The role of AP-2 alpha in predicting response to chemotherapy in breast cancer patients

Breast cancer is the most frequent cancer occurring in women in Europe1. In Switzerland, the incidence in 2009 was 32,9% and it was the primary cause of cancer related death in women, with a mortality rate of 19.2%2. The management of this cancer depends on clinical data, morphology of the tumour and its molecular profile3, 4. Five different subclasses have been described using molecular profiling: luminal A, luminal B, normal-like tumour, HER2+ and basal like4, 5. Luminal A is less aggressive than HER2+5. However, it was noticed that some patients had far worse outcomes than predicted when based on molecular criteria5. It is thought that breast cancer arises through a series of molecular alterations at the cellular level, resulting in the evasion of growth-inhibiting signals, evasion of apoptosis and spread of breast epithelial cells4. The human transcription factor and tumour suppressor activator-protein 2 (AP-2) was found to have a central role in the development of breast cancer6,7. Decrease of intracellular AP-2 is associated with more aggressive cancer types6,7. It is possible to study AP-2 levels via new method called protein-binding microarray (PBM)7. DNA-binding protein, as AP-2, is put in contact with double stranded DNA sequences fixed on a microarray8. This technique allowed the detection of protein binding on specific DNA sequences8. This method has been demonstrated to be reliable and highly sensitive7. In an initial study done at the University of Lausanne, it was demonstrated that AP-2 binding on DNA could have a better predictive value than classic molecular diagnosis and may redistribute the subtype classification. Now, there is a need to repeat this trial with more breast cancer specimens and a more robust microarray. My primary objective is to select 100 appropriate specimens from the pathology institute to repeat the trial. Specimens would be of the different subtype and also from tissue next to the tumour. For comparison we will also use tissue from reduction mammoplasties, as a healthy control. These specimens are obtained after either mastectomy or tumorectomy for the pathological tissue and after mammary reduction for the healthy control. All tissues samples were flash frozen and preserved at -80 C° to protect the cell proteins. Specimens and documentations will be rendered anonymously before processing by the lab. Secondly, the specimens will be used in the PBM microarray. The result will be analysed in conjunction with clinical history and follow-up of the patient. In conclusion, the use of PBM technique with the AP-2 protein is promising in order to improve the diagnosis of breast cancer. Using this technique we expected to better describe and understand breast cancer and the action of the tumour itself. This might lead to better prognosis of the disease and even lead to new treatment development

Comparison of pelvic floor dysfunction 6 years after uncomplicated vaginal versus elective cesarean deliveries: a cross-sectional study.

Clinicians and patients have traditionally believed that elective cesarean section may protect against certain previously ineluctable consequences of labor, including a plethora of urinary, anorectal and sexual dysfunctions. We aimed to evaluate fecal, urinary and sexual symptoms 6 years postpartum, comparing uncomplicated vaginal delivery and elective cesarean delivery, and to assess their impact on quality of life. We conducted a cross-sectional study to compare perineal functional symptomatology between women having singleton elective cesarean deliveries (eCS) and singleton uncomplicated vaginal deliveries (uVD). Women who delivered 6 years before this study were chosen randomly from our hospital database. This database includes demographic, labor, and delivery information, as well as data regarding maternal and neonatal outcomes, all of which is collected at the time of delivery by the obstetrician. Four validated self-administrated questionnaires were sent by post to the participants: the short forms of the Urogenital Distress Inventory, Incontinence Impact Questionnaire, Wexner fecal incontinence scale, and Female Sexual Function Index. Current socio-demographic details, physical characteristics, obstetrical history and mode of delivery at subsequent births were also registered using a self-reported questionnaire. A total of 309 women with uVD and 208 with eCS returned postal questionnaires. The response rate was 49%. Socio-demographic characteristics and fecal incontinence were similar between groups. After eCS, women reported significantly less urgency urinary incontinence (adjusted Relative Risk 0.55; 95% confidence interval 0.34-0.88) and stress incontinence (adjusted Relative Risk 0.53; 95% confidence interval 0.35-0.80) than after uVD. No difference in total Incontinence Impact Questionnaire score was found between both modes of delivery. Lower abdominal or genital pain (adjusted Relative Risk 1.58; 95% confidence interval 1.01-2.49) and pain related to sexual activity (adjusted Relative Risk 2.50; 95% confidence interval 1.19-5.26) were significantly more frequent after eCS than uVD. Six years postpartum, uVD is associated with urinary incontinence, while eCS is associated with sexual and urination pain

