Search

Contains fulltext : 252036.pdf (Publisher’s version ) (Closed access) BACKGROUND: Most physicians encounter pregnant women with cancer incidentally, leading to a lack of expertise or confidence to inform and treat these patients based on the most recent guidelines and expert opinions. In the Netherlands, a national multidisciplinary tumour board for cancer, infertility and pregnancy (CIP-MDT) was founded in December 2012, including 35 specialists from a variety of disciplines. This study evaluates the frequency of consultation of the CIP-MDT, the types of questions asked and the satisfaction of consulting physicians with its existence. METHODOLOGY: Of all requests to the CIP-MDT between December 2012 and June 2021, tumour type, stage, gestational age at diagnosis and recommendations were collected and analysed. For evaluating the methods of the CIP-MDT, a survey with questions regarding experiences with the CIP-MDT and its impact on treatment decisions was sent out to physicians that consulted the CIP-MDT. RESULTS: Recommendations (n = 213) concerned preferred and safest options for imaging, treatment options during pregnancy, possible effects on the child and fertility preserving options. Most frequently discussed malignancies were breast cancer (n = 66), cervical cancer (n = 34), haematological malignancies (n = 32) and melanoma (n = 21). The questionnaire was completed by 54% of the physicians (n = 50). Satisfaction with the recommendations of the CIP-MDT was high, and 94% of the physicians informed their patients about consulting the CIP-MDT and felt supported by the received recommendations. DISCUSSION: The national Dutch CIP-MDT contributes to a high level of satisfaction among physicians requesting advice. Further research should be executed to confirm that a CIP-MDT improves the outcomes for pregnant women and their children.

Fish body condition and growth are two interrelated traits closely associated with species life history and fitness, whose trade-off can ultimately impact population dynamics albeit seldom empirically demonstrated. They can intricately affect survival rates, which are particularly relevant for species under exploitation. Using individual spatiotemporal information in Northwestern Mediterranean, we document for the first time the existence of a trade-off between condition and growth in regulating survival dynamics in two important fish species for the Mediterranean fisheries that are characterized by contrasting life histories. For the European hake (Merluccius merluccius), a benthopelagic species, juveniles' body condition was detected to be positively linked to survival and negatively associated with the growth of this age group. For the red mullet (Mullus barbatus), the same pattern was observed for young adults. We also show that the observed patterns on a regional level have a clear spatial dependence as we found that observed body condition over a local scale had a broad effect on the population dynamics of the whole region, with the Ebro delta area emerging as the demographic engine of the two species. We discuss our results in the context of fisheries management and underline the importance of improving current stock assessment models and spatially based fishery management towards incorporating body condition and growth due to their influence on important parameters such as survival., We thank all the dedicated people of the Instituto Español de Oceanografía (IEO, Spain), who have worked on the research vessels and MEDITS surveys. MEDITS surveys are funded by IEO and the European Union (EU) through the European Maritime and Fisheries Fund (EMFF) within the National Program of collection, management and use of data in the fisheries sector and support for scientific advice regarding the Common Fisheries Policy. This study was supported by the PANDORA project (H2020, grant agreement 773713). GK was partially funded by the Erasmus+ Programme of the European Union. GK, AE, EG and MH acknowledge funding from the COCOCHA project (PID2019-110282RA-I00, Spanish Ministry of Science and Innovation). MGP also thanks the IMPRESS project (RTI2018-099868-B-I00, Spanish Ministry of Science and Innovation).

Age-related bone loss is a failure of balanced bone turnover and diminished skeletal mechanoadaptation. Estrogen receptors, ERα and ERβ, play critical roles in osteoprotective regulation activated by estrogen and mechanical signals. Previous studies mainly focused on ERα and showed that osteocyte-ERα (Ot-ERα) regulated trabecular, but not cortical bone, and played a minor role in load-induced cortical adaptation. However, the role of Ot-ERβ in bone mass regulation remains unrevealed. To address this issue, we characterized bone (re)modeling and gene expression in male and female mice with Ot-ERβ deletion (ERβ-dOT) and littermate control (LC) at 10 weeks (young) or 28 weeks (adult) of age, as well as their responses to in vivo tibial compressive loading. Increased cancellous bone mass appeared in the L

Type I Diabetes Mellitus (T1DM) and periodontitis have long been thought to be biologically connected. Indeed, T1DM is a risk factor for periodontal disease. With the population of diabetic individuals growing, it's more important than ever to understand the negative consequences of diabetes on the periodontium and the mechanisms. The aim of this study was to find out the early effects of T1DM on the periodontium without any experimentally induced periodontitis.We established the Streptozotocin (STZ)-induced diabetic mouse model and examined the periodontium 8 weeks later by histology, molecular and cellular assays. Micro-computed tomographic (𝜇CT) imaging and in vivo fluorochrome labeling were also employed to quantify bone volume and mineral apposition rates (MAR).The histologic appearance of epithelium tissue, connective tissue, and periodontal ligament in the diabetic condition was comparable to that of control mice. However, immune cell infiltration in the gingiva was dramatically elevated in the diabetic mice, which was accompanied by unmineralized connective tissue degeneration. Bone resorption activity was significantly increased in the diabetic mice, and quantitative 𝜇CT demonstrated the bone volume, the ratio of bone volume over tissue volume, and cementum-enamel junction to alveolar bone crest (CEJ-ABC) in the diabetic condition were equivalent to those in the control group. In vivo fluorochrome labeling revealed increased MAR and bone remodeling in the diabetic mice. Further investigation found the diabetic mice had more osteoprogenitors recruited to the periodontium, allowing more bone formation to balance the enhanced bone resorption.STZ-induced T1DM mice, at an early stage, have elevated gingival inflammation and soft tissue degeneration and increased bone resorption; but still the alveolar bone was preserved by recruiting more osteoprogenitor cells and increasing the rate of bone formation. We conclude that inflammation and periodontitis precede alveolar bone deterioration in diabetes. This article is protected by copyright. All rights reserved.

