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patients with dual pathology have worse clinical evolution and worse therapeutic response. The repeated administration of substances sensitizes the dopaminergic systemwith downregulation of the reward circuit. When the drug use stops, the exposureto stimuli produces a dopamine increase and craving appears.
to prove usefulness of paliperidone in dual pathology for craving andfor drug abuse.
Materials and Methods
18 patients diagnosed with dual pathology. They were treated with paliperidone and all of them were interviewed about craving andsubstance use.
4 groups: Cannabis (5%). Cannabis and cocaine (16.66%). Cannabis andother two or more substances (16.66%). Cocaine and alcohol (16.66%). All ofthem were diagnosed of dual pathology: induced psychotic disorder (33.33%),personality disorder (27.77%), conduct disorder (16.66%), paranoid schizophrenia (11.11%), bipolar disorder (5.55%), and dysmorphic disorder(5.55%). 38.89% achieved abstinence. 50% reduced significantly substance use.77.78% verbalized a decrease in craving.
cannabis disables the gabaergic interneurons, which stop inhibiting the dopaminergic neurons and a large amount of dopamine is released from the accumbens nucleus . Cocaine increases dopamine and 5-HT levels on thebrain. Paliperidone presents an affinity for D2 and 5TH2a receptors, so this might explain the results, because it blocks the enhancer effect, which contributes to the craving decrease and to the drug withdrawal.
paliperidone seems to be a good choice in dual pathologydue to the improvement on craving and drug abuse
Patients with dual pathology have worse clinical evolution and worse therapeutic response. Drugs modify the functioning of certain neurocerebral transmission systems, producing cognitive, emotional and behavioral changes. Vortioxetine (Brintellix®) is used as a treatment for major depressive disorder (MDD) and it is considered a new multimodal antidepressant. Preclinical data suggest that the effects on numerous serotonin receptors result in regional increases in noradrenaline and dopamine as well as glutamatergic transmission.
This analysis assessed the efficacy of vortioxetine (Brintellix®) in patients with affective disorders and abuse drugs (dual pathology).
Efficacy was assessed with a study of patients who were recruited in a qualitative and observational study. They were treated with vortioxetine (Brintellix®). Outcome measures included changes from baseline to endpoint in Hamilton Depresion Rating Scale (HDRS). They were also interviewed weekly about craving and substance use. Urine test controls were done to corroborate results.
A total of 11 vortioxetine-treated patients improved their depressive and anxiety symptomatology. Seven of them (64%) were males and four of them (36%) were women. Cocaine was the main drug of abuse (n = 9, 82%). The doses were between 5 and 20 mg/day. After the clinical evaluation and 12 weeks of treatment, they achieved to reduce significantly the drug use and verbalized a decrease in craving. Two patients dropped out of the study.
Vortioxetine (Brintellix®) was shown as efficacious in reducing depressive and anxiety symptoms in patients with dual pathology.
Disclosure of interest
The authors have not supplied their declaration of competing interest.
Studies describe patients with dual pathology as subjects with worse clinical evolution and worse therapeutic response. These subjects have high percentages of worse therapeutic compliance and low adherence to psychopharmacological treatment. The conventional antipsychotics can induce dysphoria and worse craving and drug use. The long duration-injectable antipsychotics could serve as a good therapeutic alternative because they combine efficacy and tolerability.
We analyzed subjects treated with aripiprazole injectable to demonstrate its effectiveness on symptomatology, the reduction of craving and consumption of substances.
Materials and methods
We studied subjects with dual disorders at a Center for Attention to drug addicts treated with aripiprazole extended-release injectable. All of them met criteria for the diagnosis of disorders for cannabis and cocaine use. All of them had been previously treated with oral antipsychotics and/or injectable of long duration. Evolution of craving and consumption were evaluated through clinical interviews and urine analysis.
Cannabis was the main substance for all the patients. Three of them also often abused of cocaine. All of them were taking other treatments previously. The main causes of the change were: side effects and/or poor compliance. Only one patient discontinued follow-up. The rest of them showed good therapeutic adherence and better tolerability with aripiprazole injectable. The monthly dose was 400 mg.
