Possible proteomic biomarkers for the detection of pancreatic cancer in oral fluids.

The 80% mortality rate of pancreatic-cancer (PC) makes early diagnosis a challenge. Oral fluids (OF) may be considered the ultimate body fluid for non-invasive examinations. We have developed techniques to improve visualization of minor OF proteins thereby overcoming major barriers to using OF as a diagnostic fluid. The aim of this study was to establish a short discriminative panel of OF biomarkers for the detection of PC. Unstimulated OF were collected from PC patients and controls (n = 30). High-abundance-proteins were depleted and the remaining proteins were analyzed by two-dimensional-gel-electrophoresis and quantitative dimethylation-liquid-chromatography-tandem mass-spectrometry. Label-free quantitative-mass-spectrometry analysis (qMS) was performed on 20 individual samples (n = 20). More than 100 biomarker candidates were identified in OF samples, and 21 had a highly differential expression profile. qMS analysis yielded a ROC-plot AUC value of 0.91 with 90.0% sensitivity and specificity for a combination of five biomarker candidates. We found a combination of five biomarkers for PC. Most of these proteins are known to be related to PC or other gastric cancers, but have never been detected in OF. This study demonstrates the importance of novel OF depletion methodologies for increased protein visibility and highlights the clinical applicability of OF as a diagnostic fluid.

Stability and change in depressive symptoms from pregnancy to two months postpartum in childbearing immigrant women.

The present study explored changes in mental health and functional status from pregnancy to 2 months postpartum in a sample of 106 childbearing immigrant women. Three sets of variables were examined in relation to postpartum depressive symptomatology: (1) prenatal depression, worries, and somatic symptoms; (2) social relationships (marital quality and social support), and (3) factors related to migration (premigration stress and length of stay in the host country). We found that 37.7% of the women in this community sample scored above the cutpoint of 12 on the Edinburgh Postnatal Depression Scale; prenatal depressive and somatic symptoms, as well as marital quality, were the best predictors of postpartum depressive symptomatology. An examination of differing trajectories from pregnancy to the postpartum period suggests that women with relatively few somatic complaints, low levels of perinatal stress, and satisfactory marital relations were less likely to exhibit mental health problems during pregnancy and postpartum. Women who were not depressed prenatally but reported postpartum depressive symptomatology exhibited several predisposing risk factors during pregnancy: many somatic complaints, high perinatal anxiety, and premigration stress. Women who were depressed during pregnancy but not postpartum reported improved physical function after childbirth. The implications of these findings for screening childbearing immigrant women are discussed.

Validating the subcutaneous model of injectable autologous cartilage using a fibrin glue scaffold.

