Comparative analysis of the efficacy and complications of mid-urethral slings when inserted either in isolation or in conjunction with pelvic organ prolapse surgery.

INTRODUCTION: Stress urinary incontinence (SUI) is a highly prevalent condition that affects between 20 and 50% of the female population. Pelvic organ prolapse (POP) can coexist with SUI and both can be addressed through a vaginal approach. However, it is unclear whether simultaneous surgery for these two conditions can influence the outcome of incontinence treatment. OBJECTIVE: To evaluate the objective and subjective effectiveness of the transobturator suburethral (TO) band by comparing two groups: group A, of patients undergoing surgery for stress urinary incontinence (SUI) by insertion of TO mesh, and group B, formed for patients requiring simultaneous correction of pelvic organ prolapse (POP) in addition to TO mesh insertion. MATERIALS AND METHODS: This is an observational, descriptive and retrospective study in which 91 patients participated: 33 (group A) underwent surgery for SUI and 58 (group B) underwent corrective surgery for pelvic organ prolapse (POP) and TO band simultaneously. Variables included: total urinary continence, objective urinary continence, subjective urinary continence (satisfaction levels and two validated questionnaires (PGI-1 and ICIQ-SF)) and complications. RESULTS: Regarding total continence, from the seventh to the ninth year, statistically significant differences were observed, with total continence being higher in group A. Objective continence decreased in both groups during the follow-up period. No significant differences were found between the two groups regarding subjective urinary continence (ICIQ-SF) and the degree of improvement after surgical treatment (PGI-1). The level of satisfaction after surgery was high in both groups. Regarding complications, there were no statistically significant differences. CONCLUSIONS: Isolated surgery for SUI could be considered more effective in achieving total and objective continence. However, the insertion of the TO band in both cases improves subjective urinary continence and quality of life with great safety and without differences regarding complications.

Macrophages direct cancer cells through a LOXL2-mediated metastatic cascade in pancreatic ductal adenocarcinoma.

OBJECTIVE: The lysyl oxidase-like protein 2 (LOXL2) contributes to tumour progression and metastasis in different tumour entities, but its role in pancreatic ductal adenocarcinoma (PDAC) has not been evaluated in immunocompetent in vivo PDAC models. DESIGN: Towards this end, we used PDAC patient data sets, patient-derived xenograft in vivo and in vitro models, and four conditional genetically-engineered mouse models (GEMMS) to dissect the role of LOXL2 in PDAC. For GEMM-based studies, K-Ras +/LSL-G12D;Trp53 LSL-R172H;Pdx1-Cre mice (KPC) and the K-Ras +/LSL-G12D;Pdx1-Cre mice (KC) were crossed with Loxl2 allele floxed mice (Loxl2Exon2 fl/fl) or conditional Loxl2 overexpressing mice (R26Loxl2 KI/KI) to generate KPCL2KO or KCL2KO and KPCL2KI or KCL2KI mice, which were used to study overall survival; tumour incidence, burden and differentiation; metastases; epithelial to mesenchymal transition (EMT); stemness and extracellular collagen matrix (ECM) organisation. RESULTS: Using these PDAC mouse models, we show that while Loxl2 ablation had little effect on primary tumour development and growth, its loss significantly decreased metastasis and increased overall survival. We attribute this effect to non-cell autonomous factors, primarily ECM remodelling. Loxl2 overexpression, on the other hand, promoted primary and metastatic tumour growth and decreased overall survival, which could be linked to increased EMT and stemness. We also identified tumour-associated macrophage-secreted oncostatin M (OSM) as an inducer of LOXL2 expression, and show that targeting macrophages in vivo affects Osm and Loxl2 expression and collagen fibre alignment. CONCLUSION: Taken together, our findings establish novel pathophysiological roles and functions for LOXL2 in PDAC, which could be potentially exploited to treat metastatic disease.

Pessary with perineal suture for treatment of pelvic organ prolapse: description and benefit of the technique.

