Verbal memory impairments in mood disorders and psychotic disorders: A systematic review of comparative studies.

BACKGROUND: Mood and psychotic disorders are both associated with verbal memory impairments. Verbal memory represents an important treatment target for both disorders. However, whether the neurocognitive and neurophysiological profiles of verbal memory impairments differ between specific disorders within these two diagnostic categories and healthy controls remains unclear. The current systematic review synthesized findings from comparative studies which used behavioural and neuroimaging tasks to investigate verbal memory impairments between: (1) mood disorder, psychotic disorder, and healthy control groups; and (2) mood disorder without psychotic features, mood disorder with psychotic features, and healthy control groups. METHODS: The search strategy combined terms related to three main concepts: 'mood disorders', 'psychotic disorders', and 'verbal memory'. Searches were executed in Embase, MEDLINE, PsycInfo, and PubMed databases. A total of 38 articles met the full eligibility criteria and were included in the final narrative synthesis. Findings were stratified by memory domain (overall composite score, verbal working memory, immediate recall, delayed recall, and recognition memory) and by illness phase (acute and non-acute). RESULTS: Mood and psychotic disorders displayed consistent verbal memory impairments compared to healthy controls during the acute and non-acute phases. Few significant differences were identified in the literature between mood and psychotic disorders, and between mood disorders with and without psychotic features. Individuals with schizophrenia were found to have decreased immediate and delayed verbal recall performance compared to bipolar disorder groups during the acute phase. Major depressive disorder groups with psychotic features were also found to have decreased delayed verbal recall performance compared to those without psychosis during the acute phase. No consistent differences were identified between mood and psychotic disorders during the non-acute phase. Finally, preliminary evidence suggests there may be functional abnormalities in important frontal and temporal brain regions related to verbal memory difficulties in both mood and psychotic disorders. DISCUSSION: The current findings have potential implications for the diagnosis and treatment of cognitive impairments in mood and psychotic disorders. Verbal recall memory may serve as a sensitive tool in the risk stratification of cognitive impairments for certain mood and psychotic disorders. Moreover, since no widespread differences between clinical groups were identified, the evidence supports providing targeted interventions for verbal memory, such as pharmacological and non-pharmacological interventions, through a trans-diagnostic approach in mood and psychotic disorders.

Adopting AI: how familiarity breeds both trust and contempt.

Despite pronouncements about the inevitable diffusion of artificial intelligence and autonomous technologies, in practice, it is human behavior, not technology in a vacuum, that dictates how technology seeps into-and changes-societies. To better understand how human preferences shape technological adoption and the spread of AI-enabled autonomous technologies, we look at representative adult samples of US public opinion in 2018 and 2020 on the use of four types of autonomous technologies: vehicles, surgery, weapons, and cyber defense. By focusing on these four diverse uses of AI-enabled autonomy that span transportation, medicine, and national security, we exploit the inherent variation between these AI-enabled autonomous use cases. We find that those with familiarity and expertise with AI and similar technologies were more likely to support all of the autonomous applications we tested (except weapons) than those with a limited understanding of the technology. Individuals that had already delegated the act of driving using ride-share apps were also more positive about autonomous vehicles. However, familiarity cut both ways; individuals are also less likely to support AI-enabled technologies when applied directly to their life, especially if technology automates tasks they are already familiar with operating. Finally, we find that familiarity plays little role in support for AI-enabled military applications, for which opposition has slightly increased over time. Supplementary Information: The online version contains supplementary material available at 10.1007/s00146-023-01666-5.

COVID-19 and public support for autonomous technologies-Did the pandemic catalyze a world of robots?

By introducing a novel risk to human interaction, COVID-19 may have galvanized interest in uses of artificial intelligence (AI). But was the pandemic a large enough catalyst to change public attitudes about the costs and benefits of autonomous systems whose operations increasingly rely on AI? To answer this question, we use a preregistered research design that exploits variation across the 2018 and 2020 waves of the CCES/CES, a nationally representative survey of adults in the United States. We compare support for autonomous cars, autonomous surgeries, weapons, and cyber defense pre- and post-the beginning of the COVID-19 pandemic. We find that, despite the incentives created by COVID-19, the pandemic did not increase support for most of these technologies, except in the case of autonomous surgery among those who know someone who died of COVID-19. The results hold even when controlling for a variety of relevant political and demographic factors. The pandemic did little to push potential autonomous vehicle users to support adoption. Further, American concerns about autonomous weapons, including cyber defense, remain sticky and perhaps exacerbated over the last two years. These findings suggest that the relationship between the COVID-19 pandemic and the adoption of many of these systems is far more nuanced and complex than headlines may suggest.

