Neurocognitive and Neuroimaging Predictors of Clinical Outcome in Bipolar Disorder

Historically, bipolar disorder has been conceptualized as a disease involving episodic rather than chronic dysfunction. However, increasing evidence indicates that bipolar disorder is associated with substantial inter-episode psychosocial and vocational impairment. Here we review the contributions of neurocognitive deficits and structural and functional neuroanatomic alterations to the observed functional impairments. In particular, compelling evidence now suggests that neurocognitive impairments, particularly in the areas of attention, processing speed, and memory, are associated with functional outcome. Although investigation of the neural correlates of functional disability in bipolar disorder is only in its nascent stages, preliminary evidence suggests that white matter abnormalities may be predictive of poor outcome. A better understanding of the relationship between neurocognitive and neuroimaging assays and functional outcome has the potential to improve current treatment options and provide targets for new treatment strategies in bipolar disorder

Alterations in the plasma proteome persist ten months after recovery from mild to moderate SARS-CoV-2 infection

BackgroundLimited data are available describing the effects of SARS-CoV-2 breakthrough infections on the plasma proteome.MethodsPCR-positive SARS-CoV-2 patients, enrolled in a natural history study, underwent analysis of the plasma proteome. A prospective cohort of 66 unvaccinated and 24 vaccinated persons with different degrees of infection severity were evaluated acutely (within 40 days of symptom onset), and at three and ten months. Comparisons based on vaccination status alone and unsupervised hierarchical clustering were performed. A second cohort of vaccinated Omicron patients were evaluated acutely and at ten months.ResultsAcutely, unvaccinated patients manifested overexpression of proteins involved in immune and inflammatory responses, while vaccinated patients exhibited adaptive immune responses without significant inflammation. At three and ten months, only unvaccinated patients had diminished but sustained inflammatory (C3b, CCL15, IL17RE) and immune responses (DEFA5,TREM1). Both groups had underexpression of pathways essential for cellular function, signaling, and angiogenesis (AKT1, MAPK14, HSPB1) across phases. Unsupervised clustering, based on protein expression, identified four groups of patients with variable vaccination rates demonstrating that additional clinical factors influence the plasma proteome. The proteome of vaccinated Omicron patients did not differ from vaccinated pre-Omicron patients.ConclusionsVaccination attenuates the inflammatory response to SARS-CoV-2 infection across phases. However, at ten months after symptom onset, changes in the plasma proteome persist in both vaccinated and unvaccinated individuals, which may be relevant to post-acute sequelae of SARS-CoV-2 and other viral infections associated with post-acute infection syndromes

Novel fractionated ultrashort thermal exposures with MRI-guided focused ultrasound for treating tumors with thermosensitive drugs

Focused ultrasound mild heating in short durations has an antitumor effect when combined with temperature-sensitive chemotherapy.</jats:p

Mental health and well-being of healthcare workers during the COVID-19 pandemic in the UK: contrasting guidelines with experiences in practice

Background Substantial evidence has highlighted the importance of considering the mental health of healthcare workers during the COVID-19 pandemic, and several organisations have issued guidelines with recommendations. However, the definition of well-being and the evidence base behind such guidelines remain unclear. Aims The aims of the study are to assess the applicability of well-being guidelines in practice, identify unaddressed healthcare workers’ needs and provide recommendations for supporting front-line staff during the current and future pandemics. Method This paper discusses the findings of a qualitative study based on interviews with front-line healthcare workers in the UK (n = 33), and examines them in relation to a rapid review of well-being guidelines developed in response to the COVID-19 pandemic (n = 14). Results The guidelines placed greater emphasis on individual mental health and psychological support, whereas healthcare workers placed greater emphasis on structural conditions at work, responsibilities outside the hospital and the invaluable support of the community. The well-being support interventions proposed in the guidelines did not always respond to the lived experiences of staff, as some reported not being able to participate in these interventions because of understaffing, exhaustion or clashing schedules. Conclusions Healthcare workers expressed well-being needs that aligned with socio-ecological conceptualisations of well-being related to quality of life. This approach to well-being has been highlighted in literature on support of healthcare workers in previous health emergencies, but it has not been monitored during this pandemic. Well-being guidelines should explore the needs of healthcare workers, and contextual characteristics affecting the implementation of recommendations. </jats:sec

