Recommended standardized anatomic terminology of the posterior female pelvis and vulva based on a structured medical literature review.

BACKGROUND: Anatomic terminology in both written and verbal forms has been shown to be inaccurate and imprecise. OBJECTIVE: Here, we aimed to (1) review published anatomic terminology as it relates to the posterior female pelvis, posterior vagina, and vulva; (2) compare these terms to "Terminologia Anatomica," the internationally standardized terminology; and (3) compile standardized anatomic terms for improved communication and understanding. STUDY DESIGN: From inception of the study to April 6, 2018, MEDLINE database was used to search for 40 terms relevant to the posterior female pelvis and vulvar anatomy. Furthermore, 11 investigators reviewed identified abstracts and selected those reporting on posterior female pelvic and vulvar anatomy for full-text review. In addition, 11 textbook chapters were included in the study. Definitions of all pertinent anatomic terms were extracted for review. RESULTS: Overall, 486 anatomic terms were identified describing the vulva and posterior female pelvic anatomy, including the posterior vagina. "Terminologia Anatomica" has previously accepted 186 of these terms. Based on this literature review, we proposed the adoption of 11 new standardized anatomic terms, including 6 regional terms (anal sphincter complex, anorectum, genital-crural fold, interlabial sulcus, posterior vaginal compartment, and sacrospinous-coccygeus complex), 4 structural terms (greater vestibular duct, anal cushions, nerve to the levator ani, and labial fat pad), and 1 anatomic space (deep postanal space). In addition, the currently accepted term rectovaginal fascia or septum was identified as controversial and requires further research and definition before continued acceptance or rejection in medical communication. CONCLUSION: This study highlighted the variability in the anatomic nomenclature used in describing the posterior female pelvis and vulva. Therefore, we recommended the use of standardized terminology to improve communication and education across medical and anatomic disciplines.

Cribriform prostate cancer: Morphologic criteria enabling a diagnosis, based on survey of experts.

Among four sub-patterns of Gleason grade 4 prostate cancer, voluminous evidence supports that the cribriform pattern holds an unfavorable prognostic impact, as compared with poorly-formed, fused, or glomeruloid. The International Society of Urological Pathology (ISUP) recommends specifying whether invasive grade 4 cancer is cribriform. Recently, ISUP experts published a consensus definition of cribriform pattern highlighting criteria that distinguish it from mimickers. The current study aimed to analyze morphologic features separately to identify those that define the essence of the cribriform pattern. Thirty-two selected photomicrographs were classified by 12 urologic pathologists as: definitely cribriform cancer, probably cribriform, unsure, probably not cribriform, or definitely not cribriform. Consensus was defined as 9/12 agree or disagree, with ≤1 strongly supporting the opposite choice. Final consensus was achieved in 21 of 32 cases. Generalized estimating equation (GEE) model with logit link was fitted to estimate effect of multiple morphologic predictors. Fisher exact test was used for categorical findings. Presence of intervening stroma precluded calling cribriform cancer (p = 0.006). Mucin presence detracted (p = 0.003) from willingness to call cribriform cancer (only 3 cases had mucin). Lumen number was associated with cribriform consensus (p = 0.0006), and all consensus cases had ≥9 lumens. Predominant papillary pattern or an irregular outer boundary detracted (p = NS). Invasive cribriform carcinoma should have absence of intervening stroma, and usually neither papillary pattern, irregular outer boundary, nor very few lumens. Setting the criteria for cribriform will help prevent over- or undercalling this important finding.

Aquaculture Production of the Brown Seaweeds Laminaria digitata and Macrocystis pyrifera: Applications in Food and Pharmaceuticals.

