Health literacy and cumulative social disadvantage are associated with survival and transplant in patients with hepatocellular carcinoma: a prospective study.

OBJECTIVE: To investigate how individual social determinants of health (SDOH) and cumulative social disadvantage (CSD) affect survival and receipt of liver transplant (LT) in patients with hepatocellular carcinoma (HCC). METHODS: We enrolled 139 adult patients from two Indianapolis hospital systems between June 2019 and April 2022. Structured questionnaires collected SDOH and social risk factor data. We compared SDOH and CSD by race, gender and disease aetiology, assigning one point per adverse SDOH. Multivariable competing risk survival analysis assessed associations between SDOH, CSD, survival and LT receipt. RESULTS: Black patients experienced higher CSD than white patients in the cohort (5.4±2.5 vs 3.2±2.1, p<0.001). Black patients were significantly more likely to have household incomes

Weight Loss with an AI-Powered Digital Platform for Lifestyle Intervention.

BACKGROUND: Lifestyle intervention remains the cornerstone of weight loss programs in addition to pharmacological or surgical therapies. Artificial intelligence (AI) and other digital technologies can offer individualized approaches to lifestyle intervention to enable people with obesity to reach successful weight loss. METHODS: SureMediks, a digital lifestyle intervention platform using AI, was tested by 391 participants (58% women) with a broad range of BMI (20-78 kg/m2), with the aim of losing weight over 24 weeks in a multinational field trial. SureMediks consists of a mobile app, an Internet-connected scale, and a discipline of artificial intelligence called Expert system to provide individualized guidance and weight-loss management. RESULTS: All participants lost body weight (average 14%, range 4-22%). Almost all (98.7%) participants lost at least 5% of body weight, 75% lost at least 10%, 43% at least 15%, and 9% at least 20%, suggesting that this AI-powered lifestyle intervention was also effective in reducing the burden of obesity co-morbidities. Weight loss was partially positively correlated with female sex, accountability circle size, and participation in challenges, while it was negatively correlated with sub-goal reassignment. The latter three variables are specific features of the SureMediks weight loss program. CONCLUSION: An AI-assisted lifestyle intervention allowed people with different body sizes to lose 14% body weight on average, with 99% of them losing more than 5%, over 24 weeks. These results show that digital technologies and AI might provide a successful means to lose weight, before, during, and after pharmacological or surgical therapies.

Acute MK-801 increases measures of both sign-tracking and goal-tracking in male Sprague-Dawley rats.

Sign-tracking is a Pavlovian conditioned approach behavior thought to be important in understanding cue-driven relapse to drug use, and strategies for reducing sign-tracking may have some benefit in preventing relapse. A previous study successfully employed the NMDA receptor antagonist MK-801 in preventing the development of sign-tracking (but not goal-tracking) in a conditioned approach task. In this study, we focused on whether MK-801 would have similar effects on previously established sign-tracking behavior. MK-801 was administered after training in a standard sign-/goal-tracking task using a retractable lever as a conditioned stimulus and a sucrose pellet as unconditioned stimulus. It was found that MK-801 increased measures of both sign- and goal-tracking in subjects who had previously learned the task. The NMDA receptor appears to play a complex role in governing behavior related to sign-tracking.

Thirty-Day Readmissions Are Largely Not Preventable in Patients With Cirrhosis.

