Bacterial communities of the psyllid pest Bactericera cockerelli (Hemiptera: Triozidae) Central haplotype of tomato crops cultivated at different locations of Mexico.

Background: The psyllid, Bactericera cockerelli, is an insect vector of 'Candidatus Liberibacter' causing "Zebra chip" disease that affects potato and other Solanaceae crops worldwide. In the present study, we analyzed the bacterial communities associated with the insect vector Bactericera cockerelli central haplotype of tomato crop fields in four regions from Mexico. Methods: PCR was used to amplify the mitochondrial cytochrome oxidase I gene (mtCOI) and then analyze the single nucleotide polymorphisms (SNP) and phylogenetic analysis for haplotype identification of the isolated B. cockerelli. Moreover, we carried out the microbial diversity analysis of several B. cockerelli collected from four regions of Mexico through the NGS sequencing of 16S rRNA V3 region. Finally, Wolbachia was detected by the wsp gene PCR amplification, which is the B. cockerelli facultative symbiont. Also we were able to confirm the relationship with several Wolbachia strains by phylogenetic analysis. Results: Our results pointed that B. cockerelli collected in the four locations from Mexico (Central Mexico: Queretaro, and Northern Mexico: Sinaloa, Coahuila, and Nuevo Leon) were identified, such as the central haplotype. Analyses of the parameters of the composition, relative abundance, and diversity (Shannon index: 1.328 ± 0.472; Simpson index 0.582 ± 0.167), showing a notably relatively few microbial species in B. cockerelli. Analyses identified various facultative symbionts, particularly the Wolbachia (Rickettsiales: Anaplasmataceae) with a relative abundance higher. In contrast, the genera of Sodalis and 'Candidatus Carsonella' (Gammaproteobacteria: Oceanospirillales: Halomonadaceae) were identified with a relatively low abundance. On the other hand, the relative abundance for the genus 'Candidatus Liberibacter' was higher only for some of the locations analyzed. PCR amplification of a fragment of the gene encoding a surface protein (wsp) of Wolbachia and phylogenetic analysis corroborated the presence of this bacterium in the central haplotype. Beta-diversity analysis revealed that the presence of the genus 'Candidatus Liberibacter' influences the microbiota structure of this psyllid species. Conclusions: Our data support that the members with the highest representation in microbial community of B. cockerelli central haplotype, comprise their obligate symbiont, Carsonella, and facultative symbionts. We also found evidence that among the factors analyzed, the presence of the plant pathogen affects the structure and composition of the bacterial community associated with B. cockerelli.

Pharmacogenetic Sex-Specific Effects of Methotrexate Response in Patients with Rheumatoid Arthritis.

Methotrexate (MTX) is a commonly used drug for the treatment of rheumatoid arthritis (RA), but its effectiveness can vary greatly among patients. Pharmacogenetics, the study of how genetic variations can affect drug response, has the potential to improve the personalized treatment of RA by identifying genetic markers that can predict a patient's response to MTX. However, the field of MTX pharmacogenetics is still in its early stages and there is a lack of consistency among studies. This study aimed to identify genetic markers associated with MTX efficacy and toxicity in a large sample of RA patients, and to investigate the role of clinical covariates and sex-specific effects. Our results have identified an association of ITPA rs1127354 and ABCB1 rs1045642 with response to MTX, polymorphisms of FPGS rs1544105, GGH rs1800909, and MTHFR genes with disease remission, GGH rs1800909 and MTHFR rs1801131 polymorphisms with all adverse events, and ADA rs244076 and MTHFR rs1801131 and rs1801133, However, clinical covariates were more important factors to consider when building predictive models. These findings highlight the potential of pharmacogenetics to improve personalized treatment of RA, but also emphasize the need for further research to fully understand the complex mechanisms involved.

Woodchip bioreactors for saline leachates denitrification can mitigate agricultural impacts in mediterranean areas: The Campo de Cartagena-Mar Menor environmental issue.