Calcium/calmodulin (CaM)-dependent protein kinase kinase 2 (CaMKK2) regulates bone remodeling through its effects on osteoblasts and osteoclasts. However, its role in osteocytes, the most abundant bone cell type, and the master regulator of bone remodeling, remains unknown. Here we report that the conditional deletion of CaMKK2 from osteocytes using Dentine matrix protein 1 (Dmp1)-8kb-Cre mice led to enhanced bone mass only in female mice owing to a suppression of osteoclasts. Conditioned media isolated from female CaMKK2-deficient osteocytes inhibited osteoclast formation and function in in vitro assays, indicating a role for osteocyte-secreted factors. Proteomics analysis revealed significantly higher levels of extracellular calpastatin, a specific inhibitor of calcium-dependent cysteine proteases calpains, in female CaMKK2 null osteocyte conditioned media, compared to media from female control osteocytes. Further, exogenously added non-cell permeable recombinant calpastatin domain I elicited a marked, dose-dependent inhibition of female wild-type osteoclasts and depletion of calpastatin from female CaMKK2-deficient osteocyte conditioned media reversed the inhibition of matrix resorption by osteoclasts. Our findings reveal a novel role for extracellular calpastatin in regulating female osteoclast function and unravel a novel CaMKK2-mediated paracrine mechanism of osteoclast regulation by female osteocytes.

10 pages, 9 figures, 1 table, supplementary data https://doi.org/10.1016/j.rsma.2022.102709.-- Data availability: Data will be made available on request, It is widely known that the abundance and distribution dynamics of populations of small pelagic clupeid fish, such as sardines and anchovies, are affected by large-scale climate variability, which may lead to changeovers to new regimes of small pelagics. However, long-distance climatic oscillations, such as El Niño/La Niña and the Pacific Decadal Oscillation, have been little explored in the Western Mediterranean Sea. We investigated the possible effects of the South Oscillation Index (i.e. the atmospheric oscillation coupled with the El Niño/La Niña) and Pacific Decadal Oscillation on fluctuations in catches of European anchovy (Engraulis encrasicolus) and sardine (Sardina pilchardus) in the Western Mediterranean Sea, and their association with regional climate oscillations (i.e. the Atlantic Multidecadal Oscillation, the North Atlantic Oscillation, the Western Mediterranean Oscillation index, and the Arctic Oscillation). The study covered two periods: (a) landings between 1950 and 2016; and (b) abundance, biomass, and physical condition (i.e., relative condition index) between 2004 and 2016. The main large-scale climatic oscillations in the region were studied using General Additive Models to investigate the relationship between a time series of species measures of European sardine and anchovy from Geographical Subarea 06. Results show that the long-term Pacific Decadal Oscillation favours sardine landings, whereas the combined effect of the Western Mediterranean Oscillation Index and the Atlantic Multidecadal Oscillation favours anchovy. We discuss potential links between the present findings and changes in the plankton community caused by prevailing winds in the region driven by long-distance climate oscillations and their impact on the reduction in small pelagic fish populations in the study area, This study is a contribution to the PELWEB project (“Winners, losers and shifts of PELagic food WEB changes in the western Mediterranean Sea: from ecosystem consequences to future projections”, CTM2017-88939-R, 2018–2020), and to “Fostering the capacity of marine ecosystem models to PROject the cumulative effects of global change and plausible future OCEANS” (PROOCEANS): Funding by Ministerio de Ciencia e Innovación, Proyectos de I+D+I (RETOS-PID2020-118097RB-I00), With the institutional support of the ‘Severo Ochoa Centre of Excellence’ accreditation (CEX2019-000928-S)

Nitrous oxide (N2O) is a powerful greenhouse gas and an ozone-depleting compound whose synthesis and release have traditionally been ascribed to bacteria and fungi. Although plants and microalgae have been proposed as N2O producers in recent decades, the proteins involved in this process have been only recently unveiled. In the green microalga Chlamydomonas reinhardtii, flavodiiron proteins (FLVs) and cytochrome P450 (CYP55) are two nitric oxide (NO) reductases responsible for N2O synthesis in the chloroplast and mitochondria, respectively. However, the molecular mechanisms feeding these NO reductases are unknown. In this work, we use cavity ring-down spectroscopy to monitor N2O and CO2 in cultures of nitrite reductase mutants, which cannot grow on nitrate or nitrite and exhibit enhanced N2O emissions. We show that these mutants constitute a very useful tool to study the rates and kinetics of N2O release under different conditions and the metabolism of this greenhouse gas. Our results indicate that N2O production, which was higher in the light than in the dark, requires nitrate reductase as the major provider of NO as substrate. Finally, we show that the presence of nitrate reductase impacts CO2 emissions in both light and dark conditions, and we discuss the role of NO in the balance between CO2 fixation and release.

