18F-fluorocholine PET/MRI versus ultrasound and sestamibi for the localization of parathyroid adenomas.

PURPOSE: Accurate preoperative localization is imperative to facilitate a minimally invasive parathyroidectomy (MIP) in primary hyperparathyroidism (pHPT). This study aims to compare the diagnostic value of standard-of-care localization techniques (ultrasound [US] and 99mTechnetium (99mTc) -sestamibi scintigraphy) to [F-18]-fluorocholine positron emission tomography/magnetic resonance imaging (FCH-PET/MRI) to determine the additional clinical usefulness of PET/MRI in a Canadian cohort. METHODS: We conducted a prospective, appropriately powered, study to compare the diagnostic value of -FCH PET/MRI to that of the US and 99mTc-sestamibi scintigraphy for localization of parathyroid adenomas in a patient with pHPT. The primary outcome was the per-lesion sensitivity and positive predictive value (PPV) of FCH-PET/MRI, US, and 99mTc-sestamibi scintigraphy. Intraoperative surgeon localization, parathormone levels, and histopathological findings were used as reference standards. RESULTS: Forty-one patients underwent FCH-PET/MRI of which 36 patients had parathyroidectomy. In these 36 patients, 41 parathyroid lesions were histologically confirmed as adenomas or hyperplastic glands. Per-lesion sensitivity of FCH-PET/MRI was 82.9% and of US and 99mTc-sestamibi scintigraphy combined at 50.0%, respectively. The sensitivity of FCH-PET/MRI was superior to that of US and 99mTc-sestamibi scintigraphy (p = 0.002). In the 19 patients in whom both US and 99mTc-sestamibi scintigraphy were negative, PET/MRI correctly identified the parathyroid adenoma in 13 patients (68%). CONCLUSIONS: FCH-PET/MRI is a highly accurate imaging modality for localization of parathyroid adenomas in a tertiary center in North America. It is a superior functional imaging modality to 99mTc-sestamibi scintigraphy alone and more sensitive for localization of parathyroid lesions than US and 99mTc-sestamibi scintigraphy combined. This imaging modality could become the most valuable preoperative localization study given its superior performance in localizing parathyroid adenomas.

Back to the future: breast surgery with tumescent local anesthesia (TLA)?

PURPOSE: Breast surgery is usually performed under general anesthesia. Tumescent local anesthesia (TLA) offers the possibility to anesthetize large areas with highly diluted local anesthetic. METHODS: In this paper, the implementation, and experiences with TLA in the field of breast surgery are discussed. CONCLUSION: For carefully selected indications, breast surgery in TLA represents an alternative to ITN.

Detection of PRRSV-2 alone and co-localized with CD163 positive macrophages in porcine placental areolae.

The porcine epitheliochorial placenta creates a barrier for the transplacental transfer of some nutrients from the dam to the fetus, as well as feto-lethal viruses such as porcine reproductive and respiratory syndrome virus 2 (PRRSV-2). Areolae are specialized structures within the porcine placenta with a high absorptive and substance transport capacity that facilitate embryonic development. The overarching aim of this study was to characterize the localization of PRRSV-2 in and adjacent to areolae to provide insight into whether transplacental transmission might occur through placental areolae. Control (CON) plus three phenotypic fetal groups were selected based on levels of virus in fetal placenta, sera and thymus, to determine if fetal resilience was related to differences in PRRSV-2 localization, alone or co-localized with CD163+ macrophages. These fetal groups represented a range of susceptibility: uninfected (UNINF) being resistant, infected in placenta only (PLCO) being resilient, and high viral load viable (HVL-VIA) being most susceptible. Finally, potential factors related to PRRSV-2 localization, including the severity of inflammation in endometrium and placenta, and intrauterine growth restriction, known resilience factors, were assessed. Thirty-one pregnant gilts were inoculated with PRRSV-2 at gestation day 86 ± 0.4. Seven pregnant gilts were sham-inoculated. Gilts were euthanized at 12 days post-infection. Presence of PRRSV and CD163+ macrophages were determined using immunofluorescence in cryosections of maternal-fetal interface (MFI) with and without areolae. In the maternal, fetal and cavity of areolar region PRRSV particles were found both independently and co-localized with CD163+ macrophages. Similarly, individual, and co-localized particles were observed in the maternal and fetal sides of the MFI region of infected fetuses. Weak positive correlations were observed between the counts of CD163+ macrophages and some inflammation scores in endometrial and placental tissues, but no correlations with PRRSV-2 localization. There were no differences across the four fetal groups evaluated. These results suggest that transplacental transmission of PRRSV may occur through the areolae, either as non-cell associated or in association with infected CD163 macrophages.

