Moderators of the Link Between Social Preference and Persistent Peer Victimization for Elementary School Children.

OBJECTIVE: Current antibullying programs can reduce overall rates of victimization but appear to overlook processes that give rise to persistent peer victimization. Needed are studies that delineate the interplay between social contextual and individual difference variables that contribute to persistent peer victimization. We examined the extent to which two individual-difference variables - internalizing symptoms (IS) and anxiety sensitivity (AS) - moderated the link between children's average social preference score across the school year and their status as persistent victims. METHOD: Participants included 659 4th-grade students (Mage = 9.31 years, SD = 0.50, 51.8% girls; 42.3% Latinx, 28.9% non-Hispanic White, 10.2% Pacific Islander, 7.7% Bi/Multiracial, 1.9% Black, 1.7% Asian, 1.7% Native American, and 3.4% unreported) from 10 public elementary schools in the U.S. RESULTS: As expected, higher social preference scores predicted a decreased likelihood of being persistently victimized. Conversely, IS and AS were positively linked to persistent victim status. AS significantly moderated the link between social preference and persistent victim status such that for children with high AS, compared to those with AS scores at or below the mean, the negative association between social preference and persistent victim status was attenuated. CONCLUSIONS: Findings provide evidence that children who experience high levels of IS and AS are at risk for being persistently victimized by peers and that high AS could signal increased risk for persistent victimization even when children are generally liked by peers. We discuss the implications of these findings for efforts to develop focused interventions for chronically bullied children.

A likelihood ratio approach for utilizing case-control data in the clinical classification of rare sequence variants: application to BRCA1 and BRCA2.

A large number of variants identified through clinical genetic testing in disease susceptibility genes, are of uncertain significance (VUS). Following the recommendations of the American College of Medical Genetics and Genomics (ACMG) and Association for Molecular Pathology (AMP), the frequency in case-control datasets (PS4 criterion), can inform their interpretation. We present a novel case-control likelihood ratio-based method that incorporates gene-specific age-related penetrance. We demonstrate the utility of this method in the analysis of simulated and real datasets. In the analyses of simulated data, the likelihood ratio method was more powerful compared to other methods. Likelihood ratios were calculated for a case-control dataset of BRCA1 and BRCA2 variants from the Breast Cancer Association Consortium (BCAC), and compared with logistic regression results. A larger number of variants reached evidence in favor of pathogenicity, and a substantial number of variants had evidence against pathogenicity - findings that would not have been reached using other case-control analysis methods. Our novel method provides greater power to classify rare variants compared to classical case-control methods. As an initiative from the ENIGMA Analytical Working Group, we provide user-friendly scripts and pre-formatted excel calculators for implementation of the method for rare variants in BRCA1, BRCA2 and other high-risk genes with known penetrance.

The role of TMS 12 in the staphylococcal multidrug efflux protein QacA.

OBJECTIVES: To elucidate the importance of a region in QacA predicted to be important in antimicrobial substrate recognition. METHODS: A total of 38 amino acid residues within or flanking putative transmembrane helix segment (TMS) 12 of QacA were individually replaced with cysteine using site-directed mutagenesis. The impact of these mutations on protein expression, drug resistance, transport activity and interaction with sulphhydryl-binding compounds was determined. RESULTS: Accessibility analysis of cysteine-substituted mutants identified the extents of TMS 12, which allowed for refinement of the QacA topology model. Mutation of Gly-361, Gly-379 and Ser-387 in QacA resulted in reduced resistance to at least one bivalent substrate. Interaction with sulphhydryl-binding compounds in efflux and binding assays demonstrated the role of Gly-361 and Ser-387 in the binding and transport pathway of specific substrates. The highly conserved residue Gly-379 was found to be important for the transport of bivalent substrates, commensurate with the role of glycine residues in helical flexibility and interhelical interactions. CONCLUSIONS: TMS 12 and its external flanking loop is required for the structural and functional integrity of QacA and contains amino acids directly involved in the interaction with substrates.

ASC-dependent inflammasomes contribute to immunopathology and mortality in herpes simplex encephalitis.

