Quality of life and satisfaction of patients after oncoplastic or traditional breast-conserving surgery using the BREAST-Q (BCT module): a prospective study.

INTRODUCTION: The oncoplastic conservative surgery was developed as a natural evolution of traditional surgery, attempting to improve the therapeutic and aesthetic outcomes where tumor resection could be followed by not-adequate results. Our primary aim is to evaluate how patient satisfaction and quality-of-life after conservative oncoplastic surgery, using BREAST-Q (BCT Module), change pre- and post-operatively. The secondary aim is to compare patient-reported outcome after oncoplastic or traditional conservative surgery. PATIENTS AND METHODS: We enrolled 647 patients who underwent traditional conservative surgery or oncoplastic surgery from January 2020 to December 2022. Only 232 women (35.9%) completed the BREAST-Q questionnaire on a web-based platform, at the preoperative phase and 3 months after treatment. RESULTS: The average score of "Psychosocial well-being" and "Satisfaction with Breasts" 3 months after surgery showed a statistically significant improvement, while the average score for "Physical well-being: Chest" at 3 months showed a worsening compared to the baseline. "Sexual well-being" did not show statistically significant change. A significant difference between the post-operative outcome of oncoplastic surgery and traditional surgery was observed only for Physical well-being (better for traditional surgery). CONCLUSIONS: The study showed significant improvement in patient-reported outcomes 3 months after the surgery, except for physical discomfort that increases especially after oncoplastic surgery. Furthermore, our data, as well as many others, point to the appropriateness of using OCS where there is an effective indication, while the perspective of patients cannot find significant superiority over TCS in any of the areas analyzed.

Comparison of intubating conditions after induction with propofol and remifentanil or sufentanil : Randomized controlled REMIDENT trial for surgical tooth extraction.

PURPOSE: The aim of this study was to compare tracheal intubation conditions after induction of anesthesia with a bolus of propofol-sufentanil or propofol-remifentanil and a rapid induction technique. MATERIAL AND METHODS: A total of 70 patients (American Society of Anesthesiologists (ASA) classification I­II) undergoing outpatient surgery under general anesthesia with intubation for tooth extraction were randomly assigned to two groups in this double-blind study. Patients received either a bolus of remifentanil (3 µg/kg) or sufentanil (0.3 µg/kg) together with 2.5 mg/kg propofol for intubation. The primary outcome was the percentage of excellent intubation conditions and the secondary outcomes were the percentage of patients with a decrease of over 20% in mean arterial pressure (MAP) or heart rate (HR), time to achieve spontaneous respiration, time between the end of surgery and extubation and time to achieve an Aldrete score of 10. VAS pain score was >3 or having laryngeal pain 15 min after arriving in the postanesthesia care unit (PACU) were also analyzed. RESULTS: Intubating conditions (perfect + good conditions) were significantly better with remifentanil than with sufentanil (88.5% vs. 68.6%; p = 0.01). When using remifentanil, the hemodynamic conditions were good. Using remifentanil did not significantly increase the pain score or the laryngeal pain in the recovery room. This was confirmed by no significant differences between the groups for morphine consumption. Remifentanil significantly decreased the time to achieve an Aldrete score of 10. CONCLUSION: When intubation without muscle relaxants is required, intubating conditions are much better when a remifentanil bolus is used compared to a sufentanil bolus. The remifentanil/propofol rapid induction technique is a valuable technique to quickly intubate and achieve good conditions.

Hemidiaphragmatic paralysis following ultrasound-guided anterior vs. posterior suprascapular nerve block: a double-blind, randomised control trial.

