589 research outputs found
Cofactor regeneration by a soluble pyridine nucleotide transhydrogenase for biological production of hydromorphone
We have applied the soluble pyridine nucleotide transhydrogenase of Pseudomonas fluorescens to a cell-free system for the regeneration of the nicotinamide cofactors NAD and NADP in the biological production of the important semisynthetic opiate drug hydromorphone. The original recombinant whole-cell system suffered from cofactor depletion resulting from the action of an NADP(+)-dependent morphine dehydrogenase and an NADH-dependent morphinone reductase. By applying a soluble pyridine nucleotide transhydrogenase, which can transfer reducing equivalents between NAD and NADP, we demonstrate with a cell-free system that efficient cofactor cycling in the presence of catalytic amounts of cofactors occurs, resulting in high yields of hydromorphone. The ratio of morphine dehydrogenase, morphinone reductase, and soluble pyridine nucleotide transhydrogenase is critical for diminishing the production of the unwanted by-product dihydromorphine and for optimum hydromorphone yields. Application of the soluble pyridine nucleotide transhydrogenase to the whole-cell system resulted in an improved biocatalyst with an extended lifetime. These results demonstrate the usefulness of the soluble pyridine nucleotide transhydrogenase and its wider application as a tool in metabolic engineering and biocatalysis
Cannabis and schizophrenia
BACKGROUND
Schizophrenia is a mental illness causing disordered beliefs, ideas and sensations. Many people with schizophrenia smoke cannabis, and it is unclear why a large proportion do so and if the effects are harmful or beneficial. It is also unclear what the best method is to allow people with schizophrenia to alter their cannabis intake.
OBJECTIVES
To assess the effects of specific psychological treatments for cannabis reduction in people with schizophrenia.To assess the effects of antipsychotics for cannabis reduction in people with schizophrenia.To assess the effects of cannabinoids (cannabis related chemical compounds derived from cannabis or manufactured) for symptom reduction in people with schizophrenia.
SEARCH METHODS
We searched the Cochrane Schizophrenia Group Trials Register, 12 August 2013, which is based on regular searches of BIOSIS, CINAHL, EMBASE, MEDLINE, PUBMED and PsycINFO.We searched all references of articles selected for inclusion for further relevant trials. We contacted the first author of included studies for unpublished trials or data.
SELECTION CRITERIA
We included all randomised controlled trials involving cannabinoids and schizophrenia/schizophrenia-like illnesses, which assessed:1) treatments to reduce cannabis use in people with schizophrenia;2) the effects of cannabinoids on people with schizophrenia.
DATA COLLECTION AND ANALYSIS
We independently inspected citations, selected papers and then re-inspected the studies if there were discrepancies, and extracted data. For dichotomous data we calculated risk ratios (RR) and for continuous data, we calculated mean differences (MD), both with 95% confidence intervals (CI) on an intention-to-treat basis, based on a fixed-effect model. We excluded data if loss to follow-up was greater than 50%. We assessed risk of bias for included studies and used GRADE to rate the quality of the evidence.
MAIN RESULTS
We identified eight randomised trials, involving 530 participants, which met our selection criteria.For the cannabis reduction studies no one treatment showed superiority for reduction in cannabis use. Overall, data were poorly reported for many outcomes of interest. Our main outcomes of interest were medium-term data for cannabis use, global state, mental state, global functioning, adverse events, leaving the study early and satisfaction with treatment. 1. Reduction in cannabis use: adjunct psychological therapies (specifically about cannabis and psychosis) versus treatment as usualResults from one small study showed people receiving adjunct psychological therapies specifically about cannabis and psychosis were no more likely to reduce their intake than those receiving treatment as usual (n = 54, 1 RCT, MD -0.10, 95% CI -2.44 to 2.24, moderate quality evidence). Results for other main outcomes at medium term were also equivocal. No difference in mental state measured on the PANSS positive were observed between groups (n = 62, 1 RCT, MD -0.30 95% CI -2.55 to 1.95, moderate quality evidence). Nor for the outcome of general functioning measured using the World Health Organization Quality of Life BREF (n = 49, 1 RCT, MD 0.90 95% CI -1.15 to 2.95, moderate quality evidence). No data were reported for the other main outcomes of interest 2. Reduction in cannabis use: adjunct psychological therapy (specifically about cannabis and psychosis) versus adjunct non-specific psychoeducation One study compared specific psychological therapy aimed at cannabis reduction with general psychological therapy. At three-month follow-up, the use of cannabis in the previous four weeks was similar between treatment groups (n = 47, 1 RCT, RR 1.04 95% CI 0.62 to 1.74, moderate quality evidence). Again, at a medium-term follow-up, the average mental state scores from the Brief Pscychiatric Rating Scale-Expanded were similar between groups (n = 47, 1 RCT, MD 3.60 95% CI - 5.61 to 12.81, moderate quality evidence). No data were reported for the other main outcomes of interest: global state, general functioning, adverse events, leaving the study early and satisfaction with treatment. 3. Reduction in cannabis use: antipsychotic versus antipsychotic In a small trial comparing effectiveness of olanzapine versus risperidone for cannabis reduction, there was no difference between groups at medium-term follow-up (n = 16, 1 RCT, RR 1.80 95% CI 0.52 to 6.22, moderate quality evidence). The number of participants leaving the study early at medium term was also similar (n = 28, 1 RCT, RR 0.50 95% CI 0.19 to 1.29, moderate quality evidence). Mental state data were reported, however they were reported within the short term and no difference was observed. No data were reported for global state, general functioning, and satisfaction with treatment.With regards to adverse effects data, no study reported medium-term data. Short-term data were presented but overall, no real differences between treatment groups were observed for adverse effects. 4. Cannabinoid as treatment: cannabidiol versus amisulprideAgain, no data were reported for any of the main outcomes of interest at medium term. There were short-term data reported for mental state using the BPRS and PANSS, no overall differences in mental state were observed between treatment groups.