Herpes simplex virus encephalitis (HSE) is the most common cause of sporadic viral encephalitis, and despite targeted antiviral therapy, outcomes remain poor. Although the innate immune system is critical for restricting herpes simplex virus type I (HSV-1) in the brain, there is evidence that prolonged neuroinflammation contributes to HSE pathogenesis. In this study, we investigated the contribution of inflammasomes to disease pathogenesis in a murine model of HSE. Inflammasomes are signaling platforms that activate the pro-inflammatory cytokines interleukin-1ß (IL-1ß) and IL-18. We found that mice deficient in the inflammasome adaptor protein, apoptosis-associated speck-like protein containing a caspase activation and recruitment domain (ASC), had significantly improved survival and lower levels of IL-1ß and IL-18 in the brain. Importantly, this difference in survival was independent of viral replication in the central nervous system (CNS). We found that microglia, the resident macrophages of the CNS, are the primary mediators of the ASC-dependent inflammasome response during infection. Using in vitro glial infections and a murine HSE model, we demonstrate that inflammasome activation contributes to the expression of chemokine (C-C motif) ligand 6 (CCL6), a leukocyte chemoattractant. The lower concentration of CCL6 in the brains of ASC-/- mice correlated with lower numbers of infiltrating macrophages during infection. Together, these data suggest that inflammasomes contribute to pathogenic inflammation in HSE and provide a mechanistic link between glial inflammasome activation and leukocyte infiltration. The contribution of inflammasomes to survival was independent of viral replication in our study, suggesting a promising new target in combating harmful inflammation in HSE.

Less is more: clinical utility of postoperative laboratory testing following minimally invasive hysterectomy for endometrial cancer.

BACKGROUND: With the increasing rates of same-day discharge following minimally invasive surgery for endometrial cancer, the need for and value of routine postoperative testing is unclear. OBJECTIVE: This study aimed to determine whether routine postoperative laboratory testing following minimally invasive hysterectomy for endometrial cancer leads to clinically significant changes in postoperative care. STUDY DESIGN: This was a single-institution retrospective cohort study of patients undergoing minimally invasive hysterectomy for endometrial cancer by a gynecologic oncologist between June 2014 and June 2017. Patient demographics, preoperative comorbidities, operative and postoperative data, and pathologic findings were manually extracted from the patients' medical records. The financial burden of laboratory testing was computed using hospital-level cost data. RESULTS: Of the 649 women included in the analysis, most (91.4%) were White, with a mean age of 61 years, and mean body mass index of 38.0 kg/m2. The most common comorbidities were diabetes mellitus (31.9%, n=207), chronic pulmonary disease (7.9%, n=51), and congestive heart failure (3.2%, n=21). Median operative time was 151 minutes (range, 61-278), and median estimated blood loss was 100 mL (range, 10-1500). Most patients (68.6%, n=445) underwent lymphadenectomy. All patients had postoperative laboratory tests ordered: 100% complete blood count, 99.7% chemistry, 62.9% magnesium, 46.8% phosphate, 37.4% calcium, and 1.2% liver function tests. Twenty-six patients (4.0%) had a change in management owing to postoperative laboratory test results. Of these 26 women, 88% experienced a change in clinical status that would have otherwise prompted testing. Only 3 (0.5% of entire cohort) were asymptomatic: 1 received a blood transfusion for asymptomatic anemia, and the other 2, who did not carry a diagnosis of diabetes mellitus, had interventions for hyperglycemia. On univariable analysis, peripheral and cerebrovascular disease, diabetes mellitus with end-organ damage, and a Charlson Comorbidity Index of ≥3 were associated with increased odds of change in management; these were not significant on multivariable analysis. Routine postoperative laboratory evaluation in this cohort increased hospital costs by $292,000. CONCLUSION: Routine postoperative laboratory tests are unlikely to lead to significant changes in management for women undergoing minimally invasive hysterectomy for endometrial cancer, and may increase cost without providing a discernible clinical benefit. In the setting of strict postoperative guidelines, laboratory tests should be ordered when clinically indicated rather than as part of routine postoperative management for women undergoing minimally invasive hysterectomy for endometrial cancer.

Early Stress-Response Gene REDD1 Controls Oxazolone-Induced Allergic Contact Dermatitis.

