New Tin (IV) and Organotin (IV) Complexes with a Hybrid Thiosemicarbazone/Hydrazone Ligand: Synthesis, Crystal Structure, and Antiproliferative Activity.

Nowadays, the search for new chemotherapeutic agents with low toxicity and high selectivity is a major concern. In this paper, we report the synthesis and characterization of a hybrid thiosemicarbazone/hydrazone ligand in its neutral form (L1H2) and as the chloride salt ([L1H3]Cl)-, three diorganotin (IV) complexes, and one complex with Sn (IV). The compounds have been fully characterized by IR, mass spectra, 1H, 13C, and 119Sn NMR, 119Sn CP/MAS NMR, and by single crystal X-ray diffraction. The organotin compounds have the empirical formula [SnR2L1] (R = Me, Bu, and Ph), but in the solid state, they are polymeric species with seven coordination number due to weak coordination of the pyridine nitrogen, whereas in solution, the polymeric structure is lost to afford hexacoordinate monomeric species. Reaction with SnI4 yields complex [Sn (L1)2]·EtOH, with the metal in a distorted dodecahedral arrangement. We have evaluated the antiproliferative activity of the two forms of the ligands and the four coordination compounds against MDA-MB-231, HeLa, PC3, and HepG2 cancer cell lines, and WI-38 normal cell line, and all the compounds present higher activity than cisplatin, used as the standard control. To investigate the mode of action, we have selected the most active complex, containing phenyl substituents, and used the triple negative breast cancer cell line MDA-MB-231. The results show that the complex induces apoptotic cell death promoted by generation of reactive oxygen species and by disruption of mitochondrial membrane potential.

Trajectory of Urine Albumin-Creatinine Ratio in Patients with Acute Heart Failure.

INTRODUCTION: Albuminuria is prevalent in patients with chronic heart failure and is a risk factor for disease progression. However, its clinical meaning in acute heart failure remains elusive. This study analyzed the trajectory of urine albumin to creatinine ratio (UACR) between admission and discharge and its association with decongestion. METHODS: In this prospective observational study, 63 patients were enrolled. UACR, B-type natriuretic peptide (BNP), and clinical congestion score (CCS) were obtained at admission and discharge. We used linear mixed regression analysis to compare changes in the natural logarithm of UACR (logUACR) and its association with changes in markers of decongestion. Estimates were reported as least squares mean with their respective 95% CIs. RESULTS: The median age of the study population was 87 years, 68.5% were women, and 69.8% had a left ventricular ejection fraction >50%. LogUACR at discharge significantly decreased in the overall population compared to admission (Δ -0.47, 95% CI: -0.78 to -0.15, p value = 0.003). The magnitude of UACR drop at discharge was associated with changes in surrogate markers of decongestion. Patients who showed a greater reduction in BNP at discharge exhibited a greater reduction in UACR (p = 0.016). The same trend was also found with clinical decongestion, as assessed by changes in CCS, however, without achieving statistical significance (p = 0.171). UACR change at discharge was not associated with changes in serum creatinine (p value = 0.923). CONCLUSION: In elderly patients with AHF and volume overload, the level of UACR significantly decreased upon discharge compared to admission. This reduction in UACR was closely linked to decreases in BNP.

Monitoring of recessive defects associated with low reproductive performance in dairy cattle in Uruguay.