AUTHORS' CONCLUSIONS
Results are limited and inconclusive due to the small number and size of randomised controlled trials available and quality of data reporting within these trials. More research is needed to a) explore the effects of adjunct psychological therapy that is specifically about cannabis and psychosis as currently there is no evidence for any novel intervention being better than standard treatment,for those that use cannabis and have schizophrenia b) decide the most effective drug treatment in treating those that use cannabis and have schizophrenia, and c) assess the effectiveness of cannabidiol in treating schizophrenia. Currently evidence is insufficient to show cannabidiol has an antipsychotic effect
Measuring autobiographical fluency in the self-memory system
Autobiographical memory is widely considered to be fundamentally related to concepts of self and identity. However, few studies have sought to test models of self and memory directly using experimental designs. Using a novel autobiographical fluency paradigm, the present study investigated memory accessibility for different levels of self-related knowledge. Forty participants generated 20 "I am" statements about themselves, from which the 1st, 5th, 10th, 15th, and 20th were used as cues in a two-minute autobiographical fluency task. The most salient aspects of the self, measured by both serial position and ratings of personal significance, were associated with more accessible sets of autobiographical memories. This finding supports theories that view the self as a powerful organizational structure in memory. Results are discussed with reference to models of self and memory
Pharmacy Studentsā Lived Experiences With Atopic Dermatitis Inform Perceptions of Learning in the Curriculum
ObjectiveTo explore the impact of lived experiences of pharmacy students with atopic dermatitis (AD) on perceptions of learning in pharmacy curriculum.MethodsAn exploratory qualitative study was conducted with pharmacy students in the United Kingdom to understand how their lived experiences affect their perception of AD in pharmacy curriculum. Semi-structured interviews were conducted and a thematic analysis method was followed. Firstly, codes were created and then relevant codes were combined to identify themes.ResultsThirteen pharmacy students were interviewed. Study findings showed pharmacy students support teaching with a holistic approach to management and patient-centered care in AD in pharmacy curriculum. Although students had empathy and moral support for patients, they also described a need for teaching on the mental health effects of AD in pharmacy education.ConclusionThis brief report explores the role of lived experience of pharmacy students in considering the provision of holistic, patient-centered care in AD teaching in pharmacy education. Participants also suggest the need within the pharmacy curriculum for training to provide mental health advice to patients with AD
Beyond osteogenesis: an in vitro comparison of the potentials of six bone morphogenetic proteins
Bone morphogenetic proteins (BMPs) other than the clinically available BMP-2 and BMP-7 may be useful for improving fracture healing through both increasing osteogenesis and creating a favorable healing environment by altering cytokine release by endogenous cells. Given the spectrum of potential applications for BMPs, the objective of this study was to evaluate various BMPs under a variety of conditions to provide further insight into their therapeutic capabilities. The alkaline phosphatase (ALP) activity of both C(2)C(12) and human adipose-derived stem cells (hASCs) was measured after exposure of increasing doses of recombinant human BMP-2, -4, -5, -6, -7, or -9 for 3 and 7 days. BMPs-2, -4, -5, -6, -7, and -9 were compared in terms of their ability to affect the release of stromal derived factor-1 (SDF-1), vascular endothelial growth factor (VEGF), and basic fibroblast growth factor (b-FGF) from human bone marrow stromal cells (hBMSCs). Gene expression of ALP, osteocalcin, SDF-1, VEGF, and b-FGF following shRNA-mediated knockdown of BMP-2 and BMP-6 in hBMSCs or human osteoblasts under osteogenic differentiation conditions was also evaluated. Collectively, BMPs-6 and -9 produced the greatest osteogenic differentiation of C(2)C(12) and hASCs as determined by ALP. The hBMSC secretion of SDF-1 was most affected by BMP-5, VEGF by BMP-4, and b-FGF by BMP-2. The knockdown of BMP-2 in BMSCs had no effect on any of the genes measured whereas BMP-6 knockdown in hBMSCs caused a significant increase in VEGF gene expression. BMP-2 and BMP-6 knockdown in human osteoblasts caused significant increases in VEGF gene expression and trends toward decreases in osteocalcin expression. These findings support efforts to study other BMPs as potential bone graft supplements, and to consider combined BMP delivery for promotion of multiple aspects of fracture healing
The tracks of my years: Personal significance contributes to the reminiscence bump
