The objective of this Special Issue entitled 'Role of Probiotics and Prebiotics in Gut Symbiosis' is to publish reviews, clinical trials and experimental studies that focus on probiotics and ...prebiotics that have a role in influencing disease and promoting gastrointestinal and overall health ....
Carrier screening began 50 years ago with screening for conditions that have a high prevalence in defined racial/ethnic groups (e.g., Tay–Sachs disease in the Ashkenazi Jewish population; sickle cell ...disease in Black individuals). Cystic fibrosis was the first medical condition for which panethnic screening was recommended, followed by spinal muscular atrophy. Next-generation sequencing allows low cost and high throughput identification of sequence variants across many genes simultaneously. Since the phrase “expanded carrier screening” is nonspecific, there is a need to define carrier screening processes in a way that will allow equitable opportunity for patients to learn their reproductive risks using next-generation sequencing technology. An improved understanding of this risk allows patients to make informed reproductive decisions. Reproductive decision making is the established metric for clinical utility of population-based carrier screening. Furthermore, standardization of the screening approach will facilitate testing consistency. This practice resource reviews the current status of carrier screening, provides answers to some of the emerging questions, and recommends a consistent and equitable approach for offering carrier screening to all individuals during pregnancy or preconception.
More than a hundred de novo single gene mutations and copy‐number variants have been implicated in autism, each occurring in a small subset of cases. Mutant mouse models with syntenic mutations offer ...research tools to gain an understanding of the role of each gene in modulating biological and behavioral phenotypes relevant to autism. Knockout, knockin and transgenic mice incorporating risk gene mutations detected in autism spectrum disorder and comorbid neurodevelopmental disorders are now widely available. At present, autism spectrum disorder is diagnosed solely by behavioral criteria. We developed a constellation of mouse behavioral assays designed to maximize face validity to the types of social deficits and repetitive behaviors that are central to an autism diagnosis. Mouse behavioral assays for associated symptoms of autism, which include cognitive inflexibility, anxiety, hyperactivity, and unusual reactivity to sensory stimuli, are frequently included in the phenotypic analyses. Over the past 10 years, we and many other laboratories around the world have employed these and additional behavioral tests to phenotype a large number of mutant mouse models of autism. In this review, we highlight mouse models with mutations in genes that have been identified as risk genes for autism, which work through synaptic mechanisms and through the mTOR signaling pathway. Robust, replicated autism‐relevant behavioral outcomes in a genetic mouse model lend credence to a causal role for specific gene contributions and downstream biological mechanisms in the etiology of autism.
Review of behaviors in mouse models of autism with mutations in risk genes for synaptic and mTOR pathway proteins.
Commercially produced complete nutritional formulas (CFs) are commonly delivered to children requiring enteral nutrition via gastrostomy. However, a cultural shift toward consuming a more natural ...diet consisting of whole foods has caused the use of blenderized tube feeds (BTFs) to grow in popularity among parents and carers in recent years. There are advantages and disadvantages of both BTF and CF use. There is evidence that suggests that BTFs can significantly improve tube‐feeding tolerance and reduce gastrointestinal symptoms associated with tube feeding, such as gagging, retching, and constipation, thereby resulting in an improved quality of life (QoL) for enterally fed children and their caregivers. BTFs have also been implicated in increasing the diversity of the gut microbiota in enterally fed children. However, concerns have been raised that BTFs may be inferior to CFs in energy and nutrition sufficiency. Issues such as microbial contamination, tube blockages, and difficulties in preparation and administration may also complicate the use of BTFs. Additionally, like CFs, BTFs can vary significantly in nutrition composition, and dietitian involvement with BTF use is crucial. The current literature on the clinical outcomes of BTF use is limited, and further research is needed before recommendations can be made on BTF use in children. A literature review was conducted to compare clinical outcomes between BTFs and CFs and evaluate the feasibility of BTF use in children.