REDD1 is an energy sensor and stress-induced mTOR inhibitor. Recently, its novel role in linking metabolism and inflammation/immune responses has emerged. In this study, we assessed the role of REDD1 in murine oxazolone-induced allergic contact dermatitis (ACD), a T cell-dependent model with features of human ACD. A variety of immune indices, including edema, cellular infiltration, inflammatory gene expression, and glucocorticoid response, were compared in Redd1 knockout (KO) and isogenic (C57BL/6 × 129)F1 wild-type mice after sensitization and subsequent ear challenge with oxazolone. Despite relatively normal thymic profiles and similar T cell populations in the lymph nodes of naive Redd1 KO mice, early T cell expansion and cytokine production were profoundly impaired after sensitization. Surprisingly, higher steady-state populations of CD4+ and CD8+ T cells, as well as macrophages (CD45+/Ly-6G-/CD11b+), dendritic cells (CD45+/Ly-6G-/CD11c+), neutrophils (CD45+/Ly-6G+/CD11b+), and innate lymphoid cells (CD45+/Lineage-/IL-7Ra+/ST2+/c-Kit+), were observed in the ears of naive Redd1 KO mice. Upon challenge, ear edema, T cell, macrophage, neutrophil, and dendritic cell infiltration into the ear was significantly reduced in Redd1 KO animals. Accordingly, we observed significantly lower induction of IFN-γ, IL-4, and other cytokines as well as proinflammatory factors, including TSLP, IL-33, IL-1ß, IL-6, and TNF-α, in challenged ears of Redd1 KO mice. The response to glucocorticoid treatment was also diminished. Taken together, these data establish REDD1 as an essential immune modulator that influences both the initiation of ACD disease, by driving naive T cell activation, and the effector phase, by promoting immune cell trafficking in T cell-mediated skin inflammation.

Informal mentoring support as a potential moderator of the relation between adolescent dating violence victimization and substance use.

Research links adolescent dating violence (ADV) victimization to negative developmental outcomes, including involvement in substance use. Informal mentoring is associated with several positive outcomes, including reduced risk of substance use. Addressed in this study is whether support from an informal mentor can function to protect victims of ADV from involvement in substance use. Participants were 152 adolescents (grades 9-12). Findings revealed a significant association between ADV victimization and adolescents' involvement in substance use, as well as some evidence that support from an informal mentor moderates that link. When informal mentor support was low or at the mean, ADV victimization was significantly linked to adolescents' involvement in substance use; when informal mentor support was high, ADV victimization was unrelated to substance use involvement. Discussed are research and practice implications of the potential protective role of informal mentors for victims of ADV.

Hospital water as the source of healthcare-associated infection and antimicrobial-resistant organisms.

PURPOSE OF REVIEW: Drinking water is considered one of the most overlooked and underestimated sources of healthcare-associated infections (HAIs). Recently, the prevention and control of opportunistic premise plumbing pathogens (OPPPs) in healthcare water systems has been receiving increasing attention in infection control guidelines. However, these fail to address colonization of pathogens that do not originate from source water. Subsequently, this review explores the role of water and premise plumbing biofilm in HAIs. The potential mechanisms of contamination and transmission of antimicrobial-resistant (AMR) pathogens originating both from supply water and human microbiota are discussed. RECENT FINDINGS: OPPPs, such as Legionella pneumophila, Pseudomonas aeruginosa and Mycobacterium avium have been described as native to the plumbing environment. However, other pathogens, not found in the source water, have been found to proliferate in biofilms formed on outlets devices and cause HAI outbreaks. SUMMARY: Biofilms formed on outlet devices, such as tap faucets, showers and drains provide an ideal niche for the dissemination of antimicrobial resistance. Thus, comprehensive surveillance guidelines are required to understand the role that drinking water and water-related devices play in the transmission of AMR HAIs and to improve infection control guidelines.

Factors affecting the isolation and diversity of marine sponge-associated bacteria.

Marine sponges are an ideal source for isolating as yet undiscovered microorganisms with some sponges having about 50% of their biomass composed of microbial symbionts. This study used a variety of approaches to investigate the culturable diversity of the sponge-associated bacterial community from samples collected from the South Australian marine environment. Twelve sponge samples were selected from two sites and their bacterial population cultivated using seven different agar media at two temperatures and three oxygen levels over 3 months. These isolates were identified using microscopic, macroscopic, and 16S rRNA gene analysis. A total of 1234 bacterial colonies were isolated which consisted of four phyla: Actinobacteria, Firmicutes, Proteobacteria, and Bacteroidetes, containing 21 genera. The diversity of the bacterial population was demonstrated to be influenced by the type of isolation medium, length of the incubation period and temperature, sponge type, and oxygen level. The findings of this study showed that marine sponges of South Australia can yield considerable bacterial culturable diversity if a comprehensive isolation strategy is implemented. Two sponges, with the highest and the lowest diversity of culturable isolates, were examined using next-generation sequencing to better profile the bacterial population. A marked difference in terms of phyla and genera was observed using culture-based and culture-independent approaches. This observed variation displays the importance of utilizing both methods to reflect a more complete picture of the microbial population of marine sponges. KEY POINTS: Improved bacterial diversity due to long incubations, 2 temperatures, and 3 oxygen levels. Isolates identified by morphology, restriction digests, and 16S rRNA gene sequencing. At least 70% of culturable genera were not revealed by NGS methods.