Aripiprazole extended-release injectable is a good choice for dual disorders. A good therapeutic adherence involves not only a psychopathological improvement but also respect to craving and consumption, which makes aripiprazole injectable a suitable therapeutic option.
Disclosure of interest
The authors have not supplied their declaration of competing interest.
Alcohol abuse causes dopamine release in the mesolimbic system, which activates the reward circuit. This is linked to an interdependent opioid, serotonergic and endocannabinoid system. Nalmefene is a modulator of the endogenous opioid system, with antagonistic effect on mu and delta receptors, and a partial agonist activity kappa. This means that reduces the reinforcing effects of alcohol consumption through the cortical-mesolimbic system. Therefore, when a patient takes nalmefene, the satisfaction obtained when he drinks is lower, which increases the possibility to have more control over drinking.
The efficacy of nalmefene was evaluated in two profiles of patients: 1. No abstinence in alcohol dependence disorder and continuous relapses, 2. Cocaine dependence disorder associated to alcohol abuse.
Improving the quality of life and compliance rates due to the difficulties of following a strict treatment to achieve the abstinence. Furthermore, in cases of patients with cocaine dependence disorder and alcohol abuse, the objective is to avoid cocaine use by reducing previous alcohol consumption.
nalmefene offers the possibility of treating the addiction from a new perspective. Our current clinical experience has been able to treat subjects with conventional treatments failures and those who need to achieve the necessary control to reduce cocaine use.
Disclosure of interest
The authors have not supplied their declaration of competing interest.
Cardiopulmonary dirofilariosis caused by Dirofilaria immitis produces inflammation, blood vessel obstruction and hypoxia, which are required conditions for the beginning of the process of neovascularization. Since D. immitis harbours intracellular symbiotic Wolbachia bacterium, the global understanding of the angiogenic process requires the analysis of the effect of the parasite molecules, but also that of Wolbachia. Canine primary lung microvascular endothelial cells were treated with the recombinant Wolbachia surface protein (rWSP) and the expression of angiogenic factors like Vascular Endothelial Growth Factor-A (VEGF-A), sFlt, membrane Endoglin (mEndoglin) and soluble Endoglin (sEndoglin), as well as the in vitro formation of pseudocapillaries, were measured. The analyses showed a significant increase in the expression of pro-angiogenic VEGF-A and anti-angiogenic sEndoglin, together with a significant decrease in both pro-angiogenic mEndoglin and pseudocapillary formation, compared to untreated controls. Due to the complexity of the angiogenic process and its relationship with other physiological processes like inflammation and fibrinolysis, these results might suggest that rWSP participate in various mechanisms related to each other and its effects might depend either on the balance between them or on the moment of their occurrence.
We analyse the two definitions of generalized quantifiers for logics of dependence and independence that have been proposed by F. Engström, comparing them with a more general, higher order definition of team quantifier. We show that Engström’s definitions (and other quantifiers from the literature) can be identified, by means of appropriate lifts, with special classes of team quantifiers. We point out that the new team quantifiers express a quantitative and a qualitative component, while Engström’s quantifiers only range over the latter. We further argue that Engström’s definitions are just embeddings of the first-order generalized quantifiers into team semantics, and fail to capture an adequate notion of team-theoretical generalized quantifier, save for the special cases in which the quantifiers are applied to flat formulas. We also raise several doubts concerning the meaningfulness of the monotone/nonmonotone distinction in this context. In the appendix we develop some proof theory for Engström’s quantifiers.
A linear model was used to investigate the behaviour of the Italian Western Tauri glaciers as a result of temperature changes projected for the 21st century. The model estimates the temperature variations once the glacier snout length variations are known and vice versa: it estimates the glacier snout length variations once the air temperature variations are known or predicted. The 46 glaciers of the Italian Western Tauri, 35 (76%) of which have areas smaller than 0.5 km2 and only 7 (15%) larger than 1 km2, are mostly mountain type glaciers and only three are presently valley glaciers. The model has been forced by the air temperature projections of the A1B emission scenario, which indicates an increase in temperature of 2.7°C from 2015 to 2100. The results show a shortening of more than 35% for mountain glaciers by 2100 with a surface loss of more than 60% and smaller reductions for valley glaciers. The consequent fragmentation into smaller units would lead to the extinction of 95% of the existing glaciers by the end of the century, possibly leaving only the valley glaciers surviving.
