Dendron based antifouling, MRI and magnetic hyperthermia properties of different shaped iron oxide nanoparticles.

Owing to the great potential of iron oxide nanoparticles (NPs) for nanomedicine, large efforts have been made to better control their magnetic properties, especially their magnetic anisotropy to provide NPs able to combine imaging by MRI and therapy by magnetic hyperthermia. In that context, the design of anisotropic NPs appears as a very promising and efficient strategy. Furthermore, their bioactive coating also remains a challenge as it should provide colloidal stability, biocompatibility, furtivity along with good water diffusion for MRI. By taking advantage of our controlled synthesis method of iron oxide NPs with different shapes (cubic, spherical, octopod and nanoplate), we demonstrate here that the dendron coating, shown previously to be very suitable for 10 nm sized iron oxide, also provided very good colloidal, MRI and antifouling properties to the anisotropic shaped NPs. These antifouling properties, demonstrated through several experiments and characterizations, are very promising to achieve specific targeting of disease tissues without affecting healthy organs. On the other hand, the magnetic hyperthermia properties were shown to depend on the saturation magnetization and the ability of NPs to self-align, confirming the need of a balance between crystalline and dipolar magnetic anisotropies.

Randomized clinical trial of the use of glyceryl trinitrate patches to aid arteriovenous fistula maturation.

BACKGROUND: Arteriovenous fistulas are critical for haemodialysis, but maturation rates remain poor. Experimental and anecdotal evidence has supported the use of transdermal glyceryl trinitrate (GTN) patches. The aim of this RCT was to determine whether use of a GTN patch aids arteriovenous fistula maturation. METHODS: Patients referred for arteriovenous fistula formation were eligible. The GTN or placebo patch was applied immediately after surgery and left in situ for 24 h. The primary outcome measure was the change in venous diameter at 6 weeks after fistula formation. The secondary outcome measure was clinical fistula patency at 6 weeks. RESULTS: Of 200 patients recruited (533 screened), 101 were randomized to the placebo group and 99 to the GTN group. Of these, 81 and 86 respectively completed surgery, and had follow-up data available at 6 weeks. Improvements in venous diameter were similar in the two groups: mean(s.d.) increase 2·3(1·9) mm in the placebo group compared with 2·2(1·8) mm in the GTN group (P = 0·704). The fistula failure rate did not differ significantly between the two groups: 23 per cent for placebo and 28 per cent for GTN (P = 0·596). CONCLUSION: GTN transdermal patches used for 24 h after surgery did not improve arteriovenous fistula maturation. REGISTRATION NUMBER: NCT01685710 (http://www.clinicaltrials.gov).

Integration of conflict into integrative taxonomy: fitting hybridization in species delimitation of Mesocarabus (Coleoptera: Carabidae).

In species differentiation, characters may not diverge synchronously, and there are also processes that shuffle character states in lineages descendant from a common ancestor. Species are thus expected to show some degree of incongruence among characters; therefore, taxonomic delimitation can benefit from integrative approaches and objective strategies that account for character conflict. We illustrate the potential of exploiting conflict for species delimitation in a study case of ground beetles of the subgenus Carabus (Mesocarabus), where traditional taxonomy does not accurately delimit species. The molecular phylogenies of four mitochondrial and three nuclear genes, cladistic analysis of the aedeagus, ecological niche divergence and morphometry of pronotal shape in more than 500 specimens of Mesocarabus show that these characters are not fully congruent. For these data, a three-step operational strategy is proposed for species delimitation by (i) delineating candidate species based on the integration of incongruence among conclusive lines of evidence, (ii) corroborating candidate species with inconclusive lines of evidence and (iii) refining a final species proposal based on an integrated characterization of candidate species based on the evolutionary analysis of incongruence. This procedure provided a general understanding of the reticulate process of hybridization and introgression acting on Mesocarabus and generated the hypothesis of seven Mesocarabus species, including two putative hybrid lineages. Our work emphasizes the importance of incorporating critical analyses of character and phylogenetic conflict to infer both the evolutionary history and species boundaries through an integrative taxonomic approach.

Genetic analysis of physiological components of salt tolerance conferred by Solanum rootstocks. What is the rootstock doing for the scion?