Leachates from intensive agriculture containing high nitrate have been identified as a major cause of the severe eutrophication crisis that impacts Mar Menor (SE Spain), the largest hypersaline coastal lagoon in the Mediterranean basin. A best management practice for removing NO3--N is denitrifying bioreactors. This is the first study to assess the efficiency of citrus woodchips bioreactors in treating agricultural leachates that flow to the Mar Menor via surface discharges. Denitrification capacity, woodchip degradation (by weight loss), formation of potentially harmful compounds, and greenhouse gas (GHG) emissions were assessed. Three bioreactors (6 m × 0.98 m x 1.2 m) filled with citrus woodchips (3 m3 d-1 per bioreactor) through which the untreated ditch water over 1.5 years. Bioreactors were operated at 8 h, 16 h, and 24 h hydraulic residence time respectively, in each bioreactor. The main characteristics of the ditch water were: pH ≈ 7.5-8.0, electrical conductivity ≈ 5-8 dS m-1, dissolved organic carbon ≈6-10 mg L-1, and NO3--N ≈ 22-45 mg L-1. Bioreactors were highly efficient in reducing NO3--N. The average RNO3 in effluents was for the complete experimental period 8 g N m-3 d-1, 10.9 g N m-3 d-1, and 12.6 g N m-3 d-1 for 8, 16 and 24 h residence time, respectively. Nitrate reduction efficiency was modulated by seasonal changes in temperature, with an increasing efficiency in warmer periods (maximum ≈ 85-90% for all hydraulic residence time) and decreasing in colder ones (minimum ≈ 12%, 23% and 41% for hydraulic residence time 8, 16 and 24 h respectively). Woodchips degradation was greatest during the first six months (average ≈ 29% weight loss) in the material above the water level, attributable to aerobic mineralization of the organic carbon, while weight loss was ≈11% in woodchip media continuously below the water level. Dissolved organic carbon, sulfide, ammonium, and soluble phosphorus concentrations in the effluents were mostly low, although some peaks in concentrations occurred. Design consideration must be taken to avoid environmental impacts due to the occasional presence of harmful compounds in the effluents.

A motivational interview program for cardiac rehabilitation after acute myocardial infarction: study protocol of a randomized controlled trial in primary healthcare.

BACKGROUND: Cardiac rehabilitation after acute myocardial infarction permits recovery of the heart function and enables secondary prevention programs in which changes in lifestyle habits are crucial. Cardiac rehabilitation often takes place in hospitals without coordination with primary healthcare and is not focused on individual patient preferences and goals, which is the core of the motivational interview. The objective of this study was to evaluate the efficacy of a cardiac rehabilitation program with a motivational interview in patients discharged from hospital after acute myocardial infarction. METHODS/DESIGN: A randomized, non-pharmacological clinical trial in six primary healthcare centers in Barcelona (Spain) will assess whether a tailored cardiac rehabilitation program consisting of four motivational interviews and visits with family physicians, primary healthcare nurses and a cardiologist, coordinated with the reference hospital, results in better cardiac rehabilitation than standard care. A minimum sample of 284 participants requiring cardiac rehabilitation after acute myocardial infarction will be randomized to a cardiac rehabilitation group with a motivational interview program or to standard primary healthcare. The main outcome will be physical function measured by the six-minute walk test, and the secondary outcome will be the effectiveness of secondary prevention: a composite outcome comprising control of blood pressure, cholesterol, diabetes mellitus, smoking and body weight. Results will be evaluated at 1,3 and 6 months. DISCUSSION: This is the first clinical trial to study the impact of a new primary healthcare cardiac rehabilitation program with motivational interviews for patients discharged from hospital after myocardial infarction. Changes in lifestyles and habits after myocardial infarction are a core element of secondary prevention and require patient-centered care strategies such as motivational interviews. Therefore, this study could clarify the impact of this approach on health indicators, such as functional capacity. TRIAL REGISTRATION: ClinicalTriasl.gov NCT05285969 registered on March 18, 2022.

Characterization of microbial communities from rumen and large intestine of lactating creole goats grazing in arid plant communities.