Effect of porcine reproductive and respiratory syndrome virus 2 on angiogenesis and cell proliferation at the maternal-fetal interface.

Angiogenesis and cell proliferation in reproductive tissues are essential events for the maintenance of pregnancy, and alterations can lead to compromised fetal development and survival. Porcine reproductive and respiratory syndrome virus 2 (PRRSV-2) induces reproductive disease with negative financial and production impact on the swine industry. PRRSV-2 infection alters placental physiology through inflammatory and apoptotic pathways, yet fetal susceptibility varies. This study aimed to evaluate angiogenesis and cell proliferation in the porcine maternal-fetal interface (MFI) and determine if these physiological processes were altered by PRRSV-2 infection. Thirty-one pregnant gilts were inoculated with PRRSV-2 at gestation day 86 ± 0.4 (mean ± SD). Seven control gilts were sham-inoculated. All gilts were euthanized at 12 days postinoculation. Angiogenesis and cell proliferation were determined through the detection of vascular endothelial growth factor (VEGF) and Ki-67, respectively, using immunofluorescence of the MFI from 4 fetal resilience groups: uninfected (UNIF), high viral load-viable (HVL-VIA), and HVL-meconium-stained (MEC) from PRRSV-infected gilts, as well from sham-inoculated (CON) gilts. VEGF immunolabeling in the uterine submucosa was significantly lower in MEC compared with UNIF and HVL-VIA groups. Significantly greater Ki67 immunolabeling was detected in the trophoblasts of CON fetuses versus all other groups, and in uterine epithelium of CON and UNIF fetuses versus HVL-VIA and MEC. These results suggest that fetal resilience may be related to greater cell proliferation in uterine epithelium, and fetal compromise with reduced uterine submucosal angiogenesis, except fetuses with intrauterine growth restriction, in which inherently lower submucosal angiogenesis may be protective against PRRSV infection.

Multiple endocrine neoplasia 2: an overview.

This review article discusses the diagnosis and treatment of patients with multiple endocrine neoplasia type 2 (MEN2). The most common tumors associated with MEN2 are those of the parathyroid, thyroid, and adrenal glands. Additional manifestations include characteristic clinical phenotypes or features as described in the article. This review provides an overview of clinical manifestations, screening, diagnosis, treatment, and surveillance of patients with MEN2.

Assessment of Immunological Response and Impacts on Fertility Following Intrauterine Vaccination Delivered to Swine in an Artificial Insemination Dose.