Blenderised tube feeds (BTF) have become a popular alternative to commercial formula (CF) for enterally fed children. This study sought to compare gastrointestinal (GI) symptoms, GI inflammation, and ...stool microbiome composition between children receiving BTF or CF. This prospective cohort study involved 41 gastrostomy-fed children, aged 2–18 years, receiving either BTF (n = 21) or CF (n = 20). The Paediatric Quality of Life Inventory Gastrointestinal Symptoms Scale (GI-PedsQL) was used to compare GI symptoms between the groups. Anthropometric data, nutritional intake, nutritional blood markers, faecal calprotectin levels, stool microbiota, and parental satisfaction with feeding regimen were also assessed. Caregivers of children on BTF reported greater GI-PedsQL scores indicating significantly fewer GI symptoms (74.7 vs. 50.125, p = 0.004). Faecal calprotectin levels were significantly lower for children receiving BTF compared to children on CF (33.3 mg/kg vs. 72.3 mg/kg, p = 0.043) and the BTF group had healthier, more diverse gut microbiota. Subgroup analysis found that 25% of caloric intake from BTF was sufficient to improve GI symptoms. The CF group had better body mass index (BMI) z-scores (−0.7 vs. 0.5, p = 0.040). Although growth was poorer in children receiving only BTF in comparison to the CF group, this was not seen in children receiving partial BTF. A combination of BTF and CF use may minimise symptoms of tube feeding whilst supporting growth.
•We examine the effects of nicotine on hippocampus-dependent learning through different stages of drug administration.•We examine how nicotine usurps the cellular mechanisms of synaptic ...plasticity.•We examine the physiological changes in the hippocampus that may contribute to nicotine withdrawal deficits in learning.•We examine the role of genetics and adolescence in the effects of nicotine on learning.
Addiction is a chronic disorder marked by long-lasting maladaptive changes in behavior and in reward system function. However, the factors that contribute to the behavioral and biological changes that occur with addiction are complex and go beyond reward. Addiction involves changes in cognitive control and the development of disruptive drug-stimuli associations that can drive behavior. A reason for the strong influence drugs of abuse can exert on cognition may be the striking overlap between the neurobiological substrates of addiction and of learning and memory, especially areas involved in declarative memory. Declarative memories are critically involved in the formation of autobiographical memories, and the ability of drugs of abuse to alter these memories could be particularly detrimental. A key structure in this memory system is the hippocampus, which is critically involved in binding multimodal stimuli together to form complex long-term memories. While all drugs of abuse can alter hippocampal function, this review focuses on nicotine. Addiction to tobacco products is insidious, with the majority of smokers wanting to quit; yet the majority of those that attempt to quit fail. Nicotine addiction is associated with the presence of drug-context and drug-cue associations that trigger drug seeking behavior and altered cognition during periods of abstinence, which contributes to relapse. This suggests that understanding the effects of nicotine on learning and memory will advance understanding and potentially facilitate treating nicotine addiction. The following sections examine: (1) how the effects of nicotine on hippocampus-dependent learning change as nicotine administration transitions from acute to chronic and then to withdrawal from chronic treatment and the potential impact of these changes on addiction, (2) how nicotine usurps the cellular mechanisms of synaptic plasticity, (3) the physiological changes in the hippocampus that may contribute to nicotine withdrawal deficits in learning, and (4) the role of genetics and developmental stage (i.e., adolescence) in these effects.
Crohn disease (CD) is a chronic inflammatory condition primarily affecting the gastro-intestinal tract and is characterized by reduced bacterial diversity. The exact cause of disease is unknown; ...however, evidence suggests that several components, including microbiota, may contribute to the underlying pathology and disease development. Perturbation of the host-microbe commensal relationship is considered the main driving force of tissue destruction and pathological changes seen in CD. Several putative bacterial pathogens including species from Mycobacterium, Campylobacter and Helicobacter are postulated in the aetiology of CD. However, to date, no strong evidence supports a single bacterium contributing overall to CD pathogenesis. Alternatively, dysbiosis or bacterial imbalance is more widely accepted as a leading factor in the disrupted host-immune system cross-talk resulting in subsequent intestinal inflammation. Depletion of symbiont microbes including Firmicutes, Bifidobacterium and Clostridia, in conjunction with an increase in pathobiont microbes from Bacteroidetes and Enterobacteria, is a striking feature observed in CD. No single factor has been identified as driving this dysbiosis, although diet, antibiotic exposure and possible early life events in presence of underlying genetic susceptibility may contribute. The aim of this review is to highlight the current accumulating literature on the proposed role of bacteria in the pathogenesis of CD.
