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To describe patterns of physiological and psychological stress during induced labor and their correlation to obstetrical and neonatal outcomes. This prospective, observational study included 167 women, with low-risk, singleton pregnancies, who delivered at term, at a tertiary academic center from 2015 through 2018. Among them, 72 (43%) underwent induction and 95 (57%) had spontaneous labor onset. Physiological stress was evaluated by salivary cortisol measurements and emotional stress by questionnaires (visual analogue stress scale 0–10) during latent phase, active phase and full dilation stages of labor, as well as 2 min and 2 h postpartum. Cord blood cortisol and pH were obtained. Stress patterns were compared between parturients who did or did not undergo induction. Modes of delivery, labor and delivery complications, and early neonatal outcomes were compared. Mothers completed the Hospital Anxiety and Depression Scale. Induced women had lower cortisol concentrations during the latent phase compared to spontaneous onset of labor (p = 0.003), with no differences during active (p = 0.237), full dilation (0.668), 2 min and 2 h after delivery (p = 0.666). Stress scale and Hospital Anxiety and Depression Scale scores were similar between groups. Cord cortisol (p = 0.294), 1-min Apgar score ≤ 7 (p = 0.502) and 5-min Apgar score ≤ 7 (p = 0.37) were similar. All had cord pH > 7. Induction does not increase stress during labor. Moreover, it might have a positive effect on reducing cortisol during the latent phase. These findings might reassure women who are concerned about induction of labor.

Research question What are the effects of physiological and psychological stress on fertility outcomes for women undergoing IVF? Design A prospective cohort study of 72 patients undergoing IVF in 2017 and 2018. Physiological stress was assessed by salivary cortisol measurements: (i) pretreatment, when the patient received the IVF protocol; (ii) before oocyte retrieval (follicular cortisol was also measured); and (iii) before embryo transfer. Emotional stress was evaluated at each assessment with the State-Trait Anxiety Inventory and a 1–10 Visual Analogue Scale (VAS, referred to as the ‘Stress Scale'. Correlations between cortisol concentrations, psychological stress and IVF outcome were assessed. Results Salivary cortisol concentrations increased by 28% from pretreatment phase (0.46 ± 0.28 μg/dl) to maximum concentration on oocyte retrieval day (0.59 ± 0.29 μg/dl, P = 0.029) and then decreased by 29% on embryo transfer day (0.42 ± 0.23 μg/dl, P = 0.0162). On embryo transfer day, cortisol among women in their first cycle was higher than women who underwent more than one treatment (P = 0.024). Stress Scale score increased by 39% from pretreatment to a maximum score on oocyte retrieval day and then decreased by 12% on embryo transfer day. Salivary cortisol and Stress Scale were not related to subsequent embryo transfer, fertilization rate, embryo quality or clinical pregnancy rate. Follicular cortisol concentration was positively correlated with fertilization rate (r = 0.4, P = 0.004). Conclusion It can be cautiously concluded that physiological and psychological stress do not negatively affect IVF outcomes. Moreover, high follicular cortisol concentrations might have positive effects on pregnancy rates.

Bone marrow interstitial fluid (BMIF) has not been well characterized. BMIF was isolated from 60 patients including plasma cell dyscrasias (PCD, n = 33), other primary hematologic disorders (OHD, n = 15), and patients with secondary or nonhemtologic disorders (NHD, n = 12) and analyzed for an array of chemical constituents. These included total cholesterol, glucose, phosphate, creatinine, urea, total protein, albumin, globulins, total bilirubin, aspartate aminotransferase, lactate dehydrogenase, sodium, osmolarity, free triiodothyronine (free T3), total triiodothyronine (total T3), and free tetraiodothyronine (free T4). Levels of BMIF components were compared between patient groups and to plasma levels. Compared with plasma, total cholesterol, total protein, total bilirubin, sodium, and calculated osmolarity were lower in BMIF in all groups (P

