The genomic profiling of high-risk smoldering myeloma patients treated with an intensive strategy unveils potential markers of resistance and progression.

Smoldering multiple myeloma (SMM) precedes multiple myeloma (MM). The risk of progression of SMM patients is not uniform, thus different progression-risk models have been developed, although they are mainly based on clinical parameters. Recently, genomic predictors of progression have been defined for untreated SMM. However, the usefulness of such markers in the context of clinical trials evaluating upfront treatment in high-risk SMM (HR SMM) has not been explored yet, precluding the identification of baseline genomic alterations leading to drug resistance. For this reason, we carried out next-generation sequencing and fluorescent in-situ hybridization studies on 57 HR and ultra-high risk (UHR) SMM patients treated in the phase II GEM-CESAR clinical trial (NCT02415413). DIS3, FAM46C, and FGFR3 mutations, as well as t(4;14) and 1q alterations, were enriched in HR SMM. TRAF3 mutations were specifically associated with UHR SMM but identified cases with improved outcomes. Importantly, novel potential predictors of treatment resistance were identified: NRAS mutations and the co-occurrence of t(4;14) plus FGFR3 mutations were associated with an increased risk of biological progression. In conclusion, we have carried out for the first time a molecular characterization of HR SMM patients treated with an intensive regimen, identifying genomic predictors of poor outcomes in this setting.

2-years retrospective observational case-control study on survival and marginal bone loss of implants in patients with hereditary coagulopathies.

BACKGROUND: Evaluating 2-years implant loss and marginal bone loss in patients with hereditary coagulopathies, comparing with a healthy control group. MATERIAL AND METHODS: 37 implants in 13 patients (17 haemophilia A, 20 Von-Willebrand disease) versus 26 implants in 13 healthy patients. Data measured through Lagervall-Jansson index (after surgery, at prosthetic loading, at 2 years). STATISTICS: Chi-square, Haberman's, ANOVA, Mann-Whitney-U. Significance p<0.05. RESULTS: Haemorrhagic accidents in 2 coagulopathies patients (non-statistical differences). Hereditary coagulopathies patients suffered more hepatitis (p<0.05), HIV (p<0.05) and less previous periodontitis (p<0.01). Non-statistical differences in marginal bone loss among groups. 2 implants were lost in the hereditary coagulopathies and none in the control group (non-statistical differences). Hereditary coagulopathies patients had longer (p<0.001), and narrower implants (p<0.05) placed. 43.2% external prosthetic connection in hereditary coagulopathies patients (p<0.001); change of prosthetic platform more frequent in control group (p<0.05). 2 implants lost: external connection (p<0.05). Survival rate 96.8% (hereditary coagulopathies 94.6%, control group 100%). CONCLUSIONS: Implant and marginal bone loss at 2 years is similar in patients with hereditary coagulopathies and control group. Precautions should be taken on the treatment for hereditary coagulopathies patients, through prior haematological protocol. Implant loss only occurred in in a patient with Von-Willebrand´s disease.

Photoautotrophs and macroinvertebrate trophic relations in calcareous semiarid streams: The role of Cyanobacteria.

Photoautotrophs and macroinvertebrate trophic relations in Mediterranean streams, especially from semiarid areas, are still poorly known, as is the role of Cyanobacteria, which is the most frequently dominant photoautotroph. To investigate the role of Cyanobacteria as a food resource in these systems, the fatty acid composition of primary and secondary producers was investigated in two streams on a semiarid climatic gradient between 200 and 500 mm of rainfall in SE Spain. Fatty acid composition of photoautotrophs and macroinvertebrates differed among streams in summer and among seasons in each stream. Fatty acid fingerprints show that macroinvertebrates usually fed on the dominant photoautotroph assemblage and that Cyanobacteria represent the main food for all the feeding groups in the Alhárabe stream in winter although filamentous green algae were preferred in summer. Only scrapers consuming Chlorophyta displayed a selective feeding behaviour. The results show the importance of cyanobacteria as food for all collected macroinvertebrates in winter in some semiarid streams and confirm that fatty acids can be used as temporal and spatial markers in fluvial systems.

Use of micafungin as antifungal prophylaxis in patients undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT) in Spain (GETH-MIC).