The goal of this study is to describe the development of a new tool, the Psychosocial and Spiritual Needs Evaluation scale Instrumento de Evaluación de Necesidades Psicosociales y Espirituales del Enfermo al Final de Vida (ENP-E), designed to assess the psychosocial needs of end-of-life (EOL) patients. And, secondarily, to describe the face validity and psychometric properties of this instrument in the Spanish-speaking context.
The scale was developed through a seven-stage process: (1) literature review; (2) expert panel establishment; (3) discussion and agreement on the most relevant dimensions of psychosocial care; (4) description of key indicators and consensus-based questions to evaluate such dimensions; (5) assessment of the scale by external palliative care (PC) professionals; (6) evaluation by patients; and (7) analysis of scale's psychometrics properties. To assess content validity, 30 PC professionals and 20 patients evaluated the questionnaire. To determine psychometric properties, 150 participants completed these scales: the ENP-E; the Hospital Anxiety and Depression Scale; item 15 from the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 15 Palliative; and the Distress Thermometer.
All respondents evaluated the tool as “excellent.” In terms of construct validity, the internal consistency (Cronbach's alpha = 0.74) and temporal stability (test-retest r = 0.74, p < 0.1) were both adequate. On the factorial analysis, four factors (emotional-wellbeing, social support, spiritual, and information) explained 58.4% of the variance. This scale has a sensitivity of 76.3%, specificity of 78.9%, and the cutoff is 28.
Significance of results
To provide quality PC to EOL patients, it is essential to determine the psychosocial factors that influence well-being. This requires the use of reliable and specific instruments. The ENP-E is a novel tool that provides a systematic, holistic assessment of the psychosocial needs of EOL patients. Its routine use would allow clinicians to monitor such needs over time. This would, in turn, permit comprehensive, highly individualized interventions to improve effective PC approach.
The present study used a sheep model of intrauterine growth restriction, combining maternal undernutrition and twinning, to determine possible markers of early damage to the fetal kidney. The occurrence of early deviations in fetal hemodynamics which may be indicative of changes in blood perfusion was assessed by Doppler ultrasonography. A total of 24 sheep divided in two groups were fed with the same standard grain-based diet but fulfilling either their daily maintenance requirements for pregnancy (control group; n=12, six singleton and six twin pregnancies) or only the 50% of such quantity (food-restricted group; n=12; four singleton and eight twin pregnancies). All the fetuses were assessed by both B-mode and Doppler ultrasonography at Day 115 of pregnancy. Fetal blood supply was affected by maternal undernutrition, although there were still no evidences of brain-sparing excepting in fetuses at greatest challenge (twins in underfed pregnancies). However, there were early changes in the blood supply to the kidneys of underfed fetuses and underfed twins evidenced decreases in kidney size.
PNIPAM hydrogels are widely studied materials which swell in a great extent in water and water like solvents (e.g. alcohols). The hydrophilic nature of PNIPAM networks is very attractive however it is an important disadvantage at the moment of encapsulating hydrophobic drugs, which minimize their use in other fields. In this work we studied the swelling in different solvent mixtures with water and also in pure nonaqueous solvents, some of them immiscible with water. Accordingly, PNIPAM gels swell strongly in highly polar solvents (e.g. chloroform) but it does not swell in slightly polar solvents (e.g. toluene). The main interaction between the solvent and the polymer chain seems to involve the hydrogen bonding with the amide group, according to the calculated Hansen parameters (δh). It is possible to swell the gel in binary or ternary mixtures containing toluene. In that way, non-polar substances can be loaded inside the gel to change its properties. As a proof of concept, polyaniline (PANI) solubilized in chloroform using camphorsulfonate as solubilizing counterion. The obtained nanocomposites become sensitive to pH changing color and conductivity when exposed to basic or acidic aqueous solutions.
