The use of digital escape rooms in nursing education.

Negative attitudes and prejudices towards people with a mental disorder are common across cultures and societies. The stigma associated with mental illness leads to a lower quality of life, given the discrimination and social exclusion suffered by people with this type of disorder. In the field of health, research has shown that doctors and nurses also manifest these types of stigmatizing behaviors and attitudes. The present study aims to create and apply an educational escape room for the purpose of training nursing students in mental health, promoting positive attitudes towards people who have a mental disorder. To do so, a pre-post study was conducted with an experimental group and a control group to determine whether the escape room was effective for the modification of stigmatizing behaviors compared to transmissive lecture class, and a third measurement was made at 6 months only to the experimental group to evaluate whether the changes produced by the escape room were maintained in the long term. The results indicate that the students participating in the study obtained better scores in sensitization and these remain better over time. It is concluded that the escape room used is suitable for the training and sensitization of future nursing professionals in the field of mental health, facilitating the learning of knowledge and positive attitudes towards severe mental disorder.

Endocarditis caused by anaerobic bacteria.

BACKGROUND: Infective endocarditis (IE) caused by anaerobic bacteria is a rare and poorly characterized disease. Most data reported in the literature are from case reports [1-3]. Therefore, we assessed the situation of anaerobic IE (AIE) in Spain using the database of the Spanish Collaboration on Endocarditis (GAMES). METHODS: We performed a prospective study from 2008 to 2016 in 26 Spanish centers. We included 2491 consecutive cases of definite IE (Duke criteria). RESULTS: Anaerobic bacteria caused 22 cases (0.9%) of definite IE. Median age was 66 years (IQR, 56-73), and 19 (86.4%) patients were men. Most patients (14 [63.6%]) had prosthetic valve IE and all episodes were left-sided: aortic valves, 12 (54.5%); and mitral valves, 8 (36.4%). The most common pathogens were Propionibacterium acnes (14 [63.6%]), Lactobacillus spp (3 [13.63%]), and Clostridium spp. (2 [9.0%]), and the infection was mainly odontogenic. Fifteen of the 22 patients (68.2%) underwent cardiac surgery. Mortality was 18.2% during admission and 5.5% after 1 year of follow-up. When patients with AIE were compared with the rest of the cohort, we found that although those with AIE had a similar age and Charlson comorbidity index, they were more likely to have community-acquired IE (86.4% vs. 60.9%, p = 0.01), have undergone cardiac surgery (68.2% vs 48.7% p = 0.06), and have had lower mortality rates during admission (18.2% vs. 27.3%). CONCLUSION: IE due to anaerobic bacteria is an uncommon disease that affects mainly prosthetic valves and frequently requires surgery. Otherwise, there are no major differences between AIE and IE caused by other microorganisms.

CD27+ B cells from a subgroup of common variable immunodeficiency patients are less sensitive to apoptosis rescue regardless of interleukin-21 signalling.

Common variable immunodeficiency (CVID) is a primary immunodeficiency characterized by hypogammaglobulinaemia and recurrent infections. Although the underlying cause is unknown, B cells from most CVID patients fail to differentiate to memory or plasma cells. We investigated if increased apoptosis could influence the fate of B cells. For this purpose we activated purified B lymphocytes of CVID patients with a surrogate T-dependent (anti-CD40) or T-independent [cytosine-phosphate-guanosine oligodeoxynucleotides (CpG-ODN) or anti-immunoglobulin (Ig)M)] stimulus with or without interleukin (IL)-21. We found that CD27(+) B cells were more sensitive than CD27(-) B cells to spontaneous apoptosis and less sensitive to rescue from apoptosis. The addition of IL-21 down-modulated the protective effect of all the stimuli on CD27(-) B cells and the protective effect of CpG-ODN and anti-IgM on CD27(+) B cells. In contrast, IL-21 rescued unstimulated CD27(-) B cells and improved the rescue of anti-CD40-stimulated CD27(+) B cells. When we compared patients and controls, mainly CD27(+) B cells from MB0 patients were less sensitive to rescue from apoptosis than those from MB1 patients and controls after activation, irrespective of the IL-21 effect. Increased apoptosis during an immune response could result in lower levels of immunoglobulin production in these patients.