21 pages, 8 figures, 3 tables, supplementary material https://www.frontiersin.org/articles/10.3389/fmars.2021.570354/full#supplementary-material.-- Data Availability Statement: The datasets presented in this article are not readily available because the dataset is available by request to the Spanish Institute of Oceanography. Requests to access the datasets should be directed to webmaster@ieo.es, Small pelagic fish (SPF) in the western Mediterranean Sea are key elements of the marine food web and are important in terms of biomass and fisheries catches. Significant declines in biomass, landings, and changes in the age/size structure of sardine Sardina pilchardus and anchovy Engraulis encrasicolus have been observed in recent decades, particularly in the northern area of the western Mediterranean Sea. To understand the different patterns observed in SPF populations, we analyzed key life history traits [total length at age, length at maturity, gonadosomatic index (GSI), and body condition (Kn)] of sardine and anchovy collected between 2003 and 2017, from different fishing harbors distributed along a latitudinal gradient from northern to southern Spain. We used Generalized Linear Models (GLM) to estimate the length at maturity and Generalized Additive Models (GAMs) to test the relationship with environmental variables (seawater temperature, water currents, and net primary productivity). The life history traits of both species presented seasonal, interannual and latitudinal differences with a clear decline in length at age, length at first maturity, and body condition, for both species in the northern part of the study area. In the southern part, on the contrary, life history traits did not present a clear temporal trend. The environmental conditions partially explained the long-term changes in life history traits, but the selected variables differed between areas, highlighting the importance of regional oceanographic conditions to understand the dynamics of small pelagic fish. The truncated length-at-age pattern for both species with the disappearance of the larger individuals of the population could have contributed to the poor condition of small pelagic fish populations in the northern part of the western Mediterranean Sea in recent years. In the south area, recent declines in body condition for sardine and anchovy were observed and could be a possible first sign for future population declines. This study highlights the importance of understanding the trade-off between the energy invested in reproduction, maintenance and growth at seasonal and interannual level to advance our knowledge on how environmental and human pressures influence population dynamics of small pelagic fish at local and regional scales, This study was carried out within the Spanish Research project PELWEB (CTM2017-88939-R) funded by Spanish Ministry of Science, Innovation and Universities and the European Research Contract SPELMED (SC NR 02-TENDER EASME/EMFF/2016/032XXX) funded by EC EASME. Fisheries data collection has been co-funded by the EU through the European Maritime and Fisheries Fund (EMFF) within the National Program of collection, management and use of data in the fisheries sector and support for scientific advice regarding the Common Fisheries Policy (Regulation, EU 2017/1004), With funding from the Spanish government through the ‘Severo Ochoa Centre of Excellence’ accreditation (CEX2019-000928-S)

Nitrogen (N) is an essential constituent of all living organisms and the main limiting macronutrient. Even when dinitrogen gas is the most abundant form of N, it can only be used by fixing bacteria but is inaccessible to most organisms, algae among them. Algae preferentially use ammonium (NH4+) and nitrate (NO3−) for growth, and the reactions for their conversion into amino acids (N assimilation) constitute an important part of the nitrogen cycle by primary producers. Recently, it was claimed that algae are also involved in denitrification, because of the production of nitric oxide (NO), a signal molecule, which is also a substrate of NO reductases to produce nitrous oxide (N2O), a potent greenhouse gas. This review is focused on the microalga Chlamydomonas reinhardtii as an algal model and its participation in different reactions of the N cycle. Emphasis will be paid to new actors, such as putative genes involved in NO and N2O production and their occurrence in other algae genomes. Furthermore, algae/bacteria mutualism will be considered in terms of expanding the N cycle to ammonification and N fixation, which are based on the exchange of carbon and nitrogen between the two organisms.

