Identification of Benzodiazepine Use Based on Dried Blood Stains Analysis.

Biological matrices are typically used in forensic toxicological or pharmacological analysis: mainly blood, vitreous humor or urine. However, there are many cases in which crimes are a consequence of drug intoxication or drug abuse and they are not closed because over the months or years the samples become altered or decomposed. A dried blood stains test (DBS-MS) has recently been proposed to be used in drug toxicology when blood is found at a crime scene. This test could help an investigator to reveal what a person had consumed before the perpetration of the crime. In order to check the possibilities of this test, we analyzed several dried blood stains located on a cotton fabric. Therefore, the aim of this study was to determine if the analysis of a dried blood spot located on a cotton fabric could be an alternate source of obtaining toxicological results, particularly regarding benzodiazepines. We splashed blood stains on cotton fabric with different concentrations of the following benzodiazepines: alprazolam, bromazepam, clonazepam, diazepam and lorazepam, which were dried for 96 h and subsequently quantified by high-performance liquid chromatography coupled mass spectrometry (HPLC-MS). Our results show that it is possible to identify several benzodiazepines contained in a cotton fabric blood stain; consequently, this method may add another sample option to the toxicological analysis of biological vestiges found at a crime scene.

Cut-off value for ß-trace protein (ß-TP) as a rapid diagnostic of cerebrospinal fluid (CSF) leak detection.

Objective: To find an adequate cut-off point for beta trace protein (ß-TP) in nasal secretion (NS) and validate this diagnostic test with a large sample of patients. Likewise, we evaluated ß-TP test efficacy to confirm the cerebrospinal fluid (CSF) leakage closure after treatment. Methods: We performed a retrospective analysis with 207 samples from 162 patients with suspected CSF leakage received in the Hospital Universitario Virgen de la Arrixaca between 2010 and 2016. Twenty-five samples were included in the control group. Samples were obtained from NS through a swab to determine ß-TP using a nephelometry-based assay. Sensitivity, specificity, and area under the curve (AUC) for ß-TP in NS were assessed using the receiver operator characteristic (ROC) analysis. Results: Using imaging techniques, the diagnosis of CSF leak was confirmed in 57 patients (35.19%), while 105 had a negative diagnosis (64.81%). Patients with CSF leakage had significantly higher ß-TP values in NS (16.07 ± 16.94 mg/L, p < .001) than the control group (0.33 ± 0.12 mg/L) and patients without CSF leakage (0.61 ± 2.34 mg/L). Applying a 1 mg/L cut-off point resulted in 96.5% sensitivity and 97.1% specificity. Positive and negative predictive values (PPV and NPV) at this cut-off were 94.9% and 98.6%, respectively. Finally, this cut-off point yields a test efficacy for CSF leak diagnosis of 97% (95% CI 92.9-98.9). Conclusion: Our study has established a 1 mg/L ß-TP concentration in NS as a cut-off point for CSF leakage diagnosis with high sensibility and specificity. These results suggest that ß-TP analysis could be useful to check CSF leak resolution. Level of Evidence: 4.

Upregulation of Heat-Shock Protein (hsp)-27 in a Patient with Heterozygous SPG11 c.1951C>T and SYNJ1 c.2614G>T Mutations Causing Clinical Spastic Paraplegia.

