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Muir-Torre syndrome, a variant of Lynch syndrome or hereditary nonpolyposis colorectal cancer, is an autosomal dominant disease characterized by skin neoplasms (sebaceous or keratoacanthomas) and visceral malignancies. Due to the rarity of the syndrome there are no firm guidelines on how and when to test patients with its typical skin lesions. We describe a case that highlights the importance of a detailed family history. [ABSTRACT FROM AUTHOR]

Background: Declining vaginal hysterectomy numbers in obstetrics and gynecology training programs highlights the need for innovative methods to teach vaginal surgical skills. We describe our experience with a vaginal hysterectomy skills simulation curriculum.Instrument: A low-fidelity bench model was constructed to simulate four vaginal hysterectomy suturing tasks. A polyvinyl chloride downspout adapter and low-cost materials simulate the Heaney pedicle stitch, simple pedicle stitch, double ligature, and continuous running stitch.Experience: Faculty expert vaginal surgeons established proficiency levels for each task. Resident (N=30) pass rates for tasks 1, 2, and 3 were 1 of 30 (3.3%), 7 of 30 (23.3%), and 4 of 30 (13.3%), respectively, for the left side, and 3 of 30 (10%), 9 of 30 (30%), and 10 of 30 (33.3%), respectively, for the right side. For task 4, the pass rate was 14 of 30 (46.7%). The majority of residents felt that the model simulates the technical skills required for vaginal hysterectomy and agreed that vaginal skills laboratory training would improve their ability to perform procedures in the operating room. Ninety-two percent of residents felt that a vaginal surgery skills curriculum would be a useful addition to their simulation education.Conclusion: A proficiency-based vaginal hysterectomy skills simulation curriculum using a low-fidelity model may be an important training and evaluation tool for vaginal surgical skills training. [ABSTRACT FROM AUTHOR]

Pertussis, a serious infectious disease of the respiratory tract caused by Bordetella pertussis, is reemerging in vaccinated populations. Efforts to curtail this disease are hampered by limited insight into the basis of protective immunity. Opsonophagocytosis was recently found to play a central role in cellular bactericidal activity against B. pertussis. In the present study, we studied the specificity of opsonic antibodies. Anti-pertactin antibodies, but not anti-pertussis toxin, anti-fimbriae, or anti-filamentous hemagglutinin antibodies, were found to be crucial for B. pertussis phagocytosis. These data are consistent with field studies showing that levels of antibodies to pertactin correlate with protection. [ABSTRACT FROM AUTHOR]

Background One lung ventilation ( OLV) results in inflammatory and mechanical injury, leading to intraoperative and postoperative complications in children. No interventions have been studied in children to minimize such injury. Objective We hypothesized that a single 2-mg·kg−1 dose of methylprednisolone given 45-60 min prior to lung collapse would minimize injury from OLV and improve physiological stability. Methods Twenty-eight children scheduled to undergo OLV were randomly assigned to receive 2 mg·kg−1 methylprednisolone ( MP) or normal saline (placebo group) prior to OLV. Anesthetic management was standardized, and data were collected for physiological stability (bronchospasm, respiratory resistance, and compliance). Plasma was assayed for inflammatory markers related to lung injury at timed intervals related to administration of methylprednisolone. Results Three children in the placebo group experienced clinically significant intraoperative and postoperative respiratory complications. Respiratory resistance was lower ( P = 0.04) in the methylprednisolone group. Pro-inflammatory cytokine IL-6 was lower ( P = 0.01), and anti-inflammatory cytokine IL-10 was higher ( P = 0.001) in the methylprednisolone group. Tryptase, measured before and after OLV, was lower ( P = 0.03) in the methylprednisolone group while increased levels of tryptase were seen in placebo group after OLV (did not achieve significance). There were no side effects observed that could be attributed to methylprednisolone in this study. Conclusions Methylprednisolone at 2 mg·kg−1 given as a single dose prior to OLV provides physiological stability to children undergoing OLV. In addition, methylprednisolone results in lower pro-inflammatory markers and higher anti-inflammatory markers in the children's plasma. [ABSTRACT FROM AUTHOR]

Costimulation via CD137 (4-1BB) enhances antitumor immunity mediated by cytotoxic T lymphocytes. Anti-CD137 agonist antibodies elicit mild liver inflammation in mice, and the maximum tolerated dose of Urelumab, an anti-human CD137 agonist monoclonal antibody, in the clinic was defined by liver inflammation-related side effects. A protease-activated prodrug form of the anti-mouse CD137 agonist antibody 1D8 (1D8 Probody therapeutic, Pb-Tx) was constructed and found to be selectively activated in the tumor microenvironment. This construct, which encompasses a protease-cleavable linker holding in place a peptide that masks the antigen binding site, exerted antitumor effects comparable to the unmodified antibody but did not result in liver inflammation. Moreover, it efficaciously synergized with both PD-1 blockade and adoptive T-cell therapy. Surprisingly, minimal active Pb-Tx reached tumor-draining lymph nodes, and regional lymphadenectomy did not abrogate antitumor efficacy. By contrast, S1P receptor-dependent recirculation of T cells was absolutely required for efficacy. The preferential cleavage of the anti-CD137 Pb-Tx by tumor proteases offers multiple therapeutic opportunities, including neoadjuvant therapy, as shown by experiments in which the Pb-Tx is given prior to surgery to avoid spontaneous metastases. [ABSTRACT FROM AUTHOR]

Neurofibromatosis type 1 (NF1) is an inherited disorder often associated with optic nerve gliomas, low-grade brain tumors, and readily visible signs. Though these features are frequently emphasized, the psychosocial and emotional morbidities are often overlooked. We present a patient with depressive disorder resulting in suicide in a patient with NF1. [ABSTRACT FROM AUTHOR]