INTRODUCTION: Hospital readmissions are common in patients with cirrhosis, but there are few studies describing readmission preventability. We aimed to describe the incidence, causes, and risk factors for preventable readmission in this population. METHODS: We performed a prospective cohort study of patients with cirrhosis hospitalized at a single center between June 2014 and March 2020 and followed up for 30 days postdischarge. Demographic, clinical, and socioeconomic data, functional status, and quality of life were collected. Readmission preventability was independently and systematically adjudicated by 3 reviewers. Multinomial logistic regression was used to compare those with (i) preventable readmission, (ii) nonpreventable readmission/death, and (iii) no readmission. RESULTS: Of 654 patients, 246 (38%) were readmitted, and 29 (12%) were preventable readmissions. Reviewers agreed on preventability for 70% of readmissions. Twenty-two (including 2 with preventable readmission) died. The most common reasons for readmission were hepatic encephalopathy (22%), gastrointestinal bleeding (13%), acute kidney injury (13%), and ascites (6%), and these reasons were similar between preventable and nonpreventable readmissions. Preventable readmission was often related to paracentesis timeliness, diuretic adjustment monitoring, and hepatic encephalopathy treatment. Compared with nonreadmitted patients, preventable readmission was independently associated with racial and ethnic minoritized individuals (odds ratio [OR] 5.80; 95% CI, 1.96-17.13), nonmarried marital status (OR 2.88; 95% CI, 1.18-7.05), and admission in the prior 30 days (OR 3.45; 95% CI, 1.48-8.04). DISCUSSION: For patients with cirrhosis, readmission is common, but most are not preventable. Preventable readmissions are often related to ascites and hepatic encephalopathy and are associated with racial and ethnic minorities, nonmarried status, and prior admissions.

Effects of three serotonin reuptake inhibitors on sign-tracking in male Sprague-Dawley rats.

Sign-tracking is a behavior with relevance to cue-triggered relapse addiction, a Pavlovian conditioned approach behavior directed at the conditioned stimulus. The study examined one strategy for reducing the magnetic pull of drug-associated conditioned stimuli, using selective serotonin reuptake inhibitors (SSRIs) citalopram (0, 10, and 20 mg/kg), escitalopram (0, 10, and 20 mg/kg) and fluoxetine (0, 5, and 10 mg/kg). Male Sprague-Dawley rats were first trained in a standard sign-tracking task and then acutely administered these drugs in a series of three experiments. In each study, it was found that measures of sign-tracking were reduced, although effects on goal-tracking were different between drugs. This study provides evidence that administration of serotonergic antidepressants is effective in reducing sign-tracking and may have some efficacy in preventing cue-triggered relapse.

Cognitive dysfunction and increased phosphorylated tau are associated with reduced O-GlcNAc signaling in an aging mouse model of metabolic syndrome.

Metabolic syndrome (MetS), characterized by hyperglycemia, obesity, and hyperlipidemia, can increase the risk of developing late-onset dementia. Recent studies in patients and mouse models suggest a putative link between hyperphosphorylated tau, a component of Alzheimer's disease-related dementia (ADRD) pathology, and cerebral glucose hypometabolism. Impaired glucose metabolism reduces glucose flux through the hexosamine metabolic pathway triggering attenuated O-linked N-acetylglucosamine (O-GlcNAc) protein modification. The goal of the current study was to investigate the link between cognitive function, tau pathology, and O-GlcNAc signaling in an aging mouse model of MetS, agouti KKAy+/- . Male and female C57BL/6, non-agouti KKAy-/- , and agouti KKAy+/- mice were aged 12-18 months on standard chow diet. Body weight, blood glucose, total cholesterol, and triglyceride were measured to confirm the MetS phenotype. Cognition, sensorimotor function, and emotional reactivity were assessed for each genotype followed by plasma and brain tissue collection for biochemical and molecular analyses. Body weight, blood glucose, total cholesterol, and triglyceride levels were significantly elevated in agouti KKAy+/- mice versus C57BL/6 controls and non-agouti KKAy-/- . Behaviorally, agouti KKAy+/- revealed impairments in sensorimotor and cognitive function versus age-matched C57BL/6 and non-agouti KKAy-/- mice. Immunoblotting demonstrated increased phosphorylated tau accompanied with reduced O-GlcNAc protein expression in hippocampal-associated dorsal midbrain of female agouti KKAy+/- versus C57BL/6 control mice. Together, these data demonstrate that impaired cognitive function and AD-related pathology are associated with reduced O-GlcNAc signaling in aging MetS KKAy+/- mice. Overall, our study suggests that interaction of tau pathology with O-GlcNAc signaling may contribute to MetS-induced cognitive dysfunction in aging.