Mitochondrial dysfunction in peripheral blood mononuclear cells in early experimental and clinical acute pancreatitis.

BACKGROUND/OBJECTIVES: Mitochondrial dysfunction occurs in vital organs in experimental acute pancreatitis (AP) and may play an important role in determining severity of AP. However, obtaining vital organ biopsies to measure mitochondrial function (MtF) in patients with AP poses considerable risk of harm. Being able to measure MtF from peripheral blood will bypass this problem. Furthermore, whether mitochondrial dysfunction is detectable in peripheral blood in mild AP is unknown. Therefore, the objective was to evaluate peripheral blood MtF in experimental and clinical AP. METHOD: Mitochondrial respiration was measured using high resolution oxygraphy in an experimental study in caerulein induced AP and in a separate study, in patients with mild AP. Superoxide, cytochrome c, mitochondrial membrane potential (ΔΨ) and adenine triphosphate (ATP) were also measured as other markers of MtF. RESULTS: Even though some states of mitochondrial respiration were increased in both experimental and clinical AP, this did not lead to an increase in net ATP in patients with AP. The increased leak respiration in both studies was further proof of dyscoupled mitochondria. In the clinical study there were also features of mitochondrial dysfunction with increased leak flux control ratio, superoxide, ΔΨ and decreased cytochrome c. CONCLUSION: There is evidence of mitochondrial dysfunction with dyscoupled mitochondria, increased superoxide and decreased cytochrome c in patients with mild acute pancreatitis. Further studies should now determine whether mitochondrial function alters with severity in AP and whether mitochondrial dysfunction responds to treatments.

Cellular degradation of 4-hydroxy-2-oxoglutarate aldolase leads to absolute deficiency in primary hyperoxaluria type 3.

Primary hyperoxaluria type-3 is characterized by increased oxalate production caused by mutations in the HOGA1 gene encoding 4-hydroxy-2-oxoglutarate aldolase (HOGA1). How the most commonly occurring mutations affect the cellular fates of the expressed HOGA1 mutants is still unknown. We show that two prevalent recombinant HOGA1 mutants are thermally unstable with evidence for chaperone-mediated degradation when expressed in E. coli. In stably transformed HEK-293 cells, protein expression of the Glu315 deletion mutant only becomes detectable during incubation with a 26S proteasome inhibitor. These findings suggest that failure of chaperone-assisted folding leads to targeted cellular degradation and an absolute absence of HOGA1 function.

Implications of Risk Factors for Alzheimer's Disease in Canada's Indigenous Population.

BACKGROUND: Indigenous peoples in Canada have higher prevalence of modifiable risk factors for Alzheimer's disease (AD). The relative importance of these risk factors on AD risk management is poorly understood. METHODS: Relative risks from literature and prevalence of risk factors from Statistics Canada or the First Nations Regional Health Survey were used to determine projected population attributable risk (PAR) associated with modifiable risk factors for AD (low education and vascular risk factors) among on- and off-reserve Indigenous and non-Indigenous people in Canada using the Levin formula. RESULTS: Physical inactivity had the highest PAR for AD among Indigenous and non-Indigenous peoples in Canada (32.5% [10.1%-51.1%] and 30.5% [9.2%-48.8%] respectively). The PAR for most modifiable risk factors was higher among Indigenous peoples in Canada, particularly among on-reserve groups. The greatest differences in PAR were for low educational attainment and smoking, which were approximately 10% higher among Indigenous peoples in Canada. The combined PAR for AD for all six modifiable risk factors was 79.6% among on-reserve Indigenous, 74.9% among off-reserve Indigenous, and 67.1% among non-Indigenous peoples in Canada. (All differences significant to p < .001.). CONCLUSIONS: Modifiable risk factors are responsible for the most AD cases among Indigenous peoples in Canada. Further research is necessary to determine the prevalence of AD and the impact of risk factor modification among Indigenous peoples in Canada.

