Cost of Treating Cutaneous T-Cell Lymphoma in Spain: Analysis of MICADOS Study Data by Disease Stage. / Evaluación de los costes asociados a la enfermedad de pacientes con linfoma cutáneo de células T en España: análisis en función del estadio clínico (estudio MICADOS).

BACKGROUND AND OBJECTIVE: The cost of treating cutaneous T-cell lymphoma (CTCL) in Spain is unknown. With the advent of new treatments, it is more important than ever to gain an accurate picture of the true costs involved. The MICADOS study had 2 primary objectives: 1)to evaluate the impact of CTCL on patient quality of life, and 2)to evaluate the costs associated with the disease. This article reports the results of the cost analysis. METHODS: We estimated the cost of treating CTCL over a period of 1year from the perspective of the Spanish National Health System. Twenty-three dermatologists and hematologists from 15 public hospitals analyzed data for adult patients with mycosis fungoides (MF) or Sézary syndrome (SS). RESULTS: A total of 141 patients (57.4% male) with a mean age of 63.6 years (95%CI: 61.4-65.7 years) were included. The mean direct annual cost of treating CTCL was €34,214 per patient. The corresponding costs by stage were €11,952.47 for stageI disease, €23,506.21 for stageII disease, €38,771.81 for stageIII disease, and €72,748.84 for stageIV disease. The total direct annual cost of treating MF/SS in public hospitals in Spain was estimated at €78,301,171; stageI disease accounted for 81% of all costs, stageII for 7%, and stagesIII andIV for 6% each. CONCLUSIONS: The MICADOS study offers an accurate picture of the direct cost of treating CTCL in patients with MF/SS in Spain and shows that costs vary significantly according to disease stage. Patient-borne and indirect costs should be analyzed in future studies.

[Translated article] Cost of Treating Cutaneous T-Cell Lymphoma in Spain: Analysis of MICADOS Study Data by Disease Stage.

BACKGROUND AND OBJECTIVE: The cost of treating cutaneous T-cell lymphoma (CTCL) in Spain is unknown. With the advent of new treatments, it is more important than ever to gain an accurate picture of the true costs involved. The MICADOS study had 2 primary objectives: 1)to evaluate the impact of CTCL on patient quality of life, and 2)to evaluate the costs associated with the disease. This article reports the results of the cost analysis. METHODS: We estimated the cost of treating CTCL over a period of 1year from the perspective of the Spanish National Health System. Twenty-three dermatologists and hematologists from 15 public hospitals analyzed data for adult patients with mycosis fungoides (MF) or Sézary syndrome (SS). RESULTS: A total of 141 patients (57.4% male) with a mean age of 63.6 years (95%CI: 61.4-65.7 years) were included. The mean direct annual cost of treating CTCL was €34,214 per patient. The corresponding costs by stage were €11,952.47 for stageI disease, €23,506.21 for stageII disease, €38,771.81 for stageIII disease, and €72,748.84 for stageIV disease. The total direct annual cost of treating MF/SS in public hospitals in Spain was estimated at €78,301,171; stageI disease accounted for 81% of all costs, stageII for 7%, and stagesIII andIV for 6% each. CONCLUSIONS: The MICADOS study offers an accurate picture of the direct cost of treating CTCL in patients with MF/SS in Spain and shows that costs vary significantly according to disease stage. Patient-borne and indirect costs should be analyzed in future studies.

First Reported Case of Malignant Ectomesenchymoma with p.Leu122Arg Mutation in MYOD1 Gene: Extensive Intra- and Extracranial Tumor in a 15-Year-Old Female.

BACKGROUND: Ectomesenchymomas (EMs) are extremely rare neoplasms composed of malignant mesenchymal components and neuroectodermal derivatives. They are described in a wide variety of locations, with the head and neck region being one of the most frequently involved areas. EMs are usually managed as high-risk rhabdomyosarcomas and have similar outcomes. METHODS: We present the case of a 15-year-old female with an EM that arose in the parapharyngeal space and extended into the intracranial space. RESULTS: Histologically, the tumor presented an embryonal rhabdomyosarcomatous mesenchymal component and the neuroectodermal component was constituted by isolated ganglion cells. Next-generation sequencing (NGS) revealed a p.Leu122Arg (c.365 T > G) mutation in the MYOD1 gene, a p.Ala34Gly mutation in the CDKN2A gene, and CDK4 gene amplification. The patient was treated with chemotherapy. She died 17 months after the debut of symptoms. CONCLUSION(S): To our knowledge, this is the first reported case in English literature of an EM with this MYOD1 mutation. We suggest combining PI3K/ATK pathway inhibitors in these cases. NGS should be performed in EMs cases to detect mutations with potential treatment options.