Interscalene brachial plexus block provides analgesia for shoulder surgery but is associated with hemidiaphragmatic paralysis. Before considering a combined suprascapular and axillary nerve block as an alternative to interscalene brachial plexus block, evaluation of the incidence of diaphragmatic dysfunction according to the approach to the suprascapular nerve is necessary. We randomly allocated 84 patients undergoing arthroscopic shoulder surgery to an anterior or a posterior approach to the suprascapular nerve block combined with an axillary nerve block using 10 ml ropivacaine 0.375% for each nerve. The primary outcome was the incidence of hemidiaphragmatic paralysis diagnosed by ultrasound. Secondary outcomes included: characterisation of the hemidiaphragmatic paralysis over time; numeric rating scale pain scores; oral morphine equivalent consumption; and patient satisfaction. The incidence of hemidiaphragmatic paralysis was 40% (n = 17) vs. 2% (n = 1) in the anterior and posterior groups, respectively (p < 0.001). In one third of patients with hemidiaphragmatic paralysis, it persisted beyond the eighth hour. The median (interquartile range [range]) oral morphine equivalent consumption was significantly higher in the posterior approach when compared with the anterior approach, whether in the recovery area (20 [5-31 (0-60)] mg vs. 7.5 [0-14 (0-52)] mg, respectively; p = 0.004) or during the first 24 h (82 [61-127 (12-360) mg] vs. 58 [30-86 (0-160)] mg, respectively; p = 0.01). Patient satisfaction was comparable between groups (p = 0.6). Compared with the anterior approach, diaphragmatic function is best preserved with the posterior needle approach to the suprascapular nerve block.

PROMs in post-mastectomy care: Patient self-reports (BREAST-Q™) as a powerful instrument to personalize medical services.

One of the goals of immediate breast reconstruction (IBR) is to satisfy the patient's outcome. Recent studies therefore tended to focus on the patient's perception of the care and on the impact on quality of life using patients-reported-outcome-measures (PROMs), able to measure the health status directly without the clinician's interposition. We present a preliminary prospective study on 333 patients who underwent mastectomy with IBR in a two-year period, in a single Italian centre, using a dedicated PROMs, the BREAST-Q™, to determine the patient's satisfaction. We studied two groups of IBR: Group A (two-step with tissue-expander) and Group B (one-step: prosthesis/mesh) and conducted a pre- and post-operative comparison for each group to evaluate score-gain over time, and a group-score comparison to determine whether differences were significant between reconstruction types. Two-hundred-and-nine were actually enrolled and 132 completed all the questionnaires. The response rate was 62.8% and the compliance rate (completion of all the questionnaires) was 63.1%. In both groups all the analyzed domains worsened comparing the pre and post-operative period; the differences were statistically significant only for physical and sexual-wellbeing. In the comparison between the two groups, none of the detected differences reached the statistical significance. According to our experience, we can state that PROMs could improve the health concept redefining the variables to be monitored even if data is still insufficient to draw any definitive conclusion. PROMs can help surgeons and patients decide the most appropriate surgery for a particular patient-profile and to identify those who require further support.

Radiation endurance in Al2O3 nanoceramics.

The lack of suitable materials solutions stands as a major challenge for the development of advanced nuclear systems. Most issues are related to the simultaneous action of high temperatures, corrosive environments and radiation damage. Oxide nanoceramics are a promising class of materials which may benefit from the radiation tolerance of nanomaterials and the chemical compatibility of ceramics with many highly corrosive environments. Here, using thin films as a model system, we provide new insights into the radiation tolerance of oxide nanoceramics exposed to increasing damage levels at 600 °C -namely 20, 40 and 150 displacements per atom. Specifically, we investigate the evolution of the structural features, the mechanical properties, and the response to impact loading of Al2O3 thin films. Initially, the thin films contain a homogeneous dispersion of nanocrystals in an amorphous matrix. Irradiation induces crystallization of the amorphous phase, followed by grain growth. Crystallization brings along an enhancement of hardness, while grain growth induces softening according to the Hall-Petch effect. During grain growth, the excess mechanical energy is dissipated by twinning. The main energy dissipation mechanisms available upon impact loading are lattice plasticity and localized amorphization. These mechanisms are available in the irradiated material, but not in the as-deposited films.

Impulse control behaviours in patients with Parkinson's disease after subthalamic deep brain stimulation: de novo cases and 3-year follow-up.