PURPOSE: To create and validate an injectable model for autologous in vivo cartilage engineering with ultimate clinical applicability in human subjects. HYPOTHESIS: Cartilage can be generated subcutaneously using fibrin glue and autologous chondrocyte components. BACKGROUND: To date, cartilage engineering studies have been limited by several factors. Immunocompromised animals and nonautologous chondrocytes have been successfully used to create cartilage, but results using identical designs failed in immunocompetent subjects. Recent studies using more biocompatible tissues and matrices have been performed with both in vitro and in vivo steps. Although successful, several problems are notable. In vitro cartilage displays a poor modulus of elasticity, even after in vivo implantation. Variable deformation and volume loss occurs when in vitro specimens are matured in vivo. These concerns limit the clinical utility of these methods. We therefore set out to create autologous cartilage using a model that was clinically feasible, easy to create, and could be performed with very low patient harvest morbidity. MATERIALS AND METHODS: Eight New Zealand white rabbits underwent a unilateral harvest of ear cartilage. Samples were then digested using standard methods. Cell counts and survival assays were performed before implantation. One sample of fibrin glue (Tisseel) and chondrocytes was injected subcutaneously into each donor rabbit and then left in situ for 3 months. A second sample with both basic fibroblast growth factor (b-FGF) and insulin-like growth factor (IGF)-1 in the injection suspension was also assessed (for a total of 16 samples). After harvest, analysis of overall volume, histology, and chondrocyte drop out counts was performed. RESULTS: Cartilage formation occurred in 8 of 14 (57%) specimens that were obtained at the time of sacrifice. Of note, 6 of 7 (85%) non-growth-factor containing samples yielded positive results. Comparison with the success rate using concomitant growth factors (2/7) showed a negative effect on cartilage yield (P = .015). Chondrocyte survival, based on chondrocyte dropout counts, was not effected. Angiogenesis appeared to correlate with cartilage formation in the central regions of the implant. Alcian blue demonstrated the presence of active matrix deposition, and elastin Verhoff-van Geison (EVG) stains were positive, showing an elastic cartilage phenotype. Very limited osteoid formation was seen in successful implants. Failed implants demonstrated avascular necrosis, giant cell reactions, and inflammatory infiltrates. CONCLUSIONS: This study validates the subcutaneous site as a recipient bed for the engineering of autologous cartilage in vivo. It also represents the first subcutaneous implantation of fibrin glue and chondrocytes in an immunocompetent host as well as the first published report of elastic cartilage generation in vivo. Although the model needs to be further streamlined to increase yields and overall volume, this study clearly demonstrates the feasibility of in vivo chondrogenesis (85% success). The addition of FGF and IGF-1 at the concentrations used negatively influenced cartilage yield. However, extrapolation of these results to other combinations or concentrations can not be done, and this issue deserves further investigation.

Glial growth factor/neuregulin inhibits Schwann cell myelination and induces demyelination.

During development, neuregulin-1 promotes Schwann cell proliferation and survival; its role in later events of Schwann cell differentiation, including myelination, is poorly understood. Accordingly, we have examined the effects of neuregulin-1 on myelination in neuron-Schwann cell cocultures. Glial growth factor (GGF), a neuregulin-1 isoform, significantly inhibited myelination by preventing axonal segregation and ensheathment. Basal lamina formation was not affected. Treatment of established myelinated cultures with GGF resulted in striking demyelination that frequently began at the paranodes and progressed to the internode. Demyelination was dose dependent and accompanied by dedifferentiation of Schwann cells to a promyelinating stage, as evidenced by reexpression of the transcription factor suppressed cAMP-inducible POU; a significant proportion of cells with extensive demyelination also proliferated. Two other Schwann cell mitogens, fibroblast growth factor-2 and transforming growth factor-beta, inhibited myelination but did not cause demyelination, suggesting this effect is specific to the neuregulins. The neuregulin receptor proteins, erbB2 and erbB3, are expressed on ensheathing and myelinating Schwann cells and rapidly phosphorylated with GGF treatment. GGF treatment of myelinating cultures also induced phosphorylation of phosphatidylinositol 3-kinase, mitogen-activated protein kinase, and a 120-kD protein. These results suggest that neuronal mitogens, including the neuregulins, may inhibit myelination during development and that activation of mitogen signaling pathways may contribute to the initial demyelination and subsequent Schwann cell proliferation observed in various pathologic conditions.

Does episiotomy prevent perineal trauma and pelvic floor relaxation?

