Short‐term Sirolimus Treatment Increases Cerebral Blood Flow in Asymptomatic APOE4 Females Determined by 3T MRI.

Background: Apolipoprotein ε4 allele (APOE4) is the strongest genetic risk factor for late‐onset Alzheimer’s disease (AD) with females having higher risk than males. Compared with non‐carriers, cognitively normal, middle‐aged APOE4 carriers have lower cerebral blood flow (CBF) decades before clinical symptoms appear. Early intervention to protect CBF would be critical for APOE4 carriers to mitigate AD progression.

Short‐term Sirolimus Treatment Restores Hippocampus and Caudate Volumes and Global Cerebral Blood Flow in Asymptomatic APOE4 Carriers Compared with Non‐carriers.

Background: Apolipoprotein ε4 allele (APOE4) is the strongest genetic risk factor for late‐onset Alzheimer’s disease (AD). Compared with non‐carriers, cognitively normal APOE4 individuals have shown brain atrophy and lower cerebral blood flow (CBF) decades before AD pathological and clinical symptoms appear. The goal of the study is to determine if using Sirolimus, an FDA‐approved mTOR inhibitor, could restore the brain volumes in structures related to cognitive functions and global CBF (gCBF) for asymptomatic APOE4 carriers compared with non‐carriers.

Short‐term Sirolimus Treatment Increases Cerebral Blood Flow in Asymptomatic APOE4 Females Determined by 3T MRI.

Background: Apolipoprotein e4 allele (APOE4) is the strongest genetic risk factor for late‐onset Alzheimer’s disease (AD) with females having higher risk than males. Compared with non‐carriers, cognitively normal, middle‐aged APOE4 carriers have lower cerebral blood flow (CBF) decades before clinical symptoms appear. Early intervention to protect CBF would be critical for APOE4 carriers to mitigate AD progression.

Short‐term Sirolimus Treatment Restores Hippocampus and Caudate Volumes and Global Cerebral Blood Flow in Asymptomatic APOE4 Carriers Compared with Non‐carriers.

Background: Apolipoprotein e4 allele (APOE4) is the strongest genetic risk factor for late‐onset Alzheimer’s disease (AD). Compared with non‐carriers, cognitively normal APOE4 individuals have shown brain atrophy and lower cerebral blood flow (CBF) decades before AD pathological and clinical symptoms appear. The goal of the study is to determine if using Sirolimus, an FDA‐approved mTOR inhibitor, could restore the brain volumes in structures related to cognitive functions and global CBF (gCBF) for asymptomatic APOE4 carriers compared with non‐carriers.

Ionizing radiation improves skin bacterial dysbiosis in cutaneous T-cell lymphoma.

Introduction: Cutaneous T-cell lymphoma (CTCL) is closely associated with the host microbiome. While recent evidence suggests that shifts in specific bacterial taxa are associated with response to UV-B, a form of non-ionizing radiation, the impact of ionizing radiation (IR) has not been investigated.

Methods: 16S rRNA and gene amplicon sequencing were performed on DNA extracted from swabs of lesional/non-lesional skin of 12 CTCL patients before/after TSEBT or local IR and from 25 matched healthy controls (HC).

Early Life Stress, DNA Methylation of NR3C1 and HSD11B2, and Oral Feeding Skill Development in Preterm Infants: A Pilot Study.

Background: Early life stress exposure in preterm infants may alter DNA methylation of NR3C1 and HSD11B2, disrupting neurobehaviors needed for oral feeding (PO) skill development.

Purpose: To (1) examine the feasibility of the study protocol; (2) describe early life stress, DNA methylation of NR3C1 and HSD11B2, and PO skill development; and (3) explore the association between DNA methylation of NR3C1 and HSD11B2 and infant characteristics, early life stress, and PO skill development.

Method: We employed a longitudinal descriptive pilot study (N = 10).

Uterine pathology and microbiome among patients with endometrial polyps and fibroids.

Objective: To evaluate the uterine microbiome among women with endometrial polyps and submucosal fibroids and to compare results between endometrial sampling techniques.

Design: Patients with polyps or fibroids were prospectively recruited prior to hysteroscopy, while patients undergoing retrieval for planned oocyte cryopreservation were recruited prospectively as controls. Three specimen types obtained for each patient were the distal 5 mm of an embryo catheter passed to the uterine fundus (C), endometrial tissue from an endometrial biopsy (T), and formalin fixed paraffin embedded endometrial tissue from the same endometrial biopsy (FFPE).

