Transversus abdominis plane block under laparoscopic guide versus port-site local anaesthetic infiltration in laparoscopic excision of endometriosis: a double-blind randomised placebo-controlled trial.

OBJECTIVE: To compare the efficiency of laparoscopically guided transversus abdominis plane block (LTAP) versus port-site local anaesthetic infiltration (LAI) in reducing postoperative pain following laparoscopic excision of endometriosis. DESIGN: A prospective, double-blind randomised controlled trial. SETTING: A tertiary referral centre for endometriosis and minimally invasive gynaecological surgery. POPULATION: Women undergoing laparoscopic excision of endometriosis from December 2015 through July 2016. METHODS: Participants were randomised to receive: port-site infiltration with bupivacaine and placebo LTAP (LAI group, n = 21); placebo port-site infiltration and LTAP with bupivacaine (LTAP group, n = 24); placebo port-site infiltration and placebo LTAP (placebo group, n = 25). MAIN OUTCOME MEASURES: Post-operative pain at 2-4, 6-8, 10-12 and 24 hours, analgesic requirements, TAP block-related complications and opioid-related adverse effects. RESULTS: There were no differences in patient characteristics between the groups. In comparison with placebo, both LTAP and LAI groups had significantly less pain at 2-4, 6-8, and 10-12 hours (median 3, 3, 3.5 versus 3, 6, 4 versus 8, 8, 7 for LTAP, LAI, and placebo, respectively, P < 0.05). Median differences (and 95% confidence intervals) were as follows; LTAP versus placebo -5 (-6 to -4), -4 (-5 to -3), -3 (-4 to -0.5); LAI versus placebo -4 (-5 to -2), -2 (-3 to -0.5), -1 (-4 to -0.5) at 2-4, 6-8 and 10-12 hours, respectively. There were no statistically significant differences between the LTAP and LAI groups. CONCLUSIONS: Laparoscopically guided transversus abdominis plane block and LAI both reduce postoperative pain in patients undergoing laparoscopic excision of endometriosis, compared with placebo. We found no differences in effect between LTAP and LAI. TWEETABLE ABSTRACT: TAP block and port-site local infiltration are both effective in reducing postoperative pain in major gynaecological laparoscopic surgery.

Single-Grasp Object Classification and Feature Extraction with Simple Robot Hands and Tactile Sensors.

Classical robotic approaches to tactile object identification often involve rigid mechanical grippers, dense sensor arrays, and exploratory procedures (EPs). Though EPs are a natural method for humans to acquire object information, evidence also exists for meaningful tactile property inference from brief, non-exploratory motions (a 'haptic glance'). In this work, we implement tactile object identification and feature extraction techniques on data acquired during a single, unplanned grasp with a simple, underactuated robot hand equipped with inexpensive barometric pressure sensors. Our methodology utilizes two cooperating schemes based on an advanced machine learning technique (random forests) and parametric methods that estimate object properties. The available data is limited to actuator positions (one per two link finger) and force sensors values (eight per finger). The schemes are able to work both independently and collaboratively, depending on the task scenario. When collaborating, the results of each method contribute to the other, improving the overall result in a synergistic fashion. Unlike prior work, the proposed approach does not require object exploration, re-grasping, grasp-release, or force modulation and works for arbitrary object start positions and orientations. Due to these factors, the technique may be integrated into practical robotic grasping scenarios without adding time or manipulation overheads.

Laparoscopic treatment of endometriosis and effects on quality of life: a retrospective study using the short form EHP-5 endometriosis specific questionnaire.

Complete surgical eradication is considered the mainstay of treatment for endometriosis. The aim of the present study was to investigate patients' own assessment of whether their laparoscopic treatment made a difference to their quality of life, as well as to assess local recurrence rates. We performed a retrospective analysis of 49 women who had laparoscopic treatment for endometriosis at our unit between 1 January 2008 and 1 January 2010. Patients were sent the Short Form EHP-5 questionnaire and asked to score their quality of life in relation to endometriosis symptoms, prior to the surgery and up to 48 months afterwards. Subgroup analysis of stage I/II and stage III/IV disease was performed as well as stratification of the period post-operation into 12-24, 25-36 and 37-48 months for follow-up analysis. Overall, the patients reported improvement in quality of life scores with a significant drop in mean scores from 46.9 pre- to 27.5 post-surgery, signifying benefits from the surgical intervention. All subgroups reported improvement in quality of life scores. The overall symptom recurrence rate was 18.3%. We conclude that patients, post-laparoscopic treatment of endometriosis, experience significant improvement in their quality of life, regardless of stage and this can be quantified and qualified.