The generation of filaments constituted by nanocomposites allows printing pieces with functional properties. A method is proposed for incorporating nanoparticles in plastic filaments (thermoplastic polyurethane, PU) by diffusion in the swollen material. The nanoparticles must be dispersed in solvents (or solvent mixtures) in which the polymer swells but does not dissolve. Nanoparticles are incorporated mainly at the surface as revealed by SEM/EDS mapping. The thermal properties (studied by DSC and TGA) of the PU are only slightly affected by the presence of NPs. Test pieces successfully are printed using the modified filaments. Incorporation of solid lubricant (MoS2) nanoparticles decreases the coefficient of friction of the printed test samples.
Plants’ ability to rebuild their tiller population is affected by weather changes and management strategies. The hypothesis of the present study was that frequency and severity of defoliation alter Mulato grass (Brachiaria ruziziensis × Brachiaria brizantha cv. Marandu) sward development, and the proportion of aerial and basal tillers, interfering with sward stability. The objective was to evaluate aerial, basal and total tiller population density and changes in tillering dynamics. Treatments corresponded to strategies of rotational grazing characterized by combinations between two pre-grazing (95% and maximum canopy light interception during regrowth; LI95% and LIMax) and two post-grazing conditions (15 and 20 cm stubble height). The experimental period comprised four seasons of the year: summer 2008 (February–March 2008); autumn–early spring (April to mid-November 2008); late spring (mid-November–December 2008); and summer 2009 (January–March 2009). Density of aerial tillers decreased from summer 2008 to late spring. Tiller death decreased from summer 2008 to autumn–early spring. Aerial and total tiller death increased from late spring to summer 2009, mainly for the LI95% treatment. No differences were observed in the tiller population stability index of aerial tillers for LI treatments or post-grazing heights. The balance between tiller appearance and death for basal tillers remained relatively stable from summer 2008 to late spring. For aerial tillers the balance decreased to negative values from summer 2008 to autumn–early spring for both LI treatments. For total tiller population, the balance decreased to negative values from summer 2008 to autumn–early spring. Results indicated a strong seasonal effect on Mulato grass tillering and growth. Tillering dynamics were affected primarily by grazing frequency, which changed the relative importance of basal and aerial tillers. The results suggested that basal tillering was the predominant perennation pathway.
We aimed to describe the overall quantitative and qualitative results of a “La Caixa” Foundation and World Health Organization Collaborating Center Program entitled “Comprehensive Care for Patients with Advanced Illnesses and their Families” after four years of experience.
Qualitative and quantitative methods were employed to assess the program. Quasiexperimental, prospective, multicenter, single-group, and pretest/posttest methods were utilized to assess the quantitative data. The effectiveness of psychosocial interventions was assessed at baseline (visit 1) and after four follow-up visits. The following dimensions were assessed: mood state, discomfort, anxiety, degree of adjustment or adaptation to disease, and suffering. We also assessed the four dimensions of the spiritual pain scale: faith or spiritual beliefs, valuable faith or spiritual beliefs, meaning in life, and peace of mind/forgiveness. Qualitative analyses were performed via surveys to evaluate stakeholder satisfaction.
We built 29 psychosocial support teams involving 133 professionals—mainly psychologists and social workers. During the study period, 8,964 patients and 11,810 family members attended. Significant improvements were observed in the psychosocial and spiritual dimensions assessed. Patients, family members, and stakeholders all showed high levels of satisfaction.
Significance of Results:
This model of psychosocial care could serve as an example for other countries that wish to improve psychosocial and spiritual support. Our results confirm that specific psychosocial interventions delivered by well-trained experts can help to ease suffering and discomfort in end-of-life and palliative care patients, particularly those with high levels of pain or emotional distress.