Background: Most dairy cattle breeds originate show an average generational inbreeding rate of 1%, which favors the occurrence of recessive defects associated with low reproductive performance. Aim: The objective of this study was to monitor recessive defects associated with low reproductive performance in dairy cattle. Methods: To monitor bulls carrying the Holstein Friesian haplotype (HH) 1, HH3, and HH4 haplotypes, we analyzed the records of 3,028 national and imported Holstein Friesian bulls from the 2021 updated sires' catalog published by "Evaluaciones Genéticas Lecheras"; and to determine the presence of these mentioned haplotypes, as well as Jersey haplotype (JH) 1 and complex vertebral malformation (CVM), were genotype with the GeneTitan® 2,500 single nucleotide polymorphism (SNP) bovine chip, estimate their frequencies and evaluate their impact on the fertility of 100 Holstein Friesian cows and 70 Holstein Friesian-Jersey crosses belonging to an experimental dairy. Results: From a total of 1,468 (48.5%) bulls with genetic information from the sires' catalog for HH1 and 1,471 (48.6%) for HH3 and HH4, we found 90 (6.1%) carriers for HH1, 60 (4.1%) for HH3, and 6 (0.4%) for HH4, respectively. By genotyping with the chip, we calculated the herd frequency of the mutant alleles and herd prevalence of carriers for HH1 and CVM as q = 0.003 and 0.022; 0.59% and 4.3% (call rate >0.99), respectively. No mutant alleles were found for HH3, HH4, and JH1 in the analyzed population. We examined reproductive data by observing the presence of CVM and HH1 mutant alleles in repeat cows with an average of four services to achieve pregnancy. Conclusion: This study demonstrated the presence of recessive defects associated with low reproductive performance in the analyzed population, which can affect the health and productivity of dairy cattle. Therefore, cows and bulls should be closely monitored through genetic testing to lower the incidence of recessive defects in dairy cattle.

Differential patterns of within- and between-population genetically based trait variation in Lupinus angustifolius.

BACKGROUND AND AIMS: Within-population genetic and phenotypic variation play a key role in the development of adaptive responses to environmental change. Between-population variation is also an essential element in assessing the evolutionary potential of species in response to changes in environmental conditions. In this context, common garden experiments are a useful tool to separate the genetic and environmental components of phenotypic variation. We aimed to assess within- and between-population phenotypic variation of Lupinus angustifolius L. in terms of its evolutionary potential to adapt to ongoing climate change. METHODS: We evaluated populations' phenotypic variation of foliar, phenological and reproductive traits with a common garden experiment. Patterns of functional trait variation were assessed with (1) mixed model analyses and coefficients of variation (CVs) with confidence intervals, (2) principal component analyses (PCAs) and (3) correlations between pairs of traits. Analyses were performed at the population level (four populations) and at the latitude level (grouping pairs of populations located in two latitudinal ranges). KEY RESULTS: Phenotypic variation had a significant genetic component associated with a latitudinal pattern. (1) Mixed models found lower specific leaf area, advanced flowering phenology and lower seed production of heavier seeds in southern populations, whereas CV analyses showed lower within-latitude variation especially in phenological and reproductive traits in southern populations. (2) PCAs showed a clearer differentiation of phenotypic variation between latitudes than between populations. (3) Correlation analyses showed a greater number of significant correlations between traits in southern populations (25 vs. 13). CONCLUSIONS: Between-population phenotypic variation was determined by contrasting temperature and drought at different latitude and elevation. Southern populations had differential trait values compatible with adaptations to high temperatures and drought. Moreover, they had lower within-population variation and a greater number of trait correlations probably as a result of these limiting conditions, making them more vulnerable to climate change.

Transfer of ß-lactam and tetracycline antibiotics from spiked bovine milk to Dambo-type cheese, whey, and whey powder.

The aim of this study was to investigate the transfer of residues of five ß-lactam antibiotics (ampicillin, penicillin G, cloxacillin, dicloxacillin and cephalexin) and two tetracyclines (tetracycline and oxytetracycline) in the processing of cheese and whey powder, evaluating the effect of the processes and the final concentration in each product generated. Raw milk was fortified at two concentration levels with the seven antibiotics. The first concentration level (C1) was chosen according to the maximum residue limit (MRL) of each antibiotic (ampicillin and penicillin G: 4 µg kg-1; cloxacillin and dicloxacillin: 30 µg kg-1; cephalexin, tetracycline and oxytetracycline: 100 µg kg-1). The second concentration level (C2) was spiked as follows according to each antibiotic: 0.5 MRL (cloxacillin, dicloxacillin, cephalexin), 0.1 MRL (tetracycline and oxytetracycline) and 3 MRL (ampicillin and penicillin G). The antibiotics were analyzed by LC-MS/MS. No ampicillin or penicillin G residues were found in cheese or whey powder, although they were detected in whey at concentrations similar to those added to raw milk. Cephalexin was mostly distributed in whey between 82% and 96%, being the antibiotic that presented the highest concentration in whey powder (784 ± 98 µg kg-1) when milk was spiked at the MRL. The whey distribution of cloxacillin and dicloxacillin ranged from 57% to 59% for cloxacillin and from 46% to 48% for dicloxacillin, and both concentrated in whey powder. Tetracyclines were the antibiotics that concentrated in cheese, with retentions between 75% and 80% for oxytetracycline and between 83% and 87% for tetracycline. The distribution of antibiotics in the dissimilar stages of the cheese and whey powder production processes, as well as their concentration in the final products, depend on each type of antibiotic. Knowledge of the transfer of antibiotic residues during the process and final disposal is an input for the risk assessment of their consumption.