Healthcare Workers’ Mental Health and Wellbeing During the COVID-19 Pandemic in the UK: Contrasting Guidelines with Experiences in Practice

AbstractBackgroundSubstantial evidence has highlighted the importance of considering healthcare workers’ (HCW) mental health during the COVID-19 pandemic, and several organisations have issued guidelines with recommendations. However, the definition of wellbeing and the evidence-base behind such guidelines remains unclear.ObjectivesAssessing the applicability of wellbeing guidelines in practice; identifying unaddressed HCWs’ needs; and providing recommendations for supporting frontline staff during the current and future pandemics.Methods and DesignThis paper discusses the findings of a qualitative study based on interviews with frontline healthcare staff in the UK and examines them in relation to a rapid review of wellbeing guidelines developed in response to the COVID-19 pandemic.Results14 guidelines were included in the rapid review and 33 interviews with HCWs were conducted in the qualitative study. As a whole, the guidelines placed greater emphasis on wellbeing at an individual level, while HCWs placed greater emphasis on structural conditions at work, such as understaffing and the invaluable support of the community. This in turn had implications for the focus of wellbeing intervention strategies; staff reported an increased availability of formal mental health support, however, understaffing or clashing schedules prevented them from participating in these activities.ConclusionHCWs expressed wellbeing needs which align with social-ecological conceptualisations of wellbeing related to quality of life. This approach to wellbeing has been highlighted in literature about HCWs support in previous health emergencies, yet it has not been monitored during this pandemic. Wellbeing guidelines should explore staff’s needs and contextual characteristics affecting the implementation of recommendations.</jats:sec

Relationship of cerebrospinal fluid glucose metabolites to MRI deep white matter hyperintensities and treatment resistance in bipolar disorder patients

OBJECTIVES: Both diabetes mellitus and magnetic resonance image (MRI) deep white matter hyperintensities (WMHs) are more common in bipolar disorder (BD) patients than in matched controls. Deep—as opposed to periventricular—WMHs and diabetes are associated with treatment resistance and poorer outcome. This study investigated whether brain glucose metabolism by the polyol pathway—a pathway linked to nervous tissue disease in diabetes—is related to deep WMH volume and treatment resistance in BD patients. METHODS: Volumes of fluid-attenuated inversion recovery WMHs were quantified and correlated with cerebrospinal fluid (CSF) concentrations of glucose metabolites in 20 nondiabetic patients with BD and nondiabetic comparison subjects with schizophrenia (n = 15) or transient neurologic symptoms (neurologic controls, n = 15). RESULTS: BD patients, but not schizophrenic patients, had significantly greater volumes of deep but not periventricular WMHs compared to neurologic controls. BD subjects also had significantly greater CSF concentrations of sorbitol and fructose (the polyol pathway metabolites of glucose) compared to controls. Significant positive correlations between CSF metabolites and WMH volumes were found only in the BD group and were between deep WMH volumes and CSF sorbitol (ρ = 0.487, p = 0.029) and fructose (ρ = 0.474, p = 0.035). An index of treatment resistance correlated significantly with deep WMH volume (ρ = 0.578, p = 0.008), sorbitol (ρ = 0.542, p = 0.013), and fructose (ρ = 0.692, p = 0.001) in BD subjects but not in other subjects. CONCLUSIONS: This is the first reported evidence of relationships between abnormal brain glucose metabolism and both deep WMHs and treatment resistance in a group of BD patients. Further studies are necessary to determine the significance of these findings to BD pathophysiology