To protect the health of sows and gilts, significant investments are directed toward the development of vaccines against infectious agents that impact reproduction. We developed an intrauterine vaccine that can be delivered with semen during artificial insemination to induce mucosal immunity in the reproductive tract. An in vitro culture of uterine epithelial cells was used to select an adjuvant combination capable of recruiting antigen-presenting cells into the uterus. Adjuvant polyinosinic:polycytidylic acid (poly I:C), alone or in combination, induced expression of interferon gamma, tumor necrosis factor alpha, and select chemokines. A combination adjuvant consisting of poly I:C, host defense peptide and polyphosphazene (Triple Adjuvant; TriAdj), which previously was shown to induce robust mucosal and systemic humoral immunity when administered to the uterus in rabbits, was combined with boar semen to evaluate changes in localized gene expression and cellular recruitment, in vivo. Sows bred with semen plus TriAdj had decreased γδ T cells and monocytes in blood, however, no corresponding increase in the number of monocytes and macrophages was detected in the endometrium. Compared to sows bred with semen alone, sows bred with semen plus TriAdj showed increased CCL2 gene expression in the epithelial layer. These data suggest that the adjuvants may further augment a local immune response and, therefore, may be suitable for use in an intrauterine vaccine. When inactivated porcine parvovirus (PPV) formulated with the TriAdj was administered to the pig uterus during estrus along with semen, we observed induction of PPV antibodies in serum but only when the pigs were already primed with parenteral PPV vaccines. Recombinant protein vaccines and inactivated PPV vaccines administered to the pig uterus during breeding as a primary vaccine alone failed to induce significant humoral immunity. More trials need to be performed to clarify whether repeated intrauterine vaccination can trigger strong humoral immunity or whether the primary vaccine needs to be administered via a systemic route to promote a mucosal and systemic immune response.

Simulation of a radiobiology facility for the Centre for the Clinical Application of Particles.

The Centre for the Clinical Application of Particles' Laser-hybrid Accelerator for Radiobiological Applications (LhARA) facility is being studied and requires simulation of novel accelerator components (such as the Gabor lens capture system), detector simulation and simulation of the ion beam interaction with cells. The first stage of LhARA will provide protons up to 15 MeV for in vitro studies. The second stage of LhARA will use a fixed-field accelerator to increase the energy of the particles to allow in vivo studies with protons and in vitro studies with heavier ions. BDSIM, a Geant4 based accelerator simulation tool, has been used to perform particle tracking simulations to verify the beam optics design done by BeamOptics and these show good agreement. Design parameters were defined based on an EPOCH simulation of the laser source and a series of mono-energetic input beams were generated from this by BDSIM. The tracking results show the large angular spread of the input beam (0.2 rad) can be transported with a transmission of almost 100% whilst keeping divergence at the end station very low (<0.1 mrad). The legacy of LhARA will be the demonstration of technologies that could drive a step-change in the provision of proton and light ion therapy (i.e. a laser source coupled to a Gabor lens capture and a fixed-field accelerator), and a system capable of delivering a comprehensive set of experimental data that can be used to enhance the clinical application of proton and light ion therapy.

Iatrogenic endometriosis harbors somatic cancer-driver mutations.

