A new updated prognostic index for patients with brain metastases (BMs) treated with palliative whole brain radiotherapy (WBRT) in the era of precision oncology. METASNCore project.

INTRODUCTION: Palliative WBRT is the main treatment for multiple BMs. Recent studies report no benefit in survival after WBRT compared to palliative supportive care in patients (pts) with poor prognosis. A new era of systemic treatment strategies based on targeted therapies are improving the prognosis of patients with BMs. The purpose of this study is to develop a prognostic score in palliative pts with BMs who undergo WBRT in this new setting. METHODS: 239 pts with BMs who received palliative WBRT between 2013-2022 in our center were analyzed retrospectively. The score was designed according to the value of the ß coefficient of each variable with statistical significance in the multivariate model using Cox regression. Once the score was established, a comparison was performed according to Kaplan-Meier and was analyzed by log-rank test. RESULTS: 149 pts (62.3%) were male and median (m) age was 60 years. 139 (58,2%) were lung cancer and 35 (14,6%) breast cancer. All patients received 30Gys in 10 sessions. m overall survival (OS) was 3,74 months (ms). 37 pts (15,5%) had a specific target mutation. We found that 62 pts were in group < 4 points with mOS 6,89 ms (CI 95% 3,18-10,62), 84 in group 4-7 points with mOS 4,01 ms (CI 95% 3,40-4,62) and 92 pts in group > 7 points with mOS 2,72 ms (CI 95% 1,93-3,52) (p < 0,001). CONCLUSIONS: METASNCore items are associated with OS and they could be useful to select palliative pts to receive WBRT. More studies are necessary to corroborate our findings.

Role of lateral suspension for the treatment of pelvic organ prolapse: a Delphi survey of expert panel.

INTRODUCTION AND HYPOTHESIS: Lateral suspension is an abdominal prosthetic surgical procedure used to correct apical prolapse. The procedure involves the placement of a T-shaped mesh on the anterior vaginal wall and on the isthmus or uterine cervix that is suspended laterally and posteriorly to the abdominal wall. Since its description in the late 90s, modifications of the technique have been described. So far, no consensus on the correct indications, safety, advantages, and disadvantages of this emerging procedure has been reached. METHODS: A modified Delphi process was used to build consensus within a group of 21 international surgeons who are experts in the performance of laparoscopic lateral suspension (LLS). The process was held with a first online round, where the experts expressed their level of agreement on 64 statements on indications, technical features, and other aspects of LLS. A subsequent re-discussion of statements where a threshold of agreement was not reached was held in presence. RESULTS: The Delphi process allowed the identification of several aspects of LLS that represented areas of agreement by the experts. The experts agreed that LLS is a safe and effective technique to correct apical and anterior prolapse. The experts highlighted several key technical aspects of the procedure, including clinical indications and surgical steps. CONCLUSIONS: This Delphi consensus provides valuable guidance and criteria for the use of LLS in the treatment of pelvic organ prolapse, based on expert opinion by large volume surgeons' experts in the performance of this innovative procedure.

Clinical and serological characteristics of patients allergic to LTP.

BACKGROUND: Allergy to lipid transfer proteins (LPT) is common in Mediterranean Europe, and it causes severe reactions in patients and affects multiple foods, impairing the quality of life. OBJECTIVE: This study aimed to describe the clinical and sensitization profile of patients with LTP syndrome and to determine a clinical pattern of severity. Molecular diagnosis is shown in a broad population through microarrays. MATERIAL AND METHODS: This study was performed at the LTP Allergy Consultation of the Reina Sofia Hospital in Murcia, Spain. We analyzed the patients' characteristics, reactions, cofactors, food implicated, quality of life, skin prick test to food and aeroallergens, and serologic parameters, such as total immunoglobulin E, peach LTP (Pru p 3 IgE) and immunoglobulin G4, and microarray Immuno Solid-phase Allergen Chip (ISAC). We related the severity of the reactions with other variables. RESULTS: We presented a series of 236 patients diagnosed with LTP allergy, 54.66% suffering from anaphylaxis, 36.02% from urticaria angioedema, and 9.32% from oral allergy syndrome. The most frequently implicated food was peach, producing symptoms in 70% of patients, followed by walnut in 55%, peanut in 45%, hazelnut in 44%, and apple in 38% patients. Regarding the food that provoked anaphylaxis, walnut was the most frequent instigator, along with peach, peanut, hazelnut, almond, sunflower seed, and apple. According to the severity of LPT reaction, we did not discover significant differences in gender, age, food group involved, and serologic parameters. We found differences in the presence of cofactors, with 48.84% of cofactors in patients with anaphylaxis, compared to 27.1% in patients without anaphylaxis and in family allergy background (P < 0.0001). CONCLUSION: In our series of patients, 54% presented anaphylaxis, and the foods that most frequently produced symptoms were peaches, apples, and nuts. Cofactors and family allergy backgrounds were associated with the severity of LPT reaction.

