Mucosal Tuft Cell Density Is Increased in Diarrhea-Predominant Irritable Bowel Syndrome Colonic Biopsies.

Tuft cells are rare chemosensory sentinels found in the gut epithelium. When triggered by helminth infection, tuft cells secrete interleukin-25 (IL-25) basolaterally and subsequently evoke an immune response. Irritable bowel syndrome (IBS) is a common and heterogeneous disorder characterized by bowel dysfunction and visceral pain sensitivity.

Glucagon-Like Peptide-1 Secreting L-Cells Coupled to Sensory Nerves Translate Microbial Signals to the Host Rat Nervous System.

An intact gut epithelium preserves the immunological exclusion of "non-self" entities in the external environment of the gut lumen. Nonetheless, information flows continuously across this interface, with the host immune, endocrine, and neural systems all involved in monitoring the luminal environment of the gut. Both pathogenic and commensal gastrointestinal (GI) bacteria can modulate centrally-regulated behaviors and brain neurochemistry and, although the vagus nerve has been implicated in the microbiota-gut-brain signaling axis, the cellular and molecular machinery that facilitates this communication is unclear.

GHSR-1 agonist sensitizes rat colonic intrinsic and extrinsic neurons to exendin-4: A role in the manifestation of postprandial gastrointestinal symptoms in irritable bowel syndrome?

Background: Patients with irritable bowel syndrome (IBS) may experience postprandial symptom exacerbation. Nutrients stimulate intestinal release of glucagon-like peptide 1 (GLP-1), an incretin hormone with known gastrointestinal effects. However, prior to the postprandial rise in GLP-1, levels of the hunger hormone, ghrelin, peak.

Reassessing risk models for atypical hyperplasia: age may not matter.

Purpose: The aim of this study was to investigate the influence of age at diagnosis of atypical hyperplasia ("atypia", ductal [ADH], lobular [ALH], or severe ADH) on the risk of developing subsequent invasive breast cancer or ductal carcinoma in situ (DCIS).

Methods: Using standard survival analysis methods, we retrospectively analyzed 1353 women not treated with chemoprevention among a cohort of 2370 women diagnosed with atypical hyperplasia to determine the risk relationship between age at diagnosis and subsequent breast cancer.

Results: For all atypia diagnoses combined, our cohort showed a 5-, 10-, and 15-year risk of invasive breast cancer or DCIS of 0.

A Study of the Growth Patterns of Breast Carcinoma Using 3D Reconstruction: A Pilot Study.

Lumpectomy with microscopically clear margins is a safe and effective approach for surgical management of breast carcinoma. Margins are positive for tumor in 18-50% of lumpectomies, as it is not possible to accurately determine the shape or microscopic borders of a tumor preoperatively or intraoperatively. We examined the 3D microanatomy and growth patterns of common breast carcinoma subtypes to provide guidance for lumpectomy surgery.

Using machine learning to parse breast pathology reports.

Purpose: Extracting information from electronic medical record is a time-consuming and expensive process when done manually. Rule-based and machine learning techniques are two approaches to solving this problem. In this study, we trained a machine learning model on pathology reports to extract pertinent tumor characteristics, which enabled us to create a large database of attribute searchable pathology reports.

Factors Associated with Recurrence Rates and Long-Term Survival in Women Diagnosed with Breast Cancer Ages 40 and Younger.

Background: Young age at breast cancer diagnosis has been associated with increased risk of recurrence and mortality. We reevaluated this assumption in a large, modern cohort of women diagnosed with breast cancer at age ≤40 years.

Methods: We identified women with breast cancer at age ≤40 years at a single institution from 1996-2008.

Intraoperative micro-computed tomography (micro-CT): a novel method for determination of primary tumour dimensions in breast cancer specimens.

Objectives: Micro-CT is a promising modality to determine breast tumour size in three dimensions in intact lumpectomy specimens. We compared the accuracy of tumour size measurements using specimen micro-CT with measurements using multimodality pre-operative imaging.

Methods: A tabletop micro-CT was used to image breast lumpectomy specimens.

Breast Cancer Risk and Follow-up Recommendations for Young Women Diagnosed with Atypical Hyperplasia and Lobular Carcinoma In Situ (LCIS).

Background: The risk of breast cancer in young women diagnosed with atypical hyperplasia and (LCIS) is not well defined. The objectives were to evaluate outcomes and to help determine guidelines for follow-up in this population.

Methods: A retrospective review of women under age 35 diagnosed with ADH, ALH, LCIS, and severe ADH from 1987 to 2010 was performed.

A pilot study evaluating shaved cavity margins with micro-computed tomography: a novel method for predicting lumpectomy margin status intraoperatively.

