The Efficacy of Geraniol and ß-Citronellol against Freshwater and Marine Monogeneans.

Monogeneans are parasitic flatworms that may be a threat for finfish aquaculture. In this study, the anthelmintic activity of two terpenes, geraniol and ß-citronellol, was tested in vitro against ancyrocephalin and diplectanid monogeneans. Experiments were performed in both water and a culture medium. We observed that monogeneans in culture medium may be more tolerant to treatments compared with bioassays performed only in water. Concentrations of 300 mg/L of both compounds were required to kill 100% of monogeneans at 1 h postexposure. The toxicity of ß-citronellol to fish was not evaluated. However, geraniol at 300 mg/L and 150 mg/L killed juvenile Nile Tilapia Oreochromis niloticus and White Snook Centropomus viridis, respectively, after a few minutes. Therefore, the present work suggests that other alternatives should be studied for use against monogeneans in aquaculture.

Pattern of use of radiotherapy for lung cancer: a descriptive study.

BACKGROUND: Lung cancer remains one of the most prevalent forms of cancer. Radiotherapy, with or without other therapeutic modalities, is an effective treatment. Our objective was to report on the use of radiotherapy for lung cancer, its variability in our region, and to compare our results with the previous study done in 2004 (VARA-I) in our region and with other published data. METHODS: We reviewed the clinical records and radiotherapy treatment sheets of all patients undergoing radiotherapy for lung cancer during 2007 in the 12 public hospitals in Andalusia, an autonomous region of Spain. Data were gathered on hospital, patient type and histological type, radiotherapy treatment characteristics, and tumor stage. RESULTS: 610 patients underwent initial radiotherapy. 37% of cases had stage III squamous cell lung cancer and were treated with radical therapy. 81% of patients with non-small and small cell lung cancer were treated with concomitant chemo-radiotherapy and the administered total dose was ≥60 Gy and ≥45 Gy respectively. The most common regimen for patients treated with palliative intent (44.6%) was 30 Gy. The total irradiation rate was 19.6% with significant differences among provinces (range, 8.5-25.6%; p<0.001). These differences were significantly correlated with the geographical distribution of radiation oncologists (r=0.78; p=0.02). Our results were similar to other published data and previous study VARA-I. CONCLUSIONS: Our results shows no differences according to the other published data and data gathered in the study VARA-I. There is still wide variability in the application of radiotherapy for lung cancer in our setting that significantly correlates with the geographical distribution of radiation oncologists.

Reversion of chronic to episodic migraine in working age and botulinum toxin-resistant patients treated with fremanezumab: A real-life study.

OBJECTIVES: The objectives of this real-life study were to analyze the reversion of chronic migraine (CM) to episodic migraine (EM) with fremanezumab, evaluate its benefit on the symptomatology, and determine the influence of possible clinical features on the reversion. BACKGROUND: The clinical manifestations of CM have a high impact on the quality of life of patients, and monoclonal antibodies such as fremanezumab are used as prophylactic treatment. METHODS: Diagnosed CM patients treated for at least 3 months with monthly fremanezumab were interviewed. The data to assess efficacy were before treatment and at the time of the interview: monthly headache days (MHDs), daily headache hours (DHHs), monthly symptomatic medication days (MSMDs), percentage of patients with symptomatic medication overuse (SMO), and pain intensity with the numerical rating scale (NRS) score. Possible predictors of reversion were analyzed: percentage of patients treated for at least 12 months, hypertension, diabetes mellitus, depression, anxiety, symptomatic control with non-steroidal anti-inflammatory drugs (NSAIDs), triptans or both, and amitriptyline prophylaxis. RESULTS: A total of 54 patients were included, of whom 40 (74.1%) were converters to EM. There were significant improvements in converters compared to pre-treatment in MHDs (28.0 vs. 5.0 days), as well as on the variables DHHs, MSMDs, and SMO. The percentage of erenumab failures was significantly higher in non-converters than in converters, as was the percentage of patients with anxiety. CONCLUSIONS: High reversion from CM to EM was achieved with fremanezumab and notable symptomatological improvement, establishing previous failure to erenumab and anxiety as possible detrimental factors for reversion.

Women's Autonomy and Anemia in Children under Five Years of Age: A Peruvian Population-Based Survey.