Background/Aims: Contrast induced nephropathy (CIN) is associated with adverse clinical outcomes in patients undergoing coronary interventions, particularly in patients with advanced chronic kidney. The study was aimed to assess the real-life feasibility and safety of ultra-low volume coronary procedures in patients with advanced chronic kidney disease. Methods: A prospective study that included patients with an estimated glomerular filtration rate (eGFR) 2) was conducted. Coronary procedures were performed using an ultra-low contrast volume technique. Results: The 30 patients had a mean eGFR of 31.8(±8) mL/min/1.73 m2. Indications for coronary angiography were non-ST elevation myocardial infarction (63.3%), unstable (20%), and stable angina pectoris (16.7%). Median contrast volume for diagnostic coronary angiography was 13 mL (interquartile ranges [IQR] 12–14.9), and an additional 13 mL (IQR 8.8–14.3) for percutaneous coronary intervention (PCI). In 3 patients (10%), a ≥25% increase was demonstrated in serum cystatin C levels 48 h following the procedure. None of the patients demonstrated a ≥25% increase in serum creatinine levels at 48 h. Following 6 months, no patient required renal replacement therapy or unplanned coronary intervention. Conclusions: In patients with advanced chronic kidney disease, the ultra-low contrast technique is feasible and effective and can be used safely without a significant deterioration in renal function. This technique may increase the utilization of PCI in high-risk coronary patients with chronic kidney disease.

This prospective cohort pilot study investigated the physiology of C-reactive protein (CRP) during in vitro fertilization (IVF) cycles and its effect on outcomes in women with and without obesity. The study was conducted from April to August 2014, in the IVF Unit of a university-affiliated hospital. Women aged 18-42 years were enrolled. Those with chronic inflammatory diseases or acute illness were excluded. A total of 31 patients were included: 17 with BMI < 30 kg/m2 and 14 with BMI ≥ 30 kg/m2. Serum CRP levels were measured: (i) before starting ovarian stimulation; (ii) on the day of β-HCG administration; and (iii) on day of ovum pick-up (OPU), in both serum and follicular fluid. Serum CRP levels were significantly higher in women with obesity at all time points. For the entire cohort, a positive correlation was found between basal oestradiol (E2) and basal CRP (r = 0.71, p < 0.05). A specific pattern of CRP levels was not detected during the IVF cycle. High serum CRP levels on OPU day had a negative effect on embryo quality (p = 0.056). CRP ≥ 0.5 mg/dL was associated with lower quality embryos (2.6 ± 0.3 vs. 3.3 ± 0.3; p = 0.04). High serum CRP level on OPU day negatively affects embryo quality.

Background Labor is considered a stressful event, yet no study has described the course of stress measured by cortisol during labor and postpartum. Objective The objective of the study was to describe the patterns of physiological and psychological stress during labor as measured by salivary cortisol concentrations and stress questionnaires and their correlation to obstetric and neonatal outcomes. Study Design This prospective, observational study included 167 women with low-risk, singleton, term deliveries at a tertiary academic center. Physiological stress was evaluated by salivary cortisol measurements and emotional stress by questionnaire (stress scale ranging from 0 to 10) during the latent phase, active phase, and full dilation stages of labor as well as 2 minutes, 2 hours, and 24 hours after delivery. Cord blood cortisol and pH were also obtained. Modes of delivery, complications during labor and delivery, and early neonatal outcomes were evaluated. Results Salivary cortisol concentrations increased gradually from latent phase to active phase. The maximum increase was observed within 2 minutes of the delivery (from an average of 1.06 μg/dL to 1.67 μg/dL; 57% increase). Within 2 hours after delivery, cortisol decreased and reached a nongravid concentration after 24 hours (0.16 μg/dL). Cortisol concentrations during labor and up to 2 hours postpartum were above the average concentration of nongravid women (0.5 μg/dL). Women with epidural anesthesia had lower cortisol concentrations at complete dilation (P = .026) and 2 hours postpartum (P = .016) compared with women without epidural. Psychological stress peaked during latent and full dilation phases (mean 4.56 and 4.29, respectively). Maximum decrease from 4.29 to 2.04 (52%) occurred immediately postpartum. Cord cortisol was higher among women delivered by vacuum extraction compared with spontaneous vaginal delivery (17 ± 2 vs 11 ± 3.8, P = .03). Conclusion This study reveals the course of cortisol concentrations during labor for low-risk pregnancies, with maximum increase immediately postpartum. Subjective stress levels decreased over the course of labor. Salivary cortisol portrays stress during labor and may be used as a reference to evaluate complicated pregnancies and to evaluate the role of cortisol during these deliveries.