An Inconvenient Variable: Sex Hormones and Their Impact on T Cell Responses.

Epidemiologic data demonstrate sex differences in autoimmune diseases, immune responses against infection, and antitumor immunity, and accumulating evidence suggests a major role for sex hormones in mediating these differences. In this study, we review recent advances in understanding how sex hormones regulate T cell responses to alter susceptibility to autoimmunity. Although sex hormones can directly alter gene transcriptional programs of T cells, we focus in this study on how sex hormones alter T cell development and function through their effects on thymic stromal cells and innate cell types. In addition to contributing to our understanding of sex differences, these findings also have implications for the therapeutic use of sex hormones and sex hormone modulators, which are now being prescribed to increasing numbers of patients for a wide variety of indications.

Male-specific IL-33 expression regulates sex-dimorphic EAE susceptibility.

The cellular and molecular basis of sex-dimorphic autoimmune diseases, such as the CNS demyelinating disease multiple sclerosis (MS), remains unclear. Our studies in the SJL mouse model of MS, experimental autoimmune encephalomyelitis (EAE), reveal that sex-determined differences in Il33 expression by innate immune cells in response to myelin peptide immunization regulate EAE susceptibility. IL-33 is selectively induced in PLP139-151-immunized males and activates type 2 innate lymphoid cells (ILC2s), cells that promote and sustain a nonpathogenic Th2 myelin-specific response. Without this attenuating IL-33 response, females generate an encephalitogenic Th17-dominant response, which can be reversed by IL-33 treatment. Mast cells are one source of IL-33 and we provide evidence that testosterone directly induces Il33 gene expression and also exerts effects on the potential for Il33 gene expression during mast cell development. Thus, in contrast to their pathogenic role in allergy, we propose a sex-specific role for both mast cells and ILC2s as attenuators of the pathogenic Th response in CNS inflammatory disease.

Using the RE-AIM framework to identify and describe nutritional feeding styles and intervention model best practices for primary caregivers in Africa: A narrative review.

BACKGROUND: Current research shows that across the world people are eating poorly. This is leading to increased incidences of nutrition-related health problems. AIM: This paper aims to provide a synthesis of research on the nutritional feeding programs and nutritional models used by primary caregivers in Africa, in order to identify best practice models, programs, and processes from the field of nutritional and feeding intervention development. METHODS: The research used a narrative review methodology. The Reach, Effectiveness, Adoption, Implementation and Maintenance (RE-AIM) framework was used to disseminate results to allow for cross-comparison of core components inherent in health promotion interventions. We chose the RE-AIM framework as it facilitates the development, delivery, and evaluation of health interventions. RESULTS: After screening a total of 8220 articles, four studies were deemed relevant for the purposes of this review. The selected studies were the only ones that discussed nutrition interventions or programs with a very clear aim and purpose, even though they did not include any information on implementation, review or evaluation of these interventions/program. No studies focusing on the African context were deemed relevant as none of them focused on best practice models for nutrition education interventions or programs. CONCLUSIONS: Of a review of over 8220 articles, four studies were found that discuss nutritional feeding programs and nutritional models used by primary caregivers. Of these four, only one focused on enablers, barriers, and resources, all of which are essential for engaging in health behavior change. And only one focused on sustainability of the interventions.

Implementation of an Educational Fueling Station for a National Collegiate Athletic Association Division III Athletic Program.