Strengthening the equity focus of applied public health research: introducing the FOR EQUITY platform.

OBJECTIVES: Much applied health research pays insufficient attention to potential unequal impacts across social groups or is typically focused on a single dimension (e.g. socio-economic status), rarely considering the intersecting social processes driving inequalities (e.g. racism, sexism, classism). All health research needs a strong intersectional equity focus in order to inform action to reduce health inequalities as well as improve population health. STUDY DESIGN: Focus On Research and Equity (FOR EQUITY) is a new Web-based platform aiming to strengthen the intersectional equity focus of applied health research. METHODS: The platform was developed in collaboration with members of the public, practitioners and researchers working internationally. The development involved a systematic review of academic and grey literature, a series of workshops and user testing. RESULTS: FOR EQUITY encompasses (1) a Health Inequalities Assessment Tool, with an intersectional perspective on inequalities; (2) a FOR EQUITY Guidance Inventory providing access to a range of international research toolkits and guidance; and (3) a FOR EQUITY Library including case studies illustrating how researchers have attempted to integrate an equity lens into the research process and more general resources on health inequalities. CONCLUSION: FOR EQUITY can support researchers to strengthen the equity lens in their studies to make research evidence more relevant for action to reduce social and health inequalities. However, a single focus on toolkits is unlikely to sufficiently address the barriers to embedding equity in research. A mainstreaming strategy to transform the very roots of the 'institution of research' is required.

System resilience and neighbourhood action on social determinants of health inequalities: an English Case Study.

AIMS: This article seeks to make the case for a new approach to understanding and nurturing resilience as a foundation for effective place-based co-produced local action on social and health inequalities. METHODS: A narrative review of literature on community resilience from a public health perspective was conducted and a new concept of neighbourhood system resilience was developed. This then shaped the development of a practical programme of action research implemented in nine socio-economically disadvantaged neighbourhoods in North West England between 2014 and 2019. This Neighbourhood Resilience Programme (NRP) was evaluated using a mixed-method design comprising: (1) a longitudinal household survey, conducted in each of the Neighbourhoods For Learning (NFLs) and in nine comparator areas in two waves (2015/2016 and 2018/2019) and completed in each phase by approximately 3000 households; (2) reflexive journals kept by the academic team; and (3) semi-structured interviews on perceptions about the impacts of the programme with 41 participants in 2019. RESULTS: A difference-in-difference analysis of household survey data showed a statistically significant increase of 7.5% (95% confidence interval (CI), 1.6 to 13.5) in the percentage of residents reporting that they felt able to influence local decision-making in the NFLs relative to the residents in comparator areas, but no effect attributable to the NRP in other evaluative measures. The analysis of participant interviews identified beneficial impacts of the NRP in five resilience domains: social connectivity, cultural coherence, local decision-making, economic activity, and the local environment. CONCLUSION: Our findings support the need for a shift away from interventions that seek solely to enhance the resilience of lay communities to interventions that recognise resilience as a whole systems phenomenon. Systemic approaches to resilience can provide the underpinning foundation for effective co-produced local action on social and health inequalities, but they require intensive relational work by all participating system players.

Current status of precision medicine in pediatric oncology in Spain: a consensus report by the Spanish Society of Paediatric Haematology and Oncology (SEHOP).