To determine the association between women's autonomy and the presence of childhood anemia in children under five years of age in Peru, a cross-sectional study utilizing data from the 2019 Demographic and Family Health Survey was carried out. The study employed generalized linear models with a Poisson distribution and log link function. Crude and adjusted prevalence ratios (aPR) were calculated, along with their corresponding 95% confidence intervals (CI), to assess the association of interest. A total of 15,815 women and their children under five years of age were analyzed. The prevalence of childhood anemia was 30.4% (95%CI: 29.5-31.3%), while the proportions of low, moderate and high autonomy of the mothers were 44.5%, 38.4% and 17.1%, respectively. Children under five years of age of women with a low level of autonomy were more likely to have anemia (aPR: 1.10; 95%CI: 1.00-1.21). Three out of ten children under five years of age suffer from anemia, and four out of ten mothers have a low level of autonomy. A low level of women's autonomy was associated with a higher probability of anemia in children under 5 years of age.

Outcome of mild cognitive impairment comparing early memory profiles.

BACKGROUND: : Finding variables that predict decline or stability in persons with amnestic mild cognitive impairment (aMCI) is an important step in identifying subjects in prodromal stages of dementia. This study tests a clinical observation suggesting that aMCI cases with better-preserved recognition skills, despite similar delayed recall deficits, are more likely to remain functionally stable. METHODS: : A cohort of 210 cases with aMCI, diagnosed with standardized criteria that had been followed up for 48 ± 12 months (range: 36-100), were divided into two groups according to their initial recognition memory discrimination index (DI) on the Hopkins Verbal Learning Test (DI ≥ or <8). We compared the two groups according to demographic and neuropsychological variables, cerebral small vessel disease, and outcome (progression to dementia versus stability as aMCI). RESULTS: : Thirty-seven percent progressed to dementia. In the group with the higher DI scores (n = 107), only 21.5% of the cases converted, compared with 52.4% of lower scorers (n = 103; Fisher's test: p < 0.0001). Progression to dementia occurred significantly later in cases with higher DI (50 ± 17 versus 26 ± 11 months in cases with impaired DI, Mann-Whitney test, U statistic = 1092.5, p < 0.0001). The group with lower DI showed a threefold-increased rate of progression to dementia. A multivariate regression model revealed DI, delayed recall, age, and family history of dementia as the strongest predictors of dementia, in this order. CONCLUSIONS: : The aMCI patients with better-preserved recognition at baseline have a more benign prognosis. Detection of these cases may aid in isolating other aMCI cases that are already in prodromal stages of AD and in selecting more homogeneous groups for clinical trials.

An event driven hybrid identity management approach to privacy enhanced e-health.

Credential-based authorization offers interesting advantages for ubiquitous scenarios involving limited devices such as sensors and personal mobile equipment: the verification can be done locally; it offers a more reduced computational cost than its competitors for issuing, storing, and verification; and it naturally supports rights delegation. The main drawback is the revocation of rights. Revocation requires handling potentially large revocation lists, or using protocols to check the revocation status, bringing extra communication costs not acceptable for sensors and other limited devices. Moreover, the effective revocation consent--considered as a privacy rule in sensitive scenarios--has not been fully addressed. This paper proposes an event-based mechanism empowering a new concept, the sleepyhead credentials, which allows to substitute time constraints and explicit revocation by activating and deactivating authorization rights according to events. Our approach is to integrate this concept in IdM systems in a hybrid model supporting delegation, which can be an interesting alternative for scenarios where revocation of consent and user privacy are critical. The delegation includes a SAML compliant protocol, which we have validated through a proof-of-concept implementation. This article also explains the mathematical model describing the event-based model and offers estimations of the overhead introduced by the system. The paper focus on health care scenarios, where we show the flexibility of the proposed event-based user consent revocation mechanism.

Genome-wide association analysis of susceptibility and clinical phenotype in multiple sclerosis.

Multiple sclerosis (MS), a chronic disorder of the central nervous system and common cause of neurological disability in young adults, is characterized by moderate but complex risk heritability. Here we report the results of a genome-wide association study performed in a 1000 prospective case series of well-characterized individuals with MS and group-matched controls using the Sentrix HumanHap550 BeadChip platform from Illumina. After stringent quality control data filtering, we compared allele frequencies for 551 642 SNPs in 978 cases and 883 controls and assessed genotypic influences on susceptibility, age of onset, disease severity, as well as brain lesion load and normalized brain volume from magnetic resonance imaging exams. A multi-analytical strategy identified 242 susceptibility SNPs exceeding established thresholds of significance, including 65 within the MHC locus in chromosome 6p21.3. Independent replication confirms a role for GPC5, a heparan sulfate proteoglycan, in disease risk. Gene ontology-based analysis shows a functional dichotomy between genes involved in the susceptibility pathway and those affecting the clinical phenotype.