Introduction/Background The purpose of this study was to assess obstetric and maternal outcome of pregnant patients with diagnosis of Hodgkin lymphoma (HL) to guide physicians in clinical management. Methodology Clinical data of pregnant patients diagnosed with HL between 1969 and 2018 were collected from the registry of the International Network on Cancer, Infertility and Pregnancy (INCIP). For survival analysis of classical HL treated with an ABVD-based regimen, non-pregnant controls were selected based on stage and prognostic score at diagnosis. Results The median gestational age at diagnosis of 134 eligible patients was 20 weeks (range: 3–37). Antenatal chemotherapy was initiated in 53.7% of patients. Ten (7.5%) early pregnancies were terminated. One foetus deceased in the third trimester after three cycles of chemotherapy. In total, 120 (89.6%) pregnancies ended in a live birth. Preterm delivery was observed in 47 (40.1%) singleton pregnancies. Birth weight percentiles were lower in children prenatally exposed to oncological treatment and 17.9% were small for gestational age at birth (figure 1). Four children (3.5%) had major congenital malformations. Five-year progression-free survival (PFS) for HL during pregnancy was 82.5% and 90.9% for early (n=62) and advanced stage (n=15). Five-year overall survival (OS) was 97.3% and 100%, respectively. Although not significant, patients with early stage HL appeared to have inferior PFS compared with matched non-pregnant controls (n=62, figure 2), more clearly seen in the subgroup that initiated chemotherapy during pregnancy (n=45). OS was comparable between both groups, supporting the effectiveness of salvage therapy. For advanced stage HL survival was similar to controls, albeit small numbers. Conclusion Survival of patients diagnosed with early stage HL during pregnancy appears not statistically different from matched non-pregnant controls, however future prospective research is necessary to investigate the efficacy of chemotherapy during pregnancy. Awareness of complications as preterm delivery and low birth weight is important. Disclosure This project has received funding from the European Union’s Horizon 2020 research and innovation program under grant agreement No 647047. We are grateful to the Research Foundation-Flanders (FWO., grant no G070514N) and ESGO (European Society of Gynaecological Oncology) for their support. FA is senior clinical investigator of the F.W.O. MJH was supported by Charles University research project Progres Q28 and Q34 and by grant MH CZ - DRO (‘Kralovske Vinohrady University Hospital - FNKV, 00064173’). The funding sources did not influence study design. There are no conflicting interests to declare.

This paper considers the manufacturing process of the Oloid by means of numerical control machining. Firstly, the requirements of the end part were studied, and it was decided to manufacture the Oloid via gravity die casting, and its necessary mold to be produced by CNC machining. In order to do so, the gating system and mold had to be designed and tested using sand casting methods. When the test results were optimal the die was machined and the part cast. During this process the CAD/CAM workflow was object of observation and study, which allowed for insight and conclusions on the design process.

Background The purpose of this study was to assess obstetric and maternal outcome of pregnant patients with diagnosis of Hodgkin lymphoma (HL) registered by the International Network on Cancer, Infertility and Pregnancy (INCIP) to guide physicians in clinical management. Methods Clinical data of pregnant patients diagnosed with HL between 1969 and 2018 were collected from the INCIP registry. For survival analysis of classical HL treated with an ABVD-based regimen, non-pregnant controls were selected based on stage and prognostic score at diagnosis. Results The median gestational age at diagnosis of 134 eligible patients was 20 weeks (range: 3 – 37). Antenatal chemotherapy was initiated in 53.7% of patients. Ten (7.5%) early pregnancies were terminated. One foetus deceased in the third trimester after three cycles of chemotherapy. In total, 120 (89.6%) pregnancies ended in a live birth. Preterm delivery was observed in 47 (40.1%) singleton pregnancies. Birth weight percentiles were lower in children prenatally exposed to oncological treatment and 17.9% were small for gestational age at birth. Four children (3.5%) had major congenital malformations. Five-year progression-free survival (PFS) for HL during pregnancy was 82.5% and 90.9% for early (n = 62) and advanced stage (n = 15). Five-year overall survival (OS) was 97.3% and 100%, respectively. Although not significant, patients with early stage HL appeared to have inferior PFS compared with matched non-pregnant controls (n = 62), more clearly seen in the subgroup that initiated chemotherapy during pregnancy (n = 45). OS was comparable between both groups, supporting the effectiveness of salvage therapy. For advanced stage HL survival was similar to controls, albeit small numbers. Conclusions Although further prospective research on the efficacy of chemotherapy during pregnancy is necessary, survival of patients diagnosed with early stage HL during pregnancy appears not to be statistically different from matched non-pregnant controls, Awareness of complications as preterm delivery and low birth weight is important in this population. Clinical trial identification NTC00330447. Legal entity responsible for the study The authors. Funding European Union’s Horizon 2020 Research and Innovation Program under grant agreement No 647047 Research Foundation-Flanders (FWO., grant no G070514N) and ESGO (European Society of Gynaecological Oncology) Charles University Research Project Progres Q28 and Q34 and by grant MH CZ - DRO ("Kralovske Vinohrady University Hospital - FNKV, 00064173"). Disclosure All authors have declared no conflicts of interest.

Pseudoephedrine (PSE) is a stereoisomer of ephedrine that is commonly used as a nasal decongestant in combination with other anti-inflammatory drugs for the symptomatic treatment of some common pathologies such as common cold. Herein, we describe for the first time the effects of PSE on T-cell activation events. We found that PSE inhibits interleukin-2 (IL-2) and tumor necrosis factor (TNF) alpha-gene transcription in stimulated Jurkat cells, a human T-cell leukemia cell line. To further characterize the inhibitory mechanisms of PSE at the transcriptional level, we examined the transcriptional activities of nuclear factor kappa B (NF-κB), nuclear factor of activated T cells (NFAT), and activator protein-1 (AP-1) transcription factors and found that PSE inhibited NF-κB-dependent transcriptional activity without affecting either the phosphorylation, the degradation of the cytoplasmic NF-κB inhibitory protein, IκBα or the DNA-binding activity. However, phosphorylation of the p65/RelA subunit was clearly inhibited by PSE in stimulated cells. In addition, PSE inhibited the transcriptional activity of NFAT without interfering with the calcium-induced NFAT dephosphorylation event, which represents the major signaling pathway for its activation. NFAT cooperates with c-Jun, a compound of the AP-1 complex, to activate target genes, and we also found that PSE inhibited both JNK activation and AP-1 transcriptional activity. These findings provide new mechanistic insights into the potential immunomodulatory activities of PSE and highlight their potential in designing novel therapeutic strategies to manage inflammatory diseases.

