The potential role of ocular and otolaryngological mucus proteins in myalgic encephalomyelitis/chronic fatigue syndrome.

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a debilitating illness associated with a constellation of other symptoms. While the most common symptom is unrelenting fatigue, many individuals also report suffering from rhinitis, dry eyes and a sore throat. Mucin proteins are responsible for contributing to the formation of mucosal membranes throughout the body. These mucosal pathways contribute to the body's defense mechanisms involving pathogenic onset. When compromised by pathogens the epithelium releases numerous cytokines and enters a prolonged state of inflammation to eradicate any particular infection. Based on genetic analysis, and computational theory and modeling we hypothesize that mucin protein dysfunction may contribute to ME/CFS symptoms due to the inability to form adequate mucosal layers throughout the body, especially in the ocular and otolaryngological pathways leading to low grade chronic inflammation and the exacerbation of symptoms.

Rheumatoid meningitis: a case series report and review of modern therapeutic schemes and outcome.

INTRODUCTION: Rheumatoid meningitis (RM) is an extremely rare extra-articular complication of rheumatoid arthritis (RA), with approximately 165 cases reported world-wide. RM exhibits a broad range of symptoms, with stroke-like episodes and seizures being the most common manifestations. The primary differential diagnoses include vascular and infectious diseases. The influence of immunomodulatory medications on the pathophysiology of RM remains unclear. There are no consensus guidelines on therapeutic regimen. METHODS: We present four patients with prior history of RA that developed different neurological syndromes in correlation to radiological leptomeningitis. Clinical presentations, comorbid conditions, supplementary diagnostic assessments, treatments, and prognosis are provided. A literature review of recent immunosuppressive management in RM patients was performed. RESULTS: Three patients presented to hospital with recurrent focal seizures. Only two suffered meningism, reporting headache and fever. Magnetic resonance imaging (MRI) showed different grades of leptomeningitis across all cases. Notably, three cases demonstrated bilateral involvement extending to the pachymeninges. Two patients exhibited pronounced CSF mononuclear inflammation while extended microbiological evaluations yielded negative results. Two patients required biopsy for confirmation. The initiation of immunosuppressive therapy marked a turning point for three patients who previously exhibited progressive deterioration. Mortality was absent in all cases. CONCLUSIONS: Our experience remarks the elusive nature of RM. Rigorous exclusionary diagnostics are imperative to differentiate RM from mimicking conditions. Clinical manifestations oscillate between transient episodes and progressive neurological impairments, punctuated by frequent epileptic seizures. In scenarios where clinical worsening persists or where clinical and radiological evaluations are inconclusive, aggressive immunosuppressive therapy is recommended.

Reelin Plasma Levels Identify Cognitive Decline in Alcohol Use Disorder Patients During Early Abstinence: The Influence of APOE4 Expression.

BACKGROUND: Apolipoprotein E (APOE)-4 isoform, reelin, and clusterin share very-low-density liporeceptor and apolipoprotein E receptor 2 receptors and are related to cognition in neuropsychiatric disorders. These proteins are expressed in plasma and brain, but studies involving plasma expression and cognition are scarce. METHODS: We studied the peripheral expression (plasma and peripheral blood mononuclear cells) of these proteins in 24 middle-aged patients with alcohol use disorder (AUD) diagnosed at 4 to 12 weeks of abstinence (t = 0) and 34 controls. Cognition was assessed using the Test of Detection of Cognitive Impairment in Alcoholism. In a follow-up study (t = 1), we measured reelin levels and evaluated cognitive improvement at 6 months of abstinence. RESULTS: APOE4 isoform was present in 37.5% and 58.8% of patients and controls, respectively, reaching similar plasma levels in ε4 carriers regardless of whether they were patients with AUD or controls. Plasma reelin and clusterin were higher in the AUD group, and reelin levels peaked in patients expressing APOE4 (P < .05, η2 = 0.09), who showed reduced very-low-density liporeceptor and apolipoprotein E receptor 2 expression in peripheral blood mononuclear cells. APOE4 had a negative effect on memory/learning mainly in the AUD group (P < .01, η2 = 0.15). Multivariate logistic regression analyses identified plasma reelin as a good indicator of AUD cognitive impairment at t = 0. At t = 1, patients with AUD showed lower reelin levels vs controls along with some cognitive improvement. CONCLUSIONS: Reelin plasma levels are elevated during early abstinence in patients with AUD who express the APOE4 isoform, identifying cognitive deterioration to a great extent, and it may participate as a homeostatic signal for cognitive recovery in the long term.

