Emotional response of undergraduates to cadaver dissection.

The most effective way to learn human anatomy is through cadaver dissection. Historically, cadaver dissection has been the provenance of professional schools. Increasingly, cadaver-based courses in human anatomy are shifting to the undergraduate level, which creates both problems and opportunities because of differences between undergraduate and graduate student populations. Anxiety associated with dissecting cadavers can create a barrier to learning, and ultimately, entry into the health and medical sciences for some demographic subpopulations of undergraduates. We surveyed 76 students in 2007 and 51 students in 2009 at four times in the semester to investigate the timing and sociodemographic predictors of anxiety over cadaver dissection. We followed this with a second survey of 44 students in 2014 to test the effect of humanization of cadaver donors (providing information about donor occupation and cause of death) to reduce student anxiety. Students experienced anxiety upon first exposure to cadaver dissection. Female students experienced greater anxiety than male students upon first exposure to cadavers but this effect was short-lived. Self-identified non-white, non-Christian students experienced sustained anxiety throughout the semester, likely because cadaver stress compounded social and financial stressors unique to international students. Humanization was effective in reducing anxiety in non-white, non-Christian students but had the unexpected effect of increasing anxiety in female students. We recommend that humanizing information be offered to students who seek it out, but not forced upon students for whom the information would only add to their stress. Clin. Anat. 31:224-230, 2018. © 2017 Wiley Periodicals, Inc.

Variation in habitat use along the freshwater-marine continuum by grey mullet Mugil cephalus at the southern limits of its distribution.

In this study, habitat use by Mugil cephalus was investigated in the waters of the west coast of the North Island of New Zealand by analysing microchemical composition of otoliths (laser-ablation inductively coupled plasma mass spectrometry) obtained from individuals from commercial fish stocks and research surveys. Results of this study show that M. cephalus at the southern limits of its distribution display highly flexible migratory behaviour with extensive use of freshwater and brackish habitats, potentially enabling them to maximize foraging opportunities. Mugil cephalus can tolerate a wide range of salinities and can therefore utilize higher productivity areas, such as estuaries and eutrophic riverine lakes. Finally, M. cephalus populations across a range of climates and latitudes appear to differ in the extent to which they utilize freshwater and brackish habitats, possibly with increasing penetration of fresh waters with increasing latitude.

Notch intracellular domains form transcriptionally active heterodimeric complexes on sequence-paired sites.

Notch signaling is universally conserved in metazoans where it is important for a wide variety of both normal and abnormal physiology. All four mammalian Notch receptors are activated by a conserved mechanism that releases Notch intracellular domains (NICDs) from the plasma membrane to translocate to the nucleus. Once there, NICDs interact through highly conserved ankyrin domains to form head-to-head homodimers on Notch sensitive promoters and stimulate transcription. Due to the highly conserved nature of these Notch ankyrin domains in all four mammalian Notch proteins, we hypothesized that NICDs may also engage in heterodimerization. Our results reveal the presence of two NICD dimerization states that can both engage in homo and heterodimerization. Using a Co-IP approach, we show that all NICD's can form non-transcriptionally active dimers and that the N4ICD appears to perform this function better than the other NICDs. Using a combination of ChIP analysis and transcriptional reporter assays, we also demonstrate the formation of transcriptionally active heterodimers that form on DNA. In particular, we demonstrate heterodimerization between the N2ICD and N4ICD and show that this heterodimer pair appears to exhibit differential activity on various Notch sensitive promoters. These results illustrate a new diversification of Notch signaling mechanisms which will help us better understand basic Notch function.

Alternatives to risk-reducing surgery for ovarian cancer.

BRCA1 and BRCA2 mutation carriers have an 18%-60% and 11%-27% lifetime risk of developing ovarian carcinoma, respectively. Prophylactic bilateral salpingo-oophorectomy reduces the risk of this malignancy by up to 96%. Gynecological screening programs with periodical trans-vaginal ultrasound and serum CA125 assay have been widely used in women at hereditary high risk of ovarian carcinoma, but clinical results have been conflicting. These surveillance protocols have often fallen short of expectations because of the advanced stage of ovarian carcinoma in the identified screened women. Several investigations have been addressed to the detection of additional tumor markers able to generate more reliable screening tools. The combined serum assay of leptin, prolactin, osteopontin, CA125, macrophage inhibiting factor and insulin-like growth factor-II appears to have a significant better diagnostic reliability compared with serum CA125 alone in discriminating healthy individuals from ovarian carcinoma patients, and therefore, it could have a role in the screening of women at high risk for this malignancy. As far as chemoprevention is concerned, oral contraceptives significantly reduce the ovarian carcinoma risk also in BRCA mutation carriers, whereas the efficacy of fenretinide is still under investigation.

