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Jocelyne C Whitehead,1 Sara A Gambino,1 Jeffrey D Richter,2 Jennifer D Ryan1,3,41Rotman Research Institute, Baycrest, 2Independent Human Factors Consultant, Toronto, ON, Canada; 3Department of Psychology, 4Department of Psychiatry, University of Toronto, Toronto, ON, CanadaObjective: This study provides insight into the thoughts and opinions of geriatric health-care professionals toward cognitive assessments and the use of emerging technologies, such as eye-tracking, to supplement current tools.Methods: Two focus group sessions were conducted with nurses and physicians who routinely administer neurocognitive assessments to geriatric populations. Video recordings of the focus group sessions were transcribed and a thematic analysis was performed.Results: Participants reported the need for assessment and diagnostic tools that are accessible and efficient, and that are capable of accommodating the rapid growth in the aging population. The prevalence of more complex ailments experienced by older adults has had repercussions in the quality of care that the clients receive, and has contributed to lengthy wait times and resource shortages. Health-care professionals stated that they are hampered by the disjointed structure of the health-care system and that they would benefit from a more efficient allocation of responsibilities made possible through tools that did not require extensive training or certification. Eyetracking-based cognitive assessments were thought to strongly complement this system, yet it was thought that difficulty would be faced in gaining the support and increased uptake by health-care professionals due to the nonintuitive relationship between eyetracking and cognition.Conclusion: The findings suggest that health-care professionals are receptive to the use of eyetracking technology to assess for cognitive health as it would conserve resources by allowing frontline staff to administer assessments with minimal training.Keywords: neurocognitive assessment, eyetracking, focus groups, geriatric health care

Purpose. This study was part of a larger mixed methods project aimed at adapting the Cognitive Orientation to daily Occupational Performance (CO-OP) treatment approach, originally designed for children with performance problems, for use with adults with stroke. In CO-OP, the client focuses on learning strategies and skills, rather than on remediating impairments. Therapists use guided discovery to teach cognitive strategy use. The purpose of this study was to explore participants' experiences with the approach. Method. Semistructured interviews were conducted with five participants. Transcriptions were coded by two members of the research team. Data analysis was conducted in two distinct phases: Directed content analysis was conducted to apply codes to predetermined categories; Thematic analysis was conducted to allow themes grounded in the data to emerge. Results. Participants reported learning and transferring the strategies taught, and made suggestions for modifications to the approach, such as increasing the number of sessions. One theme emerged, Balancing the need for autonomy with the need for support. Conclusions. The findings suggest the cognitive strategies were well learned and effectively used. CO-OP was able to provide participants with increased decision-making autonomy, but may require modifications to better support their transition to higher levels of independence. [ABSTRACT FROM AUTHOR]

This paper reflects upon one aspect of a qualitative study of beginner acupuncture clinicians' experiences of clinical practice -- the use of evidence in clinical decision-making. From an analysis of 42 interview transcripts of those who participated in the study it was found that participants relied heavily upon knowledge that had 'stood the test of time' (traditional theory and practice) and that which worked' (experientially based knowledge) as the basis for clinical decision-making. Conversely, evidence arising from research was not generally used in the clinical decision-making of this practitioner cohort. This paper reflects upon the apparent chasm between the priorities of evidence-based medicine and the way in which practitioners of complementary medicine approach clinical decision-making. [ABSTRACT FROM AUTHOR]

A cueing paradigm was employed to examine modulation of distraction due to a visual singleton. Subjects were required to make a saccade to a shape-singleton target. A predictive location cue indicated the hemifield where a target would appear. Older adults made more anticipatory saccades than younger adults, and were less accurate for making an eye movement in the vicinity of a target. However, younger and older adults likewise benefited from the cue; distraction was reduced when the distractor singleton appeared in an uncued hemisphere. The ability to compensate for problems with distraction in older and younger adults through use of the precue suggests that attention to a general region of space, rather than a specific location, may be enough to modulate distraction. [ABSTRACT FROM AUTHOR]

We report a haematoma in a hydrocele of the canal of Nuck in a 69-year-old female. She presented with a right-sided groin swelling, the differential for which included an irreducible inguinal hernia or haematoma given her aspirin and clopidegrel use. Successful treatment involved evacuation of the haematoma with excision of the sac. Despite a high index of suspicion for a haematoma, these swellings should ideally be explored given the potential for co-existence of a hernia. [ABSTRACT FROM AUTHOR]

Unitization - the fusion of objects into a single unit through an action/consequence sequence - can mitigate relational memory impairments, but the circumstances under which unitization is effective are unclear. Using transverse patterning (TP), we compared unitization (and its component processes of fusion, motion, and action/consequence) with extended practice on relational learning and transfer in older adults and neuropsychological cases with lesions (to varying extents) in the medial prefrontal cortex (mPFC) or hippocampus/medial temporal lobe (HC/MTL). The latter included a person with bilateral HC lesions primarily within the dentate gyrus. For older adults, TP accuracy increased, and transfer benefits were observed, with extended practice and unitization. Broadly, the lesion cases did not benefit from either extended practice or unitization, suggesting the mPFC and dentate gyrus play important roles in relational memory and in unitization. The results suggest that personalized strategy interventions must align with the cognitive and neural profiles of the user.