Quality of epilepsy care in a rural and deprived Scottish population.

INTRODUCTION: Epilepsy is among the commonest neurological disorders globally. Appropriate prescription and good adherence to anticonvulsants can achieve seizure freedom rates of 70%. Scotland is an affluent nation with free at point-of-access health care but there remain significant healthcare inequalities, particularly associated with deprivation. Anecdotally, epileptics in rural Ayrshire rarely engage with healthcare services. We describe the prevalence and management of epilepsy in a deprived and rural Scottish population. METHODS: Electronic records were used to obtain the following for patients with coded diagnoses of 'Epilepsy' or 'Seizures' within a general practice list of 3500 patients: demographics; diagnosis; seizure types; date and level (primary, secondary) of last review; last seizure date; anticonvulsant prescription; adherence; and any clinic discharge due to non-attendance. RESULTS: 92 patients were coded as above. 56 had a current diagnosis of epilepsy (prev 16.1/100,000). 69% had good adherence. 56% had good seizure control, with adherence associated with control. Of the 68% managed by primary care, 33% were uncontrolled and 13% had had an epilepsy review in the previous year. 45% of patients referred to secondary care were discharged for non-attendance. DISCUSSION: We demonstrate a high prevalence of epilepsy, low anticonvulsant adherence and sub-optimal rates of seizure freedom. These may be linked to poor attendance at specialist clinics. Management in primary care is challenging as evidenced by low review rates and high rates of ongoing seizures. We propose that the synergistic factors of uncontrolled epilepsy, deprivation and rurality make it difficult to attend clinics, with resultant health inequalities.

Effects of bupropion on sign- and goal-tracking in male Sprague Dawley rats.

Relapse into addiction is often triggered by cues that have a Pavlovian association with drugs and drug-taking. Sign-tracking involves approach of and interaction with Pavlovian conditioned signals for appetitive events (as opposed to goal-tracking, which involves approach of the site of the appetitive events themselves) and may be important in understanding cue-driven relapse. Bupropion is an atypical antidepressant and smoking cessation aid with effects on dopamine and norepinephrine that may have some utility in reducing sign-tracking. Male Sprague-Dawley rats were trained in a task where sign- and goal-tracking were possible and then administered doses of bupropion during a test phase. Bupropion decreased measures of sign-tracking and increased goal-tracking. This suggests that bupropion might be a useful adjunct medication for many kinds of behavioral disorders in which cue-driven behavior is problematic.

Embodied nonlinear dynamics of cognitive performance.

Study participants are typically unable to generate binary button-press sequences that pass as classically random sequences, such as from successive "fair coin" flips. Instead, their sequences repeat or alternate between responses too often. These deviations from randomness are commonly explained in terms of limitations or idiosyncrasies in cognitive processing. This article tests a novel hypothesis that randomness departures in participant-generated binary sequences are driven by coordination dynamics; alternating and repeating sequences are related to bimanual coordination attractors. Participants (N = 128) were asked to generate sequences that were representative of a random sequence, by successively pressing either of two buttons across 1,600 trials. Statistical analyses identify the binary button-press dynamics with a discrete sine-circle version of the Haken, Kelso, Bunz bimanual coordination model. Permutation analyses revealed the most common one- to five-trial subsequences were identified with the most dynamically stable coordinative relationships, consistent with bimanual coordination predictions. The sequences were consistent with scaling noises. Thus, participants' sequences departed from classical randomness by virtue of membership in a more inclusive category of variability that subsumes classical randomness. Recurrence quantification analysis revealed the mixture of stochasticity and determinism in the sequences was better approximated by the sine-circle model than by phase-randomized surrogate data sets that preserved both the power spectral densities and distributions of each participant's sequence. A relationship between randomness production and two-alternative forced-choice performance is established that constrains response time distribution models. The article's organization illustrates a nonreductive approach to inference for cognitive systems, inspired by statistical physics concepts such as renormalization group theory and universality. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Acute caffeine enhances sign-tracking in male Sprague-Dawley rats.