OBJECTIVE: To document the occurrence of impulse control behaviours (ICBs) in patients with Parkinson's disease after 3 years of continuous deep brain stimulation (DBS) of the subthalamic nucleus (STN). METHODS: Detailed neurological and ICB assessments were performed before STN DBS and up to 3 years after implant. RESULTS: 13 out of 56 patients (23.2%) had ICBs at baseline; they took higher doses of dopamine agonists (DAA). Three years after implant 11 had fully remitted with a 60.8% reduction of DAA medication; the remaining two, who had a similar medication reduction, had only compulsive eating, having recovered from hypersexuality. Six of the 43 patients without ICBs at baseline (14%) developed transient de novo ICBs after implant; none of them had ICBs at the 3-year observation. CONCLUSIONS: ICBs were abolished in patients 3 years after STN DBS and DAA dosages were lowered. New ICBs may occur after implant and are transient in most cases. Compulsive eating may be specifically related to STN stimulation.

[Preoperative management to reduce morbidity and mortality of hip fracture]. / Stratégie de prise en charge préopératoire visant à diminuer la morbidité et la mortalité de la fracture du col fémoral.

Hip femur is extremely common in the elderly and is one of the most common reasons for admission in trauma care. The main reported causes of death after hip fracture were cardiovascular (29%), neurological (20%) and pulmonary. Large epidemiological studies have shown a relatively small decrease in mortality for 20 years despite an active approach to medical and surgical management. Yet 57% of deaths occurring within 30 days post-surgery are preventable because they are not related to a pre-existing disease. Preoperative management to optimize these patients could help to reduce morbidity and mortality and is thus a crucial issue. The anesthesia consultation is used to evaluate the perioperative risk, treat pain, manage treatment and stabilize the patient. An operative delay of more than 48hours after admission increases mortality. This period should not be prolonged by unnecessary investigations that will not change the perioperative management. The preoperative period is a key moment because it allows to choose the anesthetic technique. Even if this choice is controversial, continuous spinal anesthesia (titrated) do not modify the cardiovascular and neurological physiological balance of these precarious patients.

DiANNA 1.1: an extension of the DiANNA web server for ternary cysteine classification.

DiANNA is a recent state-of-the-art artificial neural network and web server, which determines the cysteine oxidation state and disulfide connectivity of a protein, given only its amino acid sequence. Version 1.0 of DiANNA uses a feed-forward neural network to determine which cysteines are involved in a disulfide bond, and employs a novel architecture neural network to predict which half-cystines are covalently bound to which other half-cystines. In version 1.1 of DiANNA, described here, we extend functionality by applying a support vector machine with spectrum kernel for the cysteine classification problem-to determine whether a cysteine is reduced (free in sulfhydryl state), half-cystine (involved in a disulfide bond) or bound to a metallic ligand. In the latter case, DiANNA predicts the ligand among iron, zinc, cadmium and carbon. Available at: http://bioinformatics.bc.edu/clotelab/DiANNA/.

DiANNA: a web server for disulfide connectivity prediction.

Correctly predicting the disulfide bond topology in a protein is of crucial importance for the understanding of protein function and can be of great help for tertiary prediction methods. The web server http://clavius.bc.edu/~clotelab/DiANNA/ outputs the disulfide connectivity prediction given input of a protein sequence. The following procedure is performed. First, PSIPRED is run to predict the protein's secondary structure, then PSIBLAST is run against the non-redundant SwissProt to obtain a multiple alignment of the input sequence. The predicted secondary structure and the profile arising from this alignment are used in the training phase of our neural network. Next, cysteine oxidation state is predicted, then each pair of cysteines in the protein sequence is assigned a likelihood of forming a disulfide bond--this is performed by means of a novel architecture (diresidue neural network). Finally, Rothberg's implementation of Gabow's maximum weighted matching algorithm is applied to diresidue neural network scores in order to produce the final connectivity prediction. Our novel neural network-based approach achieves results that are comparable and in some cases better than the current state-of-the-art methods.

Disulfide connectivity prediction using secondary structure information and diresidue frequencies.

MOTIVATION: We describe a stand-alone algorithm to predict disulfide bond partners in a protein given only the amino acid sequence, using a novel neural network architecture (the diresidue neural network), and given input of symmetric flanking regions of N-terminus and C-terminus half-cystines augmented with residue secondary structure (helix, coil, sheet) as well as evolutionary information. The approach is motivated by the observation of a bias in the secondary structure preferences of free cysteines and half-cystines, and by promising preliminary results we obtained using diresidue position-specific scoring matrices. RESULTS: As calibrated by receiver operating characteristic curves from 4-fold cross-validation, our conditioning on secondary structure allows our novel diresidue neural network to perform as well as, and in some cases better than, the current state-of-the-art method. A slight drop in performance is seen when secondary structure is predicted rather than being derived from three-dimensional protein structures.

