An annotated bibliography of materials suitable for use in teaching French in the elementary school

Thesis (Ed.M.)--Boston Universit

ST-Producing E. coli Oppose Carcinogen-Induced Colorectal Tumorigenesis in Mice.

There is a geographic inequality in the incidence of colorectal cancer, lowest in developing countries, and greatest in developed countries. This disparity suggests an environmental contribution to cancer resistance in endemic populations. Enterotoxigenic bacteria associated with diarrheal disease are prevalent in developing countries, including enterotoxigenic E. coli (ETEC) producing heat-stable enterotoxins (STs). STs are peptides that are structurally homologous to paracrine hormones that regulate the intestinal guanylyl cyclase C (GUCY2C) receptor. Beyond secretion, GUCY2C is a tumor suppressor universally silenced by loss of expression of its paracrine hormone during carcinogenesis. Thus, the geographic imbalance in colorectal cancer, in part, may reflect chronic exposure to ST-producing organisms that restore GUCY2C signaling silenced by hormone loss during transformation. Here, mice colonized for 18 weeks with control E. coli or those engineered to secrete ST exhibited normal growth, with comparable weight gain and normal stool water content, without evidence of secretory diarrhea. Enterotoxin-producing, but not control, E. coli, generated ST that activated colonic GUCY2C signaling, cyclic guanosine monophosphate (cGMP) production, and cGMP-dependent protein phosphorylation in colonized mice. Moreover, mice colonized with ST-producing E. coli exhibited a 50% reduction in carcinogen-induced colorectal tumor burden. Thus, chronic colonization with ETEC producing ST could contribute to endemic cancer resistance in developing countries, reinforcing a novel paradigm of colorectal cancer chemoprevention with oral GUCY2C-targeted agents

The Ground on Which We All Stand: A Conversation About Menstrual Equity Law and Activism

This essay grows out of a panel discussion among five lawyers on the subject of menstrual equity activism. Each of the authors is a scholar, activist or organizer involved in some form of menstrual equity work. The overall project is both enriched and complicated by an intersectional analysis. This essay increases awareness of existing menstrual equity and menstrual justice work; it also identifies avenues for further inquiry, next steps for legal action, and opportunities that lie ahead. After describing prior and current work at the junction of law and menstruation, the contributors evaluate the successes and limitations of recent legal changes. The authors then turn to conceptual issues about the relationship between menstrual equity and gender justice, as well as the difference between equity and equality. The essay concludes with consideration of the future of menstrual equity and menstrual justice work. The authors envision an expanded, inclusive group of individuals working for greater gender justice

Guanylate cyclase C as a target for prevention, detection, and therapy in colorectal cancer.

INTRODUCTION: Colorectal cancer remains the second leading cause of cancer death in the United States, and new strategies to prevent, detect, and treat the disease are needed. The receptor, guanylate cyclase C (GUCY2C), a tumor suppressor expressed by the intestinal epithelium, has emerged as a promising target. Areas covered: This review outlines the role of GUCY2C in tumorigenesis, and steps to translate GUCY2C-targeting schemes to the clinic. Endogenous GUCY2C-activating ligands disappear early in tumorigenesis, silencing its signaling axis and enabling transformation. Pre-clinical models support GUCY2C ligand supplementation as a novel disease prevention paradigm. With the recent FDA approval of the GUCY2C ligand, linaclotide, and two more synthetic ligands in the pipeline, this strategy can be tested in human trials. In addition to primary tumor prevention, we also review immunotherapies targeting GUCY2C expressed by metastatic lesions, and platforms using GUCY2C as a biomarker for detection and patient staging. Expert commentary: Results of the first GUCY2C targeting schemes in patients will become available in the coming years. The identification of GUCY2C ligand loss as a requirement for colorectal tumorigenesis has the potential to change the treatment paradigm from an irreversible disease of genetic mutation, to a treatable disease of ligand insufficiency