We report a 49-year-old patient suffering from spastic paraplegia with a novel heterozygous mutation and analyzed the levels of heat shock proteins (hsp)-27, dopamine (DA), and its metabolites in their cerebrospinal fluid (CSF). The hsp27 protein concentration in the patient's CSF was assayed by an ELISA kit, while DA levels and its metabolites in the CSF, 3,4-dihydroxyphenylacetic acid (DOPAC), Cys-DA, and Cys-DOPA were measured by HPLC. Whole exome sequencing demonstrated SPG-11 c.1951C>T and novel SYNJ1 c.2614G>T mutations, both heterozygous recessive. The patient's DA and DOPAC levels in their CSF were significantly decreased (53.0 ± 6.92 and 473.3 ± 72.19, p < 0.05, respectively) while no differences were found in their Cys-DA. Nonetheless, Cys-DA/DOPAC ratio (0.213 ± 0.024, p < 0.05) and hsp27 levels (1073.0 ± 136.4, p < 0.05) were significantly higher. To the best of our knowledge, the c.2614G>T SYNJ1 mutation has not been previously reported. Our patient does not produce fully functional spatacsin and synaptojanin-1 proteins. In this line, our results showed decreased DA and DOPAC levels in the patient's CSF, indicating loss of DAergic neurons. Many factors have been described as being responsible for the increased cys-DA/DOPAC ratio, such as MAO inhibition and decreased antioxidant activity in DAergic neurons which would increase catecholquinones and consequently cysteinyl-catechols. In conclusion, haploinsufficiency of spatacsin and synaptojanin-1 proteins might be the underlying cause of neurodegeneration produced by protein trafficking defects, DA vesicle trafficking/recycling processes, autophagy dysfunction, and cell death leading to hsp27 upregulation as a cellular mechanism of protection and/or to balance impaired protein trafficking.

Carbamazepine Overdose after Psychiatric Conditions: A Case Study for Postmortem Analysis in Human Bone.

Carbamazepine is the main option used as a preventive medication to treat bipolar disorder when there is no response to lithium. Carbamazepine toxicity is defined as serum levels greater than 12 µg/mL, with severe toxicity occurring over 40 µg/mL, reduced to 30 µg/mL when combined with pharmacological treatment, i.e., benzodiazepines or antidepressants. For these reasons, it is necessary to find a validated tool to determine carbamazepine levels in an autopsy to rule out suicide or to know if the death was a consequence of an adverse drug reaction (ADR), especially when only bones can be accessed. We have validated a tool to detect and quantify drug concentration in bone. Our results showed a peak for carbamazepine at minute 12 and a mass fragment of 193 m/z. This case study is the first time in the literature that carbamazepine has been detected and quantified in bone. These results demonstrate that carbamazepine can be detected in bone tissue from forensic cases, but almost more importantly, that the method proposed is valid, reliable, and trustworthy.

Cardiac Changes in Parkinson's Disease: Lessons from Clinical and Experimental Evidence.

Dysautonomia is a common non-motor symptom in Parkinson's disease (PD). Most dysautonomic symptoms appear due to alterations in the peripheral nerves of the autonomic nervous system, including both the sympathetic and parasympathetic nervous systems. The degeneration of sympathetic nerve fibers and neurons leads to cardiovascular dysfunction, which is highly prevalent in PD patients. Cardiac alterations such as orthostatic hypotension, heart rate variability, modifications in cardiogram parameters and baroreflex dysfunction can appear in both the early and late stages of PD, worsening as the disease progresses. In PD patients it is generally found that parasympathetic activity is decreased, while sympathetic activity is increased. This situation gives rise to an imbalance of both tonicities which might, in turn, promote a higher risk of cardiac damage through tachycardia and vasoconstriction. Cardiovascular abnormalities can also appear as a side effect of PD treatment: L-DOPA can decrease blood pressure and aggravate orthostatic hypotension as a result of a negative inotropic effect on the heart. This unwanted side effect limits the therapeutic use of L-DOPA in geriatric patients with PD and can contribute to the number of hospital admissions. Therefore, it is essential to define the cardiac features related to PD for the monitorization of the heart condition in parkinsonian individuals. This information can allow the application of intervention strategies to improve the course of the disease and the proposition of new alternatives for its treatment to eliminate or reverse the motor and non-motor symptoms, especially in geriatric patients.

Could Small Heat Shock Protein HSP27 Be a First-Line Target for Preventing Protein Aggregation in Parkinson's Disease?