STUDY QUESTION: Does incisional endometriosis (IE) harbor somatic cancer-driver mutations? SUMMARY ANSWER: We found that approximately one-quarter of IE cases harbor somatic-cancer mutations, which commonly affect components of the MAPK/RAS or PI3K-Akt-mTor signaling pathways. WHAT IS KNOWN ALREADY: Despite the classification of endometriosis as a benign gynecological disease, it shares key features with cancers such as resistance to apoptosis and stimulation of angiogenesis and is well-established as the precursor of clear cell and endometrioid ovarian carcinomas. Our group has recently shown that deep infiltrating endometriosis (DE), a form of endometriosis that rarely undergoes malignant transformation, harbors recurrent somatic mutations. STUDY DESIGN, SIZE, DURATION: In a retrospective study comparing iatrogenically induced and endogenously occurring forms of endometriosis unlikely to progress to cancer, we examined endometriosis specimens from 40 women with IE and 36 women with DE. Specimens were collected between 2004 and 2017 from five hospital sites in either Canada, Germany or the Netherlands. IE and DE cohorts were age-matched and all women presented with histologically typical endometriosis without known history of malignancy. PARTICIPANTS/MATERIALS, SETTING, METHODS: Archival tissue specimens containing endometriotic lesions were macrodissected and/or laser-capture microdissected to enrich endometriotic stroma and epithelium and a hypersensitive cancer hotspot sequencing panel was used to assess for presence of somatic mutations. Mutations were subsequently validated using droplet digital PCR. PTEN and ARID1A immunohistochemistry (IHC) were performed as surrogates for somatic events resulting in functional loss of respective proteins. MAIN RESULTS AND THE ROLE OF CHANCE: Overall, we detected somatic cancer-driver events in 11 of 40 (27.5%) IE cases and 13 of 36 (36.1%) DE cases, including hotspot mutations in KRAS, ERBB2, PIK3CA and CTNNB1. Heterogeneous PTEN loss occurred at similar rates in IE and DE (7/40 vs 5/36, respectively), whereas ARID1A loss only occurred in a single case of DE. While rates of detectable somatic cancer-driver events between IE and DE are not statistically significant (P > 0.05), KRAS activating mutations were more prevalent in DE. LIMITATIONS, REASONS FOR CAUTION: Detection of somatic cancer-driver events were limited to hotspots analyzed in our panel-based sequencing assay and loss of protein expression by IHC from archival tissue. Whole genome or exome sequencing, or epigenetic analysis may uncover additional somatic alterations. Moreover, because of the descriptive nature of this study, the functional roles of identified mutations within the context of endometriosis remain unclear and causality cannot be established. WIDER IMPLICATIONS OF THE FINDINGS: The alterations we report may be important in driving the growth and survival of endometriosis in ectopic regions of the body. Given the frequency of mutation in surgically displaced endometrium (IE), examination of similar somatic events in eutopic endometrium, as well as clinically annotated cases of other forms of endometriosis, in particular endometriomas that are most commonly linked to malignancy, is warranted. STUDY FUNDING/COMPETING INTEREST(S): This study was funded by a Canadian Cancer Society Impact Grant [701603, PI Huntsman], Canadian Institutes of Health Research Transitional Open Operating Grant [MOP-142273, PI Yong], the Canadian Institutes of Health Research Foundation Grant [FDN-154290, PI Huntsman], the Canadian Institutes of Health Research Project Grant [PJT-156084, PIs Yong and Anglesio], and the Janet D. Cottrelle Foundation through the BC Cancer Foundation [PI Huntsman]. D.G. Huntsman is a co-founder and shareholder of Contextual Genomics Inc., a for profit company that provides clinical reporting to assist in cancer patient treatment. R. Aguirre-Hernandez, J. Khattra and L.M. Prentice have a patent MOLECULAR QUALITY ASSURANCE METHODS FOR USE IN SEQUENCING pending and are current (or former) employees of Contextual Genomics Inc. The remaining authors have no competing interests to declare. TRIAL REGISTRATION NUMBER: Not applicable.

Expression of pattern recognition receptors in porcine uterine epithelial cells in vivo and in culture.

Preservation of a pathogen free uterine environment is critical for maintaining healthy swine herds with high reproductive performance. Considering that uterine epithelial cells are the most numerous and thus likely point of cellular contact for pathogens in the uterus, we hypothesize that these cells may be critical for activating the immune system to clear uterine infections. Although uterine epithelial cells have not been well characterized in pigs, studies in several other species have shown that these cells express several pattern recognition receptors (PRR) and thus may act as sentinels for the uterine immune response. To characterize PRR expression in the porcine uterine epithelia, we used laser-capture microdissection to isolate epithelial cells lining the porcine uterus to quantify in vivo mRNA expression levels for select PRRs. As well, primary uterine epithelial cells (UECs) were isolated, cultured, polarized and PRR expression was quantified. Immunohistofluorescence and immunofluorescence were used to determine subcellular localization of TLR3, TLR4 and TLR9 in both uterine tissue and in polarized primary UECs. Finally, polarized primary UECs were stimulated with ligands for TLR3, TLR4, TLR9 and NOD2 to determine their functional innate immune response. Uterine epithelial cells (in vivo and in vitro) were shown to express TLR1-7, TLR9, NOD1, NOD2, NLRP3, NLRP6, NLRX1, RIG1, MDA5 and LGP2. Subcellular localization of in vivo and polarized primary UECs exhibited TLR3 and TLR9 localized to the apical cell surface whereas TLR4 was localized to the intracellular space. Polarized primary UECs stimulated with TLR3, TLR4 and TLR9 ligands showed induced secretion of IL-6, IL-13 and IL-10, respectively indicating that these receptors were functional. These results indicate that pig uterine epithelial cells are functional innate immune cells that may act as sentinels to protect against uterine infection.