INTRODUCTION AND HYPOTHESIS: Vaginal pessaries are used as a conservative treatment for POP in women who do not want or are not candidates for surgery, or as a preliminary step to surgery. Our goals are: evaluate the evolution of patients with advanced POP and repeated expulsion of the pessary, who underwent perineal suture to try to maintain the device. Describe the epidemiological characteristics of patients treated with pessaries in our environment, with or without perineal closure. METHODS: Observational, descriptive and prospective study (October 2016-March 2021) that includes 352 women with advanced-stage POP treated with a pessary, of which 55, after repeated expulsion of the pessary, were treated with a pessary and perineal suture. RESULTS: After pessary insertion associated with perineal closure, 26 patients (47.2%) expelled the pessary and underwent surgery, and 29 (52.8%) kept the device, avoiding surgery. Regarding the women who required perineal suture: The mean age was higher than in the group of patients who did not need this intervention (75.3 vs. 68.3 years), 94.5% had POP ≥ grade III and 100% had a perineal width > 2.5 cm. CONCLUSIONS: Treatment with pessary and perineal closure avoids surgery in women with advanced age and repeated expulsion. Although age should not be an independent factor that limits surgical treatment or the type of intervention, it would be useful to have scales to quantify the frailty of patients, being able to standardize perineal closure in elderly and/or frail women, and in those who do not want or have contraindications for surgery.

Indomethacin for intracranial hypertension secondary to severe traumatic brain injury in adults.

BACKGROUND: Among people who have suffered a traumatic brain injury, increased intracranial pressure continues to be a major cause of early death; it is estimated that about 11 people per 100 with traumatic brain injury die. Indomethacin (also known as indometacin) is a powerful cerebral vasoconstrictor that can reduce intracranial pressure and, ultimately, restore cerebral perfusion and oxygenation. Thus, indomethacin may improve the recovery of a person with traumatic brain injury. OBJECTIVES: To assess the effects of indomethacin for adults with severe traumatic brain injury. SEARCH METHODS: We ran the searches from inception to 23 August 2019. We searched the Cochrane Central Register of Controlled Trials (CENTRAL; 2019, Issue 8) in the Cochrane Library, Ovid MEDLINE, Ovid Embase, CINAHL Plus (EBSCO), four other databases, and clinical trials registries. We also screened reference lists and conference abstracts, and contacted experts in the field. SELECTION CRITERIA: Our search criteria included randomised controlled trials (RCTs) that compared indomethacin with any control in adults presenting with severe traumatic brain injury associated with elevated intracranial pressure, with no previous decompressive surgery. DATA COLLECTION AND ANALYSIS: Two review authors independently decided on the selection of the studies. We followed standard Cochrane methods. MAIN RESULTS: We identified no eligible studies for this review, either completed or ongoing. AUTHORS' CONCLUSIONS: We found no studies, either completed or ongoing, that assessed the effects of indomethacin in controlling intracranial hypertension secondary to severe traumatic brain injury. Thus, we cannot draw any conclusions about the effects of indomethacin on intracranial pressure, mortality rates, quality of life, disability or adverse effects. This absence of evidence should not be interpreted as evidence of no effect for indomethacin in controlling intracranial hypertension secondary to severe traumatic brain injury. It means that we have not identified eligible research for this review.

Successful management of anemia with sirolimus in blue rubber bleb nevus syndrome: case report and update.

Blue rubber bleb nevus syndrome (BRBNS) is a rare disorder with characteristic skin hemangiomas and vascular malformations, mostly in the gastrointestinal (GI) tract. The GI lesions are mainly located in the stomach and small intestine, usually more than a hundred, leading to gastrointestinal bleeding and severe chronic anemia. Parenteral iron infusions and scheduled transfusions are frequently necessary. We describe the case of a 21-year-old male with anemia secondary to BRBNS, who becomes unresponsive to octreotide and shows an excellent response to sirolimus (SRL), dismissing the intravenous iron supplementations and being free of transfusions. During the treatment, the patient presents avascular hip necrosis, which is adequately treated with an injection of stem cells with complete recovery, and without the suspension of SRL. Two years later, adequate response persists with no other relevant side effects.

Cannabinoid CB2 receptors in the mouse brain: relevance for Alzheimer's disease.

BACKGROUND: Because of their low levels of expression and the inadequacy of current research tools, CB2 cannabinoid receptors (CB2R) have been difficult to study, particularly in the brain. This receptor is especially relevant in the context of neuroinflammation, so novel tools are needed to unveil its pathophysiological role(s). METHODS: We have generated a transgenic mouse model in which the expression of enhanced green fluorescent protein (EGFP) is under the control of the cnr2 gene promoter through the insertion of an Internal Ribosomal Entry Site followed by the EGFP coding region immediately 3' of the cnr2 gene and crossed these mice with mice expressing five familial Alzheimer's disease (AD) mutations (5xFAD). RESULTS: Expression of EGFP in control mice was below the level of detection in all regions of the central nervous system (CNS) that we examined. CB2R-dependent-EGFP expression was detected in the CNS of 3-month-old AD mice in areas of intense inflammation and amyloid deposition; expression was coincident with the appearance of plaques in the cortex, hippocampus, brain stem, and thalamus. The expression of EGFP increased as a function of plaque formation and subsequent microgliosis and was restricted to microglial cells located in close proximity to neuritic plaques. AD mice with CB2R deletion exhibited decreased neuritic plaques with no changes in IL1ß expression. CONCLUSIONS: Using a novel reporter mouse line, we found no evidence for CB2R expression in the healthy CNS but clear up-regulation in the context of amyloid-triggered neuroinflammation. Data from CB2R null mice indicate that they play a complex role in the response to plaque formation.