Small heat shock proteins (HSPs), such as HSP27, are ubiquitously expressed molecular chaperones and are essential for cellular homeostasis. The major functions of HSP27 include chaperoning misfolded or unfolded polypeptides and protecting cells from toxic stress. Dysregulation of stress proteins is associated with many human diseases including neurodegenerative diseases, such as Parkinson's disease (PD). PD is characterized by the presence of aggregates of α-synuclein in the central and peripheral nervous system, which induces the degeneration of dopaminergic neurons in the substantia nigra pars compacta (SNpc) and in the autonomic nervous system. Autonomic dysfunction is an important non-motor phenotype of PD, which includes cardiovascular dysregulation, among others. Nowadays, the therapies for PD focus on dopamine (DA) replacement. However, certain non-motor symptoms with a great impact on quality of life do not respond to dopaminergic drugs; therefore, the development and testing of new treatments for non-motor symptoms of PD remain a priority. Since small HSP27 was shown to prevent α-synuclein aggregation and cytotoxicity, this protein might constitute a suitable target to prevent or delay the motor and non-motor symptoms of PD. In the first part of our review, we focus on the cardiovascular dysregulation observed in PD patients. In the second part, we present data on the possible role of HSP27 in preventing the accumulation of amyloid fibrils and aggregated forms of α-synuclein. We also include our own studies, highlighting the possible protective cardiac effects induced by L-DOPA treatment through the enhancement of HSP27 levels and activity.

Naloxone-induced conditioned place aversion score and extinction period are higher in C57BL/6J morphine-dependent mice than in Swiss: Role of HPA axis.

Intense associative memories develop between drug-paired contextual cues and the drug withdrawal associated aversive feeling. They have been suggested to contribute to the high rate of relapse. Our study was aimed to elucidate the involvement of hypothalamic-pituitary-adrenocortical (HPA) axis activity in the expression and extinction of aversive memory in Swiss and C57BL/6J (B6) mice. The animals were rendered dependent on morphine by i.p. injection of increasing doses of morphine (10-60 mg/kg). The negative state associated with naloxone (1 mg/kg s.c.) precipitated morphine withdrawal was examined by using conditioned place aversion (CPA) paradigm. B6 mice obtained a higher aversion score and took longer to extinguish the aversive memory than Swiss mice. In addition, corticosterone levels were increased after CPA expression. Moreover, corticosterone levels were decreased during CPA extinction in Swiss mice without changes in B6 mice. Pre-treatment with the selective CRF1 receptor antagonist CP-154,526 before naloxone, impaired morphine-withdrawal aversive memory acquisition and decreased the extinction period. CP-154,526 also antagonized the increased levels of corticosterone observed after CPA expression in Swiss mice, without any changes in B6 mice. These results indicate that HPA axis could be a critical factor governing opioid withdrawal memory storage and retrieval, but in a strain or stock-specific manner. The differences observed between Swiss and B6 mice suggest that the treatment of addictive disorders should consider different individual predisposition to associate the aversive learning with the context.

[Action before ethical dilemmas in the consultation after divorce. Role of the minor according to age and level of maturity]. / Actuación ante los dilemas éticos en la consulta tras divorcio. Papel del menor según edad y nivel de madurez.

Lately, number of divorces is increasing, nevertheless, a parents' divorce can become a traumatic problem for paediatric patients. Consequently, the aim of this study was to analyze the ethical conflicts that appear in the relationship between physician/parents/son/daughter, and more specifically those that a divorce generates. A descriptive study was developed through a survey composed by 39 items. Previously, an exhaustive bibliographic analysis was carried out. Our results show that only 35% of paediatricians interviewed have been educated in bioethics although this issue is important in daily practice. Other items show that 57,5% would not cancel a pharmacological treatment in order to improve quality of life. Also, they would react against a wrong parents' decision (82,5%). They give low value to the minor`s decision (6,05%), and rarely inform exclusively to adolescents (5%). In contrast, paediatricians sometimes ask to adolescents (20%) in first place and involved them to decide in 90% of cases. Besides, there are differences in the relation with fathers and mothers, 17,5% of mothers are informed exclusively, a fact that never happens with fathers. Ethics has an intrinsic value very important in daily clinical decisions in order to respect the rules and to adapt them to the situation of every paediatric patient. When an important ethical conflict become, as a divorce is, it is essential to know who must be informed and the rights everyone has to make a decision. It is complicated to the paediatricians yet to develop 41/2002 law for Patient's autonomy.