Open-source, low-cost, compliant, modular, underactuated fingers: towards affordable prostheses for partial hand amputations.

In this paper we present a series of design directions for the development of affordable, compliant, modular, underactuated robot fingers, that can be used as prostheses by amputees that suffer from various partial hand amputations (index to pinky fingers are considered). Our design is based on parametric models that have been derived from hand anthropometry studies. Various interfaces have been considered in order to control the prosthesis, depending on the type and level of amputation. More precisely: 1) An Electromyography (EMG) based interface is used to control the robot fingers employing the EMG signals of the human forearm muscles 2) A flex sensors based interface is used to record the motion of the intact finger/fingers and predict the motion of the prosthesis implementing a synergistic behavior in an efficient manner, 3) A body powered interface is used for those that want to achieve even lower cost, with robust intuitive operation. Following the proposed design directions, an amputee will be able to replicate our fingers and develop personalized, affordable, light-weight but yet efficient prostheses.

Task discrimination from myoelectric activity: a learning scheme for EMG-based interfaces.

A learning scheme based on Random Forests is used to discriminate the task to be executed using only myoelectric activity from the upper limb. Three different task features can be discriminated: subspace to move towards, object to be grasped and task to be executed (with the object). The discrimination between the different reach to grasp movements is accomplished with a random forests classifier, which is able to perform efficient features selection, helping us to reduce the number of EMG channels required for task discrimination. The proposed scheme can take advantage of both a classifier and a regressor that cooperate advantageously to split the task space, providing better estimation accuracy with task-specific EMG-based motion decoding models, as reported in [1] and [2]. The whole learning scheme can be used by a series of EMG-based interfaces, that can be found in rehabilitation cases and neural prostheses.

A learning scheme for reach to grasp movements: on EMG-based interfaces using task specific motion decoding models.

A learning scheme based on random forests is used to discriminate between different reach to grasp movements in 3-D space, based on the myoelectric activity of human muscles of the upper-arm and the forearm. Task specificity for motion decoding is introduced in two different levels: Subspace to move toward and object to be grasped. The discrimination between the different reach to grasp strategies is accomplished with machine learning techniques for classification. The classification decision is then used in order to trigger an EMG-based task-specific motion decoding model. Task specific models manage to outperform "general" models providing better estimation accuracy. Thus, the proposed scheme takes advantage of a framework incorporating both a classifier and a regressor that cooperate advantageously in order to split the task space. The proposed learning scheme can be easily used to a series of EMG-based interfaces that must operate in real time, providing data-driven capabilities for multiclass problems, that occur in everyday life complex environments.

Aberrant expression of corticotropin-releasing hormone in pre-eclampsia induces expression of FasL in maternal macrophages and extravillous trophoblast apoptosis.

Corticotropin-releasing hormone (CRH) and its receptors are expressed in human placenta. Recently, the impaired function of this system has been associated with a number of complications of pregnancy, including pre-eclampsia. The aim of the study was to test the hypothesis that CRH participates in the pathophysiology of pre-eclampsia through the induction of macrophage-mediated apoptosis of extravillous trophoblasts (EVTs). We found that the expression of CRH was increased in the EVT of the placental bed biopsy specimens from pre-eclamptic pregnancies (1.8-fold increase; P < 0.05). In addition, significantly larger numbers of apoptotic EVT were detected in pre-eclamptic placentas compared with normal ones (P < 0.05), and only in pre-eclamptic placentas, decidual macrophages were found to be Fas ligand (FasL)-positive. In vitro studies on the effect of CRH on human macrophages suggested that CRH induced the expression of the FasL protein in human macrophages and potentiated their ability to induce the apoptosis of a Fas-expressing EVT-based hybridoma cell line in co-cultures. These findings demonstrate a possible mechanism by which the aberrant expression of CRH in pre-eclampsia may activate the FasL-positive decidual macrophages, impair the physiological turnover of EVT and eventually disturb placentation.