Robot-assisted pelvic floor reconstructive surgery: an international Delphi study of expert users.

BACKGROUND: Robotic surgery has gained popularity for the reconstruction of pelvic floor defects. Nonetheless, there is no evidence that robot-assisted reconstructive surgery is either appropriate or superior to standard laparoscopy for the performance of pelvic floor reconstructive procedures or that it is sustainable. The aim of this project was to address the proper role of robotic pelvic floor reconstructive procedures using expert opinion. METHODS: We set up an international, multidisciplinary group of 26 experts to participate in a Delphi process on robotics as applied to pelvic floor reconstructive surgery. The group comprised urogynecologists, urologists, and colorectal surgeons with long-term experience in the performance of pelvic floor reconstructive procedures and with the use of the robot, who were identified primarily based on peer-reviewed publications. Two rounds of the Delphi process were conducted. The first included 63 statements pertaining to surgeons' characteristics, general questions, indications, surgical technique, and future-oriented questions. A second round including 20 statements was used to reassess those statements where borderline agreement was obtained during the first round. The final step consisted of a face-to-face meeting with all participants to present and discuss the results of the analysis. RESULTS: The 26 experts agreed that robotics is a suitable indication for pelvic floor reconstructive surgery because of the significant technical advantages that it confers relative to standard laparoscopy. Experts considered these advantages particularly important for the execution of complex reconstructive procedures, although the benefits can be found also during less challenging cases. The experts considered the robot safe and effective for pelvic floor reconstruction and generally thought that the additional costs are offset by the increased surgical efficacy. CONCLUSION: Robotics is a suitable choice for pelvic reconstruction, but this Delphi initiative calls for more research to objectively assess the specific settings where robotic surgery would provide the most benefit.

Optimization of caseinolytic and coagulating activities of Solanum tuberosum rennets for cheese making.

BACKGROUND: In recent years, the rising global demand for cheese, the high cost and limited supply of calf rennet, and consumer choices have increased research into new alternatives to animal or recombinant chymosins for cheese making. Plant proteases with caseinolytic activity (CA) and milk-clotting activity (MCA) have been proposed as alternatives for milk clotting to obtain artisanal cheeses with new organoleptic properties. They have been named vegetable rennets (vrennets). The aim of this study was to evaluate the performance of two Solanum tuberosum aspartic proteases (StAP1 and StAP3) as vrennets for cheese making and to obtain a statistical model that could predict and optimize their enzymatic activity. RESULTS: To optimize the CA and MCA activities, a response surface methodology was used. Maximum values of CA and MCA for both enzymes were found at pH 5.0 and 30-35 °C. Analysis of the degradation of casein subunits showed that it is possible to tune the specificity of both enzymes by changing the pH. At pH 6.5, the αS - and ß- subunit degradation is reduced while conserving a significant MCA. CONCLUSION: The statistical models obtained in this work showed that StAP1 and StAP3 exert CA and MCA under pH and temperature conditions compatible with those used for cheese making. The casein subunit degradation percentages obtained also allowed us to select the best conditions for the degradation of the κ-casein subunit by StAPs. These results suggest that StAP1 and StAP3 are good candidates as vrennets for artisan cheese making. © 2023 Society of Chemical Industry.

Nano-immunotherapy: Overcoming tumour immune evasion.

