Regression of fibrous dysplasia in response to denosumab therapy: a report of two cases

We present two patients with fibrous dysplasia who showed a decrease in lesional size and activity after denosumab therapy. Both patients also experienced a reduction in pain and bone turnover markers, which had not been accomplished during previous bisphosphonate therapy. These cases highlight the potential of denosumab to decrease lesional size in fibrous dysplasia. This finding has been reported in mice, but not in humans. Denosumab may be considered when bisphosphonates are not tolerated or not effective (enough), or in severe cases as neoadjuvant therapy to improve surgical possibilities and outcome. In addition, these results show that Na[F-18]F PET-CT is suitable for detecting change in each fibrous dysplasia lesion distinctively.Imaging- and therapeutic targets in neoplastic and musculoskeletal inflammatory diseas

Scintigraphic assessment of bone status at one year following hip resurfacing : comparison of two surgical approaches using SPECT-CT scan

Objectives: To study the vascularity and bone metabolism of the femoral head/neck following hip resurfacing arthroplasty, and to use these results to compare the posterior and the trochanteric-flip approaches. Methods: In our previous work, we reported changes to intra-operative blood flow during hip resurfacing arthroplasty comparing two surgical approaches. In this study, we report the vascularity and the metabolic bone function in the proximal femur in these same patients at one year after the surgery. Vascularity and bone function was assessed using scintigraphic techniques. Of the 13 patients who agreed to take part, eight had their arthroplasty through a posterior approach and five through a trochanteric-flip approach. Results: One year after surgery, we found no difference in the vascularity (vascular phase) and metabolic bone function (delayed phase) at the junction of the femoral head/neck between the two groups of patients. Higher radiopharmaceutical uptake was found in the region of the greater trochanter in the trochanteric-flip group, related to the healing osteotomy. Conclusions: Our findings using scintigraphic techniques suggest that the greater intra-operative reduction in blood flow to the junction of the femoral head/neck, which is seen with the posterior approach compared with trochanteric flip, does not result in any difference in vascularity or metabolic bone function one year after surgery

Parent-child interactions and adolescent anxiety: a systematic review

Parental behaviours have been implicated in the development and maintenance of anxiety in children and young people; however the degree to which findings apply to adolescents specifically remains unclear. We conducted a systematic review of studies examining the evidence for an association between parental behaviours and adolescent anxiety. Twenty two studies were identified. The results of this systematic review provide fairly consistent preliminary evidence for an association between anxiety and perceived parental control and anxious rearing in adolescence. The findings relating to an association between adolescent anxiety and perceived parental rejection and lack of warmth are somewhat less consistent. Methodological shortcomings in the studies mean that these results should be interpreted with caution. Future research should be conducted using observational and experimental design with adolescents from referred, clinical populations to help identify the critical parental processes and clarify the direction of effects

Treatment solutions to cure Xylella fastidiosa diseased plants

This opinion addresses the question of the efficacy of current treatment solutions to cure Xylella fastidiosa diseased plants, and discusses the experimental treatments under evaluation by two research groups in Apulian olive orchards infected by strain CoDiRO (Complesso del Disseccamento Rapido dell'Olivo). The increasing problems from newly emerging vascular bacterial diseases and the limited success to cure plants from such infections have stimulated numerous studies on treatments with chemical and biological compounds. Under field conditions, various formulations of copper and zinc as spray or root drench are currently used while further options, for example the application of bioactive substances, are at an experimental stage. In Apulia, preliminary results from intensive treatments with such formulations, in combination with the use of good crop management practices, reported more vigorous new growth of diseased trees. However, results provided so far confirmed the continued presence of X. fastidiosa after the treatments under evaluation. This is in agreement with current knowledge that there are no means to cure plants from this bacterial disease, in the sense of eliminating the pathogen from plant tissues. The reported positive response of the treated olive trees is most probably due to the effect of micronutrients and other bioactive compounds that, together with soil cultivation and agronomical practices, improve the vigour of the plants and their resilience to stress caused by bacterial infections. Notwithstanding the preliminary status of these findings, the Panel acknowledged the potentially positive effects of such treatments in prolonging the productive phase of olive trees and their putative relevance for the management of olive orchards, particularly in the containment area where eradication of the pathogen is considered no longer possible. The Panel also concluded that long-term studies are needed to confirm that the reported positive effects on crop performance can be sustained over many years

Incidence of cancer in the area around Amsterdam Airport Schiphol in 1988–2003: a population-based ecological study