Robotic single-site hysterectomy: feasibility, learning curve and surgical outcome.

BACKGROUND: The field of laparoscopy has undergone several changes to improve the morbidity and cosmesis of laparoscopic surgery. The robotic single-site surgery is the inevitable hybridization of robotic technology with laparoendoscopic single-site surgery. METHODS: Perioperative information of 12 robotic single-site hysterectomies (R-SSH) were collected to evaluate the surgical feasibility and the possible influence of the body mass index (BMI) and the uterine weight on operative times. RESULTS: The mean operative time was 85 ± 33 min (range, 355 to 149 min), the mean docking time was 9 ± 3 min, and the mean console time was 76 ± 33 min. The mean blood loss was 80 ± 18 mL, and the median weight of resected uteri was 220 ± 45 g. No serious postoperative complications occurred. The CUSUM learning curve was observed to consist of two different phases: phase 1 (the initial 6 cases) and phase 2 (the last 6 cases) with significant reduction in operative and console time observed between the two phases. For BMI, no correlation was found with operative times, console times, and docking times, and no correlation was found between uterine weight and operative time. CONCLUSIONS: This series, identifying two different phases of the learning curve and suggesting that the initial learning phase for the procedure can be achieved after six cases, confirms the feasibility and safety of a robotic approach for single-site hysterectomy. However, the limits of this study mainly rely on the limited casuistic and short follow-up, although the preliminary results appear promising. Larger series and prospective studies comparing R-SSH hysterectomy with standard robotic multiport hysterectomy are necessary to define properly the role of this innovative surgical technique.

Fertility and endocrine outcome after robot-assisted laparoscopic myomectomy (RALM).

INTRODUCTION: Laparoscopic myomectomy has recently gained wide acceptance but this procedure remains technically highly demanding and concerns have been raised about the increased blood loss and an higher risk of postoperative uterine rupture of the pregnant uterus. OBJECTIVE: The aim of the present study is to evaluate the fertility and endocrine outcome in women underwent robot-assisted laparoscopic myomectomy (RALM). METHODS: Data from 48 RALM performed in our department between the years 2007 and 2011 have been collected. Conception rate, abortion rate, incidence of feto-maternal morbidity or severe pregnancy and labor-related complications were reported; FSH and AMH levels and ultrasound valuation of AFC has been made before and 6 months after operation. Number of cesarean sections and vaginal deliveries were described. RESULTS: The average age of the patients was 35 years and median Body Mass Index was 23 kg/m(2) (range 18-35 kg/m(2)). Seven women (13%) became pregnant after RALM with eight pregnancies. One pregnancy is actually on going; there were six deliveries with caesarian section and one spontaneous delivery. No spontaneous abortions. No uterine ruptures occurred. No significant modification of ovarian function was found after myomectomy. CONCLUSION: RALM seems to have a favorable impact on the reproductive outcome of young patients with no impact on the ovarian function.

Analysis of failures and clinical outcome of advanced epithelial ovarian cancer in patients with microscopic residual disease at second-look reassessment following primary cytoreductive surgery and first-line platinum-based chemotherapy.

AIM: To assess the pattern of failure and survival of advanced ovarian cancer patients with microscopic residual disease at second-look following cytoreductive surgery and platinum-based chemotherapy. MATERIALS AND METHODS: Nine-five women were retrospectively analyzed. Residual disease after initial surgery was > one cm in 58 (61.1%) patients, first-line chemotherapy was paclitaxel/platinum-based in 70 (73.7%) patients, second-look findings showed no macroscopic residuum but positive random peritoneal biopsies and/or positive washing ("true" microscopic residual disease) in 79 (83.2%) patients, and a macroscopic residuum which was completely resected (converted complete response) in 16(16.8%) patients. RESULTS: Eight-one (85.2%) patients developed recurrent disease after a median time of 14 months (range four to 51). The abdomen (29.6%) and the pelvis (28.4%) were the most common sites of failure. Two- and five-year survival after second-look were 78.1% and 31.0%, respectively. The clinical and pathological features with prognostic relevance at presentation (age, histotype, and tumor grade), as well as type of first-line chemotherapy and treatment after second-look were not related to the clinical outcome. There was a trend for a better survival in patients with optimal primary cytoreduction compared with those with suboptimal primary cytoreduction (five-year survival = 42.7% vs 23.4%). There was no significant difference in survival between the converted complete responders and the patients with "true" microscopic residual disease. CONCLUSIONS: These data confirm the unsatisfactory clinical outcome of patients with microscopic residual disease after first-line chemotherapy and the limited benefit of second-look reassessment.