The study analyzes the current status of personalized medicine in pediatric oncology in Spain. It gathers national data on the tumor molecular studies and genomic sequencing carried out at diagnosis and at relapse, the centers that perform these studies, the technology used and the interpretation and clinical applicability of the results. Current challenges and future directions to achieve a coordinated national personalized medicine strategy in pediatric oncology are also discussed. Next generation sequencing-based (NGS) gene panels are the technology used in the majority of centers and financial limitations are the main reason for not incorporating these studies into routine care. Nowadays, the application of precision medicine in pediatric oncology is a reality in a great number of Spanish centers. However, its implementation is uneven and lacks standardization of protocols; therefore, national coordination to overcome the inequalities is required. Collaborative work within the Personalized Medicine Group of SEHOP is an adequate framework for encouraging a step forward in the effort to move precision medicine into the national healthcare system.

[Postural control and gait changes in subacute stroke patients after receiving interdisciplinary rehabilitation and related factors: a retrospective study]. / Cambios en el control postural y la marcha en pacientes con ictus en fase subaguda tras recibir rehabilitación interdisciplinar y factores relacionados: estudio retrospectivo.

INTRODUCTION: Although early post-stroke rehabilitation is essential to optimize recovery, its effects and prognostic factors are yet under discussion. OBJECTIVE: To assess postural control and gait changes in post-stroke patients who underwent interdisciplinary rehabilitation in subacute phase and evaluate potential associated factors. PATIENTS AND METHODS: An observational retrospective study that analyzed sociodemographic and clinical data, including Trunk Impairment Scale (TIS), Postural Assessment Scale for Stroke (PASS), Functional Ambulatory Categories (FAC) and Tinetti scale, at admission and two months after rehabilitation. RESULTS: Data were collected from 63 patients with stroke in subacute phase. Interdisciplinary rehabilitation had a moderate and relevant clinical impact (p < 0,01; d mayor de 0,5) in postural control and gait. Ambulatory rehabilitation, psychotropic medication absence and dislipemia absence were moderate associated factors (p < 0,05; d mayor de 0,5) with a greater evolution in postural control measured with TIS and PASS. TIS at admission showed significant association with all scales' results at two months after rehabilitation, except with PASS changing posture subscale. CONCLUSIONS: Interdisciplinary rehabilitation promotes moderate and clinically relevant changes in postural control and gait recovery in subacute stroke patients, after two-month rehabilitation period. Ambulatory rehabilitation, dyslipidemia absence and psychotropic medication absence were associated with patients' evolution, but further research is required to confirm their actual influence in larger samples.

TITLE: Cambios en el control postural y la marcha en pacientes con ictus en fase subaguda tras recibir rehabilitación interdisciplinar y factores relacionados: estudio retrospectivo.Introducción. La rehabilitación precoz tras el ictus resulta fundamental para optimizar la recuperación, pero sus efectos y los factores pronósticos están aún en discusión. Objetivo. Evaluar los cambios en el control postural y la marcha en los pacientes con ictus que reciben rehabilitación interdisciplinar en fase subaguda y valorar los posibles factores relacionados. Pacientes y métodos. Estudio observacional retrospectivo que analizó datos sociodemográficos y clínicos, incluyendo el control postural y la capacidad de marcha, mediante las escalas Trunk Impairment Scale (TIS), Postural Assessment Scale for Stroke (PASS), Functional Ambulation Categories (FAC) y de Tinetti, tanto en el inicio como a los dos meses de rehabilitación. Resultados. Se recogieron datos de 63 pacientes con ictus en fase subaguda. La rehabilitación interdisciplinar tuvo un impacto clínico moderado (p menor de 0,01; d mayor de 0,5) y relevante sobre el control postural y la marcha. Los factores asociados moderadamente (p menor de 0,05; d > 0,5) a una mayor evolución en el control postural evaluado con la TIS y la PASS fueron la rehabilitación ambulatoria, la ausencia de medicación psicótropa y la ausencia de dislipidemia. La TIS en el inicio se asoció significativamente (p menor de 0,05) con los valores de todas las escalas tras dos meses de rehabilitación, excepto con la PASS movilidad. Conclusiones. La rehabilitación interdisciplinar favorece cambios moderados y clínicamente relevantes en la recuperación del control postural y la marcha de pacientes con ictus subagudo tras dos meses de tratamiento. La rehabilitación ambulatoria y la ausencia de dislipidemia y de medicación psicótropa se asocian con la evolución, pero son necesarios más estudios para confirmar su influencia en muestras mayores.

Antimicrobial and osteoconductive properties of two different types of titanium silver coating.