Cardiac Protective Role of Heat Shock Protein 27 in the Stress Induced by Drugs of Abuse.

Heat shock proteins (HSP) are induced after different stress situations. Some of these proteins, particularly HSP-27, function as markers to indicate cellular stress or damage and protect the heart during addictive processes. Morphine withdrawal induces an enhancement of sympathetic activity in parallel with an increased HSP-27 expression and phosphorylation, indicating a severe situation of stress. HSP-27 can interact with different intracellular signaling pathways. Propranolol and SL-327 were able to antagonize the activation of hypothalamic-pituitary adrenal (HPA) axis and the phosphorylation of HSP-27 observed during morphine withdrawal. Therefore, ß-adrenergic receptors and the extracellular signal-regulated kinase (ERK) pathway would be involved in HPA axis activity, and consequently, in HSP-27 activation. Finally, selective blockade of corticotrophin releasing factor (CRF)-1 receptor and the genetic deletion of CRF1 receptors antagonize cardiac adaptive changes. These changes are increased noradrenaline (NA) turnover, HPA axis activation and decreased HSP-27 expression and phosphorylation. This suggests a link between the HPA axis and HSP-27. On the other hand, morphine withdrawal increases µ-calpain expression, which in turn degrades cardiac troponin T (cTnT). This fact, together with a co-localization between cTnT and HSP-27, suggests that this chaperone avoids the degradation of cTnT by µ-calpain, correcting the cardiac contractility abnormalities observed during addictive processes. The aim of our research is to review the possible role of HSP-27 in the cardiac changes observed during morphine withdrawal and to understand the mechanisms implicated in its cardiac protective functions.

Conditioned aversive memory associated with morphine withdrawal increases brain-derived neurotrophic factor in dentate gyrus and basolateral amygdala.

Morphine has been shown to increase the expression of brain-derived neurotrophic factor (BDNF) in the brain. However, little is known about the effect of conditioned naloxone-precipitated morphine withdrawal on BDNF and its precursor protein, proBDNF. We used the conditioned place aversion (CPA) paradigm to evaluate the role of corticotropin-releasing factor (CRF)/CRF1 receptor signaling on the BDNF expression and corticosterone plasma levels after CPA expression and extinction. Male mice were rendered dependent on morphine and injected acutely with naloxone before paired to confinement in a naloxone-associated compartment. The expression of BDNF and proBDNF in the dentate gyrus (DG) and basolateral amygdala (BLA) was measured in parallel with the corticosterone plasma levels with and without CRF1 receptor blockade. Mice subjected to conditioned naloxone-induced morphine withdrawal showed an increased expression of BDNF (in DG and BLA) in parallel with an enhancement of corticosterone plasma levels. These results demonstrated that BDNF expression together with the increased activity of hypothalamic-pituitary-adrenocortical (HPA) axis are critical to the acquisition of aversive memory. However, we have observed a decrease in corticosterone plasma levels and BDNF expression after CPA extinction reaffirming the importance of BDNF in the maintenance of aversive memory. In addition, the pre-treatment with the CRF1 receptor antagonist CP-154 526 before naloxone conditioning session impaired morphine withdrawal-induced aversive memory acquisition, the increased corticosterone plasma levels, and the expression of BDNF observed after CPA expression in the DG and BLA. Altogether, present results are suggesting a clear connection between HPA axis and BDNF in the formation and extinction of aversive memory.

Pharmacological modulation of the behavioral effects of social defeat in memory and learning in male mice.