Facilitated Adaptation as A Conservation Tool in the Present Climate Change Context: A Methodological Guide.

Climate change poses a novel threat to biodiversity that urgently requires the development of adequate conservation strategies. Living organisms respond to environmental change by migrating to locations where their ecological niche is preserved or by adapting to the new environment. While the first response has been used to develop, discuss and implement the strategy of assisted migration, facilitated adaptation is only beginning to be considered as a potential approach. Here, we present a review of the conceptual framework for facilitated adaptation, integrating advances and methodologies from different disciplines. Briefly, facilitated adaptation involves a population reinforcement that introduces beneficial alleles to enable the evolutionary adaptation of a focal population to pressing environmental conditions. To this purpose, we propose two methodological approaches. The first one (called pre-existing adaptation approach) is based on using pre-adapted genotypes existing in the focal population, in other populations, or even in closely related species. The second approach (called de novo adaptation approach) aims to generate new pre-adapted genotypes from the diversity present in the species through artificial selection. For each approach, we present a stage-by-stage procedure, with some techniques that can be used for its implementation. The associated risks and difficulties of each approach are also discussed.

Population origin determines the adaptive potential for the advancement of flowering onset in Lupinus angustifolius L. (Fabaceae).

In the present framework of global warming, it is unclear whether evolutionary adaptation can happen quick enough to preserve the persistence of many species. Specifically, we lack knowledge about the adaptive potential of the different populations in relation to the various constraints that may hamper particular adaptations. There is evidence indicating that early flowering often provides an adaptive advantage to plants in temperate zones in response to global warming. Thus, the objective of this study was to assess the adaptive potential for advancing flowering onset in Lupinus angustifolius L. (Fabaceae). Seeds from four populations from two contrasting latitudes in Spain were collected and sown in a common garden environment. Selecting the 25% of the individuals that flowered earlier in the first generation, over three generations, three different early flowering selection lines were established, involving both self-crosses and outcrosses. All artificial selection lines advanced their flowering significantly with respect to the control line in the northernmost populations, but not in the southern ones. Selection lines obtained from outcrossing had a greater advancement in flowering than those from self-crossing. No differences were found in the number or weight of the seeds produced between control and artificial selection lines, probably because plants in the common garden were drip irrigated. These results suggest that northern populations may have a greater adaptive potential and that southern populations may be more vulnerable in the context of climate warming. However, earlier flowering was also associated with changes in other traits (height, biomass, shoot growth, specific leaflet area, and leaflet dry matter content), and the effects of these changes varied greatly depending on the latitude of the population and selection line. Assessments of the ability of populations to cope with climate change through this and other approaches are essential to manage species and populations in a more efficient way.

Incidence of recurrent lumbar disc herniation: A narrative review.

Background: Recurrent disc herniation is a common condition that often results in months of disabling symptoms and additional costs. Objective: The objective of this study was to investigate the incidence of recurrent disc herniation in patients treated surgically. Materials and Methods: Clinical trials and prospective studies involving patients treated with different techniques, such as open, percutaneous, or microendoscopic discectomy, were included. The incidence of recurrence as well as the level and the time until the recurrent disc herniation was collected. Results: Thirteen studies were included. Recurrence of disc herniation ranged from 0% to 14% of patients. Most recurrences occurred at the same level of herniation and on the same side. The time to recurrence of disc herniation ranged from 1 to 5 years. Conclusion: This study answers the question of how much, when, and where in lumbar recurrent disc herniation.

Abnormal Prothrombin (PIVKA-II) Expression in Canine Tissues as an Indicator of Anticoagulant Poisoning.

