Reevaluating Biota Alteration: Reframing Environmental Influences on Chronic Immune Disorders and Exploring Novel Therapeutic Opportunities.

Environmental mismatches are defined as changes in the environment that induce public health crises. Well known mismatches leading to chronic disease include the availability of technologies that facilitate unhealthy diets and sedentary lifestyles, both factors that adversely affect cardiovascular health. This commentary puts these mismatches in context with biota alteration, an environmental mismatch involving hygiene-related technologies necessary for avoidance of infectious disease.

Reversal of mutation-induced transcriptional dysregulation and pathology in cultured human neurons by allele-specific excision.

Efforts to genetically reverse C9orf72 pathology have been hampered by our incomplete understanding of the regulation of this complex locus. We generated five different genomic excisions at the locus in a patient-derived induced pluripotent stem cell (iPSC) line and a non-diseased wild-type (WT) line (11 total isogenic lines), and examined gene expression and pathological hallmarks of C9 frontotemporal dementia/amyotrophic lateral sclerosis in motor neurons differentiated from these lines. Comparing the excisions in these isogenic series removed the confounding effects of different genomic backgrounds and allowed us to probe the effects of specific genomic changes.

The Perineuronal Net Protein Brevican Acts in Nucleus Accumbens Parvalbumin-Expressing Interneurons of Adult Mice to Regulate Excitatory Synaptic Inputs and Motivated Behaviors.

Background: Experience-dependent functional adaptation of nucleus accumbens (NAc) circuitry underlies the development and expression of reward-motivated behaviors. Parvalbumin-expressing GABAergic (gamma-aminobutyric acidergic) interneurons (PVINs) within the NAc are required for this process. Perineuronal nets (PNNs) are extracellular matrix structures enriched around PVINs that arise during development and have been proposed to mediate brain circuit stability.

COVID-19 morbidity in lower versus higher income populations underscores the need to restore lost biodiversity of eukaryotic symbionts.

The avoidance of infectious disease by widespread use of 'systems hygiene', defined by hygiene-enhancing technology such as sewage systems, water treatment facilities, and secure food storage containers, has led to a dramatic decrease in symbiotic helminths and protists in high-income human populations. Over a half-century of research has revealed that this 'biota alteration' leads to altered immune function and a propensity for chronic inflammatory diseases, including allergic, autoimmune and neuropsychiatric disorders. A recent Ethiopian study (EClinicalMedicine 39: 101054), validating predictions made by several laboratories, found that symbiotic helminths and protists were associated with a reduced risk of severe COVID-19 (adjusted odds ratio = 0.

Age-dependent cognitive impairment, hydrocephalus and leukocyte infiltration in transgenic mice with endothelial expression of human EPHX2.

Soluble epoxide hydrolase (sEH) is upregulated in microvascular endothelium of human brain with vascular cognitive impairment (VCI). Transgenic endothelial expression of human sEH in mice (Tie2hsEH) induces endothelial dysfunction (ED), a pathogenetic mechanism of VCI. We sought to determine if endothelial upregulation of sEH is sufficient to cause cognitive impairment, and if cognitive impairment due to chronic hypoperfusion induced by unilateral common carotid artery occlusion (CCAO) is exacerbated in Tie2hsEH mice.

The safety of pediatric use of paracetamol (acetaminophen): a narrative review of direct and indirect evidence.

Paracetamol (acetaminophen) use during pregnancy and early childhood was accepted as safe in the 1970s, but is now a subject of considerable concern. Careful analysis shows that initial acceptance of the drug was based on the false assumption that drug interactions in babies and adults are the same, and on a complete absence of knowledge regarding the impact of the drug on brain development. At least fourteen epidemiological studies now indicate that prenatal exposure to paracetamol is associated with neurodevelopmental problems.

Effects of Chronic Secondhand Smoke (SHS) Exposure on Cognitive Performance and Metabolic Pathways in the Hippocampus of Wild-Type and Human Tau Mice.