Immunotherapy is emerging as a groundbreaking cancer treatment, offering the unprecedented opportunity to effectively treat and in several cases, even cure previously untreatable malignancies. Anti-tumour immunotherapies designed to amplify T cell responses against defined tumour antigens have long been considered effective approaches for cancer treatment. Despite a clear rationale behind such immunotherapies, extensive past efforts were unsuccessful in mediating clinically relevant anti-tumour activity in humans. This is mainly because tumours adopt specific mechanisms to circumvent the host´s immunity. Emerging data suggest that the full potential of cancer immunotherapy will be only achieved by combining immunotherapies designed to generate or amplify anti-tumour T cell responses with strategies able to impair key tumour immune-evasion mechanisms. However, many approaches aimed to re-shape the tumour immune microenvironment (TIME) are commonly associated with severe systemic toxicity, require frequent administration, and only show modest efficacy in clinical settings. The use of nanodelivery systems is revealing as a valid means to overcome these limitations by improving the targeting efficiency, minimising systemic exposure of immunomodulatory agents, and enabling the development of novel combinatorial immunotherapies. In this review, we examine the emerging field of therapeutic modulation of TIME by the use of nanoparticle-based immunomodulators and potential future directions for TIME-targeting nanotherapies.

Pseudocrossidium replicatum (Taylor) R.H. Zander is a fully desiccation-tolerant moss that expresses an inducible molecular mechanism in response to severe abiotic stress.

KEY MESSAGE: The moss Pseudocrossidium replicatum is a desiccation-tolerant species that uses an inducible system to withstand severe abiotic stress in both protonemal and gametophore tissues. Desiccation tolerance (DT) is the ability of cells to recover from an air-dried state. Here, the moss Pseudocrossidium replicatum was identified as a fully desiccation-tolerant (FDT) species. Its gametophores rapidly lost more than 90% of their water content when exposed to a low-humidity atmosphere [23% relative humidity (RH)], but abscisic acid (ABA) pretreatment diminished the final water loss after equilibrium was reached. P. replicatum gametophores maintained good maximum photosystem II (PSII) efficiency (Fv/Fm) for up to two hours during slow dehydration; however, ABA pretreatment induced a faster decrease in the Fv/Fm. ABA also induced a faster recovery of the Fv/Fm after rehydration. Protein synthesis inhibitor treatment before dehydration hampered the recovery of the Fv/Fm when the gametophores were rehydrated after desiccation, suggesting the presence of an inducible protective mechanism that is activated in response to abiotic stress. This observation was also supported by accumulation of soluble sugars in gametophores exposed to ABA or NaCl. Exogenous ABA treatment delayed the germination of P. replicatum spores and induced morphological changes in protonemal cells that resembled brachycytes. Transcriptome analyses revealed the presence of an inducible molecular mechanism in P. replicatum protonemata that was activated in response to dehydration. This study is the first RNA-Seq study of the protonemal tissues of an FDT moss. Our results suggest that P. replicatum is an FDT moss equipped with an inducible molecular response that prepares this species for severe abiotic stress and that ABA plays an important role in this response.

In vivo tumor growth inhibition by Solanum tuberosum aspartic protease 3 (StAP3) treatment.

Solanum tuberosum aspartic Proteases (StAPs) show selective plasma membrane permeabilization, inducing cytotoxicity of cancer cells versus normal cells in vitro. Herein, we aimed to evaluate both StAP3 systemic toxicity and antitumoral activity against human melanoma in vivo. The toxicity of a single high dose of StAP3 (10 µg/g body weight, intraperitoneally) was assessed in a Balb/c mice model. Subcutaneous A375 human melanoma xenografts in athymic nude (nu/nu) mice were induced. Once tumors developed (mean larger dimension = 3.8 ± 0.09 mm), mice were StAP3-treated (6 µg/g body weight, subcutaneously under the tumor at a single dose). For both models, controls were treated with physiologic saline solution. StAP3-treated mice showed a significant inhibition of tumor growth (p < 0.05) compared with controls. No signs of toxicity were detected in StAP3-treated mice in both models. These results suggest the potential of these plant proteases as anticancer agents.

Simulation training program for vacuum application to improve technical skills in vacuum-assisted vaginal delivery.