Seaweeds have a long history of use as food, as flavouring agents, and find use in traditional folk medicine. Seaweed products range from food, feed, and dietary supplements to pharmaceuticals, and from bioenergy intermediates to materials. At present, 98% of the seaweed required by the seaweed industry is provided by five genera and only ten species. The two brown kelp seaweeds Laminaria digitata, a native Irish species, and Macrocystis pyrifera, a native New Zealand species, are not included in these eleven species, although they have been used as dietary supplements and as animal and fish feed. The properties associated with the polysaccharides and proteins from these two species have resulted in increased interest in them, enabling their use as functional foods. Improvements and optimisations in aquaculture methods and bioproduct extractions are essential to realise the commercial potential of these seaweeds. Recent advances in optimising these processes are outlined in this review, as well as potential future applications of L. digitata and, to a greater extent, M. pyrifera which, to date, has been predominately only wild-harvested. These include bio-refinery processing to produce ingredients for nutricosmetics, functional foods, cosmeceuticals, and bioplastics. Areas that currently limit the commercial potential of these two species are highlighted.

Follow-up of Prostatectomy versus Observation for Early Prostate Cancer.

BACKGROUND: We previously found no significant differences in mortality between men who underwent surgery for localized prostate cancer and those who were treated with observation only. Uncertainty persists regarding nonfatal health outcomes and long-term mortality. METHODS: From November 1994 through January 2002, we randomly assigned 731 men with localized prostate cancer to radical prostatectomy or observation. We extended follow-up through August 2014 for our primary outcome, all-cause mortality, and the main secondary outcome, prostate-cancer mortality. We describe disease progression, treatments received, and patient-reported outcomes through January 2010 (original follow-up). RESULTS: During 19.5 years of follow-up (median, 12.7 years), death occurred in 223 of 364 men (61.3%) assigned to surgery and in 245 of 367 (66.8%) assigned to observation (absolute difference in risk, 5.5 percentage points; 95% confidence interval [CI], -1.5 to 12.4; hazard ratio, 0.84; 95% CI, 0.70 to 1.01; P=0.06). Death attributed to prostate cancer or treatment occurred in 27 men (7.4%) assigned to surgery and in 42 men (11.4%) assigned to observation (absolute difference in risk, 4.0 percentage points; 95% CI, -0.2 to 8.3; hazard ratio, 0.63; 95% CI, 0.39 to 1.02; P=0.06). Surgery may have been associated with lower all-cause mortality than observation among men with intermediate-risk disease (absolute difference, 14.5 percentage points; 95% CI, 2.8 to 25.6) but not among those with low-risk disease (absolute difference, 0.7 percentage points; 95% CI, -10.5 to 11.8) or high-risk disease (absolute difference, 2.3 percentage points; 95% CI, -11.5 to 16.1) (P=0.08 for interaction). Treatment for disease progression was less frequent with surgery than with observation (absolute difference, 26.2 percentage points; 95% CI, 19.0 to 32.9); treatment was primarily for asymptomatic, local, or biochemical (prostate-specific antigen) progression. Urinary incontinence and erectile and sexual dysfunction were each greater with surgery than with observation through 10 years. Disease-related or treatment-related limitations in activities of daily living were greater with surgery than with observation through 2 years. CONCLUSIONS: After nearly 20 years of follow-up among men with localized prostate cancer, surgery was not associated with significantly lower all-cause or prostate-cancer mortality than observation. Surgery was associated with a higher frequency of adverse events than observation but a lower frequency of treatment for disease progression, mostly for asymptomatic, local, or biochemical progression. (Funded by the Department of Veterans Affairs and others; PIVOT ClinicalTrials.gov number, NCT00007644 .).

A Genomic Classifier for Predicting Clinically Aggressive Luminal Bladder Tumors with Higher Rates of Pathological Up Staging.