OBJECTIVE: The fungal infections remain an important problem in the allogeneic stem cell trasnsplantation (allo-SCT) setting and thus, anti-fungal prophylaxis is commonly used. The antifungal drug should offer activity, at least against Candida and Aspergillus spp., a good safety profile and low probability interactions. Micafungin could theoretically fulfill these requisites. The aim of the study was to describe the experience with micafungin as primary prophylaxis in patients undergoing allo-SCT in a cohort of Spanish centres, and to evaluate its efficacy and tolerability in this population. METHODS: Retrospective multicentre observational study including all consecutive adult patients admitted for allo-SCT in participating centres of the Grupo Español de Trasplante Hematopoyético (GETH), from January 2010 to December 2013, who received micafungin as primary prophylaxis during the neutropenic period. RESULTS: A total of 240 patients from 13 centres were identified and 159 patients were included for the analysis. Most patients (95.6%) received 50 mg/day of micafungin. During the follow-up, 7 (4.4%) patients developed breakthrough invasive fungal disease, 1 proven and 6 probable; one patient discontinued the drug because of serious drug interactions. Prophylaxis with micafungin was considered effective in 151 (94.9%) patients. CONCLUSIONS: According to our experience, micafungin is an appropriate alternative for antifungal prophylaxis in patients undergoing an allo-HSCT, because its efficacy, its low profile of drug interactions and side-effects.

Influence of aquaculture waste on fatty acid profiles and gonad maturation of wild fish aggregations at fish farms.

Wild fish belonging to four species belonging to different trophic groups were captured at three distances from fish farm facilities: long distance (>5 Km), medium distance (1.5 Km) and close to sea-cages. Flesh, brain, liver and gonads were sampled for fatty acid analysis. Fish aggregated near sea-cages showed accumulation of fatty acids of vegetable origin in the studied tissues, due to surplus feed consumption or via predation of fish that consumed the feed. Gonads accumulated vegetable fatty acids in different manner in the different species, and the species least and most influenced by fish-feeds were selected for gonad histological examination. Results showed an acceleration of the final stages of the oocyte development in fish aggregated near fish farms compared to fish captured at long distance. Differences in oocyte development were more acute in the species which incorporated higher quantities of vegetable fatty acids.

Distribution of IFITM3 polymorphism (dbSNP: rs12252) in mestizo populations in four states of Mexico.

Interferon-inducible transmembrane protein 3 (IFITM3) participates in the defense against viral infections. This study identified and compared the frequency of the IFITM3 rs12252 polymorphism in 410 individuals in western Mexico. The western Mexican allelic frequencies (frequency of the "C" allele = 0.18) differ from some American, East Asian and European populations.

The short-term effects of farmed fish food consumed by wild fish congregating outside the farms.

We simulated in the laboratory the possible effects on fatty acids and immune status of wild fish arriving for the first time in the vicinity of a sea-cage fish farm, shifting their natural diet to commercial feed consumption, rich in fatty acids of vegetable origin. The flesh fatty acid profile of golden mullet specimens was altered after 2weeks of commercial feed consumption, showing an increase in fatty acids of vegetable origin. The serum peroxidase and bactericidal activities, and head-kidney leucocyte phagocytic capacity, increased after eight weeks of the new diet, while the respiratory burst activity decreased. The extent of these changes cannot be considered large enough to regard them as compromising the health status of fish. More research is needed in order to elucidate whether the rapid assimilation of the dietary fatty acids could harm the immune status of fish when feeding for longer periods than two months.

Molecular thrombophilic profile in Mexican patients with idiopathic recurrent pregnancy loss.

Idiopathic recurrent pregnancy loss (IRPL) is defined by three or more consecutive miscarriages occurring before the twentieth week of gestation as a result of unidentified etiological factors. The results of previous studies have indicated that prothrombotic factors play a pathogenic role in early and late pregnancy. This study aimed to identify inherited prothrombotic and hypofibrinolytic risk factors in Mexican-Mestizo patients with IRPL. Fifty-six women with IRPL and 50 control women with at least two full-term pregnancies and no history of RPL were included in this case-control study. Four prothrombotic (F5 G1691A, F2 G20210A, MTHFR C677T-A1298C) and one hypofibrinolytic (PAI1 4G/5G) restricted fragment length polymorphisms were subjected to molecular analysis. In the case of hypofibrinolytic ACE Ins/Del (I/D), identification was performed by direct PCR. The independent risk correlated with the presence of polymorphisms in IRPL patients was estimated using odds ratio (OR) with a 95% confidence interval (CI). MTHFR 677TT was the most frequent prothrombotic factor in the IRPL group (23%), followed by the compound-heterozygous C677T-A1298C (16%) and heterozygous F2 20210GA (3.6%). The heterozygous ACE I/D (62%) was the main hypofibrinolytic risk factor of IRPL, followed by the homozygote PAI1 4G/4G (18%). The ACE I/D polymorphism was the only significantly different factor among the cases and controls. The dominant genetic model D/D+I/D vs I/I showed an OR (95%CI) of 2.89 (1.22-6.89) and P = 0.019 in Mexican-Mestizo women. The results of this study support an association between the ACE I/D polymorphism and IRPL risk in a Mexican population.

Current methods of sedation in dental patients - a systematic review of the literature.