In prosthetic joint surgery, Ag coating of implant areas in direct contact with bone has been met with hesitation for fear of compromising osseointegration. The physicochemical, antibacterial and osteoconductive properties of three different Ti samples were studied: Ti6Al4V alloy that was grit-blasted (GB), Ti6Al4V alloy with an experimental Ti-Ag-nitride layer (SN) applied by physical vapour deposition (PVD) and commercially available PVD-coated Ti6Al4V alloy with a base Ag layer and a surface Ti-Ag-nitride layer (SSN, clinically known as PorAg®). Ag content on the surface of experimental SN and SSN discs was 27.7 %wt and 68.5 % wt, respectively. At 28 d, Ag release was 4 ppm from SN and 26.9 ppm from SSN substrates. Colonisation of discs by Staphylococcus aureus was the highest on GB [944 (± 91) × 10 4 CFU/mL], distinctly lower on experimental SN discs [414 (± 117) × 104 CFU/mL] and the lowest on SSN discs [307 (± 126) × 10 4 CFU/mL]. Primary human osteoblasts were abundant 28 d after seeding on GB discs but their adhesion and differentiation, measured by alkaline-phosphatase production, was suppressed by 73 % on SN and by 96 % on SSN discs, in comparison to GB discs. Thus, the PVD-applied Ag coatings differed considerably in their antibacterial effects and osteoconductivity. The experimental SN coating had similar antibacterial effects to the commercially available SSN coating while providing slightly improved osteoconductivity. Balancing the Ag content of Ti implants will be vital for future developments of implants designed for cementless fixation into bone.

[Prevalence of microbiologically-confirmed influenza in patients with influenza-like illness in primary care and clinical and epidemiological characteristics]. / Prevalencia de gripe confirmada microbiológicamente en pacientes con síntomas gripales en atención primaria y características clínico-epidemiológicas.

OBJECTIVE: We evaluated the prevalence of microbiologically-confirmed influenza infection among patients with influenza-like symptoms and compared the clinical and epidemiological characteristics of patients with and without influenza infection. METHODS: Retrospective study of a cohort of patients with influenza-like symptoms from 2016 to 2018 who participated in a clinical trial in thirteen urban primary centres in Catalonia. Different epidemiological data were collected. Patients rated the different symptoms and signs on a Likert scale (absent, little problem, moderate problem and severe problem) and self-reported the measure of health status with the EuroQol visual analogue scale. A nasopharyngeal swab was taken for microbiological isolation of influenza and other microorganisms. RESULTS: A total of 427 patients were included. Microbiologically confirmed influenza was found in 240 patients (56.2%). The percentage of patients with moderate-to-severe cough, muscle aches, tiredness and dizziness was greater among patients with microbiologically confirmed influenza. The self-reported health status was significantly lower among patients with true flu infection (mean of 36.3 ± 18.2 vs 41.7 ± 17.8 in patients without influenza; p<0.001). CONCLUSIONS: Clinical findings are not particularly useful for confirming or excluding the diagnosis of influenza when intensity is not considered. However, the presence of moderate-to-severe cough, myalgias, tiredness and dizziness along with a poor health status is more common in patients with confirmed flu infection.

Insights on the role of acetaldehyde and other aldehydes in the odour and tactile nasal perception of red wine.

Wine models with or without a dearomatised and lyophilized red wine extract containing a young red aroma base (control) plus one vector with one or several aroma compounds (unsaturated-aldehydes, saturated-aldehydes, benzaldehyde, isoamyl-alcohol, methoxypyrazines and (Z)-1,5-octadien-3-one) were prepared. Models were spiked with increasing amounts of acetaldehyde whose headspace concentrations were controlled. Odour and nasal chemesthesic properties were assessed by a trained sensory panel. Results confirm the contribution of the different players, notably isoamyl-alcohol, (Z)-1,5-octadien-3-one, benzaldehyde and methoxypyrazines, to wine aroma and tactile nasal characteristics and demonstrate that acetaldehyde levels play an outstanding role in their modulation. At low levels, it can play positive roles in some specific aromatic contexts, while at higher levels, enhance the negative effects associated to the generic presence of other aldehydes (saturated, unsaturated and Strecker aldehydes) by enhancing "green vegetable" notes and "itching" character and the "burning" effects linked to high levels of isoamyl alcohol.