PURPOSE: Urothelial carcinoma of the luminal molecular subtype is associated with lower rates of pathological up staging from clinical stage T1-T2 to nonorgan confined (pT3 or greater and/or pN+) disease at radical cystectomy. However, approximately a third of luminal urothelial carcinoma cases were up staged to nonorgan confined disease, and these may be under treated if neoadjuvant chemotherapy is withheld. In this study we trained a genomic classifier to predict luminal nonorgan confined disease in patients diagnosed with clinically organ confined (cT1/T2) disease. MATERIALS AND METHODS: Specimens from transurethral resected high grade cT1-T2N0M0 urothelial carcinoma of the bladder that belonged to the luminal subtype (Seiler 2017) were randomly split into training (75) and testing (25) sets for the development of a single sample luminal up staging classifier using lasso/ridge-penalized logistic regression. All patients underwent radical cystectomy without neoadjuvant chemotherapy and the primary end point was up staging to nonorgan confined disease. A radical cystectomy cohort and a platinum treated neoadjuvant chemotherapy cohort were used to evaluate the luminal up staging classifier. RESULTS: Up staging to nonorgan confined disease occurred in 34% of luminal cases. The luminal up staging classifier predicted up staging in 32 of 34 cases, with 6 false-positives (AUC 0.96). The sensitivity for detection of luminal pN+ disease was 95% (20 of 21). Patients with predicted nonorgan confined luminal tumors had worse survival than those with organ confined luminal tumors (p=0.001). On multivariable analysis the luminal up staging classifier was a significant predictor of overall survival after adjusting for clinical variables available at transurethral resection. The luminal up staging classifier also predicted overall survival for aggressive luminal TCGA (The Cancer Genome Atlas) cases (n=83, p=0.043). In the neoadjuvant chemotherapy cohort the luminal up staging classifier predicted 9 up staging cases, all of which had excellent prognosis. CONCLUSIONS: A luminal up staging classifier was developed that distinguishes a subset of cT1-T2N0M0 luminal urothelial carcinoma cases at high risk for up staging to nonorgan confined disease at radical cystectomy and of death. Validation of this model in an independent, large patient cohort is necessary to determine how molecular stratification of luminal tumors could be used to guide treatment of these patients.

The parotid secretory protein BPIFA2 is a salivary surfactant that affects lipopolysaccharide action.

NEW FINDINGS: What is the central question of this study? The salivary protein BPIFA2 binds lipopolysaccharide, but its physiological function is not known. This study uses a new knockout mouse model to explore the physiological role of BPIFA2 in the oral cavity and systemic physiology. What is the main finding and its importance? BPIFA2 is a crucial surfactant in mouse saliva. In its absence, saliva exhibits the surface tension of water. Depletion of BPIFA2 affects salivary and ingested lipopolysaccharide and leads to systemic sequelae that include increased insulin secretion and metabolomic changes. These results suggest that the lipopolysaccharide-binding activity of BPIFA2 affects the activity of ingested lipopolysaccharide in the intestine and that BPIFA2 depletion causes mild metabolic endotoxaemia. ABSTRACT: Saliva plays important roles in the mastication, swallowing and digestion of food, speech and lubrication of the oral mucosa, antimicrobial and anti-inflammatory activities, and the control of body temperature in grooming animals. The salivary protein BPIFA [BPI fold containing family A member 2; former names: parotid secretory protein (PSP), SPLUN2 and C20orf70] is related to lipid-binding and lipopolysaccharide (LPS)-binding proteins expressed in the mucosa. Indeed, BPIFA2 binds LPS, but the physiological role of BPIFA2 remains to be determined. To address this question, Bpifa2 knockout (Bpifa2tm1(KOMP)Vlcg ) (KO) mice were phenotyped, with emphasis on the saliva and salivary glands. Stimulated whole saliva collected from KO mice was less able to spread on a hydrophobic surface than wild-type saliva, and the surface tension of KO saliva was close to that of water. These data suggest that BPIFA2 is a salivary surfactant that is mainly responsible for the low surface tension of mouse saliva. The reduced surfactant activity of KO saliva did not affect consumption of dry food or grooming, but saliva from KO mice contained less LPS than wild-type saliva. Indeed, mice lacking BPIFA2 responded to ingested LPS with an increased stool frequency, suggesting that BPIFA2 plays a role in the solubilization and activity of ingested LPS. Consistent with these findings, BPIFA2-depleted mice also showed increased insulin secretion and metabolomic changes that were consistent with a mild endotoxaemia. These results support the distal physiological function of a salivary protein and reinforce the connection between oral biology and systemic disease.

Standardized terminology of apical structures in the female pelvis based on a structured medical literature review.

