Mental health care: perceptions of people with schizophrenia and their carers

The current study aims to discover the opinions of patients and their (informal and formal) carers concerning the mental health care of individuals with long term schizophrenic disorders within different contexts and cultures. It's a qualitative study with focus groups, in which 6 research centers (from Argentina, Brazil, Chile, Spain, England and Venezuela) participated. Eight focus groups were conducted in each center, totaling 303 individuals in 46 groups. The data were analyzed with the aid of the Qualitative Solutions and Research/Non-numerical Unstructured Data Indexing program (QSR NUD*IST 4.0). The perception regarding the quality of care is influenced by the professional-patient relationship and the availability of resources. Poor quality of care is also perceived as discrimination. People with schizophrenia in general consider themselves to be ostracized by professionals and services and lacking in more humanized care. In the contexts in which community care is less advanced, the complaints center on resources and services that do not meet demands. On the other hand, in more developed contexts criticism centers more on the attitude of the professionals and the professional-patient relationship. Over and above the need for resources and services, people with schizophrenia require more humanized health care

High Energy Cosmic Rays From Supernovae

Cosmic rays are charged relativistic particles that reach the Earth with extremely high energies, providing striking evidence of the existence of effective accelerators in the Universe. Below an energy around $\sim 10^{17}$ eV cosmic rays are believed to be produced in the Milky Way while above that energy their origin is probably extragalactic. In the early '30s supernovae were already identified as possible sources for the Galactic component of cosmic rays. After the '70s this idea has gained more and more credibility thanks to the the development of the diffusive shock acceleration theory, which provides a robust theoretical framework for particle energization in astrophysical environments. Afterwards, mostly in recent years, much observational evidence has been gathered in support of this framework, converting a speculative idea in a real paradigm. In this Chapter the basic pillars of this paradigm will be illustrated. This includes the acceleration mechanism, the non linear effects produced by accelerated particles onto the shock dynamics needed to reach the highest energies, the escape process from the sources and the transportation of cosmic rays through the Galaxy. The theoretical picture will be corroborated by discussing several observations which support the idea that supernova remnants are effective cosmic ray factories.Comment: Final draft of a chapter in "Handbook of Supernovae" edited by Athem W. Alsabti and Paul Murdi

Transcorneal electrical stimulation for the treatment of retinitis pigmentosa: results from the TESOLAUK trial

OBJECTIVE: To explore the impact of weekly transcorneal electrical stimulation (TES) over a 6-month period as a treatment for retinitis pigmentosa (RP). METHODS AND ANALYSIS: A prospective open-label observational trial was carried out assessing weekly TES in participants with RP for a period of 6 months followed by observation for a further 6 months. Clinical examination and investigations were carried out at 3 monthly intervals for a total of 12 months. The primary outcome measure explored safety through a descriptive analysis of adverse effects with secondary outcome measures evaluating structural and functional efficacy. RESULTS: Seven male and seven female participants with RP aged 18-80 years were recruited. TES was well tolerated with no serious adverse events reported. Two participants reported transient foreign body sensation and one participant had discomfort underneath the skin electrode. Following 6 months of TES, best-corrected visual acuity increased by 1.1±1.4 letters in the control arm and 0.93±1.4 letters in the treated arm. Central microperimetry threshold sensitivity rose by 0.02±0.5 decibels (dB) and 0.37±0.4 dB and Goldmann visual field volume by 0.16±0.09 steradians (sr) vs 0.22±0.12 sr for the control and treated eye, respectively. There was no statistical significance seen between eyes following the treatment or observation period. CONCLUSION:: This small open-label clinical trial showed that TES was safe and well tolerated in patients with RP. Visual function measurements at 6 months demonstrated no significant difference between the control and treated eyes. The results justify a larger clinical trial over a longer period of time in order to identify any treatment effect

Fifty years of spellchecking

A short history of spellchecking from the late 1950s to the present day, describing its development through dictionary lookup, affix stripping, correction, confusion sets, and edit distance to the use of gigantic databases