The purpose of this study was to compare the effects of estrogen deficiency and bone mass loss on normal knee cartilage in mature rabbits. Bilateral ovariectomy (OVX) was performed in 13 rabbits, 6 of which also received systemic glucocorticoid for 4 weeks. Seven additional healthy rabbits were used as controls. Bone mineral density (BMD) was measured by dual X-ray absorptiometry in lumbar spine, knee, and subchondral bone of the knee at baseline and 22 weeks after OVX. After sacrifice, the knees were dissected, macroscopy was assessed, and histological cartilage abnormalities were evaluated according to the Mankin score. Correlations of Mankin with BMD at different regions were also performed. When compared to baseline, differences in BMD were only found in spine and knee of the animals receiving glucocorticoids. All the animals subjected to OVX had a significantly higher Mankin score than controls. Mankin was upper in OVX animals receiving glucocorticoids, but differences were not significant. The Mankin score was inversely related with BMD in lumbar spine (r = -0.67; p < 0.01). Although low bone mineral density contributes to the minor osteoarthritic alterations observed in our model, estrogen deficiency itself seems to act directly to induce the main pathogenic effects in healthy cartilage of the rabbit.

[EN]: Background and objective: Hypertensive disorders of pregnancy could be favoured by polymorphisms in genes affecting vascular physiology. The aim of our work was to study several variants in the genes regulating oxidative stress, plasma lipids metabolism and endothelial function (observational study). Material and methods: We studied the −930A/G polymorphism of the CYBA gene promoter, the apolipoprotein E (APOE) genotype and the methylene-tetrahydrofolate reductase (MTHFR) gene C677T polymorphism in 134 healthy pregnant women, 266 pregnant with non-proteinuric hypertension (NPH) and 184 patients with preeclampsia (PE). Results: The GG genotype of the CYBA gene promoter was present in 32.1% of the control population, 38.7% of patients with NPH (P=0.19) and 21.2% of the women with PE (P=0.03). A higher frequency of 3/ 4 and 4/ 4 genotypes of APOE was observed in patients with PE or NPH compared with controls (P, [ES]: Fundamento y objetivo: Nos propusimos valorar en un estudio observacional si algunos polimorfismos en genes que regulan el estrés oxidativo, los niveles de homocisteina y el metabolismo de los lípidos, podrían predisponer a diferentes trastornos hipertensivos del embarazo. Material y métodos: Estudiamos el polimorfismo −930A/G del gen promotor del CYBA, el genotipò de la apolipoproteína E (ApoE) y el polimorfismo C677T del gen de la metilen tetrahidrofolato-reductasa (MTHFR) en 134 embarazadas sanas, 266 embarazadas con hipertensión no proteinurica (HNP) y 184 pacientes con preeclampsia (PE). Resultados: El genotipo GG del promotor del gen del CYBA estuvo presente en el 32,1% de la población de control, en el 38,7% de las pacientes con HNP (p=0,19) y el 21,2% de las mujeres con PE (p=0,03). Los pacientes con PE o HNP, en comparación con los controles, mostraron una mayor frecuencia de genotipos 3/ 4 y 4/ 4 (p

Increased fracture risk is commonly reported in cancer patients receiving radiotherapy, particularly at sites within the field of treatment. The direct and systemic effects of ionizing radiation on bone at a therapeutic dose are not well-characterized in clinically relevant animal models. Using 20-week-old male C57Bl/6 mice, effects of irradiation (right hindlimb; 2 Gy) on bone volume and microarchitecture were evaluated prospectively by microcomputed tomography and histomorphometry and compared to contralateral-shielded bone (left hindlimb) and non-irradiated control bone. One week postirradiation, trabecular bone volume declined in irradiated tibias (-22%; p 0.0001) and femurs (-14%; p = 0.0586) and microarchitectural parameters were compromised. Trabecular bone volume declined in contralateral tibias (-17%; p = 0.003), and no loss was detected at the femur. Osteoclast number, apoptotic osteocyte number, and marrow adiposity were increased in irradiated bone relative to contralateral and non-irradiated bone, whereas osteoblast number was unchanged. Despite no change in osteoblast number 1 week postirradiation, dynamic bone formation indices revealed a reduction in mineralized bone surface and a concomitant increase in unmineralized osteoid surface area in irradiated bone relative to contralateral and non-irradiated control bone. Further, dose-dependent and time-dependent calvarial culture and in vitro assays confirmed that calvarial osteoblasts and osteoblast-like MC3T3 cells were relatively radioresistant, whereas calvarial osteocyte and osteocyte-like MLO-Y4 cell apoptosis was induced as early as 48 hours postirradiation (4 Gy). In osteoclastogenesis assays, radiation exposure (8 Gy) stimulated murine macrophage RAW264.7 cell differentiation, and coculture of irradiated RAW264.7 cells with MLO-Y4 or murine bone marrow cells enhanced this effect. These studies highlight the multifaceted nature of radiation-induced bone loss by demonstrating direct and systemic effects on bone and its many cell types using clinically relevant doses; they have important implications for bone health in patients treated with radiation therapy.