Phenotypic characterisation of T-lymphocytes in COPD: abnormal CD4+CD25+ regulatory T-lymphocyte response to tobacco smoking.

Tobacco smoking induces an inflammatory response in the lungs of all smokers but, for reasons that are still poorly understood, only a proportion of them develop chronic obstructive pulmonary disease (COPD). Recent evidence indicates that this inflammatory response persists after smoking cessation, suggesting some type of auto-perpetuation mechanism similar to that described in autoimmune disorders. T-lymphocytes (CD4+ and CD8+) have been implicated in the pathogenesis of both COPD and several autoimmune processes. A subtype of regulatory CD4+ T-cells expressing CD25 (Tregs) plays a critical role in the maintenance of peripheral tolerance and the prevention of autoimmunity, but their potential role in COPD has not been explored. The present study sought to evaluate maturation (CD45RA/CD45R0) and activation markers (CD28) of T-lymphocytes and to explore potential Treg abnormalities in COPD. Flow cytometry was used to characterise T-lymphocytes obtained from blood and bronchoalveolar lavage fluid (BALF) in 23 patients with moderate COPD, 29 smokers with normal lung function and seven never-smokers. The main findings were that in BALF: patients with COPD showed higher CD8+CD45RA+ and lower CD8+CD45R0+ than smokers with normal lung function; and compared with never-smokers, smokers with preserved lung function showed a prominent upregulation of Tregs that was absent in patients with COPD. These observations indicate a final maturation-activation state of CD8+ T-lymphocytes in chronic obstructive pulmonary disease and, for the first time, identify a blunted regulatory T-cell response to tobacco smoking in these patients, further supporting a potential involvement of the acquired immune response in the pathogenesis of the disease.

Effect of exercise on skeletal muscle proteolytic enzyme activity and meat quality characteristics in Iberian pigs.

The effects of physical activity on performance, carcass traits, Psoas major lysosomal and exoprotease acitivies and meat quality were studied in 24 castrated male Iberian pigs during the last fattening period (from 111.1±SD: 5.2kg). Pigs were randomly distributed in three groups. Two groups receiving the same diet were reared in confinement, one housed in individual pens of 8m(2) (sedentary group) and the other was housed outdoor with daily (up to 2km) forced walking (exercise group). And one group was reared under the traditional production system walking daily several km and fed mostly with acorn from Quercus ilex and Quercus rotundifolia and grass (free-range group). No differences were found in performance and carcass traits. In exercised pigs a lower activity of cathepsin B+L and total cathepsins (P<0.05) was observed. Exercise induced the inhibition of dipeptidyl peptidases II and III and arginyl aminopeptidase and the activation of dipeptidyl peptidases IV and leucyl aminopeptidase (P<0.05). Although no effects on total free amino acids in Psoas major muscle were observed the concentration of branched chain amino acids decreased in the free-range pig group probably related to an increase in physical activity. Exercise had no effects in Psoas major postmortem tenderness and water holding capacity.

The use of ertapenem for the treatment of community-acquired pneumonia in routine hospital practice: a matched cohort study.

OBJECTIVE: The clinical response to ertapenem in community-acquired pneumonia (CAP) at the setting of routine hospital practice has been scarcely evaluated. METHODS: We retrospectively compared CAP cases treated with ertapenem or with other standard antimicrobials (controls) at a tertiary 1,434-bed center from 2005 to 2014. RESULTS: Out of 6,145 patients hospitalized with CAP, 64 (1%) ertapenem-treated and 128 controls were studied (PSI IV-V 72%, mean age 73 years.). A significant higher proportion of bedridden patients (41% vs. 21%), residence in nursing homes (19% vs. 7%), previous use of antibiotics (39% vs. 29%) and necrotizing (13% vs. 1%) or complicated (36% vs. 19%) pneumonia, was observed in the ertapenem vs. non-ertapenem patients. Initial treatment with ertapenem was independently associated with an earlier resolution of signs of infection. In patients aged 65 or older the independent risks factors for mortality were: PSI score (7.0, 95%CI 1.8-27.7), bedridden status (4.6, 95%CI 1.1-20.9) and Health Care Associated Pneumonia (HCAP) (4.6, 95%CI 1.3-16.5). First-line treatment with ertapenem was an independent protector factor in this subgroup of patients (0.1, 95%CI 0.1-0.7). CONCLUSIONS: Ertapenem showed a superior clinical response in frail elderly patients with complicated community-acquired pneumonia, and it may be considered as a first-line therapeutic regimen in this setting.