Background: Common metabolic diseases, such as type 2 diabetes mellitus (T2DM), hypertension, obesity, hypercholesterolemia, and metabolic dysfunction-associated steatotic liver disease (MASLD), have become a global health burden in the last three decades. The Global Burden of Disease, Injuries, and Risk Factors Study (GBD) data enables the first insights into the trends and burdens of these metabolic diseases from 1990 to 2021, highlighting regional, temporal and differences by sex., Methods: Global estimates of disability-adjusted life years (DALYs) and deaths from GBD 2021 were analyzed for common metabolic diseases (T2DM, hypertension, obesity, hypercholesterolemia, and MASLD). Age-standardized DALYs (mortality) per 100,000 population and annual percentage change (APC) between 1990 and 2021 were estimated for trend analyses. Estimates are reported with uncertainty intervals (UI)., Results: In 2021, among five common metabolic diseases, hypertension had the greatest burden (226 million [95 % UI: 190-259] DALYs), whilst T2DM (75 million [95 % UI: 63-90] DALYs) conferred much greater disability than MASLD (3.67 million [95 % UI: 2.90-4.61]). The highest absolute burden continues to be found in the most populous countries of the world, particularly India, China, and the United States, whilst the highest relative burden was mostly concentrated in Oceania Island states. The burden of these metabolic diseases has continued to increase over the past three decades but has varied in the rate of increase (1.6-fold to 3-fold increase). The burden of T2DM (0.42 % [95 % UI: 0.34-0.51]) and obesity (0.26 % [95 % UI: 0.17-0.34]) has increased at an accelerated rate, while the rate of increase for the burden of hypertension (-0.30 % [95 % UI: -0.34 to -0.25]) and hypercholesterolemia (-0.33 % [95 % UI: -0.37 to -0.30]) is slowing. There is no significant change in MASLD over time (0.05 % [95 % UI: -0.06 to 0.17])., Conclusion: In the 21st century, common metabolic diseases are presenting a significant global health challenge. There is a concerning surge in DALYs and mortality associated with these conditions, underscoring the necessity for a coordinated global health initiative to stem the tide of these debilitating diseases and improve population health outcomes worldwide., Competing Interests: Declaration of competing interest John D. Ryan received consultancy fees from Falk, Gilead, Pfizer and a speaker honorarium from Takeda. Luca Valenti reports consulting fees from Gilead, Pfizer, Astra Zeneca, Novo Nordisk, Intercept pharmaceuticals, Diatech Pharmacogenetics, IONIS, Viatris; honoraria from MSD, Gilead, AlfaSigma, AbbVie, Resalis, grants from Gilead. Alice Pik-Shan Kong has received research grants and/or speaker honoraria from Abbott, Astra Zeneca, Bayer, Boehringer Ingelheim, Dexcom, Eli-Lilly, Kyowa Kirin, Merck Serono, Nestle, Novo-Nordisk, Pfizer and Sanofi and Zuellig Pharma. Gregory Y. H. Lip serves as consultant and speaker for BMS/Pfizer, Boehringer Ingelheim, Daiichi-Sankyo, Anthos. He is a National Institute for Health and Care Research (NIHR) Senior Investigator and co-PI of the AFFIRMO project on multimorbidity in AF (grant agreement No 899871), TARGET project on digital twins for personalised management of atrial fibrillation and stroke (grant agreement No 101136244) and ARISTOTELES project on artificial intelligence for management of chronic long term conditions (grant agreement No 101080189), which are all funded by the EU's Horizon Europe Research & Innovation programme. Anoop Misra has received honorarium from Abbott, Roche, Jannsen, Boehringer Ingelheim, Lupin, Cipla, US Vitamins, and Novo Nordisk. Christopher D. Byrne has received grant support from Echosens. Wah-Kheong Chan is a consultant or advisory board member for Abbott, Roche, Abbvie, Boehringer Ingelheim and Novo Nordisk; and a speaker for Abbott, Novo Nordisk, Echosens, Viatris and Hisky Medical. Christos S. Mantzoros reports grants through his institution from Merck, Massachusetts Life Sciences Center and Boehringer Ingelheim, has received grants through his Institution and personal consulting fees from Coherus Inc. and AltrixBio, he reports personal consulting fees and support with research reagents from Ansh Inc., collaborative research support from LabCorp Inc., reports personal consulting fees from Olympus, Genfit, Lumos, Novo Nordisk, Amgen, Biodexa, Laekna, Corcept, Intercept, 89 Bio, Madrigal, Aligos, Esperion and Regeneron, travel support and fees from UptoDate, TMIOA, Elsevier, and the Cardio Metabolic Health Conference. Ming-Hua Zheng has received honoraria for lectures from AstraZeneca, Hisky Medical Technologies and Novo Nordisk, consulting fees from Boehringer Ingelheim. No other disclosures were reported., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Early stages of Alzheimer's disease (AD) are associated with volume reductions in specific subregions of the medial temporal lobe (MTL). Using a manual segmentation method-the Olsen-Amaral-Palombo (OAP) protocol-previous work in healthy older adults showed that reductions in grey matter volumes in MTL subregions were associated with lower scores on the Montreal Cognitive Assessment (MoCA), suggesting atrophy may occur prior to diagnosis of mild cognitive impairment, a condition that often progresses to AD. However, current "gold standard" manual segmentation methods are labour intensive and time consuming. Here, we examined the utility of Automatic Segmentation of Hippocampal Subfields (ASHS) to detect volumetric differences in MTL subregions of healthy older adults who varied in cognitive status as determined by the MoCA. We trained ASHS on the OAP protocol to create the ASHS-OAP atlas and then examined how well automated segmentation replicated manual segmentation. Volumetric measures obtained from the ASHS-OAP atlas were also contrasted against those from the ASHS-PMC atlas, a widely used atlas provided by the ASHS team. The pattern of volumetric results was similar between the ASHS-OAP atlas and manual segmentation for anterolateral entorhinal cortex and perirhinal cortex, suggesting that ASHS-OAP is a viable alternative to current manual segmentation methods for detecting group differences based on cognitive status. Although ASHS-OAP and ASHS-PMC produced varying volumes for most regions of interest, they both identified early signs of neurodegeneration in CA 2 /CA 3 /DG and identified marginal differences in entorhinal cortex. Our findings highlight the utility of automated segmentation methods but still underscore the need for a unified and harmonized MTL segmentation atlas., (© 2024 The Author(s). Human Brain Mapping published by Wiley Periodicals LLC.)

Background: Obesity represents a major global health challenge with important clinical implications. Despite its recognized importance, the global disease burden attributable to high body mass index (BMI) remains less well understood., Methods: We systematically analyzed global deaths and disability-adjusted life years (DALYs) attributable to high BMI using the methodology and analytical approaches of the Global Burden of Disease Study (GBD) 2021. High BMI was defined as a BMI over 25 kg/m 2 for individuals aged ≥20 years. The Socio-Demographic Index (SDI) was used as a composite measure to assess the level of socio-economic development across different regions. Subgroup analyses considered age, sex, year, geographical location, and SDI., Findings: From 1990 to 2021, the global deaths and DALYs attributable to high BMI increased more than 2.5-fold for females and males. However, the age-standardized death rates remained stable for females and increased by 15.0% for males. Similarly, the age-standardized DALY rates increased by 21.7% for females and 31.2% for males. In 2021, the six leading causes of high BMI-attributable DALYs were diabetes mellitus, ischemic heart disease, hypertensive heart disease, chronic kidney disease, low back pain and stroke. From 1990 to 2021, low-middle SDI countries exhibited the highest annual percentage changes in age-standardized DALY rates, whereas high SDI countries showed the lowest., Interpretation: The worldwide health burden attributable to high BMI has grown significantly between 1990 and 2021. The increasing global rates of high BMI and the associated disease burden highlight the urgent need for regular surveillance and monitoring of BMI., Funding: National Natural Science Foundation of China and National Key R&D Program of China., Competing Interests: Christopher D. Byrne has received grant support from Echosens. Ming-Hua Zheng has received honoraria for lectures from AstraZeneca, Hisky Medical Technologies and Novo Nordisk, consulting fees from Boehringer Ingelheim. Anoop Misra has received honoraria from Novo Nordisk, AstraZendeca, Janssen, and Boehringer Ingelheim. Wah-Kheong Chan is a consultant or advisory board member for Abbott, Roche, Abbvie, Boehringer Ingelheim and Novo Nordisk; and a speaker for Abbott, Novo Nordisk, Echosens, Viatris and Hisky Medical. No other disclosures were reported; John D. Ryan received consultancy fees from Falk, Gilead, Pfizer and a speaker honorarium from Takeda. Christos S. Mantzoros reports grants through his institution from Merck, Massachusetts Life Sciences Center and Boehringer Ingelheim, has received grants through his Institution and personal consulting fees from Coherus Inc. and AltrixBio, he reports personal consulting fees and support with research reagents from Ansh Inc., collaborative research support from LabCorp Inc., reports personal consulting fees from Olympus, Genfit, Lumos, Novo Nordisk, Amgen, Biodexa, Laekna, Corcept, Intercept, 89 Bio, Madrigal, Aligos, Esperion and Regeneron, travel support and fees from UptoDate, TMIOA, Elsevier, and the Cardio Metabolic Health Conference. The other authors report no disclosure., (© 2024 The Author(s).)