Home-based prehabilitation improves physical conditions measured by ergospirometry and 6MWT in colorectal cancer patients: a randomized controlled pilot study.

PURPOSE/BACKGROUND: Prehabilitation aims to improve physical condition in the preoperative period and, therefore, decrease the loss of cardiopulmonary capacity postoperatively, with the aim of reducing complications and promoting an early recovery. This study aims to evaluate the impact of home-based prehabilitation on the physical condition of patients treated surgically for colorectal cancer. METHODS: A prospective and randomized clinical study was conducted on 60 patients during two periods from October 2018 to February 2019 and from September 2019 to September 2020, in a single university hospital. Patients were randomized into two study groups (30 per group): prehabilitation vs. standard care. Changes in physical condition, measured at diagnosis, the day before surgery, and at 6-8 weeks after surgery using the cardiopulmonary exercise testing (CPET) and the 6-minute walk test (6MWT) were evaluated. RESULTS: Prehabilitation reduced postoperative complications (17.4% vs. 33.3%, p = 0.22) and hospital stay (5.74 vs. 6.67 days, p = 0.30). 6MWT showed a significant improvement in the prehabilitation group (+78.9 m). Six weeks after surgery, prehabilitation showed a significant improvement in the 6MWT (+68.9 m vs. -27.2 m, p = 0.01). Significant differences were also observed in the ergospirometry between the diagnosis and postoperative study (+0.79 METs vs. -0.84 METs, p = 0.001). A strong correlation was observed between CPET and 6MWT (0.767 (p < 0.001)). CONCLUSION: Home prehabilitation achieved lower overall postoperative complications than standard care and reached significant improvements in 6MWT and CET. A strong correlation was observed between CET and 6MWT, which allows validation of 6MWT as a valid and reliable measure of functional exercise capacity in colorectal patients when other, more specific and expensive tests are not available. TRIAL REGISTRATION: Registered in ClinicalTrials.gov in August 2018 with registration number https://clinicaltrials.gov/study/NCT03618329?cond=Prehabilitation%20cancer&term=arroyo&distance=50&rank=1  (NCT03618329). Initial results published in Supportive Care in Cancer: Effect of home-based prehabilitation in an enhanced recovery after surgery program for patients undergoing colorectal cancer surgery during the COVID-19 pandemic. DOI: https://doi.org/10.1007/s00520-021-06343-1 .

The Influence of the Socioeconomic Status and the Density of the Population on the Outcome After Peripheral Artery Disease.

BACKGROUND: Low socioeconomic status (SES) and living in a rural environment are associated with poorer health and a higher number of amputations among the population at large. The purpose of this study is to determine the influence of low SES and of the degree of urbanization on the short-term and long-term results of patients after revascularization for peripheral artery disease. METHODS: An observational retrospective follow-up study of 770 patients operated on for peripheral artery disease at three university centers in north-western Spain from January 2015 to December 2016. The events studied were Rutherford classification of severity upon admission, direct amputation, amputations in the follow-up period, new revascularization procedures, major adverse cardiovascular events (MACE), and overall mortality. Mean personal income and income of the household associated with the street in which each patient lived and the degree of urbanization in three areas as per Eurostat criteria: densely populated areas, intermediate density areas, and thinly populated areas. Comorbidity, surgical, and follow-up variables were also collected. Descriptive analysis and Cox regression were used. Approval was obtained from the regional ethics committee. RESULTS: Median follow-up was 47.5 months. MACE occurred in 21.5% of the series and overall mortality was 47.0%. Living in a thinly populated area is associated with a lower risk of MACE (adjusted subhazard ratio = 0.60; 95% confidence interval [CI]: 0.39-0.91). Overall survival is lower in intermediate density area patients (adjusted Hazard Ratio = 1.46; 95% CI: 1.07-2.00). The third quartile of mean personal and household income is associated with a higher risk of major amputation at follow-up (adjusted Odds Ratio 1.92, 95% CI: 1.05-3.52 and adjusted Odds Ratio 1.93, 95% CI: 1.0.3-3.61, respectively). CONCLUSIONS: Patients who live in a densely populated area run a higher risk of MACE. SES is neither associated with worse outcomes after surgery nor with MACE in long-term follow-up.

Impact of the legalisation of recreational cannabis use. / Impacto de la legalización del consumo recreativo del cannabis.