Notch Intracellular Domains form Transcriptionally Active Heterodimeric Complexes on Sequence-paired Sites.

Notch signaling is universally conserved in metazoans where it is important for a wide variety of both normal and abnormal physiology. All four mammalian Notch receptors are activated by a conserved mechanism that releases Notch intracellular domains (NICDs) from the plasma membrane to translocate to the nucleus. Once there, NICDs interact through highly conserved ankyrin domains to form head-to-head homodimers on Notch sensitive promoters and stimulate transcription. Due to the highly conserved nature of these Notch ankyrin domains in all four mammalian Notch proteins, we hypothesized that NICDs may also engage in heterodimerization. Our results reveal the presence of two NICD dimerization states that can both engage in homo and heterodimerization. Using a Co-IP approach, we show that all NICD's can form non-transcriptionally active dimers and that the N4ICD appears to perform this function better than the other NICDs. Using a combination of ChIP analysis and transcriptional reporter assays, we also demonstrate the formation of transcriptionally active heterodimers that form on DNA. In particular, we demonstrate heterodimerization between the N2ICD and N4ICD and show that this heterodimer pair appears to exhibit differential activity on various Notch sensitive promoters. These results illustrate a new diversification of Notch signaling mechanisms which will help us better understand basic Notch function.

Prognostic value of lymph node status and number of removed nodes in patients with squamous cell carcinoma of the vulva treated with modified radical vulvectomy and inguinal-femoral lymphadenectomy.

PURPOSE OF INVESTIGATION: To assess the outcome of patients with squamous cell vulvar carcinoma treated with deep partial or total vulvectomy and inguinal-femoral lymphadenectomy. MATERIALS AND METHODS: The authors assessed 87 patients who underwent primary surgery. RESULTS: Tumor recurred in 34 patients, and the first relapse was local in 19, inguinal in ten, and distant in five. Five-year disease-free survival was 56.7% and was related to Stage (p < 0.0001), grade (p = 0.023), and node status (p < 0.0001). Groin failure occurred in 4.9% of node-negative patients compared with 29.6% of node-positive patients (p = 0.0096). Distant recurrences only developed in women with positive nodes. Among the 47 patients who underwent bilateral lymphadenectomy and who had negative nodes, groin recurrence occurred in 12% of those who had < or = 15 nodes removed and 0% of those who had > 15 nodes removed. CONCLUSIONS: Stage and node status were the most important prognostic variables. There was a trend favoring a better groin control in patients with node-negative disease who underwent extensive lymphadenectomy.

Analysis of the pattern of hypersensitivity reactions in patients receiving carboplatin retreatment for recurrent ovarian cancer.

The aim of this paper was to assess hypersensitivity reactions in 69 patients who received carboplatin (CBDCA) retreatment for recurrent ovarian cancer. Hypersensitivity reactions developed in 15 (21.7%) patients and occurred during the second cycle of retreatment in 13 (86.7%) of them. Reactions consisted of skin rash, flushing, itching, or abdominal cramping in eight (53.3%) and severe respiratory or cardiovascular events in seven patients (46.7%). One patient had a chest pain, without any other symptoms suggestive of hypersensitivity, followed by cardiac arrest unresponsive to standard resuscitative measures. All the other cases promptly recovered from symptoms. Logistic regression analysis showed that allergy history and CBDCA retreatment interval (interval time between the last cycle of first-line chemotherapy and CBDCA retreatment) were independent predictive variables for the risk of hypersensitivity, whereas patient age, first-line chemotherapy, total CBDCA dose given during first-line treatment, recurrence treated with CBDCA (first versus other), and CBDCA regimen at recurrence had no predictive value. Hypersensitivity reaction rate was higher in patients with CBDCA retreatment interval longer than 23.4 months compared to those with a shorter interval (36.3% versus 8.3%, P = 0.0132). Nine patients were subsequently treated with cisplatin, and two (22.2%) still developed allergic reactions. In conclusion, hypersensitivity reactions to CBDCA retreatment can occur in approximately one fifth of the cases, and a CBDCA retreatment interval longer than 2 years appears to be the strongest predictive variable for the development of allergic reactions.

A new myelomonoblastic cell line (M20): analysis of properties, differentiation, and comparison with other established lines of similar origin.