ABSTRACT: Gomez-Hixson, K, and Brown, ML. Implementation of an educational fueling station for a NCAA division III athletic program. J Strength Cond Res 35(8): 2346-2350, 2021-The purpose of this project was to evaluate the effectiveness and sustainability of an educational fueling station for National Collegiate Athletic Association (NCAA) Division III student-athletes. Subjects included student-athletes participating in the fall 2018 athletic season (n = 82). Once the mobile fueling station was established, the athletes were informed of the mobile fueling station policies and educated on the appropriate use and timing of the fueling station. The fueling station remained in operation until the end of the 2018 fall athletic season, after which the effectiveness and athlete acceptance of the mobile fueling station was assessed. An anonymous online survey was used as the assessment tool and was created by the authors based on the information pertinent to our institution and mobile fueling station goals and objectives. An itemized inventory usage tracking system was used to calculate actual costs. Data analysis was limited to basic descriptive statistics including the overall response rate and the frequency and percentage of responses to the survey questions. Outcome assessment indicated that 97% of athletes found that the foods provided helped their performance; 95% felt they were properly oriented to the fueling station, and 51% used the fueling station 1-2 times per week on game days. Furthermore, inventory tracking revealed that the operational costs came in under the projected budget. Overall, the mobile fueling station was successfully implemented for student-athletes within a NCAA Division III university and demonstrated feasibility and sustainability within a low-budget athletic program. Establishing proof of concept led to the permanent adoption of the mobile fueling station.

Long Noncoding RNAs CUPID1 and CUPID2 Mediate Breast Cancer Risk at 11q13 by Modulating the Response to DNA Damage.

Breast cancer risk is strongly associated with an intergenic region on 11q13. We have previously shown that the strongest risk-associated SNPs fall within a distal enhancer that regulates CCND1. Here, we report that, in addition to regulating CCND1, this enhancer regulates two estrogen-regulated long noncoding RNAs, CUPID1 and CUPID2. We provide evidence that the risk-associated SNPs are associated with reduced chromatin looping between the enhancer and the CUPID1 and CUPID2 bidirectional promoter. We further show that CUPID1 and CUPID2 are predominantly expressed in hormone-receptor-positive breast tumors and play a role in modulating pathway choice for the repair of double-strand breaks. These data reveal a mechanism for the involvement of this region in breast cancer.

Emulsion Droplet Crystallinity Attenuates Short-Term Satiety in Healthy Adult Males: A Randomized, Double-Blinded, Crossover, Acute Meal Study.

BACKGROUND: The influence of triacylglycerol (TAG) physical properties on satiety remains poorly understood. OBJECTIVES: The objective was to investigate if and how TAG digestion and absorption, modulated only by differences in TAG crystallinity, would differentially affect short-term satiety in healthy men. METHODS: We tempered 500 mL 10% palm stearin oil-in-water emulsions such that the lipid droplets were either undercooled liquid (LE) or partially crystalline solid (SE). Fifteen healthy men (mean ± SD age: 27.5 ± 5.7 y; BMI: 24.1 ± 2.5 kg/m2; fasting TAG: 0.9 ± 0.3 mmol/L) consumed each beverage at two 6-h study visits separated by ≥6 d after an overnight fast, along with 1500 mg acetaminophen suspended in water. The participants characterized the emulsion sensory properties, completed satiety visual analog scale ratings, and had serial blood samples collected for 6-h analysis of plasma peptide YY (PYY), glucagon-like peptide-1 (GLP-1), ghrelin, leptin, glucose-dependent insulinotropic polypeptide (GIP), insulin, and acetaminophen (for assessing gastric emptying). Repeated-measures ANOVAs and 2-tailed paired t tests were used to analyze the changes from baseline and incremental area under the curve (iAUC) values, respectively. RESULTS: With consumption of LE compared with SE, there was a 358% higher fullness (P = 0.015) and a 103% lower average appetite (P = 0.041) score, along with higher iAUC values for PYY (P = 0.011) and GLP-1 (P = 0.028) (103% and 66% higher, respectively), but not for ghrelin (P = 0.39), based on change from baseline values. Acetaminophen response trended toward significance (P = 0.08) and was 15% higher with LE. SE was rated as 44% thicker (P = 0.034) and 24% creamier (P = 0.05) than LE. CONCLUSIONS: The suppression of TAG digestion by the presence of partially crystalline lipid droplets blunted the appetite-suppressing effects of an oil-in-water emulsion.This trial was registered at clinicaltrials.gov as NCT03990246.

Emulsion Droplet Crystallinity Attenuates Postprandial Plasma Triacylglycerol Responses in Healthy Men: A Randomized Double-Blind Crossover Acute Meal Study.

