Introduction to special issue on Webster

John Webster’s Theater of (Dis)obedience and Damnation: A collection of essays exploring the forms and functions of violence, evil, and social realities in Webster's drama

SMO Inhibition Modulates Cellular Plasticity and Invasiveness in Colorectal Cancer

Colon Cancer (CC) is the fourth most frequently diagnosed tumor and the second leading cause of death in the USA. Abnormalities of Hedgehog pathway have been demonstrated in several types of human cancers, however the role of Hedgehog (Hh) in CC remain controversial. In this study, we analyzed the association between increased mRNA expression of GLI1 and GLI2, two Hh target genes, and CC survival and recurrence by gene expression microarray from a cohort of 382 CC patients. We found that patients with increased expression of GLI1 showed a statistically significant reduction in survival. In order to demonstrate a causal role of Hh pathway activation in the pathogenesis of CC, we treated HCT 116, SW480 and SW620 CC cells lines with GDC-0449, a pharmacological inhibitor of Smoothened (SMO). Treatment with GDC-0449 markedly reduced expression of Hh target genes GLI1, PTCH1, HIP1, MUC5AC, thus indicating that this pathway is constitutively active in CC cell lines. Moreover, GDC-0449 partially reduced cell proliferation, which was associated with upregulation of p21 and downregulation of CycD1. Finally, treatment with the same drug reduced migration and three-dimensional invasion, which were associated with downregulation of Snail1, the EMT master gene, and with induction of the epithelial markers Cytokeratin-18 and E-cadherin. These results were confirmed by SMO genetic silencing. Notably, treatment with 5E1, a Sonic Hedgehog-specific mAb, markedly reduced the expression of Hedgehog target genes, as well as inhibited cell proliferation and mediated reversion toward an epithelial phenotype. This suggests the existence of a Hedgehog autocrine signaling loop affecting cell plasticity and fostering cell proliferation andmigration/invasion in CC cell lines. These discoveries encourage future investigations to better characterize the role of Hedgehog in cellular plasticity and invasion during the different steps of CC pathogenesis.Peer reviewe

Terapia cognitivo-comportamental: A preparação do paciente com transtorno de pânico para as exposições agorafóbicas interoceptivas e in vivo

Objetivo: O estudo com terapia cognitivo-comportamental (TCC) procurou demonstrar a preparaçãodo paciente com transtorno do pânico para exposições agorafóbicas. Foram usadas as técnicas dasexposições interoceptivas, às próprias sensações corporais, e in vivo, a locais ou situações temidas.Metodologia: 50 indivíduos, divididos em dois grupos de 25 participantes cada um. O grupo 1 realizou 10 sessões de TCC semanais e individuais com uma hora de duração e fez uso de medicamentos e o grupo 2, controle, usou apenas medicação sem TCC. A medicação prescrita consistiu em antidepressivos tricíclicos e inibidores seletivos de recaptação da serotonina. Foram aplicados instrumentos de avaliação no início e ao fim das intervenções médica e psicológica. Resultados: Observamos uma diferença significativa entre a avaliação inicial e final no grupo 1, como: redução nos ataques de pânico, ansiedade antecipatória, esquiva agorafobia e medo das sensações corporais. Na escala de avaliação global do funcionamento, um aumento do bem-estar global de 60.8% a 72.5% entre pacientes do grupo 1 com terapia, diferentemente do grupo 2 sem terapia. Conclusões: As técnicas de TCC para as exposições foram consideradas essenciais na preparação dos pacientes com transtorno de pânico, para enfrentarem os ataques de pânico e as situações agorafóbicas subsequentes

Evolving trends in the management of acute appendicitis during COVID-19 waves. The ACIE appy II study

Background: In 2020, ACIE Appy study showed that COVID-19 pandemic heavily affected the management of patients with acute appendicitis (AA) worldwide, with an increased rate of non-operative management (NOM) strategies and a trend toward open surgery due to concern of virus transmission by laparoscopy and controversial recommendations on this issue. The aim of this study was to survey again the same group of surgeons to assess if any difference in management attitudes of AA had occurred in the later stages of the outbreak. Methods: From August 15 to September 30, 2021, an online questionnaire was sent to all 709 participants of the ACIE Appy study. The questionnaire included questions on personal protective equipment (PPE), local policies and screening for SARS-CoV-2 infection, NOM, surgical approach and disease presentations in 2021. The results were compared with the results from the previous study. Results: A total of 476 answers were collected (response rate 67.1%). Screening policies were significatively improved with most patients screened regardless of symptoms (89.5% vs. 37.4%) with PCR and antigenic test as the preferred test (74.1% vs. 26.3%). More patients tested positive before surgery and commercial systems were the preferred ones to filter smoke plumes during laparoscopy. Laparoscopic appendicectomy was the first option in the treatment of AA, with a declined use of NOM. Conclusion: Management of AA has improved in the last waves of pandemic. Increased evidence regarding SARS-COV-2 infection along with a timely healthcare systems response has been translated into tailored attitudes and a better care for patients with AA worldwide