Arid plant communities provide variable diets that can affect digestive microbial communities of free-foraging ruminants. Thus, we used next-generation sequencing of 16S and 18S rDNA to characterize microbial communities in the rumen (regurgitated digesta) and large intestine (faeces) and diet composition of lactating creole goats from five flocks grazing in native plant communities in the Sonoran Desert in the rainy season. The bacterial communities in the rumen and large intestine of the five flocks had similar alpha diversity (Chao1, Shannon, and Simpson indices). However, bacterial community compositions were different: a bacterial community dominated by Proteobacteria in the rumen transitioned to a community dominated by Firmicutes in the large intestine. Bacterial communities of rumen were similar across flocks; similarly occurred with large-intestine communities. Archaea had a minimum presence in the goat digestive tract. We detected phylum Basidiomycota, Ascomycota, and Apicomplexa as the main fungi and protozoa. Analyses suggested different diet compositions; forbs and grasses composed the bulk of plants in the rumen and forbs and shrubs in faeces. Therefore, lactating goats consuming different diets in the Sonoran Desert in the rainy season share a similar core bacterial community in the rumen and another in the large intestine and present low archaeal communities.

Milk production and quality patterns of double-purpose goats grazing in arid rangelands.

Lactation curves are a valuable tool for improving flock production efficiency, adjusting flock sizes, and improving farmers' income in grazing-based livestock production. Therefore, we used natural cubic splines to estimate (a) a general flock production pattern throughout a year, (b) an average lactation curve, and (c) patterns of milk chemical components in dual-purpose goats grazing in arid plant communities in the Sierra de San Francisco, Baja California Peninsula, during years of abundant precipitation. Also, milk chemical composition was compared between flocks. Annual flock milk production showed a wiggly pattern with two greater waves in summer and spring. The average individual lactation curve (kg/doe/day) and production curves of fat, protein, lactose, and ashes (g/doe/day) showed a decreasing and wiggly pattern across 35-week lactation; the greatest average daily production was in week 2. Milk, protein, lactose, and ash production curves had similar persistency values that were greater than those of the fat production curve. Milk production had a high-positive correlation with fat production and very high-positive correlations with protein, lactose, and ash production. Density (g/ml) and fat, protein, lactose, and ash contents (%) showed a ditch-shaped pattern across lactation, with greater values at the end. Goat flocks grazing across plant communities produced different quality milk. Thus, native plant communities are a valuable resource that favors a great fat content and moderate protein content in local goat milk. Also, breeding programs must pay attention that an increment in individual milk production could decrease fat and protein production, which are valuable for cheesemaking.

Woodchip bioreactors provide sustained denitrification of brine from groundwater desalination plants.

Woodchip bioreactors are widely known as a best management practice to reduce excess nitrate loads that are discharged with agricultural leachates. The aim of this study was to evaluate the performance of citrus woodchip bioreactors for denitrification of brine (electrical conductivity ≈ 17 mS cm-1) from groundwater desalination plants with high nitrate content (NO3--N ≈ 48 mg L-1) in the Campo de Cartagena agricultural watershed, one of the main providers of horticultural products in Europe. The performance was evaluated relative to seasonal changes in temperature, dissolved organic carbon (DOC) provided by woodchips, hydraulic residence time (HRT) and woodchip aging. Bioreactors (capacity 1 m3) operated for 2.5 years (121 weeks) in batch mode (24 h HRT) with three batches per week. Denitrification efficiency was modulated by DOC concentration, temperature, hydraulic residence time and the drying-rewetting cycles. High salinity of brine did not prevent nitrate removal from occurring. The high DOC availability (>25 mg C L-1) during the first ≈48 weeks resulted in high nitrate removal rate (>75%) and nitrate removal efficiency (until ≈ 25 g N m-3 d-1) regardless of temperature. Moreover, the high DOC contents in the effluents during this period may present environmental drawbacks. Denitrification was still high after 2.5 years (reaching ≈9.3 g N m-3 d-1 in week 121), but dependence on warm temperature became more apparent with woodchips aging from week ≈49 onwards. Nitrate removal efficiency was highest on the first weekly batch, immediately after woodchips had been unsaturated for four days. It was attributable to a flush of DOC produced by aerobic microbial metabolism during drying that stimulated denitrification following re-saturation. Hence, alternance of drying-rewetting cycles is an operation practice that increase bioreactors nitrate removal performance.