Sign-tracking, as a classically conditioned behavior, is of interest due to its relation to impulsivity and addiction. Caffeine affects the activity of neurotransmitters linked to sign-tracking such as dopamine and acetylcholine. As such, acute caffeine administration may enhance sign-tracking behavior. Caffeine was found to enhance measures of sign-tracking behavior in Sprague-Dawley rats in a sign/goal-tracking procedure. It is suggested that part of caffeine's effects on cognition may be due to its ability to enhance incentive salience in conditioned stimuli.

Successful rechallenge after clozapine-associated myocarditis.

Clozapine is a highly effective medication used in management of treatment-resistant schizophrenia. Clozapine-associated myocarditis (CAM) is a rare but increasingly recognised complication of clozapine titration. Following an episode of CAM, clinicians can face a challenging dilemma of balancing the risks of recurrent myocarditis against the harms of ongoing psychosis. We describe the case of a woman in her 60s who developed acute myocarditis during clozapine titration and was then cautiously rechallenged with a successful outcome.

Dextromethorphan reduces sign-tracking but not goal-tracking in male Sprague-Dawley rats.

Sign-tracking is a well-known phenomenon in appetitive Pavlovian conditioning in which subjects approach the site of a conditioned stimulus (CS) associated with an appetitive unconditioned stimulus (US) even when the two are located separately. Control of sign-tracking may be important in rehabilitation from drug dependence to help ward off relapse. Recent studies have found success in using ketamine to reduce sign-tracking. In this study, we employed a similar but unscheduled drug, dextromethorphan (DXM), which affects many of the same molecular targets as ketamine, in an attempt to reduce sign-tracking in a standard paradigm. DXM was found to reduce sign-tracking at the doses examined in this study, while goal-tracking (approaching the site of the US rather than CS) was relatively unaffected. DXM offers advantages over ketamine in terms of use with patients and may have some utility in rehabilitation.

Neighborhood poverty is associated with failure to be waitlisted and death during liver transplantation evaluation.

Liver transplantation (LT) is the final step in a complex care cascade. Little is known about how race, gender, rural versus urban residence, or neighborhood socioeconomic indicators impact a patient's likelihood of LT waitlisting or risk of death during LT evaluation. We performed a retrospective cohort study of adults referred for LT to the Indiana University Academic Medical Center from 2011 to 2018. Neighborhood socioeconomic status indicators were obtained by linking patients' addresses to their census tract defined in the 2017 American Community Survey. Descriptive statistics were used to describe completion of steps in the LT evaluation cascade. Multivariable analyses were performed to assess the factors associated with waitlisting and death during LT evaluation. There were 3454 patients referred for LT during the study period; 25.3% of those referred were waitlisted for LT. There was no difference seen in the proportion of patients from vulnerable populations who progressed to the steps of financial approval or evaluation start. There were differences in waitlisting by insurance type (22.6% of Medicaid vs. 34.3% of those who were privately insured; p < 0.01) and neighborhood poverty (quartile 1 29.6% vs. quartile 4 20.4%; p < 0.01). On multivariable analysis, neighborhood poverty was independently associated with waitlisting (odds ratio 0.56, 95% confidence interval [CI] 0.38-0.82) and death during LT evaluation (hazard ratio 1.49, 95% CI 1.09-2.09). Patients from high-poverty neighborhoods are at risk of failing to be waitlisted and death during LT evaluation.

Effects of two kinds of noradrenergic ADHD medicines on sign-tracking and goal-tracking in male rats.

Sign- and goal-tracking are behaviors seen in many species when a conditioned stimulus and it's corresponding unconditioned stimulus are presented at separate locations, and have been the focus of studies on appetitive conditioned and drug dependence. The neurochemical basis of sign-tracking is of interest for both studies of basic conditioning and addiction. In this work, I examined the role of norepinephrine by employing two noradrenergic drugs used for attention-deficit hyperactivity disorder (ADHD)-(a) atomoxetine, a norepinephrine reuptake blocker, and (b) guanfacine, an α2A-adrenergic receptor agonist. Sprague-Dawley rats were trained using a standard Pavlovian conditioning procedure with a retractable lever as conditioned stimulus and sucrose pellets as unconditioned stimulus. It was found that while atomoxetine reduced both sign- (both doses) and goal-tracking (only at the higher dose), guanfacine did not have any effect on either behavior. While norepinephrine reuptake blocking may be an effective strategy for reducing sign-tracking, manipulation of the α2A-adrenergic receptor appears less viable. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Farey Trees Explain Sequential Effects in Choice Response Time.