Water source, latrine type, and rainfall are associated with detection of non-optimal and enteric bacteria in the vaginal microbiome: a prospective observational cohort study nested within a cluster randomized controlled trial.

Background: Less than one-third of sub-Saharan Africans have access to improved water sources. In US, Indian, and African studies, Bacterial vaginosis (BV) is increased among women with poor water, sanitation, and hygiene (WASH). We examined water source, sanitation (latrine type), and rainfall in relation to the vaginal microbiome (VMB).

Epigenetics Embedding of Oral Feeding Skill Development in Preterm Infants: A Study Protocol.

Background: Preterm infants face challenges to feed orally, which may lead to failure to thrive. Oral feeding skill development requires intact neurobehaviors. Early life stress results in DNA methylation of NR3C1 and HSD11B2, which may disrupt neurobehaviors.

Menstrual cups to reduce bacterial vaginosis and STIs through reduced harmful sexual and menstrual practices among economically vulnerable women: protocol of a single arm trial in western Kenya.

Background: In western Kenya, menstrual hygiene management (MHM) is a pervasive problem. Challenges are compounded for economically constrained women who continue to engage in sex during menses and resort to practices such as vaginal insertion of tissue and cotton to maintain dryness during sex. These practices can be harmful to the vaginal microbiome (VMB) and can lead to high rates of sexually transmitted infections (STIs) and HIV.

Medicinal Plant Microbiomes: Factors Affecting Bacterial and Fungal Community Composition.

This exploratory study was designed to identify factors implicating microbial influence on medicinal plant metabolomes. Utilizing a whole-microbiome approach, amplicon sequencing was used to identify the makeup of fungal and bacterial assemblages from endophytic (interior) and epiphytic (external) environments in two different sets of congeneric host-plant pairs, with collection of multiple samples of two medicinal plant species () and two generic analogs (). Diversity analysis of microbial assemblages revealed the influence of three primary factors driving variance in microbial community composition: host-plant taxonomy, the compartmentalization of microbial communities within discrete plant parts, and the scale of distance (microhabitat heterogeneity) between sampling locations.

The Bidirectional Effects of Periodontal Disease and Oral Dysbiosis on Gut Inflammation in Inflammatory Bowel Disease.

Background And Aims: Inflammatory bowel disease (IBD) flares can lead to excessive morbidity and mortality. This study aimed to determine whether oral dysbiosis/periodontal disease (PD) is common in IBD and is associated with disease activity in IBD.

Methods: This single-center, prospective, cross-sectional, proof-of-concept, observational study assessed the frequency of periodontal inflammatory disease and interrogated oral and stool microbiota using 16S rRNA gene amplicon sequencing of active-IBD (aIBD), inactive-IBD (iIBD), and healthy controls (HC).

Foxa deficiency restricts hepatitis B virus biosynthesis through epigenic silencing.

Unlabelled: In the hepatis B virus (HBV) transgenic mouse model of chronic infection, the forkhead box protein A/hepatocyte nuclear factor 3 (Foxa/HNF3) family of pioneer transcription factors are required to support postnatal viral demethylation and subsequent HBV transcription and replication. Liver-specific Foxa-deficient mice with hepatic expression of only Foxa3 do not support HBV replication but display biliary epithelial hyperplasia with bridging fibrosis. However, liver-specific Foxa-deficient mice with hepatic expression of only Foxa1 or Foxa2 also successfully restrict viral transcription and replication but display only minimal alterations in liver physiology.

Quantitating primer-template interactions using deconstructed PCR.

When the polymerase chain reaction (PCR) is used to amplify complex templates such as metagenomic DNA using single or degenerate primers, preferential amplification of templates (PCR bias) leads to a distorted representation of the original templates in the final amplicon pool. This bias can be influenced by mismatches between primers and templates, the locations of mismatches, and the nucleotide pairing of mismatches. Many studies have examined primer-template interactions through interrogation of the final products of PCR amplification with controlled input templates.

Effect of progestin-based contraceptives on HIV-associated vaginal immune biomarkers and microbiome in adolescent girls.