The objectives of this study were to review the published literature and selected textbooks, to compare existing usage to that in Terminologia Anatomica, and to compile standardized anatomic nomenclature for the apical structures of the female pelvis. MEDLINE was searched from inception until May 30, 2017, based on 33 search terms generated by group consensus. Resulting abstracts were screened by 11 reviewers to identify pertinent studies reporting on apical female pelvic anatomy. Following additional focused screening for rarer terms and selective representative random sampling of the literature for common terms, accepted full-text manuscripts and relevant textbook chapters were extracted for anatomic terms related to apical structures. From an initial total of 55,448 abstracts, 193 eligible studies were identified for extraction, to which 14 chapters from 9 textbooks were added. In all, 293 separate structural terms were identified, of which 184 had Terminologia Anatomica-accepted terms. Inclusion of several widely used regional terms (vaginal apex, adnexa, cervico-vaginal junction, uretero-vesical junction, and apical segment), structural terms (vesicouterine ligament, paracolpium, mesoteres, mesoureter, ovarian venous plexus, and artery to the round ligament) and spaces (vesicocervical, vesicovaginal, presacral, and pararectal) not included in Terminologia Anatomica is proposed. Furthermore, 2 controversial terms (lower uterine segment and supravaginal septum) were identified that require additional research to support or refute continued use in medical communication. This study confirms and identifies inconsistencies and gaps in the nomenclature of apical structures of the female pelvis. Standardized terminology should be used when describing apical female pelvic structures to facilitate communication and to promote consistency among multiple academic, clinical, and surgical disciplines.

ORIGIN AND DEVELOPMENT OF AMERICAN SURGICAL PATHOLOGY.

Although the discipline of pathology had its very beginnings in the earliest development and evolution of what became "modern medicine," the subset of pathology known as "surgical pathology" had its origins only in the last two centuries. Surgical pathology began as a clinico-pathologic analysis of gross morphologic findings with clinical outcomes, beginning with findings at autopsy. With the advent of microscopy, which enabled a higher level of morphologic classification and disease understanding, along with advances in surgery (anesthesia, antisepsis, and then antibiotics), the need for accurate pathologic classification in the living patient became of paramount importance. This review chronicles the evolution of surgical pathology in the United States in the context of advances in the science and practice of medicine generally and surgery specifically.

Recommended standardized terminology of the anterior female pelvis based on a structured medical literature review.

BACKGROUND: The use of imprecise and inaccurate terms leads to confusion amongst anatomists and medical professionals. OBJECTIVE: We sought to create recommended standardized terminology to describe anatomic structures of the anterior female pelvis based on a structured review of published literature and selected text books. STUDY DESIGN: We searched MEDLINE from its inception until May 2, 2016, using 11 medical subject heading terms to identify studies reporting on anterior female pelvic anatomy; any study type published in English was accepted. Nine textbooks were also included. We screened 12,264 abstracts, identifying 200 eligible studies along with 13 textbook chapters from which we extracted all pertinent anatomic terms. RESULTS: In all, 67 unique structures in the anterior female pelvis were identified. A total of 59 of these have been previously recognized with accepted terms in Terminologia Anatomica, the international standard on anatomical terminology. We also identified and propose the adoption of 4 anatomic regional terms (lateral vaginal wall, pelvic sidewall, pelvic bones, and anterior compartment), and 2 structural terms not included in Terminologia Anatomica (vaginal sulcus and levator hiatus). In addition, we identified 2 controversial terms (pubourethral ligament and Grafenberg spot) that require additional research and consensus from the greater medical and scientific community prior to adoption or rejection of these terms. CONCLUSION: We propose standardized terminology that should be used when discussing anatomic structures in the anterior female pelvis to help improve communication among researchers, clinicians, and surgeons.

Nonantimuscarinic treatment for overactive bladder: a systematic review.