Endothelin-2 down-regulation occurs in parallel with the anti-proliferative effect of dimethylsulfoxide in BeWO human choriocarcinoma cell line.

Endothelins exhibit growth regulating properties in many cell types, and there is now considerable evidence that they play a critical pathophysiological role in human diseases such as carcinogenesis. In the choriocarcinoma cell lines JEG-3, JAR and BeWO, we demonstrate by RT-PCR that prepro endothelin (ET)-1 and prepro ET-2 mRNA were expressed, whereas prepro ET-3 was never expressed. Only ET-1 and ET-2 peptides were identified by HPLC/RIA analyses in culture media from these three choriocarcinoma cell lines. In the BeWO line, the cellular growth measured as the cell count and DNA content decreased with increasing concentrations of dimethyl sulfoxide (DMSO; range 0.5-3%). The expression of prepro ET-2 was also suppressed by DMSO, whereas no change was noticed inprepro ET-1 mRNA. All these effects were reversible when DMSO was replaced by 15% foetal calf serum. These effects of DMSO which are correlated to ET-2 down regulation in dividing BeWO cells suggest a role for this endothelin isoform in trophoblast proliferation.

Alpha-fetoprotein gene expression in early and full-term human trophoblast.

Alpha-fetoprotein (AFP) is a major serum glycoprotein synthesized during fetal life mainly by the yolk sac and the fetal liver. At term, it reaches high concentrations in the maternal intervillous blood, which is in direct contact with the placental trophoblastic microvillous membrane, and this suggests the placental origin of the AFP at the fetal-maternal interface. We used several experimental approaches to investigate the expression of AFP gene and fetal protein production in early gestation and term placentas. RT-PCR and immunological studies clearly identified AFP messenger RNA and AFP protein in the placental villi from first trimester of pregnancy. The AFP gene was also expressed in highly purified cytotrophoblasts from early placentas, and enzymo-immunoassay showed that AFP protein was synthesized and secreted by early cytotrophoblasts. AFP was also detected in the cytoplasm of these cells by immuno-cytochemistry. However, none of these methods detected any expression of the AFP gene in full-term placental villi or in cultured trophoblasts. These findings demonstrate that both AFP mRNA and protein are present in trophoblastic cells early in pregnancy. The absence of AFP gene expression in term placental villi also suggests, that the AFP at the fetal-maternal interface is attributable to a notable transplacental passage of AFP from fetal blood in late pregnancy.

Phytoestrogens as modulators of steroid action in target cells.

Although numerous reports exist on the potential beneficial role of nutritional phytoestrogens in human health, their molecular mechanism in target cells is still not completely understood. Phytoestrogens promote estrogen and antiestrogen effects by interacting with numerous molecules, carrier proteins, enzymes and membrane and nuclear receptors, directly or indirectly involved in the transfer of estrogen signals. The hypothesis that the ER beta subtype plays a key role in antiproliferative effect of phytoestrogens, especially in breast cancer, is examined here. This review focus on the effects of phytoestrogens in developmental processes such as those linked to reproductive function, tumorigenesis and angiogenesis.

Antigenic and immunologic characterization of an allogeneic colon carcinoma vaccine.