New negatively charged water-soluble bacteriochlorophyll (Bchl) derivatives were developed in our laboratory for vascular-targeted photodynamic therapy (VTP). Here we focused on the synthesis, characterization and interaction of the new candidates with serum proteins and particularly on the effect of serum albumin on the photocytotoxicity of WST11, a representative compound of the new derivatives. Using several approaches, we found that aminolysis of the isocyclic ring with negatively charged residues markedly increases the hydrophilicity of the Bchl sensitizers, decreases their self-association constant and selectively increases their affinity to serum albumin, compared with other serum proteins. The photocytotoxicity of the new candidates in endothelial cell culture largely depends on the concentration of the serum albumin. Importantly, after incubation with physiological concentrations of serum albumin (500-600 microM), WST11 was found to be poorly photocytotoxic (80% endothelial cell survival in cell cultures). However, in a recent publication (Mazor, O. et al. [2005] Photochem. Photobiol. 81, 342-351) we showed that VTP of M2R melanoma xenografts with a similar WST11 concentration resulted in approximately 100% tumor flattening and70% cure rate. We therefore propose that the two studies collectively suggest that the antitumor activity of WST11 and probably of other similar candidates does not depend on direct photointoxication of individual endothelial cells but on the vascular tissue response to the VTP insult.

Critical laboratory results require prompt reporting to the attending physician, as they may indicate that a patient is in a life-threatening condition. Although this important subject has been covered in many publications, it needs more attention from our healthcare organizations, which have no official policy on the subject. Matching expectations between the doctor and the laboratory needs to be better defined.The aim of this work was to inform the community of doctors and laboratories about the multiple problems concerning the reporting of critical laboratory results, to create a platform for exchanging views and ideas, and to build an extensive infrastructure for developing a unified plan to address this important issue.We present the results of four years of experience of reporting critical laboratory values at the Meir Medical Center Laboratories. The idea leading this work was to present the relatively low rate of critical results reported by the laboratories in 2010, sharing the problems discovered while investigating the situation in depth, and presenting the solutions that enabled us to obtain the desired results within four years.Gradual implementation of these improvements resulted in critical value reporting increasing from 55% in 2010 to 95% currently.We suggest a model for improving critical laboratory values reporting based on our 4-year experience, which emphasizes: (1) The importance of selecting proper tests and values for critical results; (2) The significance of using technology and computerized measures to support the process; and (3) Developing quick procedures for monitoring and controlling the process.

