Gut Microbiota to Microglia: Microbiome Influences Neurodevelopment in the CNS.

The brain is traditionally viewed as an immunologically privileged site; however, there are known to be multiple resident immune cells that influence the CNS environment and are reactive to extra-CNS signaling. Microglia are an important component of this system, which influences early neurodevelopment in addition to modulating inflammation and regenerative responses to injury and infection. Microglia are influenced by gut microbiome-derived metabolites, both as part of their normal function and potentially in pathological patterns that may induce neurodevelopmental disabilities or behavioral changes.

The impact of national income and vaccine hesitancy on country-level COVID-19 vaccine uptake.

Background: The rapid development and rollout of COVID-19 vaccines helped reduce the pandemic's mortality burden. The vaccine rollout, however, has been uneven; it is well known that vaccination rates tend to be lower in lower income countries. Vaccine uptake, however, ultimately depends on the willingness of individuals to get vaccinated.

Gut Microbiota Modulation of Short Bowel Syndrome and the Gut-Brain Axis.

Short bowel syndrome (SBS) is a condition that results from a reduction in the length of the intestine or its functional capacity. SBS patients can have significant side effects and complications, the etiology of which remains ill-defined. Thus, facilitating intestinal adaptation in SBS remains a major research focus.

An Cell-Based Delivery Platform for Zinc Finger Artificial Transcription Factors in Pre-clinical Animal Models.

Zinc finger (ZF), transcription activator-like effectors (TALE), and CRISPR/Cas9 therapies to regulate gene expression are becoming viable strategies to treat genetic disorders, although effective delivery systems for these proteins remain a major translational hurdle. We describe the use of a mesenchymal stem/stromal cell (MSC)-based delivery system for the secretion of a ZF protein (ZF-MSC) in transgenic mouse models and young rhesus monkeys. Secreted ZF protein from mouse ZF-MSC was detectable within the hippocampus 1 week following intracranial or cisterna magna (CM) injection.

The iNs and Outs of Direct Reprogramming to Induced Neurons.

Understanding of cell-type specific transcription factors has promoted progress in methods for cellular reprogramming, such as directly reprogramming somatic cells to induced neurons (iN). Methods for direct reprogramming require neuronal-fate determining gene activation via neuron-specific microRNAs, chemical modulation of key neuronal signaling pathways or overexpression via viral vectors, with some reprogramming strategies requiring a combination of these methods to induce the neuronal-cell fate. These methods have been employed in a multitude of cell types, including fibroblasts, hepatocytes, peripheral blood mononuclear, and T cells.

Deletion of a non-canonical regulatory sequence causes loss of Scn1a expression and epileptic phenotypes in mice.

Background: Genes with multiple co-active promoters appear common in brain, yet little is known about functional requirements for these potentially redundant genomic regulatory elements. SCN1A, which encodes the Na1.1 sodium channel alpha subunit, is one such gene with two co-active promoters.

Artificial escape from XCI by DNA methylation editing of the CDKL5 gene.

A significant number of X-linked genes escape from X chromosome inactivation and are associated with a distinct epigenetic signature. One epigenetic modification that strongly correlates with X-escape is reduced DNA methylation in promoter regions. Here, we created an artificial escape by editing DNA methylation on the promoter of CDKL5, a gene causative for an infantile epilepsy, from the silenced X-chromosomal allele in human neuronal-like cells.

Age-Related Improvements in Peak Cardiorespiratory Fitness among Coronary Heart Disease Patients Following Cardiac Rehabilitation.

While cardiorespiratory fitness (VO₂peak) can be improved with exercise and training, it is unclear whether older age is associated with an attenuated VO₂peak improvement among patients with coronary artery disease (CAD) who complete a cardiac rehabilitation (CR) program. A retrospective review of patient demographics and VO₂peak data from January 2012 to December 2017 was performed. CAD patients were included if they had successfully completed the supervised 6-month CR program (>75% of exercise prescription) and two VO₂peak assessments (respiratory exchange ratio (RER) >1.

Antipsychotic discontinuation after the initiation of selective serotonin reuptake inhibitors therapy for the treatment of behavioral and psychological symptoms associated with dementia.

Introduction: Antipsychotics are used off label to treat behavioral and psychological symptoms of dementia (BPSD). Due to the emerging data of selective serotonin reuptake inhibitors (SSRIs) for treatment of BPSD, clinicians may choose to use this medication class instead of antipsychotics when pharmacologic therapy is necessary. The objective of this study was to evaluate the prevalence of antipsychotic discontinuation 6 months after SSRI initiation for the treatment of BPSD.

Validity of the Center for Epidemiological Studies Depression scale in Type 2 diabetes.

Objective: Depressive symptoms are common among people with Type 2 diabetes mellitus (T2DM). This study aimed to validate the 3-factor structure of the 14-item Center for Epidemiological Studies Depression (CES-D) scale proposed by Carleton et al. (2013) in a T2DM population.

Mood and metabolism: Anhedonia as a clinical target in Type 2 diabetes.

Epidemiological evidence suggests a bidirectional relationship between depression and Type 2 diabetes mellitus. In Type 2 diabetes, depression affects behavioural factors such as diet and physical activity that promote positive energy balance and influence diabetes outcomes. Examinations of depressive symptoms by dimension have suggested that anhedonia, the inability to anticipate, seek, choose and enjoy reward, may be of particular clinical importance.