Melatonin increases intracellular calcium in the liver, muscle, white adipose tissues and pancreas of diabetic obese rats.

Melatonin, a widespread substance with antioxidant and anti-inflammatory properties, has been found to act as an antidiabetic agent in animal models, regulating the release and action of insulin. However, the molecular bases of this antidiabetic action are unknown, limiting its application in humans. Several studies have recently shown that melatonin can modify calcium (Ca(2+)) in diabetic animals, and Ca(2+) has been reported to be involved in glucose homeostasis. The objective of the present study was to assess whether the antidiabetic effect of chronic melatonin at pharmacological doses is established via Ca(2+) regulation in different tissues in an animal model of obesity-related type 2 diabetes, using Zücker diabetic fatty (ZDF) rats and their lean littermates, Zücker lean (ZL) rats. After the treatments, flame atomic absorption spectrometry was used to determine Ca(2+) levels in the liver, muscle, main types of internal white adipose tissue, subcutaneous lumbar fat, pancreas, brain, and plasma. This study reports for the first time that chronic melatonin administration (10 mg per kg body weight per day for 6 weeks) increases Ca(2+) levels in muscle, liver, different adipose tissues, and pancreas in ZDF rats, although there were no significant changes in their brain or plasma Ca(2+) levels. We propose that this additional peripheral dual action mechanism underlies the improvement in insulin sensitivity and secretion previously documented in samples from the same animals. According to these results, indoleamine may be a potential candidate for the treatment of type 2 diabetes mellitus associated with obesity.

Left-sided infective endocarditis in patients with liver cirrhosis.

OBJECTIVE: To evaluate the course of left-sided infective endocarditis (LsIE) in patients with liver cirrhosis (LC) analyzing its influence on mortality and the impact of surgery. METHODS: Prospective cohort study, conducted from 1984 to 2013 in 26 Spanish hospitals. RESULTS: A total of 3.136 patients with LsIE were enrolled and 308 had LC: 151 Child-Pugh A, 103 B, 34 C and 20 were excluded because of unknown stage. Mortality was significantly higher in the patients with LsIE and LC (42.5% vs. 28.4%; p < 0.01) and this condition was in general an independent worse factor for outcome (HR 1.51, 95% CI: 1.23-1.85; p < 0.001). However, patients in stage A had similar mortality to patients without cirrhosis (31.8% vs. 28.4% p = NS) and in this stage heart surgery had a protective effect (28% in operated patients vs. 60% in non-operated when it was indicated). Mortality was significantly higher in stages B (52.4%) and C (52.9%) and the prognosis was better for patients in stage B who underwent surgery immediately (mortality 50%) compared to those where surgery was delayed (58%) or not performed (74%). Only one patient in stage C underwent surgery. CONCLUSIONS: Patients with liver cirrhosis and infective endocarditis have a poorer prognosis only in stages B and C. Early surgery must be performed in stages A and although in selected patients in stage B when indicated.

Organization of association projections from area 17 to areas 18 and 19 and to suprasylvian areas in the cat's visual cortex.

Cells in area 17 that are labelled by single, discrete injections of retrogradely transported tracers into extrastriate visual areas are discontinuously distributed in dense patches. In this study we made multiple, closely spaced injections of fluorescent dyes into extrastriate areas, to generate large deposits that would reveal whether the distributions of corticocortical cell bodies in area 17 are truly patchy or appear clustered only after small injections. By injecting a different tracer into each extrastriate area, or group of areas, we examined the spatial relationships between the populations of association cells. All deposits of tracers in areas 18, 19, or suprasylvian cortex, irrespective of size, label cells in a series of clusters in topographically related parts of area 17. We conclude that the complete populations of cells in area 17 that project to areas 18, 19, and the lateral suprasylvian cortex are all genuinely distributed in a patchy fashion. There appears to be a complex relationship between the sets of association cells projecting to different extrastriate regions: they do not completely overlap, only partially, and share some cortical zones but not others. In these experiments, only tiny percentages (2-5%) of labelled cells in the overlapping regions were filled with both tracers, suggesting that very few association cells in area 17 project to more than one of the extrastriate areas we studied. By comparing the dimensions of each injection site and of the labelled region in area 17, we estimated the extent of the convergence from area 17 to areas 18, 19, and posteromedial suprasylvian areas in retinotopic terms. The functional convergence was very similar in these pathways.

