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Tamoxifen (TX), a selective estrogen receptor modulator, exerts antagonistic effects on breast tissue and is used to treat breast cancer. Recent evidence also suggests that it may act as an agonist in brain tissue. We reported previously that TX enhanced the expression and function of glutamate transporter 1 (GLT-1) in rat astrocytes, an effect that was mediated by TGF-α To gain further insight into the mechanisms that mediate TX-induced up-regulation ofGLT-1 (EAAT2 in humans),we investigated its effect on GLT-1 at the transcriptional level. TX phosphorylated the cAMP response element-binding protein (CREB) and recruited CREB to the GLT-1 promoter consensus site. The effect of TX on astrocytic GLT-1 was attenuated by the inhibition of PKA, the upstream activator of the CREB pathway. In addition, the effect of TX on GLT-1 promoter activity was abolished by the inhibition of theNF-κB pathway. Furthermore, TX recruited the NF-κB subunits p65 and p50 to the NF-κB binding domain of the GLT-1 promoter. Mutation of NF-κB (triple,583/-282/-251) or CRE (-308) sites on the GLT-1 promoter led to significant repression of the promoter activity, but neither mutant completely abolished the TX-induced GLT-1 promoter activity. Mutation of both the NF-κB (-583/-282/- 251) and CRE (-308) sites led to a complete abrogation of the effect of TX on GLT-1 promoter activity. Taken together, our findings establish that TX regulates GLT-1 via the CREB and NF-κB pathways. [ABSTRACT FROM AUTHOR]

Context: Probiotics are live microorganisms that, when administered in adequate amounts, confer a health benefit on the host. One of the most common indications for probiotic treatment is the prevention of antibiotic-associated diarrhea (AAD). Unfortunately, many probiotic products used for AAD are not supported by rigorous independent research, and often results in non-evidence-based usage. The overarching objective is to move research forward for the most well-studied Bifidobacterium strain. Objectives: The primary aim is to test the efficacy of high dose, BB-12-supplemented yogurt in preventing AAD, compared to yogurt without BB-12, in children receiving antibiotics. Other aims are to further assess the safety of yogurt supplemented with BB-12, and to carry out longitudinal community structure and gene expression analysis of fecal microbiota to evaluate the impact of high dose BB-12 in a pediatric population receiving antibiotics. The microbiota includes hundreds of species, and its disruption is hypothesized to be an important factor in the development of AAD. AIM 1: To test the efficacy of high dose, BB-12-supplemented yogurt in preventing AAD, compared to yogurt without BB-12, in children receiving antibiotics. Hypothesis: Children receiving antibiotics who receive the yogurt with BB-12 will demonstrate less diarrhea than those receiving a control yogurt without BB-12. This is a Phase II trial that requires additional safety evaluation of high dose BB-12. Hypotheses 3: Administration of antibiotics will alter the composition and gene expression profile of the gut microbiota in pediatric patients, and concomitant ingestion of BB-12 in yogurt will mitigate the antibiotic-induced disturbance in the gut microbiota, as identified using 16S rRNA and metatranscriptomic profiling. Study Design and Analysis: We will finish in the June 2023 a Phase II, randomized, doubleblinded controlled trial with allocation concealment. Setting: Capital Areal Primary Care Practice Based Research Network. Population Studied: 270 patients, ages 3-12 years, clinically diagnosed with a respiratory infection requiring 7-10 days of antibiotics. Interventions: The two arms are, BB-12-supplemented yogurt and non-supplemented control yogurt, in a 1:1 randomized allocation. Participants of all ages will be asked to consume the same dose, 100 ml, of product per day. The 100 ml serving of probiotic yogurt will deliver ≥1010 CFU of BB-12. The BB-12 probiotic was not be added., Competing Interests: Authors report none., (2023 Annals of Family Medicine, Inc.)

Context: Probiotics are live microorganisms that, when administered in adequate amounts, confer a health benefit on the host. One of the most common indications for probiotic treatment is the prevention of antibiotic-associated diarrhea (AAD). Unfortunately, many probiotic products used for AAD are not supported by rigorous independent research, and often results in non-evidence-based usage. Additionally, it is not clear when is the most appropriate time to take a probiotic when on an antibiotic course. Objectives: The primary aim is to determine the ability of BB-12 to impact antibiotic-induced reduction in short chain fatty acid concentration (SCFA), as reflected by the levels of acetate on day 14. Secondarily to determine the ability of BB-12 to impact antibiotic-induced disruption of the gut microbiota with 16S rDNA profiling, with the addition of the time variable of probiotic consumption. Study Design and Interventions: A five group randomized controlled trial, finished in December 2022, we are currently analyzing all the data, but will be finished much prior to NAPCRG. All participants were given a 7-day prescription for amoxicillin-clavulanic acid 875mg taken twice daily. One group received no other interventions. While the other participants were broken into 4 groups. Two groups consumed the yogurt intervention (either yogurt+probiotic or control yogurt) four hours after the antibiotic and two groups consumed the yogurt intervention (either yogurt+probiotic or control yogurt) concomitantly with antibiotics. This timing question is important, as it is unknown if the optimal time for patients to administer probiotics is concurrently with, or after four hours following antibiotic consumption. Setting: Capital Areal Primary Care Practice Based Research Network. Population Studied: 118 participants, ages 18-65 years, generally healthy. Outcome Measures: Change in SCFA among the five groups, microbiome reduced disruption and clinically diagnosed diarrhea. Results: Study is complete and analysis is underway. Should have full results by end of July 2023, much before NAPCRG. ., Competing Interests: Authors report none., (2023 Annals of Family Medicine, Inc.)