The latencies of successive two-alternative, forced-choice response times display intricately patterned sequential effects, or dependencies. They vary as a function of particular trial-histories, and in terms of the order and identity of previously presented stimuli and registered responses. This article tests a novel hypothesis that sequential effects are governed by dynamic principles, such as those entailed by a discrete sine-circle map adaptation of the Haken Kelso Bunz (HKB) bimanual coordination model. The model explained the sequential effects expressed in two classic sequential dependency data sets. It explained the rise of a repetition advantage, the acceleration of repeated affirmative responses, in tasks with faster paces. Likewise, the model successfully predicted an alternation advantage, the acceleration of interleaved affirmative and negative responses, when a task's pace slows and becomes more variable. Detailed analyses of five studies established oscillatory influences on sequential effects in the context of balanced and biased trial presentation rates, variable pacing, progressive and differential cognitive loads, and dyadic performance. Overall, the empirical patterns revealed lawful oscillatory constraints governing sequential effects in the time-course and accuracy of performance across a broad continuum of recognition and decision activities.

Oncologic indications of liver transplantation and deceased donor liver allocation in the United States.

PURPOSE OF REVIEW: Liver transplantation is a standard therapy for certain liver cancers. The majority of liver transplantation in the United States is through deceased donor liver transplantation (DDLT). A significant disparity between the demand of livers and patients awaiting liver transplantation still remains, relying on United Network for Organ Sharing (UNOS) to make policies to determine priority amongst recipients, including for patients with liver cancer. We review the scope of liver transplantation in patients with liver cancer with a focus on hepatocellular carcinoma (HCC), intrahepatic cholangiocarcinoma (iCCA), and unresectable colorectal liver metastases (CRLM) with respect to current liver allocation policy. RECENT FINDINGS: Recently, liver allocation changed in the United States. Under the current allocation policy, select patients with HCC and hilar CCA (hCCA) receive priority with an exception score of median MELD score at transplant (MMAT)-3. There is scope for other liver cancers, such as iCCA and CRLM to be considered, as reasonable outcomes have been achieved in these patients outside of the United States through DDLT and living donor liver transplantation (LDLT). SUMMARY: With the growing experience of liver transplantation for nonconventional oncologic indications, the current policy for prioritization of liver cancer within deceased donor liver allocation may need to be re-evaluated.

Early learning differences between intra- and interpersonal interlimb coordination.

Intrinsic coordination patterns exist between limbs such that 1) coordination at these states is inherently stable, 2) any other pattern requires learning to produce, and 3) this learning is subject to interference from a systemic bias towards intrinsic patterns. The dynamics that govern intrapersonal interlimb coordination also govern interpersonal coordination. However, intrapersonal coordination exhibits greater coupling strength and thus more stable intrinsic dynamics than interpersonal coordination. Because the strength of intrinsic coordination tendencies has consequences for learning coordination patterns, the differences in coupling strength between intra- and interpersonal coordination should impact the ability to perform new coordination patterns via greater or less interference from intrinsic dynamics. This was investigated by measuring participants' performance as they learned a new coordination pattern alone (intrapersonal) or in pairs (interpersonal). Participants were implicitly tasked with learning the pattern as they separately controlled the vertical and horizontal position of an on-screen cursor to trace a circling target. We observed better performance of dyads on first trial and steeper learning trajectories for individuals. Overall, these results indicate that individuals experienced greater interference from stronger intrinsic coordination dynamics during early learning but could overcome this interference and achieve similar performance to that of dyads with very little practice.