The purpose of the study was to determine the efficacy and safety of nonantimuscarinic treatments for overactive bladder. Medline, Cochrane, and other databases (inception to April 2, 2014) were used. We included any study design in which there were 2 arms and an n > 100, if at least 1 of the arms was a nonantimuscarinic therapy or any comparative trial, regardless of number, if at least 2 arms were nonantimuscarinic therapies for overactive bladder. Eleven reviewers double-screened citations and extracted eligible studies for study: population, intervention, outcome, effects on outcome categories, and quality. The body of evidence for categories of interventions were summarized and assessed for strength. Ninety-nine comparative studies met inclusion criteria. Interventions effective to improve subjective overactive bladder symptoms include exercise with heat and steam generating sheets (1 study), diaphragmatic (1 study), deep abdominal (1 study), and pelvic floor muscle training exercises (2 studies). Pelvic floor exercises are more effective in subjective and objective outcomes with biofeedback or verbal feedback. Weight loss with diet and exercise, caffeine reduction, 25-50% reduction in fluid intake, and pelvic floor muscle exercises with verbal instruction and or biofeedback were all efficacious. Botulinum toxin A improves urge incontinence episodes, urgency, frequency, quality of life, nocturia, and urodynamic testing parameters. Acupuncture improves quality of life and urodynamic testing parameters. Extracorporeal magnetic stimulation improves urodynamic parameters. Mirabegron improves daily incontinence episodes, nocturia, number of daily voids, and urine volume per void, whereas solabegron improves daily incontinence episodes. Short-term posterior tibial nerve stimulation is more efficacious than pelvic floor muscle training exercises and behavioral therapy for improving: urgency, urinary incontinence episodes, daily voids, volume per void, and overall quality of life. Sacral neuromodulation is more efficacious than antimuscarinic treatment for subjective improvement of overactive bladder and quality of life. Transvaginal electrical stimulation demonstrates subjective improvement in overactive bladder symptoms and urodynamic parameters. Multiple therapies, including physical therapy, behavioral therapy, botulinum toxin A, acupuncture, magnetic stimulation, mirabegron, posterior tibial nerve stimulation, sacral neuromodulation, and transvaginal electrical stimulation, are efficacious in the treatment of overactive bladder.

Radical prostatectomy versus observation for localized prostate cancer.

BACKGROUND: The effectiveness of surgery versus observation for men with localized prostate cancer detected by means of prostate-specific antigen (PSA) testing is not known. METHODS: From November 1994 through January 2002, we randomly assigned 731 men with localized prostate cancer (mean age, 67 years; median PSA value, 7.8 ng per milliliter) to radical prostatectomy or observation and followed them through January 2010. The primary outcome was all-cause mortality; the secondary outcome was prostate-cancer mortality. RESULTS: During the median follow-up of 10.0 years, 171 of 364 men (47.0%) assigned to radical prostatectomy died, as compared with 183 of 367 (49.9%) assigned to observation (hazard ratio, 0.88; 95% confidence interval [CI], 0.71 to 1.08; P=0.22; absolute risk reduction, 2.9 percentage points). Among men assigned to radical prostatectomy, 21 (5.8%) died from prostate cancer or treatment, as compared with 31 men (8.4%) assigned to observation (hazard ratio, 0.63; 95% CI, 0.36 to 1.09; P=0.09; absolute risk reduction, 2.6 percentage points). The effect of treatment on all-cause and prostate-cancer mortality did not differ according to age, race, coexisting conditions, self-reported performance status, or histologic features of the tumor. Radical prostatectomy was associated with reduced all-cause mortality among men with a PSA value greater than 10 ng per milliliter (P=0.04 for interaction) and possibly among those with intermediate-risk or high-risk tumors (P=0.07 for interaction). Adverse events within 30 days after surgery occurred in 21.4% of men, including one death. CONCLUSIONS: Among men with localized prostate cancer detected during the early era of PSA testing, radical prostatectomy did not significantly reduce all-cause or prostate-cancer mortality, as compared with observation, through at least 12 years of follow-up. Absolute differences were less than 3 percentage points. (Funded by the Department of Veterans Affairs Cooperative Studies Program and others; PIVOT ClinicalTrials.gov number, NCT00007644.).

Recruitment of CD34(+) fibroblasts in tumor-associated reactive stroma: the reactive microvasculature hypothesis.