Changes in mitochondrial function and mitochondria associated protein expression in response to 2-weeks of high intensity interval training.

PURPOSE: High-intensity short-duration interval training (HIT) stimulates functional and metabolic adaptation in skeletal muscle, but the influence of HIT on mitochondrial function remains poorly studied in humans. Mitochondrial metabolism as well as mitochondrial-associated protein expression were tested in untrained participants performing HIT over a 2-week period. METHODS: Eight males performed a single-leg cycling protocol (12 × 1 min intervals at 120% peak power output, 90 s recovery, 4 days/week). Muscle biopsies (vastus lateralis) were taken pre- and post-HIT. Mitochondrial respiration in permeabilized fibers, citrate synthase (CS) activity and protein expression of peroxisome proliferator-activated receptor gamma coactivator (PGC-1α) and respiratory complex components were measured. RESULTS: HIT training improved peak power and time to fatigue. Increases in absolute oxidative phosphorylation (OXPHOS) capacities and CS activity were observed, but not in the ratio of CCO to the electron transport system (CCO/ETS), the respiratory control ratios (RCR-1 and RCR-2) or mitochondrial-associated protein expression. Specific increases in OXPHOS flux were not apparent after normalization to CS, indicating that gross changes mainly resulted from increased mitochondrial mass. CONCLUSION: Over only 2 weeks HIT significantly increased mitochondrial function in skeletal muscle independently of detectable changes in mitochondrial-associated and mitogenic protein expression.

Could thermal sensitivity of mitochondria determine species distribution in a changing climate?

For many aquatic species, the upper thermal limit (Tmax) and the heart failure temperature (THF) are only a few degrees away from the species' current environmental temperatures. While the mechanisms mediating temperature-induced heart failure (HF) remain unresolved, energy flow and/or oxygen supply disruptions to cardiac mitochondria may be impacted by heat stress. Recent work using a New Zealand wrasse (Notolabrus celidotus) found that ATP synthesis capacity of cardiac mitochondria collapses prior to T(HF). However, whether this effect is limited to one species from one thermal habitat remains unknown. The present study confirmed that cardiac mitochondrial dysfunction contributes to heat stress-induced HF in two additional wrasses that occupy cold temperate (Notolabrus fucicola) and tropical (Thalassoma lunare) habitats. With exposure to heat stress, T. lunare had the least scope to maintain heart function with increasing temperature. Heat-exposed fish of all species showed elevated plasma succinate, and the heart mitochondria from the cold temperate N. fucicola showed decreased phosphorylation efficiencies (depressed respiratory control ratio, RCR), cytochrome c oxidase (CCO) flux and electron transport system (ETS) flux. In situ assays conducted across a range of temperatures using naive tissues showed depressed complex II (CII) and CCO capacity, limited ETS reserve capacities and lowered efficiencies of pyruvate uptake in T. lunare and N. celidotus. Notably, alterations of mitochondrial function were detectable at saturating oxygen levels, indicating that cardiac mitochondrial insufficiency can occur prior to HF without oxygen limitation. Our data support the view that species distribution may be related to the thermal limits of mitochondrial stability and function, which will be important as oceans continue to warm.

Ob/ob mouse livers show decreased oxidative phosphorylation efficiencies and anaerobic capacities after cold ischemia.