PIVKA-II is an aberrant form of vitamin K that has been demonstrated to be increased in human coagulation disorders and in some neoplastic diseases. In veterinary medicine, PIVKA-II levels have been demonstrated to be useful for distinguishing anticoagulant poisoning from other coagulopathies. In forensic pathology, there is the need to distinguish malicious poisoning from other causes of death and, in some cases, identifying poisoned dogs from dogs that died as a result of other coagulative disorders can be challenging. In this study, dogs that suddenly died underwent necropsy, histological examination, and toxicological analysis to establish cause of death. PIVKA-II immunohistochemical expression was evaluated on hepatic and renal tissues, and on neoplastic lesions when present. A total of 61 dogs were analyzed and anticoagulant substances were identified in 16 of the 61. Immunolabelling for PIVKA-II was observed in 27 of 61 cases in the liver and in 24 of 61 cases in the kidneys. Among the poisoned dogs, the PIVKA-II expression was present in the liver in 15 of 16 cases and in the kidneys in 16 of 16. Neoplastic lesions represented mainly by haemangiosarcomas were negative. This study highlights how the immunohistochemical expression of PIVKA-II in hepatic and renal tissues can be useful to identify patients with coagulative disorders due to clinical condition or the ingestion of anticoagulants substances.

Improved Mechanical, Thermal, and Hydrophobic Properties of PLA Modified with Alkoxysilanes by Reactive Extrusion Process.

An eco-friendly strategy for the modification of polylactic acid (PLA) surface properties, using a solvent-free process, is reported. Reactive extrusion (REX) allowed the formation of new covalent bonds between functional molecules and the PLA polymeric matrix, enhancing its mechanical properties and modifying surface hydrophobicity. To this end, the PLA backbone was modified using two alkoxysilanes, phenyltriethoxysilane and N-octyltriethoxysilane. The reactive extrusion process was carried out under mild conditions, using melting temperatures between 150 and 180 °C, 300 rpm as screw speed, and a feeding rate of 3 kg·h-1. To complete the study, flat tapes of neat and functionalized PLA were obtained through monofilament melt extrusion to quantify the enhancement of mechanical properties and hydrophobicity. The results verified that PLA modified with 3 wt% of N-octyltriethoxysilane improves mechanical and thermal properties, reaching Young's modulus values of 4.8 GPa, and PLA hydrophobic behavior, with values of water contact angle shifting from 68.6° to 82.2°.

Development and Characterization of Polyester and Acrylate-Based Composites with Hydroxyapatite and Halloysite Nanotubes for Medical Applications.

We aimed to study the distribution of hydroxyapatite (HA) and halloysite nanotubes (HNTs) as fillers and their influence on the hydrophobic character of conventional polymers used in the biomedical field. The hydrophobic polyester poly (ε-caprolactone) (PCL) was blended with its more hydrophilic counterpart poly (lactic acid) (PLA) and the hydrophilic acrylate poly (2-hydroxyethyl methacrylate) (PHEMA) was analogously compared to poly (ethyl methacrylate) (PEMA) and its copolymer. The addition of HA and HNTs clearly improve surface wettability in neat samples (PCL and PHEMA), but not that of the corresponding binary blends. Energy-dispersive X-ray spectroscopy mapping analyses show a homogenous distribution of HA with appropriate Ca/P ratios between 1.3 and 2, even on samples that were incubated for seven days in simulated body fluid, with the exception of PHEMA, which is excessively hydrophilic to promote the deposition of salts on its surface. HNTs promote large aggregates on more hydrophilic polymers. The degradation process of the biodegradable polyester PCL blended with PLA, and the addition of HA and HNTs, provide hydrophilic units and decrease the overall crystallinity of PCL. Consequently, after 12 weeks of incubation in phosphate buffered saline the mass loss increases up to 48% and mechanical properties decrease above 60% compared with the PCL/PLA blend.

Complex fine-scale spatial genetic structure in Epidendrum rhopalostele: an epiphytic orchid.