OBJECTIVE: To compare the outcomes of the current practice of liberally or routinely employing episiotomy to prevent perineal tears and pelvic floor relaxation (control group) to a policy of restricting episiotomy use to specific fetal and maternal indications (experimental group). DESIGN: A randomized controlled trial (RCT). SETTING: Three university hospitals in Montreal. SUBJECTS: Seven hundred three low-risk women enrolled at 30 to 34 weeks of gestation were randomized late in labor to the designated trial arm, by parity, and followed up to 3 months postpartum. MAIN OUTCOME MEASURES: Antepartum and postpartum information on perineal trauma and pain, pelvic floor symptoms (urinary incontinence), and sexual activity was collected through the use of standard questionnaires; pelvic floor function was measured by electromyographic (EMG) perineometry. RESULTS: Restricting episiotomy use in primiparous women was associated with similar sutured perineal trauma to the liberal or routine approach. Multiparous women in the restricted episiotomy group more often gave birth with an intact perineum (31% compared with 19%, odds ratio (OR) = 1.85, 95% confidence interval (CI) = 1.09 to 3.16). All but one 3rd/4th-degree perineal tear was associated with median episiotomy (46 of 47 in primiparous women and 6 of 6 among multiparous women). No difference between trial groups was found in postpartum perineal pain, antepartum and 3-month postpartum EMG perineometry, and urinary and pelvic floor symptoms. CONCLUSIONS: We found no evidence that liberal or routine use of episiotomy prevents perineal trauma or pelvic floor relaxation. Virtually all severe perineal trauma was associated with median episiotomy. Restriction of episiotomy use among multiparous women resulted in significantly more intact perineums and less perineal suturing.

The influence of birth setting on the father's behavior toward his partner and infant.

As part of a controlled, clinical trial conducted to compare medical and psychological outcomes of a birth room and a conventional hospital setting, we examined the behavior of fathers toward their partners and infants. One hundred fourteen couples were systematically assigned to either locale by strict alternation. They learned about this allocation on arrival at the hospital in labor. Observations of fathers' behavior were made at midlabor and during home visits at three months and one year. During labor, fathers assigned to the conventional setting were more involved in helping and encouraging their partners. Parenting behavior was not influenced by the birth setting. Unexpectedly, fathers were more involved with their infants when the mothers had expressed less satisfaction with childbirth. Compensation behavior may explain these results, which can be seen as appropriately adaptive in the face of perceived environmental deficiencies affecting the laboring woman and the infant.

Care in a birth room versus a conventional setting: a controlled trial.

A controlled clinical trial was carried out to assess whether a birth room setting would influence the care of mothers and newborns. Of the 163 low-risk women enrolled, 49 (30%) manifested some prenatal risk and were excluded. The remaining 114 were allocated by strict alternation to a birth room or a conventional setting. Of the 56 women allocated to the birth room, 63% of the primiparas and 19% of the multiparas were later transferred. The numbers in the two settings who had oxytocin stimulation, epidural anesthesia, forceps delivery or cesarean section did not show statistically significant differences. The episiotomy rates were slightly lower in the birth room than in the conventional setting, and the rates of an intact perineum were higher in the birth room. Neither the Apgar scores nor the morbidity rates of the infants showed statistically significant differences related to the setting to which the mother had been allocated, although more infants from the conventional setting were admitted to a special care unit. Both "experimental" groups of women less often received routine perineal shaving, enemas or intravenous infusions than did an obstetrically similar nonexperimental comparison group. Despite the apparent inability in this setting for the birth room to influence the rate of major obstetric procedures (except for episiotomy) and outcomes, the authors believe that a birth room is desirable in tertiary care centres as well as in community hospitals.

[Satisfaction of couples towards birth when using a birthing room or the traditional delivery room.]. / La satisfaction à l'égard de la naissance parmi les couples utilisant la chambre de naissance ou la chambre traditionnelle.

Following a random distribution, two groups of couples, users of the B.R. (birth room) and users of the T. R. (traditional room) were compared in terms of each partner's feeling of satisfaction in relation to the giving birth process. Statistical analysis of the means of the B.R. and T.R. fathers, of the B.R. and T.R. mothers, three days after delivery and three months later, yields the following results : following birth, both fathers and mothers of the B.R. group indicate a higher feeling of satisfaction than the T.R. mothers and fathers in relation to the environment. Mothers of the B.R. and T.R. are equally satisfied in relation to the amount of time spent with their infant, whereas fathers of the B. R. are more satisfied than their spouses and more satisfied than the T.R. fathers. Three months later, the only difference to these above-mentioned results, is the higher degree of satisfaction of B.R. mothers over T.R. mothers in relation to the length of contact with their infant right after birth.