Infected pancreatic necrosis: outcomes and clinical predictors of mortality. A post hoc analysis of the MANCTRA-1 international study

: The identification of high-risk patients in the early stages of infected pancreatic necrosis (IPN) is critical, because it could help the clinicians to adopt more effective management strategies. We conducted a post hoc analysis of the MANCTRA-1 international study to assess the association between clinical risk factors and mortality among adult patients with IPN. Univariable and multivariable logistic regression models were used to identify prognostic factors of mortality. We identified 247 consecutive patients with IPN hospitalised between January 2019 and December 2020. History of uncontrolled arterial hypertension (p = 0.032; 95% CI 1.135-15.882; aOR 4.245), qSOFA (p = 0.005; 95% CI 1.359-5.879; aOR 2.828), renal failure (p = 0.022; 95% CI 1.138-5.442; aOR 2.489), and haemodynamic failure (p = 0.018; 95% CI 1.184-5.978; aOR 2.661), were identified as independent predictors of mortality in IPN patients. Cholangitis (p = 0.003; 95% CI 1.598-9.930; aOR 3.983), abdominal compartment syndrome (p = 0.032; 95% CI 1.090-6.967; aOR 2.735), and gastrointestinal/intra-abdominal bleeding (p = 0.009; 95% CI 1.286-5.712; aOR 2.710) were independently associated with the risk of mortality. Upfront open surgical necrosectomy was strongly associated with the risk of mortality (p < 0.001; 95% CI 1.912-7.442; aOR 3.772), whereas endoscopic drainage of pancreatic necrosis (p = 0.018; 95% CI 0.138-0.834; aOR 0.339) and enteral nutrition (p = 0.003; 95% CI 0.143-0.716; aOR 0.320) were found as protective factors. Organ failure, acute cholangitis, and upfront open surgical necrosectomy were the most significant predictors of mortality. Our study confirmed that, even in a subgroup of particularly ill patients such as those with IPN, upfront open surgery should be avoided as much as possible. Study protocol registered in ClinicalTrials.Gov (I.D. Number NCT04747990)

Shakespeare and Crisis. One Hundred Years of Italian Narratives

Shakespeare and Crisis: One hundred years of Italian narratives explores how Shakespeare intervened in the Italian socio-political and cultural scene between his third and fourth centenaries, at times which were manifestly perceived as ‘critical’. It asks which complex mythopoietic processes contributed to shaping regimes of reading Shakespeare in response to those times of crisis. Crises of national identity during the Great War and the Fascist regime, crises of history in the 1970s, and crises of representation in the second half of the twentieth century extending into the new millennium constitute the three main areas of a discussion that ultimately aims at probing into the role of literature at times of crisis. The volume situates itself at the juncture of European Shakespeare studies and studies of Shakespeare and Italy. It addresses essential questions about the position of literature in society, offering at different levels new insights for scholars, students, and the general reader

Assessment of quality of life of patients who underwent anterior cruciate ligament reconstruction and a rehabilitation program

Introduction: Quality of life can be defined as the expression of aconceptual model that tries to represent patient’s perspectivesand his/her level of satisfaction expressed by numbers. Theobjective of this study is to evaluate the parameters of quality oflife of 23 patients who underwent surgery for anterior cruciateligament reconstruction. Methods: We adopted SF-36, a generichealth-related evaluation questionnaire, to obtain informationregarding several aspects of patients’ health conditions, and theLysholm questionnaire, specific to evaluate the symptoms andfunction of the knee. The questionnaires were applied at two stagesof the treatment: pre- and postoperatively (after the rehabilitationprogram). Results: Before surgery, the Lysholm questionnairepresented the following results: excellent in 4% of the cases, goodin 22%, fair in 22%, and poor in 52%. After surgery (Lysholm e SF-36) the correlation level was approximately 44% (p = 0.041).Discussion: The correlation between the Lysholm and the SF-36questionnaires showed the following: the lower the level of pain,the higher the Lysholm score. The high scores presented by theLysholm questionnaire are directly proportional to physical andemotional aspects, and to functional capacity. Conclusion:Analysis of both questionnaires, as well as of their correlation,showed some improvement in patients´ quality of life. We werealso able to demonstrate the importance and usefulness of applyingthe two questionnaires at three different moments: before, duringand after physiotherapeutic intervention

Evolving trends in the management of acute appendicitis during COVID-19 waves. The ACIE appy II study (vol 46, pg 2021, 2022)

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