Cardiovascular disease risk stratification by the Framigham score is markedly improved by ambulatory compared with office blood pressure.

INTRODUCTION AND OBJECTIVES: Ambulatory blood pressure (BP) better predicts cardiovascular disease (CVD) outcomes than office BP measurements (OBPM). Nonetheless, current CVD risk stratification models continue to rely on exclusively daytime OBPM along with traditional factors, eg, age, sex, smoking, dyslipidemia, and/or diabetes. METHODS: Data from 19 949 participants of the primary care-based Hygia Project assessed by 48-hour ambulatory BP monitoring (ABPM) and without prior CVD events were used to compare the diagnostic accuracy, discrimination, and performance of the original Framingham risk score (RSOFG) and its adjusted version to the Hygia Project study population (RSAFG) with that of a novel CVD risk stratification model constructed by replacing OBPM with ABPM-derived prognostic parameters (RSABPM). RESULTS: During the follow-up, lasting up to 12.7 years, 1854 participants experienced a primary CVD outcome of CVD death, myocardial infarction, coronary revascularization, heart failure, stroke, transient ischemic attack, angina pectoris, or peripheral artery disease. Asleep systolic BP (SBP) mean and sleep-time relative SBP decline were the only joint significant ABPM-derived predictive factors of CVD risk and were therefore used to substitute for in-clinic SBP in the RSABPM model. The RSABPM model, in comparison with the RSOFG and RSAFG models, showed significantly improved calibration, diagnostic accuracy, discrimination, and performance (always P<.001). The RSAFG-derived event-probabilities of 57.3% of the participants were outside the 95% confidence limits of the event probability determined by the RSABPM model. CONCLUSIONS: These collective findings reveal important limitations of CVD risk stratification when based upon OBPM, as in the Framingham score, and corroborate the clinical value of around-the-clock ABPM to properly diagnose true hypertension and reliably stratify CVD vulnerability.

The Hygia Project and Hygia Chronotherapy Trial: insights of we clinical investigators on the impact of the embedded continuing medical education on primary-care practice and improved patient cardiovascular health.

The participating doctors of the Hygia Chronotherapy Trial (HCT) are aware of the criticisms of its published findings, which have been unjustifiably misrepresented in letters to the editors and commentaries, perhaps because of lack of understanding of the foundations of the Hygia Project, in which the HCT is nested. Thus, our purpose through this communication is to highlight the unique features of the Hygia Project and HCT in terms of: (i) organization, management, and quality control, (ii) physician training/continuing medical education, and (iii) impact on every-day primary-care clinical practice specifically improved patient care through 48 h ambulatory blood pressure monitoring to diagnose and optimally manage by bedtime hypertension chronotherapy true arterial hypertension to markedly improve the cardiovascular health of our patients.

Bedtime hypertension chronotherapy best reduces cardiovascular disease risk as corroborated by the Hygia Chronotherapy Trial. Rebuttal to European Society of Hypertension officials.

Reinhold Kreutz and colleagues in a recent editorial claim the Hygia Chronotherapy Trial lacks credibility because of deficient methods, thereby dismissing both the plausibility and clinical significance of its reported findings. They misstate and misrepresent crucial information, findings and conclusions unambiguously detailed in the published report of the Hygia Chronotherapy Trial. The purpose of this communication is to provide a complete rebuttal to each and every one of the misleading and scientifically unsupported claims by Kreutz et al. that calls into question their expertise to decry the merits, advantages, limitations and validity of correctly designed and conducted ambulatory blood pressure monitoring-based chronotherapy trials.

Bioreactors for brine denitrification produced during polluted groundwater desalination in fertigation areas of SE Spain: batch assays for substrate selection.