Reactive stroma co-evolves with cancer, exhibiting tumor-promoting properties. It is also evident at sites of wound repair and fibrosis, playing a key role in tissue homeostasis. The specific cell types of origin and the spatial/temporal patterns of reactive stroma initiation are poorly understood. In this study, we evaluated human tumor tissue arrays by using multiple labeled, quantitative, spectral deconvolution microscopy. We report here a novel CD34/vimentin dual-positive reactive fibroblast that is observed in the cancer microenvironment of human breast, colon, lung, pancreas, thyroid, prostate, and astrocytoma. Recruitment of these cells occurred in xenograft tumors and Matrigel plugs in vivo and was also observed in stromal nodules associated with human benign prostatic hyperplasia. Because spatial and temporal data suggested the microvasculature as a common site of origin for these cells, we analyzed microvasculature fragments in organ culture. Interestingly, fibroblasts with identical phenotypic properties and markers expanded radially from microvasculature explants. We propose the concept of reactive microvasculature for the evolution of reactive stroma at sites of epithelial disruption common in both benign and malignant disorders. Data suggest that the reactive stroma response is conserved among tissues, in normal repair, and in different human cancers. A more clear understanding of the nature and origin of reactive stroma is needed to identify novel therapeutic targets in cancer and fibrosis.

Usefulness of transurethral biopsy for staging the prostatic urethra before radical cystectomy.

PURPOSE: We determined the likelihood that transurethral resection biopsy of the prostatic urethra adjacent to the verumontanum would detect prostatic involvement of urothelial carcinoma in patients with bladder carcinoma. MATERIALS AND METHODS: We compared precystectomy transurethral resection biopsy specimens of the prostatic urethra with those of the matched radical cystoprostatectomy in 272 patients with urothelial carcinoma of the bladder. All prostates were evaluated by whole mount step sections. RESULTS: Prostatic involvement by urothelial carcinoma was detected by transurethral resection biopsy or radical cystoprostatectomy in 101 patients (37.1%). Transurethral resection biopsy detected urothelial carcinoma in 72 cases with 71.3% sensitivity and 100% specificity. The overall accuracy of transurethral resection biopsy to detect urothelial carcinoma of the prostate was 89% (positive and negative predictive values 100% and 86%, respectively). Invasive prostatic urothelial carcinoma arising from the prostatic urethra was detected by transurethral resection biopsy in 21 of 26 patients (81%) while prostatic carcinoma in situ was detected in 39 of 52 (75%). Transurethral resection biopsy detected prostatic invasive urothelial carcinoma resulting from transmural invasion of a bladder tumor in 4 of 15 patients. CONCLUSIONS: Prostatic involvement by urothelial carcinoma of the bladder was found in 37.1% of patients. Transurethral resection biopsy missed most tumors resulting from transmural invasion of the bladder primary lesion. Carcinoma in situ and invasive urothelial carcinoma arising from the prostatic urethra were detected in most cases. Transurethral resection biopsy of the prostatic urethra can complement staging and support clinical decision making with respect to neoadjuvant chemotherapy and planning for an orthotopic neobladder.

Keratin and S100 calcium-binding proteins are major constituents of the bovine teat canal lining.

The bovine teat canal provides the first-line of defence against pathogenic bacteria infecting the mammary gland, yet the protein composition and host-defence functionality of the teat canal lining (TCL) are not well characterised. In this study, TCL collected from six healthy lactating dairy cows was subjected to two-dimensional electrophoresis (2-DE) and mass spectrometry. The abundance and location of selected identified proteins were determined by western blotting and fluorescence immunohistochemistry. The variability of abundance among individual cows was also investigated. Two dominant clusters of proteins were detected in the TCL, comprising members of the keratin and S100 families of proteins. The S100 proteins were localised to the teat canal keratinocytes and were particularly predominant in the cornified outermost layer of the teat canal epithelium. Significant between-animal variation in the abundance of the S100 proteins in the TCL was demonstrated. Four of the six identified S100 proteins have been reported to have antimicrobial activity, suggesting that the TCL has additional functionality beyond being a physical barrier to invading microorganisms. These findings provide new insights into understanding host-defence of the teat canal and resistance of cows to mastitis.

Extracellular milieu grossly alters pathogen-specific immune response of mammary epithelial cells.