Role of the mesoamygdaloid dopamine projection in emotional learning

Amygdala dopamine is crucially involved in the acquisition of Pavlovian associations, as measured via conditioned approach to the location of the unconditioned stimulus (US). However, learning begins before skeletomotor output, so this study assessed whether amygdala dopamine is also involved in earlier 'emotional' learning. A variant of the conditioned reinforcement (CR) procedure was validated where training was restricted to curtail the development of selective conditioned approach to the US location, and effects of amygdala dopamine manipulations before training or later CR testing assessed. Experiment 1a presented a light paired (CS+ group) or unpaired (CS- group) with a US. There were 1, 2 or 10 sessions, 4 trials per session. Then, the US was removed, and two novel levers presented. One lever (CR+) presented the light, and lever pressing was recorded. Experiment 1b also included a tone stimulus. Experiment 2 applied intra-amygdala R(+) 7-OH-DPAT (10 nmol/1.0 A mu l/side) before two training sessions (Experiment 2a) or a CR session (Experiment 2b). For Experiments 1a and 1b, the CS+ group preferred the CR+ lever across all sessions. Conditioned alcove approach during 1 or 2 training sessions or associated CR tests was low and nonspecific. In Experiment 2a, R(+) 7-OH-DPAT before training greatly diminished lever pressing during a subsequent CR test, preferentially on the CR+ lever. For Experiment 2b, R(+) 7-OH-DPAT infusions before the CR test also reduced lever pressing. Manipulations of amygdala dopamine impact the earliest stage of learning in which emotional reactions may be most prevalent

Protein disulfide-isomerase interacts with a substrate protein at all stages along its folding pathway

In contrast to molecular chaperones that couple protein folding to ATP hydrolysis, protein disulfide-isomerase (PDI) catalyzes protein folding coupled to formation of disulfide bonds (oxidative folding). However, we do not know how PDI distinguishes folded, partly-folded and unfolded protein substrates. As a model intermediate in an oxidative folding pathway, we prepared a two-disulfide mutant of basic pancreatic trypsin inhibitor (BPTI) and showed by NMR that it is partly-folded and highly dynamic. NMR studies show that it binds to PDI at the same site that binds peptide ligands, with rapid binding and dissociation kinetics; surface plasmon resonance shows its interaction with PDI has a Kd of ca. 10−5 M. For comparison, we characterized the interactions of PDI with native BPTI and fully-unfolded BPTI. Interestingly, PDI does bind native BPTI, but binding is quantitatively weaker than with partly-folded and unfolded BPTI. Hence PDI recognizes and binds substrates via permanently or transiently unfolded regions. This is the first study of PDI's interaction with a partly-folded protein, and the first to analyze this folding catalyst's changing interactions with substrates along an oxidative folding pathway. We have identified key features that make PDI an effective catalyst of oxidative protein folding – differential affinity, rapid ligand exchange and conformational flexibility

Adaptation of rat fast-twitch muscle to endurance activity is underpinned by changes to protein degradation as well as protein synthesis.

Muscle adaptations to exercise are underpinned by alterations to the abundance of individual proteins, which may occur through a change either to the synthesis or degradation of each protein. We used deuterium oxide (2 H2 O) labeling and chronic low-frequency stimulation (CLFS) in vivo to investigate the synthesis, abundance, and degradation of individual proteins during exercise-induced muscle adaptation. Independent groups of rats received CLFS (10 Hz, 24 h/d) and 2 H2 O for 0, 10, 20, or 30 days. The extensor digitorum longus (EDL) was isolated from stimulated (Stim) and contralateral non-stimulated (Ctrl) legs. Proteomic analysis encompassed 38 myofibrillar and 46 soluble proteins and the rates of change in abundance, synthesis, and degradation were reported in absolute (ng/d) units. Overall, synthesis and degradation made equal contributions to the adaptation of the proteome, including instances where a decrease in protein-specific degradation primarily accounted for the increase in abundance of the protein

PPARβ activation inhibits melanoma cell proliferation involving repression of the Wilms’ tumour suppressor WT1

