Epidemiological research has shown that hallucinations and delusions, the classic symptoms of psychosis, are far more prevalent in the population than actual psychotic disorder. These symptoms are ...especially prevalent in childhood and adolescence. Longitudinal research has demonstrated that psychotic symptoms in adolescence increase the risk of psychotic disorder in adulthood. There has been a lack of research, however, on the immediate clinicopathological significance of psychotic symptoms in adolescence.
To investigate the relationship between psychotic symptoms and non-psychotic psychopathology in community samples of adolescents in terms of prevalence, co-occurring disorders, comorbid (multiple) psychopathology and variation across early v. middle adolescence.
Data from four population studies were used: two early adolescence studies (ages 11-13 years) and two mid-adolescence studies (ages 13-16 years). Studies 1 and 2 involved school-based surveys of 2243 children aged 11-16 years for psychotic symptoms and for emotional and behavioural symptoms of psychopathology. Studies 3 and 4 involved in-depth diagnostic interview assessments of psychotic symptoms and lifetime psychiatric disorders in community samples of 423 children aged 11-15 years.
Younger adolescents had a higher prevalence (21-23%) of psychotic symptoms than older adolescents (7%). In both age groups the majority of adolescents who reported psychotic symptoms had at least one diagnosable non-psychotic psychiatric disorder, although associations with psychopathology increased with age: nearly 80% of the mid-adolescence sample who reported psychotic symptoms had at least one diagnosis, compared with 57% of the early adolescence sample. Adolescents who reported psychotic symptoms were at particularly high risk of having multiple co-occurring diagnoses.
Psychotic symptoms are important risk markers for a wide range of non-psychotic psychopathological disorders, in particular for severe psychopathology characterised by multiple co-occurring diagnoses. These symptoms should be carefully assessed in all patients.
This paper proposes two heuristic algorithms for finding fixed-length circuits and cycles in undirected edge-weighted graphs. It focusses particularly on a largely unresearched practical application ...where we are seeking attractive round trips for pedestrians and joggers in urban street networks. Our first method is based on identifying suitable pairs of paths that are combined to form a solution; our second is based on local search techniques. Both algorithms display high levels of accuracy, producing solutions within just a few meters of the target. Run times for the local search algorithm are also short, with solutions in large cities often being found in less than one second.
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CEKLJ, EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
The retinoic acid receptor (RAR) α system plays a key role in the adult brain, participating in the homeostatic control of synaptic plasticity, essential for memory function. Here we show that RARα ...signalling is down‐regulated by amyloid beta (Aβ), which inhibits the synthesis of the endogenous ligand, retinoic acid (RA). This results in the counteraction of a variety of RARα‐activated pathways that are key in the aetiopathology of Alzheimer's disease (AD) but which can be reversed by an RARα agonist. RARα signalling improves cognition in the Tg2576 mice, it has an anti‐inflammatory effect and promotes Aβ clearance by increasing insulin degrading enzyme and neprilysin activity in both microglia and neurons. In addition, RARα signalling prevents tau phosphorylation. Therefore, stimulation of the RARα signalling pathway using a synthetic agonist, by both clearing Aβ and counteracting some of its toxic effects, offers therapeutic potential for the treatment of AD.
The Retinoic Acid Receptor (RAR) α system plays a key role in the adult brain, participating in the homeostatic control of synaptic plasticity, essential for memory function. Here we show that RARα signalling is down regulated by amyloid beta (Aβ), which inhibits the synthesis of the endogenous ligand, retinoic acid (RA).
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BFBNIB, DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, SIK, UILJ, UKNU, UL, UM, UPUK
Spontaneous pneumothorax is a common pathology. International guidelines suggest pleurodesis for non-resolving air leak or recurrence prevention at second occurrence. This study comprehensively ...reviews the existing literature regarding chemical pleurodesis efficacy.
We systematically reviewed the literature to identify relevant randomised controlled trials (RCTs), case-control studies and case series. We described the findings of these studies and tabulated relative recurrence rates or ORs (in studies with control groups). Meta-analysis was not performed due to substantial clinical heterogeneity.