BACKGROUND: Amsterdam Airport Schiphol is a major source of complaints about aircraft noise, safety risks and concerns about long term adverse health effects, including cancer. We investigated whether residents of the area around Schiphol are at higher risk of developing cancer than the general Dutch population. METHODS: In a population-based study using the regional cancer registry, we estimated the cancer incidence during 1988–2003 in residents of the area surrounding Schiphol. We defined a study area based on aircraft noise contours and 4-digit postal code areas, since historical data on ambient air pollution were not available and recent emission data did not differ from the background urban air quality. RESULTS: In residents of the study area 13 207 cancer cases were diagnosed, which was close to the expected number, using national incidence rates as a reference (standardized incidence ratio [SIR] 1.02). We found a statistically significantly increased incidence of hematological malignancies (SIR 1.12, 95% confidence interval [CI]: 1.05, 1.19), mainly due to high rates for non-Hodgkin lymphoma (SIR 1.22, 95% CI: 1.12, 1.33) and acute lymphoblastic leukemia (SIR 1.34, 95% CI: 0.95, 1.83). The incidence of cancer of the respiratory system was statistically significantly decreased (SIR 0.94, 95% CI: 0.90, 0.99), due to the low rate in males (SIR 0.89). In the core zone of the study area, cancer incidence was slightly higher than in the remaining ring zone (rate ratio of the core zone compared to the ring zone 1.05, 95% CI 1.01, 1.10). This was caused by the higher incidence of cancer of the respiratory system, prostate and the female genital organs in the core zone in comparison to the ring zone. CONCLUSION: The overall cancer incidence in the Schiphol area was similar to the national incidence. The moderately increased risk of hematological malignancies could not be explained by higher levels of ambient air pollution in the Schiphol area. This observation warrants further research, for example in a study with focus on substances in urban ambient air pollution, as similar findings were observed in Greater Amsterdam

Pest categorisation of Pseudocercospora pini-densiflorae

Following a request from the European Commission, the EFSA Plant Health (PLH) Panel performed a pest categorisation of Pseudocercospora pini-densiflorae, a well-defined and distinguishable fungal species of the family Mycosphaerellaceae. The regulated harmful organism is the anamorph Cercoseptoria pini-densiflorae (synonym Cercospora pini-densiflorae) with the corresponding teleomorph Mycosphaerella gibsonii. P. pini-densiflorae causes a needle blight of Pinus spp. also known as Cercospora blight of pines or Cercospora needle blight. P. pini-densiflorae is reported from sub-Saharan Africa, Central and South America, Asia and Oceania, but not from the EU. The pathogen is regulated in Council Directive 2000/29/EC (Annex IIAI) as a quarantine organism whose introduction into the EU is banned on plants (other than fruit and seeds) and wood of Pinus. The pest could enter the EU via plants for planting and other means (uncleaned seed, cut branches of pine trees, isolated bark, growing media accompanying plants, and mycorrhizal soil inocula). Hosts are widespread in the EU and favourable climatic conditions are present in Mediterranean countries. Pinus halepensis, Pinus nigra, Pinus pinea, Pinus pinaster and Pinus sylvestris are reported to be highly susceptible to the pathogen. The pest would be able to spread following establishment after introduction in the EU mainly on infected plants for planting. The pest introduction could have impacts in nurseries and young plantations. Cleaning seeds from needles and removing infected seedlings and pine litter from affected nurseries can reduce the risk of establishment in nurseries and of spread from nurseries to forests, especially given the limited scale of splash dispersal. The main knowledge gaps concern (i) the role of means of entry/spread other than plants for planting and (ii) the potential consequences in mature tree plantations and forests. The criteria assessed by the Panel for consideration as potential quarantine pest are met. For regulated nonquarantine pests, the criterion on the pest presence in the EU is not met

Pest categorisation of Ips cembrae

The Panel on Plant Health performed a pest categorisation of the large larch bark beetle, Ips cembrae (Heer) (Coleoptera: Curculionidae, Scolytinae), for the EU. I. cembrae is a well-defined and distinguishable species, native to Europe and recognised mainly as a pest of larch (Larix spp.) and occasionally of pine (Pinus spp.) and spruce (Picea spp.). It is distributed in 16 Member States of the EU and listed in Annex IIB of Council Directive 2000/29/EC. Protected zones are in place in Greece, Ireland and the United Kingdom (Northern Ireland and Isle of Man). Wood, wood products, bark and wood packaging material are considered as pathways for this pest, which is also able to disperse by flight. The insects normally establish on fallen or weakened trees but, when their populations are high, can also mass-attack healthy trees. The males produce aggregation pheromones that attract conspecifics of both sexes. The insects also inoculate pathogenic fungi to their hosts. There are one to two generations per year. Before establishing their broods, the young adults need to proceed to maturation feeding either within the bark of the tree where they developed or in 2–18 years old twigs. I. cembrae has been expanding its geographical range in Europe during the second half of the 20th century. Sanitary thinning or clear felling is the major control methods. Quarantine measures are implemented to prevent entry in the protected zones. All criteria for consideration as potential protected zone quarantine pest are met. The criteria for considering I. cembrae as a potential regulated non-quarantine pest are not met since plants for planting are not viewed as a major pathway