Aims: Patients with haemochromatosis (HFE) are known to have an increased risk of developing hepatocellular carcinoma (HCC). Available data are conflicting on whether such patients have poorer prognosis, and there is lack of data regarding the biology of HFE-HCC. We compared the course of HFE-HCC with a matched non-HFE-HCC control group and examined tumour characteristics using immunohistochemistry., Methods: In this tertiary care-based retrospective analysis, 12 patients with HFE and 34 patients with alcohol/non-alcoholic steatohepatitis who underwent initially successful curative HCC therapy with ablation or resection were identified from our registry. Time to tumour progression was compared. Resected liver tissue from a separate cohort of 11 matched patients with HFE-HCC and without HFE-HCC was assessed for the expression of progenitor and epithelial-mesenchymal transition markers using immunohistochemistry., Results: The median follow-up was 24.39 and 24.28 months for patients with HFE-HCC and those without HFE-HCC, respectively (p>0.05). The mean time to progression was shorter in the HFE group compared with the non-HFE group (12.87 months vs 17.78 months; HR 3.322, p<0.05). Patients with HFE-HCC also progressed to more advanced disease by the end of follow-up (p<0.05). Immunohistochemical analysis of matched HFE-HCC and non-HFE-HCC explants demonstrated increased expression of the cancer stem cell markers EpCAM (epithelial cell adhesion molecule) and EpCAM/SALL4 (spalt-like transcription factor 4) coexpression in HFE-HCC specimens (p<0.05). There was a high frequency of combined tumour subtypes within the HFE cohort., Conclusions: This study demonstrates that the clinical course of patients with HFE-HCC is more aggressive and provides the first data indicating that their tumours have increased expression of progenitor markers. These findings suggest patients with HFE-HCC may need to be considered for transplant at an earlier stage., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY. Published by BMJ.)

Path integration (PI) is a navigation process that allows an organism to update its current location in reference to a starting point. PI can involve updating self-position continuously with respect to the starting point (continuous updating) or creating a map representation of the route which is then used to compute the homing vector (configural updating). One of the brain areas involved in PI, the entorhinal cortex, is modulated similarly by whole-body and eye movements, suggesting that if PI updates self-position, an analogous process may be used to update gaze position, and may undergo age-related changes. Here, we created an eyetracking version of a PI task in which younger and older participants followed routes with their eyes as guided by visual onsets; at the end of each route, participants were cued to return to the starting point or another enroute location. When only memory for the starting location was required for successful task performance, younger and older adults were generally not influenced by the number of locations, indicative of continuous updating. However, when participants could be cued to any enroute location, thereby requiring memory for the entire route, processing times increased, accuracy decreased, and overt revisits to enroute locations increased with the number of locations in a route, indicative of configural updating. Older participants showed evidence for similar updating strategies as younger participants, but they were less accurate and made more overt revisits to mid-route locations. These findings suggest that spatial updating mechanisms are generalizable across effector systems., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Research has documented changes in autobiographical memory and episodic future thinking in mild cognitive impairment (MCI) and Alzheimer's disease (AD). However, cognitive decline occurs gradually and recent findings suggest that subtle alterations in autobiographical cognition may be evident earlier in the trajectory towards dementia, before AD-related symptoms emerge or a clinical diagnosis has been given. The current study used the Autobiographical Interview to examine the episodic and semantic content of autobiographical past and future events generated by older adults (N = 38) of varying cognitive functioning who were grouped into High (N = 20) and Low Cognition (N = 18) groups based on their Montreal Cognitive Assessment (MoCA) scores. Participants described 12 past and 12 future autobiographical events, and transcripts were scored to quantify the numbers of internal (episodic) or external (non-episodic, including semantic) details. Although the Low Cognition group exhibited a differential reduction for internal details comprising both past and future events, they did not show the expected overproduction of external details relative to the High Cognition group. Multilevel modelling demonstrated that on trials lower in episodic content, semantic content was significantly increased in both groups. Although suggestive of a compensatory mechanism, the magnitude of this inverse relationship did not differ across groups or interact with MoCA scores. This finding indicates that external detail production may be underpinned by mechanisms not affected by cognitive decline, such as narrative style and the ability to contextualize one's past and future events in relation to broader autobiographical knowledge., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

The assessment of mental effort is increasingly relevant in neurocognitive and life span domains. Pupillometry, the measure of the pupil size, is often used to assess effort but has disadvantages. Analysis of eye movements may provide an alternative, but research has been limited to easy and difficult task demands in younger adults. An effort measure must be sensitive to the whole effort profile, including "giving up" effort investment, and capture effort in different age groups. The current study comprised three experiments in which younger (n = 66) and older (n = 44) adults listened to speech masked by background babble at different signal-to-noise ratios associated with easy, difficult, and impossible speech comprehension. We expected individuals to invest little effort for easy and impossible speech (giving up) but to exert effort for difficult speech. Indeed, pupil size was largest for difficult but lower for easy and impossible speech. In contrast, gaze dispersion decreased with increasing speech masking in both age groups. Critically, gaze dispersion during difficult speech returned to levels similar to easy speech after sentence offset, when acoustic stimulation was similar across conditions, whereas gaze dispersion during impossible speech continued to be reduced. These findings show that a reduction in eye movements is not a byproduct of acoustic factors, but instead suggest that neurocognitive processes, different from arousal-related systems regulating the pupil size, drive reduced eye movements during high task demands. The current data thus show that effort in one sensory domain (audition) differentially impacts distinct functional properties in another sensory domain (vision)., (© 2024 Massachusetts Institute of Technology.)