Neurologic complications associated with hepatitis C virus infection.

A series of nine patients with neurologic complications of hepatitis C virus infection is reported. Seven patients presented a combination of chronic sensory polyneuropathy, multineuropathy, and encephalopathy related to cryoglobulinemia. The noncryoglobulinemic symptoms consisted of an anterior optic neuropathy and a restless legs syndrome with small-fiber neuropathy. Corticosteroids and cyclophosphamide were useful in controlling vasculitic episodes. Interferon-alpha caused remission in half of the treated patients.

Regressive changes among corticocortical neurons projecting from the lateral suprasylvian cortex to area 18 of the kitten's visual cortex.

The postnatal development of corticocortical neurons projecting from the medial bank of the lateral suprasylvian cortex to area 18 of the kitten's visual cortex was examined using retrograde fluorescent tracers. Area 18 was injected in young kittens aged nine days or less and in older kittens aged 30 days or more. Many of the injected kittens were perfused with fixative four to five days later, but some of the youngest were killed after longer survival periods of 35-50 days (long-survival animals). Labelled neurons in the medial bank of the lateral suprasylvian cortex were densely distributed in both superficial layers (II and III) and deep layers (V and VI) in the kittens injected less than nine days postnatal, irrespective of whether survival was short or long, but they were found almost exclusively in layers V and VI in the old, short-survival animals. Only in the group of old kittens did we find a clear topographical arrangement of projections in the rostrocaudal direction and a correlation between the rostrocaudal lengths of the injection sites and labelled areas. In the other two groups, for a similarly sized injection site, the labelled areas were much longer rostrocaudally than in the old, short-survival kittens, and occupied roughly the posterior two-thirds of the medial bank of the lateral suprasylvian cortex, irrespective of the positions of the injections. In the frontal plane, topography was unclear in all groups. These findings demonstrate that there is considerable postnatal refinement of the projection from the medial bank of the lateral suprasylvian cortex to area 18. This involves a loss of connections originating from superficial layers and a decrease of convergence with the appearance of topography. Our results from long-survival kittens suggest that most of the early exuberant population of corticocortical neurons projecting from the medial bank of the lateral suprasylvian cortex to area 18 survive beyond the first postnatal month but undergo axonal elimination during this period.

Mediation by neurotensin-receptors of effects of neurotensin on self-stimulation of the medial prefrontal cortex.

1 Intracortical microinjections of neurotensin (NT) selectively decreased intracranial self-stimulation (ICSS) of the medial prefrontal cortex in the rat. 2 To elucidate whether this effect is mediated by NT receptors or by the formation of NT-dopamine complexes, we investigated the effects on ICSS of intracortical microinjections of neurotensin (1-11), an NT fragment that forms extracellular complexes with dopamine but does not bind to NT receptors. 3 We also studied the effects of the peripheral administration of SR 48692, a selective antagonist of NT receptors, on the inhibition of ICSS produced by the intracortical administration of NT. 4 Unilateral microinjections of neurotensin (1-11) at doses of 10, 20 and 40 nmol into the medial prefrontal cortex did not change the basal ICSS rate of this area. 5 The intraperitoneal administration of SR 48692 at doses of 0.08 and 0.16 mg kg-1 30 min before microinjection of 10 nmol of NT into the medial prefrontal cortex, antagonized the inhibition of ICSS produced by the neuropeptide. 6 These results demonstrate that the inhibitory effect of NT on ICSS is mediated by NT receptors.

Adverse drug reactions in children reported by means of the yellow card in Spain.

OBJECTIVE: To analyze the case reports concerning children (14 years or younger) in the Spanish Pharmacovigilance System over a 10-year period (1982-1991). FINDINGS: The study of 1419 reports of adverse drug reaction (9.8% of all those received) showed the most commonly involved organs and systems to be the skin, digestive tract, and nervous system (62.8%). The most commonly involved pharmacological groups were antibiotics, respiratory medications, and vaccines (69%). The absolute number of reports is higher in children between 1 and 4 years of age (37.9%). There were more reports among males than in females. Less than 5% of the reports notified directly life-threatening or fatal reactions. CONCLUSIONS: Adverse drug reaction are not common in pediatric patients, and most are mild. However, due to limitations of clinical trials in children, pharmacoepidemiological studies may be the only source of information on the benefit-risk profile of drugs received by these patients, and as such require special attention.