Persistent ischiorectal fistula secondary to rectal extrusion of posterior vaginal mesh: Case report.

INTRODUCTION AND HYPOTHESIS: Vaginal mesh has been used for years to try to improve the results of pelvic organ prolapse surgery, but current evidence does not confirm this improvement and instead describes serious and frequent adverse events. CLINICAL CASE: 64-year-old patient with rectal extrusion of posterior vaginal mesh placed 8 years earlier, and persistent left ischiorectal fistula refractory to surgery. She required 5 surgeries, carried out jointly between gynecology and general surgery, to solve, firstly, the bilateral perianal abscess secondary to extrusion of the posterior vaginal mesh into the rectum and then the persistent left ischiorectal fistula, despite the removal of the material prosthetic. Finally, the fistula was solved by injection of platelet-rich plasma. CONCLUSIONS: Vaginal mesh complications often need a multidisciplinary approach, and treatment may require multiple approaches and more than one surgical procedure. In the case of a persistent fistula refractory to surgery, after removing the mesh, non-invasive regenerative therapies that promote vascular growth and tissue regeneration could be considered such as platelet-rich plasma.

Predictors of outcomes after internal fixation of periprosthetic femoral hip fractures Subgroup analysis of the peri-implant and peri-prosthetic fractures Spanish registry (PIPPAS).

PURPOSE: To identify risk factors predisposing patients to poor outcomes after fixation of periprosthetic hip fractures around femoral stems. METHODS: Prospective multicentre cohort study of fractures around a hip replacement stem managed by internal fixation. The primary outcome was one-year mortality, while secondary outcomes were local complications and healthcare burden-related outcomes (nursing facility utilization and hospital length of stay). RESULTS: One-year mortality was 16.2%. Age-adjusted Charlson Comorbidity Index score (OR=1.17; 95%CI=1.03-1.33)), Pfeiffer Short Portable Mental Status Questionnaire (SPMSQ) score (OR=1.16; 1.06-1.28), prosthetic dysfunction (OR=1.90; 1.00-3.61), and postoperative medical complications (OR=1.97; 1.06-3.68) were predictors of mortality. Patients with prior prosthetic dysfunction, lower Pfeiffer SPMSQ scores, Vancouver A fractures, and fractures fixed only using cerclages were at higher risk of local complications, which occurred in 9.3% of cases. Medical (OR=1.81; 1.05-3.13) and local complications (OR=5.56; 2.42-3.13) emerged as consistent risk factors for new institutionalization. Average hospitalization time was 13.9±9.2 days. Each day of fixation delay led to an average 1.4-day increase in total hospitalization. CONCLUSION: Frail periprosthetic hip-fracture patients with poorer functional status, dysfunctional replacements, and postoperative complications are at increased risk of mortality. Postoperative complications are more common in patients with dysfunctional arthroplasties, Vancouver A fractures, and fixation using cerclages alone. Postoperative complications were the most consistent predictor of higher healthcare resource utilization.

Hybridization for human epidermal growth factor receptor 2 testing in gastric carcinoma: a comparison of fluorescence in-situ hybridization with a novel fully automated dual-colour silver in-situ hybridization method.