OBJECTIVE: The main objective of this systematic literature review is to identify the safest and most effective sedative drugs so as to ensure successful sedation with as few complications as possible. STUDY DESIGN: A systematic literature review of the PubMed MEDLINE database was carried out using the key words "conscious sedation," "drugs," and "dentistry." A total of 1,827 scientific articles were found, and these were narrowed down to 473 articles after applying inclusion and exclusion criteria. These 473 studies were then individually assessed for their suitability for inclusion in this literature review. RESULTS: A total of 21 studies were selected due to their rigorous study design and conduciveness to further, more exhaustive analysis. The selected studies included a total of 1,0003 patients classified as ASA I or II. Midazolam was the drug most frequently used for successful sedation in dental surgical procedures. Ketamine also proved very useful when administered intranasally, although some side effects were observed when delivered via other routes of administration. Both propofol and nitrous oxide (N2O) are also effective sedative drugs. CONCLUSIONS: Midazolam is the drug most commonly used to induce moderate sedation in dental surgical procedures, and it is also very safe. Other sedative drugs like ketamine, dexmedetomidine and propofol have also been proven safe and effective; however, further comparative clinical studies are needed to better demonstrate which of these are the safest and most effective.

UGT2B17 minor histocompatibility mismatch and clinical outcome after HLA-identical sibling donor stem cell transplantation.

Minor histocompatibility Ags (mHags) have been implicated in the pathogenesis of GVHD after allogeneic hematopoietic stem cell transplantation (HSCT). Uridine diphospho-glucuronosyltransferase 2B17 (UGT2B17) gene deletion may act as a mHag and its association with acute GVHD (aGVHD) has been described. We retrospectively studied the clinical impact of a UGT2B17 mismatch in a cohort of 1127 patients receiving a HSCT from an HLA-identical sibling donor. UGT2B17 mismatch was present in 69 cases (6.1%). Incidence of severe aGVHD was higher in the UGT2B17 mismatched pairs (22.7% vs 14.6%), but this difference was not statistically significant (P: 0.098). We did not detect differences in chronic GVHD, overall survival, relapse-free survival, transplant-related mortality or relapse. Nevertheless, when we analyzed only those patients receiving grafts from a male donor (616 cases), aGVHD was significantly higher in the UGT2B17 mismatched group (25.1% vs 12.8%; P: 0.005) and this association was confirmed by the multivariate analysis (P: 0.043; hazard ratio: 2.16, 95% confidence interval: 1.03-4.57). Overall survival was worse for patients mismatched for UGT2B17 (P: 0.005). We conclude that UGT2B17 mismatch has a negative clinical impact in allogeneic HSCT from HLA-identical sibling donors only when a male donor is used. These results should be confirmed by other studies.

Mediterranean fouling communities assimilate the organic matter derived from coastal fish farms as a new trophic resource.

Currently, the lipid content of fish feeds includes high amounts of terrestrial vegetable oils, rich in n-6 fatty acids and poor in n-3 fatty acids. Sinking organic matter in the shape of fragmented pellets and fish faeces could be ingested by the surrounding fauna attracted to the submerged structures of aquaculture facilities or living in natural benthic habitats. Fatty acids contained in feed pellets were used as trophic markers to shed light on the assimilation and incorporation of aquaculture wastes by the invertebrate fauna associated to sea-cages. Eighteen macroinvertebrate species, and zooplankton, seaweeds and sediments were collected from two fish farms, one of which (control) had not been used as such for two years. This study demonstrates that macroinvertebrate fauna present in fouling can take up sinking organic matter from farms. Further research should be directed at assessing the potential implications of aquaculture production for the surrounding ecosystem.

Molecular mechanisms by which white tea prevents oxidative stress.

The flavonoid content of tea (Camellia sinensis) has beneficial properties in the prevention of diseases. However, the mechanisms by which white tea can protect against oxidative stress remain unclear. To shed light on this issue, rats were given distilled water (controls), 0.15 mg/day (dose 1) or 0.45 mg/day (dose 2) of solid tea extract/kg body weight for 12 months. All the animals received an injection of adriamycin (ADR; 10 mg/kg body weight), except half of the control group, which were given an injection of saline solution. The expression of the nuclear factor, E2-related factor 2 (Nrf2), NAD(P)H:quinone oxidoreductase 1 (Nqo1), glutathione S-transferase (Gst), haem oxygenase-1 (Ho1), catalase (Cat), superoxide dismutase (Sod) and glutathione reductase (Gr) in liver was analysed by real-time PCR, and the activity of catalase (CAT), superoxide dismutase (SOD) and glutathione reductase (GR) was measured spectrophotometrically. ADR significantly increased the expression of Nrf2, Gst, Nqo1, Ho1, Cat, Sod and Gr with respect to the control levels and also increased the activity of CAT, SOD and GR. The intake of white tea increased in a higher degree the expression of Nrf2, Gst, Nqo1 and Ho1 in the tea + ADR group compared with the control group and C + ADR group. In addition, tea + ADR groups decreased the expression and activity of CAT, SOD and GR in a dose-dependent manner.