BACKGROUND: The presence of triacylglycerol (TAG) cystallinity is assumed to influence digestibility and postprandial lipemia (PPL), although studies to date are limited. OBJECTIVE: This study aimed to investigate whether the presence of solid fat compared with undercooled liquid oil, specifically, plays a role in determining PPL by comparing emulsion droplets differing only in terms of physical state. METHODS: Ten percent palm stearin and 0.4% sorbitan monostearate emulsions were tempered to contain identically sized, charged, and shaped (spherical) undercooled liquid (LE) compared with partially crystalline solid (SE; mean ± SEM: 33.2% ± 0.03% solid fat at 37°C) droplets. Fifteen healthy fasting adult men (mean ± SD age: 27.5 ± 5.7 y; BMI: 24.1 ± 2.5 kg/m2) consumed 500 mL of each emulsion on separate occasions and plasma TAG concentrations, particle size of the plasma chylomicron-rich fraction (CMRF), and fatty acid (FA) composition of the CMRF-TAG were serially determined in a 6-h postprandial randomized double-blind crossover acute meal study. Changes from baseline values were analyzed by repeated-measures ANOVA. RESULTS: An earlier (2 compared with 3 h, P < 0.05) significant rise, a 39.9% higher mean postprandial TAG change from baseline (P = 0.08), and higher peak concentration (mean ± SEM: 1.47 ± 0.19 compared with 1.20 ± 0.15 mmol/L, P = 0.04) and iAUC (1.95 ± 0.39 compared with 1.45 ± 0.31 mmol/L × h, P = 0.03) values were observed for LE compared with SE. The compositions of the CMRF-TAG FAs shifted toward those of the ingested palm stearin by 4 h but did not differ between SE and LE (P = 0.90). Nor were there differences in postprandial changes in CMRF particle size (P = 0.79) or nonesterified FAs (P = 0.72) based on lipid physical state. CONCLUSIONS: Despite their identical compositions and colloidal properties, differences in lipid absorption were observed between SE and LE in healthy adult men. This is direct evidence that TAG physical state contributes to PPL, with the presence of solid fat having an attenuating influence.This trial was registered at clinicaltrials.gov as NCT03515590.

Towards controlled terminology for reporting germline cancer susceptibility variants: an ENIGMA report.

The vocabulary currently used to describe genetic variants and their consequences reflects many years of studying and discovering monogenic disease with high penetrance. With the recent rapid expansion of genetic testing brought about by wide availability of high-throughput massively parallel sequencing platforms, accurate variant interpretation has become a major issue. The vocabulary used to describe single genetic variants in silico, in vitro, in vivo and as a contributor to human disease uses terms in common, but the meaning is not necessarily shared across all these contexts. In the setting of cancer genetic tests, the added dimension of using data from genetic sequencing of tumour DNA to direct treatment is an additional source of confusion to those who are not experienced in cancer genetics. The language used to describe variants identified in cancer susceptibility genetic testing typically still reflects an outdated paradigm of Mendelian inheritance with dichotomous outcomes. Cancer is a common disease with complex genetic architecture; an improved lexicon is required to better communicate among scientists, clinicians and patients, the risks and implications of genetic variants detected. This review arises from a recognition of, and discussion about, inconsistencies in vocabulary usage by members of the ENIGMA international multidisciplinary consortium focused on variant classification in breast-ovarian cancer susceptibility genes. It sets out the vocabulary commonly used in genetic variant interpretation and reporting, and suggests a framework for a common vocabulary that may facilitate understanding and clarity in clinical reporting of germline genetic tests for cancer susceptibility.

MicroRNA-196a is regulated by ER and is a prognostic biomarker in ER+ breast cancer.

BACKGROUND: MicroRNAs are potent post-transcriptional regulators involved in all hallmarks of cancer. Mir-196a is transcribed from two loci and has been implicated in a wide range of developmental and pathogenic processes, with targets including Hox, Fox, Cdk inhibitors and annexins. Genetic variants and altered expression of MIR196A are associated with risk and progression of multiple cancers including breast cancer, however little is known about the regulation of the genes encoding this miRNA, nor the impact of variants therein. METHODS: Genomic data and chromatin interaction analysis were used to discover functional promoter and enhancer elements for MIR196A. Expression data were used to associate MIR196A with mechanisms of resistance, breast cancer subtypes and prognosis. RESULTS: Here we demonstrate that MIR196A displays complex and dynamic expression patterns, in part controlled by long-range transcriptional regulation between promoter and enhancer elements bound by ERα. Expression of this miRNA is significantly increased in drug-resistant models of hormone-receptor positive disease. The expression of MIR196A also proves to be a robust prognostic factor for patients with advanced and post-menopausal ER+ disease. CONCLUSION: This work sheds light on the normal and abnormal regulation of MIR196A and provides a novel stratification method for therapeutically resistant breast cancer.