Grafting desirable crop varieties on stress-tolerant rootstocks provides an opportunity to increase crop salt tolerance. Here, a commercial hybrid tomato variety was grafted on two populations of recombinant inbred lines developed from a salt-sensitive genotype of Solanum lycopersicum var. cerasiforme, as female parent, and two salt-tolerant lines, as male parents, from S. pimpinellifolium, the P population, and S. cheesmaniae, the C population, to identify an easy screening method for identifying rootstocks conferring salt tolerance in terms of fruit yield. Potential physiological components of salt tolerance were assessed in the scion: leaf biomass, [Na(+)], nutrition, water relations and xylem ABA concentration. A significant correlation between scion fruit yield and scion leaf fresh weight, water potential or the ABA concentration was found in the C population under salinity, but the only detected QTL did not support this relationship. The rootstocks of the P population clearly affected seven traits related to the sodium, phosphorous and copper concentrations and water content of the scion leaf, showing heritability estimates around 0.4 or higher. According to heritability estimates in the P population, up to five QTLs were detected per trait. QTLs contributing over 15% to the total variance were found for P and Cu concentrations and water content of the scion leaf, and the proportion of fresh root weight. Correlation and QTL analysis suggests that rootstock-mediated improvement of fruit yield in the P population under salinity is mainly explained by the rootstock's ability to minimise perturbations in scion water status.

Comparison of the toxicity of two treatment schemes with benznidazole for chronic Chagas disease: a prospective cohort study in two Spanish referral centres.

OBJECTIVES: Chagas disease (CD) treatment is limited to two therapeutic options: benznidazole (generally the first option in Spain) and nifurtimox. Both drugs present high rates of adverse reactions and treatment discontinuation and there is no consensus regarding the most effective administration schedule for benznidazole or how to prevent and manage treatment toxicity. We aim to compare the tolerability and treatment discontinuation rate between two different treatment schemes with benznidazole. METHODS: This was a prospective observational study of adult patients with CD, enrolled from January 2014 to March 2018 in two referral centres in Madrid (Spain). Participants were treated either with benznidazole 5 mg/kg/day (full dose) over 60 days (benznidazole standard dose scheme (BSD)), or with an escalating dose lasting 5 days up to a maximum of 300 mg/day (benznidazole increasing dose scheme (BID)). RESULTS: 471 patients were analysed: 201 in the BSD group and 270 in the BID group. There were no significant differences regarding age (40.4 (SD 8.7) vs 41 (SD 8.2) years), sex (74.1% (149/201) vs 68.5% (185/270) women), weight (69.4 (SD 12.8) vs 68.9 (SD 11) kg) or nationality (97.5% (196/201) vs 96.7% (261/270) Bolivians) between groups. There were also no differences in adverse reactions rate (55.2% (111/201) vs 55.6% (150/270)), number of adverse reactions per patient, adverse reactions type (except for arthralgias and myalgias which occurred more frequently in the BID group (0% (0/111) BSD vs 8% (12/150) BID; p 0.002)) and degree and time to first adverse reactions. There was significantly more treatment discontinuation (49.8% (100/201) vs 33.0% (89/270); p <0.001) in the BSD group, but not during the first 30 days of treatment (32.3% (65/201) vs 25.6% (69/270); p 0.08). CONCLUSION: The use of increasing doses of benznidazole for 5 days and a maximum dose of 300 mg, does not significantly improve drug tolerability. However, while the treatment discontinuation rates were similar during the first 30 days of treatment, it may improve the treatment completion rate at 60 days.

Toxicity of nifurtimox as second-line treatment after benznidazole intolerance in patients with chronic Chagas disease: when available options fail.

OBJECTIVE: To describe the tolerability and rate of nifurtimox discontinuation when administered as a second-line treatment to patients with previous treatment interruptions due to adverse reactions with benznidazole. METHODS: We studied a prospective cohort study of adult patients with chronic Chagas disease in a referral centre in Spain treated from July 2007 to July 2017. We analysed the tolerability profile and treatment interruption rate due to adverse reactions (ARs) to nifurtimox in patients previously incompletely treated (less than 30 days) with benznidazole due to ARs. RESULTS: A total of 472 patients initiated treatment with benznidazole during the study period. Of these, 118 (25%) developed ARs that led to treatment discontinuation before 30 days of therapy. Fifty-three (44.9%) of 118 initiated nifurtimox as second-line treatment; most were women (79.3%), were of Bolivian origin (98.1%) and had a median age of 37.3 years (interquartile range, 29.8-43.2). The most common ARs with nifurtimox were cutaneous hypersensitivity (24.1%), digestive disorders (22.2%), fever (12.9%), neurologic disturbances (11.1%), depression, anxiety or insomnia (9.2%), dyspnoea (7.4%), myalgia (5.5%), and dizziness, asthenia or malaise (7.4%). Twenty-six (49.1%) of 53 patients discontinued nifurtimox due to ARs, all of them before the required minimal therapy duration of 60 days. There were no deaths. CONCLUSIONS: Treatment of chronic Chagas disease relies on two drugs with a poor tolerability profile. In our cohort, 12.3% of the patients who initiated benznidazole and subsequently nifurtimox in case of nontolerance developed ARs that led to permanent treatment discontinuation. Most were women of childbearing age, a group for whom therapy has the added benefit of interrupting vertical transmission.