Microscopically clear lumpectomy margins are essential in breast conservation, as involved margins increase local recurrence. Currently, 18-50% of lumpectomies have close or positive margins that require re-excision. We assessed the ability of micro-computed tomography (micro-CT) to evaluate lumpectomy shaved cavity margins (SCM) intraoperatively to determine if this technology could rapidly identify margin involvement by tumor and reduce re-excision rates.

Micro-computed tomography (Micro-CT): a novel approach for intraoperative breast cancer specimen imaging.

Intraoperative radiographic examination of breast specimens is commonly performed to confirm excision of image-detected breast lesions, but it is not reliable for assessing margin status. A more accurate method of intraoperative breast specimen imaging is needed. Micro-CT provides quantitative imaging parameters, image rotation, and virtual "slicing" of intact breast specimens.

The role of chemoprevention in modifying the risk of breast cancer in women with atypical breast lesions.

Women with atypical ductal hyperplasia (ADH), atypical lobular hyperplasia (ALH), lobular carcinoma in situ (LCIS), and severe ADH are at increased risk of breast cancer, but a systematic quantification of this risk and the efficacy of chemoprevention in the clinical setting is still lacking. The objective of this study is to evaluate a woman's risk of breast cancer based on atypia type and to determine the effect of chemoprevention in decreasing this risk. Review of 76,333 breast pathology reports from three institutions within Partners Healthcare System, Boston, from 1987 to 2010 using natural language processing was carried out.

The feasibility of using natural language processing to extract clinical information from breast pathology reports.

Objective: The opportunity to integrate clinical decision support systems into clinical practice is limited due to the lack of structured, machine readable data in the current format of the electronic health record. Natural language processing has been designed to convert free text into machine readable data. The aim of the current study was to ascertain the feasibility of using natural language processing to extract clinical information from >76,000 breast pathology reports.

Cost comparison of radiation treatment options after lumpectomy for breast cancer.

Background: Radiation therapy (RT) after lumpectomy for breast cancer can be delivered with several different regimens. We evaluated a cost-minimization strategy to select among RT options.

Methods: An institutional review board (IRB)-approved retrospective review identified a sample of 100 women who underwent lumpectomy for invasive or in situ breast cancer during 2009.

Lumpectomy cavity shaved margins do not impact re-excision rates in breast cancer patients.

Background: The benefits of taking shaved cavity margins (SCM) at the time of lumpectomy are unclear. We sought to determine if taking SCM decreases re-excision rates by increasing the total breast tissue volume excised.

Methods: We undertook a retrospective review of breast cancer patients who underwent lumpectomy from 2004 to 2006.

Increased susceptibility of ST2-deficient mice to polymicrobial sepsis is associated with an impaired bactericidal function.

ST2, a member of the Toll/IL-1R superfamily, negatively regulates both TLR2 and TLR4 signaling. In this study, we report that ST2-deficient mice were more susceptible to polymicrobial sepsis than their wild-type littermates, with increased production of proinflammatory cytokines. Bacterial clearance from the circulation and visceral organs following polymicrobial infection was markedly impaired in ST2-deficient mice.

The safety of multiple re-excisions after lumpectomy for breast cancer.

Background: Breast cancer patients may undergo multiple re-excisions after lumpectomy in an attempt to obtain clear margins and avoid mastectomy. We sought to determine the overall local recurrence rate and surgical outcome of patients undergoing two or more re-excisions and to identify predictors of success in attaining clear margins.

Methods: Retrospective review of breast cancer patients who underwent lumpectomy for invasive cancer or ductal carcinoma in situ (DCIS) from 1997 to 2007.

ST2 negatively regulates TLR2 signaling, but is not required for bacterial lipoprotein-induced tolerance.

Activation of TLR signaling is critical for host innate immunity against bacterial infection. Previous studies reported that the ST2 receptor, a member of the Toll/IL-1 receptor superfamily, functions as a negative regulator of TLR4 signaling and maintains LPS tolerance. However, it is undetermined whether ST2 negatively regulates TLR2 signaling and furthermore, whether a TLR2 agonist, bacterial lipoprotein (BLP)-induced tolerance is dependent on ST2.

Cellular reprogramming by gram-positive bacterial components: a review.

LPS tolerance has been the focus of extensive scientific and clinical research over the last several decades in an attempt to elucidate the sequence of changes that occur at a molecular level in tolerized cells. Tolerance to components of gram-positive bacterial cell walls such as bacterial lipoprotein and lipoteichoic acid is a much lesser studied, although equally important, phenomenon. This review will focus on cellular reprogramming by gram-positive bacterial components and examines the alterations in cell surface receptor expression, changes in intracellular signaling, gene expression and cytokine production, and the phenomenon of cross-tolerance.