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Missed opportunities in early psychosis care: Retrospective chart review of cardiovascular disease monitoring, disengagement and weight changes in a Ghanaian psychiatric hospital
Background Patients with psychosis face an elevated risk of cardiovascular mortality and are more likely to disengage from care. While antipsychotics are essential for treatment, they further increase this risk. Despite this, Ghana lacks a national policy for monitoring cardiovascular risk factors in individuals on antipsychotics. Aims To evaluate disengagement in care and weight changes among newly diagnosed psychotic patients at Accra Psychiatric Hospital, and to inform clinical practice. Method A retrospective review of medical records was conducted for patients newly diagnosed with non-affective psychotic disorders between June 2022 and May 2023. Patients were reviewed for 6 months, with assessments at baseline, 3 months and 6 months. Outcomes included antipsychotic prescription patterns, dropout rates, cardiovascular disease monitoring and weight changes. Descriptive statistics, multinomial logistic regression and linear mixed-effects models were used for analysis. Results The number of patients disengaged from care within the first month was 53.1%, and within 6 months 75.5%; 62.8% received olanzapine at baseline. Weight gain was exponential, with 40% experiencing clinically significant weight gain at 3 months, increasing to 58% at 6 months. Less than 50% of patients had their blood sugar and lipid profiles checked before starting antipsychotics. Higher baseline weight was associated with increased weight over time (β = 0.96, t = 80, P < 0.001, 95% CI 0.93, 0.98). Conclusions High disengagement rates, low cardiovascular disease monitoring and exponential weight gain were observed. Targeted interventions, robust monitoring protocols and further research are needed to improve patient outcomes.
Nutraceuticals: using food to enhance brain health by modulating postnatal neurogenesis in animal models and patient populations
Adult hippocampal neurogenesis, while occurring throughout life, decreases with age and in some neurodegenerative diseases. As decreased hippocampal neurogenesis is correlated with cognitive decline, efforts have been made to increase levels of neurogenesis, either through natural compounds, environmental interventions or novel pharmacological compounds. Nutraceuticals are food products with medical benefits such as antioxidation, anti-inflammation or neuroprotection. There has been increasing interest in these “functional foods” and their active compounds in recent years, providing natural alternatives to de novo pharmaceuticals. This review highlights key nutraceuticals that promote neurogenesis and/or improve cognitive outcomes. By outlining the effects of these compounds in the animal models employed and in clinical populations, we also suggest further investigations. We examine common targets and pathways through which these nutraceuticals are believed to exert pro-neurogenic effects. Most nutraceutical preparations contain multiple components, any of which may exert effects on neurogenesis. Identifying key active compounds in nutraceuticals may enable researchers to better understand their effects and standardize doses across studies. The less stringent regulatory requirements for nutraceuticals can be a double-edged sword. While allowing easier access to the beneficial effects, higher doses of these compounds may have detrimental effects. Hence, research in this field should not only aim to identify the benefits of these compounds but also to identify efficacious and safe dosages for them. Our aims are to provide understanding of nutraceuticals, provide evidence for their benefits on neurogenesis and neurogenesis-related behaviors and finally to summarize potential mechanisms and help guide future work.
Neurofeedback modulation of insula activity via MEG-based brain-machine interface: a double-blind randomized controlled crossover trial.
Insula activity has often been linked to pain perception, making it a potential target for therapeutic neuromodulation strategies such as neurofeedback. However, it is not known whether insula activity is under cognitive control and, if so, whether this activity is consequently causally related to pain. Here, we conducted a double-blind randomized controlled crossover trial to test the modulation of insula activity and pain thresholds using neurofeedback training. Nineteen healthy subjects underwent neurofeedback training for upmodulation and downmodulation of right insula activity using our magnetoencephalography (MEG)-based brain-machine interface. We observed significant differences in insula activity between the upmodulation and downmodulation training sessions. Furthermore, resting-state insula activity significantly decreased following downmodulation training compared to following upmodulation training. Compared with upmodulation training, downmodulation training was also associated with increased pain thresholds, albeit with no significant interaction effect. These findings show that humans can cognitively modulate insula activity as a potential route to develop therapeutic MEG neurofeedback systems for clinical testing. However, the present findings do not provide direct evidence of a causal link between modulation of insula activity and changes in pain thresholds.