Intratumoral CRH modulates immuno-escape of ovarian cancer cells through FasL regulation.

Although corticotropin-releasing hormone (CRH) and Fas ligand (FasL) have been documented in ovarian carcinoma, a clear association with tumour progression and immuno-escape has not been established. FasL plays an important role in promoting tumour cells' ability to counterattack immune cells. Here, we examined immunohistochemically the expression of CRH, CRHR1, CRHR2 and FasL in 47 human ovarian cancer cases. The ovarian cancer cell lines OvCa3 and A2780 were further used to test the hypothesis that CRH might contribute to the immune privilege of ovarian tumours, by modulating FasL expression on the cancer cells. We found that CRH, CRHR1, CRHR2 and FasL were expressed in 68.1, 70.2, 63.8 and 63.8% of the cases respectively. Positivity for CRH or FasL expression was associated with higher tumour stage. Finally, CRH increased the expression of FasL in OvCa3 and A2780 cells through CRHR1 thereby potentiated their ability to induce apoptosis of activated peripheral blood lymphocytes. Corticotropin-releasing hormone produced by human ovarian cancer might favour survival and progression of the tumour by promoting its immune privilege. These findings support the hypothesis that CRHR1 antagonists could potentially be used against ovarian cancer.

Abortion is associated with increased expression of FasL in decidual leukocytes and apoptosis of extravillous trophoblasts: a role for CRH and urocortin.

Human reproduction is remarkably inefficient, with more than half of spontaneous conceptions failing to complete the first trimester. However, little is known on the molecular events that take place at the implantation site during abortion. Here, we examined the hypothesis that the expression of the proapoptotic Fas/FasL system at the implantation site is impaired in abortions. We found that, in contrast to normal pregnancy, abortive deciduas contain leukocytes that are positive for FasL and extravillous trophoblasts (EVTs), which show increased expression of Fas and increased rates of apoptosis. In addition, the neuropeptides, corticotropin-releasing hormone and urocortin, were elevated in placental material obtained from abortions. In vitro, these peptides induced the expression of FasL in decidual lymphocytes (DL) obtained from elective termination of pregnancy placentas and thus potentiated the cells' ability to induce Fas-mediated apoptosis in an EVT-based hybridoma cell line. Finally, DL from abortion sites effectively induced apoptosis of EVT without prior treatment. It is possible that these events may impede successful early placentation and thus contribute to the pathophysiology of human abortion.

The corticotropin-releasing factor (CRF) family of peptides as local modulators of adrenal function.

Corticotropin-releasing factor (CRF), also termed corticotropin-releasing hormone (CRH) or corticoliberin, is the major regulator of the adaptive response to internal or external stresses. An essential component of the adaptation mechanism is the adrenal gland. CRF regulates adrenal function indirectly through the central nervous system (CNS) via the hypothalamic-pituitary-adrenal (HPA) axis and via the autonomic nervous system by way of locus coeruleus (LC) in the brain stem. Accumulating evidence suggests that CRF and its related peptides also affect the adrenals directly, i.e. not through the CNS but from within the adrenal gland where they form paracrine regulatory loops. Indeed, CRF and its related peptides, the urocortins (UCNs: UCN1, UCN2 and UCN3), their receptors CRF type 1 (CRF(1)) and 2 (CRF(2)) as well as the endogenous pseudo-receptor CRF-binding protein (CRF-BP) are all expressed in adrenal cortical, medullary chromaffin and resident immune cells. The intra-adrenal CRF-based regulatory system is complex and depends on the balance between the local concentration of CRF ligands and the availability of their receptors.

Maternal serum corticotropin-releasing hormone and ACTH levels as predictive markers of premature labor.

OBJECTIVE: To investigate whether corticotropin-releasing hormone (CRH) and corticotropin (ACTH) plasma concentrations in women diagnosed with preterm labor are of potential clinical value in the assessment of the risk of preterm birth. METHOD: Plasma samples of 79 women diagnosed with preterm labor were used in this study. Samples were divided into three groups based on the week of gestation (24th-28th, 29th-32nd, 33rd-37th). CRH and ACTH values were determined by ELISA. RESULT: Mean maternal peripheral plasma values of CRH and ACTH were significantly higher (p<0.001) in women who were initially diagnosed with preterm labor and finally delivered a preterm birth, compared to women with the same diagnosis but with term birth. CONCLUSION: CRH and ACTH serum levels in women diagnosed with preterm labor could be used as predictors for the timing of parturition.