In recent years, there have been important legislative changes in many countries regarding the use of cannabis for medicinal and/or recreational purposes, which have facilitated access to it.  Uruguay, Canada and some of the US states are the only jurisdictions that have legalised recreational consumption, applying different legislative models. The aim of this review is to analyse the effects that the legalisation of recreational cannabis has had on its use and its consequences. In general, the evidence accumulated to date indicates that the legalisation of cannabis has been associated with a decrease in the price of the substance, higher concentration of THC (potency), greater diversity of presentations for consumption, lower risk perception and an increase in consumption in adults and moderately in adolescents (even though it is illegal for them to consume), as well as an increase in the adverse consequences derived from cannabis consumption on public health. There has been a decrease in drug-related arrests, but the illegal market continues to be frequently used. No increase in the demand for treatment due to cannabis consumption has been detected. Therefore, these legislative changes have so far failed to achieve their main objectives, which were to suppress the illegal market and protect the most vulnerable groups, while on the contrary, they seem to imply an increase in some of the negative aspects associated with cannabis consumption. However, taking into account that most of these legislative changes have entered into force relatively recently, a longer follow-up period is required to be able to draw definitive conclusions.

En los últimos años se han producido importantes cambios legislativos en numerosos países respecto al consumo de cannabis con fines medicinales y/o recreativos, que han facilitado su accesibilidad. Actualmente, Uruguay, Canadá y algunos estados de EE.UU. han legalizado el consumo recreativo, aplicando distintos modelos legislativos. El objetivo de la presente revisión es analizar los efectos que ha tenido la legalización del cannabis recreativo sobre su consumo y sus consecuencias. En general, las evidencias indican que la legalización se ha asociado a un descenso en el precio, mayor concentración de THC (potencia), mayor diversidad de presentaciones para su consumo, una menor percepción de riesgo y un incremento en el consumo en adultos y de forma moderada en adolescentes (aunque sea ilegal el consumo para ellos), así como un aumento de las consecuencias adversas derivadas del consumo en la salud pública. Se ha producido un descenso en los arrestos relacionados con el consumo, pero el mercado ilegal sigue utilizándose de forma habitual. No se ha detectado un incremento de la demanda de tratamiento por este consumo. Por el momento, estos cambios legislativos no han conseguido alcanzar sus objetivos principales que eran suprimir el mercado ilegal y proteger a los grupos más vulnerables, mientras que, por el contrario, parecen implicar un incremento de algunos aspectos negativos asociados al consumo de cannabis. Sin embargo, teniendo en cuenta que la mayoría de estos cambios legislativos han entrado en vigor hace relativamente poco tiempo, se requiere un periodo de seguimiento mayor para poder extraer conclusiones definitivas.

Psychological recovery stages of alcohol dependent patients after an intensive outpatient treatment: A 4-year follow-up study. / Fases de la recuperación psicológica en pacientes dependientes del alcohol tras un tratamiento intensivo: Un seguimiento de 4 años.

The aim of this work is to determine if relapses can hinder the sequence of psychological recovery and to rebuild this sequence in patients with severe alcohol dependence that seek treatment. The sample was comprised of 159 patients seeking an intensive outpatient treatment of two years duration and who were subject to follow-up during four years after discharge. Patients were grouped according to the presence of relapse during follow-up, resulting in abstainers (n = 80) and relapsers (n = 79). Assessments were carried out in the following periods: baseline, at discharge, and at the second- and fourth-year follow-ups. The measurement variables were avoidance behavior, anxiety, depression, impulsivity and meaning in life (MiL). A control group (n = 74) was evaluated at the same periods as the patients. Results indicate a slower recovery in relapsers in comparison to abstainers in all psychological dimensions and periods assessed. At the second-year follow-up, the abstainers achieved similar scores in depression as the control participants, in addition to higher scores in Meaning in Life at the end of treatment. In patients with severe alcohol dependence, our data supports a sequence of recovery that could continue beyond the four years of follow-up after treatment. This sequence would begin with the avoidance of risk situations and continue with the rest of dimensions (anxiety, depression, impulsivity).