OBJECTIVE: evaluation of technical skills of the operators during the obstetrical device application for operative vaginal delivery, named kiwi-cup in a simulation training program. METHODS: Thirty-five residents in obstetrics and gynecology of the University of Pisa, Italy were recruited and evaluated with an assessment scale on technical skills from 0 to 55 points. They performed various operative vaginal delivery simulations with kiwi-cup and were evaluated at time 0 by a tutor. After 8 weeks, simulation training was repeated and trainees were re-evaluated by the same tutor. RESULTS: after 8 weeks from the first simulation session, trainees have been shown to increase technical skills (46.27 ± 4.6 with p-value < 0.0001), the successful application rate (85.71% with p-value 0.0161).) and to reduce the time to complete the procedure (86.2 ± 29.9 s with p-value < 0.0001). CONCLUSION: simulation training on operational vaginal delivery significantly increases technical skills, improves successful rate, and reduces the time taken to complete the procedure. CLINICAL TRIAL REGISTRATION: Not applicable.

The Pediatric Autism Spectrum Therapy Observation System: Development, Psychometric Properties, and Sensitivity to Treatment.

An observational coding system was developed to track clinical change in children with autism spectrum disorder (ASD) during psychotherapy. The Pediatric Autism Spectrum Therapy Observation System (PASTOS) consists of 23 items divided into 5 subscales and is used to rate child behaviors in individual psychotherapy sessions. Manual-based cognitive behavioral therapy session transcripts of 22 children diagnosed with ASD (IQ > 70) and a concurrent anxiety disorder (M = 9.41 years, SD = 1.56 years) enrolled in a randomized, controlled trial were coded. Results suggested that the PASTOS exhibited promising interrater reliability, internal consistency, convergent validity at post-treatment, and treatment sensitivity. The PASTOS may be a useful tool for studying process and outcome in psychotherapy research on children with ASD.

Acid exposure disrupts mucus secretion and impairs mucociliary transport in neonatal piglet airways.

Tenacious mucus produced by tracheal and bronchial submucosal glands is a defining feature of several airway diseases, including cystic fibrosis (CF). Airway acidification as a driving force of CF airway pathology has been controversial. Here we tested the hypothesis that transient airway acidification produces pathologic mucus and impairs mucociliary transport. We studied pigs challenged with intra-airway acid. Acid had a minimal effect on mucus properties under basal conditions. However, cholinergic stimulation in acid-challenged pigs revealed retention of mucin 5B (MUC5B) in the submucosal glands, decreased concentrations of MUC5B in the lung lavage fluid, and airway obstruction. To more closely mimic a CF-like environment, we also examined mucus secretion and transport following cholinergic stimulation under diminished bicarbonate and chloride transport conditions ex vivo. Under these conditions, airways from acid-challenged pigs displayed extensive mucus films and decreased mucociliary transport. Pretreatment with diminazene aceturate, a small molecule with ability to inhibit acid detection through blockade of the acid-sensing ion channel (ASIC) at the doses provided, did not prevent acid-induced pathologic mucus or transport defects but did mitigate airway obstruction. These findings suggest that transient airway acidification early in life has significant impacts on mucus secretion and transport properties. Furthermore, they highlight diminazene aceturate as an agent that might be beneficial in alleviating airway obstruction.

Airway cholinergic history modifies mucus secretion properties to subsequent cholinergic challenge in diminished chloride and bicarbonate conditions.