Expression of urocortin in the extravillous human trophoblast at the implantation site.

Urocortin (UCN) is a 40 amino acid peptide which is closely related to corticotropin-releasing hormone and binds with high affinity to both CRH type 1 and type 2 receptors. UCN is expressed in human reproductive tissues including endometrium, ovary, and placenta. This study was designed to investigate the cellular localization of UCN at the implantation site of the human blastocyst, as well as the regulation of the UCN promoter by two major intracellular signaling pathways, the cAMP/PKA and diacylglycerol/PKC pathways, in cells of placental origin. For this reason, immunohistochemistry was performed on tissue sections from paraffin-embedded human first trimester placentas and freshly isolated human invasive extravillous trophoblast cells (EVT) were analyzed for UCN expression using RT-PCR and immunofluorescence. Finally, UCN promoter activity was analyzed in the JEG3 human choriocarcinoma cell line. Immunohistochemistry revealed expression of UCN in the cytotrophoblast, the EVT and decidual cells. Both UCN mRNA and peptide were detectable in freshly isolated EVT. Finally, a human UCN promoter luciferase reporter construct transfected into JEG3 cells was significantly inducible by phorbol ester plus ionomycin, but not by phorbol ester alone or by forskolin. Collectively, the present study reports the expression of UCN in EVT and the activation of the UCN gene promoter by the diacylglycerol/PKC pathway. The functional significance of urocortin for the physiology of EVT requires further investigation.

Corticotropin-releasing factor (CRF) and the urocortins differentially regulate catecholamine secretion in human and rat adrenals, in a CRF receptor type-specific manner.

Corticotropin-releasing factor (CRF) affects catecholamine production both centrally and peripherally. The aim of the present work was to examine the presence of CRF, its related peptides, and their receptors in the medulla of human and rat adrenals and their direct effect on catecholamine synthesis and secretion. CRF, urocortin I (UCN1), urocortin II (UCN2), and CRF receptor type 1 (CRF1) and 2 (CRF2) were present in human and rat adrenal medulla as well as the PC12 pheochromocytoma cells by immunocytochemistry, immunofluorescence, and RT-PCR. Exposure of dispersed human and rat adrenal chromaffin cells to CRF1 receptor agonists induced catecholamine secretion in a dose-dependent manner, an effect peaking at 30 min, whereas CRF2 receptor agonists suppressed catecholamine secretion. The respective effects were blocked by CRF1 and CRF2 antagonists. CRF peptides affected catecholamine secretion via changes of subplasmaliminal actin filament polymerization. CRF peptides also affected catecholamine synthesis. In rat chromaffin and PC12 cells, CRF1 and CRF2 agonists induced catecholamine synthesis via tyrosine hydroxylase. However, in human chromaffin cells, activation of CRF1 receptors induced tyrosine hydroxylase, whereas activation of CRF2 suppressed it. In conclusion, it appears that a complex intraadrenal CRF-UCN/CRF-receptor system exists in both human and rat adrenals controlling catecholamine secretion and synthesis.

CRF receptor antagonists: utility in research and clinical practice.

CRF, CRF-related peptides and CRF receptors constitute a complex physiological system which has a key role in facilitating the adaptation of the organism to the stressful stimuli of the environment. The behavioral, endocrine, autonomic and immune branches of stress response are considered to be under the coordinating effects of CRF and its related peptides. The effects of these peptides are mediated through two distinct receptors, types 1 and 2 CRF receptors (CRF(1) and CRF(2)). The two receptors are encoded by separate genes and belong to the G-coupled receptor superfamily. The wide influence of the CRF system on physiological processes in both brain and periphery, suggests the implication of the respective peptides in the pathophysiology of numerous disorders which involve dysregulated stress responses. The potential use of CRF antagonists in such disorders is currently under intense investigation. Furthermore, such compounds have been invaluable in elucidating the physiology of the CRF system. This review will focus on existing data on the structural and pharmacological characteristics as well as the experimental and potential clinical uses of non-peptide, small molecule CRF antagonists.