El objetivo de este trabajo es comprobar si las recaídas dificultan la secuencia de la recuperación psicológica y reconstruir la secuencia de la recuperación de pacientes graves que solicitan tratamiento. Los participantes fueron 159 pacientes tratados durante dos años en un programa ambulatorio intensivo y tras ser dados de alta fueron seguidos durante cuatro años. En función de la presencia o no de recaída durante el seguimiento se configuraron dos grupos, el de abstinentes (n = 80) y el de pacientes que recaen (n = 79). Las evaluaciones se realizaron: basal, al alta del tratamiento, al 2.º y 4.º año de seguimiento. Las variables fueron: conductas de evitación, ansiedad, depresión, impulsividad y sentido de la vida. Se incluyó un grupo de control (n = 74) que fue evaluado con la misma cadencia que los pacientes. Los resultados indican una recuperación más lenta en el grupo con recaídas frente a los abstinentes, en todas las dimensiones psicológicas y los períodos estudiados. A los dos años de seguimiento, los pacientes abstinentes obtuvieron puntuaciones en depresión similares a los controles, además de puntuaciones superiores en sentido de la vida (MiL) a partir del final del tratamiento. Al menos en pacientes con dependencia grave del alcohol, nuestros resultados apoyan una secuencia de recuperación que podría continuar más allá de los cuatro años de seguimiento. Se inicia con la evitación de situaciones de riesgo y continúa con el resto de las dimensiones (ansiedad, depresión, impulsividad).

Results of Surgical Treatment for Popliteal Aneurysm.

BACKGROUND: Evaluate the results of open surgery treatment of popliteal artery aneurysms (PAAs), performed in our department for over 25 years, comparing those treated with a medial approach with those treated with a posterior approach. MATERIAL AND METHOD: A retrospective analysis of a total of 88 PAAs, performed between January 1994 and December 2018, with an average of 65 months follow-up, comparing the results of 59 patients operated by a medial approach (group 1) in which aneurysm exclusion and femoro-popliteal bypass below the knee was carried out, with 29 cases treated by a direct posterior approach (group 2) - aneurismectomy and graft interposition-. The postoperative complications, immediate and long term patency, limb salvage and mortality rate were studied. RESULTS: In group 1 the chosen material for the bypass was reversed greater saphenous vein (GSV) in 45 cases (76.3%), expanded polytetrafluoroethylene (ePTFE) grafts in 12 (20.3%) and Dacron grafts on 2 (3.4%), while in group 2, a 6 mm diameter ringed ePTFE graft was used in 27 cases (93.1%) and reversed GSV in 2 (6.9%). There were eight (13.6%) postoperative graft thrombosis in group 1, 5 (8.9%) of them needing amputation, and 1 (3.4%) graft thrombosis in group 2 (P = 0.077). During the follow up, major amputation was necessary in 2 cases (3.7%) in group 1, while there were no cases of major amputation in group 2. Mortality was 61% (36 patients) in group 1 and 27% (8 patients) in group 2 (p = 0.003), at the end of surveillance. CONCLUSION: In our experience, in the open surgical treatment of PAAs, the posterior approach could be considered as the first choice in selected cases.

A First Assessment of an Aerodynamic Barrier Layer for Filtering Airborne Hygroscopic Particles.

In this work, consideration is given to an aerodynamic concept to boost the filtration in face masks of airborne hygroscopic particles such as those caused by an infected person when coughs or sneezes. Nowadays, increasing the filtration efficiency of face masks implies either increasing the number of crisscrossing fiber layers or decreasing the equivalent hydraulic diameter of the pore, however, both measures are in clear detriment of its breathability. Here, a novel strategy is proposed in which the filtration of an airborne particle is boosted by increasing its diameter. We called properly this concept as the aerodynamic barrier layer. In this concept, a traditional crisscrossing fiber layer is replaced by a parallel rearranged of the fibers in the direction of the flow. This rearrangement will promote central lift forces which will push the particles toward the center of the channel where after clustering they will coalesce resulting in a bigger particle that can be now easily captured by a conventional fiber crisscrossing layer. Utilizing a simplified geometrical model, an expression for the required length of the aerodynamic barrier layer was derived. It is shown that an aerodynamic barrier layer with a length of only a few millimeters can aerodynamically focus water droplets around 1 µm-diameter and the penetration of airborne particles can be reduced up to 55%.

Effect of home-based prehabilitation in an enhanced recovery after surgery program for patients undergoing colorectal cancer surgery during the COVID-19 pandemic.