Molecular and Physiological Effects on the Small Intestine of Weaner Pigs Following Feeding with Deoxynivalenol-Contaminated Feed.

We intended to assess how exposure of piglets to deoxynivalenol (DON)-contaminated feed impacted their growth, immune response and gut development. Piglets were fed traditional Phase I, Phase II and Phase III diets with the control group receiving 0.20-0.40 ppm DON (referred to as the Control group) and treatment group receiving much higher level of DON-contaminated wheat (3.30-3.80 ppm; referred to as DON-contaminated group). Feeding a DON-contaminated diet had no impact on average daily feed intake (ADFI) (p < 0.08) or average daily gain (ADG) (p > 0.10) but it did significantly reduce body weight over time relative to the control piglets (p < 0.05). Cytokine analysis after initial exposure to the DON-contaminated feed did not result in significant differences in serum interleukin (IL) IL1ß, IL-8, IL-13, tumor necrosis factor (TNF)-α or interferon (IFN)-γ. After day 24, no obvious changes in jejunum or ileum gut morphology, histology or changes in gene expression for IL-1ß, IL-6, IL-10, TNFα, or Toll-like receptor (TLR)-4 genes. IL-8 showed a trend towards increased expression in the ileum in DON-fed piglets. A significant increase in gene expression for claudin (CLDN) 7 gene expression and a trend towards increased CLDN 2-expression was observed in the ileum in piglets fed the highly DON-contaminated wheat. Because CLDN localization was not negatively affected, we believe that it is unlikely that gut permeability was affected. Exposure to DON-contaminated feed did not significantly impact weaner piglet performance or gut physiology.

Flow cytometry as an improved method for the titration of Chlamydiaceae and other intracellular bacteria.

Chlamydiaceae is a family of intracellular bacteria causing a range of diverse pathological outcomes. The most devastating human diseases are ocular infections with C. trachomatis leading to blindness and genital infections causing pelvic inflammatory disease with long-term sequelae including infertility and chronic pelvic pain. In order to enable the comparison of experiments between laboratories investigating host-chlamydia interactions, the infectious titer has to be determined. Titer determination of chlamydia is most commonly performed via microscopy of host cells infected with a serial dilution of chlamydia. However, other methods including fluorescent ELISpot (Fluorospot) and DNA Chip Scanning Technology have also been proposed to enumerate chlamydia-infected cells. For viruses, flow cytometry has been suggested as a superior alternative to standard titration methods. In this study we compared the use of flow cytometry with microscopy and Fluorospot for the titration of C. suis as a representative of other intracellular bacteria. Titer determination via Fluorospot was unreliable, while titration via microscopy led to a linear read-out range of 16 - 64 dilutions and moderate reproducibility with acceptable standard deviations within and between investigators. In contrast, flow cytometry had a vast linear read-out range of 1,024 dilutions and the lowest standard deviations given a basic training in these methods. In addition, flow cytometry was faster and material costs were lower compared to microscopy. Flow cytometry offers a fast, cheap, precise, and reproducible alternative for the titration of intracellular bacteria like C. suis. © 2016 International Society for Advancement of Cytometry.

Claudin-4 undergoes age-dependent change in cellular localization on pig jejunal villous epithelial cells, independent of bacterial colonization.