Increasing knowledge of nitrate removal using denitrifying bioreactors has illustrated the usefulness of this management practice for treating discharge water from agricultural land uses. The objective of this study was to assess the viability of almond shell, chopped carob, olive bone, and citrus woodchip as carbon media for denitrification of brine with high nitrate load (EC ≈ 20 dS m-1, NO3--N concentration ≈ 65-80 mg NO3--N L-1) in bioreactors. To the authors' knowledge, this is the first test of denitrifying brine using organic wastes as the carbon substrate, and the first use of these carbon media for that purpose. Nitrate removal efficiency and efficiency:cost ratio were considered. The results indicated that the best removal efficiency and cheapest cost were provided by citrus woodchip (3.02 ± 0.15 mg NO3--N m-3 d-1) at a cost of ≈ 6€ m-3, followed by almond shell (1.54 ± 0.20 mg NO3--N m-3 d-1) at a cost of ≈ 19€ m-3. Chopped carob and olive bone showed negligible nitrate removal in the brine; chopped carob generated acidic leachate with extremely high dissolved organic carbon, and olive bone resulted in a highly saline leachate. Of the four media tested, the results of this study indicated that citrus woodchip was the most suitable media for denitrification of the brine.

Bedtime hypertension treatment improves cardiovascular risk reduction: the Hygia Chronotherapy Trial.

AIMS: The Hygia Chronotherapy Trial, conducted within the clinical primary care setting, was designed to test whether bedtime in comparison to usual upon awakening hypertension therapy exerts better cardiovascular disease (CVD) risk reduction. METHODS AND RESULTS: In this multicentre, controlled, prospective endpoint trial, 19 084 hypertensive patients (10 614 men/8470 women, 60.5 ± 13.7 years of age) were assigned (1:1) to ingest the entire daily dose of ≥1 hypertension medications at bedtime (n = 9552) or all of them upon awakening (n = 9532). At inclusion and at every scheduled clinic visit (at least annually) throughout follow-up, ambulatory blood pressure (ABP) monitoring was performed for 48 h. During the 6.3-year median patient follow-up, 1752 participants experienced the primary CVD outcome (CVD death, myocardial infarction, coronary revascularization, heart failure, or stroke). Patients of the bedtime, compared with the upon-waking, treatment-time regimen showed significantly lower hazard ratio-adjusted for significant influential characteristics of age, sex, type 2 diabetes, chronic kidney disease, smoking, HDL cholesterol, asleep systolic blood pressure (BP) mean, sleep-time relative systolic BP decline, and previous CVD event-of the primary CVD outcome [0.55 (95% CI 0.50-0.61), P < 0.001] and each of its single components (P < 0.001 in all cases), i.e. CVD death [0.44 (0.34-0.56)], myocardial infarction [0.66 (0.52-0.84)], coronary revascularization [0.60 (0.47-0.75)], heart failure [0.58 (0.49-0.70)], and stroke [0.51 (0.41-0.63)]. CONCLUSION: Routine ingestion by hypertensive patients of ≥1 prescribed BP-lowering medications at bedtime, as opposed to upon waking, results in improved ABP control (significantly enhanced decrease in asleep BP and increased sleep-time relative BP decline, i.e. BP dipping) and, most importantly, markedly diminished occurrence of major CVD events. TRIAL REGISTRATION: ClinicalTrials.gov, number NCT00741585.

About the correct definition of acanthocytes for their use as markers of glomerular haematuria / Sobre la correcta definición de los acantocitos para su uso como marcadores de hematuria glomerular

Acanthocytes, when≥5% of urinary erythrocytes examined, are considered as the most reliable marker of glomerular haematuria. However, some uncertainties still exist in the literature about their morphological definition. The aim of this paper is to discuss this topic and to suggest a univocal definition of acanthocytes as erythrocytes with the shape of a ring with one or more protrusions

Los acantocitos, cuando son≥5% de los eritrocitos urinarios examinados, se consideran el marcador más fiable de la hematuria glomerular. Sin embargo, todavía existen algunas incertidumbres en la literatura acerca de su definición morfológica. El objetivo de este artículo es discutir este tema y proponer una definición unívoca de los acantocitos como eritrocitos con la forma de un anillo con una o más protuberancias

Asleep blood pressure: significant prognostic marker of vascular risk and therapeutic target for prevention.