We report the immunological characterization of three colon carcinoma cell lines, COLO 205, SW620 and SW403, which we selected to combine with cytokine-secreting fibroblasts for the development of an allogeneic tumour cell vaccine. The cell lines expressed HLA-A2 as well as shared tumour-associated antigens (TAAs) representative of colon carcinomas: CEA, Ep-CAM, MUC1, HER2/neu and MAGE antigens. They did not secrete high levels of the immunosuppressive factors TGF-beta, IL-10 or prostaglandins. The lines presented TAAs in a manner recognized by immune effector cells, which was demonstrated by the lysis of SW620 by HLA-A2-restricted anti-p53 cytotoxic T lymphocytes (CTL). COLO 205 and SW620 were genetically modified to express the co-stimulatory molecule CD80 (B7.1), which increased the ability of the cells to stimulate CTL in vitro. CTL clones derived from HLA-A2+ peripheral blood mononuclear cells stimulated with the CD80-expressing lines lysed the stimulator cell and an HLA-A2+ colon cancer cell line, but did not lyse an isogeneic fibroblast line or an HLA-A2- colon cancer cell line. CTL clones derived from colon carcinoma patients immunized with an allogeneic vaccine containing these lines demonstrated killing of autologous tumour cells, the vaccine cell lines and other HLA-A2+ colon cancer cell lines, but not fibroblasts isogeneic to certain of the target cell lines. Our studies demonstrate that these colon carcinoma cell lines express shared TAAs that can induce CTLs which recognize and lyse other colon carcinoma cells, and support the continued clinical evaluation of the CD80 gene modified allogeneic colon cell/cytokine-secreting fibroblast carcinoma vaccine.

Is up-regulation of phosphodiesterase 4 activity by PGE2 involved in the desensitization of beta-mimetics in late pregnancy human myometrium?

Elevation of cAMP content resulting from stimulation of the receptor-adenylyl cyclase complex is involved in maintaining the quiescence of the human myometrium during pregnancy. The magnitude of this elevation is critically influenced by the rate of cAMP hydrolysis by phosphodiesterase (PDE) isoenzymes. In the present study we report that in term myometrium, enhanced cAMP-specific PDE4 activity takes part in the heterologous desensitization to the beta-mimetic, salbutamol. Indeed, pretreatment with a PDE4-selective inhibitor potentiates the relaxant effect of salbutamol on myometrial strips of women at term. Furthermore, the reduced relaxant effect of salbutamol after long-term treatment of myometrial strips with PGE2, a potent myometrial effector, can be reversed by PDE4 inhibition. Using a model of cultured myometrial cells, we also demonstrated that PGE2 is able to up-regulate PDE4 activity, at least through the induction of synthesis of PDE4B and PDE4D short forms, which, in turn, dampen the cAMP accumulation provoked by the stimulation of adenylyl cyclase. Such data suggest that in late pregnancy endogenous PGE2 might up-regulate PDE4 activity and lessen the responsiveness of myometrium to beta-mimetic activation. Accordingly, coapplication of a selective PDE4 inhibitor might greatly improve the usefulness of beta-mimetic in tocolysis.

Potentiation response of cultured human uterine leiomyoma cells to various growth factors by endothelin-1: role of protein kinase C.

OBJECTIVE: Factors responsible for the abnormal proliferation of myometrial cells that accompanies leiomyoma formation are unknown, although steroid hormones and peptide growth factors have been implicated. We hypothesized that endothelin-1 (ET-1) is a physiological regulator of tumor growth. DESIGN: In this study, we investigated the role of ET-1 on growth of human leiomyoma cells and its synergistic effect with growth factors, as well as the signaling pathway involved in this interaction. METHODS: Leiomyoma cell proliferation was assayed by [H]thymidine incorporation and cell number. Protein kinase C (PKC) isoforms were analyzed by Western blot using specific antibodies. RESULTS: ET-1 on its own was unable to stimulate DNA synthesis but potentiated the leiomyoma cell growth effects of basic fibroblast growth factor (bFGF), epidermal growth factor (EGF), IGF-I and IGF-II. The failure of a protein tyrosine kinase (PTK) inhibitor, tyrphostin 51, to affect the potentiating effect of ET-1, supports the hypothesis of non-involvement of PTK in this process. The inhibition of PKC by calphostin C or its down-regulation by phorbol 12,13-dibutyrate (PDB) eliminated the potentiating effect of ET-1, but did not block cell proliferation induced by the growth factors alone. Five PKC isoforms (alpha, beta1, epsilon, delta and zeta) were detected in leiomyoma cells, but only phorbol ester-sensitive PKC isoforms (PKCalpha, epsilon and delta) contribute to the potentiating effect of leiomyoma cell growth by ET-1. CONCLUSIONS: We have demonstrated that ET-1 potentiates leiomyoma cell proliferation to growth factors through a PKC-dependent pathway. These findings suggest a possible involvement of ET-1 in the pathogenesis of leiomyomas.

