Is Non-Alcoholic Fatty Liver Disease Connected with Cognition?: The Complex Interplay between Liver and Brain

The prevalence of non-alcoholic fatty liver disease (NAFLD) and its progressive form, non-alcoholic steatohepatitis (NASH), is increasing in parallel with the rising rates of obesity and type 2 diabetes. Approximately one in four adults are diagnosed with liver steatosis globally. NAFLD is associated with insulin resistance, hypertension, obesity, visceral adiposity, and dyslipidaemia. These risk factors are often accompanied by inflammation and oxidative stress, which also play a role in extrahepatic diseases, including conditions related to the central nervous system, such as mild cognitive impairment and Alzheimer’s disease. The number of people living with dementia is approximately 55 million and is estimated to increase to approximately 2 billion people by 2050. Recent studies have found that NAFLD is associated with poorer cognition. The aim of this review was to summarise the findings of hitherto studies that have linked NAFLD with cognition and dementia, as well as to discuss the potential liver–brain pathways

Exome Sequencing as a Diagnostic Tool for Pediatric-Onset Ataxia

Ataxia demonstrates substantial phenotypic and genetic heterogeneity. We set out to determine the diagnostic yield of exome sequencing in pediatric patients with ataxia without a molecular diagnosis after standard-of-care assessment in Canada. FORGE (Finding Of Rare disease GEnes) Canada is a nation-wide project focused on identifying novel disease genes for rare pediatric diseases using whole-exome sequencing. We retrospectively selected all FORGE Canada projects that included cerebellar ataxia as a feature. We identified 28 such families and a molecular diagnosis was made in 13; a success rate of 46%. In 11 families, we identified mutations in genes associated with known neurological syndromes and in two we identified novel disease genes. Exome analysis of sib pairs and/or patients born to consanguineous parents was more likely to be successful (9/13) than simplex cases (4/15). Our data suggest that exome sequencing is an effective first line test for pediatric patients with ataxia where a specific single gene is not immediately suspected to be causative. © 2013 The Authors. *Human Mutation published by Wiley Periodicals, Inc

Nutraceuticals as Potential Targets for the Development of a Functional Beverage for Improving Sleep Quality

Functional beverages can be a valuable component of the human diet with the ability to not only provide essential hydration but to deliver important bioactive compounds that can contribute to chronic disease treatment and prevention. One area of the functional beverage market that has seen an increase in demand in recent years are beverages that promote relaxation and sleep. Sleep is an essential biological process, with optimal sleep being defined as one of adequate duration, quality and timing. It is regulated by a number of neurotransmitters which are, in turn, regulated by dietary intake of essential bioactive compounds. This narrative review aimed to evaluate the latest evidence of the sleep promoting properties of a selection of bioactive compounds (such as L-theanine and L-tryptophan) for the development of a functional beverage to improve sleep quality; and the effectiveness of traditional sleep promoting beverages (such as milk and chamomile). Overall, the bioactive compounds identified in this review, play essential roles in the synthesis and regulation of important neurotransmitters involved in the sleep-wake cycle. There is also significant potential for their inclusion in a number of functional beverages as the main ingredient on their own or in combination. Future studies should consider dosage; interactions with the beverage matrix, medications and other nutraceuticals; bioavailability during storage and following ingestion; as well as the sensory profile of the developed beverages, among others, when determining their effectiveness in a functional beverage to improve sleep quality

The Effects of L-Theanine Supplementation on Quality of Sleep: A Systematic Review

Background/Objectives: Sleep disturbances are considered a major public health issue due to their negative impact on overall health and the economy. There is an increasing interest in plant bioactive compounds as natural alternatives to common pharmaceutical treatment options for improving sleep quality. The green tea amino acid, L-theanine (L-THE), has been shown to induce relaxation, reduce stress, anxiety, and depressive symptoms by influencing the several neurotransmitters associated with the sleep–wake cycle. Therefore, the aim of this systematic literature review was to evaluate the effects of L-THE consumption on sleep quality in humans. Methods: Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA 2020) guidelines, systematic literature searches were conducted in six electronic databases (PsycINFO, CINAHL, Web of Science, Medline, Scopus, and Cochrane Central Register of Controlled Trials). This systematic literature review was pre-registered with the international prospective register of systematic reviews PROSPERO (CRD42022304635). Results/Discussion: In total, eleven journal articles were identified that met the inclusion criteria where L-THE supplementation (alone or in combination with other bioactives) was compared to the supplementation of a placebo (or comparator) for the treatment of sleep disturbances. The duration of treatments varied from one day to eight weeks. The majority of the included studies were conducted in adults (n = 373) while two studies were completed in children (n = 107). Improvements in several sleep parameters were observed including sleep onset latency (7), total sleeping time (2), sleep duration (2), sleep efficiency (2), overall sleep quality (5), daytime dysfunction (2), early awakenings (1), morning sleepiness (3), the use of sleep medication (1), and sleep disturbances (4) (All p’s < 0.05). The findings indicate that L-THE (50–655 mg) may be effective at improving sleep quality either as an individual supplement or in combination with other bioactives. Furthermore, the treatment of sleep disturbances with L-THE at doses higher than 655 mg may not be beneficial and may be detrimental to overall sleep quality. Conclusion: The findings of this systematic literature review indicate promising effects on the use of L-THE in the management of sleep disturbances and highlight the need for further studies to determine if there is an optimal concentration of L-THE for improving sleep

β-cell genes and diabetes:quantitative and qualitative differences in the pathophysiology of hepatic nuclear factor-1α and glucokinase mutations