A new myelomonoblastic cell line (M20) was established from the peripheral blood of a ten-year-old child with acute myeloblastic leukemia, using an improved method for supporting the initial stages of cell proliferation. The addition of irradiated macrophage monolayers to the proliferating cells appeared to overcome the deterioration of the primary cultures and enable them to continue proliferating until they became independent of this environment. The cell line that developed consisted of myeloblasts and promyelocytes characterized by light and scanning electron microscopy, cytochemistry, and enzymatic activities. The cells expressed Fc receptors and WT1 antigens but did not exhibit HLA-DR, HMA1, Epstein-Barr virus nuclear antigen, and surface Ig. The M20 cells produced colonies when cultured in semisolid medium and secreted lysozyme, prostaglandin E2, and interleukin 1. An attempt was also made to analyse the position of the M20 cells in the scheme of differentiation of the myelomonocytic lineage using different approaches. Treatment of the cells with 12-O-tetradecanoyl phorbol 13-acetate induced their adherence to plastic surfaces and partial maturation to macrophages as judged by morphological criteria, cytochemistry, and enzyme activities. However, comparison of the M20 cells to other well-established myelomonoblastic cell lines did not reveal any pattern suggesting a possible relationship between surface markers, cell function, and differentiation pathway of the various cell lines tested. Establishment of additional cell lines and identification of new markers may assist in defining the mechanisms involved in normal differentiation and malignant transformation of this cell lineage. In addition, such cell lines may also provide a tool for the quantitative recovery of a variety of monokines.

Differentiating human leukemia cells express heparanase that degrades heparan sulfate in subendothelial extracellular matrix.

Human promyelocytic (HL-60) and monoblast-like (U-937) leukemia cell lines were tested for expression of an endoglycosidase (heparanase) capable of degrading heparan sulfate (HS) side chains in the subendothelial extracellular matrix (ECM). Heparanase activity has been previously shown to be expressed by activated lymphocytes and macrophages and by highly metastatic tumor cells, in correlation with their ability to invade blood vessels and extracellular matrices. Incubation of HL-60 and U-937 cells with sulfate-labeled ECM in the presence of 12-O-tetradecanoyl-phorbol-13-acetate (TPA) resulted in heparanase-mediated release of heparan sulfate degradation products. This degradation was inhibited by heparin, stimulated by plasminogen and not expressed by cells treated with retinoic acid or dimethylsulfoxide and undergoing neutrophilic differentiation. Heparanase activity was not detected in media conditioned by HL-60 and U-937 cells but was found in their cell lysates, regardless of whether or not the cells were exposed to TPA. These findings imply that TPA-induced differentiation of human myeloid leukemic cells to macrophage-like cells, but not to neutrophilic granulocytes, is associated with expression on the cell surface of a preformed heparanase activity. The enzyme may serve as a marker for human cell differentiation into macrophages, allowing the differentiating cells to traverse the vascular compartment and reach their target sites.

Complications in the surgical treatment of carcinoma of the endometrium.

The authors report their experience in medical and surgical complications after surgical treatment of endometrial carcinoma, from January 1976 to December 1992, 301 cases of adenocarcinoma were operated by abdominal or vaginal route. From 1980 onwards abdominal route was the most frequent (radical hysterectomy with bilateral adnexectomy Rutledge type II-III with pelvic and/or aortic lymphadenectomy). No lesion occurred either during surgery or later, in the urinary or intestinal apparatus or to the great abdomino-pelvic vessels. The only medical complication observed was one episode of cerebral ictus three days after operation. Two cases of adynamic ileus and five of ventral hernia occurred.

The urine of SLE patients contains antibodies that bind to the laminin component of the extracellular matrix.

Direct immunofluorescence of tissues derived from patients affected with SLE demonstrates antibodies bound to the extracellular matrix (ECM). In the present work we have tested whether such antibodies are found in the serum and urine of lupus patients and mice. We found that the urine of patients with active SLE and of MRL/lpr/lpr mice contains antibodies that bind ECM and that a major target for these antibodies is the 200 kDa light chain of laminin which is one of the matrix components. The level of the anti-ECM, anti-laminin antibodies correlates with disease activity.

Lymph node cell vaccination against the lupus syndrome of MRL/lpr/lpr mice.