Of 560 abstracts identified by our search strategy, 50 were included in our systematic review following screening. Recurrence rates in patients with chest tube drainage only were between 26.1% and 50.1%. Thoracoscopic talc poudrage (four studies (n=249)) provided recurrence rates of between 2.5% and 10.2% with the only RCT suggesting an OR of 0.10 compared with drainage alone. In comparison, talc administration during video-assisted thoracic surgery (VATS) from eight studies (n=2324) recurrence was between 0.0% and 3.2%, but the RCT did not demonstrate a significant difference compared with bleb/bullectomy alone. Minocycline appears similarly effective post-VATS (recurrence rates 0.0-2.9%). Prolonged air leak and recurrence prevention using tetracycline via chest drain (n=726) is likely to provide recurrence rates between 13.0% and 33.3% and autologous blood patch pleurodesis (n=270) between 15.6% and 18.2%.
Chemical pleurodesis postsurgical treatment or via thoracoscopy appears to be most effective. Evidence for definitive success rates of each agent is limited by the small number of randomised trials or other comparative studies.
A range of factors including mental disorders, adverse events and history of self-harm are associated with suicide risk. Further examination is needed of the characteristics of suicides which occur ...without established risk factors, using national surveillance systems.
Data on all suicides in Ireland from 2015 to 2017 were drawn from the Irish Probable Suicide Deaths Study (IPSDS). Variables examined included socio-demographics, psychiatric history and precipitant stressors. Suicide data were linked with data on prior self-harm from the National Self-Harm Registry Ireland (NSHRI). Latent Class Analysis (LCA) was used to identify sub-groups of suicide cases.
Of the 1809 individuals who died by suicide, 401 (22.2 %) had a history of hospital-treated self-harm. Four distinct profiles of suicides were identified. One group was marked by high levels of prior self-harm and mental health conditions. Two of the groups included few individuals with a history of self-harm but had notably high levels of mental health conditions. These two groups had relatively high levels of reported chronic pain or illness but differed in terms of socio-demographics. The final group, predominantly male, had markedly low levels of mental health conditions or self-harm but high levels of personal stressors and substance use.
The use of coronial data may be limited by bias in the collecting of information from the deceased's family members.
A sub-group of suicide cases exists without any psychiatric or self-harm history but with salient occupational or health-related proximal stressors. Suicide prevention interventions should include occupational settings and should promote mental health literacy.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Failure of axonal regeneration in the central nervous system (CNS) is mainly attributed to a lack of intrinsic neuronal growth programs and an inhibitory environment from a glial scar. Phosphatase ...and tensin homolog (PTEN) is a major negative regulator of neuronal regeneration and, as such, inhibiting its activity has been considered a therapeutic target for spinal cord (SC) injuries (SCIs). Using a novel model of rat cervical avulsion, we show that treatment with a retinoic acid receptor β (RARβ) agonist results in locomotor and sensory recovery. Axonal regeneration from the severed roots into the SC could be seen by biotinylated dextran amine labeling. Light micrographs of the dorsal root entry zone show the peripheral nervous system (PNS)-CNS transition of regrown axons. RARβ agonist treatment also resulted in the absence of scar formation. Mechanism studies revealed that, in RARβ-agonist-treated neurons, PTEN activity is decreased by cytoplasmic phosphorylation and increased secretion in exosomes. These are taken up by astrocytes, resulting in hampered proliferation and causing them to arrange in a normal-appearing scaffold around the regenerating axons. Attribution of the glial modulation to neuronal PTEN in exosomes was demonstrated by the use of an exosome inhibitor in vivo and PTEN siRNA in vitro assays. The dual effect of RARβ signaling, both neuronal and neuronal-glial, results in axonal regeneration into the SC after dorsal root neurotmesis. Targeting this pathway may open new avenues for the treatment of SCIs.
Spinal cord injuries (SCIs) often result in permanent damage in the adult due to the very limited capacity of axonal regeneration. Intrinsic neuronal programs and the formation of a glial scar are the main obstacles. Here, we identify a single target, neuronal retinoic acid receptor β (RARβ), which modulates these two aspects of the postinjury physiological response. Activation of RARβ in the neuron inactivates phosphatase and tensin homolog and induces its transfer into the astrocytes in small vesicles, where it prevents scar formation. This may open new therapeutic avenues for SCIs.