NEW FINDINGS: What is the central question of this study? What is the impact of airway cholinergic history on the properties of airway mucus secretion in a cystic fibrosis-like environment? What is the main finding and its importance? Prior cholinergic challenge slightly modifies the characteristics of mucus secretion in response to a second cholinergic challenge in a diminished bicarbonate and chloride transport environment. Such modifications might lead to retention of mucus on the airway surface, thereby potentiating exacerbations of airway disease. ABSTRACT: Viral infections precipitate exacerbations in many airway diseases, including asthma and cystic fibrosis. Although viral infections increase cholinergic transmission, few studies have examined how cholinergic history modifies subsequent cholinergic responses in the airway. In our previous work, we found that airway resistance in response to a second cholinergic challenge was increased in young pigs with a history of airway cholinergic stimulation. Given that mucus secretion is regulated by the cholinergic nervous system and that abnormal airway mucus contributes to exacerbations of airway disease, we hypothesized that prior cholinergic challenge would also modify subsequent mucus responses to a secondary cholinergic challenge. Using our established cholinergic challenge-rechallenge model in pigs, we atomized the cholinergic agonist bethanechol or saline control to pig airways. Forty-eight hours later, we removed tracheas and measured mucus secretion properties in response to a second cholinergic stimulation. The second cholinergic stimulation was conducted in conditions of diminished chloride and bicarbonate transport to mimic a cystic fibrosis-like environment. In pigs previously challenged with bethanechol, a second cholinergic stimulation produced a mild increase in sheet-like mucus films; these films were scarcely observed in animals originally challenged with saline control. The subtle increase in mucus films was not associated with changes in mucociliary transport. These data suggest that prior cholinergic history might modify mucus secretion characteristics with subsequent stimulation in certain environmental conditions or disease states. Such modifications and/or more repetitive stimulation might lead to retention of mucus on the airway surface, thereby potentiating exacerbations of airway disease.

'Calibrating to scale: a framework for humanitarian health organizations to anticipate, prevent, prepare for and manage climate-related health risks'.

Climate Change is adversely affecting health by increasing human vulnerability and exposure to climate-related stresses. Climate change impacts human health both directly and indirectly, through extreme weather events, changing distribution of health risks, increased risks of undernutrition, population displacement, and greater risks of injuries, disease, and death (Ebi, K., Campbell-Lendrum, D., & Wyns, A. The 1. 5 health report. WHO. 2018). This risk amplification is likely to increase the need for humanitarian support. Recent projections indicate that under a business as usual scenario of sustained greenhouse gas emissions, climate change could double the demand for humanitarian assistance by 2050 (World Health Organization. Operational Framework for building climateresilient health systems. WHO. 2015). Humanitarian assistance is currently not meeting the existing needs, therefore, any additional burden is likely to be highly challenging.Global health advocates, researchers, and policymakers are calling for urgent action on climate change, yet there is little clarity on what that action practically entails for humanitarian organizations. While some humanitarian organizations may consider themselves well designed to respond, climate change as a transversal threat requires the incorporation of a resilience approach to humanitarian action and policy responses.By bringing together authors from two historically disparate fields - climate change and health, and humanitarian assistance - this paper aims to increase the capacity of humanitarian organizations to protect health in an unstable climate by presenting an adapted framework. We adapted the WHO operational framework for climate-resilient health systems for humanitarian organizations and present concrete case studies to demonstrate how the framework can be implemented. Rather than suggest a re-design of humanitarian operations we recommend the application of a climate-lens to humanitarian activities, or what is also referred to as mainstreaming climate and health concerns into policies and programs. The framework serves as a starting point to encourage further dialogue, and to strengthen collaboration within, between, and beyond humanitarian organizations.

Angiotensin-Converting Enzyme (ACE) genetic variation and longevity in Peruvian older people: a cross-sectional study.

Background: Some studies have suggested that the insertion(I)/deletion(D) polymorphism of the Angiotensin-Converting Enzyme (ACE) gene may be associated with human longevity, especially in centenarians. However, this association is still controversial. Besides, there have been no studies in Peruvians.Aim: To describe the age distribution of the ACE polymorphism in a convenience sample of Peruvian older people.Subjects and methods: This was a cross-sectional study in 104 Geriatric Day Hospital patients in Lima, Perú. The ACE polymorphism was determined in all patients. For the purpose of association with age, the sample was divided into four categories: young (< 65), youngest-old (65-74), middle-old (75-84) and oldest-old (85 or more).Results: The distribution of genotype frequencies was consistent with a population in Hardy-Weinberg equilibrium (p = 0.62). The number (%) of D/D, I/D and I/I genotypes in the young was 2 (14.3%), 3 (21.4%) and 9 (64.3%), respectively; in youngest-old: 4 (11.4%), 15 (42.9%) and 16 (45.7%); in middle-old: 6 (12.2%), 20 (40.8%) and 23 (46.9%); and in oldest-old: 0 (0.0%), 4 (66.7%) and 2 (33.3%). A chi-square analysis showed no significant differences in genotype distribution between age groups (p = 0.647).Conclusion: No significant age differences were found in the distribution of the ACE polymorphism in this sample. Further studies with greater statistical power are recommended.