RATIONALE: Previous studies have demonstrated that repeated social defeat (RSD) stress only induces cognitive deficits when experienced during adulthood. However, RSD increases cocaine-rewarding effects in adult and adolescent mice, inducing different expressions of proBDNF in the ventral tegmental area. OBJECTIVE: The aim of the present study was to evaluate the effect of cocaine administration in socially defeated adult or adolescent mice on learning, memory, and anxiety. Additionally, the role of BDNF was also studied. METHODS: Adolescent and young adult mice were exposed to four episodes of social defeat or exploration (control), being treated with a daily injection of four doses of saline or 1 mg/kg of cocaine 3 weeks after the last social defeat. Other groups were treated with the TrkB receptor antagonist ANA-12 during this 21-day period. After this treatment, their cognitive and anxiogenic profiles were evaluated, along with the expression of BDNF, pCREB, and pERK1/2 in the dentate gyrus (DG) and basolateral amygdala (BLA). RESULTS: Cocaine induced an increased expression of pCREB and BDNF in the DG and BLA only in defeated animals. Although RSD did not affect memory, the administration of cocaine induced memory impairments only in defeated animals. Defeated adult mice needed more time to complete the mazes, and this effect was counteracted by cocaine administration. RSD induced anxiogenic effects only when experienced during adulthood and cocaine induced a general anxiolytic effect. Blockade of Trkb decreased memory retention without affecting spatial learning and modified anxiety on non-stressed mice depending on their age. CONCLUSION: Our results demonstrate that the long-lasting effects of social defeat on anxiety and cognition are modulated by cocaine administration. Our results highlight that the BDNF signaling pathway could be a target to counteract the effects of cocaine on socially stressed subjects.

Binge ethanol and MDMA combination exacerbates HSP27 and Trx-1 (biomarkers of toxic cardiac effects) expression in right ventricle.

AIMS: Oxidative stress caused by exposure to drugs of abuse such as ethanol or 3, 4 methylenedioxymethamphetamine (MDMA) may derive from direct or indirect effects in many organs including the heart. The aim of the present work was to evaluate cardiac sympathetic activity and the expression and activation of two antioxidant proteins: heat shock protein27 (HSP27) and thioredoxin-1 (Trx-1) after voluntary binge ethanol consumption, alone and in combination with MDMA. MATERIAL AND METHODS: Adolescent mice received MDMA, ethanol or both. Drinking in the dark (DID) procedure was used as a model of binge. HSP27 expression and phosphorylation at serine 82 (pHSP27), Trx-1 expression, tyrosine hydroxylase (TH) and TH phosphorylated at serine 31 (pTH) were evaluated in adolescent mice 48 h and 7 days after treatments in the right ventricle. TH, HSP27 expression and phosphorylation and Trx-1 expression were measured by quantitative blot immunolabeling using specific antibodies. KEY FINDINGS: The expression of HSP27, pHSP27, Trx-1, total TH and pTH in the right ventricle was increased after binge ethanol or MDMA alone. In addition, the combination of binge ethanol + MDMA enhanced TH expression and phosphorylation versus their individual administration. SIGNIFICANCE: These results indicate that this combination could produce higher activation of sympathetic pathways, which could trigger an increased cell stress. On the other hand, increased HSP27, pHSP27 and Trx-1 expression in the right ventricle by ethanol + MDMA could be a protective mechanism to reduce the adverse effects of oxidative stress caused by both drugs of abuse.

Development and validation of a gas chromatography-mass spectrometry method for opiates and cocaine in human bone.