Summary
MicF is a textbook example of a small regulatory RNA (sRNA) that acts on a trans‐encoded target mRNA through imperfect base pairing. Discovery of MicF as a post‐transcriptional repressor of ...the major Escherichia coli porin OmpF established the paradigm for a meanwhile common mechanism of translational inhibition, through antisense sequestration of a ribosome binding site. However, whether MicF regulates additional genes has remained unknown for almost three decades. Here, we have harnessed the new superfolder variant of GFP for reporter–gene fusions to validate newly predicted targets of MicF in Salmonella. We show that the conserved 5′ end of MicF acts by seed pairing to repress the mRNAs of global transcriptional regulator Lrp, and periplasmic protein YahO, while a second targeting region is also required to regulate the mRNA of the lipid A‐modifying enzyme LpxR. Interestingly, MicF targets lpxR at both the ribosome binding site and deep within the coding sequence. MicF binding in the coding sequence of lpxR decreases mRNA stability through exacerbating the use of a native RNase E site proximal to the short MicF‐lpxR duplex. Altogether, this study assigns the classic MicF sRNA to the growing class of Hfq‐associated regulators that use diverse mechanisms to impact multiple loci.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
The purpose of this 3-year longitudinal study was to examine pre-service teachers' personality trajectories as measured by the IPIP Big-Five factor markers during teacher preparation. The ...relationship between students' personality traits, social desirability, and prior academic attainment was also examined.
This 3-year longitudinal study invited participants from the first year of a 4-year undergraduate (UG) pre-service teacher education program, the class of 2017. The sample consisted of 305 students.
The results suggest that extraversion, agreeableness, conscientiousness, emotional stability, and openness to experience were best represented by a non-significant longitudinal change in means. Results also suggest that social desirability predicts agreeableness and emotional stability with small to moderate effect sizes.
The study concludes that no value is added to pre-service teachers' personality traits during 3 years of tertiary education. Furthermore, the data presented does not support the view that academic attainment is a good predictor of personality traits. Implications for educational research, theory, and practice are considered.
Xenotransplantation of genetically modified pig organs offers great potential to address the shortage of human organs for allotransplantation. Rejection in Gal knockout (GTKO) pigs due to elicited ...non‐Gal antibody response required further genetic modifications of donor pigs and better control of the B‐cell response to xenoantigens. We report significant prolongation of heterotopic alpha Galactosyl transferase “knock‐out” and human CD46 transgenic (GTKO.hCD46Tg) pig cardiac xenografts survival in specific pathogen free baboons. Peritransplant B‐cell depletion using 4 weekly doses of anti‐CD20 antibody in the context of an established ATG, anti‐CD154 and MMF‐based immunosuppressive regimen prolonged GTKO.hCD46Tg graft survival for up to 236 days (n = 9, median survival 71 days and mean survival 94 days). B‐cell depletion persisted for over 2 months, and elicited anti‐non‐Gal antibody production remained suppressed for the duration of graft follow‐up. This result identifies a critical role for B cells in the mechanisms of elicited anti‐non‐Gal antibody and delayed xenograft rejection. Model‐related morbidity due to variety of causes was seen in these experiments, suggesting that further therapeutic interventions, including candidate genetic modifications of donor pigs, may be necessary to reduce late morbidity in this model to a clinically manageable level.
The authors describe the use of recipient B cell depletion and genetically modified donor pigs in a series of heterotopic pig to baboon cardiac xenografts with survival up to 8 months.
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BFBNIB, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Mounting evidence indicates that elevated intramyocellular triacylglycerol concentrations are associated with diminished insulin sensitivity in skeletal muscle. This lipid accumulation is most likely ...due to enhanced fatty acid uptake into the muscle coupled with diminished mitochondrial lipid oxidation. The excess fatty acids are esterified and either stored or metabolized to various molecules that may participate or interfere with normal cellular signaling, particularly insulin-mediated signal transduction, thus altering cellular and, subsequently, whole-body glucose metabolism. Impaired insulin responsiveness, if not managed, can further progress to type 2 diabetes mellitus, an all too common condition. For most of the human population this is avoidable, given that causes of intramyocellular lipid deposition are predominantly lifestyle-mediated. Chronic overconsumption of calories coupled with deleterious intakes of saturated or trans-unsaturated fatty acids inconsistent with the recommendations outlined in the Dietary Guidelines for Americans have been shown to increase the risk of insulin resistance. Furthermore, lack of exercise, which can have a profound effect on skeletal muscle lipid turnover, is implicated in this lipid-induced insulin resistance. This review summarizes the current understanding of the effects of elevated intramyocellular lipids on insulin signaling and how these effects may be altered by varying dietary fat composition and exercise.
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CMK, GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
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