The case is reported of acute retinal necrosis with bilateral involvement due to Varicella Zoster virus in a 77 year-old man. Polymerase chain reaction (PCR) of aqueous humor was positive for Varicella Zoster virus (VZV). He developed a Kyrieleis' vasculitis a month after the starting treatment, when the PCR analysis was negative.PCR is a quick and safe technique, with a high sensitivity and specificity of 97%, useful to diagnose and monitor the viral activity. The intervention must be urgent, due to the dramatically rapid evolution. Oral famciclovir oral is good alternative owing to its bioavailability.

Aim : To determine the efficacy of flow cytometry (FC) in the assessment of bone marrow (BM) in B-cell non-Hodgkin lymphoma (B-NHL). FC is a common practice, but is far from being validated. Methods and results : Morphological analysis and FC immunophenotyping were perfomed on 421 samples. T-cell lymphomas, Hodgkin's disease, chronic lymphocytic leukaemia and hairy cell leukaemia were not included in the study. Clonality was assessed by the standard κ/λ/CD19 test. Aberrant immunophenotypes present in the B-cell subpopulation were also investigated. A double-step procedure was employed in all cases to increase the sensitivity of the FC procedure. Of 380 evaluable samples, 188 corresponded to follicular lymphoma (FL), 58 to diffuse large B-cell lymphoma (DLBCL), 57 to mantle cell lymphoma (MCL), seven to Burkitt's lymphoma and the remaining 70 samples to other low-grade lymphomas. Morphological marrow infiltration was found in 148 cases, and flow immunophenotyping identified 138 cases with BM involvement. A concordance between the two methods was detected in 298 cases (79%). There was a discordance in 82 cases (21%): morphology positive/FC negative in 46 cases and morphology negative/FC positive in 36 (61% of all cases with discordance were from FL). There was no difference in outcome when patients with discordances were compared with patients without discordances. Conclusions : Most samples showed concordance between morphological and FC results. FC identified BM involvement in the absence of morphological infiltration. Morphology/FC discordance seems to have no influence on the outcome of FL patients.

We report a case of simultaneous diagnosis of chronic lymphocytic leukemia (CLL) and acute myeloid leukemia (AML), in which the use of flow cytometry analysis allowed the demonstration of two different cell populations and the study of both immunophenotyping patterns with a large panel of monoclonal antibodies (MoAbs). CLL cells showed a typical immunophenotype with coexpression of B cell markers with CD5, CD23, CD43, and weak surface immunoglobulin light chain restriction expression, whereas the AML population had a very uncommon phenotype with expression of myeloid markers and CD56 and lack of expression of other natural killer (NK) antigens, CD34 and HLA-DR. After chemotherapeutic treatment of AML with two induction courses, the patient achieved complete remission of the AML with persistence of a CD19/CD5 positive population. After consolidation chemotherapy, this latter population was no longer detectable despite the presence of lymphoid nodules in a bone marrow biopsy. Six months after diagnosis, the patient relapsed with AML and died shortly afterwards.

Basic information on the distribution and habitat preferences of ecologically important species is essential for their management and protection. In the Mediterranean Sea there is increasing concern over elasmobranch species because their biological (ecological) characteristics make them highly vulnerable to fishing pressure. Their removal could affect the structure and function of marine ecosystems, inducing changes in trophic interactions at the community level due to the selective elimination of predators or prey species, competitors and species replacement. In this study Bayesian hierarchical spatial models are used to map the sensitive habitats of the three most caught elasmobranch species (Galeus melastomus, Scyliorhinus canicula, Etmopterus spinax) in the western Mediterranean Sea, based on fishery-dependent bottom trawl data. Results show that habitats associated with hard substrata and sandy beds, mainly in deep waters and with a high seabed gradient, have a greater probability registering the presence of the studied species than those associated with muddy shallow waters. Temperature and chlorophyll-α concentration show a negative relationship with S. canicula occurrence. Our results identify some of the sensitive habitats for elasmobranchs in the western Mediterranean Sea (GSA06 South), providing essential and easy-to-use interpretation tools, such as predictive distribution maps, with the final aim of improving management and conservation of these vulnerable species.