BACKGROUND: Surgery remains the first curative treatment for colorectal cancer. Prehabilitation seems to attenuate the loss of lean mass in the early postoperative period. However, its long-term role has not been studied. Lockdown due to the COVID-19 pandemic has forced to carry out the prehabilitation program at home. This study aimed to assess the effect of home prehabilitation on body composition, complications, and hospital stay in patients undergoing oncological colorectal surgery. METHODS: A prospective and randomized clinical study was conducted in 20 patients operated of colorectal cancer during COVID-19 lockdown (13 March to 21 June 2020) in a single university clinical hospital. Patients were randomized into two study groups (10 per group): prehabilitation vs standard care. Changes in lean mass and fat mass at 45 and 90 days after surgery were measured using multifrequency bioelectrical impedance analysis. RESULTS: Prehabilitation managed to reduce hospital stay (4.8 vs 7.2 days, p = 0.052) and postoperative complications (20% vs 50%, p = 0.16). Forty-five days after surgery, the loss of lean mass decreased (1.7% vs 7.1%, p = 0.17). These differences in lean mass were attenuated at 90 days; however, the standard care group increased considerably their fat mass compared to the prehabilitation group (+ 8.72% vs - 8.16%). CONCLUSIONS: Home prehabilitation has proven its effectiveness, achieving an attenuation of lean mass loss in the early postoperative period and a lower gain in fat mass in the late postoperative period. In addition, it has managed to reduce hospital stays and postoperative complications. REGISTRATION NUMBER: This article is part of an ongoing, randomized, and controlled clinical trial approved by the ethics committee of our hospital and registered in ClinicalTrials.gov in August 2018 with registration number NCT03618329.

The mechanical effect of moisturization on airborne COVID-19 transmission and its potential use as control technique.

Mounting evidence from scientific community seems to suggest that COVID-19 virus can potentially spread by airborne transmission. As a result, methods and techniques for preventing environmental contagious, such as ventilation or air filtration have been proposed. Here, it is investigated the effect of moisturization on airborne COVID-19 transmission from a mechanical point of view in which comparatively large water droplets promote the growth -by collision and coalescence, of suspended airborne COVID-19 and then accelerating its gravitational settling. Utilizing a classical raindrop collisional model from cloud science and the available experimental data an expression for the removal time of suspended airborne COVID-19 as function of the relative humidity was derived. The mechanical model is in good agreement with the recent reported experimental research in which high temperature and high relative humidity reduce COVID-19 contagious and then is a point in favor of the mechanic model of the effect of moisture in the COVID-19 airborne transmission. The results encourage further research on the deliberate moisturization of room air (by using ceiling mounted humidifiers) as a potential technique for control of airborne COVID-19 transmission.

Modeling Neuroimmune Interactions in Human Subjects and Animal Models to Predict Subtype-Specific Multidrug Treatments for Gulf War Illness.

Gulf War Illness (GWI) is a persistent chronic neuroinflammatory illness exacerbated by external stressors and characterized by fatigue, musculoskeletal pain, cognitive, and neurological problems linked to underlying immunological dysfunction for which there is no known treatment. As the immune system and the brain communicate through several signaling pathways, including the hypothalamic-pituitary-adrenal (HPA) axis, it underlies many of the behavioral and physiological responses to stressors via blood-borne mediators, such as cytokines, chemokines, and hormones. Signaling by these molecules is mediated by the semipermeable blood-brain barrier (BBB) made up of a monocellular layer forming an integral part of the neuroimmune axis. BBB permeability can be altered and even diminished by both external factors (e.g., chemical agents) and internal conditions (e.g., acute or chronic stress, or cross-signaling from the hypothalamic-pituitary-gonadal (HPG) axis). Such a complex network of regulatory interactions that possess feed-forward and feedback connections can have multiple response dynamics that may include several stable homeostatic states beyond normal health. Here we compare immune and hormone measures in the blood of human clinical samples and mouse models of Gulf War Illness (GWI) subtyped by exposure to traumatic stress for subtyping this complex illness. We do this via constructing a detailed logic model of HPA-HPG-Immune regulatory behavior that also considers signaling pathways across the BBB to neuronal-glial interactions within the brain. We apply conditional interactions to model the effects of changes in BBB permeability. Several stable states are identified in the system beyond typical health. Following alignment of the human and mouse blood profiles in the context of the model, mouse brain sample measures were used to infer the neuroinflammatory state in human GWI and perform treatment simulations using a genetic algorithm to optimize the Monte Carlo simulations of the putative treatment strategies aimed at returning the ill system back to health. We identify several ideal multi-intervention strategies and potential drug candidates that may be used to treat chronic neuroinflammation in GWI.

Effectiveness of tianeptine in patients with major depressive disorder and substance use disorder.