Newborn piglets are immunologically naïve and must receive passive immunity via colostrum within 24 hours to survive. Mechanisms by which the newborn piglet gut facilitates uptake of colostral cells, antibodies, and proteins may include FcRn and pIgR receptor-mediated endocytosis and paracellular transport between tight junctions (TJs). In the present study, FcRn gene (FCGRT) was minimally expressed in 6-week-old gut and newborn jejunum but it was expressed at significantly higher levels in the ileum of newborn piglets. pIgR was highly expressed in the jejunum and ileum of 6-week-old animals but only minimally in neonatal gut. Immunohistochemical analysis showed that Claudin-5 localized to blood vessel endothelial cells. Claudin-4 was strongly localized to the apical aspect of jejunal epithelial cells for the first 2 days of life after which it was redistributed to the lateral surface between adjacent enterocytes. Claudin-4 was localized to ileal lateral surfaces within 24 hours after birth indicating regional and temporal differences. Tissue from gnotobiotic piglets showed that commensal microbiota did not influence Claudin-4 surface localization on jejunal or ileal enterocytes. Regulation of TJs by Claudin-4 surface localization requires further investigation. Understanding the factors that regulate gut barrier maturation may yield protective strategies against infectious diseases.

Oral antigen exposure in newborn piglets circumvents induction of oral tolerance in response to intraperitoneal vaccination in later life.

BACKGROUND: We previously determined that newborn piglets orally gavaged with Ovalbumin (OVA) responded to systemic OVA re-exposure with tolerance; if adjuvants were included in oral vaccine, piglets responded with antibody-mediated immunity (Vet Immunol Immunopathol 161(3-4):211-21, 2014). Here, we will investigate whether newborn piglets gavaged with a vaccine comprised of OVA plus unmethylated CpG oligodeoxynucleotides (CpG; soluble component; OVA/CpG) combined with OVA plus CpG encapsulated within polyphosphazene microparticles (MP; particulate component) responded with systemic and mucosal immunity. To monitor the response to systemic antigen re-exposure, piglets were i.p.-immunized with OVA plus Incomplete Freund's Adjuvant (IFA) one month later. RESULTS: Newborn piglets (n = 5/group) were gavaged with a combined soluble and particulate vaccine consisting of OVA (0.5-0.05 mg) plus 50 µg CpG and 0.5 mg OVA plus 50 µg CpG encapsulated within a polyphosphazene MP (0.5 mg) referred to as OVA/CpG + MP. Control piglets were gavaged with saline alone. Piglets were i.p. immunized with 10 mg OVA (or saline) in IFA at four weeks of age and then euthanized at eight weeks of age. We observed significantly higher titres of serum anti-OVA immunoglobulin (Ig) IgM, IgA, IgG, IgG1, IgG2 and IgG in piglets immunized with 0.05 mg OVA/CpG + MP relative to saline control animals. Thus, a single oral exposure at birth to a combined soluble and particulate OVA vaccine including adjuvants can circumvent induction of oral tolerance which impacts response to i.p. vaccination in later life. Further, piglets gavaged with 0.05 mg OVA/CpG + MP generated significant anti-OVA IgG and IgG1 titres in lung compared to saline control piglets but results were comparable to titres measured in parenteral control piglets. Peripheral blood mononuclear cells (PBMCs) ex vivo-stimulated with OVA showed markedly decreased production of IL-10 cytokine after 72 hours relative to animal-matched cells incubated with media alone. No production of IFN-γ was observed from any groups. CONCLUSION: Newborn piglets gavaged with low dose soluble and particulate OVA plus CpG ODN and polyphosphazene adjuvants produced antigen-specific antibodies in serum and lung after systemic re-exposure in later life. These data indicate circumvention of oral tolerance but not induction of oral immunity.

Patient fear of anesthesia complications according to surgical type: potential impact on informed consent for anesthesia.