How well do we know our city? It turns out, much more poorly than we might imagine. We used declarative memory and eye-tracking techniques to examine people's ability to detect modifications to real-world landmarks and scenes in Toronto locales with which they have had extensive experience. Participants were poor at identifying which scenes contained altered landmarks, whether the modification was to the landmarks' relative size, internal features, or relation to surrounding context. To determine whether an indirect measure would prove more sensitive, we tracked eye movements during viewing. Changes in overall visual exploration, but not to specific regions of change, were related to participants' explicit endorsement of scenes as modified. These results support the contention that very familiar landmarks are represented at a global or gist level, but not local or fine-grained, level. These findings offer a unified view of memory for gist across verbal and spatial domains, and across recent and remote memory, with implications for hippocampal-neocortical interactions., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Tau pathology accumulates in the perirhinal cortex (PRC) of the medial temporal lobe (MTL) during the earliest stages of the Alzheimer's disease (AD), appearing decades before clinical diagnosis. Here, we leveraged perceptual discrimination tasks that target PRC function to detect subtle cognitive impairment even in nominally healthy older adults. Older adults who did not have a clinical diagnosis or subjective memory complaints were categorized into "at-risk" (score <26; n = 15) and "healthy" (score ≥26; n = 23) groups based on their performance on the Montreal Cognitive Assessment. The task included two conditions known to recruit the PRC: faces and complex objects (greebles). A scene condition, known to recruit the hippocampus, and a size control condition that does not rely on the MTL were also included. Individuals in the at-risk group were less accurate than those in the healthy group for discriminating greebles. Performance on either the face or size control condition did not predict group status above and beyond that of the greeble condition. Visual discrimination tasks that are sensitive to PRC function may detect early cognitive decline associated with AD., (© 2024 The Authors. Hippocampus published by Wiley Periodicals LLC.)

In 2013, the Alberta Colorectal Cancer Screening Program (ACRCSP) initially published recommendations for post-colonoscopy follow-up and polypectomy. Over time, emerging evidence and evolving surveillance guidelines from various expert groups necessitated a comprehensive review to align with the healthcare landscape in Alberta. To accomplish this, an expert panel was convened. Using the Agree II tool, we identified high-quality Clinical Practice Guidelines that were relevant to the Alberta medical context. Recommendations from these guidelines were adapted to fit the specific needs of Alberta. Recognizing inconsistencies and gaps within the existing guidelines, we conducted targeted literature reviews to ensure a comprehensive and evidence-based approach to our recommendations. Our revised recommendations build upon the assumption that a high-quality index colonoscopy has been performed at baseline. They are intended to enhance the quality of care and reduce unnecessary procedures. As well, they align with the growing consensus in the scientific literature that individuals with low-risk tubular adenomas may not require aggressive colonoscopy surveillance. The updated Alberta recommendations aim to provide clear recommendations for practicing endoscopists, referring physicians, and their patients. They address crucial questions such as determining which patients should commence surveillance via colonoscopy and which individuals should return to average-risk screening using the fecal immunochemical test (FIT). Additionally, our recommendations outline the appropriate surveillance intervals for those requiring continued monitoring., Competing Interests: Daniel Sadowski—support in kind from AHS for systematic reviews and manuscript preparation. Member, Advisory Board ACRCSP. Physician Lead for Quality, Alberta Health Services; Previous publications related to guideline. Michael R Kolber—Founder and President of EMPRSS (Electronic Medical Procedure Reporting Systems). Robert Hilsden—Medical Director, Forzani and MacPhail Colon Cancer Screening Centre, Professor, University of Calgary; various publications related to guideline. Dereck Mok—Lecture honoraria Johnson and Johnson, Member Alberta Endoscopy and Screening Quality Committee, Johnson and Johnson stocks held. Richard Sultanian—Co-Chair Alberta Colorectal Cancer Screening Program. Huiming Yang—Employed by AHS, Member ACRCSP Advisory Committee., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Canadian Association of Gastroenterology.)

Background: Minimum unit pricing (MUP) was recently introduced in Ireland to reduce alcohol-related harms. The size of the impact of alcohol on hospital emergency departments (EDs) in Ireland is poorly understood due to inconsistent alcohol screening and documentation., Aims: We sought to systematically characterise the volume, timing, and nature of alcohol-related presentations and admissions to a busy urban ED in Dublin, Ireland., Method: Patients presenting to the ED were assessed by a dedicated clinician during selected time periods before (Nov-Dec 2021) and after (Feb-Apr 2022) the introduction of MUP. A total of 725 interviews were conducted over 168 h in the ED., Findings: Alcohol consumption was a factor in 19.4% of ED presentations and in 17.3% of hospital admissions across the entire study period. A reduction in overall alcohol-related ED presentations was noted in the period following MUP, although it is not possible to conclude a direct effect., Conclusion: Alcohol-related harm places a significant strain on EDs and hospitals, and the impact of MUP on hospital burden in Ireland merits further evaluation. Effective measures at local and population levels are urgently required to address this burden., (Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Weight gain post-liver transplant can lead to adverse patient outcomes in the post-transplant period. Pharmacotherapy and other measures can be utilised to reduce the burden and occurrence of weight gain in this population. We explored the mechanism of action, safety, and efficacy of these medications, specifically GLP-1 receptor agonists and metformin, focusing on liver transplant patients. This scoping review was conducted in line with the scoping review structure as outlined by the PRISMA guidelines. Metformin and GLP-1 receptor agonists have been observed to be safe and effective in liver transplant patients. Experimental models have found liver-centric weight loss mechanisms in this drug cohort. There is a paucity of evidence about the use of antihyperglycemics in a post-transplant population for weight loss purposes. However, some small studies have shown strong safety and efficacy data. The evidence in relation to using these medications in patients with metabolic syndrome for weight loss warrants further study in a transplant population., Competing Interests: There is no conflict of interest for authors of this article., (© 2024, Gastroenterology and Hepatology From Bed to Bench (GHFBB).)

Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Prof. John Ryan reports a relationship with Bond Biosciences that includes: consulting or advisory. Prof. John Ryan reports a relationship with Pfizer that includes: consulting or advisory. Prof. John Ryan reports a relationship with Gilead Sciences Inc that includes: consulting or advisory. Prof. John Ryan reports a relationship with Falk that includes: speaking and lecture fees. Prof. John Ryan reports a relationship with Kyowa Kirin that includes: speaking and lecture fees. Prof. John Ryan reports a relationship with Irish Liver Foundation Charity that includes: board membership. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Background: Fatty liver disease in the absence of excessive alcohol consumption is an increasingly common condition with a global prevalence of ~ 25-30% and is also associated with cardiovascular disease (CVD). Since systemic metabolic dysfunction underlies its pathogenesis, the term metabolic (dysfunction)-associated fatty liver disease (MAFLD) has been proposed for this condition. MAFLD is closely intertwined with obesity, type 2 diabetes mellitus and atherogenic dyslipidemia, which are established cardiovascular risk factors. Unlike CVD, which has received attention in the literature on fatty liver disease, the CVD risk associated with MAFLD is often underestimated, especially among Cardiologists., Methods and Results: A multidisciplinary panel of fifty-two international experts comprising Hepatologists, Endocrinologists, Diabetologists, Cardiologists and Family Physicians from six continents (Asia, Europe, North America, South America, Africa and Oceania) participated in a formal Delphi survey and developed consensus statements on the association between MAFLD and the risk of CVD. Statements were developed on different aspects of CVD risk, ranging from epidemiology to mechanisms, screening, and management., Conculsions: The expert panel identified important clinical associations between MAFLD and the risk of CVD that could serve to increase awareness of the adverse metabolic and cardiovascular outcomes of MAFLD. Finally, the expert panel also suggests potential areas for future research., (© 2023. Asian Pacific Association for the Study of the Liver.)

Hyperferritinaemia is a common laboratory finding that is often associated with metabolic dysfunction and fatty liver. Metabolic hyperferritinaemia reflects alterations in iron metabolism that facilitate iron accumulation in the body and is associated with an increased risk of cardiometabolic and liver diseases. Genetic variants that modulate iron homeostasis and tissue levels of iron are the main determinants of serum levels of ferritin in individuals with metabolic dysfunction, raising the hypothesis that iron accumulation might be implicated in the pathogenesis of insulin resistance and the related organ damage. However, validated criteria for the non-invasive diagnosis of metabolic hyperferritinaemia and the staging of iron overload are still lacking, and there is no clear evidence of a benefit for iron depletion therapy. Here, we provide an overview of the literature on the relationship between hyperferritinaemia and iron accumulation in individuals with metabolic dysfunction, and on the associated clinical outcomes. We propose an updated definition and a provisional staging system for metabolic hyperferritinaemia, which has been agreed on by a multidisciplinary global panel of expert researchers. The goal is to foster studies into the epidemiology, genetics, pathophysiology, clinical relevance and treatment of metabolic hyperferritinaemia, for which we provide suggestions on the main unmet needs, optimal design and clinically relevant outcomes., (© 2023. Springer Nature Limited.)

The modulation of gaze fixations on neural activity in the hippocampus, a region critical for memory, has been shown to be weaker in older adults compared to younger adults. However, as such research has relied on indirect measures of memory, it remains unclear whether the relationship between visual exploration and direct measures of memory is similarly disrupted in aging. The current study tested older and younger adults on a face memory eye-tracking task previously used by our group that showed that recognition memory for faces presented across variable, but not fixed, viewpoints relies on a hippocampal-dependent binding function. Here, we examined how aging influences eye movement measures that reveal the amount ( cumulative sampling ) and extent ( distribution of gaze fixations ) of visual exploration. We also examined how aging influences direct ( subsequent conscious recognition ) and indirect ( eye movement repetition effect ) expressions of memory. No age differences were found in direct recognition regardless of facial viewpoint. However, the eye movement measures revealed key group differences. Compared to younger adults, older adults exhibited more cumulative sampling, a different distribution of fixations, and a larger repetition effect. Moreover, there was a positive relationship between cumulative sampling and direct recognition in younger adults, but not older adults. Neither age group showed a relationship between the repetition effect and direct recognition. Thus, despite similar direct recognition, age-related differences were observed in visual exploration and in an indirect eye-movement memory measure, suggesting that the two groups may acquire, retain, and use different facial information to guide recognition.

Objective: To determine the impact of minimum unit pricing (MUP) on the primary outcome of alcohol-related hospitalisation, and secondary outcomes of length of stay, hospital mortality and alcohol-related liver disease in hospital., Design: Databases MEDLINE, Embase, Scopus, APA Psycinfo, CINAHL Plus and Cochrane Reviews were searched from 1 January 2011 to 11 November 2022. Inclusion criteria were studies evaluating the impact of minimum pricing policies, and we excluded non-minimum pricing policies or studies without alcohol-related hospital outcomes. The Effective Public Health Practice Project tool was used to assess risk of bias, and the Bradford Hill Criteria were used to infer causality for outcome measures., Setting: MUP sets a legally required floor price per unit of alcohol and is estimated to reduce alcohol-attributable healthcare burden., Participant: All studies meeting inclusion criteria from any country INTERVENTION: Minimum pricing policy of alcohol PRIMARY AND SECONDARY OUTCOME MEASURES: RESULTS: 22 studies met inclusion criteria; 6 natural experiments and 16 modelling studies. Countries included Australia, Canada, England, Northern Ireland, Ireland, Scotland, South Africa and Wales. Modelling studies estimated that MUP could reduce alcohol-related admissions by 3%-10% annually and the majority of real-world studies demonstrated that acute alcohol-related admissions responded immediately and reduced by 2%-9%, and chronic alcohol-related admissions lagged by 2-3 years and reduced by 4%-9% annually. Minimum pricing could target the heaviest consumers from the most deprived groups who tend to be at greatest risk of alcohol harms, and in so doing has the potential to reduce health inequalities. Using the Bradford Hill Criteria, we inferred a 'moderate-to-strong' causal link that MUP could reduce alcohol-related hospitalisation., Conclusions: Natural studies were consistent with minimum pricing modelling studies and showed that this policy could reduce alcohol-related hospitalisation and health inequalities., Prospero Registration Number: CRD42021274023., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction: The Transverse Patterning (TP) task has been used to measure episodic relational memory (RM) deficits in clinical populations. Individuals with schizophrenia often fail to learn TP with standard, and sometimes extensive training. Identifying the differences between TP learners and non-learners can improve our understanding of successful TP performance and its underlying mechanisms, which may help improve interventions aimed at ameliorating RM performance. We investigated sociodemographic, clinical and neuropsychological factors associated with TP performance in schizophrenia., Methods: Sixty-six participants with schizophrenia completed a semantically rich and a relational-binding dependent version of the TP task and reported on their task awareness and strategy use., Results: Twenty-six participants failed to learn the task rules after extensive training. Learners had superior verbal, visual and working memory, executive functions and overall cognitive functioning compared to non-learners. Learners also had superior awareness of task rules and pairs relationships and used elaborated cognitive strategies more often., Conclusions: Our results support previous findings that some individuals with schizophrenia show RM impairment even with extensive TP training. We shed light on neuropsychological and metacognitive factors associated with TP performance. This knowledge could enhance interventions targeted to improve relational memory in schizophrenia when extensive training fails.