BACKGROUND: Hepatic steatosis is a major risk factor for graft failure in liver transplantation. Hepatic steatosis shows a greater negative influence on graft function following prolonged cold ischaemia. As the impact of steatosis on hepatocyte metabolism during extended cold ischaemia is not well-described, we compared markers of metabolic capacity and mitochondrial function in steatotic and lean livers following clinically relevant durations of cold preservation. METHODS: Livers from 10-week old leptin-deficient obese (ob/ob, n = 9) and lean C57 mice (n = 9) were preserved in ice-cold University of Wisconsin solution. Liver mitochondrial function was then assessed using high resolution respirometry after 1.5, 3, 5, 8, 12, 16 and 24 hours of storage. Metabolic marker enzymes for anaerobiosis and mitochondrial mass were also measured in conjunction with non-bicarbonate tissue pH buffering capacity. RESULTS: Ob/ob and lean mice livers showed severe (>60%) macrovesicular and mild (<30%) microvesicular steatosis on Oil Red O staining, respectively. Ob/ob livers had lower baseline enzymatic complex I activity but similar adenosine triphosphate (ATP) levels compared to lean livers. During cold storage, the respiratory control ratio and complex I-fueled phosphorylation deteriorated approximately twice as fast in ob/ob livers compared to lean livers. Ob/ob livers also demonstrated decreased ATP production capacities at all time-points analyzed compared to lean livers. Ob/ob liver baseline lactate dehydrogenase activities and intrinsic non-bicarbonate buffering capacities were depressed by 60% and 40%, respectively compared to lean livers. CONCLUSIONS: Steatotic livers have impaired baseline aerobic and anaerobic capacities compared to lean livers, and mitochondrial function indices decrease particularly from after 5 hours of cold preservation. These data provide a mechanistic basis for the clinical recommendation of shorter cold storage durations in steatotic donor livers.

Hepatic mitochondrial function analysis using needle liver biopsy samples.

BACKGROUNDS AND AIM: Current assessment of pre-operative liver function relies upon biochemical blood tests and histology but these only indirectly measure liver function. Mitochondrial function (MF) analysis allows direct measurement of cellular metabolic function and may provide an additional index of hepatic health. Conventional MF analysis requires substantial tissue samples (>100 mg) obtained at open surgery. Here we report a method to assess MF using <3 mg of tissue obtained by a Tru-cut® biopsy needle making it suitable for percutaneous application. METHODS: An 18G Bard® Max-core® biopsy instrument was used to collect samples. The optimal Tru-cut® sample weight, stability in ice-cold University of Wisconsin solution, reproducibility and protocol utility was initially evaluated in Wistar rat livers then confirmed in human samples. MF was measured in saponin-permeabilized samples using high-resolution respirometry. RESULTS: The average mass of a single rat and human liver Tru-cut® biopsy was 5.60±0.30 and 5.16±0.15 mg, respectively (mean; standard error of mean). Two milligram of sample was found the lowest feasible mass for the MF assay. Tissue MF declined after 1 hour of cold storage. Six replicate measurements within rats and humans (n = 6 each) showed low coefficient of variation (<10%) in measurements of State-III respiration, electron transport chain (ETC) capacity and respiratory control ratio (RCR). Ischemic rat and human liver samples consistently showed lower State-III respiration, ETC capacity and RCR, compared to normal perfused liver samples. CONCLUSION: Consistent measurement of liver MF and detection of derangement in a disease state was successfully demonstrated using less than half the tissue from a single Tru-cut® biopsy. Using this technique outpatient assessment of liver MF is now feasible, providing a new assay for the evaluation of hepatic function.

The redox status of experimental hemorrhagic shock as measured by cyclic voltammetry.

Hemorrhagic shock (HS) leads to reactive oxygen species production. However, clinicians do not have access to bedside measurements of the redox status during HS. Cyclic voltammetry (CyV) is a simple electrochemical method of measuring redox status. The aims of this study were to 1) report the first application of cyclic voltammetry to measure the acute changes in serum redox status after HS, 2) to contrast it with another severe systemic disease with a different redox pathology (acute pancreatitis [AP]), and 3) to describe the response of CyV over time in a resolving model of AP. In the acute study, 24 male Wistar rats were randomized into three groups: groups 1 (control), 2 (AP), and 3 (HS). In the time-course study, 28 rats were randomized to a sham-control as well as 6 and 24 h post-AP cohorts, respectively.Cyclic voltammetry was performed using a three-electrode system. In the acute study, the first and second voltammetric peaks increased significantly in HS. In contrast, within the AP group, only the first voltammetric peak showed a significant increase. The first voltammetric peak correlated with plasma protein carbonyls (PCs) and with thiobarbituric acid-reactive substances, whereas the second voltammetric peak correlated positively with plasma protein carbonyls. In the second study, the first voltammetric peak correlated with physiological improvements. Here, we showed that serum CyV could respond to the serum redox change in HS and AP. Cyclic voltammetry warrants evaluation as a potential real-time beside measure of a patient's redox status during shock.