Blunted blood pressure response to exercise and isolated muscle metaboreflex activation in patients with cirrhosis.

We sought to test the hypothesis that the cardiovascular responses to isolated muscle metaboreflex activation would be blunted in patients with cirrhosis. Eleven patients with cirrhosis and 15 healthy controls were evaluated. Blood pressure (BP; oscillometric method), contralateral forearm blood flow (FBF; venous occlusion plethysmography), and heart rate (HR; electrocardiogram) were measured during baseline, isometric handgrip at 30% of maximal voluntary contraction followed by postexercise ischemia (PEI). Forearm vascular conductance (FVC) was calculated as follows: (FBF / mean BP) × 100. Changes in HR during handgrip were similar between groups but tended to be different during PEI (controls: Δ 0.5 ± 1.1 bpm vs. cirrhotic patients: Δ 3.6 ± 1.0 bpm, P = 0.057). Mean BP response to handgrip (controls: Δ 20.9 ± 2.7 mm Hg vs. cirrhotic patients: Δ 10.6 ± 1.5 mm Hg, P = 0.006) and PEI was attenuated in cirrhotic patients (controls: Δ 16.1 ± 1.9 mm Hg vs. cirrhotic patients: Δ 7.2 ± 1.4 mm Hg, P = 0.001). In contrast, FBF and FVC increased during handgrip and decreased during PEI similarly between groups. These results indicate that an abnormal muscle metaboreflex activation explained, at least partially, the blunted pressor response to exercise exhibited by cirrhotic patients. Novelty: Patients with cirrhosis present abnormal muscle metaboreflex activation. BP response was blunted but forearm vascular response was preserved. HR response was slightly elevated.

Rationale for the Use of Radiation-Activated Mesenchymal Stromal/Stem Cells in Acute Respiratory Distress Syndrome.

We have previously shown that the combination of radiotherapy with human umbilical-cord-derived mesenchymal stromal/stem cells (MSCs) cell therapy significantly reduces the size of the xenotumors in mice, both in the directly irradiated tumor and in the distant nonirradiated tumor or its metastasis. We have also shown that exosomes secreted from MSCs preirradiated with 2 Gy are quantitatively, functionally and qualitatively different from the exosomes secreted from nonirradiated mesenchymal cells, and also that proteins, exosomes and microvesicles secreted by MSCs suffer a significant change when the cells are activated or nonactivated, with the amount of protein present in the exosomes of the preirradiated cells being 1.5 times greater compared to those from nonirradiated cells. This finding correlates with a dramatic increase in the antitumor activity of the radiotherapy when is combined with MSCs or with preirradiated mesenchymal stromal/stem cells (MSCs*). After the proteomic analysis of the load of the exosomes released from both irradiated and nonirradiated cells, we conclude that annexin A1 is the most important and significant difference between the exosomes released by the cells in either status. Knowing the role of annexin A1 in the control of hypoxia and inflammation that is characteristic of acute respiratory-distress syndrome (ARDS), we designed a hypothetical therapeutic strategy, based on the transplantation of mesenchymal stromal/stem cells stimulated with radiation, to alleviate the symptoms of patients who, due to pneumonia caused by SARS-CoV-2, require to be admitted to an intensive care unit for patients with life-threatening conditions. With this hypothesis, we seek to improve the patients' respiratory capacity and increase the expectations of their cure.

Cardiac baroreflex function and vascular reactivity recovery after aerobic exercise in patients with early cirrhosis.