Susceptibility of Phoenix roebelenii to Xylella fastidiosa

Following a request from the European Commission, the EFSA Plant Health Panel analysed a dossier submitted by Costa Rica Authorities to reach a conclusion on the host status of Phoenix roebelenii for Xylella fastidiosa. The Panel wishes first to stress the difficulties faced in providing compelling evidence for the non-susceptibility status of any particular plant species. The Panel acknowledges that the listing of P. roebelenii as a host of X. fastidiosa rests on a single report from California. Because isolation of X. fastidiosa from some hosts can be difficult, the Panel considers that the failure to isolate X. fastidiosa from P. roebelenii cannot be used to totally discard the detection of X. fastidiosa by ELISA and PCR. The Panel concludes that the detection of X. fastidiosa by two independent techniques provides sufficient evidence, although not totally conclusive, for the listing of P. roebelenii as a X. fastidiosa host plant. Concerning the survey data provided in the Costa Rican dossier, the Panel wishes to stress that such surveys cannot demonstrate the non-host status but can only provide a probability bound, upper estimate of the proportion of infected plants in the field. In the present case, and assuming all survey parameters to be optimal, the 95% confidence incidence threshold obtained is 0.2%, leaving the possibility that close to 25,000 P. roebelenii plants could be infected but undetected in the country. Accepting a scenario of local, non-systemic infection of P. roebelenii by X. fastidiosa would further increase uncertainties. In addition, the absence of data on the vector infection pressure further affects the ability to derive meaningful information on the P. roebelenii host status from the survey data. Appropriately conducted mechanical and/or vector-mediated inoculation experiments are critical to reach a more solid conclusion on the X. fastidiosa host status of P. roebelenii

Pest risk assessment of Radopholus similis for the EU territory

The Panel on Plant Health performed a pest risk assessment on Radopholus similis, the burrowing nematode for the EU. The quantitative assessment focused on entry, establishment, spread and impact on tropical and subtropical ornamental host plants, the main pathways for entry of R. similis into the EU. Infested consignments are expected to enter the risk assessment area on ornamentals under all scenarios. For citrus, which is a closed pathway for entry, outdoor establishment was assessed. Establishment may only take place after successful transfer from ornamental plants to citrus production systems. This event is called ‘shift’ in this assessment, to indicate that this is an unusual transfer. It has been estimated that establishment of this nematode in the open field in the EU citrus production areas under current temperatures is possible in most parts of the citrus production area in the EU. Temperature conditions will prevent the nematode from establishing only in the northernmost citrus areas and at higher altitudes in the south. Host plants for planting originating from infested places of production (greenhouses) within the risk assessment area are considered the main pathway for spread within the risk assessment area. Under current climatic conditions, the population of R. similis is not expected to reach damaging population levels in the open field. In case of increased temperatures due to global warming, the nematode population may reach damaging levels in very few places outdoors. Currently, main impact is considered for ornamental greenhouse production in the risk assessment area. Impact will be either caused by direct plant growth reductions or loss due to phytosanitary measures applied on regulated plants. Despite the fact that R. similis is globally considered as one of the most destructive plant parasitic nematodes, the impact in the risk assessment area is considered low

MAGE-A cancer/testis antigens inhibit MDM2 ubiquitylation function and promote increased levels of MDM4

Melanoma antigen A (MAGE-A) proteins comprise a structurally and biochemically similar sub-family of Cancer/Testis antigens that are expressed in many cancer types and are thought to contribute actively to malignancy. MAGE-A proteins are established regulators of certain cancer-associated transcription factors, including p53, and are activators of several RING finger-dependent ubiquitin E3 ligases. Here, we show that MAGE-A2 associates with MDM2, a ubiquitin E3 ligase that mediates ubiquitylation of more than 20 substrates including mainly p53, MDM2 itself, and MDM4, a potent p53 inhibitor and MDM2 partner that is structurally related to MDM2. We find that MAGE-A2 interacts with MDM2 via the N-terminal p53-binding pocket and the RING finger domain of MDM2 that is required for homo/hetero-dimerization and for E2 ligase interaction. Consistent with these data, we show that MAGE-A2 is a potent inhibitor of the E3 ubiquitin ligase activity of MDM2, yet it does not have any significant effect on p53 turnover mediated by MDM2. Strikingly, however, increased MAGE-A2 expression leads to reduced ubiquitylation and increased levels of MDM4. Similarly, silencing of endogenous MAGE-A expression diminishes MDM4 levels in a manner that can be rescued by the proteasomal inhibitor, bortezomid, and permits increased MDM2/MDM4 association. These data suggest that MAGE-A proteins can: (i) uncouple the ubiquitin ligase and degradation functions of MDM2; (ii) act as potent inhibitors of E3 ligase function; and (iii) regulate the turnover of MDM4. We also find an association between the presence of MAGE-A and increased MDM4 levels in primary breast cancer, suggesting that MAGE-A-dependent control of MDM4 levels has relevance to cancer clinically