Genetic predisposition to fetal and neonatal cancer.

BACKGROUND: Neonatal tumors represent an extremely rare and heterogeneous disease with an unknown etiology. Due to its early onset, it has been proposed that genetic factors could play a critical role; however, germline genetic analysis is not usually performed in neonatal cancer patients PATIENTS AND METHODS: To improve the identification of cancer genetic predisposition syndromes, we retrospectively review clinical characteristics in 45 patients with confirmed tumor diagnosis before 28 days of age, and we carried out germline genetic analysis in 20 patients using next-generation sequencing and directed sequencing. RESULTS: The genetic studies did not find any germline mutation except patients diagnosed with bilateral retinoblastoma who harbored RB1 germline mutations. CONCLUSIONS: Our results suggest that genetic factors have almost no higher impact in most neonatal tumors. However, since the heterogeneity of the tumors and the small sample size analyzed, we recommend complementary and centralized germline studies to discard the early onset as an additional criterion to take into account to improve the identification of cancer genetic predisposition syndromes in neonates.

Habitat fragmentation and population features differently affect fruit predation, fecundity and offspring performance in a non-specialist gypsum plant.

The effects of habitat fragmentation on plant populations are complex, as it might disrupt many ecological processes, including plant reproduction and plant-animal interactions. Gypsum specialist plants may be resilient to fragmentation due to their evolutionary history in fragmented landscapes, but the effects on non-specialist plants occurring in gypsum are unknown. We conducted a study focusing on different aspects of the reproductive cycle of Astragalus incanus subsp. incanus, a plant facultatively linked to gypsum soils. We focused on plant fecundity and pre-dispersal predation, obtained from field observations, and offspring performance, assessed in a common garden. Beyond fragment size and connectivity, we also considered habitat quality, population size and density and plant size as predictors. Fragment size and connectivity had no effect on plant fecundity, but jointly determined fruit predation, while fragment size was positively related to offspring growth. Population density, rather than population size, had a positive effect on predation but negatively affected plant fecundity and offspring performance. Habitat quality reduced both plant fecundity and predation incidence. In this non-specialist species, habitat fragmentation, population features and habitat quality affect different facets of plant performance. Predation was the only process clearly affected by fragmentation variables, fecundity mainly depended on population features and offspring performance and was better explained by mother plant identity. Our results show the need to consider habitat and population features together with fragment size and connectivity in order to assess the effects of fragmentation. Importantly, these effects can involve different aspects of plant reproduction, including plant-animal interactions.

[Family physician's role in the primary and secondary prevention and in the treatment of depression in the elderly]. / Rol del médico de familia en la prevención primaria y secundaria de la depresión en el adulto mayor.

In recent years, the demographic transition has resulted in an aging population, which has increased the number of illnesses such as depression. Often, the family physician is the first contact with these patients, therefore, comprehensive patient management is essential, emphasizing the primary and secondary prevention of depression in the elderly population. From primary health care, all risk and protective factors related to depression should be comprehensively evaluated. Among the former, widowhood, disability, and chronic diseases stand out. Likewise, the diagnostic criteria must be known to provide timely treatment. And, on the other hand, knowing the appropriate treatment will reduce the symptoms of depression, suicidal behavior, relapse, or recurrence of symptoms. Treatment usually consists of psychotherapy, psychosocial interventions, antidepressants, and electroconvulsive therapy. Therefore, the objective of this review is to offer family physicians a guide on the primary prevention, secondary prevention, and treatment of depression in the elderly.

Memory inception and preservation in slime moulds: the quest for a common mechanism.