Spain is one of the few countries in the EU where Islam has had a historical role in the social and cultural construction of its identity. However, its modern history is marked by acts of repudiation of non-Christian cultures. Opinion polls indicate that certain groups of immigrants from North Africa, Latin America and Eastern Europe, but mainly Muslims, are considered to be incompatible with the popular conception of Spanish identity. The reason for this perception is related to the social construction of the immigrant as the ‘other to govern’ by political, academic and media discourses. The aim of this paper is to demonstrate that immigration law also plays a fundamental role in this strategy of ‘orientalisation’, namely the attribution of certain qualities to immigrant groups (illegal, antisocial, criminal, inassimilable, terrorist), the aim of which is to legitimise the selective control of immigration. The Spanish immigration and citizenship regime contributes to the construction of otherness, and therefore to the political and legal (re)definition of what ‘being Spanish’ means.
Deception Island is an active volcano located in Bransfield Strait. Its volcanic activity is linked to the presence of gravity anomalies that influence the definition of the geoid. In this paper, a precise undulation geoid model (GeoiDEC14) has been computed from GPS, gravimetric and levelling measurements. GeoiDEC14 highlights local anomalies of the island that match with hot spots, such as the minimum values shown in Fumarole Bay and Whalers Bay (fumarole areas), or the maximum values found in the remains of lava at Colatinas, Black Glacier and Murature Point. Comparison of GeoiDEC14 with global models always shows negative values due to an average of 18.80 m for our model compared to 19.80–20.60 m for models such as ITSG-Grace2014s, EGM08, AIUG-Grace03s or EGM96. This difference is due to the lack of resolution of global models and to the volcanic activity on the island. To confirm the results, the same measurements were taken on nearby Livingston Island. The values of geoid undulation on this island reaffirm the lack of detail in the global geoid in the area, presenting an average of 18.90 m, similar to the average value of GeoiDEC14.
Echinacea pallida (EPAL), a herbaceous flowering plant with immunomodulatory properties, has been chosen to determine the pre- and post-supplementary effects on the growth performances, bacterial community, blood parameters and immunity of growing rabbits. The same Grimaud does (14-week-old) from the studied in the first part of this study were randomly divided into two groups (n=50/group). The first group was fed a basal diet without supplementation (Control group, C) while the another group was fed a basal diet supplemented with 3 g EPAL/kg diet (Echinacea group, E). From the second parturition, 80 weaned kits (40 from the C does and 40 from the E does) were randomly assigned to four groups of 20 animals each and were fed a growing commercial diet supplemented with or without a 3 g EPAL/kg diet: the CC group (rabbits from the C does fed the control diet), CE group (rabbits from the C does fed the supplemented diet), EC (rabbits from the E does fed the control diet) and EE group (rabbits from the E does fed the supplemented diet). The dietary EPAL treatment did not affect the growth performance. Ten fattening rabbits from each group were selected to evaluate the bacterial community and blood parameters, while the remaining rabbits (n=10/group) were used to study phagocytosis and the humoral immune response. The variability was evaluated from hard faeces at 35, 49 and 89 days, and the caecal content at 89 days. The variability of the bacterial community of the EE group was higher than that of the other groups. The phagocytic activity was higher in the CE and EE groups than in the CC and EC ones (30.9 and 29.7 v. 21.2 and 21.8%; P<0.05), whereas no statistically significant difference was observed for the blood parameters or humoral immune response against vaccination (rabbit haemorrhagic disease virus) at 95 days old which the serum was collected at 88, 102, 109, 116 and 123 days old. In conclusion, no impact of EPAL dietary supplementation has been observed on the growth performances, bacterial community, blood parameters or humoral immune responses in growing rabbits, except for an increase in phagocytic activities.