A method based on gas chromatography-mass spectrometry (GC-MS) is described for the determination of opioids (6-monoacetylmorphine, morphine, methadone and tramadol) and cocaine and its major metabolite in human bone. After the addition of nalorphine as internal standard, pulverized samples were incubated in acetonitrile for 1 h under ultrasounds. After adjusting the pH of the samples to 6, they were subjected to solid phase extraction and the analytes were eluted using 2 ml of dichloromethane/isopropanol/ammonia (78:20:2). Chromatography was performed on a fused silica capillary column and analytes were determined in the selected-ion-monitoring (SIM) mode. The assay was validated in the range 0.3-1 ng/mg (depending on the drug) to 150 ng/mg, the mean absolute recoveries ranging from 66% to 110%, the matrix effect from 62% to 121% and process efficiency from 61% to 89% depending on the analyte. The intra- and inter-assay accuracy values were always better than 20%. The validated method was then successfully applied to real bone samples from forensic cases in which toxicological analysis for these drugs in blood was positive. Drugs were detected in bone in 12 of the 15 blood positive results. The approximate concentration range was 3-5 ng/g for 6-monoacetylmorphine, 3-7 ng/g for morphine, 14-28 ng/g for methadone and 6 ng/g and 11 ng/g for tramadol and benzoylecgonine.

Perceived barriers to implementing screening and brief intervention for alcohol consumption by adolescents in hospital emergency department in Spain. / Barreras percibidas contra la implementación en los servicios de urgencias hospitalarios en España de un protocolo de cribado de consumo de alcohol e intervención breve en adolescentes.

BACKGROUND: Screening for alcohol consumption in adolescents is widely justified in the health care field because of the particular vulnerability of this population, which starts drinking alcohol at a very early age and frequently consumes high levels of the same. Hospital emergency departments (ED) could be a good venue to manage early detection and carry out brief intervention (BI) programmes. OBJECTIVES: The aim of this study was to identify perceived barriers for medical staff of three hospitals in Spain to successfully implement a protocol for alcohol detection and BI for minors in the ED. METHODS: Exploratory qualitative analysis using focus groups with semi-structured, flexible and open-ended questions to explore beliefs, attitudes, and barriers perceived by professionals to screening alcohol consumption and implementing BI in adolescents attended at the ED. RESULTS: The main perceived barriers by health professionals were lack of time, work overload, mistrust, lack of validated and simple screening tools, lack of training/awareness and legal concerns about informed consent and confidentiality. CONCLUSIONS: Barriers to screening and intervention in ED are similar to those described previously. It is necessary to improve organization of time allocated for medical consultations, avoid limiting ED resources, motivate staff and provide appropriate training.

Introducción: El cribado de consumo de alcohol en menores está ampliamente justificado en el ámbito sanitario por la evidencia epidemiológica de consumo y por la especial vulnerabilidad de este colectivo, que además se inicia a edades muy tempranas e ingiere grandes cantidades. Los servicios de urgencias (ED) podrían ser un entorno donde realizar la detección precoz e implementar una intervención breve (IB) por parte de los profesionales. Objetivo: El objetivo de este estudio es conocer las barreras percibidas por los profesionales sanitarios para implantar con éxito en los servicios de urgencias hospitalarios un protocolo de detección e IB en menores. Material y métodos: Análisis cualitativo exploratorio mediante grupos focales con preguntas semiestructuradas, flexibles y abiertas para conocer las creencias, actitudes y barreras percibidas por los profesionales de los centros donde se desarrollará un proyecto de cribado de consumo de alcohol e IB en adolescentes que acuden a Urgencias. Resultados: Las principales barreras percibidas fueron falta de tiempo, sobrecarga de trabajo, desconfianza en la sinceridad de las respuestas, necesidad de protocolos estandarizados de trabajo, desconocimiento de herramientas de cribado validadas y sencillas, falta de entrenamiento/concienciación y dudas médico-legales sobre el consentimiento informado y la confidencialidad del menor. Conclusiones: Las barreras percibidas para implementar la herramienta de cribado e IB son similares a las descritas por otros autores y sería necesario mejorar la organización de los circuitos asistenciales, no limitar los recursos dedicados a la atención en urgencias y favorecer la motivación y la formación de los profesionales.

Repeated social defeat and the rewarding effects of cocaine in adult and adolescent mice: dopamine transcription factors, proBDNF signaling pathways, and the TrkB receptor in the mesolimbic system.