OBJECTIVE: To investigate the effects of aerobic exercise on the cardiac baroreflex function and vascular reactivity in patients with cirrhosis. METHODS: Thirteen patients with cirrhosis were submitted to exercise and control intervention. At baseline and at 30 and 60 min following intervention, we evaluated cardiac baroreflex sensitivity (cBRS) and the baroreflex effectiveness index (BEI) using sequence technique. Vascular reactivity was assessed inducing reactive hyperemia before and 60 min after intervention. RESULTS: At baseline, there was no difference (P interaction = 0.848) between exercise (from 3.0 ± 0.34 to 14.60 ± 1.06 ml/100ml/min) and control sessions (from 2.38 ± 0.10 to 13.73 ± 1.05 ml/100ml/min) regarding the increase in forearm blood flow during reactive hyperemia. However, this response was higher postexercise (from 3.38 ± 0.31 to 16.58 ± 1.58 ml/100ml/min) than postcontrol intervention (from 2.04 ± 0.23 to 11.98 ± 1.16 ml/100ml/min, P interaction < 0.001). BEI increased at 30- and 60-min postexercise (from 32 ± 7 to 42 ± 7 and 46 ± 7%), but not after control intervention (from 33 ± 6 to 31 ± 5 and 33 ± 7%, P interaction = 0.014). In contrast, cBRS decreased at 30-min postexercise (from 10.3 ± 1.9 to 8.2 ± 1.4 and 10.3 ± 2.1 ms/mmHg) and increased postcontrol intervention (from 7.9 ± 0.9 to 10.5 ± 1.5 and 10.3 ± 1.3 ms/mmHg, P interaction = 0.012). CONCLUSION: The results suggest that a single bout of aerobic exercise improved cardiac baroreflex function and increased vascular reactivity in patients with early-stage cirrhosis.

Hippocampus, aging, and segregating memories.

Rats use time-of-day cues to modulate learned taste aversion memories. If adult rats are accustomed to drinking saline in the evening and they receive a lithium chloride injection after drinking saline in the morning, they form a stronger aversion to saline than rats that were conditioned after drinking saline at the familiar time. The difference indicated that the rats formed segregated representations of saline taste and the time of day the saline was consumed. This was inferred because the modulation of learning by time of day was observed when the aversions were tested at the familiar evening drinking time. If the rats had formed a compound representation of saline taste and the time of day it was consumed, the opposite pattern of differences would be expected. We used this modulation of learning by time of day to assay whether aged rats have an impaired ability to form segregated representations of experience. We find that aged rats had similar saline aversions if they were conditioned at either the familiar or the unfamiliar time of day. Furthermore, dorsal hippocampal lesions affecting also the overlying parietal cortex in the aged rats caused greater saline aversions if the rats were conditioned after drinking saline at the familiar time of day. This indicated that aged rats are aware of the time of day but after the lesion, they act as if they do not segregate saline taste from the time of day it was consumed. The results suggest that the ability to form segregated representations of a complex experience is impaired in aging and abolished by hippocampal lesions.

Hyperphosphorylated tau aggregates in the cortex and hippocampus of transgenic mice with mutant human FTDP-17 Tau and lacking the PARK2 gene.

Mutations in the PARK2 gene encoding parkin cause autosomal recessive juvenile parkinsonism, but have also been found in patients diagnosed with certain tauopathies. Conversely, mutations in the MAPT gene encoding tau are present in some types of parkinsonism. In order to investigate the possible relationship between these two proteins, we generated a double mutant mouse that is deficient in PARK2 and that over-expresses the hTauVLW transgene, a mutant form of the tau protein present in FTDP-17. Independent deletion of PARK2 or over-expression of the hTauVLW transgene produces mild phenotypic alterations, while a substantial increase in parkin expression is observed in hTauVLW transgenic mice. However, double mutant mice present memory and exploratory deficits, and accumulation of PHF-1 and AT8 hyperphosphorylated tau epitopes in neurons. These phenomena are coupled with reactive astrocytosis, DNA fragmentation, and variable cerebral atrophy. Here, we show that cortical and hippocampal neurons of double mutant mice develop argyrophilic Gallyas-Braak aggregates of phosphorylated tau from 3 months of age. Their number decreases in old animals. Moreover, numerous phosphorylated tau aggregates were identified with the conformation-dependent Alz-50 antibody and the S-Thioflavin staining. Ventral motor nuclei of the spinal cord also present Alz-50, AT8, and PHF1 hyperphosphorylated tau aggregates when parkin is deleted in mice over-expressing the hTauVLW transgene, begining at early ages. Thus, the combination of PARK2 gene deletion with hTauVLW over-expression in mice produces abnormal hyperphosphorylated tau aggregates, similar to those observed in the brain of patients diagnosed with certain tauopathies. In the light of these changes, these mice may help to understand the molecular processes responsible for these diseases, and they may aid the development of new therapeutic strategies to treat neurodegenerative diseases related to tau and parkin proteins.