Aims: Sleep-time blood pressure (BP) is a stronger risk factor for cardiovascular disease (CVD) events than awake and 24 h BP means, but the potential role of asleep BP as therapeutic target for diminishing CVD risk is uncertain. We investigated whether CVD risk reduction is most associated with progressive decrease of either office or ambulatory awake or asleep BP mean. Methods and results: We prospectively evaluated 18 078 individuals with baseline ambulatory BP ranging from normotension to hypertension. At inclusion and at scheduled visits (mainly annually) during follow-up, ambulatory BP was measured for 48 consecutive hours. During the 5.1-year median follow-up, 2311 individuals had events, including 1209 experiencing the primary outcome (composite of CVD death, myocardial infarction, coronary revascularization, heart failure, and stroke). The asleep systolic blood pressure (SBP) mean was the most significant BP-derived risk factor for the primary outcome [hazard ratio 1.29 (95% CI) 1.22-1.35 per SD elevation, P < 0.001], regardless of office [1.03 (0.97-1.09), P = 0.32], and awake SBP [1.02 (0.94-1.10), P = 0.68]. Most important, the progressive attenuation of asleep SBP was the most significant marker of event-free survival [0.75 (95% CI 0.69-0.82) per SD decrease, P < 0.001], regardless of changes in office [1.07 (0.97-1.17), P = 0.18], or awake SBP mean [0.96 (0.85-1.08), P = 0.47] during follow-up. Conclusion: Asleep SBP is the most significant BP-derived risk factor for CVD events. Furthermore, treatment-induced decrease of asleep, but not awake SBP, a novel hypertension therapeutic target requiring periodic patient evaluation by ambulatory monitoring, is associated with significantly lower risk for CVD morbidity and mortality.

Axonal Injury in the Lateral Geniculate Body: Radiological Diagnosis.

Damage to the lateral geniculate body by diffuse axonal injury in brain trauma is uncommon. The authors present the clinical case and in vivo fibre tractography using diffusion tensor magnetic resonance imaging of this lesion in a patient presenting with homonymous sectoranopia after a traumatic head injury.

3D Cultivation Techniques for Primary Human Hepatocytes.

One of the main challenges in drug development is the prediction of in vivo toxicity based on in vitro data. The standard cultivation system for primary human hepatocytes is based on monolayer cultures, even if it is known that these conditions result in a loss of hepatocyte morphology and of liver-specific functions, such as drug-metabolizing enzymes and transporters. As it has been demonstrated that hepatocytes embedded between two sheets of collagen maintain their function, various hydrogels and scaffolds for the 3D cultivation of hepatocytes have been developed. To further improve or maintain hepatic functions, 3D cultivation has been combined with perfusion. In this manuscript, we discuss the benefits and drawbacks of different 3D microfluidic devices. For most systems that are currently available, the main issues are the requirement of large cell numbers, the low throughput, and expensive equipment, which render these devices unattractive for research and the drug-developing industry. A higher acceptance of these devices could be achieved by their simplification and their compatibility with high-throughput, as both aspects are of major importance for a user-friendly device.

The peopling of Greenland: further insights from the analysis of genetic diversity using autosomal and X-chromosomal markers.