The progression of breast cancer is affected by multiple cellular and microenvironmental components. The monocyte chemoattractant MCP-1, IL-6 and matrix metalloproteinases (MMP) were suggested to promote, each on its own, breast cancer progression. We recently demonstrated that the high-tumorigenicity phenotype of the DA3 and CSML murine mammary adenocarcinoma cells is correlated with a high expression of MCP-1, IL-6 and MMP. This raised the possibility that common intrinsic tumor-derived factors regulate the concordant expression of these 3 components. The aim of the present study was to gain insight into the mode by which the secretion of MCP-1, IL-6 and MMP from murine mammary adenocarcinoma cells is regulated. This was investigated in cellular clones established from a highly malignant variant of the DA3 tumor (DA3-high). We also determined the secretion of the antimalignancy chemokine IP-10 from these cells. The results indicate that the secretion levels of IL-6, MMP and IP-10 varied between the clones. In contrast, all the clones secreted uniformly high levels of MCP-1, suggesting that MCP-1 constitutes an important feature of the malignancy phenotype of mammary carcinoma. In most of the clones, elevated levels of 1 of the 3 promalignancy factors did not correlate with a high expression of the other 2 factors and vice versa. These findings indicate that the 3 promalignancy factors are not coregulated by a common intrinsic tumor-derived factor. Rather, these results suggest that the individual capacities of the different clones to secrete these factors are summed up in the high-malignancy DA3 parental tumor population, which secretes relatively high levels of MCP-1, IL-6 and MMP as compared to DA3 cells expressing a low-malignancy phenotype. In contrast to the lack of coordinated intrinsic regulation of MCP-1, IL-6 and MMP, it was found that recombinant TNFα, a product of tumor-associated macrophages contributing to breast cancer progression, upregulated the secretion of MCP-1, IL-6 and MMP from all the clones. These results suggest a key role for this microenvironmental, monocyte-derived cytokine in the coordinated regulation of these 3 molecules. Furthermore, additional results demonstrated that monocytic cell-derived TNFα upregulated MCP-1 secretion from the tumor cells and that MCP-1 in turn promoted the secretion of TNFα from monocytic cells. This may result in a positive feedback loop, whereby the tumor cells and the monocytic cells at tumor site promote each other's ability to express and secrete promalignancy factors. We next attempted to assess the contribution of the promalignancy factors MCP-1, IL-6 and MMP and of the antimalignancy factor IP-10 to mammary adenocarcinoma progression. To this end, a preliminary formula was developed in which the net balance between secretion levels of the promalignancy factors and that of the antimalignancy IP-10 chemokine from different clones was related to their in vivo tumorigenicity profile. This formula suggests that a balance between the secretion levels of these factors plays an important role in determining the malignancy phenotype of mammary carcinomas. In all, our findings demonstrate that the mammary tumor cell population is composed of a heterogeneous assortment of clones whose individual characteristics are averaged in the whole population. The malignancy potential of such tumors is thus determined, inter alia, by a combinatorial effect of several promalignancy and antimalignancy factors secreted from each of the clones comprising these tumors. Our results also suggest that the expression of such factors is determined by several nonmutually exclusive regulatory mechanisms. © 2003 Wiley-Liss, Inc.

Tumor progression is a multistep process in which alterations in the expression of numerous gene products may give rise to highly malignant cellular variants. In the present study, we analyzed the differential expression of several genes in cellular variants of mammary adenocarcinomas with high or low malignancy potential, which originated in a common ancestor. To assess the generality of our findings, high and low malignancy variants were derived from two different mammary adenocarcinoma cell lines, namely DA3 and CSML cells. Of major importance is the fact that the differences between high- and low-malignancy variants observed in one system of mammary adenocarcinoma cells (DA3 cells) were identically reproduced in the other system of mammary adenocarcinoma cells (CSML cells). The high malignancy variants of tumors both DA3-high and CSML-high (previously called CSML-100), expressed higher levels of factors that induce monocyte migration than the low malignancy DA3-low and CSML-low (previously called CSML-0) variants. In addition, it was found that DA3-high and CSML-high cell variants expressed higher levels of monocyte chemoattractant protein-1 (MCP-1), interleukin-6 (IL-6) and matrix metalloproteinases (MMPs) than the low malignancy variants (DA3-low and CSML-low). These results suggest that MCP-1, IL-6 and MMPs potentially contribute to mammary adenocarcinoma progression and that their expression is regulated by a common pathway. The expression of MCP-1, IL-6 and MMPs in both DA3-high and CSML-high cells was up-regulated by tumor necrosis factor alpha (TNFalpha). The fact that TNFalpha exerted similar effects on the expression of these three factors in both cell systems raises the possibility of a coordinated co-regulation of tumor-promoting factors.