BACKGROUND: Past research has explored patients' expectations about the informed consent process. However, it is currently unknown if the complexity of the surgical procedure influences the type of anesthesia-related risks that patients wish disclosed. This study explored fears of anesthesia-related complications and whether these changed based on severity of surgery classification. METHODS: Patients presenting to our pre-operative evaluation clinic from February 2013 to May 2013 were asked to participate in a survey-based study meant to evaluate their perception of five possible anesthetic risks (peripheral nerve injury, death, nausea and vomiting, heart attack and stroke) when confronted with differing levels of surgical severity. RESULTS: One thousand surveys were administered, and 894 were returned for an overall response rate of 89%. Fear of death was the greatest concern as compared to the other risk factors independent of the severity of surgery. The level of fear for all risk factors, with the exception of stroke and heart attack, were dependent on the severity of surgery. Fear of death decreased as the severity of surgery decreased (major 46%, moderate 38%, minor 25%). For major surgery, the fear of perioperative death differed significantly with age (P < 0.001); specifically, with increasing age came a lessened fear of death. CONCLUSION: Awareness by anesthesia providers of those fears that patients report may allow for a more personalized approach to providing information that may better allay anxiety. Further, these results may better tailor the informed consent process to one that meets particular patient concerns.

A single, low dose oral antigen exposure in newborn piglets primes mucosal immunity if administered with CpG oligodeoxynucleotides and polyphosphazene adjuvants.

By definition, soluble antigens ingested orally trigger mucosal tolerance such that any subsequent re-exposure by a systemic route results in suppression of immunity. We propose that antigens introduced in extreme early life can readily traverse the gut wall and therefore circumvent induction of mucosal tolerance and instead induce immunity. Piglets were drenched with low-doses of ovalbumin (OVA; 5mg or 0.05 mg) alone, OVA plus adjuvants (CpG oligodeoxynucleotides and PCEP polyphosphazene) or saline within 6h of birth. At 28 days of age, they were administered 10mg OVA plus 1:1 Montanide adjuvant (or saline) via the intraperitoneal (i.p.) route or via the oral route. Serum was obtained on day 28 and day 49 to measure OVA-specific antibodies titres. All piglets boosted orally with OVA plus Montanide, regardless of prior OVA exposure, failed to induce immunity. As expected, piglets drenched with saline but boosted via the i.p. route with OVA plus Montanide showed significant induction of anti-OVA IgA, IgG, IgG1 and IgG2 relative to saline control piglets. Newborn animals drenched with 5mg or 0.05 mg OVA failed to induce oral immunity. A second intramuscular injection in adulthood triggered immunity in the piglets that were drenched with 0.05 mg OVA and boosted initially by the i.p. route suggesting that some systemic lymphocytes were primed despite initial lack of induction of humoral immunity. In contrast, piglets orally immunized with 5mg or 0.05 mg OVA plus adjuvants resulted in significant induction of anti-OVA IgA (5mg only), IgM, IgG, IgG1 and IgG2 in serum relative to saline control piglets as well as significant induction of anti-OVA IgA, IgM (5mg only) IgG, IgG1 (5mg only) or IgG2 relative to piglets drenched with OVA alone. These data clearly show that the response was sensitive to the oral vaccine components and was not simply a response to the i.p. immunization at day 28. This work demonstrates that newborn piglets respond to oral antigens with immunity if re-exposure to the antigen occurs via a systemic route and if adjuvants are included with the oral vaccine administered at birth. These results should be further explored to establish whether early life oral vaccination can be exploited to protect this susceptible population against infectious diseases.

Patient perspectives on informed consent for anaesthesia and surgery: American attitudes.

BACKGROUND: Principles of informed consent are ethically, morally, and legally grounded in physicians' responsibility to patients. This study examined patient expectations regarding the informed consent during the perioperative process, specifically risk information exchange, preferred method and timing of delivery, and the roles that patient anxiety and understanding might play. METHODS: Five hundred patients seen in our pre-operative clinic were surveyed by written questionnaire. Patients were asked about their level of agreement with a number of statements pertaining to informed consent and their preferences for discussion of types of risks. Anxiety concerns, impact of ability to understand complexities of care, preferences for timing, and method of presentation were assessed. RESULTS: Four hundred eleven of 500 surveys (82%) were completed. A majority of respondents (92% and 80%, respectively) believed the risk of common but less consequential complications and rare yet severe complications should be discussed. Only 21% agreed that anxiety generated by discussion of risks outweighed benefit and only 6% agreed that discussion of risks should be restricted based on patient inability to appreciate complexities of care. Discussion was preferred on the day of surgery, 1 week before, and 1 month before in 46%, 35%, and 16% of respondents, respectively, and independent of level of anxiety generated by such discussion (P = 0.87). Respondents preferred discussion with their anaesthesia provider alone (44%) or in combination with written information (52%) as compared with written information only (4%) (P < 0.01). CONCLUSIONS: Greater awareness of patient preferences and expectations may result in better information exchange between anaesthesia providers and their patients.