Scene construction is a key component of memory recall, navigation, and future imagining, and relies on the medial temporal lobes (MTL). A parallel body of work suggests that eye movements may enable the imagination and construction of scenes, even in the absence of external visual input. There are vast structural and functional connections between regions of the MTL and those of the oculomotor system. However, the directionality of connections between the MTL and oculomotor control regions, and how it relates to scene construction, has not been studied directly in human neuroimaging. In the current study, we used dynamic causal modeling (DCM) to interrogate effective connectivity between the MTL and oculomotor regions using a scene construction task in which participants' eye movements were either restricted (fixed-viewing) or unrestricted (free-viewing). By omitting external visual input, and by contrasting free- versus fixed- viewing, the directionality of neural connectivity during scene construction could be determined. As opposed to when eye movements were restricted, allowing free-viewing during construction of scenes strengthened top-down connections from the MTL to the frontal eye fields, and to lower-level cortical visual processing regions, suppressed bottom-up connections along the visual stream, and enhanced vividness of the constructed scenes. Taken together, these findings provide novel, non-invasive evidence for the underlying, directional, connectivity between the MTL memory system and oculomotor system associated with constructing vivid mental representations of scenes., Competing Interests: Declaration of Competing Interest The authors declare no competing financial interest., (Copyright © 2022. Published by Elsevier Inc.)

Fear generalization is a conserved survival mechanism that can become maladaptive in the face of traumatic situations, a feature central to certain anxiety disorders including posttraumatic stress disorder (PTSD). However, the neural circuitry and molecular mechanisms underlying fear generalization remain unclear. Recent studies have shown that prophylactic treatment with (R,S)-ketamine confers protective effects in stress-induced depressive behaviors and enhances contextual fear discrimination, but the extent to which these effects extend to fear generalization after auditory fear conditioning remains unclear. Here, we build on this work by using a behavioral model of fear generalization in mice involving foot shocks with differential intensity levels during auditory fear conditioning. We find that prophylactic (R,S)-ketamine treatment exerts protective effects that results in enhanced fear discrimination in wild type mice. As the growth factor, brain-derived neurotrophic factor (BDNF), has been shown to mediate the rapid antidepressant actions of (R,S)-ketamine, we used a loss-of-function BDNF mouse line (BDNF Val66Met) to determine whether BDNF is involved in (R,S)-ketamine's prophylactic effects on fear generalization. We found that BDNF Val66Met mice were resistant to the protective effects of prophylactic (R,S)-ketamine administration on fear generalization and extinction. We then used fiber photometry to parse out underlying neural activity and found that in the ventral hippocampus there were significant fear generalization-dependent patterns of activity for wild type and BDNF Val66Met mice that were altered by prophylactic (R,S)-ketamine treatment. Overall, these findings indicate a role for the ventral hippocampus and BDNF signaling in modulating the mitigating effects of prophylactic (R,S)-ketamine treatment on generalized fear., (© 2022. The Author(s).)

Mounting evidence linking gaze reinstatement-the recapitulation of encoding-related gaze patterns during retrieval-to behavioral measures of memory suggests that eye movements play an important role in mnemonic processing. Yet, the nature of the gaze scanpath, including its informational content and neural correlates, has remained in question. In this study, we examined eye movement and neural data from a recognition memory task to further elucidate the behavioral and neural bases of functional gaze reinstatement. Consistent with previous work, gaze reinstatement during retrieval of freely viewed scene images was greater than chance and predictive of recognition memory performance. Gaze reinstatement was also associated with viewing of informationally salient image regions at encoding, suggesting that scanpaths may encode and contain high-level scene content. At the brain level, gaze reinstatement was predicted by encoding-related activity in the occipital pole and BG, neural regions associated with visual processing and oculomotor control. Finally, cross-voxel brain pattern similarity analysis revealed overlapping subsequent memory and subsequent gaze reinstatement modulation effects in the parahippocampal place area and hippocampus, in addition to the occipital pole and BG. Together, these findings suggest that encoding-related activity in brain regions associated with scene processing, oculomotor control, and memory supports the formation, and subsequent recapitulation, of functional scanpaths. More broadly, these findings lend support to Scanpath Theory's assertion that eye movements both encode, and are themselves embedded in, mnemonic representations., (© 2021 Massachusetts Institute of Technology.)

The hippocampus (HPC), and the dentate gyrus (DG) subregion in particular, is purported to be a pattern separator, orthogonally representing similar information so that distinct memories may be formed. The HPC may also be involved in complex perceptual discrimination. It is unclear if this role is limited to spatial/scene stimuli or extends to the discrimination of objects. Also unclear is whether the DG itself contributes to pattern separation beyond memory. BL, an individual with bilateral DG lesions, was previously shown to have poor discrimination of similar, everyday objects in memory. Here, we demonstrate that BL's deficit extends to complex perceptual discrimination of novel objects. Specifically, BL was presented with closely matched possible and impossible objects, which give rise to fundamentally different 3D perceptual representations despite being visually similar. BL performed significantly worse than controls when asked to select an odd object (e.g., impossible) amongst three identical counterpart objects (e.g., possible) presented at different rotations. His deficit was also evident in an atypical eye fixation pattern during this task. In contrast, BL's performance was indistinguishable from that of controls on other tasks involving the same objects, indicating that he could visually differentiate the object pairs, that he perceived the objects holistically in 3D, and that he has only a mild weakness in categorizing object possibility. Furthermore, his performance on standardized neuropsychological measures indicated intact mental rotation, visual-spatial attention, and working memory (visual and auditory). Collectively, these results provide evidence that the DG is necessary for complex perceptual discrimination of novel objects, indicating that the DG might function as a generic pattern separator of a wide range of stimuli within high-level perception, and that its role is not limited to memory., (Crown Copyright © 2022. Published by Elsevier Ltd. All rights reserved.)

Emerging evidence suggests transcranial direct current stimulation (tDCS) can improve cognitive performance in older adults. Similarly, music listening may improve arousal and stimulate subsequent performance on memory-related tasks. We examined the synergistic effects of tDCS paired with music listening on auditory neurobehavioral measures to investigate causal evidence of short-term plasticity in speech processing among older adults. In a randomized sham-controlled crossover study, we measured how combined anodal tDCS over dorsolateral prefrontal cortex (DLPFC) paired with listening to autobiographically salient music alters neural speech processing in older adults compared to either music listening (sham stimulation) or tDCS alone. EEG assays included both frequency-following responses (FFRs) and auditory event-related potentials (ERPs) to trace neuromodulation-related changes at brainstem and cortical levels. Relative to music without tDCS (sham), we found tDCS alone (without music) modulates the early cortical neural encoding of speech in the time frame of ∼100-150 ms. Whereas tDCS by itself appeared to largely produce suppressive effects (i.e., reducing ERP amplitude), concurrent music with tDCS restored responses to those of the music+sham levels. However, the interpretation of this effect is somewhat ambiguous as this neural modulation could be attributable to a true effect of tDCS or presence/absence music. Still, the combined benefit of tDCS+music (above tDCS alone) was correlated with listeners' education level suggesting the benefit of neurostimulation paired with music might depend on listener demographics. tDCS changes in speech-FFRs were not observed with DLPFC stimulation. Improvements in working memory pre to post session were also associated with better speech-in-noise listening skills. Our findings provide new causal evidence that combined tDCS+music relative to tDCS-alone (i) modulates the early (100-150 ms) cortical encoding of speech and (ii) improves working memory, a cognitive skill which may indirectly bolster noise-degraded speech perception in older listeners., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Bidelman, Chow, Noly-Gandon, Ryan, Bell, Rizzi and Alain.)