Differential regulation of protein kinase C isoforms in human uterine leiomyoma.

The protein kinase C (PKC) isoenzyme expression pattern in human uterine leiomyoma was compared with that obtained in homologous myometrium distal from the tumor. The six PKC isoforms (PKCalpha, PKCbeta1, PKCbeta2, PKCdelta, PKCepsilon and PKCzeta) evidenced in the myometrium were found to be similarly expressed in leiomyoma. Quantitative immunoblotting revealed that all PKC isoforms were preferentially localized in the particulate fraction. To gain insight into the possible functional consequences of PKC expression patterns, subcellular redistribution in response to the mitogenic peptide endothelin-1 (ET-1) was studied. After stimulation with ET-1, differential redistribution occurred in leiomyoma and myometrium, suggesting a selective role of PKC isoforms in the myometrial growth process.

EP(4) receptors mediate prostaglandin E(2)-stimulated glycosaminoglycan synthesis in human cervical fibroblasts in culture.

The aim of this study was to determine the prostaglandin E (EP) receptors and second messengers implicated in glycosaminoglycan (GAG) synthesis by human cervical fibroblasts in culture. Human cervical fibroblasts were obtained from cervical biopsies in pre-menopausal, cycling women. Cultured cells were incubated with prostaglandin E(2) (PGE(2)) and an array of agonists and antagonists. Glycosaminoglycan synthesis was assayed after extraction by measuring the [(3)H]glucosamine and [(35)S]sulphate incorporated into GAG and cAMP production was determined by radioimmunoassay. PGE(2) significantly stimulated GAG synthesis. Neither 17-phenyl-trinor-PGE(2), the EP(1) selective agonist, nor sulprostone, an EP(3) agonist, had any effect on GAG production. Butaprost, the EP(2) selective agonist, also failed to increase GAG synthesis. AH6809, an EP(2) antagonist, had no effect on PGE(2)-stimulated GAG production. AH23848, an EP(4) antagonist, inhibited the GAG synthesis provoked by PGE(2). PGE(2) and butaprost significantly increased cAMP production. Both AH6809 and AH23848 inhibited the PGE(2)-stimulated cAMP production. H89, a cAMP-dependent protein kinase (PKA) inhibitor, did not inhibit PGE(2)-stimulated GAG synthesis and Sp-cAMPS, a selective PKA activator, failed to increase GAG production. In conclusion, both EP(4) and EP(2) receptors are present and functional in human cervical fibroblasts. Only EP(4) receptors mediate PGE(2) stimulated GAG synthesis in a PKA-independent pathway.

Corticosteroid-binding globulin status at the fetomaternal interface during human term pregnancy.

The status of the corticosteroid-binding globulin (CBG) at the fetomaternal interface, especially in the maternal intervillous blood space (I), was investigated and compared to that of CBG in the maternal (M) and fetal (umbilical arteries [A] and vein [V]) peripheral circulations at term. Immunoquantitation of plasma CBG showed that the CBG concentration in I was 30% less than that in M (P < 0.001) and threefold higher than that in umbilical cord blood (P < 0.001). The microheterogeneity of CBG studied by immunoaffinoelectrophoresis in the presence of concanavalin A and Western blotting indicated that the CBG in I was mainly of maternal origin and different from fetal CBG. A CBG mRNA, but no classic 50- to 59-kDa CBG, was found in isolated term trophoblastic cells. The steroid environment of the CBG in I differed greatly from that in the peripheral maternal and fetal circulations, because the progesterone:cortisol molar ratio in I was 75-fold higher than that in M and 7- to 10-fold higher than that in the fetal circulation. Binding studies revealed that the affinity constants of CBG for cortisol in I, A, and V were significantly lower than that in M plasma (P < 0.02) in their respective hormonal contexts. The binding parameters for I-CBG stripped of endogenous steroids and lipids were close to those for M-CBG but different from those of fetal CBG (P < 0.001). These data reflect the physiological relevance of the CBG-steroid interaction, especially with very CBG-loaded progesterone at the fetomaternal interface during late pregnancy.