GUCY2C maintains intestinal LGR5+ stem cells by opposing ER stress

Long-lived multipotent stem cells (ISCs) at the base of intestinal crypts adjust their phenotypes to accommodate normal maintenance and post-injury regeneration of the epithelium. Their long life, lineage plasticity, and proliferative potential underlie the necessity for tight homeostatic regulation of the ISC compartment. In that context, the guanylate cyclase C (GUCY2C) receptor and its paracrine ligands regulate intestinal epithelial homeostasis, including proliferation, lineage commitment, and DNA damage repair. However, a role for this axis in maintaining ISCs remains unknown. Transgenic mice enabling analysis of ISCs (Lgr5-GFP) in the context of GUCY2C elimination (Gucy2c-/-) were combined with immunodetection techniques and pharmacological treatments to define the role of the GUCY2C signaling axis in supporting ISCs. ISCs were reduced in Gucy2c-/- mice, associated with loss of active Lgr5+ cells but a reciprocal increase in reserve Bmi1+ cells. GUCY2C was expressed in crypt base Lgr5+ cells in which it mediates canonical cyclic (c) GMPdependent signaling. Endoplasmic reticulum (ER) stress, typically absent from ISCs, was elevated throughout the crypt base in Gucy2c-/- mice. The chemical chaperone tauroursodeoxycholic acid resolved this ER stress and restored the balance of ISCs, an effect mimicked by the GUCY2C effector 8Br-cGMP. Reduced ISCs in Gucy2c-/-mice was associated with greater epithelial injury and impaired regeneration following sub-lethal doses of irradiation. These observations suggest that GUCY2C provides homeostatic signals that modulate ER stress and cell vulnerability as part of the machinery contributing to the integrity of ISCs. © Kraft et al

The pharmacokinetics of nebulized nanocrystal budesonide suspension in healthy volunteers.

Nanocrystal budesonide (nanobudesonide) is a suspension for nebulization in patients with steroid-responsive pulmonary diseases such as asthma. The pharmacokinetics and safety of the product were compared to those of Pulmicort Respules. Sixteen healthy volunteers were administered nanobudesonide 0.5 and 1.0 mg, Pulmicort Respules 0.5 mg, and placebo in a four-way, randomized crossover design. All nebulized formulations were well tolerated, with no evidence of bronchospasm. Nebulization times were significantly shorter for nanobudesonide compared to Pulmicort Respules. Because of a low oral bioavailability, plasma concentration of budesonide is a good marker of lung-delivered dose. The pharmacokinetics of nanobudesonide 0.5 and 1.0 mg were approximately dose proportional with respect to Cmax, AUC(0-t), and AUC(0-infinity). Nanobudesonide 0.5 mg and Pulmicort Respules 0.5 mg exhibited similar AUCs, suggesting a similar extent of pulmonary absorption. A higher Cmax was noted with nanobudesonide 0.5 mg, and the tmax was significantly different, suggesting a more rapid rate of drug delivery of nanobudesonide 0.5 mg than Pulmicort Respules. In conclusion, nebulized nanobudesonide 0.5 mg was safe in healthy volunteers, with a similar extent of absorption as Pulmicort Respules

APC-β-catenin-TCF signaling silences the intestinal guanylin-GUCY2C tumor suppressor axis.

Sporadic colorectal cancer initiates with mutations in APC or its degradation target β-catenin, producing TCF-dependent nuclear transcription driving tumorigenesis. The intestinal epithelial receptor, GUCY2C, with its canonical paracrine hormone guanylin, regulates homeostatic signaling along the crypt-surface axis opposing tumorigenesis. Here, we reveal that expression of the guanylin hormone, but not the GUCY2C receptor, is lost at the earliest stages of transformation in APC-dependent tumors in humans and mice. Hormone loss, which silences GUCY2C signaling, reflects transcriptional repression mediated by mutant APC-β-catenin-TCF programs in the nucleus. These studies support a pathophysiological model of intestinal tumorigenesis in which mutant APC-β-catenin-TCF transcriptional regulation eliminates guanylin expression at tumor initiation, silencing GUCY2C signaling which, in turn, dysregulates intestinal homeostatic mechanisms contributing to tumor progression. They expand the mechanistic paradigm for colorectal cancer from a disease of irreversible mutations in APC and β-catenin to one of guanylin hormone loss whose replacement, and reconstitution of GUCY2C signaling, could prevent tumorigenesis