Background: Exposure to secondhand smoke (SHS) is a risk factor for developing sporadic forms of sporadic dementia. A human tau (htau) mouse model is available that exhibits age-dependent tau dysregulation, neurofibrillary tangles, neuronal loss, neuroinflammation, and oxidative stress starting at an early age (3-4 months) and in which tau dysregulation and neuronal loss correlate with synaptic dysfunction and cognitive decline.

Objective: The goal of this study was to assess the effects of chronic SHS exposure (10 months' exposure to ) on behavioral and cognitive function, metabolism, and neuropathology in mice.

Novel Antimicrobial Peptides Formulated in Chitosan Matrices are Effective Against Biofilms of Multidrug-Resistant Wound Pathogens.

Introduction: Infection frequently complicates the treatment of combat-related wounds, impairs healing, and leads to worse outcomes. To better manage wound infections, antimicrobial therapies that are effective against biofilm and designed for direct wound application are needed. The primary objective of this work was to evaluate a chitosan matrix for delivery of two engineered antimicrobial peptides, (ASP)-1 and ASP-2, to treat biofilm-associated bacteria.

Dlx1/2 and Otp coordinate the production of hypothalamic GHRH- and AgRP-neurons.

Despite critical roles of the hypothalamic arcuate neurons in controlling the growth and energy homeostasis, the gene regulatory network directing their development remains unclear. Here we report that the transcription factors Dlx1/2 and Otp coordinate the balanced generation of the two functionally related neurons in the hypothalamic arcuate nucleus, GHRH-neurons promoting the growth and AgRP-neurons controlling the feeding and energy expenditure. Dlx1/2-deficient mice show a loss-of-GHRH-neurons and an increase of AgRP-neurons, and consistently develop dwarfism and consume less energy.

A Novel Peptide-Based Antimicrobial Wound Treatment is Effective Against Biofilms of Multi-Drug Resistant Wound Pathogens.

Wound infections are a common complication of combat-related injuries that significantly increase morbidity and mortality. Multi-drug resistant (MDR) organisms and their associated biofilms play a significant role in the pathogenicity and chronicity of wound infections. A critical barrier to progress in the treatment of traumatic wounds is the need for broad spectrum antimicrobials that are effective against biofilms and compatible with topical delivery.

Apolipoprotein E4 mediates insulin resistance-associated cerebrovascular dysfunction and the post-prandial response.

Metabolic dysfunction, commonly a result of diets high in saturated fats and sugar, is associated with impaired cognitive function and an increased risk of age-related cognitive decline (ACD) and Alzheimer's disease (AD). Compared to the E3 isoform of apolipoprotein (apoE), the E4 isoform is a major genetic risk factor for ACD, AD, and for developing cognitive impairments following various environmental challenges, including dietary challenges such as a high-fat diet (HFD). Both insulin resistance (IR) and E4 are associated with metabolic and vascular impairments.

Microbial evaluation of Limnophila rugosa Roth. (Merr) leaf.

Background: Limphonia rugosa Roth. (Merr.), family-Scrophulariaceae is considered as a botanical source of classical Ayurvedic drug Bhringaraja by the traditional practitioners of Odisha and is being used for the management of various disorders.

Detection and analysis of Staphylococcus aureus isolates found in ambulances in the Chicago metropolitan area.

Background: Given the frequency with which many different strains of Staphylococcus aureus are found in various prehospital settings, this study sought to characterize S aureus isolates taken from one such environment. The objectives were to determine the frequency of S aureus in front-line, advanced life support (ALS) ambulances throughout the Chicago metropolitan area, and to generate antibiograms (antibiotic resistance profiles) for each S aureus isolate using 8 clinically relevant antibiotics.

Methods: Samples were obtained from 26 sites in 71 ambulances from 34 different Chicago-area municipalities.