Urban Latinx parents' attitudes towards mental health: Mental health literacy and service use.

Latinx youth report elevated internalizing symptomatology as compared to their non-Latinx White counterparts and are less likely to access mental health care for these problems. This qualitative study examined the knowledge, beliefs and perceptions that Latinx parents (86% foreign-born; 66.7% monolingual Spanish speakers) living in urban communities have about mental health and service use for anxiety and depression in children. We used thematic analysis to analyze interview data from 15 Latinx parents who expressed concerns about their child's (age 6-13) worry or sadness. Analyses revealed that Latinx parents often have difficulty identifying mental health problems, report stigma about mental health problems and help-seeking and want more information about how they can help their children. Although Latinx parents report significant mental health and treatment-seeking stigma, the majority were open to seeking mental health services for their children or were already receiving services. Findings suggest that stigma although prevalent, may not deter service utilization for some Latinx families. Implications for community health and future research are discussed.

Aedes aegypti, the dengue fever mosquito in Mexico City. Early invasion and its potential risks.

INTRODUCTION: Mexico City has no endemic presence of Aedes aegypti, and it is therefore free of vector-borne diseases, such as dengue fever, Zika and chikungunya. However, evidence has shown the presence of Aedes aegypti eggs in the city since 2015. OBJECTIVE: To report the constant and increasing presence of Aedes aegypti eggs in Mexico City from 2015 to 2018. METHODS: Surveillance was carried out using ovitraps. Eggs were counted and hatched in order to determine the species. RESULTS: From 2015 to 2018, 378 organisms were identified as Ae. aegypti. In total, 76 Aedes aegypti-positive ovitraps were collected at 50 different places in 11 boroughs of the city. Northeastern Mexico City was the area with the highest number of positive traps. CONCLUSIONS: The results may be indicating a period of early colonization and the probable existence of cryptic colonies of the mosquito; Mexico City could be at risk of experiencing vector-borne epidemics.

INTRODUCCIÓN: La Ciudad de México no tiene presencia endémica de Aedes aegypti, por lo que está libre de enfermedades transmitidas por vector como dengue, Zika y chikunguña. Sin embargo, existe evidencia de la presencia de huevecillos en la urbe desde 2015. OBJETIVO: Reportar la presencia constante y en aumento de huevecillos de Aedes aegypti en la Ciudad de México de 2015 a 2018. MÉTODO: Se realizó vigilancia a través de ovitrampas; se contabilizaron y eclosionaron huevecillos para determinar la especie. RESULTADOS: De 2015 a 2018 fueron identificados 378 organismos como Aedes aegypti. En total fueron colectadas 76 ovitrampas positivas a Aedes aegypti en 50 sitios distintos de 11 alcaldías. El noreste de la Ciudad de México fue el área con mayor positividad. CONCLUSIONES: Los resultados pueden estar indicando un periodo de colonización incipiente y la probable la existencia de colonias crípticas del mosquito, por lo que la Ciudad de México podría estar en riesgo de presentar epidemias de enfermedades transmitidas por vector.

Sex-specific airway hyperreactivity and sex-specific transcriptome remodeling in neonatal piglets challenged with intra-airway acid.

Acute airway acidification is a potent stimulus of sensory nerves and occurs commonly with gastroesophageal reflux disease, cystic fibrosis, and asthma. In infants and adults, airway acidification can acutely precipitate asthma-like symptoms, and treatment-resistant asthma can be associated with gastroesophageal reflux disease. Airway protective behaviors, such as mucus secretion and airway smooth muscle contraction, are often exaggerated in asthma. These behaviors are manifested through activation of neural circuits. In some populations, the neural response to acid might be particularly important. For example, the immune response in infants is relatively immature compared with adults. Infants also have a high frequency of gastroesophageal reflux. Thus, in the current study, we compared the transcriptomes of an airway-nervous system circuit (e.g., tracheal epithelia, nodose ganglia, and brain stem) in neonatal piglets challenged with intra-airway acid. We hypothesized that the identification of parallel changes in the transcriptomes of two neutrally connected tissues might reveal the circuit response, and, hence, molecules important for the manifestation of asthma-like features. Intra-airway acid induced airway hyperreactivity and airway obstruction in male piglets. In contrast, female piglets displayed airway obstruction without airway hyperreactivity. Pairwise comparisons revealed parallel changes in genes directly implicated in airway hyperreactivity ( scn10a) in male acid-challenged piglets, whereas acid-challenged females exhibited parallel changes in genes associated with mild asthma ( stat 1 and isg15). These findings reveal sex-specific responses to acute airway acidification and highlight distinct molecules within a neural circuit that might be critical for the manifestation of asthma-like symptoms in pediatric populations.