Neuromedin N decreases self-stimulation of the medial prefrontal cortex.

Intracerebral microinjections of neurotensin (NT) decrease intracranial self-stimulation (ICSS) of the medial prefrontal cortex (MPC) in the rat. This effect could be due to the ability of NT to bind dopamine. To test this hypothesis we studied the effects of intracerebral microinjections of neuromedin N, a natural NT analogue that does not bind dopamine, on ICSS of the rat MPC. Unilateral microinjections of neuromedin N into the MPC at doses of 2.5, 5, 10, 20 and 40 nmol produced a dose-related decrease in ICSS of the ipsilateral MPC. ICSS of the contralateral MPC, used as a control, was not affected by the microinjections. These results suggest that the inhibitory effect of NT on ICSS is independent of NT-dopamine binding. Because neuromedin N is also present in the MPC, these results also suggest a possible neuromodulatory role of this neuropeptide on ICSS of the prefrontal cortex.

Peptidase inhibitors potentiate the effects of neurotensin and neuromedin N on self-stimulation of the medial prefrontal cortex.

The purpose of this study was to examine the possible role of endogenous peptidases in the inhibition of intracranial self-stimulation (ICSS) produced by injections of neurotensin (NT) and neuromedin N (NN) into the medial prefrontal cortex (MPC) of the rat. We studied the effects on ICSS of the MPC of the administration of thiorphan and bestatin, two specific inhibitors of the peptidases that inactivate NT and NN respectively. Microinjections into MPC of thiorphan (10 micrograms) and bestatin (25 micrograms) potentiated in inhibition of ICSS produced by the intracortical administration of NT (10 nmol) and NN (20 nmol) respectively. This potentiation affected both the amplitude and the duration of the inhibition of ICSS produced by the neuropeptides. Our data indicate that endogenous peptidases are involved in the inactivation of NT and NN in the prefrontal cortex.

Plasticity of an aberrant geniculocortical pathway in neonatally lesioned cats.

Geniculocortical afferents to the lateral suprasylvian (LS) visual area come only from the C layers in normal adult cats. After neonatal lesions of areas 17 and 18, inputs to the LS area also arise from the A layers. We studied the plasticity of this aberrant pathway. We made lesions in areas 17 and 18 of newborn kittens, some of which were then monocularly deprived. In lesioned undeprived cats, retrograde tracing confirmed projections to the LS area from both the A and A1 as well as the C geniculate layers. In lesioned deprived cats, geniculate afferents from the A layers to the LS area came mainly from the layer receiving a normal visual input. We conclude that the development of the abnormal pathway from the A layers to the LS area is influenced by patterned visual activity.

Immediate endoscopic diagnosis of upper gastrointestinal bleeding. Its accuracy and value in relation to associated pathology.

Two hundred sixty-two patients with active upper gastrointestinal (GI) bleeding underwent panendoscopy between July 1970 and March 1973. There was 100% accuracy of endoscopic diagnosis as to the anatomical site of bleeding; the etiopathologic definition was 94.7% accurate. The series was divided into two groups, 116 with "liver disease" and 146 with "no liver disease." There were 107 patients with varices: 21 fell into no liver disease (small varices) and 86 into liver disease (39 small and 47 large varices). All had associated gastritis. Three endoscopic bleeding patterns were identified in the liver disease group. Only 27% of the patients in the liver disease group with varices (cirrhotics) had frank variceal hemorrhage, whereas 57% bled from hemorrhagic gastritis. The diagnostic unit provided early diagnosis, meaningful therapy, organized data gathering, and rough estimates of ultimate prognosis.

Peptides and self-stimulation of the medial prefrontal cortex in the rat: effects of intracerebral microinjections of substance P and cholecystokinin.