Title IX & Menstruation

“Oh no. Could I borrow a tampon or pad?” These (or similar) words are familiar to almost everyone who has ever had a period. Even for adults, menstruation can at times be a challenge. For some schoolchildren, it can be an insurmountable obstacle to receiving an education. Students are subject to constant observation by classmates and teachers; they may not have autonomous access to a bathroom during the school day; or they may not be able to afford menstrual products. They may experience menstruation-related peer harassment, restrictive school policies, a lack of access to menstrual products, and inadequate menstruation-related education. As a result, a menstruating student may find it difficult to concentrate in school or even attend school at all, depending on the circumstances. This Article explores the intersection of menstruation and education to uncover the related impediments students face. Because menstruation is uniquely associated with female biology, a school’s failure to address the needs of menstruating students amounts to a denial of educational opportunities on the basis of sex under Title IX. In recent years, students themselves have played notable roles in successful efforts to cause schools to provide free pads or tampons to students. Currently most states do not require schools to do so. Even in states where schools have a legal obligation to provide menstrual products to students, availability is only one part of a larger problem. Unless students can access bathroom facilities in response to their biological needs, and do so without shame, stigma or restriction, students may risk bleeding during class, failing to change tampons or pads as medically recommended, or even leaving (or skipping) school. This Article argues that pursuant to Title IX, schools should provide students with an education free of unnecessary anxiety about the biological process of menstruation. This freedom from anxiety is a necessary precondition for having meaningful opportunities to fully participate in school and all aspects of public life. In its final section, the Article buttresses its analysis by employing multiple theoretical frameworks to examine the intersection of menstruation and education, concluding that menstruation is a foundational issue that the law must take into account so that society can benefit from the full participation of all of its members

Title IX and Menstruation

“Oh no. Could I borrow a tampon or pad?” These (or similar) words are familiar to almost everyone who has ever had a period. Even for adults, menstruation can at times be a challenge. For some schoolchildren, it can be an insurmountable obstacle to receiving an education. Students are subject to constant observation by classmates and teachers; they may not have autonomous access to a bathroom during the school day; or they may not be able to afford menstrual products. They may experience menstruation-related peer harassment, restrictive school policies, a lack of access to menstrual products, and inadequate menstruation-related education. As a result, a menstruating student may find it difficult to concentrate in school or even attend school at all, depending on the circumstances. This Article explores the intersection of menstruation and education to uncover the related impediments students face. Because menstruation is uniquely associated with female biology, a school’s failure to address the needs of menstruating students amounts to a denial of educational opportunities on the basis of sex under Title IX. In recent years, students themselves have played notable roles in successful efforts to cause schools to provide free pads or tampons to students. Currently most states do not require schools to do so. Even in states where schools have a legal obligation to provide menstrual products to students, availability is only one part of a larger problem. Unless students can access bathroom facilities in response to their biological needs, and do so without shame, stigma or restriction, students may risk bleeding during class, failing to change tampons or pads as medically recommended, or even leaving (or skipping) school. This Article argues that pursuant to Title IX, schools should provide students with an education free of unnecessary anxiety about the biological process of menstruation. This freedom from anxiety is a necessary precondition for having meaningful opportunities to fully participate in school and all aspects of public life. In its final section, the Article buttresses its analysis by employing multiple theoretical frameworks to examine the intersection of menstruation and education, concluding that menstruation is a foundational issue that the law must take into account so that society can benefit from the full participation of all of its members