Learning and memory are indisputably key features of animal success. Using information about past experiences is critical for optimal decision-making in a fluctuating environment. Those abilities are usually believed to be limited to organisms with a nervous system, precluding their existence in non-neural organisms. However, recent studies showed that the slime mould Physarum polycephalum, despite being unicellular, displays habituation, a simple form of learning. In this paper, we studied the possible substrate of both short- and long-term habituation in slime moulds. We habituated slime moulds to sodium, a known repellent, using a 6 day training and turned them into a dormant state named sclerotia. Those slime moulds were then revived and tested for habituation. We showed that information acquired during the training was preserved through the dormant stage as slime moulds still showed habituation after a one-month dormancy period. Chemical analyses indicated a continuous uptake of sodium during the process of habituation and showed that sodium was retained throughout the dormant stage. Lastly, we showed that memory inception via constrained absorption of sodium for 2 h elicited habituation. Our results suggest that slime moulds absorbed the repellent and used it as a 'circulating memory'. This article is part of the theme issue 'Liquid brains, solid brains: How distributed cognitive architectures process information'.

Addition of N-terminal pro-B natriuretic peptide to soluble fms-like tyrosine kinase-1/placental growth factor ratio > 38 improves prediction of pre-eclampsia requiring delivery within 1 week: a longitudinal cohort study.

OBJECTIVE: Short-term prediction of pre-eclampsia (PE) using the soluble fms-like tyrosine kinase-1 (sFlt-1)/placental growth factor (PlGF) ratio is characterized by frequent false-positive results. As such, no treatment can be recommended to test-positive patients and multiple measurements are often required. The aim of this study was to evaluate the effectiveness of N-terminal pro-B natriuretic peptide (NT-proBNP), uric acid and the sFlt-1/PlGF ratio for prediction of delivery with PE within 1 week in singleton pregnancies with suspected PE and sFlt-1/PlGF ratio > 38. METHODS: This was a longitudinal prospective cohort study of singleton pregnancies presenting at 24 + 0 to 36 + 6 weeks of gestation with clinically suspected PE and sFlt-1/PlGF ratio > 38, enrolled between January 2015 and June 2017. Multiple samples per patient were allowed but were restricted to one sample per gestational week. From 495 enrolled patients, 270 blood samples from 134 patients were ultimately analyzed. By using generalized estimating equations (GEE), the best-fit model was selected for prediction of delivery with PE within 1 week. The predictive value of this model was then assessed using area under the paired-ROC curve (AUC) analysis. RESULTS: The best-fit model included the sFlt-1/PlGF ratio, NT-proBNP and the gestational week at the time of the measurement. This combined model was compared with the GEE model based on the sFlt-1/PlGF ratio and the gestational week at the time of the measurement (reduced model). The AUC for the combined model was 0.845 (95% CI, 0.787-0.896), which was significantly greater (P = 0.011) than that of the reduced model (0.786 (95% CI, 0.722-0.844)). CONCLUSION: The addition of NT-proBNP assessment improves the short-term prediction of delivery as a result of PE compared with sFlt-1/PlGF ratio alone, when the sFlt-1/PlGF ratio is > 38. This finding should be considered in future research on the assessment of short-term risk of delivery as a result of PE. Copyright © 2018 ISUOG. Published by John Wiley & Sons Ltd.

Haploidentical IL-15/41BBL activated and expanded natural killer cell infusion therapy after salvage chemotherapy in children with relapsed and refractory leukemia.

Primary refractory or relapsed pediatric leukemia yield significant morbidity and mortality, with long-term survival rates <40%. Here we present a post-hoc analysis assessing safety and efficacy of infusing activated and expanded Natural Killer cells (NKAE) from haploidentical donors in patients from 2 clinical trials. In total, 18 children, adolescents and young adults with relapse or refractory acute leukemia were treated with two cycles of rescue chemotherapy followed by fresh NKAE cells infusions and low doses of IL-2. The overall response rate, complete remission achievement at the end of the study, was 72% (13 of 18). We infused 52 NKAE cell products containing a median of 6.76 × 106 NK cells/kg (0.7-34.16) and 0.49 × 106 T cells/kg (0-11). All infusions were well tolerated with no graft versus host disease nor other serious adverse events. Among the 14 patients who completed treatment, 4 of them are alive and leukemia-free more than 750 days post-transplant. We conclude that infusion of fresh NKAE cell therapy is feasible and safe in heavily pretreated pediatric population, and should be further investigated in advanced-phase clinical trials as well as a consolidation therapy to decrease relapse in patients with high-risk leukemia. TRIALS REGISTRATION: Registered at www.clinicaltrials.gov as NCT01944982 and NCT02074657.

