinking water for 4 weeks were examined with histological, histochemical, and radiographic methods. Blood removed from the rats prior to sacrifice was analyzed for calcium, phosphorus, and alkaline phosphatase. Results of this study indicated that the ingestion of fluoride produced wide osteoid seams on the periosteal surface of the femoral diaphysis within 4 weeks. The increase in osteoid appeared to be due to an increase in the number of osteoid-producing cells (osteoblasts) along with a subsequent delay in the mineralization of this tissue. The metabolic activity of osteoblasts did not appear to be affected since the intracellular production of acid and alkaline phosphatase was not inhibited. However, due to the high concentration of fluoride ingested, abnormal collagen deposition and a change in bone mineral may have combined to cause a delay in osteoid mineralization. Mineralization was also delayed in the distal femoral epiphyseal plate resulting in an increase in the number of hypertrophied cells. Resorption of metaphyseal trabecular bone, presumably formed prior to fluoride administration, was increased causing a reduction in the amount of trabeculae extending into the shaft of the femur. Concurrent with these changes in bone, the serum levels of calcium, phosphorus, and alkaline phosphatase remained within normal ranges.