Altered bone turnover is a key pathologic feature of chronic kidney disease-mineral and bone disorder (CKD-MBD). Expression of TGF-β1, a known regulator of bone turnover, is increased in bone biopsies from individuals with CKD. Similarly, TGF-β1 mRNA and downstream signaling is increased in bones from jck mice, a model of high-turnover renal osteodystrophy. A neutralizing anti-TGF-β antibody (1D11) was used to explore TGF-β's role in renal osteodystrophy. 1D11 administration to jck significantly attenuated elevated serum osteocalcin and type I collagen C-telopeptides. Histomorphometric analysis indicated that 1D11 administration increased bone volume and suppressed the elevated bone turnover in a dose-dependent manner. These effects were associated with reductions in osteoblast and osteoclast surface areas. Micro-computed tomography (µCT) confirmed the observed increase in trabecular bone volume and demonstrated improvements in trabecular architecture and increased cortical thickness. 1D11 administration was associated with significant reductions in expression of osteoblast marker genes (Runx2, alkaline phosphatase, osteocalcin) and the osteoclast marker gene, Trap5. Importantly, in this model, 1D11 did not improve kidney function or reduce serum parathyroid hormone (PTH) levels, indicating that 1D11 effects on bone are independent of changes in renal or parathyroid function. 1D11 also significantly attenuated high-turnover bone disease in the adenine-induced uremic rat model. Antibody administration was associated with a reduction in pSMAD2/SMAD2 in bone but not bone marrow as assessed by quantitative immunoblot analysis. Immunostaining revealed pSMAD staining in osteoblasts and osteocytes but not osteoclasts, suggesting 1D11 effects on osteoclasts may be indirect. Immunoblot and whole genome mRNA expression analysis confirmed our previous observation that repression of Wnt/β-catenin expression in bone is correlated with increased osteoclast activity in jck mice and bone biopsies from CKD patients. Furthermore, our data suggest that elevated TGF-β may contribute to the pathogenesis of high-turnover disease partially through inhibition of β-catenin signaling.

Introduction Dental implant osseointegration can be impaired in medical conditions with low bone mass, such as glucocorticoid-induced osteoporosis. Intermittent human parathyroid hormone (PTH) [1-34] administration has shown relevant anabolic bone activity in various animal models of osteoporosis. Therefore, we studied the effects of intermittent PTH [1-34] on bone response around titanium implants in experimental osteoporosis induced by ovariectomy and glucocorticoid administration. Methods Titanium dental implants were placed in the proximal tibia metaphysis in 38 animals. Twenty-eight rabbits had undergone bilateral ovariectomy and further methylprednisolone administration for 4 weeks to induce osteoporosis. Ten healthy rabbits were used as controls. At week 8, osteoporotic rabbits started saline vehicle or intermittent PTH administration for 12 weeks. Bone mineral density (BMD) was assessed in peri-implant area, lumbar spine, and global and subchondral knee bone at baseline, and weeks 6 and 20. Animal sacrifice was carried out at week 21. Afterward, tibiae were removed for μCT morphometry and undecalcified sections were evaluated by light and scanning electron microscopy. Results PTH increased bone-to-implant contact compared with control rabbits or vehicle administration in osteoporotic rabbits (P

SummaryPurposeSynoviopathy contributes to cartilage degradation in osteoarthritis (OA). Intermittent parathyroid hormone (PTH) [1-34] administration inhibits terminal differentiation of human chondrocytes and prevents cartilage damage. We aimed to determine whether PTH [1-34] could modify synovial changes in experimental OA preceded by osteoporosis (OP).MethodsTwenty osteoporosis (OP) rabbits underwent knee surgery to induce OA. They were administered either saline vehicle or PTH for 10 weeks. Ten healthy rabbits were used as controls. Following sacrifice, synovial changes were assessed by Krenn synovitis score, immunohistochemistry for macrophages (RAM-11), B and T lymphocytes, type I collagen, parathyroid hormone 1 receptor (PTH1R), and anti-proliferating cell nuclear antigen (PCNA). Synovial mRNA levels of Col1A1, IL-1β, cyclooxygenase 2 (COX-2), matrix-degrading metalloproteinases (MMP-9, MMP-13), and monocyte chemotactic protein-1 (MCP-1), as well as protein expression of PTH1R were also determined. Cartilage damage was analyzed by Mankin score.ResultsOPOA + vehicle rabbits showed an increase in synovitis score vs controls (P = 0.003), mainly due to synovial hyperplasia and fibrosis, while PTH reduced these changes (P = 0.017). Mankin and Krenn scores were well correlated in all groups (r = 0.629, P = 0.012). Immunostaining for RAM-11 and B lymphocytes was increased (P ≤ 0.05), whereas PTH1R protein levels tended to be higher in OPOA + vehicle animals vs controls. PTH did not modify RAM-11 staining or PTH1R levels; however, it restored PTH1R localization to the vicinity of synovial vessels. PTH also decreased type I collagen, MCP-1, and MMP-13 expression (P

The aim of this study was to assess the importance of immunohistochemical markers in the diagnosis of pigmented conjunctival lesions. Due to the difficulty of making an exact clinical diagnosis, the suspicion of malignancy requires the removal of the lesion and performing a histopathology study in which immunohistochemical markers may help to determine the nature of the lesion.A case is presented of a 25 year-old woman with a pigmented lesion in the caruncle. It appeared recently and was growing fast with increasing pigmentation. Due to a suspicion of malignancy, the total lesion was removed. The microscopic study revealed cellular alterations which suggested malignancy. However, after carrying out immunohistochemical markers the diagnosis was conjunctival compound nevus.