BACKGROUND: Considerably divergent data have been published from attempts to model the E. coli vs. S. aureus specific immune reaction of the udder using primary cultures of bovine mammary epithelial cells from cows (pbMEC). Some groups reported a swift, strong and transient inflammatory response against challenges with E. coli and only a weak and retarded response against S. aureus, in agreement with the respective reaction of the udder. Others found almost the reverse. Presence or absence of fetal calf serum distinguished the experimental setting between both groups. We examined here if this causes the divergent reaction of the pbMEC towards both pathogen species. We challenged pbMEC with proteins from heat killed E. coli or S. aureus pathogens or purified TLR2 and TLR4 ligands. The stimuli were applied in normal growth medium with (SM10) or without (SM0) 10% fetal calf serum, or in the basal medium supplemented with 10 mg/ml milk proteins (SM Milk). RESULTS: Withdrawal of FCS slowed down and decreased the extent by which E. coli or LPS enhanced the expression of cyto- and chemokine encoding genes through impaired TLR4 signalling but enforced their expression during stimulation with S. aureus. SM Milk strongly quenched the induction of those genes. S. aureus strain specific differences in the reaction of the pbMEC could only be recorded in SM0. NF-κB factors were activated by E. coli in all stimulation media, but only to a small extent by S. aureus, solely in SM0. Purified ligands for TLR2 stimulated expression of those genes and activated NF-κB equally well in SM10 and SM0. The mRNA destabilizing factor tristetraproline was only induced by E. coli in SM10 and by purified PAMPs. CONCLUSIONS: Our data cross validate the correctness of previously published divergent data on the pathogen-specific induction of key immune genes in pbMEC. The differences are due to the presence of FCS, modulating signalling through TLR4 and TLR-unrelated pathogen receptors. S. aureus does not substantially activate any TLR signalling in MEC. Rather, receptors distinct from TLRs perceive the presence of S. aureus and control the immune response against this pathogen in MEC.

Pain Scores and Exposure Rates after Polypropylene Mesh for Pelvic Organ Prolapse.

OBJECTIVES: To characterize pain and exposure after Prolift placement and identify risk factors. METHODS: A case series of women who underwent Prolift vaginal mesh were surveyed. Pain was assessed using a visual analog scale. Exposure was evaluated clinically. RESULTS: Of 183 eligible patients, 160 completed the survey, and 45 returned for examination. Mean preoperative pain score was 0.97 and postoperative was 1.35 (P = 0.12). Pre- and postoperative pain scores by compartment were: anterior (1.34 vs 1.25, mean change -0.09, P = 0.84), posterior (1.30 vs 1.56, mean change 0.26, P = 0.72), and total (0.63 vs 1.34, mean change 0.71, P = 0.05). Graft exposure was confirmed in 23 of 183 patients (12.6%); however, because asymptomatic patients were not examined, the true exposure rate may be underestimated. Hematoma formation is independently associated with mesh exposure, adjusted odds ratio 18.4 (95% confidence interval 3.4-147.4, P = 0.01). CONCLUSIONS: Although pain scores did not increase overall, there was a trend toward increased pain score in the patients with total (anterior and posterior) Prolift. Hematoma formation was significantly associated with mesh exposure.

Transcobalamin derived from bovine milk stimulates apical uptake of vitamin B12 into human intestinal epithelial cells.

Intestinal uptake of vitamin B12 (hereafter B12) is impaired in a significant proportion of the human population. This impairment is due to inherited or acquired defects in the expression or function of proteins involved in the binding of diet-derived B12 and its uptake into intestinal cells. Bovine milk is an abundant source of bioavailable B12 wherein it is complexed with transcobalamin. In humans, transcobalamin functions primarily as a circulatory protein, which binds B12 following its absorption and delivers it to peripheral tissues via its cognate receptor, CD320. In the current study, the transcobalamin-B12 complex was purified from cows' milk and its ability to stimulate uptake of B12 into cultured bovine, mouse and human cell lines was assessed. Bovine milk-derived transcobalamin-B12 complex was absorbed by all cell types tested, suggesting that the uptake mechanism is conserved across species. Furthermore, the complex stimulated the uptake of B12 via the apical surface of differentiated Caco-2 human intestinal epithelial cells. These findings suggest the presence of an alternative transcobalamin-mediated uptake pathway for B12 in the human intestine other than that mediated by the gastric glycoprotein, intrinsic factor. Our findings highlight the potential for transcobalamin-B12 complex derived from bovine milk to be used as a natural bioavailable alternative to orally administered free B12 to overcome B12 malabsorption.