RATIONALE: Repeated social defeat (RSD) increases the rewarding effects of cocaine in adolescent and adult rodents. OBJECTIVE: The aim of the present study was to compare the long-term effects of RSD on the conditioned rewarding effects of cocaine and levels of the transcription factors Pitx3 and Nurr1 in the ventral tegmental area (VTA), the dopamine transporter (DAT), the D2 dopamine receptor (D2DR) and precursor of brain-derived neurotrophic factor (proBDNF) signaling pathways, and the tropomyosin-related kinase B (TrkB) receptor in the nucleus accumbens (NAc) in adult and adolescent mice. METHODS: Male adolescent and young adult OF1 mice were exposed to four episodes of social defeat and were conditioned 3 weeks later with 1 mg/kg of cocaine. In a second set of mice, the expressions of the abovementioned dopaminergic and proBDNF and TrkB receptor were measured in VTA and NAc, respectively. RESULTS: Adolescent mice experienced social defeats less intensely than their adult counterparts and produced lower levels of corticosterone. However, both adult and adolescent defeated mice developed conditioned place preference for the compartment associated with this low dose of cocaine. Furthermore, only adolescent defeated mice displayed diminished levels of the transcription factors Pitx3 in the VTA, without changes in the expression of DAT and D2DR in the NAc. In addition, stressed adult mice showed a decreased expression of proBDNF and the TrkB receptor, while stressed adolescent mice exhibited increased expression of latter without changes in the former. CONCLUSION: Our findings suggest that dopaminergic pathways and proBDNF signaling and TrkB receptors play different roles in social defeat-stressed mice exposed to cocaine.

[Ethical Dilemmas in Practice of Medicine Child]. / Dilemas Éticos en la Práctica de la Medicina Infantil.

After reviewing the existing bibliography in the last 20 years, we concluded that there is a lack of information regarding the ethical conflicts that affect to pediatrics in their daily practice. It produces certain degree of uncertainty in these professionals at the time of solving these problems. We made a systematic search in the main data bases, finding more than 150 articles related, of which 80 were considered outstanding. After studying them, we have found 40 ethical dilemmas, related to some principle of solution and that we described in this article. Through them we can find such important dilemmas as those related to physical disability, palliative care or consent from children.

Conocimientos sobre el tratamiento y baja adhesión terapéutica de los pacientes anticoagulados / Knowledge about treatments and low adherence to therapy of anticoagulated patients

The main objective of this study is to measure health literacy in patients treated with oral anticoagulants and their knowledge about their treatment, and to analyze the relationships between health literacy, knowledge of their treatment, adherence, the occurrence of adverse drug reactions and several demographic and socioeconomic factors. The studied population consisted of patients going to a pharmacy with a medical prescription for oral anticoagulants. We used the abbreviated questionnaire of the European Project of Health Literacy HLS-EU-Q16 to measure health literacy and structured interviews in order to measure general knowledge about the treatment. From 133 patients in treatment with anticoagulants, 49.6% were male and the mean age was 69.72 ± 12.66 years. The levels of health literacy were in accordance with those reported by recent literature, with 51.1% of the sample having an adequate level of health literacy, 33.8% a problematic level and 15% an insufficient level. One in two patients had limited health literacy. Health literacy levels and patient knowledge were poor, and there was a relationship between them. Both decrease with age and increase with formal educational level and perceived socioeconomic status. We found no relationship between self-reported compliance or self-reported complications and health literacy or knowledge. Strategies should be implemented to promote empowerment, especially in chronic patients and those populations with fewer competencies in health information management