Over the last two decades, knowledge on fecal biomarkers has substantially increased. Nowadays, these non-invasive markers of inflammation have significant clinical utility in the management of ...inflammatory bowel disease. Their use informs the decision to perform endoscopy before diagnosis is made right through to influencing therapeutic choices and the need for interval endoscopic assessment. In this review, the roles of two S100 proteins, calprotectin, and S100A12 are described along with that of lactoferrin, in the context of inflammatory bowel disease.
Mutant mouse models of neurodevelopmental disorders with intellectual disabilities provide useful translational research tools, especially in cases where robust cognitive deficits are reproducibly ...detected. However, motor, sensory and/or health issues consequent to the mutation may introduce artifacts that preclude testing in some standard cognitive assays. Touchscreen learning and memory tasks in small operant chambers have the potential to circumvent these confounds. Here we use touchscreen visual discrimination learning to evaluate performance in the maternally derived Ube3a mouse model of Angelman syndrome, the Ts65Dn trisomy mouse model of Down syndrome, and the Mecp2Bird mouse model of Rett syndrome. Significant deficits in acquisition of a 2‐choice visual discrimination task were detected in both Ube3a and Ts65Dn mice. Procedural control measures showed no genotype differences during pretraining phases or during acquisition. Mecp2 males did not survive long enough for touchscreen training, consistent with previous reports. Most Mecp2 females failed on pretraining criteria. Significant impairments on Morris water maze spatial learning were detected in both Ube3a and Ts65Dn, replicating previous findings. Abnormalities on rotarod in Ube3a, and on open field in Ts65Dn, replicating previous findings, may have contributed to the observed acquisition deficits and swim speed abnormalities during water maze performance. In contrast, these motor phenotypes do not appear to have affected touchscreen procedural abilities during pretraining or visual discrimination training. Our findings of slower touchscreen learning in 2 mouse models of neurodevelopmental disorders with intellectual disabilities indicate that operant tasks offer promising outcome measures for the preclinical discovery of effective pharmacological therapeutics.
The Ube3a mouse model of Angelman syndrome, in which the heterozygous mutation is maternally derived, displayed deficits on acquisition of a pairwise 2‐choice visual discrimination operant touchscreen task. A, Pretraining survival curve. Number of days to reach criterion indicated no gross differences in the rate of procedural learning. B, Visual discrimination survival curve indicated that Ube3a mutant mice required more days of training to reach the criterion of ≥80% correct, in learning the discrimination between the X image and the equal sign = image on the touchscreen, when compared with wildtype littermates (WT). C, WT and Ube3a required similar numbers of days to reach criterion on the pretraining phase, indicating similar procedural abilities. D, Ube3a required more days to reach criterion than WT on the visual discrimination task, indicating a slower learning curve. E, During pretraining, the number of trials to reach criterion (active screen touches per day, representing trials completed), was similar between WT and Ube3a. F, During visual discrimination learning, the number of trials to reach criterion (active screen touches) showed a trend for slower acquisition in Ube3a than WT. G, Response latencies during the last 2 training days indicated that physical movements were similar between genotypes, since a similar amount of time elapsed between image onset and selection of image choice. H, Latencies to reach the reinforcement magazine during the last 2 training days indicated that motivation for food reward was similar between genotypes, and corroborated generally normal motor function. Results indicate that Ube3a mice can learn the procedural components of an operant discrimination task, but episodic learning of specific image pairs was acquired more slowly by Ube3a than by WT. N = 9 WT, 10 Ube3a, *P < .05
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