Intermittent parathyroid hormone (PTH) administration has been shown to be a promising therapy for systemic bone loss. Accordingly, we hypothesized that PTH could have positive results in treating oral complications of osteoporosis. Hence, we evaluated both mandibular bone loss and its response to PTH in a rabbit model of osteoporosis induced by ovariectomy and glucocorticoid administration. There was a significant and marked decrease in bone mineral density (BMD), bone mineral content (BMC), and calcium content in ash from the osteoporotic peri-alveolar region, which influenced global jaw loss. Remarkably, PTH (1–34) administration to osteoporotic rabbits almost completely reversed BMD, BMC, and calcium content fall in the peri-alveolar region, subsequently reducing global mandibular bone loss. Thus, although the peri-alveolar region is particularly susceptible to osteoporosis, it also responds well to intermittent PTH. Therefore, these results suggest that PTH might represent a valid therapy for improving the osseointegration of dental implants in persons with osteoporosis.

International audience; Between 2003 and 2004, 264 face-to-face interviews were undertaken to determine farmers’ perceptions of silvoarable agroforestry across 14 sample areas in seven European countries. Across the 14 sample areas, 40% of respondents had heard the term “agroforestry” and 33% then defined it as an association of trees with crops or livestock. By contrast those farmers, who had not heard of the term, were almost as likely to define “agroforestry” as “silviculture” (24%) as an “ association of trees and crops or trees and livestock” (25%). Farmers were then shown pictures of silvoarable agroforestry, where trees and arable crops were grown on the same land unit. Farmers in Mediterranean areas felt that the principal benefit of silvoarable systems would be increased farm profitability (37%), whereas farmers in Northern Europe placed greatest value on environmental benefits (28%). When asked to identify the greatest negative attribute, Mediterranean farmers tended to identify intercrop yield decline (31%), whereas farmers in Northern Europe tended to highlight the general complexity of work (21%) and difficulties with mechanisation (17%). When asked to design a silvoarable system for their farm, Mediterranean farmers tended to envisage systems with a higher tree density (100 trees per hectare) than those in Northern Europe (55 trees per hectare). Overall half of all farmers interviewed indicated that they would “attempt” silvoarable agroforestry on their farm, ranging from 18% to 90% within the individual sample areas. These results suggest that with appropriate promotion and support, silvoarable agroforestry would become a more common feature of the European landscape.

Objectives. Synoviocytes play a crucial role in the inflammatory response leading to structural damage in OA. Our aim was to assess the effects of diacerein and NSAIDs on cellular responses of synoviocytes associated with inflammation and structural integrity of cartilage in OA. Methods. The effects of diacerein, celecoxib, diclofenac, meloxicam and indomethacin on prostaglandin (PG) E2 production, cyclooxygenase-2 (COX-2) protein expression, nitrite levels, presence of MMP-1 and -13, and activation of nuclear factor-� B (NF-� B) were studied on stimulated OA synoviocytes and chondrocytes. Results. Diacerein and NSAIDs inhibited IL-1� -stimulated NF-� B activation in synoviocytes and chondrocytes except indomethacin in synoviocytes. Diacerein further increased COX-2 protein expression and PGE2 synthesis in synoviocytes stimulated with IL-1� , while no effect was observed on stimulated chondrocytes. NSAIDs diminished until almost basal levels PGE2 release in both cells and, surprisingly, these drugs also diminished COX-2 protein expression both in synoviocytes and chondrocytes. With regard to structural mediators, diacerein decreased MMP-13 levels in synoviocytes but did not modify MMP-1 presence. NSAIDs induced a significant increase in MMP-1 levels in both cell types and in MMP-13 levels in chondrocytes. Conclusions. Diacerein does not seem to reduce but rather increase inflammatory mediators in synoviocytes, while it does not overall affect chondrocyte inflammatory profile.

Between 2003 and 2004, 264 face-to-face interviews were undertaken to determine farmers' perceptions of silvoarable agroforestry across 14 sample areas in seven European countries. Across the 14 sample areas, 40% of respondents had heard the term "agroforestry" and 33% then defined it as an association of trees with crops or livestock. By contrast those farmers, who had not heard of the term, were almost as likely to define "agroforestry" as "silviculture" (24%) as an "association of trees and crops or trees and livestock" (25%). Farmers were then shown pictures of silvoarable agroforestry, where trees and arable crops were grown on the same land unit. Farmers in Mediterranean areas felt that the principal benefit of silvoarable systems would be increased farm profitability (37%), whereas farmers in Northern Europe placed greatest value on environmental benefits (28%). When asked to identify the greatest negative attribute, Mediterranean farmers tended to identify intercrop yield decline (31%), whereas farmers in Northern Europe tended to highlight the general complexity of work (21%) and difficulties with mechanisation (17%). When asked to design a silvoarable system for their farm, Mediterranean farmers tended to envisage systems with a higher tree density (100 trees per hectare) than those in Northern Europe (55 trees per hectare). Overall half of all farmers interviewed indicated that they would "attempt" silvoarable agroforestry on their farm, ranging from 18% to 90% within the individual sample areas. These results suggest that with appropriate promotion and support, silvoarable agroforestry would become a more common feature of the European landscape.