El objetivo principal de este trabajo es medir la alfabetización en salud en pacientes anticoagulados y sus conocimientos sobre el tratamiento que están utilizando, y analizar su relación con la adhesión, la aparición de complicaciones derivadas del medicamento y distintos factores sociodemográficos. La población en estudio consistió en pacientes que acuden a la Oficina de Farmacia con prescripción de anticoagulantes orales. Empleamos el cuestionario abreviado del Proyecto Europeo de Alfabetización en Salud HLS-EU-Q16 y realizamos entrevistas para medir los conocimientos sobre el tratamiento. De los 133 pacientes en tratamiento, 49.6% eran hombres y la media de edad era 69.72 ± 12.66 años. Los niveles de alfabetización en salud están en consonancia con los informados en la literatura reciente, de forma que el 51.1% presentaba un nivel de alfabetización en salud suficiente; el 33.8%, problemática, y el 15%, insuficiente. Uno de cada dos pacientes tenía un nivel limitado de alfabetización en salud. Los niveles de alfabetización en salud y el conocimiento de los pacientes son bajos, están relacionados entre sí y disminuyen con la edad, aumentan con el nivel educativo y socioeconómico. No encontramos elación entre la adhesión terapéutica y la aparición de complicaciones con alfabetización en salud o el conocimiento. Es necesario implementar estrategias para favorecer el empoderamiento, especialmente en los enfermos crónicos y los colectivos que presentan menos competencias a la hora de desenvolverse en el manejo de la información en salud

The Nexus of Trauma, Victimization, and Mental Health Disorders Among Incarcerated Adults in Spain.

Victimization and exposure to trauma, commonly linked to co-occurring mental health disorders, are prevalent among prison populations. The purpose of this study is to shed light on the prevalence of various kinds of victimization and trauma exposure at distinct life stages (childhood, adulthood and during prison) among incarcerated persons in Spain. The research team surveyed a random sample of 453 male and female inmates, serving time in two Spanish prisons, to gather information on experiences of physical and sexual victimization in both childhood and adulthood along with the presence or absence of in-prison treatment for a mental health disorder(s). More than 80% of participants reported experiencing some kind of traumatic/shocking life event - and this was significantly higher for those receiving in-prison mental health treatment than their non-treated counterparts (96.3 versus 83.3%, respectively). Logistic regression analyses revealed that inmates who were receiving in-prison treatment for a mental health disorder reported significantly higher rates of both physical and sexual victimization in prison, prior to prison, and during childhood. The results of this study strongly suggest the importance of comprehensive and accurate identification of inmates' traumatic, victimization, and mental health histories that necessitate treatment during incarceration. We discuss the implications of our study for correctional practice, policy and future research in order to reduce victimization in the Spanish Prison System.

Glucocorticoid receptor but not mineralocorticoid receptor mediates the activation of ERK pathway and CREB during morphine withdrawal.

Recent research suggests that glucocorticoids are involved in the development of addiction to drugs of abuse. They share this role with dopamine (DA), and with different signalling pathways and/or transcription factors such as extracellular-signal regulated kinases (ERK) and cAMP response element binding protein (CREB). However, the relation between them is not completely elucidated. In this report, we further characterize the role of glucocorticoid and mineralocorticoid receptor (GR and MR) signalling in DA turnover at the Nacc, and in opiate withdrawal-induced tyrosine hydroxylase (TH) expression, ERK and CREB phosphorylation (activation) in the nucleus of tractus solitarius (NTS-A2 ). The role of GR and MR signalling was assessed with the selective GR antagonist, mifepristone or the MR antagonist, spironolactone (i.p.). Rats were implanted two morphine (or placebo) pellets. Six days later rats were pretreated with mifepristone, spironolactone or vehicle 30 min before naloxone, and DA turnover, TH expression, ERK and CREB phosphorylation, were measured using HPLC and immunoblotting. Glucocorticoid receptor blockade attenuated ERK and CREB phosphorylation and the TH expression induced by morphine withdrawal. In contrast, no changes were seen after MR blockade. Finally, GR and MR blockade did not alter the morphine withdrawal-induced increase seen both in DA turnover and DA metabolite production, in the NAcc. These results show that not only ERK and CREB phosphorylation but also TH expression in the NTS is modulated by GR signalling. The present results suggest that GR is a therapeutic target to improve aversive events associated with opiate withdrawal.