Echinacea pallida (EPAL), also known as pale purple coneflower, is a herbaceous flowering plant with immune-enhancement and antioxidative properties. The effect of EPAL on the reproductive performance, serum biochemistry and haematological parameters of rabbit does has been studied here. A total of 100, 21-week-old Grimaud rabbit does, were randomly assigned to two groups. One group was fed a basal diet supplemented with 3 g EPAL/kg diet (Echinacea group, E), while the other was fed the basal diet without the supplementation (control group, C). The reproductive performance of the does was not affected by the treatment (P>0.05). The haematological parameters of pregnant rabbits showed that there was no interaction between gestation day and treatment. The EPAL supplementation induced a reduction (−47.3%) in the basophil cell rate (0.55% and 0.29%, for the control and treatment groups, respectively; P=0.049). The gestation day significantly affected most of the haematological parameters (P<0.05). The white blood cell counts declined progressively after day 14. The mean corpuscular haemoglobin, mean corpuscular haemoglobin concentration, red cell distribution width, mean platelet volume and eosinophils increased steadily throughout the study, and reached a maximum value on day 28. The red blood cells, haemoglobin, haematocrit, mean corpuscular volume and neutrophils increased slightly up to day 14, and then subsequently decreased progressively until day 28. The lymphocytes and platelet distribution width decreased until day 14, and then increased to a maximum value on day 28. No significant effect of gestation day or treatment was observed on the blood serum chemistry. As far as the immune parameters are concerned, no significant differences were observed between groups, while a significant effect of gestation day was observed for lysozymes (6.02 v. 7.99 v. 1.91; for 0, 14 and 28 days, respectively; P=0.014). In conclusion, a lack of effect of EPAL has been observed. In fact, no impacts of EPAL have been observed on the reproductive or haematological parameters of the does. The effects of dietary supplementation with EPAL on the performances, bacterial community, blood parameters and immunity in growing rabbits are reported in the second part of this study.
Intrauterine growth restriction (IUGR) is associated with adverse perinatal outcomes and late-onset diseases in offspring. Eating disorders, voluntary caloric restriction and maternal undernutrition can all induce IUGR but a relevant model is required to measure all its possible consequences. In this work, pregnant rabbits were used as an IUGR model. Control females (n=4) received ad libitum diet throughout pregnancy, whereas underfed females (n=5) were restricted to 50% of their daily requirements. Offspring size was measured by ultrasonography and in vivo at birth. Hemodynamic features of the umbilical cords and middle cerebral arteries (systolic peak velocity, end diastolic velocity, pulsatility index and resistance index) were characterized by Doppler ultrasonography. At day 21, maternal underfeeding resulted in a significant reduction of fetal size (occipito-nasal length). At birth, the size of kits from the underfed group was significantly lower (lower crown-rump length, biparietal and transversal thoracic diameters) and a reduced weight with respect to the control group. Feed restriction altered blood flow perfusion compared with does fed ad libitum (significant higher systolic peak, time-averaged mean velocities and lower end diastolic velocity). Fetuses affected by IUGR presented with compensative brain-sparing effects when compared with the control group. In conclusion, the present study supports using rabbits and the underfeeding approach as a valuable model for IUGR studies. These results may help to characterize IUGR alterations due to nutrient restriction of mothers in future research.
The main role of early nutritional programming in the current rise of obesity and associated diseases is well known. However, translational studies are mostly based in postnatal food excess and, thus, there is a paucity of information on the phenotype of individuals with prenatal deficiencies but adequate postnatal conditions. Thus, we assessed the effects of prenatal programming (comparing descendants from females fed with a diet fulfilling 100 or only 50% of their nutritional requirements for pregnancy) on gene expression, patterns of growth and fattening, metabolic status and puberty attainment of a swine model of obesity/leptin resistance with controlled postnatal nutrition and opportunity of exercise. Maternal restriction was related to changes in the relationships among gene expression of positive (insulin-like growth factors 1 and 2) and negative (myostatin) regulators of muscle growth, with negative correlations in gilts from restricted pregnancies and positive relationships in the control group. In spite of these differences, the patterns of growth and fattening and the metabolic features during juvenile growth were similar in control gilts and gilts from restricted pregnancies. Concomitantly, there was a lack of differences in the timing of puberty attainment. However, after reaching puberty and adulthood, females from restricted pregnancies were heavier and more corpulent than control gilts, though such increases in weight and size were not accompanied by increases in adiposity. In conclusion, in spite of changes in gene expression induced by developmental programming, the propensity for higher weight and adiposity of individuals exposed to prenatal malnutrition may be modulated by controlled food intake and opportunity of physical exercise during infant and juvenile development.