Metabolic engineering of stomatal precursor cells enhances photosynthetic water-use efficiency and vegetative growth under water-deficit conditions in Arabidopsis thaliana.
Stomata are epidermal pores that control the exchange of gaseous CO2 and H2O between plants and their environment. Modulating stomatal density can alter this exchange and thus presents a viable target for engineering improved crop productivity and climate resilience. Here, we show that stomatal density in Arabidopsis thaliana can be decreased by the expression of a water-forming NAD(P)H oxidase targeted to stomatal precursor cells. We demonstrate that this reduction in stomatal density occurs irrespective of whether the expressed enzyme is localized to the cytosol, chloroplast stroma or chloroplast intermembrane space of these cells. We also reveal that this decrease in stomatal density occurs in the absence of any measurable impact on the efficiency and thermal sensitivity of photosynthesis, or on stomatal dynamics. Consequently, overexpression plants exhibit a higher intrinsic water-use efficiency due to an increase in CO2 fixed per unit water transpired. Finally, we demonstrate that this enhanced water-use efficiency translates to an improvement in vegetative growth and biomass accumulation under water-deficit conditions. Together, these results thus provide a novel approach for enhancing plant productivity through metabolic engineering of stomatal density.
Bacterial pathogenomics.
Genomes from all of the crucial bacterial pathogens of humans, plants and animals have now been sequenced, as have genomes from many of the important commensal, symbiotic and environmental microorganisms. Analysis of these sequences has revealed the forces that shape pathogen evolution and has brought to light unexpected aspects of pathogen biology. The finding that horizontal gene transfer and genome decay have key roles in the evolution of bacterial pathogens was particularly surprising. It has also become evident that even the definitions for 'pathogen' and 'virulence factor' need to be re-evaluated.
Mutations in γ-aminobutyric acid (GABA) transaminase genes in plants or Pseudomonas syringae reduce bacterial virulence.
Pseudomonas syringae pv. tomato DC3000 is a bacterial pathogen of Arabidopsis and tomato that grows in the apoplast. The non-protein amino acid γ-amino butyric acid (GABA) is produced by Arabidopsis and tomato and is the most abundant amino acid in the apoplastic fluid of tomato. The DC3000 genome harbors three genes annotated as gabT GABA transaminases. A DC3000 mutant lacking all three gabT genes was constructed and found to be unable to utilize GABA as a sole carbon and nitrogen source. In complete minimal media supplemented with GABA, the mutant grew less well than wild-type DC3000 and showed strongly reduced expression of hrpL and avrPto, which encode an alternative sigma factor and effector, respectively, associated with the type III secretion system. The growth of the gabT triple mutant was weakly reduced in Arabidopsis ecotype Landberg erecta (Ler) and strongly reduced in the Ler pop2-1 GABA transaminase-deficient mutant that accumulates higher levels of GABA. Much of the ability to grow on GABA-amended minimal media or in Arabidopsis pop2-1 leaves could be restored to the gabT triple mutant by expression in trans of just gabT2. The ability of DC3000 to elicit the hypersensitive response (HR) in tobacco leaves is dependent upon deployment of the type III secretion system, and the gabT triple mutant was less able than wild-type DC3000 to elicit this HR when bacteria were infiltrated along with GABA at levels of 1 mm or more. GABA may have multiple effects on P. syringae-plant interactions, with elevated levels increasing disease resistance.
Effects of 28-day simvastatin administration on emotional processing, reward learning, working memory, and salivary cortisol in healthy participants at-risk for depression: OxSTEP, an online experimental medicine trial.