Adolescent girls bear a disproportionate burden of both the HIV epidemic and unintended pregnancies; yet important questions remain unanswered regarding the effects of hormonal contraceptives on the vaginal immune microenvironment, which can impact HIV susceptibility in this group. Multiple studies report genital immune alterations associated with the progestin-based contraceptive Depot medroxyprogesterone acetate (DMPA) in adult women, but there is little available data in adolescents. The objective of this longitudinal cohort study was to evaluate the effects of short-term use of three progestin-based contraceptives, levonorgestrel intrauterine device (LNG-IUD), subdermal etonogestrel (ETNG), and injectable DMPA, on HIV-associated vaginal immune biomarkers and microbiome in adolescent girls.

The Gut Microbiome and Symptom Burden After Kidney Transplantation: An Overview and Research Opportunities.

Many kidney transplant recipients continue to experience high symptom burden despite restoration of kidney function. High symptom burden is a significant driver of quality of life. In the post-transplant setting, high symptom burden has been linked to negative outcomes including medication non-adherence, allograft rejection, graft loss, and even mortality.

Evidence that the loss of colonic anti-microbial peptides may promote dysbiotic Gram-negative inflammaging-associated bacteria in aging mice.

Aging studies in humans and mice have played a key role in understanding the intestinal microbiome and an increased abundance of "inflammaging" Gram-negative (Gn) bacteria. The mechanisms underlying this inflammatory profile in the aging microbiome are unknown. We tested the hypothesis that an aging-related decrease in colonic crypt epithelial cell anti-microbial peptide (AMP) gene expression could promote colonic microbiome inflammatory Gn dysbiosis and inflammaging.

Topical antibiotics limit depigmentation in a mouse model of vitiligo.

Oral neomycin administration impacts the gut microbiome and delays vitiligo development in mice, and topical antibiotics may likewise allow the microbiome to preserve skin health and delay depigmentation. Here, we examined the effects of 6-week topical antibiotic treatment on vitiligo-prone pmel-1 mice. Bacitracin, Neosporin, or Vaseline were applied to one denuded flank, while the contralateral flank was treated with Vaseline in all mice.

Gut microbiota analyses of cutaneous T-cell lymphoma patients undergoing narrowband ultraviolet B therapy reveal alterations associated with disease treatment.

Recent studies have shown a close relationship between cutaneous T-cell lymphoma (CTCL) and its microbiome. CTCL disease progression is associated with gut dysbiosis and alterations in bacterial taxa parallel those observed in immunologically similar atopic dermatitis. Moreover, the microbial profile of lesional skin may predict response to narrowband ultraviolet B (nbUVB), a common skin-directed therapy.

Short- and long-term effects of continuous compost amendment on soil microbiome community.

Organic amendment, and especially the use of composts, is a well-accepted sustainable agricultural practice. Compost increases soil carbon and microbial biomass, changes enzymatic activity, and enriches soil carbon and nitrogen stocks. However, relatively little is known about the immediate and long-term temporal dynamics of agricultural soil microbial communities following repeated compost applications.

Enrichment of polycyclic aromatic hydrocarbon metabolizing microorganisms on the oral mucosa of tobacco users.

Certain soil microbes resist and metabolize polycyclic aromatic hydrocarbons (PAHs). The same is true for a subset of skin microbes. In the human mouth, oral microbes have the potential to oxidize tobacco PAHs, thereby increasing these chemicals' ability to cause cancer of adjacent epithelium.

Ten-eleven translocation (Tet) methylcytosine dioxygenase-dependent viral DNA demethylation mediates hepatitis B virus (HBV) biosynthesis.

Liver-specific ten-eleven translocation (Tet) methylcytosine dioxygenases 2 and 3 (Tet2 plus Tet3)-deficient hepatitis B virus (HBV) transgenic mice fail to support viral biosynthesis. The levels of viral transcription and replication intermediates are dramatically reduced. Hepatitis B core antigen is only observed in a very limited number of pericentral hepatocytes in a pattern that is similar to glutamate-ammonia ligase (Glul), a β-catenin target gene.

A response playbook for early detection and population surveillance of new SARS-CoV-2 variants in a regional public health laboratory.

Background: Timely genomic surveillance is required to inform public health responses to new SARS-CoV-2 variants. However, the processes involved in local genomic surveillance introduce inherent time constraints. The Regional Innovative Public Health Laboratory in Chicago developed and employed a genomic surveillance response playbook for the early detection and surveillance of emerging SARS-CoV-2 variants.