Landscape effects on pollination networks in Mediterranean gypsum islands.

Habitat fragmentation is a major driver of global change that has operated historically on Mediterranean ecosystems. However, more needs to be understood about how fragmentation influences ecological interactions, particularly pollination. Gypsum outcrops are historically fragmented Mediterranean habitats and settings for the evolution of many endangered soil-specialist plants with narrow ranges. In this study, we aimed to determine how fragmentation (area and connectivity) affects: (i) pollinator community composition and (ii) structural properties of pollination networks; and whether there are differences in the effects of fragmentation on: (iii) the number of interactions and visits among pollinator functional groups; and (iv) the number of interactions and specialisation degree between soil-specialist and soil-generalist plants. We characterised the degree of fragmentation and the pollination network structures in 12 gypsum habitat fragments embedded in a cropland matrix during two consecutive years. We found significant relationships between fragmentation and network structure. The effects of fragmentation differed among pollinator functional groups, but not between soil-specialist and soil-generalist plants, in terms of number of interactions. However, the relatively higher pollinator specialisation of soil-specialist plants suggested greater dependence on pollinators. Inter-annual variations in the network structures demonstrated the importance of temporal replication. The observed patterns related to the landscape structure and pollination at both the network and species levels provide insights into the key ecological processes in gypsum islands. These findings may help to identify the potential drivers of species persistence, especially for endangered soil-specialist plants with narrow ranges in a changing scenario with exacerbated habitat fragmentation.

Pharmacokinetics of deflazacort in rabbits after intravenous and oral administration and its interaction with erythromycin.

The pharmacokinetic of deflazacort after intravenous and oral administration and the effect of erythromycin on the disposition of deflazacort in rabbits were investigated. A parallel study was carried out in twelve rabbits. The plasma concentration-time profiles of deflazacort were determined after intravenous and oral administration of single dosages of 5 mg/kg in the presence and absence (baseline) of multiple dose erythromycin regimens. Plasma concentrations of 21-desacetyldeflazacort were determined by HPLC. Plasma concentration-time curves were analysed by compartmental pharmacokinetic and noncompartmental methods. The t½λz values following intravenous and oral administration were 3.67 and 4.96 hr, respectively. The apparent volume of distribution at steady-state (Vss ) was 4.08 ± 0.31 L/kg, this value indicates that deflazacort is widely distributed into the extravascular tissues. Moreover, bioavailability after oral administration of deflazacort (F = 87.48%) was high. Pharmacokinetic analysis after both routes of administration revealed a significant reduction in total body clearance, a significant increase in mean residence time, half-life and plasma concentrations of the steroid in the presence of multiple dose erythromycin. The results indicated the influence of the erythromycin on deflazacort disposition, which is consistent with a pharmacokinetic-type interaction in the elimination of the drug from the body. Moreover, this interaction should be considered to avoid adverse effects when using both drugs concomitantly.

How does climate change affect regeneration of Mediterranean high-mountain plants? An integration and synthesis of current knowledge.

Mediterranean mountains are extraordinarily diverse and hold a high proportion of endemic plants, but they are particularly vulnerable to climate change, and most species distribution models project drastic changes in community composition. Retrospective studies and long-term monitoring also highlight that Mediterranean high-mountain plants are suffering severe range contractions. The aim of this work is to review the current knowledge of climate change impacts on the process of plant regeneration by seed in Mediterranean high-mountain plants, by combining available information from observational and experimental studies. We also discuss some processes that may provide resilience against changing environmental conditions and suggest some research priorities for the future. With some exceptions, there is still little evidence of the direct effects of climate change on pollination and reproductive success of Mediterranean high-mountain plants, and most works are observational and/or centred only in the post-dispersal stages (germination and establishment). The great majority of studies agree that the characteristic summer drought and the extreme heatwaves, which are projected to be more intense in the future, are the most limiting factors for the regeneration process. However, there is an urgent need for studies combining elevational gradient approaches with experimental manipulations of temperature and drought to confirm the magnitude and variability of species' responses. There is also limited knowledge about the ability of Mediterranean high-mountain plants to cope with climate change through phenotypic plasticity and local adaptation processes. This could be achieved by performing common garden and reciprocal translocation experiments with species differing in life history traits.