Immunization with pathogenic lymphoid cells has been shown to induce resistance to disease in experimental animal models of cell mediated autoimmunity. In the present work we tested the effectiveness of this approach in a spontaneous murine autoimmune disease, the MRL/lpr/lpr (MRL/1) murine lupus model. We now report that the anti-DNA antibodies and glomerulonephritis of MRL/1 mice could be prevented by the adoptive transfer of spleen cells from MRL/+ mice that had been vaccinated with MRL/1 lymph node T lymphocytes, but not by direct vaccination of MRL/1 mice with their cells. These results indicate that the lupus of MRL/1 mice is susceptible to regulation by adoptive vaccination and that these autoimmune mice lack the ability to raise a suppressive response against their own pathogenic cells.

Abundance of house dust mites in relation to climate in contrasting agricultural settlements in Israel.

The correlation between climatic conditions and mite numbers in houses from rural areas was studied in 13 agricultural communities (kibbutzim and moshavim) in nine geo-climatic subregions of Israel. Mites were present in 97% of the dust samples. The average number of mites per gram of dust in the different localities ranged between 84 and 2053. The maximum number of mites (7440/g dust) was found in a carpet from a house in Geva Carmel in the northern coastal region. The most prevalent species of mites were Dermatophagoides pteronyssinus and Dermatophagoides farinae, which were found in 85.6% and 71.3% of the samples, respectively. The house dust mites D. pteronyssinus, D. farinae and Euroglyphus maynei constituted 94.8% of the mites. Most of the mites were isolated from the carpets and sofas (37.0% and 33.7%, respectively), and a smaller number from beds (29.3%). The smallest number of mites (< or = 250/g dust) were found at a minimum relative humidity (RH) of 30% and lower, with a maximum temperature of 32 degrees C and higher, i.e. in the Jordan valley and Negev mountains. A greater number of mites (250-500/g dust) were found at a minimum ambient RH of 35-40% and a maximum temperature of 32 degrees C and higher, i.e. the Hula valley. A large number of mites (500-1000/g dust) were found at a minimum RH of 35-40% with a maximum temperature of 30 degrees C and lower, i.e. in the Judean and Samarian range, as well as in upper Galilee. The largest number of mites (1000-2000/g dust) was found at a minimum RH of 45% and higher, with a maximum temperature ranging between 30 and 32 degrees C. These conditions occur in the coastal strip, the coastal plain and in the Judean and Samarian foothills. A monthly examination of two houses in Zova, a kibbutz in the Judean hills next to Jerusalem, and two houses from Palmachim, a kibbutz in the coastal region, revealed that the highest prevalence of mites was found in the months April-November and May-November, respectively. In Zova, the highest number of mites were found during the months of June and July while the highest concentrations of D. pteronyssinus-antigen (Der p I) were measured during the month of September. A positive correlation between mite numbers and the quantity of Der p I in house dust was found.

Binding of anti-DNA antibodies and inhibition of glomerulonephritis in MRL-lpr/lpr mice by heparin.

Heparin was found to inhibit the DNA binding of antibodies eluted from kidneys of both humans and MRL-lpr/lpr mice with systemic lupus erythematosus. Treatment of MRL-lpr/lpr mice with low doses of heparin significantly inhibited renal damage. These results suggest that low-dose heparin might be useful in preventing renal damage in patients with lupus nephritis.

Inhibition of T lymphocyte heparanase by heparin prevents T cell migration and T cell-mediated immunity.

Previously we reported that activated T lymphocytes express a heparanase enzyme that degrades the heparan sulfate moiety of the proteoglycan of the extracellular matrix (ECM). Expression of the heparanase enzyme was found to be associated with the ability of activated T lymphocytes to penetrate blood vessel walls and accumulate in target organs. We recently found that relatively low doses of heparin administered to mice or rats inhibited T cell-mediated immune reactions. In the present study we investigated the effects in vitro and in vivo of the heparanase inhibitor, heparin, on the expression of T lymphocyte heparanase and on the ability of T lymphocytes to mediate a delayed-type hypersensitivity (DTH) reaction. We found that heparanase was induced by immunizing mice with antigen in vivo or by activating T lymphocytes with concanavalin A in vitro. Relatively low doses of heparin administered once daily in vivo (5 micrograms) or present in vitro (0.1 microgram/ml) inhibited the expression of heparanase induced by immunization or by concanavalin A incubation. Higher or lower doses of heparin did not have these effects. The same doses of heparin that inhibited expression of heparanase also inhibited the ability of the lymph node cells to migrate to a site of antigen and adoptively produce a DTH reaction. These findings suggest that modulation of cell-mediated immune reactions may be achieved by relatively low doses of heparin which inhibit expression of T lymphocyte heparanase.