The mitogenome of Hydropsyche pellucidula (Hydropsychidae): first gene arrangement in the insect order Trichoptera.

We describe the mitochondrial genome of Hydropsyche pellucidula Curtis 1834, which is first described for the suborder Annulipalpia and the first in the order Trichoptera to show a non-canonical gene order. The mitogenome was obtained by de novo assembly of shotgun sequenced total genomic DNA using Illumina Miseq technology, which produced an average coverage of 115× and a minimum coverage of 48×. The mitochondrial genome includes 13 protein-coding genes, 2 rRNAs and 22 tRNAs. The genome is characterized by a rearrangement in the relative position of protein-coding and ribosomal genes. This mitogenome sequence will be useful for studying the family Hydropsychidae, which is commonly used for freshwater pollution biomonitoring.

Genetic analysis of rootstock-mediated nitrogen (N) uptake and root-to-shoot signalling at contrasting N availabilities in tomato.

Selecting rootstocks for high nitrogen acquisition ability may allow decreased N fertilizer application without reducing tomato yields, minimizing environmental nitrate pollution. A commercial hybrid tomato variety was grafted on a genotyped population of 130 recombinant inbred lines (RILs) derived from Solanum pimpinellifolium, and compared with self- and non-grafted controls under contrasting nitrate availabilities (13.8 vs 1.0mM) in the nutrient solution. Grafting itself altered xylem sap composition under N-sufficient conditions, particularly Na+ (8.75-fold increase) concentration. N deprivation decreased shoot dry weight by 72.7% across the grafted RIL population, and one RIL rootstock allowed higher total leaf N content than the best of controls, suggesting more effective N uptake. Sixty-two significant QTLs were detected by multiple QTL mapping procedure for leaf N concentration (LNC), vegetative growth, and the xylem sap concentrations of Mn and four phytohormone groups (cytokinins, gibberellins, salicylic acid and jasmonic acid). Only three LNC QTLs could be common between nitrogen treatments. Clustering of rootstock QTLs controlling LNC, leaf dry weight and xylem sap salicylic acid concentration in chromosome 9 suggests a genetic relationship between this rootstock phytohormone and N uptake efficiency. Some functional candidate genes found within 2 Mbp intervals of LNC and hormone QTLs are discussed.

Lessons from genome skimming of arthropod-preserving ethanol.

Field-collected specimens of invertebrates are regularly killed and preserved in ethanol, prior to DNA extraction from the specimens, while the ethanol fraction is usually discarded. However, DNA may be released from the specimens into the ethanol, which can potentially be exploited to study species diversity in the sample without the need for DNA extraction from tissue. We used shallow shotgun sequencing of the total DNA to characterize the preservative ethanol from two pools of insects (from a freshwater habitat and terrestrial habitat) to evaluate the efficiency of DNA transfer from the specimens to the ethanol. In parallel, the specimens themselves were subjected to bulk DNA extraction and shotgun sequencing, followed by assembly of mitochondrial genomes for 39 of 40 species in the two pools. Shotgun sequencing from the ethanol fraction and read-matching to the mitogenomes detected ~40% of the arthropod species in the ethanol, confirming the transfer of DNA whose quantity was correlated to the biomass of specimens. The comparison of diversity profiles of microbiota in specimen and ethanol samples showed that 'closed association' (internal tissue) bacterial species tend to be more abundant in DNA extracted from the specimens, while 'open association' symbionts were enriched in the preservative fluid. The vomiting reflex of many insects also ensures that gut content is released into the ethanol, which provides easy access to DNA from prey items. Shotgun sequencing of DNA from preservative ethanol provides novel opportunities for characterizing the functional or ecological components of an ecosystem and their trophic interactions.

High performance multi-core iron oxide nanoparticles for magnetic hyperthermia: microwave synthesis, and the role of core-to-core interactions.

The adoption of magnetic hyperthermia as either a stand-alone or adjunct therapy for cancer is still far from being optimised due to the variable performance found in many iron oxide nanoparticle systems, including commercially available formulations. Herein, we present a reproducible and potentially scalable microwave-based method to make stable citric acid coated multi-core iron oxide nanoparticles, with exceptional magnetic heating parameters, viz. intrinsic loss parameters (ILPs) of up to 4.1 nH m(2) kg(-1), 35% better than the best commercial equivalents. We also probe the core-to-core magnetic interactions in the particles via remanence-derived Henkel and ΔM plots. These reveal a monotonic dependence of the ILP on the magnetic interaction field Hint, and show that the interactions are demagnetising in nature, and act to hinder the magnetic heating mechanism.

[Cerebrovascular accident in young adults. A study of 52 cases]. / Accidente cerebrovascular en adultos jóvenes. Estudio de 52 casos.