The peopling of Greenland has a complex history shaped by population migrations, isolation and genetic drift. The Greenlanders present a genetic heritage with components of European and Inuit groups; previous studies using uniparentally inherited markers in Greenlanders have reported evidence of a sex-biased, admixed genetic background. This work further explores the genetics of the Greenlanders by analysing autosomal and X-chromosomal data to obtain deeper insights into the factors that shaped the genetic diversity in Greenlanders. Fourteen Greenlandic subsamples from multiple geographical settlements were compared to assess the level of genetic substructure in the Greenlandic population. The results showed low levels of genetic diversity in all sets of the genetic markers studied, together with an increased number of X-chromosomal loci in linkage disequilibrium in relation to the Danish population. In the broader context of worldwide populations, Greenlanders are remarkably different from most populations, but they are genetically closer to some Inuit groups from Alaska. Admixture analyses identified an Inuit component in the Greenlandic population of approximately 80%. The sub-populations of Ammassalik and Nanortalik are the least diverse, presenting the lowest levels of European admixture. Isolation-by-distance analyses showed that only 16% of the genetic substructure of Greenlanders is most likely to be explained by geographic barriers. We suggest that genetic drift and a differentiated settlement history around the island explain most of the genetic substructure of the population in Greenland.

(1)H-MRS is useful to reinforce the suspicion of primary central nervous system lymphoma prior to surgery.

OBJECTIVES: To assess whether (1)H-MRS may be useful to reinforce the radiological suspicion of PCNSL. METHODS: In this retrospective study, we included 546 patients with untreated brain tumours in which single-voxel spectroscopy at TE 30 ms and 136 ms had been performed. The patients were split into two subgroups: "training set" and "test set." Differences between PCNSL and five other types of intracranial tumours were assessed in the test set of patients using the Mann-Whitney U nonparametric test and cut-off values for pair-wise comparisons defined by constructing receiver operating characteristic curves. These thresholds were used to construct classifiers for binary comparison between PCNSL and non-PCNSL. The performance of the obtained classifiers was assessed in the independent test set of patients. RESULTS: Significant differences were found between PCNSL and the other groups evaluated. All bilateral comparisons performed in the test set obtained accuracy values above 70 % (71-89 %). Lipids were found to be useful to discriminate between PCNSL and glioblastoma/metastasis at short TE. Myo-inositol resonance was found to be very consistent for discriminating between PCNSL and astrocytomas at short TE. CONCLUSIONS: (1)H-MRS is useful to reinforce diagnostic suspicion of PCNSL on MRI. KEY POINTS: • (1) H-MRS can be used to reinforce the diagnostic suspicion of PCNSL. • Lipids can be used to discriminate between PCNSL and GB/MET. • Myo-inositol resonance can be used to discriminate between PCNSL and astrocytomas.

Darbepoetin inhibits proliferation of hepatic cancer cells in the presence of TGF-ß.

Darbepoetin (DPO), an erythropoietin (EPO) derivative, was licensed in 2002 to treat patients with solid tumors suffering from chemotherapy-dependent anemia, although various tumors express EPO to improve vascularization, thus favoring tumor growth and spreading. Therefore, we wanted to investigate direct effects of DPO on the liver tumor cell lines HepG2, SkHep1, Huh-7, AKN1, HCC-T and HCC-M, as well as on primary human hepatocytes (hHeps). DPO (0-40 ng/ml) did not affect viability of hHeps, HepG2, SkHep1, AKN1, HCC-T and HCC-M cells, as determined by Resazurin conversion. However, Huh-7 cells' viability dose-dependently decreased from 5 ng/ml DPO on. Lack of LDH release into culture medium and negative DNA laddering excluded apoptosis or necrosis as the cause for the reduced Resazurin conversion. In Huh-7 cells, DPO increased the expression of p53. Interestingly, Huh-7 cells showed the highest basal TGF-ß1 expression as compared to the other cell lines. Upon inhibition of TGF-ß1 signaling, DPO no longer reduced viability in Huh-7 cells. On the contrary, co-incubation with TGF-ß1 made the other cell lines responsive to DPO. Summarizing our data, we show that DPO reduces the growth of Huh-7 cells by up-regulation of the tumor-suppressor gene p53. This mechanism seems to be dependent on a strong TGF-ß expression and corresponding signaling in these cells, as other cell lines became responsive to DPO with TGF-ß1 supplementation. The knowledge of this mechanism offers great perspectives for the understanding and treatment of solid liver tumors.