The depressive disorder coexists in a high prevalence with a substance-related disorder, which is asso- ciated with a worst prognosis. The therapeutic interventions for this co-morbidity lack of the appropriate scientific sup- port. The existing evidence suggest that the currently avail- able anti-depressive drugs are of minor efficacy in this group of patients. An alternative would be the use of different drugs with distinctive neurobiological mechanism of action. The aim of this study was to describe the clinical develop- ment of a series of patients affected by this comorbidity un- der treatment with tianeptine under usual clinical practices.

Cannabis-induced psychosis: clinical characteristics and its differentiation from schizophrenia with and without cannabis use. / Psicosis inducida por cannabis: características clínicas y su diferenciación con la esquizofrenia con y sin consumo de cannabis asociado.

Cannabis use is considered an established risk factor for psychosis development. Differentiating between cannabis-induced disorders and schizophrenia is useful for prognostic and therapeutic purposes. Three inpatients groups were differentiated: cannabis-induced psychosis (CIP) (n = 69; mean age = 27.4, SD = 6.5; 82.6% males), schizophrenia with cannabis abuse or dependence (SZ + CB) (n = 57; mean age = 31.9, SD = 10.1; 94.7% males) and schizophrenia without cannabis abuse or dependence (SZ) (n = 181; mean age = 41.8, SD = 13.3; 54.1% males). The Psychiatric Research Interview for Substance and Mental Disorders (PRISM-IV) scale was used to differentiate induced psychosis. The CIP group presented lower mean scores on the negative PANSS subscale (M = 12.9, SD = 5.9; F = 32.24, p < 0.001), fewer auditory hallucinations (60.3%; X² = 6.60, p = 0.037) and greater presence of mania (26.1% vs. 12.3%; X² = 32.58, p < 0.001) than the SZ + CB group. There were few clinical differences between patients with schizophrenia, regardless of previous cannabis use. The age of first admission due to psychosis was lower in both psychotic inpatients groups with cannabis use (M = 26.1, SD = 6.4 in CIP and M = 25.3, SD = 6.2 in SZ + CB; X² = 20.02, p < 0,001). A clinical pattern characteristic of cannabis-induced psychosis was not observed, but the precipitating role of cannabis in the appearance of psychotic symptoms was demonstrated, given the lower age of first admission due to psychosis in cannabis user groups.

El consumo de cannabis se considera un factor de riesgo establecido para el desarrollo de psicosis. Diferenciar los trastornos inducidos por cannabis de la esquizofrenia resulta útil desde el punto de vista pronóstico y terapéutico. Se diferenciaron tres grupos de pacientes hospitalizados: psicosis inducida por cannabis (PIC) (n = 69; Media de edad = 27,4, DE = 6,5; 82,6 % varones), esquizofrenia con abuso o dependencia de cannabis (EZ + CB) (n = 57; Media de edad = 31,9, DE = 10,1; 94,7% varones) y esquizofrenia sin abuso o dependencia de cannabis (EZ) (n = 181; Media de edad = 41,8, DE = 13,3; 54,1% varones). Se utilizó la escala Psychiatric Research Interview for Substance and Mental Disorders (PRISM-IV) para la diferenciación de cuadros inducidos. El grupo PIC presentó puntaciones inferiores en la subescala PANSS negativa (M = 12,9, DE = 5,9; F = 32,24; p < 0,001), menos alucinaciones auditivas (60,3%; X²  = 6,60; p = 0,037) y mayor presencia de manía (26,1% vs. 12,3%; X² = 32,58; p < 0,001) en comparación con el grupo EZ + CB. Hubo pocas diferencias clínicas entre los pacientes con esquizofrenia, independientemente del consumo de cannabis. La edad del primer ingreso por psicosis fue menor en ambos grupos de psicóticos consumidores (M = 26,1, DE = 6,4 en PIC y M = 25,3, DE = 6,2 en EZ + CB; X² = 20,02; p < 0,001). No se observó un patrón clínico característico de las psicosis inducidas por cannabis, aunque sí se demostró el papel precipitante del cannabis en la aparición de psicosis, dada la menor edad de ingreso en los consumidores.

Influence of the Thermodynamic and Kinetic Control of Self-Assembly on the Microstructure Evolution of Silk-Elastin-Like Recombinamer Hydrogels.