Breast cancer progression may be affected by various cellular components expressed by the tumor cells and/or by microenvironmental factors. Many studies report the correlation between breast cancer progression and monocyte infiltration into the tumor site. We have identified recently the CC chemokine regulated on activation, normal T cell expressed and secreted (RANTES), a major monocyte chemoattractant expressed by breast tumor cells, as a potential contributor to breast cancer progression. In the present study, analysis of the regulation of RANTES expression demonstrates that the expression of RANTES in breast tumor cells is elevated significantly and in a synergistic manner by IFN-gamma and tumor necrosis factor-alpha. Identification of the mechanisms by which RANTES may contribute to breast cancer progression included the analysis of the potential ability of RANTES to act in paracrine and indirect mechanisms, as well as directly on the tumor cells, to promote disease progression. Our results suggest that breast tumor cell-derived RANTES may promote breast cancer progression by its partial contribution to monocyte migration into breast tumor sites. Moreover, RANTES promotes the expression of matrix metalloproteinase (MMP) 9 by THP-1 monocytic cells and elevates vascularity in chick chorioallantoic membrane assays. Tumor necrosis factor-alpha, a major monocyte-derived cytokine, was found to promote the expression of MMP9 and MMP2 by MCF-7 and T47D breast adenocarcinoma cells, respectively, and to induce the de novo expression of an additional proteolytic enzyme by T47D cells, presumably MMP9. The possibility that RANTES may act directly on breast tumor cells was supported by detection of the expression of the CCR5 RANTES receptor in biopsy sections of breast cancer patients and by the ability of RANTES to promote the expression of MMP9 by MCF-7 cells. In all, our study suggests that the expression of RANTES by breast tumor cells results not only in monocyte migration to the tumor site but also in protumorigenic activities of RANTES and of proinflammatory cytokines that may facilitate metastasis formation and contribute to disease progression.

The search for mechanisms that regulate tumor progression has motivated the authors' laboratory to establish a unique murine model system, consisting of two lines of DA3 mammary adenocarcinoma cells that were derived originally from a common ancestor but differed in their malignant potential. Studies indicated that the highly malignant phenotype manifested by one of the cell lines (termed Ly-6hi DA3 cells) was associated with high expression of the Ly-6E.1 antigen. To characterize the mechanisms controlling the high malignancy phenotype expressed by Ly-6hi DA3 cells, the study was focussed on the potential contribution of tumor-derived factors to the high malignancy phenotype expressed by these cells. To this end, the expression of CC chemokines, major chemoattractants of monocytes and T cells, by the highly malignant Ly-6hi DA3 cells as compared to the low malignancy Ly-6lo DA3 cells was evaluated. The results indicate that the highly malignant cells express higher levels of factors that induce monocyte migration than the low malignancy cells. Two CC chemokines were shown to be highly produced by Ly-6hi DA3 cells, MIP-1alpha and MCP-1, of which only the latter was shown to contribute to the high migratory activity expressed by the high malignancy Ly-6hi DA3 cells. Since MCP-1 may attract monocytes to tumor sites, these findings suggest that monocyte-derived mediators, such as growth factors or angiogenic cytokines, have pro-malignancy effects that contribute to the high malignancy phenotype expressed by Ly-6hi DA3 cells.

In breast carcinoma, high levels of tumor-associated macrophages are correlated with lymph node metastases and clinical aggressiveness. Potential candidates that may support the recruitment of monocytes from the circulation into breast tumors are the members of the CC subfamily of chemokines. In the present study we evaluated the expression of the CC chemokine RANTES in sections of breast cancer patients diagnosed in different stages of disease. Our results indicate that high incidence and intensity of RANTES expression were directly correlated with a more advanced disease, suggesting that the chemokine may be involved in breast cancer progression. Analyses performed by using the T47D and MCF-7 human breast adenocarcinoma cells indicated that RANTES expression is tightly regulated by cytokines. Furthermore, the results of our study indicate that T47D-derived RANTES partially contributes to monocyte migration, and suggest that in vivo this chemokine may be involved in inducing monocyte infiltration to breast tumor sites. In the present study we further characterized the paracrine and autocrine mechanisms by which RANTES may support breast cancer progression. The results suggest that RANTES may be involved in a complex process, in which a crosstalk between infiltrating monocytes and the tumor cells may affect tumor progression.