Orchid seeds are presumably dispersed by wind due to their very small size and thus can potentially travel long distances. However, the few related studies indicate that seeds fall close to their mother plants. Because seed dispersal and colonization patterns can have relevant consequences for long-term species persistence, we assessed the fine-scale genetic structure of the epiphytic orchid Epidendrum rhopalostele to provide insight into these patterns. All individuals in the studied population were georeferenced and genotyped with AFLP-markers. Genetic structure was evaluated at two levels (forest and tree) using three approaches: principal coordinates analysis, model-based clustering, and spatial autocorrelation analysis. Results showed two genetic groups, composed of individuals from almost every tree with orchids. Spatial autocorrelation analysis at the forest level found no significant genetic structure when all individuals were considered, but a pattern of genetic patches was revealed when the analysis was performed separately for each group. Genetic patches had an estimated diameter of 4 m and were composed of individuals from more than one tree. A weak genetic structure was detected at the tree level at distances less than 1.5 m. These results suggest that many seeds fall close to the mother plant and become established in the same host tree. Additionally, a sequential colonization process seems to be the predominant mode of expansion, whereby progeny from orchids in one tree colonize neighboring trees. Thus, the existence of two distinct genetic groups and the presence of genetic patches should be considered when seed sampling for ex situ conservation.

Gold(III) bis(thiosemicarbazonate) compounds in breast cancer cells: Cytotoxicity and thioredoxin reductase targeting.

Gold(III) compounds have received increasing attention in cancer research. Three gold complexes of general formula [AuIIIL]Cl, where L is benzil bis(thiosemicarbazonate), compound 1, benzil bis(4-methyl-3-thiosemicarbazonate), compound 2, or benzil bis(4-cyclohexyl-3-thiosemicarbazonate), compound 3, have been synthesized and fully characterized, including the X-ray crystal structure of compound 3, confirming square-planar geometry around the gold(III) centre. Compound 1 showed moderate cytotoxicity and accumulation in MCF7 breast cancer cells but did not inhibit thioredoxin reductase (TrxR) activity and did not induce reactive oxygen species (ROS) production. Compound 2, the least cytotoxic, was found to be capable of modestly inhibiting TrxR activity and produced low levels of ROS in the MCF7 cell line. The most cytotoxic compound, 3, had the highest cellular accumulation and its distribution pattern showed a clear preference for the cytosol and mitochondria of MCF7 cells. It readily hampered intracellular TrxR activity leading to a dramatic alteration of the cellular redox state and to the induction of cell death.

Synthesis and antimicrobial activity of tetradentate ligands bearing hydrazone and/or thiosemicarbazone motifs and their diorganotin(IV) complexes.

Four novel ligands derived from 2,3-butanedione have been synthesized, two dissymmetric thiosemicarbazone/3-hydroxy-2-naphthohydrazone ligands, H2L1 (bearing 4-isopropyl-3-thiosemicarbazone) and H2L2 (containing 4-cyclohexyl-3-thiosemicarbazone) and the symmetric H2L3, diacetyl bis(3-hydroxy-2-naphthohydrazone), and H2L4, diacetyl bis(4-cyclohexyl-3-thiosemicarbazone). Their reactivity with SnR2Cl2 (R=methyl, n-butyl and phenyl) was explored and the resulting complexes were characterized by elemental analysis, molar conductivity, mass spectrometry, IR, 1H, 13C and 119Sn NMR and seven of them also by single crystal X-ray diffraction. The results showed that the reactivity of the dissymmetric ligands is strongly different and while the cyclohexyl derivative is very stable, with isopropyl easily undergoes a symmetrization reaction to yield the corresponding symmetric ligands. The antimicrobial activity of the ligands and the corresponding diorganotin(IV) complexes was investigated in vitro against seven species of microorganisms and minimum inhibitory concentrations (MICs) were determined. The results showed that the ligand H2L2 and several of its derivatives, together with methyl and phenyl complexes of H2L1, have the ability of inhibiting the growth of tested bacteria and fungi to different extents. Bacillus subtilis and Staphylococcus aureus Gram positive strains were the most sensitive microorganisms.