Complex recombinant biomaterials that merge the self-assembling properties of different (poly)peptides provide a powerful tool for the achievement of specific structures, such as hydrogel networks, by tuning the thermodynamics and kinetics of the system through a tailored molecular design. In this work, elastin-like (EL) and silk-like (SL) polypeptides are combined to obtain a silk-elastin-like recombinamer (SELR) with dual self-assembly. First, EL domains force the molecule to undergo a phase transition above a precise temperature, which is driven by entropy and occurs very fast. Then, SL motifs interact through the slow formation of ß-sheets, stabilized by H-bonds, creating an energy barrier that opposes phase separation. Both events lead to the development of a dynamic microstructure that evolves over time (until a pore size of 49.9 ± 12.7 µm) and to a delayed hydrogel formation (obtained after 2.6 h). Eventually, the network is arrested due to an increase in ß-sheet secondary structures (up to 71.8 ± 0.8%) within SL motifs. This gives a high bond strength that prevents the complete segregation of the SELR from water, which results in a fixed metastable microarchitecture. These porous hydrogels are preliminarily tested as biomimetic niches for the isolation of cells in 3D cultures.

The dual role of the centrosome in organizing the microtubule network in interphase.

Here, we address the regulation of microtubule nucleation during interphase by genetically ablating one, or two, of three major mammalian γ-TuRC-binding factors namely pericentrin, CDK5Rap2, and AKAP450. Unexpectedly, we find that while all of them participate in microtubule nucleation at the Golgi apparatus, they only modestly contribute at the centrosome where CEP192 has a more predominant function. We also show that inhibiting microtubule nucleation at the Golgi does not affect centrosomal activity, whereas manipulating the number of centrosomes with centrinone modifies microtubule nucleation activity of the Golgi apparatus. In centrosome-free cells, inhibition of Golgi-based microtubule nucleation triggers pericentrin-dependent formation of cytoplasmic-nucleating structures. Further depletion of pericentrin under these conditions leads to the generation of individual microtubules in a γ-tubulin-dependent manner. In all cases, a conspicuous MT network forms. Strikingly, centrosome loss increases microtubule number independently of where they were growing from. Our results lead to an unexpected view of the interphase centrosome that would control microtubule network organization not only by nucleating microtubules, but also by modulating the activity of alternative microtubule-organizing centers.

National Diagnostic Reference Levels for Endovascular Aneurysm Repair and Optimisation Strategies.

OBJECTIVE: The International Commission on Radiological Protection (ICRP) has highlighted the large number of medical specialties using fluoroscopy outside imaging departments without programmes of radiation protection (RP) for patients and staff. Vascular surgery is one of these specialties and endovascular aneurysm repair (EVAR) is one of the most challenging procedures requiring RP guidance and optimisation actions. The recent European Directive on Basic Safety Standards requires the use and regular update of diagnostic reference levels (DRL) for interventional procedures. The objective of the study was to know the doses of patients undergoing EVAR with mobile Xray systems and with hybrid rooms (fixed Xray systems), to obtain national DRLs and suggest optimisation actions. METHODS: The Spanish Chapter of Endovascular Surgery launched a national survey that involved hospitals for 10 autonomous communities representing the 77% of the Spanish population (46.7 million inhabitants). Patient dose values from mobile Xray systems were available from nine hospitals (sample of 165 EVAR procedures) and data from hybrid rooms, from seven hospitals, with dosimetric data from 123 procedures. The initial national DRLs have been obtained, as the third quartile of the median values from the different centres involved in the survey. RESULTS: The proposed national DRLs are 278 Gy cm2 for hybrid rooms and 87 Gy cm2 for mobile Xray systems, and for cumulative air kerma (cumulative AK) at the patient entrance reference point, 1403 mGy for hybrid rooms, and 292 mGy for mobile systems. CONCLUSION: An audit of patient doses for EVAR procedures to identify optimised imaging protocol strategies is needed. It is also appropriate to evaluate the diagnostic information required for EVAR procedures. The increase by a factor of 3.2 (for kerma area product) and 4.8 (for cumulative AK) in the DRLs needs to be justified when the procedures are performed in the hybrid rooms rather than with mobile Xray systems.

[Effects of including mutual aid groups in the adherence of a continuing care programme of alcohol dependent patients carried out in a Primary Care setting]. / Efectos de la integración de grupos de ayuda mutua sobre la adherencia al programa de continuidad en el cuidado a pacientes con dependencia del alcohol realizado en Atención Primaria.