The effects of intracerebral microinjections of substance P and cholecystokinin on self-stimulation of the medial prefrontal cortex of the rat were studied. Intracerebroventricular administration of substance P at doses of 2.5, 5, 10 and 20 micrograms produced a dose-related decrease in self-stimulation of the medial prefrontal cortex; spontaneous motor activity, measured as a control, was not affected. Unilateral microinjections into the medial prefrontal cortex of substance P at doses of 10 and 20 micrograms produced a decrease of self-stimulation of the ipsilateral side, but self-stimulation of the contralateral cortex, used as a control, was not affected. On the contrary, cholecystokinin in both intracerebroventricular administration at doses of 100, 200 and 400 ng, or intracortical microinjections into the medial prefrontal cortex at doses of 200, 400 and 800 ng, had no effect on self-stimulation of this cortical area. These results suggest that substance P, but not cholecystokinin, could be part of the neurochemical substrate underlying self-stimulation of the medial prefrontal cortex in the rat.

Neurotransmitters, pathways and circuits as the neural substrates of self-stimulation of the prefrontal cortex: facts and speculations.

Through a multidisciplinary approach considerable progress has been made in understanding the neural substrates of self-stimulation (SS) of the medial prefrontal cortex (MPC). Thus, neuroanatomical studies have revealed that intrinsic neurones in the MPC seem to be the central elements responsible for initiating and maintaining this phenomenon in this area of the brain. Complementary to this central finding are the electrophysiological and neurohistological data reviewed here, showing that neurones in the MPC are directly activated and have monosynaptic feed-back connections with neurones located in areas which also support SS. These findings have given rise to the hypothesis that several single feed-back pathways or single circuits exist between points of SS in the MPC and points of SS in other areas of the brain. This hypothesis implies that SS in a particular area would depend not only on the intrinsic local activity induced by the electrical stimulation but on the functional and specific activity of other nuclei in the brain. The fact that lesions of single circuits, which are apparently involved in SS of the MPC such as the medial prefrontal cortex-ventrotegmental area-medial prefrontal cortex and medial prefrontal cortex-n. dorsomedialis of the thalamus-medial prefrontal cortex, do not produce a permanent decrease of SS, together with the finding that transynaptic connections seem to exist between MPC and other areas of the brain, suggests further that a complex rather than several single independent circuits could be at the neural basis of SS of the MPC. If that were the case, then SS of the MPC would not only depend upon local and single feed-back activity but upon specific functional feed-back activity among the nuclei, which in turn have single feed-back connections with the MPC (see the concept of 'complex circuit' outlined in the section of Behavioural studies). On the basis of this hypothesis no permanent changes should be expected after lesions of single pathways since physiological and even anatomical compensation could be reached through the rest of the undamaged circuit. That terminals containing specific neurotransmitters exist in layers of the PC where electrodes for SS are located has been reviewed in this paper. Some of these neurotransmitters have been suggested to be part of the local substrates activated by SS.(ABSTRACT TRUNCATED AT 400 WORDS)

The role of the lateral cortico-cortical prefrontal pathway in self-stimulation of the medial prefrontal cortex in the rat.

Effects of electrolytic and kainic acid lesions at several stereotaxic planes of the lateral cortico-cortical prefrontal efferent pathway on self-stimulation of the medial prefrontal cortex were investigated. Electrolytic bilateral lesion of the sulcal prefrontal cortex, the first terminal area of this pathway, produced no effects on self-stimulation of the medial prefrontal cortex. However, bilateral electrolytic lesion of this pathway at the rostral part of the external capsule produced a permanent abolition of self-stimulation of the medial prefrontal cortex. These effects seemed selective since operant behaviour to obtain water, similar to that performed for self-stimulation and used as a control, was not affected by the lesion except on the 1st, 3rd (P less than 0.01) and 5th (P less than 0.05) days postlesion. Interestingly, bilateral microinjections of kainic acid (10 nmol in 0.8 microliters) at the same stereotaxic planes of the external capsule where electrolytic lesion was produced, had no effects on self-stimulation. These results suggest that fibres-of-passage through the external capsule are responsible for the abolition of self-stimulation. Bilateral electrolytic lesion of the entorhinal cortex, one of the caudal terminal areas of this descending set of fibres, produced a short transient decrease of self-stimulation of the medial prefrontal cortex. These results are discussed on the basis that complex, rather than single circuits are involved in maintaining self-stimulation in this neocortical area.