AIMS: Amplification of the human epidermal growth factor receptor 2 (HER2) gene has been reported in gastric carcinoma (GC). Accordingly, trastuzumab plus chemotherapy has recently become the new standard treatment for HER2-positive advanced GCs. The aim was to compare the alleged gold standard for hybridization [fluorescence in-situ hybridization (FISH)] with a novel, fully automated brightfield dual-colour silver-enhanced in-situ hybridization (SISH) method. METHODS AND RESULTS: The studies series was comprised of 166 GC samples. Additionally, tumours with discordant results obtained by FISH and SISH were analysed by real-time quantitative polymerase chain reaction (PCR) with the LightMix kit HER-2/neu. Of the samples, 17.5% and 21% were amplified by FISH and SISH, respectively. Heterogeneity was identified in up to 52% of cases. In 96.4% of cases, FISH showed the same results as SISH. All six discordant cases were positive by SISH and negative by FISH. On review of the FISH slides, all contradictory cases were polysomic and were confirmed to be negative for amplification by real-time PCR. Interestingly, all ratios in this latter group were between 2.06 and 2.50, so setting the cut-off for amplification at ≥3 resulted in perfect concordance. CONCLUSIONS: Dual-colour SISH represents a novel method for the determination of HER2 status in GC.

Substance Use and Addictive Behavior in Spanish Adolescents in Secondary School.

The detection and prevention of addictive behaviour at an early age is essential given the relationship between the age of the onset of consumption and the appearance of addiction disorders. The aim of this study was to describe the behavior related to substance use and addictive behaviors in adolescents at secondary school from 12 to 16 years of age. A cross-sectional descriptive study has been conducted. The prevalence of consumption of different addictive substances (alcohol, tobacco, cannabis, cocaine) and addictive behaviours (use of social networks and video games) were collated, and the influence of the surrounding social environment and risk perception were evaluated. The final sample was 1298 students. Alcohol, tobacco and cannabis use reflect the prevalence of last month's consumption: 14% (11.8-15.6), 15% (13.4-17.4) and 3% (1.9-2.7) respectively. 76% of the sample frequently use the Internet (5-7 days per week). There is a positive association between the frequency of use and use in the immediate environment. The relationships found show the need for educational and preventive intervention aimed at parents and students that will allow them to know and effectively deal with possible problems associated with the consumption of addictive substances.

Real-World Data and Machine Learning to Predict Cardiac Amyloidosis.

(1) Background: Cardiac amyloidosis or "stiff heart syndrome" is a rare condition that occurs when amyloid deposits occupy the heart muscle. Many patients suffer from it and fail to receive a timely diagnosis mainly because the disease is a rare form of restrictive cardiomyopathy that is difficult to diagnose, often associated with a poor prognosis. This research analyses the characteristics of this pathology and proposes a statistical learning algorithm that helps to detect the disease. (2) Methods: The hospitalization clinical (medical and nursing ones) records used for this study are the basis of the learning and training techniques of the algorithm. The approach consisted of using the information generated by the patients in each admission and discharge episode and treating it as data vectors to facilitate their aggregation. The large volume of clinical histories implied a high dimensionality of the data, and the lack of diagnosis led to a severe class imbalance caused by the low prevalence of the disease. (3) Results: Although there are few patients with amyloidosis in this study, the proposed approach demonstrates that it is possible to learn from clinical records despite the lack of data. In the validation phase, the algorithm first acted on data from the general study population. It then was applied to a sample of patients diagnosed with heart failure. The results revealed that the algorithm detects disease when data vectors profile each disease episode. (4) Conclusions: The prediction levels showed that this technique could be useful in screening processes on a specific population to detect the disease.

A direct pancreatic cancer xenograft model as a platform for cancer stem cell therapeutic development.

There is an enormous gap between the antiproliferative and in vivo antitumor efficacy of gemcitabine in cell line-based models and its clinical efficacy. This may be due to insensitiveness of the precursor, cancer stem cell (CSC) compartment to cytotoxic agents. The hedgehog pathway is associated with CSC signaling and control. We used a direct xenograft model of pancreatic cancer and a two-stage approach was used to test the hypotheses that targeting CSC could increase the efficacy of gemcitabine. Tumors from a gemcitabine-sensitive xenograft were treated with gemcitabine first, and randomized, after tumor regression to continuing treatment with gemcitabine, a hedgehog inhibitor alone or in combination with gemcitabine. We tested markers described as associated with CSC such as CD24, CD44, ALDH, nestin, and the hedgehog pathway. After induction with gemcitabine, treated tumor showed an enrichment in CSC markers such as ALDH and CD24. Subsequently, a release from gemcitabine prompted a repopulation of proliferating cells and a decrease in such markers to equilibrate from pretreatment levels. Combined treatment with gemcitabine and cyclopamine induced tumor regression and decrease in CSC markers and hedgehog signaling. Cytoplasmic CD24 and ALDH were inversely and strongly associated with growth and were expressed in a minority of cells that we propose constitute the CSC compartment. Hedgehog inhibitors as part of a dual compartment therapeutic approach were able to further reduce tumor growth and decreased both static and dynamic markers of CSC. Direct tumor xenografts are a valid platform to test multicompartment therapeutic approaches in pancreatic cancer.