The influence of prior knowledge on memory is ubiquitous, making the specific mechanisms of this relationship difficult to disentangle. Here, we show that expert knowledge produces a fundamental shift in the way that interitem similarity (i.e., the perceived resemblance between items in a set) biases episodic recognition. Within a group of expert birdwatchers and matched controls, we characterized the psychological similarity space for a set of well-known local species and a set of less familiar, nonlocal species. In experts, interitem similarity was influenced most strongly by taxonomic features, whereas in controls, similarity judgments reflected bird color. In controls, perceived episodic oldness during a recognition memory task increased along with measures of global similarity between items, consistent with classic models of episodic recognition. Surprisingly, for experts, high global similarity did not drive oldness signals. Instead, for local birds memory tracked the availability of species-level name knowledge, whereas for nonlocal birds, it was mediated by the organization of generalized conceptual space. These findings demonstrate that episodic memory in experts can benefit from detailed subcategory knowledge, or, lacking that, from the overall relational structure of concepts. Expertise reshapes psychological similarity space, helping to resolve mnemonic separation challenges arising from high interitem overlap. Thus, even in the absence of knowledge about item-specific details or labels, the presence of generalized knowledge appears to support episodic recognition in domains of expertise by altering the typical relationship between psychological similarity and memory.

The use of multi-modal approaches, particularly in conjunction with multivariate analytic techniques, can enrich models of cognition, brain function, and how they change with age. Recently, multivariate approaches have been applied to the study of eye movements in a manner akin to that of neural activity (i.e., pattern similarity ). Here, we review the literature regarding multi-modal and/or multivariate approaches, with specific reference to the use of eyetracking to characterize age-related changes in memory. By applying multi-modal and multivariate approaches to the study of aging, research has shown that aging is characterized by moment-to-moment alterations in the amount and pattern of visual exploration, and by extension, alterations in the activity and function of the hippocampus and broader medial temporal lobe (MTL). These methodological advances suggest that age-related declines in the integrity of the memory system has consequences for oculomotor behavior in the moment, in a reciprocal fashion. Age-related changes in hippocampal and MTL structure and function may lead to an increase in, and change in the patterns of, visual exploration in an effort to upregulate the encoding of information. However, such visual exploration patterns may be non-optimal and actually reduce the amount and/or type of incoming information that is bound into a lasting memory representation. This research indicates that age-related cognitive impairments are considerably broader in scope than previously realized.

In memory, representations of spatial features are stored in different reference frames; features relative to our position are stored egocentrically and features relative to each other are stored allocentrically. Accessing these representations engages many cognitive and neural resources, and so is susceptible to age-related breakdown. Yet, recent findings on the heterogeneity of cognitive function and spatial ability in healthy older adults suggest that aging may not uniformly impact the flexible use of spatial representations. These factors have yet to be explored in a precisely controlled task that explicitly manipulates spatial frames of reference across learning and retrieval. We used a lab-based virtual reality task to investigate the relationship between object-location memory across frames of reference, cognitive status, and self-reported spatial ability. Memory error was measured using Euclidean distance from studied object locations to participants' responses at testing. Older adults recalled object locations less accurately when they switched between frames of reference from learning to testing, compared with when they remained in the same frame of reference. They also showed an allocentric learning advantage, producing less error when switching from an allocentric to an egocentric frame of reference, compared with the reverse direction of switching. Higher MoCA scores and better self-assessed spatial ability predicted less memory error, especially when learning occurred egocentrically. We suggest that egocentric learning deficits are driven by difficulty in binding multiple viewpoints into a coherent representation. Finally, we highlight the heterogeneity of spatial memory performance in healthy older adults as a potential cognitive marker for neurodegeneration, beyond normal aging.

Introduction: Relational memory (RM) is severely impaired in schizophrenia. Unitisation can circumvent RM impairments in clinical populations as measured by the transverse-patterning (TP) task, a well-established measure of RM capacity. We compared memory performance on a new ecological RM measure, the Relational Trip Task (RTT), to that of TP at baseline and examined the effects of a unitisation intervention in RTT performance. RTT involves learning relational information of real-life stimuli, such as the relationship between people and places or objects., Methods: TP and RTT performances were examined in 45 individuals with schizophrenia. TP-impaired participants ( n  = 22) were randomised to either the intervention or an active control group. TP and RTT were administered again after unitisation training. Task validity and reliability were assessed. Intervention group's pre- and post-RTT accuracies were compared and contrasted to that in the control group., Results: RTT and TP were moderately correlated. TP non-learners had inferior performance in RTT at baseline. Improvement in RTT performance after unitisation training was observed in the intervention group; no pre-post improvement was observed in the control group., Conclusion: RTT has an acceptable criterion validity and excellent alternate-form reliability. Unitisation seemed to be successfully generalized to support associations of real-life stimuli.

Older adults often mistake new information as 'old', yet the mechanisms underlying this response bias remain unclear. Typically, false alarms by older adults are thought to reflect pattern completion - the retrieval of a previously encoded stimulus in response to partial input. However, other work suggests that age-related retrieval errors can be accounted for by deficient encoding processes. In the present study, we used eye movement monitoring to quantify age-related changes in behavioral pattern completion as a function of eye movements during both encoding and partially cued retrieval. Consistent with an age-related encoding deficit, older adults executed more gaze fixations and more similar eye movements across repeated image presentations than younger adults, and such effects were predictive of subsequent recognition memory. Analysis of eye movements at retrieval further indicated that in response to partial lure cues, older adults reactivated the similar studied image, indexed by the similarity between encoding and retrieval gaze patterns, and did so more than younger adults. Critically, reactivation of encoded image content via eye movements was associated with lure false alarms in older adults, providing direct evidence for a pattern completion bias. Together, these findings suggest that age-related changes in both encoding and retrieval processes, indexed by eye movements, underlie older adults' increased vulnerability to memory errors., (Copyright © 2021 Elsevier B.V. All rights reserved.)