Peroxisome proliferator-activated receptors (PPARs) are ligand-activated transcription factors that strongly influence molecular signalling in normal and cancer cells. Although increasing evidence suggests a role of PPARs in skin carcinogenesis, only expression of PPARγ has been investigated in human melanoma tissues. Activation of PPARα has been shown to inhibit the metastatic potential, whereas stimulation of PPARγ decreased melanoma cell proliferation. We show here that the third member of the PPAR family, PPARβ/δ is expressed in human melanoma samples. Specific pharmacological activation of PPARβ using GW0742 or GW501516 in low concentrations inhibits proliferation of human and murine melanoma cells. Inhibition of proliferation is accompanied by decreased expression of the Wilms’ tumour suppressor 1 (WT1), which is implicated in melanoma proliferation. We demonstrate that PPARβ directly represses WT1 as (1) PPARβ activation represses WT1 promoter activity; (2) in chromatin immunoprecipitation and electrophoretic mobility shift assays, we identified a binding element for PPARβ in the WT1 promoter; (3) deletion of this binding element abolishes repression by PPARβ and (4) the WT1 downstream molecules nestin and zyxin are down-regulated upon PPARβ activation. Our findings elucidate a novel mechanism of signalling by ligands of PPARβ, which leads to suppression of melanoma cell growth through direct repression of WT1

Wind from the black-hole accretion disk driving a molecular outflow in an active galaxy

Powerful winds driven by active galactic nuclei (AGN) are often invoked to play a fundamental role in the evolution of both supermassive black holes (SMBHs) and their host galaxies, quenching star formation and explaining the tight SMBH-galaxy relations. Recent observations of large-scale molecular outflows in ultra-luminous infrared galaxies (ULIRGs) have provided the evidence to support these studies, as they directly trace the gas out of which stars form. Theoretical models suggest an origin of these outflows as energy-conserving flows driven by fast AGN accretion disk winds. Previous claims of a connection between large-scale molecular outflows and AGN activity in ULIRGs were incomplete because they were lacking the detection of the putative inner wind. Conversely, studies of powerful AGN accretion disk winds to date have focused only on X-ray observations of local Seyferts and a few higher redshift quasars. Here we show the clear detection of a powerful AGN accretion disk wind with a mildly relativistic velocity of 0.25c in the X-ray spectrum of IRAS F11119+3257, a nearby (z = 0.189) optically classified type 1 ULIRG hosting a powerful molecular outflow. The AGN is responsible for ~80% of the emission, with a quasar-like luminosity of L_AGN = 1.5x10^46 erg/s. The energetics of these winds are consistent with the energy-conserving mechanism, which is the basis of the quasar mode feedback in AGN lacking powerful radio jets.Comment: Revised file including the letter, methods and supplementary information. Published in the March 26th 2015 issue of Natur

Effect of sedation with detomidine and butorphanol on pulmonary gas exchange in the horse

<p>Abstract</p> <p>Background</p> <p>Sedation with α₂-agonists in the horse is reported to be accompanied by impairment of arterial oxygenation. The present study was undertaken to investigate pulmonary gas exchange using the Multiple Inert Gas Elimination Technique (MIGET), during sedation with the α₂-agonist detomidine alone and in combination with the opioid butorphanol.</p> <p>Methods</p> <p>Seven Standardbred trotter horses aged 3–7 years and weighing 380–520 kg, were studied. The protocol consisted of three consecutive measurements; in the unsedated horse, after intravenous administration of detomidine (0.02 mg/kg) and after subsequent butorphanol administration (0.025 mg/kg). Pulmonary function and haemodynamic effects were investigated. The distribution of ventilation-perfusion ratios (V_A/Q) was estimated with MIGET.</p> <p>Results</p> <p>During detomidine sedation, arterial oxygen tension (PaO₂) decreased (12.8 ± 0.7 to 10.8 ± 1.2 kPa) and arterial carbon dioxide tension (PaCO₂) increased (5.9 ± 0.3 to 6.1 ± 0.2 kPa) compared to measurements in the unsedated horse. Mismatch between ventilation and perfusion in the lungs was evident, but no increase in intrapulmonary shunt could be detected. Respiratory rate and minute ventilation did not change. Heart rate and cardiac output decreased, while pulmonary and systemic blood pressure and vascular resistance increased. Addition of butorphanol resulted in a significant decrease in ventilation and increase in PaCO₂. Alveolar-arterial oxygen content difference P(A-a)O₂remained impaired after butorphanol administration, the V_A/Q distribution improved as the decreased ventilation and persistent low blood flow was well matched. Also after subsequent butorphanol no increase in intrapulmonary shunt was evident.</p> <p>Conclusion</p> <p>The results of the present study suggest that both pulmonary and cardiovascular factors contribute to the impaired pulmonary gas exchange during detomidine and butorphanol sedation in the horse.</p