Optimization of roasting conditions in hydroSOStainable almonds using volatile and descriptive sensory profiles and consumer acceptance.

HydroSOStainable almonds are harvested from trees cultivated under controlled water stress by using a regulated deficit irrigation (RDI) strategy. The aim of this study was to investigate consumers' perception to select the best roasting temperature for the hydroSOStainable almonds and its correlation with volatile compounds, descriptive sensory attributes, instrumental color, and texture. Thirty-five volatile compounds were identified and the key compounds for the roasting process were 2,5-dimethylpyrazine, furfural, and trimethyl pyrazine. Pyrazines, furans and, in general, volatiles were higher in hydroSOStainable almonds than in control. Instrumental color and trained panel showed that almonds roasted at 190 °C presented intense color and burnt notes in both irrigation treatments, while almonds roasted at 150 °C were under-roasted. Principal component analysis (PCA) grouped together the samples of the same irrigation treatment, but separated samples roasted at different temperatures. Partial least square regression (PLS) results indicated that consumers overall liking was positively linked to specific volatiles (alkanes, alcohols, aldehydes, and furans) and sensory attributes (sweetness, roasted, almond ID, nutty, hardness, and crispiness), but, negatively correlated with pyrazines, bitterness, astringency, woody, and burnt flavor notes. Penalty analysis showed that almonds roasted at 150 and 190 °C were penalized due to low roasted aroma and soft almonds, and over-roasted samples with too intense color and burn notes, respectively. While no penalization being found for almonds roasted at 170 °C. Overall, roasting at 170 °C for 10 min in a convective oven were the optimum conditions for roasting Vairo almonds. PRACTICAL APPLICATION: This research describes the link between physicochemical and sensory analysis of roasted almonds giving evidence about possible sensory quality markers. Besides, it provides valuable information for the food industry to produce roasted almonds that meet consumer demands and for the agricultural sector by encouraging reduction of irrigation water consumption by almond trees.

How a Spanish Group of Millennial Generation Perceives the Commercial Novel Smoothies?

The World Health Organization (WHO) and the Food and Agriculture Organization of the United Nations (FAO) constantly emphasize the importance of increasing fruit and vegetable consumption; these natural products help in the prevention of major diseases. Smoothies are a simple and convenient way of doing so; thus, their demand is constantly growing and their market is becoming important for the food industry. Therefore, the objective of this research was to determine Millennial consumer opinion towards novel fruit- and vegetable-smoothies available on the retail market. Napping®, descriptive sensory analysis, and consumer studies were conducted. Napping® results group samples into four clusters of smoothies; the main grouping factor was the type of fruit and the percentage of vegetables. Penalty analysis showed that smoothies need improvement mainly dealing with sweetness, bitterness, and vegetable flavors. Millennial consumers formed a homogeneous sensory group in which the overall liking was negatively correlated with the level of sweetness, and earthy, carrot, beetroot, and pear flavors. The key liking drivers were sourness and notes of mango, banana, and peach flavors. This research is a new insight into the perception of smoothies, provides comprehensive knowledge for the food industry, and can guide the design of new healthy smoothies.

Applying Lean in Process Innovation in Healthcare: The Case of Hip Fracture.

Academic literature and practitioners acknowledge that there is a need to improve efficiency and service quality in the healthcare industry. In Spain, osteoporotic fractures represent a great cost in socio-economic and morbi-mortality terms, hip fracture being the surgical pathology with the second highest consumption of resources. The research questions that govern this study concern the use of Lean principles to identify waste, and an evaluation of the application of an innovative approach in the hip fracture surgery process. A research design based on a case study and action research was developed. Findings relate to (i) the identification of the main types of waste or muda (being the most frequent delay, transportation, over-processing and defects); (ii) the analysis of existing processes based on a Lean approach (identifying opportunities for improvement as a reduction of the number of steps and participants, improving communication, automation, standardization, etc.); and (iii) the application of an innovative process based on the Lean approach and action research in the healthcare industry. This research provides insights for academia, practitioners, management, and society: waste identification and process redesign helps to continue the improvement of operations, increase efficiency, reduce costs, and enhance services, providing benefits to patients, families, hospital employees, and the healthcare system.

Enantioselective approach to Securinega alkaloids. Total synthesis of securinine and (-)-norsecurinine.