The importance of timing in surgical treatment of unruptured symptomatic aneurysm of abdominal aorta.

AIM OF STUDY: Aim of this study is to define an entity of unruptured symptomatic AAA, to examine the influence of timing of the surgical treatment and to analyze the results of the treatment of unruptured symptomatic AAA in acute expansion. MATERIALS AND METHOD: The study is designed as retrospective analysis of 390 operatively treated patients in the last five years at the Clinics of Vascular Surgery in Novi Sad. All patients were grouped into four categories: elective operative surgical treatment, surgical treatment 24 hours after the admission through the Department of Urgent Surgery with an urgent CT diagnosis (in first 2 hours), surgical treatment within 24 hours since the admission through the Department of Urgent Surgery with an urgent CT diagnosis (in first 2 hours) and immediate surgical treatment of ruptured AAA. RESULTS: In the period from Jan 1, 2005 to Dec 31, 2009, 390 patients with AAA were operatively treated. 89 patients had ruptured AAA, 52 were operated 24 hours after the urgent admission, 18 patients were operated in the first 24 hours after the urgent admission and 231 patients were planned for elective surgery. Mortality rates between the groups were as follows: elective surgery-5.1 %, patients operated 24 hours after the urgent admission 7.2 %, patients operated in the first 24 hours after the urgent admission 23 %, and patients who had ruptured AAA 34 %. CONCLUSION: Considering the obtained data, it can be concluded that the treatment of unruptured symptomatic AAA is related to a higher risk of postoperative mortality in relation to an elective surgery. Moreover, surgical treatment in the first 24 hours after the urgent admission of unruptured symptomatic AAA has higher rate of mortality and morbidity compared to surgical treatment 24 hours after the urgent admission of the patients, so we can conclude that the early (semi) elective surgery is a method of choice for the treatment of unruptured symptomatic AAA in acute expansion (Tab. 2, Fig. 2, Ref. 21).

Restricted feed intake in lactating primiparous sows. II. Effects on subsequent litter sex ratio and embryonic gene expression.

Expression of panels of candidate genes controlling myogenesis, angiogenesis and gender-specific imprinting of development were analysed in embryonic, placental and endometrial tissues recovered at Day 30 of gestation from a subset of primiparous sows that were either feed restricted (Restrict; n=17) or fed to appetite (Control; n=15) during the last week of the previous lactation. Embryos were also sex typed to investigate gender bias in response to treatments. Average embryonic weight was lower in the subset of Restrict compared with Control litters (1.38±0.07vs 1.59±0.08g, respectively) and the male:female sex ratio was higher (P<0.05) in embryos (litters) recovered from Restrict sows. Treatment affected (P≤0.05) the expression of embryonic and placental genes involved in insulin-like growth factor (IGF) 2 signalling, including IGF2, INSR and IGF2R. Embryonic expression of ESR1 was also affected by treatment (P<0.03) and sex×treatment interactions were observed for the expression of embryonic ESR1 (P<0.05) and placental ANGPT2 (P<0.03). At the molecular level, these results support the suggestion that changes in placental function are not the primary mechanism mediating detrimental effects of previous sow catabolism on early embryonic development in the feed-restricted lactational sow model. However, perturbations in the IGF2 system are implicated as mediators of these effects.