āTwo studies investigated the role of the self in the reminiscence bump (heightened retrieval for events from young adulthood). Participants over the age of 40 years were presented with top-grossing films and songs, and were asked to select the five that were most personally significant. Study 1 produced reminiscence bumps for personally significant songs, when measured by both participantsā age at release (AaR) and age when songs were reported as most important (AaI). This effect was not shown for films. In Study 2, participants again selected their personally significant songs but also rated all songs for whether they were known, remembered (e.g., associated with an episodic memory), or not known. Personally significant songs were significantly more likely to be associated with episodic memories, compared to personally non-significant songs. Again, only personally significant songs formed a reminiscence bump. Findings underline a critical role of personal significance in the reminiscence bump, which we argue is consistent with the formation of identity in this lifetime period
Effect of Amoxicillin in combination with Imipenem-Relebactam against Mycobacterium abscessus
Infections caused by Mycobacterium abscessus are increasing in prevalence in cystic fibrosis patients. This opportunistic pathogenā²s intrinsic resistance to most antibiotics has perpetuated an urgent demand for new, more effective therapeutic interventions. Here we report a prospective advance in the treatment of M. abscessus infection; increasing the susceptibility of the organism to amoxicillin, by repurposing the Ī²-lactamase inhibitor, relebactam, in combination with the front line M. abscessus drug imipenem. We establish by multiple in vitro methods that this combination works synergistically to inhibit M. abscessus. We also show the direct competitive inhibition of the M. abscessus Ī²-lactamase, BlaMab, using a novel assay, which is validated kinetically using the nitrocefin reporter assay and in silico binding studies. Furthermore, we reverse the susceptibility by overexpressing BlaMab in M. abscessus, demonstrating relebactam-BlaMab target engagement. Finally, we highlight the in vitro efficacy of this combination against a panel of M. abscessus clinical isolates, revealing the therapeutic potential of the amoxicillin-imipenem-relebactam combination
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Autobiographical memory, autonoetic consciousness, and identity in Asperger syndrome
Previous results from research on individuals with Asperger syndrome (AS) suggest a diminished ability for recalling episodic autobiographical memory (AM). The primary aim of this study was to explore autobiographical memory in individuals with Asperger syndrome and specifically to investigate whether memories in those with AS are characterized by fewer episodic 'remembered' events (due to a deficit in autonoetic consciousness). A further aim was to examine whether such changes in AM might also be related to changes in identity, due to the close relationship between memory and the self and to the established differences in self-referential processes in AS. Eleven adults with AS and fifteen matched comparison participants were asked to recall autobiographical memories from three lifetime periods and for each memory to give either a remember response (autonoetic consciousness) or a know response (noetic consciousness). The pattern of results shows that AS participants recalled fewer memories and that these memories were more often rated as known, compared to the comparison group. AS participants also showed differences in reported identity, generating fewer social identity statements and more abstract, trait-linked identities. The data support the view that differences in both memory and reported personal identities in AS are characterized by a lack of specificity
Self-images in the present and future: Role of affect and the bipolar phenotype
Background
Bipolar Spectrum Disorder (BPSD) is associated with changes in self-related processing and affect, yet the relationship between self-image and affect in the BPSD phenotype is unclear.
Methods
47 young adults were assessed for hypomanic experiences (BPSD phenotype) using the Mood Disorders Questionnaire. Current and future self-images (e.g. I amā¦ I will beā¦) were generated and rated for emotional valence, stability, and (for future self-images only) certainty. The relationship between self-image ratings and measures of affect (depression, anxiety and mania) were analysed in relation to the BPSD phenotype.
Results
The presence of the BPSD phenotype significantly moderated the relationship between (1) affect and stability ratings for negative self-images, and (2) affect and certainty ratings for positive future self-images. Higher positivity ratings for current self-images were associated with lower depression and anxiety scores.
Limitations
This was a non-clinical group of young adults sampled for hypomanic experiences, which limits the extension of the work to clinical levels of psychopathology. This study cannot address the causal relationships between affect, self-images, and BPSD. Future work should use clinical samples and experimental mood manipulation designs.
Conclusions
BPSD phenotype can shape the relationship between affect and current and future self-images. This finding will guide future clinical research to elucidate BPSD vulnerability mechanisms and, consequently, the development of early interventions
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