Responsabilidad social universitaria en el curriculum de la carrera de medicina de la FCM-UNA del levantamiento de demandas y necesidades a la declaración del perfil genérico del egresado / University social responsibility in the curriculum career of medicine at the FCM-UNA About the obtainment of demands and needs to the development of a quality assurance system in medical training

Este trabajo se realiza en el contexto de un Proyecto de Innovación Curricular (PIC) de la FCM-UNA, basado en un modelo desarrollado por K, Troncoso y sobre la base de las tendencias y lineamientos actuales de la educación superior y la formación profesional universitaria que orienta y guía la construcción, tanto en el diseño como en la instalación y gestión, de currículos universitarios basados en competencias. Considera Hitos, fases, criterios y productos y forma parte de una propuesta metodológica y conceptual que se ha utilizado como marco de referencia y que permite organizar y estructurar la innovación curricular en la carrera de medicina. El hito 1 se refiere al levantamiento de información de las demandas y necesidades de formación a través del análisis de fuentes de investigación, actores claves y diversos marcos de referencia, para organizar y estructurar compromisos formativos para la elaboración y declaración del perfil de egreso. Por lo tanto significa justificar las decisiones tomadas, argumentando desde la lógica de la formación, la racionalidad que se espera modelar y los problemas, situaciones o contexto sobre los que el egresado actuará, utilizando como referencia las respuestas y posición frente al levantamiento de información. Esto responde a exigencias por parte de la sociedad, y así también para poder instalar una propuesta educativa con formación profesional universitaria pertinente. El hito 2 se refiere al análisis y síntesis de la información obtenida de los actores relevantes, de manera a tomar decisiones sobre cuáles son las demandas y necesidades en la formación de los estudiantes de la FCM-UNA. De esta forma ir avanzando hacia la declaración de los compromisos formativos y su representación en el perfil de egreso.

This work is done in the context of Curricular Innovation Project (CIP) of the FCM UNA, based on a model developed by K, Troncoso and based on current trends and guidelines of superior education and degree training that guides the construction, both in the design and installation of university curricula based on competencies. It considers milestones, stages, criteria and products, and forms part of a methodological and conceptual approach which has been used as a reference that allows to organize and structure the curriculum innovation in medical career. Milestone 1 refers to the obtainment of demands and needs of training through the analysis of research sources, stakeholders and various frameworks, to organize and structure training commitments for the development and declaration of the graduate profile. Therefore it means justify the decisions taken, arguing from the logic of training, the rationality that is expected to model and the problems, situation or context on which the graduate will act, using as reference the responses and position on the collection of information This responds to demands from society, and thus also to install an educational proposal with relevant university training. The milestone 2 refers to the analysis and synthesis of information from relevant stakeholders, in order to make decisions about what are the demands and needs in the training of students of the FCM-UNA. Thus moving towards the declaration of training commitments and its representation in the graduate profile.

Adult community health-promoting interventions in primary health care: A systematic review.

OBJECTIVE: To examine evidence on the effectiveness of health-promoting community interventions carried out in primary health care. METHODS: Systematic review of originals and systematic reviews of health-promoting community interventions with the participation of primary health care. A working definition of community activities was used in the inclusion criteria. Databases searched up to 2013: PUBMED, EMBASE, CINHAL, Web of SCIENCE, IBECS, IME, and PSICODOC. No restrictions on year of publication or design. Articles were reviewed by separate researchers to identify risks of bias. RESULTS: Fifty-one articles published between 1966 and 2013 were included: 11 systematic reviews and 40 originals that described 39 community interventions. There is evidence on the effectiveness of community interventions in reducing cardiovascular risk factors, encouraging physical exercise, preventing falls and improving self-care among chronic patients compared with usual individual care. The effectiveness of some interventions increases when the community is involved in their development. Most assessments show positive results despite design limitations. CONCLUSIONS: The community approach may be more effective than the individual in usual preventive interventions in primary care. There is a lack of evidence on many community interventions in primary care and further research is needed.

The crystal structure of sulfamethoxazole, interaction with DNA, DFT calculation, and molecular docking studies.