Cytogenetics findings in a histiocytic sarcoma case.

Histiocytic sarcoma (HS) is a neoplasm derived from histiocytes. Its diagnosis was not clear until its immunohistochemistry profile was correctly established. Not much is known about its genetic properties. We report a case of a 48-year-old male patient whose bone marrow was almost completely occupied by monomorphic medium size neoplastic cellularity. Its immunohistochemical profile was CD68(+), CD4(+), CD45(+) with negativity of other dendritic cells, and other lineage markers. Cytogenetic study showed 4 related clones: one with trisomy 8 and extra material on the short arms of chromosome 4; a second line with tetrasomy of chromosome 8, add(4)(p16); the third clone had the same alterations as the previous and deletion of chromosome 3 at q11; the fourth line had tetrasomy 8 and translocation t(3;5)(q25;q35). To our knowledge this is the first HS case showing chromosome 8 trisomy and tetrasomy and the other described alterations.

Trophic ecology of the sea urchin Spatangus purpureus elucidated from gonad fatty acids composition analysis.

Irregular sea urchins such as the spatangoid Spatangus purpureus are important bioturbators that contribute to natural biogenic disturbance and the functioning of biogeochemical cycles in soft sediments. In the coastal waters of the Balearic Islands S. purpureus occurs in soft red algal beds, and can reach high densities. The diet of S. purpureus is unknown and it is particularly difficult to analyze the stomach contents of this group; therefore, we analyzed the fatty acid (FA) composition of the gonads and potential food resources in order to assess the trophic relationships of this species. The FA profiles of the gonads of S. purpureus agree well with the FA composition of the potential trophic resources (algae and sediment) and reveals changes between localities with different available resources. Three polyunsaturated FAs mainly contributes in the composition in the S. purpureus gonads: eicosapentaenoic acid (C20:5n-3) and arachidonic acid (C20:4n-6), both abundant in the macroalgal material, and palmitoleic acid (C16:1n-7), which is characteristic of sediment samples. Trophic markers of bacterial input and carnivorous feeding were significantly more abundant in sea urchins caught on bottoms with less vegetation. The current study demonstrates that the FA content of S. purpureus gonads is a useful marker of diet, as differences in the profiles reflected the variations in detritus composition. The results of this study show that this species has omnivorous feeding behavior; however, viewed in conjunction with available abundance data the results suggest that phytodetritus found within algal beds is an important carbon source for this species.

Membrane fluidity determines sensitivity of filamentous fungi to chitosan.

The antifungal mode of action of chitosan has been studied for the last 30 years, but is still little understood. We have found that the plasma membrane forms a barrier to chitosan in chitosan-resistant but not chitosan-sensitive fungi. The plasma membranes of chitosan-sensitive fungi were shown to have more polyunsaturated fatty acids than chitosan-resistant fungi, suggesting that their permeabilization by chitosan may be dependent on membrane fluidity. A fatty acid desaturase mutant of Neurospora crassa with reduced plasma membrane fluidity exhibited increased resistance to chitosan. Steady-state fluorescence anisotropy measurements on artificial membranes showed that chitosan binds to negatively charged phospholipids that alter plasma membrane fluidity and induces membrane permeabilization, which was greatest in membranes containing more polyunsaturated lipids. Phylogenetic analysis of fungi with known sensitivity to chitosan suggests that chitosan resistance may have evolved in nematophagous and entomopathogenic fungi, which naturally encounter chitosan during infection of arthropods and nematodes. Our findings provide a method to predict the sensitivity of a fungus to chitosan based on its plasma membrane composition, and suggests a new strategy for antifungal therapy, which involves treatments that increase plasma membrane fluidity to make fungi more sensitive to fungicides such as chitosan.

Nódulos cutáneos en paciente con leucemia mieloide aguda / Cutaneous nodules in patient with acute myeloid leukemia

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Use of light, scanning electron microscopy and bioassays to evaluate parasitism by entomopathogenic fungi of the red scale insect of palms (Phoenicococcus marlatti Ckll., 1899).

We have evaluated the parasitism of the red scale insect of the date palm (Phoenicococcus marlatti) by entomopathogenic fungi, using light microscopy (LM), scanning electron microscopy (SEM) and low temperature scanning electron microscopy (LTSEM). Beauveria bassiana, Lecanicillium dimorphum and Lecanicillium cf. psalliotae, were inoculated directly on the scale insects or on insect infested plant material. We found that L. dimorphum and L. cf. psalliotae developed on plant material and on scale insects, making infection structures. B. bassiana was a bad colonizer of date palm leaves (Phoenix dactylifera L.) and did not parasite the scale insects.