The ventromedial prefrontal cortex (vmPFC) is involved in diverse cognitive operations, from inhibitory control to processing of semantic schemas. When accompanied by damage to the basal forebrain, vmPFC lesions can also impair relational memory, the ability to form and recall relations among items. Impairments in establishing direct relations among items (e.g., A is related to B, B is related to C) can also hinder the transitive processing of indirect relationships (e.g., inferring that A and C are related through direct relations that each contain B). Past work has found that transitive inference improves when the direct relations are organized within an existing knowledge structure, or schema. This type of semantic support is most effective for individuals whose relational memory deficits are mild (e.g., healthy age-related decline) rather than pronounced (e.g., hippocampal amnesia, amnestic mild cognitive impairment). Given that vmPFC damage can produce both relational memory and schema processing deficits, such damage may pose a particular challenge in establishing the type of relational structure required for transitive inference, even when supported by preexisting knowledge. To examine this idea, we tested individuals with lesions to the mPFC on multiple conditions that varied in pre-experimental semantic support and explored the extent to which they could identify both previously studied (direct) and novel transitive (indirect) relations. Most of the mPFC cases showed marked transitive inference deficits and even showed impaired knowledge of preexisting, direct, semantic relations, consistent with disruptions to schema-related processes. However, one case with more dorsal mPFC damage showed preserved ability to identify direct relations and make novel inferences, particularly when pre-experimental knowledge could be used to support performance. These results suggest that damage to the mPFC and basal forebrain can impede establishment of ad hoc relational schemas upon which transitive inference is based, but that appealing to prior knowledge may still be useful for those neurological cases that have some degree of preserved relational memory., (© 2021 Massachusetts Institute of Technology.)

Listening to autobiographically-salient music (i.e., music evoking personal memories from the past), and transcranial direct current stimulation (tDCS) have each been suggested to temporarily improve older adults' subsequent performance on memory tasks. Limited research has investigated the effects of combining both tDCS and music listening together on cognition. The present study examined whether anodal tDCS stimulation over the left dorsolateral prefrontal cortex (2 mA, 20 min) with concurrent listening to autobiographically-salient music amplified subsequent changes in working memory and recognition memory in older adults than either tDCS or music listening alone. In a randomized sham-controlled crossover study, 14 healthy older adults (64-81 years) participated in three neurostimulation conditions: tDCS with music listening (tDCS + Music), tDCS in silence (tDCS-only), or sham-tDCS with music listening (Sham + Music), each separated by at least a week. Working memory was assessed pre- and post-stimulation using a digit span task, and recognition memory was assessed post-stimulation using an auditory word recognition task (WRT) during which electroencephalography (EEG) was recorded. Performance on the backwards digit span showed improvement in tDCS + Music, but not in tDCS-only or Sham + Music conditions. Although no differences in behavioural performance were observed in the auditory WRT, changes in neural correlates underlying recognition memory were observed following tDCS + Music compared to Sham + Music. Findings suggest listening to autobiographically-salient music may amplify the effects of tDCS for working memory, and highlight the potential utility of neurostimulation combined with personalized music to improve cognitive performance in the aging population.

Chlamydiae are obligate intracellular pathogens that rely on secreted effector proteins to establish their intracellular niche. In this issue of the Journal of Bacteriology , Yanatori et al describe a screen for C. pneumoniae effectors, performed in C. trachomatis , which identified several new proteins that are translocated during infection (Yanatori, Miura et al. 2021). More broadly, they demonstrate how new genetic approaches in C. trachomatis can be used to characterize the virulence factors of other Chlamydia species., (Copyright © 2021 American Society for Microbiology.)

Background: Cirrhosis develops in <10% of individuals homozygous for the C282Y variant in the homeostatic iron regulator (HFE) gene. Carriage of PCSK7:rs236918 is associated with an increased risk of cirrhosis in this population., Aim: To determine if genetic variants significantly associated with the risk of alcohol- and NAFLD-related cirrhosis also modulate the cirrhosis risk in C282Y homozygotes., Methods: Variants in PCSK7, PNPLA3, TM6SF2, MBOAT7 and HSD17B13 were genotyped in 1319 C282Y homozygotes, from six European countries, of whom 171 (13.0%) had cirrhosis. Genotypic and allelic associations with the risk for developing cirrhosis were assessed, adjusting for age and sex. Fixed effects meta-analyses of the adjusted summary data for each country were performed. Post hoc association testing was undertaken in the 131 (76.6%) cases and 299 (26.0%) controls with available liver histology., Results: Significant associations were observed between PCSK7:rs236918 (OR = 1.52 [95% CI 1.06-2.19]; P = 0.022; I 2  = 0%); PNPLA3:rs738409 (OR = 1.60 [95% CI 1.22-2.11]; P = 7.37 × 10 -4 ; I 2  = 45.5%) and TM6SF2:rs58542926 (OR = 1.94 [95% CI 1.28-2.95]; P = 1.86 × 10 -3 ; I 2  = 0%) and the cirrhosis risk in C282Y homozygotes. These findings remained significant in the subpopulation with available liver histology. The population-attributable fractions were 5.6% for PCSK7:rs236918, 13.8% for PNPLA3:rs738409, 6.5% for TM6SF2:rs58542926 and 24.0% for carriage of all three variants combined., Conclusions: The risk of cirrhosis associated with carriage of PCSK7:rs236918 was confirmed in this much larger population of C282Y homozygotes. In addition, PNPLA3:rs738409 and TM6SF2:rs58542926 were established as significant additional risk factors. More detailed genetic testing of C282Y homozygotes would allow risk stratification and help guide future management., (© 2021 John Wiley & Sons Ltd.)

There are marked individual differences in the recollection of personal past events or autobiographical memory (AM). Theory concerning the relationship between mnemonic and visual systems suggests that eye movements promote retrieval of spatiotemporal details from memory, yet assessment of this prediction within naturalistic AM has been limited. We examined the relationship of eye movements to free recall of naturalistic AM and how this relationship is modulated by individual differences in AM capacity. Participants freely recalled past episodes while viewing a blank screen under free and fixed viewing conditions. Memory performance was quantified with the Autobiographical Interview, which separates internal (episodic) and external (non-episodic) details. In Study 1, as a proof of concept, fixation rate was predictive of the number of internal (but not external) details recalled across both free and fixed viewing. In Study 2, using an experimenter-controlled staged event (a museum-style tour) the effect of fixations on free recall of internal (but not external) details was again observed. In this second study, however, the fixation-recall relationship was modulated by individual differences in autobiographical memory, such that the coupling between fixations and internal details was greater for those endorsing higher than lower episodic AM. These results suggest that those with congenitally strong AM rely on the visual system to produce episodic details, whereas those with lower AM retrieve such details via other mechanisms., (Copyright © 2020 Elsevier B.V. All rights reserved.)