Mutations in the beta-cell genes encoding the glycolytic enzyme glucokinase (GCK) and the transcription factor hepatocyte nuclear factor (HNF)-1alpha are the most common causes of maturity-onset diabetes of the young (MODY). Studying patients with mutations in these genes gives insights into the functions of these two critical beta-cell genes in humans. We studied 178 U.K. and French MODY family members, including 45 GCK mutation carriers and 40 HNF-1alpha mutation carriers. Homeostasis model assessment of fasting insulin and glucose showed reduced beta-cell function in both GCK (48% controls, P<0.0001) and HNF-1alpha (42% controls, P<0.0001). Insulin sensitivity was similar to that of control subjects in the GCK subjects (93% controls, P = 0.78) but increased in the HNF-1alpha subjects (134.5% controls, P = 0.005). The GCK patients showed a similar phenotype between and within families with mild lifelong fasting hyperglycemia (fasting plasma glucose [FPG] 5.5-9.2 mmol/l, interquartile [IQ] range 6.6-7.4), which declined slightly with age (0.017 mmol/l per year) and rarely required pharmacological treatment (17% oral hypoglycemic agents, 4% insulin). HNF-1alpha patients showed far greater variation in fasting glucose both between and within families (FPG 4.1-18.5 mmol/l, IQ range 5.45-10.4), with a marked deterioration with age (0.06 mmol/l per year), and 59% of patients required treatment with tablets or insulin. Proinsulin-to-insulin ratios are increased in HNF-1alpha subjects (29.5%) but not in GCK (18.5%) subjects. In an oral glucose tolerance test, the 0- to 120-min glucose increment was small in GCK patients (2.4+/-1.8 mmol/l) but large in HNF-1alpha patients (8.5+/-3.0 mmol/l, P< 0.0001). This comparison shows that the clear clinical differences in these two genetic subgroups of diabetes reflect the quantitative and qualitative differences in beta-cell dysfunction. The defect in GCK is a stable defect of glucose sensing, whereas the HNF-1alpha mutation causes a progressive defect that alters beta-cell insulin secretion directly rather than the sensing of glucose

Comparative Performance of Latest-Generation and FDA-Cleared Serology Tests for the Diagnosis of Chagas Disease.

Confirmed diagnosis of chronic Chagas disease (CD) requires positive results by two different IgG serology tests. Variable sensitivity has been reported among tests and in different geographic regions. Inadequate specificity presents a particular challenge in low-prevalence settings such as the United States. This study provides a direct comparison of the latest-generation IgG serology assays with four previously assessed FDA-cleared tests. Seven hundred ten blood donor plasma specimens were evaluated by Wiener Lisado and Wiener v.4.0 enzyme-linked immunosorbent assays (ELISAs) and Abbott PRISM Chagas chemiluminescent assay (ChLIA). Sensitivity and specificity were assessed relative to infection status as determined by the original blood donation testing algorithm. All three latest-generation assays demonstrated 100% specificity (95% confidence interval [CI], 98.6 to 100.0). Wiener Lisado, Wiener v.4.0, and Abbott PRISM had sensitivities of 97.1% (95% CI, 95.1 to 98.4), 98.9% (95% CI, 97.4 to 99.6), and 95.5% (95% CI, 93.2 to 97.3), respectively. As with previously evaluated FDA-cleared tests, all three assays had the highest reactivity and sensitivity in samples from donors born in South America and lowest reactivity and sensitivity in specimens from those born in Mexico, with intermediate results in specimens from Central American donors. Wiener v.4.0 had the highest diagnostic sensitivity in all comparisons. Our findings suggest that the latest-generation CD serology tests could improve diagnostic sensitivity without affecting specificity

Nutrition and Healthy Ageing Trajectories in Retirement Living in the Australian Capital Territory: Study Protocol

OBJECTIVES: There are a growing number of people aged over 55 years living in retirement communities in Australia. These communities typically consist of accommodation, services and community facilities which cater to older people and the desire to maintain independence. The Nutrition and Healthy Ageing Trajectories in Retirement Living (NutriHAT-RL) study aims to investigate the nutrition and lifestyle-based behaviours which contribute to healthy ageing and the maintenance of social and physical functioning among older people living in retirement communities. METHODS: This study will recruit a total of 2,770 people aged 55 years or over living in retirement communities in the Australian Capital Territory and southern New South Wales regions of Australia for a four-year prospective longitudinal study commencing in March 2021. A range of measures, including nutritional intake, health and lifestyle behaviours, cognitive and psychological function, and physical health, will be completed on three occasions over a total of four years. Participants will complete a face-to-face comprehensive, validated food frequency questionnaire at each time point. Risk of malnutrition and nutritional behaviour (emotional appetite and intuitive eating) will also be evaluated. Multiple mental, social, and physical health domains will be assessed at each time point. This will include cognitive and mental health (depression, anxiety, and loneliness) screening, social and occupational functioning questionnaires, self-reported and observed physical function assessments, and sleep quality. Bitter taste endophenotype, salivary C-reactive protein, telomere length, and blood biomarkers associated with healthy ageing will also be evaluated. RESULTS: Ethics approval has been obtained through the University of Canberra Human Ethics Research Committee (UCHREC-2306). To reduce risk of COVID-19 transmissions, a risk mitigation plan has been developed. CONCLUSIONS: The NutriHAT-RL study will be the first Australian longitudinal study with a focus on nutrition and healthy ageing in people living in retirement communities. Findings from this study will contribute to understanding of nutrition and healthy ageing in this growing population and will inform policy and practice related to nutrition and ageing in place. FUNDING SOURCES: N/A