Sulfamethoxazole (SMX) [4-amino-N-(5-methyl-1,2-oxazol-3-yl)benzenesulfonamide] is structurally established by single crystal X-ray diffraction measurement. The crystal packing shows H-bonded 2D polymer through N(7)-H(7A)-O(2), N(7)-H(7B)-O(3), N(1)-H(1)-N(2), C(5)-H(5)-O(3)-S(1) and N(7)-(H7A)-O(2)-S(1). Density Functional Theory (DFT) and Time Dependent-DFT (TD-DFT) computations of optimized structure of SMX determine the electronic structure and has explained the electronic spectral transitions. The interaction of SMX with CT-DNA has been studied by absorption spectroscopy and the binding constant (Kb) is 4.37×10(4)M(-1). The in silico test of SMX with DHPS from Escherichia coli and Streptococcus pneumoniae helps to understand drug metabolism and accounts the drug-molecule interactions. The molecular docking of SMX-DNA also helps to predict the interaction feature.

Escape and lipodystrophy in acromegaly during pegvisomant therapy, a retrospective multicentre Spanish study.

BACKGROUND: Pegvisomant is an effective treatment for acromegaly. OBJECTIVE: To investigate escape (loss of biochemical control in patients previously controlled) and lipodystrophy in acromegalic patients treated with pegvisomant and to evaluate possible associations with clinical features. PATIENTS AND METHODS: Multicentre retrospective study involving 19 Spanish centres. RESULTS: Ninety-seven patients were included (59% women, mean age at diagnosis 42 ± 13 years, 80% macroadenomas); mean follow-up on pegvisomant was 5 ± 2·5 years, and 89 (92%) achieved normal IGF-1. Escape was reported in 30/89 (34%) of responders, after a mean treatment duration of 25 ± 21 months. The mean initial dose of pegvisomant was 11 ± 5 mg/day, and mean dose at escape was 14 ± 7 mg/day. Most patients (26/30, 87%) achieved control with dose increase (57%), additional medical treatment (3%) or both (27%). Mean new dose that controlled IGF-1 after escape was 20 ± 7 mg/day. Treatments associated were somatostatin analogues (SSA in 47%), cabergoline (CAB in 47%) and both (6%). Lipodystrophy was observed in 15 patients (13 females), mild in six, moderate in six, severe in three and persistent in four. Among patients with lipodystrophy, three escaped and three were nonresponders to pegvisomant. Four patients discontinued the drug, and four had dose reductions because of lipodystrophy. It tended to be more frequent in females (P = 0·06) and in patients treated with triple association SSA+CAB+PEG (P = 0·018). No relationship between escape and clinical variables was found, except prior CAB (P = 0·04) and metformin treatment (0·02) and grade of lipodystrophy (P = 0·02). CONCLUSIONS: A significant proportion of patients treated with pegvisomant escaped (34%); however, the majority (87%) was easily controlled with either dose increase, further medical treatment or both. Lipodystrophy developed in 15%, mostly females, and influenced the response to treatment.

Mycorrhizal preferences and fine spatial structure of the epiphytic orchid Epidendrum rhopalostele.

PREMISE OF THE STUDY: The presence of compatible fungi is necessary for epiphytic orchid recruitment. Thus, identifying associated mycorrhizal fungi at the population level is essential for orchid conservation. Recruitment patterns may also be conditioned by factors such as seed dispersal range and specific environmental characteristics. METHODS: In a forest plot, all trees with a diameter at breast height >1 cm and all individuals of the epiphytic orchid Epidendrum rhopalostele were identified and mapped. Additionally, one flowering individual of E. rhopalostele per each host tree was randomly selected for root sampling and DNA extraction. KEY RESULTS: A total of 239 E. rhopalostele individuals were located in 25 of the 714 potential host trees. Light microscopy of sampled roots showed mycorrhizal fungi in 22 of the 25 sampled orchids. Phylogenetic analysis of ITS1-5.8S-ITS2 sequences yielded two Tulasnella clades. In four cases, plants were found to be associated with both clades. The difference between univariate and bivariate K functions was consistent with the random labeling null model at all spatial scales, indicating that trees hosting clades A and B of Tulasnella are not spatially segregated. The analysis of the inhomogenous K function showed that host trees are not clustered, suggesting no limitations to population-scale dispersal. χ(2) analysis of contingency tables showed that E. rhopalostele is more frequent on dead trees than expected. CONCLUSIONS: EPIDENDRUM RHOPALOSTELE establishes mycorrhizal associations with at least two different Tulasnella species. The analysis of the distribution patterns of this orchid suggests a microsite preference for dead trees and no seed dispersal limitation.