BACKGROUND: Statins are among the most prescribed medications worldwide. Both beneficial (e.g. antidepressant and pro-cognitive) and adverse (e.g. depressogenic and cognitive-impairing) mental health outcomes have been described in clinical studies. The underlying neuropsychological mechanisms, whether positive or negative, are, however, not established. Clarifying such activities has implications for the safe prescribing and repurposing potential of these drugs, especially in people with depression. METHODS: In this double-blind, randomized, placebo-controlled experimental medicine study, we investigated the effects of simvastatin on emotional processing, reward learning, working memory, and waking salivary cortisol (WSC) in 101 people at-risk for depression due to reported high loneliness scores (mean 7.3 ± 1.2 on the UCLA scale). This trial was largely conducted during periods of social distancing due to the COVID-19 pandemic (July 2021-February 2023), and we employed a fully remote design within a UK-wide sample. RESULTS: High retention rates, minimal outlier data, and typical main effects of task condition (e.g. emotion) were seen in all cognitive tasks, indicating this approach was comparable to in-person testing. After 28 days, we found no statistically significant differences (F's 0.20) for any of the measures of emotional processing, reward learning, working memory, and WSC. CONCLUSIONS: Study results do not substantiate concerns regarding adverse neuropsychiatric events due to statins and support the safety of their prescribing in at-risk populations. Although other unmeasured cognitive processes may be involved, our null findings are also in line with more recent clinical evidence suggesting statins do not show antidepressant or pro-cognitive efficacy.
Cognitive Therapy for PTSD in Children and Adolescents
Children and adolescents exposed to traumatic events are at high risk of developing post-traumatic stress disorder (PTSD). With the rare exception of young children, their PTSD presentations at the symptom level are similar to those of trauma-exposed adults, as are their patterns of psychiatric comorbidity, particularly for adolescents. Untreated, at least a significant proportion will carry on with symptoms at or above the diagnostic threshold or at sub-threshold levels that are still clinically impairing. The presence of untreated or poorly treated PTSD symptoms leaves the young person at significantly increased risk of developing other psychiatric disorders, a worsening of any pre-existing conditions, and with greater long-term impairments in education, family, and peer functioning. Fortunately, evidence-based treatments exist with the first-line recommendation being trauma-focused cognitive behavioural therapies, with a growing body of evidence for the efficacy of eye movement desensitization and reprocessing therapy (EMDR). This chapter provides an update on the state of the literature with respect to the evidence base for trauma-focused cognitive behavioral therapy (CBT), and in particular, for an explicitly cognitive approach, originally developed for use with adults and successfully adapted for use with children and adolescents across the age range. The chapter describes the theoretical underpinning for this approach, guidance on reliving (a form of exposure to update the trauma memory) and the modification of trauma-related beliefs (two primary targets in treatment), parental involvement in treatment, dealing with comorbidity, and a case example.
Alzheimer's disease patient-derived high-molecular-weight tau impairs bursting in hippocampal neurons.
Tau accumulation is closely related to cognitive symptoms in Alzheimer's disease (AD). However, the cellular drivers of tau-dependent decline of memory-based cognition remain elusive. Here, we employed in vivo Neuropixels and patch-clamp recordings in mouse models and demonstrate that tau, independent of β-amyloid, selectively debilitates complex-spike burst firing of CA1 hippocampal neurons, a fundamental cellular mechanism underpinning learning and memory. Impaired bursting was associated with altered hippocampal network activities that are coupled to burst firing patterns (i.e., theta rhythms and high-frequency ripples) and was concurrent with reduced neuronal expression of CaV2.3 calcium channels, which are essential for burst firing in vivo. We subsequently identify soluble high molecular weight (HMW) tau, isolated from human AD brain, as the tau species responsible for suppression of burst firing. These data provide a cellular mechanism for tau-dependent cognitive decline in AD and implicate a rare species of intracellular HMW tau as a therapeutic target.