Cooperative and Escaping Mechanisms between Circulating Tumor Cells and Blood Constituents.

Metastasis is the leading cause of cancer-related deaths and despite measurable progress in the field, underlying mechanisms are still not fully understood. Circulating tumor cells (CTCs) disseminate within the bloodstream, where most of them die due to the attack of the immune system. On the other hand, recent evidence shows active interactions between CTCs and platelets, myeloid cells, macrophages, neutrophils, and other hematopoietic cells that secrete immunosuppressive cytokines, which aid CTCs to evade the immune system and enable metastasis. Platelets, for instance, regulate inflammation, recruit neutrophils, and cause fibrin clots, which may protect CTCs from the attack of Natural Killer cells or macrophages and facilitate extravasation. Recently, a correlation between the commensal microbiota and the inflammatory/immune tone of the organism has been stablished. Thus, the microbiota may affect the development of cancer-promoting conditions. Furthermore, CTCs may suffer phenotypic changes, as those caused by the epithelial-mesenchymal transition, that also contribute to the immune escape and resistance to immunotherapy. In this review, we discuss the findings regarding the collaborative biological events among CTCs, immune cells, and microbiome associated to immune escape and metastatic progression.

In vitro efficacy of two terpenes against ancyrocephalid monogeneans from Nile tilapia.

Terpenes are naturally produced compounds with a broad range of biological activities. Currently, there is limited information regarding the anthelminthic effect of terpenes against monogenean parasites of fish. The aim of this work was to evaluate the in vitro efficacy of two terpenes [α-terpinene and (+)-limonene oxide] against ancyrocephalid monogeneans found on farmed Nile tilapia (Oreochromis niloticus). (+)-Limonene oxide was more effective in killing these parasites than α-terpinene, with 86 and 90% mortality at concentrations of 36 and 55.4 mg/L, respectively, with a 5-h treatment. The estimated 5-h EC50 of (+)-limonene oxide was 4.8 mg/L. Even though this compound has the potential to be used as an anthelmintic compound in finfish aquaculture, before in vivo experiments are performed, additional studies are needed to find a more effective concentration, as well as to evaluate other terpenic compounds.

Park2-null/tau transgenic mice reveal a functional relationship between parkin and tau.

Mutations, haplotypes, and polymorphisms of tau and Park-2 genes constitute risk factors for developing tauopathies. In order to analyze the possible relationship between parkin and tau we generated a double-mutant mouse deficient for Park-2 expression and overexpressing a mutant tau protein (hTauVLW). Mice develop normally, although the median survival rate is considerably reduced with respect to wild type (45%). Aggregates of phosphorylated tau in neurons and reactive gliosis are quite abundant in cortex and hippocampus of these mice. Moreover, while in young transgenic mice the hTauVLW immunostained transgene product is observed in both cell bodies and dendrites, the hTauVLW mutant protein is only detected in the neuronal cell bodies when Park-2 gene is additionally deleted. Moreover, DNA fragmentation was detected by the TUNEL method, and cerebral atrophy is also present in these regions. The levels of phosphorylated tau and Hsp70 are increased in the double-mutant mice, while CHIP expression in hippocampus is lower when the Park-2 gene is deleted. Thus, the combination of Park-2 gene deletion with hTauVLW transgene overexpression in mice produces serious neuropathological effects, which reflect the existence of some relationship between both proteins.

Memory and exploratory impairment in mice that lack the Park-2 gene and that over-express the human FTDP-17 mutant Tau.

While mutations in the Park-2 gene are the most frequent cause of autosomal-recessive juvenile parkinsonism (AR-JP), they are also present in several forms of tauopathies. Conversely, in some forms of parkinsonism, mutations in the tau gene have also been observed. Deletion of the Park-2 gene and over-expression of mutant tau independently produce mild brain alterations in mice. However, the presence of both mutations simultaneously causes a tau neuropathology, involving reactive astrocytosis, neuron loss in the cortex and hippocampus, and lesions in nigrostriatal and motor neurons. Furthermore, mutant tau over-expression in mice produces important memory impairment. When "parkin" function was abolished in young tau transgenic mice, the memory alterations were exaggerated. Moreover, additional exploratory and motor deficits were observed in older mice, causing the memory alterations to be underestimated. Thus, while memory deficits are more severe in young mice they were somehow attenuated by exploratory impairments in ageing mutants. This double mutant animal will serve as a useful experimental tool to investigate the abnormal processing of hyperphosphorylated tau and its relationship to the development of the cognitive deficits associated with certain neurodegenerative diseases.