OBJECTIVE: A retrospective study of ischaemic and haemorrhagic cerebral vascular accidents in patients under 45 years of age, admitted to hospital Severo Ochoa (Area sanitaria 9 de la Comunidad de Madrid) during a 6 year period. METHOD: 23 CVAs in women and 29 in men were studied. The aetiology of each episode was determined following preestablished criteria. RESULTS: Aetiology: cardiac 13 (25%), atherosclerosis: 8 (15%), haematological: 6 (11%), non-atherosclerotic: 8 (15%), migraine: 1 (2%), hypertensive: 2 (3%), unknown: 15 (29%). There was a predominance of men in the patients with atherosclerosis. These also had more cardiovascular risk factors and were older than the other patients. All patients with CVA due to antiphospholipid antibodies had multiple CVAs. Examinations used to establish the aetiology were: echocardiogram, angiography, carotid doppler, hypercoagulability studies and the clinical history. CONCLUSIONS: In spite of extensive study, 30% of the CVAs in young people still have no aetiological diagnosis. In general in ischaemic CVAs, there is good recovery of the neurological defects and a low mortality. The detection and oral anticoagulation of patients with a source of cardiac emboli, and the elimination of cardiovascular risk factors would probably considerably reduce the incidence of ischaemic stroke in young adults.

Elevated plasma lipoprotein(a) level and its association with impaired fibrinolysis in patients with antiphospholipid syndrome.

OBJECTIVE: To assess the significance of lipoprotein(a) [Lp(a)], a risk factor for atherothrombosis, and its relationship with fibrinolysis in a cohort of patients with antiphospholipid syndrome (APS). METHODS: Plasma levels of Lp(a) were measured in 68 patients with APS (42 primary, 26 secondary to systemic lupus erythematosus). RESULTS: Elevated plasma levels of Lp(a) were found in patients with APS compared to 22 healthy controls (p = 0.0001). The significance persisted after comparing Lp(a) levels in 3 APS subgroups (arterial thrombosis, n = 37; venous thrombosis, n = 31; recurrent miscarriages, n = 24) with those of controls (p < 0.0001). Patients with APS with maximal elevation of Lp(a) showed a lower fibrinolytic activity (lower D-dimer and higher plasminogen activator inhibitor) than patients whose Lp(a) was within a normal range. CONCLUSION: These findings suggest that Lp(a) may represent a marker of APS and that Lp(a) has a negative effect on the fibrinolytic system that might contribute to the thrombotic tendency of APS.

Thalidomide in the treatment of the cutaneous manifestations of lupus erythematosus: experience in sixteen consecutive patients.

We review the efficacy, tolerability and safety of low-dose thalidomide in the treatment of refractory disfiguring rash in 16 patients with cutaneous manifestations of lupus. Rashes, which included discoid lupus erythematosus (DLE), subacute cutaneous lupus (SCLE), photosensitive malar rash and non-specific chronic erythema, were diagnosed on clinical grounds, supported by skin biopsy in 11/16 patients. Using starting doses of 50-100 mg/day, 7/16 (44%) patients gained complete or near-complete remission of skin disease and 6/16 (37%) partial remission. Three out of 16 patients failed to respond. Maximum benefit was achieved within 16 weeks in all patients. Doses of 25-50 mg/day were effective in maintaining response. Rapid relapse occurred in 6/8 (75%) patients following drug withdrawal, but the response to thalidomide in those requiring repeat courses appeared to be maintained. There was no detectable improvement in systemic disease. One patient developed symptoms of mild peripheral neuropathy which resolved on drug withdrawal. Our experience suggests that thalidomide is effective in the treatment of severe skin manifestations of lupus refractory to other treatment and can be used safely in specialist rheumatological practice.

Hiperlipoproteinemia en pacientes con insuficiencia renal crónica / Hyperlipoproteinemia in patients with chronic renal insufficiency

Se realizó un estudio prospectivo, longitudinal y descriptivo en el Hospital Salvador B. Gautier, Santo Domingo, República Dominicana, en el período Septiembre-noviembre de 1990 con el objetivo de determinar el tipo de hiperlipoproteinemia de los pacientes con insuficiencia renal crónica. La muestra estuvo constituida por todos los pacientes ingresados con diagnósticos de insuficiencia renal en este período lo cual hizo un total de 20 pacientes. Los níveles séricos de colesterol y triglicéricos no sufrieron alteraciones significativas. El patrón lipoprotéico más frecuentemente observado fue una hiperlipoproteinemia tipo II-A, con aumento de LDL. No se pudo relacionar la aparición de esta hiperlipoproteina con otro factor que no sea el estado intermedio de la enfermedad renal en que se encontraban estos pacientes