Simulation as tool for evaluating and improving technical skills in laparoscopic gynecological surgery.

BACKGROUND: Simulation in laparoscopic surgery is nowadays recognized as a valid instrument for learning and training surgeons in different procedures. However, its role as evaluation test and self-assessment tool to verify basic surgical skills is still under discussion. METHODS: Thirty-three residents in obstetrics and gynecology at University of Pisa, Italy were recruited, and they received a simulation program consisting of 5 tasks. They had to perform basic laparoscopic surgery maneuvers as creating pneumoperitoneum, positioning trocars under vision, demonstrating the appropriate use of dominant and non-dominant hand and making single stitch and knot. They were evaluated with a modified OSATs scale. RESULTS: Senior trainees had better score than junior trainees (p value< 0,005) and after different sessions of simulation scores of both groups significantly improved (p < 0,001), especially for the junior group. All the trainees reported self-assessments that matched with the evaluation of external observers demonstrating the importance of simulation also as auto-evaluation test. CONCLUSIONS: In this study, we demonstrated the role of simulation as powerful tool to evaluate and to self-assess surgical technical skills and to improve own capacities, with the use of a modified OSATs scale adapted to specific exercises.

Solitary Cholinergic Stimulation Induces Airway Hyperreactivity and Transcription of Distinct Pro-inflammatory Pathways.

Airway hyperreactivity is a hallmark feature of asthma and can be precipitated by airway insults, such as ozone exposure or viral infection. A proposed mechanism linking airway insults to airway hyperreactivity is augmented cholinergic transmission. In the current study, we tested the hypothesis that acute potentiation of cholinergic transmission is sufficient to induce airway hyperreactivity. We atomized the cholinergic agonist bethanechol to neonatal piglets and forty-eight hours later measured airway resistance. Bethanechol-treated piglets displayed increased airway resistance in response to intravenous methacholine compared to saline-treated controls. In the absence of an airway insult, we expected to find no evidence of airway inflammation; however, transcripts for several asthma-associated cytokines, including IL17A, IL1A, and IL8, were elevated in the tracheas of bethanechol-treated piglets. In the lungs, prior bethanechol treatment increased transcripts for IFNγ and its downstream target CXCL10. These findings suggest that augmented cholinergic transmission is sufficient to induce airway hyperreactivity, and raise the possibility that cholinergic-mediated regulation of pro-inflammatory pathways might contribute.

A Liposome Encapsulated Ruthenium Polypyridine Complex as a Theranostic Platform for Triple-Negative Breast Cancer.

Ruthenium coordination complexes have the potential to serve as novel theranostic agents for cancer. However, a major limitation in their clinical implementation is effective tumor accumulation. In this study, we have developed a liposome-based theranostic nanodelivery system for [Ru(phen)2dppz](ClO4)2 (Lipo-Ru). This ruthenium polypyridine complex emits a strong fluorescent signal when incorporated in the hydrophobic lipid bilayer of the delivery vehicle or in the DNA helix, enabling visualization of the therapeutic agent in tumor tissues. Incubation of MDA-MB-231 breast cancer cells with Lipo-Ru induced double-strand DNA breaks and triggers apoptosis. In a mouse model of triple-negative breast cancer, treatment with Lipo-Ru dramatically reduced tumor growth. Biodistribution studies of Lipo-Ru revealed that more than 20% of the injected dose accumulated in the tumor. These results suggest that Lipo-Ru could serve as a promising theranostic platform for cancer.