Application of CMO (capacity, motivation, and opportunity) methodology in pharmaceutical care to optimize the pharmacotherapy in older people living with HIV. DISPIMDINAC project / Intervención farmacéutica basada en la metodología CMO para optimizar la farmacoterapia en pacientes VIH mayores. Proyecto DISPIMDINAC

Objective. To determine the effectiveness of a pharma ceutical intervention, based on the CMO methodology (capac ity, motivation and opportunity), to decrease the prevalence of the PIMDINAC concept (potentially inappropriate medica tion+drug interactions+non-adherence to concomitant med ication) in people living with HIV infection. Material and methods. Longitudinal prospective multi center study, conducted between October 2021 and October 2022. Patients living with HIV older than 65 years, on antiret roviral treatment and concomitant drug prescription were included. Demographic, clinical, and pharmacotherapeutic variables were collected. Pharmaceutical care was provided for 6 months according to the CMO model in each patient. The main variable was the percentage of patients who simultane ously fulfilled the PIMDINAC concept, comparing the baseline value with the same value at the end of the study. In addi tion, the percentage of patient’s adherent to concomitant and antiretroviral treatment and the percentage of patients meet ing the pharmacotherapeutic targets established for the pre scribed medication at 24 weeks of follow-up were compared. Results. Sixty-eight patients were included. Seventy-two percent were men, with a median age of 68 years. The medi an number of concomitant drugs was 7. A 60.6% of the pa tients had polypharmacy. The prevalence of the presence of the PIMDINAC concept decreased significantly (10.3 vs. 0%). In isolation, each of the aspects also decreased significantly (p <0.031) The percentage of patients who met the objectives improved significantly from 48,5 at baseline to 88.2 (p <0.001). Conclusions. The pharmaceutical intervention based on the CMO methodology significantly decreased the prevalence of the PIMDINAC concept and increased the number of pa tients who achieved the objectives, optimising their pharma cotherapy (AU)

Objetivo. Determinar la efectividad de una intervención farmacéutica, basada en la metodología CMO (Capacidad, Motivación y oportunidad) para disminuir la prevalencia de criterios PIMDINAC (medicación potencialmente inapropiada interacciones farmacológica-no adherencia a la medicación concomitante) en pacientes VIH+. Material y métodos. Estudio multicéntrico prospectivo longitudinal, realizado entre octubre-2021 y octubre-2022. Se incluyeron pacientes VIH+ ≥65 años, en tratamiento an tirretroviral activo y medicación concomitante prescrita. Se recogieron variables demográficas, clínicas y farmacote rapéuticas. La intervención de atención farmacéutica se rea lizó durante los 6 meses de seguimiento a través de la me todología CMO. La variable principal fue la diferencia en el porcentaje de pacientes que presentaban los tres criterios PIMDINAC de forma simultánea al inicio-fin del estudio. Se analizó la variación del porcentaje de pacientes adheren tes tanto al TAR y a la medicación concomitante, así como el porcentaje de pacientes que alcanzaron sus objetivos farma coterapéuticos previamente definidos a los 6 meses de segui miento. Resultados. Se incluyeron 67 pacientes, 72.0% varones con una mediana de edad de 68 años. El 60.6% de los pacientes tenían polifarmacia de forma basal con una mediana de fárma cos de 7.0. La presencia de criterios PIMDINAC disminuyó sig nificativamente de un 10.3 a 0%. De forma individual se redujo el porcentaje de cada criterio de forma significativa (p=0.031). Se incrementó el porcentaje de pacientes que alcanzaron sus objetivos farmacoterapéuticos (48,5% vs 88,2%; p<0.001). Conclusiones. La estrategia basada en la metodología CMO disminuye significativamente la prevalencia de los cri terios PIMDINAC, así como incrementa la consecución de los objetivos farmacoterapéuticos de los pacientes, optimizando su farmacoterapia (AU)

Radiation-induced DNA damage as a predictor of long-term toxicity in locally advanced breast cancer patients treated with high-dose hyperfractionated radical radiotherapy.