The most representative securinega alkaloids have been synthesized through a new strategy involving the palladium-catalyzed enantioselective allylation of a cyclic imide, a vinylogous Mannich reaction, and a ring-closing metathesis process, as the key steps. The diastereoselectivity of the vinylogous Mannich reaction was in partial agreement with DFT theoretical calculations performed in a model system. The synthesis of (-)-norsecurine has been accomplished in nine steps from succinimide and 14% overall yield and that of securinine in 10 steps from glutarimide and 20% overall yield. Both syntheses compare favorably with those previously described. The three key transformations have been performed in a synthetically useful scale (more than 500 mg). Moreover, since the enantioselectivity was originated by a chiral phosphine ligand, the antipode of which is readily available, the same route is expected to give access to (+)-norsecurinine and virosecurinine.

Loss of the mitochondrial bioenergetic capacity underlies the glucose avidity of carcinomas.

The down-regulation of the catalytic subunit of the mitochondrial H+-ATP synthase (beta-F1-ATPase) is a hallmark of most human carcinomas. This characteristic of the cancer cell provides a proteomic signature of cellular bioenergetics that can predict the prognosis of colon, lung, and breast cancer patients. Here we show that the in vivo tumor glucose uptake of lung carcinomas, as assessed by positron emission tomography in 110 patients using 2-deoxy-2-[18F]fluoro-d-glucose as probe, inversely correlates with the bioenergetic signature determined by immunohistochemical analysis in tumor surgical specimens. Further, we show that inhibition of the activity of oxidative phosphorylation by incubation of cancer cells with oligomycin triggers a rapid increase in their rates of aerobic glycolysis. Moreover, we show that the cellular expression level of the beta-F1-ATPase protein of mitochondrial oxidative phosphorylation inversely correlates (P < 0.001) with the rates of aerobic glycolysis in cancer cells. The results highlight the relevance of the alteration of the bioenergetic function of mitochondria for glucose capture and consumption by aerobic glycolysis in carcinomas.

Antitumor activity and molecular effects of the novel heat shock protein 90 inhibitor, IPI-504, in pancreatic cancer.

Targeting Hsp90 is an attractive strategy for anticancer therapy because the diversity and relevance of biological processes are regulated by these proteins in most cancers. However, the role and mode of action of Hsp90 inhibitors in pancreatic cancer has not been studied. This study aimed to assess the antitumor activity of the Hsp90 inhibitor, IPI-504, in pancreatic cancer and to determine the biological effects of the agent. In vitro, we show that pharmacologic inhibition of Hsp90 by IPI-504 exerts antiproliferative effects in a panel of pancreatic cancer cells in a dose- and time-dependent manner. In pancreatic cancer xenografts obtained directly from patients with pancreas cancer, the agent resulted in a marked suppression of tumor growth. Although known Hsp90 client proteins were significantly modulated in IPI-504-treated cell line, no consistent alteration of these proteins was observed in vivo other than induction of Hsp70 expression in the treated xenografted tumors. Using a proteomic profiling analysis with isotope tags for relative and absolute quantitation labeling technique, we have identified 20 down-regulated proteins and 42 up-regulated proteins on IPI-504 treatment.tumor growth Identical changes were observed in the expression of the genes coding for these proteins in a subset of proteins including HSPA1B, LGALS3, CALM1, FAM84B, FDPS, GOLPH2, HBA1, HIST1H1C, HLA-B, and MARCKS. The majority of these proteins belong to the functional class of intracellular signal transduction, immune response, cell growth and maintenance, transport, and metabolism. In summary, we show that IPI-504 has potent antitumor activity in pancreatic cancer and identify potential pharmacologic targets using a proteomics and gene expression profiling.

Coccyx pain in women after childbirth. / El dolor de cóccix en la mujer tras el parto.

The coccyx is a bone with its own morphology and mobility and pain can occur due to trauma such as a difficult or instrumental delivery. Coccydynia can make it impossible to carry out the activities of daily life, its affects can be both physical and psychosocial, and causes great maternal morbidity. This article highlights the factors that predispose women to coccydynia and actions to relieve and improve it. Postpartum coccydynia is pain that appears as soon as a sitting position is adopted after delivery. Coccyx morphology, body mass index, vaginal delivery, instrumental delivery, multiparity, female sex, mature age and short perineum in women with difficult delivery are risk factors. The activities to improve pain begin with analgesia and coadjuvants, rehabilitation and pelvic floor massage, infiltrations, psychotherapy or, finally, surgery.