OBJECTIVES: To demonstrate the effects of including mutual aid associations into a continuing care programme for patients with alcohol dependence carried out by Primary Care teams. SITE: Primary Care Teams belonging to the attendance area of the University Hospital 12 de Octubre at Madrid. PARTICIPANTS: 207 participants with alcohol dependence treated in an intensive hospital outpatient-setting programme were included in a continuing care programme carried out by a Primary Care team for a four-year period. INTERVENTIONS: Patients were randomised into two intervention modalities. The first group was followed up while receiving a treatment modality known as «monitoring recovery¼ (Group A, n = 97). The other group, in addition to the above-mentioned intervention, attended to a mutual aid association included in the Federation of Alcoholics of the Community of Madrid (FACOMA) in which the programme «Help Yourself-Help Us¼ was carried out (Group B, n = 112). MAIN OUTCOMES: Dropout rates on the sessions designed to monitor their recovery from their alcohol dependence and other comorbid medical conditions. RESULTS: Patients in Group B reached higher rates of therapeutic adherence to the programme (47.9% vs. 14.7%, p < 0.01), as well as for the comorbid medical issues when compared to Group A. CONCLUSIONS: Including mutual aid associations that carried out the «Help yourself-Help Us¼ programme for a four-year period improves outcomes related to therapeutic adherence in patients with alcohol dependence attending Primary Care teams.

Coexistence between personality disorders and substance use disorder. Madrid study about prevalence of dual pathology.

INTRODUCTION: Personality disorders (PD) and substance use disorders (SUD) have a high prevalence and an important health and socioeconomic impact so, it is interesting to study the relationship between them. The objectives of the study are: to compare the prevalence of SUD between patients with and without diagnosis of PD, to analyze if any PD is related to the SUD, and if a specific PD is associated with a specific SUD. MATERIAL AND METHODS: Cross-sectional study in 837 patients from centers of attention to drug addiction and mental health in Madrid, Spain. The Mini International Neuropsychiatric Interview (MINI) and the Personality Diagnostic Questionnaire-4+ (PDQ4+) are used to detect mental disorder and PD, respectively. RESULTS: SUD is significantly higher in antisocial PD (p<0.01); sedative (p<0.01) and alcohol (p<0.05) use disorder in borderline PD; cocaine (p<0.05) and alcohol (p<0.01) use disorder in paranoid PD; and alcohol use disorder in histrionic PD (p<0.01). The SUD for cocaine is lower in obsessive- compulsive PD (p<0.05) and depressive PD (p<0.01). There is a positive correlation between the number of PD of a subject and the number of SUD that it presents. The risk of an alcohol [OR of 1,08 CI (1,01-1,16)] or sedatives [OR of 1,08 CI (1,001-1,17)] use disorders increases if an individual presents more than one type of PD. CONCLUSIONS: There is not differences of SUD prevalence between PD and not PD groups. We found an association between SUD and PD of cluster B (antisocial, borderline and histrionic) and also with paranoid PD. The SUD are more common among man with the exception of sedatives.

Inclusion of Alcoholic Associations Into a Public Treatment Programme for Alcoholism Improves Outcomes During the Treatment and Continuing Care Period: A 6-Year Experience.

AIMS: To investigate whether inclusion of self-help groups into the hospital treatment programme improves the prognosis of alcohol dependence through the treatment period; and to examine therapeutic adherence and prognosis during continuing care. METHOD: Patients attending the treatment programme at the 'Hospital 12 de Octubre' were randomized into two groups. In Group A (n = 123), patients received the usual treatment included in our programme, whereas in Group B (n = 126), patients also attended self-help groups. Patients were assessed with psychological scales at baseline, at the end of the treatment period and after completing the continuing care visits. Data were collected over a total of 6 years. RESULTS: During the treatment period, patients in Group B accumulated more months of abstinence and dropped out less. During continuing care, patients in Group B accumulated more months of abstinence and therapeutic adherence was higher. Variables that were associated with these results during the continuing care period were: visits to the GP, scores on anxiety, impulsivity and meaning of life scales, and belonging to the group that attended the alcoholic associations. CONCLUSIONS: Mutual help groups incorporated into a public treatment programme appear to improve outcomes during treatment and on into continuing care. This experience supports cooperation between public health centres and alcoholic associations in treating alcoholism. SHORT SUMMARY: Including alcoholic associations into the public treatment programme for alcoholism of the 'Hospital 12 de Octubre' in Madrid was shown to be associated with better outcomes in terms of months of accumulated abstinence, dropout rates and therapeutic adherence, during the treatment and continuing care periods.