This 14-year-long study makes a novel contribution to the debate on the relationship between the in vitro radiosensitivity of peripheral blood lymphocytes and normal tissue reactions after radiation therapy. The aims were (1) to prospectively assess the degree and time of onset of skin side effects in 40 prospectively recruited consecutive patients with locally advanced breast cancer treated with a hyperfractionated dose-escalation radiotherapy schedule and (2) to assess whether initial radiation-induced DNA damage in peripheral blood lymphocytes of these patients could be used to determine their likelihood of suffering severe late damage to normal tissue. Initial radiation-induced DNA double-strand breaks (DSBs) were assessed in peripheral blood lymphocytes of these patients by pulsed-field electrophoresis. Acute and late cutaneous and subcutaneous toxicity was evaluated using the Radiation Therapy Oncology Group morbidity score. A wide interindividual variation was observed in toxicity grades and in radiation-induced DNA DSBs in peripheral blood lymphocytes (mean 1.61 +/- 0.76 DSBs/Gy per 200 MBp, range 0.63- 4.08), which were not correlated. Multivariate analysis showed a correlation (P < 0.008) between late toxicity and higher prescribed protocol dose (81.6 Gy). Analysis of the 29 patients referred to 81.6 Gy revealed significantly (P < 0.031) more frequent late subcutaneous toxicity in those with intrinsic sensitivity to radiation-induced DNA DSBs of >1.69 DSBs/Gy per DNA unit. Our demonstration of a relationship between the sensitivity of in vitro-irradiated peripheral blood lymphocytes and the risk of developing late toxic effects opens up the possibility of predicting normal tissue response to radiation in individual patients, at least in high-dose non-conventional radiation therapy regimens.

Collaborative eHealth Meets Security: Privacy-Enhancing Patient Profile Management.

Collaborative healthcare environments offer potential benefits, including enhancing the healthcare quality delivered to patients and reducing costs. As a direct consequence, sharing of electronic health records (EHRs) among healthcare providers has experienced a noteworthy growth in the last years, since it enables physicians to remotely monitor patients' health and enables individuals to manage their own health data more easily. However, these scenarios face significant challenges regarding security and privacy of the extremely sensitive information contained in EHRs. Thus, a flexible, efficient, and standards-based solution is indispensable to guarantee selective identity information disclosure and preserve patient's privacy. We propose a privacy-aware profile management approach that empowers the patient role, enabling him to bring together various healthcare providers as well as user-generated claims into an unique credential. User profiles are represented through an adaptive Merkle Tree, for which we formalize the underlying mathematical model. Furthermore, performance of the proposed solution is empirically validated through simulation experiments.

Novel antihelmintic activity of tinidazole coordination compounds. Relevance of the metal ion and structural properties.

The in vitro and in vivo antihelmintic activity of cobalt(II), copper(II) and zinc(II) coordination compounds of tinidazole (tnz) were investigated in cultivated spotted rose snapper, infested with dactylogyrid monogeneans. The tinidazole coordination compounds [Co(tnz)2Cl2], [Co(tnz)2Br2], [Cu(tnz)2Cl2], [Cu(tnz)2Br2], [Zn(tnz)2Cl2] and [Zn(tnz)2Br2] were synthesized and spectroscopically characterized. Their molecular structures were determined by their single crystal X-ray diffraction. The metal ions presented distorted tetrahedral geometries, with an intramolecular bifurcated lone pair SO⋯π, from the sulfone group with the imidazolic ring, which contributed to the stability of the compounds in solid state and in solution. Adults of dactylogyrids were exposed in vitro to tinidazole and its coordination compounds. The effective median concentrations of copper(II) coordination compounds were lower than those of cobalt(II) and zinc(II), tnz showed no activity. In vivo oral intubation tests were carried out with [Cu(tnz)2Br2], [Zn(tnz)2Br2] and tnz on snappers infected with dactylogyrids, where the copper(II) compound showed better activity. The absorption and distribution assessment for the [Cu(tnz)2Br2], showed that copper concentrations in liver were significantly higher than in blood and gills, indicating bioaccumulation in this organ. In vivo baths of [Cu(tnz)2Br2] at 25mg/L showed an effective (95% at 8h) antihelmintic effect, while [Zn(tnz)2Br2] had low antihelmintic efficacy. This study indicates that [Cu(tnz)2Br2] has an effective antihelmintic activity towards dactylogyrids monogeneans affecting cultivated spotted red snapper.