Bordetella pertussis is the causative agent of pertussis, aka whooping cough. Although generally considered an extracellular pathogen, this bacterium has been found inside respiratory epithelial cells, which might represent a survival strategy inside the host. Relatively little is known, however, about the mechanism of internalization and the fate of B. pertussis inside the epithelia. We show here that B. pertussis is able to enter those cells by a mechanism dependent on microtubule assembly, lipid raft integrity, and the activation of a tyrosine-kinase-mediated signaling. Once inside the cell, a significant proportion of the intracellular bacteria evade phagolysosomal fusion and remain viable in nonacidic lysosome-associated membrane-protein-1-negative compartments. In addition, intracellular B. pertussis was found able to repopulate the extracellular environment after complete elimination of the extracellular bacteria with polymyxin B. Taken together, these data suggest that B. pertussis is able to survive within respiratory epithelial cells and by this means potentially contribute to host immune system evasion. [ABSTRACT FROM AUTHOR]

Background: The cell envelope of a bacterial pathogen can be damaged by harsh conditions in the environment outside a host and by immune factors during infection. Cell envelope stress responses preserve the integrity of this essential compartment and are often required for virulence. Bordetella species are important respiratory pathogens that possess a large number of putative transcription factors. However, no cell envelope stress responses have been described in these species. Among the putative Bordetella transcription factors are a number of genes belonging to the extracytoplasmic function (ECF) group of alternative sigma factors, some of which are known to mediate cell envelope stress responses in other bacteria. Here we investigate the role of one such gene, sigE, in stress survival and pathogenesis of Bordetella bronchiseptica. Results: We demonstrate that sigE encodes a functional sigma factor that mediates a cell envelope stress response. Mutants of B. bronchiseptica strain RB50 lacking sigE are more sensitive to high temperature, ethanol, and perturbation of the envelope by SDS-EDTA and certain β-lactam antibiotics. Using a series of immunocompromised mice deficient in different components of the innate and adaptive immune responses, we show that SigE plays an important role in evading the innate immune response during lethal infections of mice lacking B cells and T cells. SigE is not required, however, for colonization of the respiratory tract of immunocompetent mice. The sigE mutant is more efficiently phagocytosed and killed by peripheral blood polymorphonuclear leukocytes (PMNs) than RB50, and exhibits decreased cytotoxicity toward macrophages. These altered interactions with phagocytes could contribute to the defects observed during lethal infection. Conclusions: Much of the work on transcriptional regulation during infection in B. bronchiseptica has focused on the BvgAS two-component system. This study reveals that the SigE regulon also mediates a discrete subset of functions associated with virulence. SigE is the first cell envelope stress-sensing system to be described in the bordetellae. In addition to its role during lethal infection of mice deficient in adaptive immunity, our results indicate that SigE is likely to be important for survival in the face of stresses encountered in the environment between hosts. [ABSTRACT FROM AUTHOR]

Objectives: To test the hypothesis that protective ventilation strategy (PVS) as defined by the use of low stretch ventilation (tidal volume of 5 ml·kg−1 and employing 5 cm of positive end expiratory pressure (PEEP) during one lung ventilation (OLV) in piglets would result in reduced injury compared to a control group of piglets who received the conventional ventilation (tidal volume of 10 ml·kg−1 and no PEEP). Background: PVS has been found to be beneficial in adults to minimize injury from OLV. We designed the current study to test the beneficial effects of PVS in a piglet model of OLV. Methods: Ten piglets each were assigned to either ‘Control’ group (tidal volume of 10 ml·kg−1 and no PEEP) or ‘PVS’ group (tidal volume of 5 ml·kg−1 during the OLV phase and PEEP of 5 cm of H2O throughout the study). Experiment consisted of 30 min of baseline ventilation, 3 h of OLV, and again 30 min of bilateral ventilation. Respiratory parameters and proinflammatory markers were measured as outcome. Results: There was no difference in PaO2 between groups. PaCO2 ( P < 0.01) and ventilatory rate ( P < 0.01) were higher at 1.5 h OLV and at the end point in the PVS group. Peak inflating pressure (PIP) and pulmonary resistance were higher ( P < 0.05) in the control group at 1.5 h OLV. tumor necrosis factor-alpha ( P < 0.04) and IL-8 were less ( P < 0.001) in the plasma from the PVS group, while IL-6 and IL-8 were less ( P < 0.04) in the lung tissue from ventilated lungs in the PVS group. Conclusions: Based on this model, PVS decreases inflammatory injury both systemically and in the lung tissue with no adverse effect on oxygenation, ventilation, or lung function. [ABSTRACT FROM AUTHOR]

Abstract: Kaposi''s sarcoma (KS) shows a distinct geographical and ethnic distribution. The variable K1 gene serves to differentiate the KSHV subtypes A–E, M, N, and Q. Phylogenetic characterization of 19 classical and epidemic German KS specimens revealed the Eurasian KSHV subtypes C (n = 13, including 6 classical KS) and A (n = 6), while 27 Cuban specimens showed a variety of different subtypes (A: n = 16, 4 being A5; C: n = 8; B: n = 2; and the new subtype E: n = 1). Three pairs of isolates from KS patients and peripheral blood mononuclear cells (PBMC) of their sexual partners without KS were studied for the first time and found identical, strongly arguing for sexual transmission of KSHV in this unique cohort. The unique ethnic background of the Cuban population may explain the variety of different KSHV strains. [Copyright &y& Elsevier]