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Abstract Background Media fills are used to demonstrate the adequacy of the aseptic conditions of a pharmaceutical production process, according to good manufacturing practice (GMP), using a growth medium in place of the product solution. For advanced therapy medicinal product (ATMP), where the final product consists of viable cells, the media fill is still a challenge, but represents the starting point for process validation. Methods The aim of this paper is to describe the media fill test procedure in the context of ATMP manufacturing, in particular of Cytokine-Induced Killer (CIK) cell expansion process under GMP conditions, including quality control tests and environmental monitoring. The media fill test has been designed to cover all the critical steps of the process, including worst cases and deviations. Results From July 2019 to August 2022, we performed 16 media fill tests. During these years, the media fill protocol has been gradually improved and the worst cases were designed to be closer to reality and occurring cases. Although some deviations occurred, all the media fills performed were compliant. Conclusions A good media fill design combined with a robust environmental monitoring program provides a high degree of assurance of the microbial safety of ATMPs.

Abstract Background Neuronal migration is a crucial process that allows neurons to reach their correct target location to allow the nervous system to function properly. AP-2α is a transcription factor essential for neural crest cell migration and its mutation results in apoptosis within this cell population, as demonstrated by genetic models. Results We down-modulated AP-2α expression in GN-11 neurons by RNA interference and observe reduced neuron migration following the activation of a specific genetic programme including the Adhesion Related Kinase (Axl) gene. We prove that Axl is able to coordinate migration per se and by ChIP and promoter analysis we observe that its transcription is directly driven by AP-2α via the binding to one or more functional AP-2α binding sites present in its regulatory region. Analysis of migration in AP-2α null mouse embryo fibroblasts also reveals an essential role for AP-2α in cell movement via the activation of a distinct genetic programme. Conclusion We show that AP-2α plays an essential role in cell movement via the activation of cell-specific genetic programmes. Moreover, we demonstrate that the AP-2α regulated gene Axl is an essential player in GN-11 neuron migration.

Several essays have been dealt with the life and suicide of Italia Donati, the young primary schoolteacher whose death moved and shocked Italian public opinion in 1886. Nevertheless, no contribution analyzed why the episode exerted such a remarkable influence on Italian society. This paper is going to examine how the report the «Corriere della Sera» published on her death described characters involved and circumstances. Letters written by the newspapers’ readers and the following literature about the topic will be taken also into account for examinate how the investigative report influenced schoolteachers’ mentality on a mid-term basis.

With this article based on his fieldwork in Šuto Orizari, a Municipality in the suburbs of Skopje (Macedonia), the author analyses how theatrical language and narrative techniques can be used to oppose the strengthening of anti-gypsism in public opinion. Šuto Orizari is the only Municipality in the world where romanés is used as an official language, and the Mayor and the majority of the members of the assembly of the municipality come from the Roma community, thus enjoying a degree of effective self-government. Andrea Mochi Sismondi and Fiorenza Menni lived there for two years trying to understand the different visions of the world originating among Roma, while collecting dramaturgical materials later used in the production of two theatrical performances, a book and several public events where Roma and Gadžé can exchange their points of view on fundamental issues concerning political philosophy. Freedom, equality, the legitimate aspiration to a better life, freedom of movement: all values modern constitutions are based on, and on which the two artists focused their long interviews and conversations with Šuto Orizari citizens and Roma colleagues. The work has been presented all over Italy and its results reveal how literary non-fiction and performing arts can be successfully used to show the weakness of the arguments alleging the cultural distance that would make the dialogue between Roma and Gadžé impossible.

We report our experience of a 29-year-old female with a complete atrio-ventricular septal defect leading to a single ventricle physiology and Eisenmenger syndrome. The patient successfully underwent spinal anesthesia for cesarean section in the 31 st week of pregnancy. A multidisciplinary approach involving cardiologist, cardiac surgeon, obstetrician, and anesthesiologist was utilized to achieve a safe pregnancy and cesarean for the delivery of the baby. A close clinical assessment is required, especially during the third trimester when the risk of acute right ventricular dysfunction increases. The use of extracorporeal membrane oxygenation (ECMO) (as a bridge to recovery or bridge to salvage) was planned to support oxygenation and circulation in case of acute biventricular dysfunction. The delivery/cesarean section was performed in a cardiac surgery operating room, and to reduce the time-frame for ECMO institution the femoral vessels were exposed surgically before the cesarean section.

El ileo duodenal por litiasis biliar, se manifiesta como un síndrome de estenosis gastroduodenal. Fue descrito por Bouveret en 1896. Se comunican dos casos con características singulares. En uno de ellos, la presentación clínica como voluminosa tumoración de hipocondrio derecho, hizo imposible diferenciar en el preoperatorio entre un quiste hidático calcificado y una litiasis única gigante. El otro paciente se diagnosticó mediante fibrogastroscopía, pero fracasó el intento de extracción endoscópica del cálculo. La revisión de la literatura, analiza el espectro de posibilidades diagnósticas y terapéuticas. Se insiste en la vigencia de la cirugía como procedimiento integral y curativo, considerando que la extracción endoscópica y eventualmente la litotriopsia extracorpórea deben limitarse a pacientes con muy elevado riesgo anestésico-quirúrgico.

Background. Postpartum haemorrhage (PPH) is a significant contributor to worldwide maternal morbidity and mortality. When PPH continues despite aggressive medical treatment, early consideration should be given to surgical intervention. Various surgical interventions may be used but conservative interventions are recommended primarily. Case. This case report describes laparoscopic coagulation of hypogastric artery technique in a patient with PPH. Conclusions. Laparoscopic ligature of the hypogastric artery for PPH treatment can be a valid alternative to laparotomy in patients with vaginal delivery.

BackgroundEstrogen is an established enhancer of breast cancer development, but less is known on its effect on local progression or metastasis. We studied the effect of estrogen receptor recruitment on actin cytoskeleton remodeling and breast cancer cell movement and invasion. Moreover, we characterized the signaling steps through which these actions are enacted.Methodology/principal findingsIn estrogen receptor (ER) positive T47-D breast cancer cells ER activation with 17beta-estradiol induces rapid and dynamic actin cytoskeleton remodeling with the formation of specialized cell membrane structures like ruffles and pseudopodia. These effects depend on the rapid recruitment of the actin-binding protein moesin. Moesin activation by estradiol depends on the interaction of ER alpha with the G protein G alpha(13), which results in the recruitment of the small GTPase RhoA and in the subsequent activation of its downstream effector Rho-associated kinase-2 (ROCK-2). ROCK-2 is responsible for moesin phosphorylation. The G alpha(13)/RhoA/ROCK/moesin cascade is necessary for the cytoskeletal remodeling and for the enhancement of breast cancer cell horizontal migration and invasion of three-dimensional matrices induced by estrogen. In addition, human samples of normal breast tissue, fibroadenomas and invasive ductal carcinomas show that the expression of wild-type moesin as well as of its active form is deranged in cancers, with increased protein amounts and a loss of association with the cell membrane.Conclusions/significanceThese results provide an original mechanism through which estrogen can facilitate breast cancer local and distant progression, identifying the extra-nuclear G alpha(13)/RhoA/ROCK/moesin signaling cascade as a target of ER alpha in breast cancer cells. This information helps to understand the effects of estrogen on breast cancer metastasis and may provide new targets for therapeutic interventions.

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