Planning and Designing Walkable Cities: A Smart Approach

Walking may be considered one of the most sustainable and democratic ways of travelling within a city, thus providing benefits not only to pedestrians but also to the urban environment. Besides, walking is also one of the means of transport most likely subjected to factors outside an individual\u2019s control, like social or physical abilities to walk and the presence of comfortable and safe street infrastructures and services. Therefore, improving urban conditions provided to pedestrians has positive impacts on walkability. At the same time technological solutions and innovations have the power to encourage and support people to walk by overcoming immaterial barriers due to a lack of information or boring travel and they give to decision makers the possibility to gain data to understand how and where people travel. Merging these two dimensions into a unique approach can drastically improve accessibility, attractiveness, safety, comfort and security of urban spaces. In this context, this paper aims to draw a more multifaceted context for walkability, where new technologies assume a key role for introducing new approaches to pedestrian paths planning and design and thus for enhancing this mode of transport. Indeed, by combining more traditional spatial-based and perceptual analysis of the urban environment with technological applications and social media exploitation there will be room to better support the decision on and to enhance satisfaction of walking as well as to easier plan and design more walkable cities

Diabetes mellitus, maternal adiposity, and insulin-dependent gestational diabetes are associated with COVID-19 in pregnancy: the INTERCOVID study

BACKGROUND: Among nonpregnant individuals, diabetes mellitus and high body mass index increase the risk of COVID-19 and its severity.OBJECTIVE: This study aimed to determine whether diabetes mellitus and high body mass index are risk factors for COVID-19 in pregnancy and whether gestational diabetes mellitus is associated with COVID-19 diagnosis.STUDY DESIGN: INTERCOVID was a multinational study conducted between March 2020 and February 2021 in 43 institutions from 18 countries, enrolling 2184 pregnant women aged >= 18 years; a total of 2071 women were included in the analyses. For each woman diagnosed with COVID-19, 2 nondiagnosed women delivering or initiating antenatal care at the same institution were also enrolled. The main exposures were preexisting diabetes mellitus, high body mass index (overweight or obesity was defined as a body mass index >= 25 kg/m(2)), and gestational diabetes mellitus in pregnancy. The main outcome was a confirmed diagnosis of COVID-19 based on a real-time polymerase chain reaction test, antigen test, antibody test, radiological pulmonary findings, or >= 2 predefined COVID-19 symptoms at any time during pregnancy or delivery. Relationships of exposures and COVID-19 diagnosis were assessed using generalized linear models with a Poisson distribution and log link function, with robust standard errors to account for model misspecification. Furthermore, we conducted sensitivity analyses: (1) restricted to those with a real-time polymerase chain reaction test or an antigen test in the last week of pregnancy, (2) restricted to those with a real-time polymerase chain reaction test or an antigen test during the entire pregnancy, (3) generating values for missing data using multiple imputation, and (4) analyses controlling for month of enrollment. In addition, among women who were diagnosed with COVID-19, we examined whether having gestational diabetes mellitus, diabetes mellitus, or high body mass index increased the risk of having symptomatic vs asymptomatic COVID-19.RESULTS: COVID-19 was associated with preexisting diabetes mellitus (risk ratio, 1.94; 95% confidence interval, 1.55-2.42), overweight or obesity (risk ratio, 1.20; 95% confidence interval, 1.06-1.37), and gestational diabetes mellitus (risk ratio, 1.21; 95% confidence interval, 0.99-1.46). The gestational diabetes mellitus association was specifically among women requiring insulin, whether they were of normal weight (risk ratio, 1.79; 95% confidence interval, 1.06-3.01) or overweight or obese (risk ratio, 1.77; 95% confidence interval, 1.28-2.45). A somewhat stronger association with COVID-19 diagnosis was observed among women with preexisting diabetes mellitus, whether they were of normal weight (risk ratio, 1.93; 95% confidence interval, 1.18-3.17) or overweight or obese (risk ratio, 2.32; 95% confidence interval, 1.82-2.97). When the sample was restricted to those with a real-time polymerase chain reaction test or an antigen test in the week before delivery or during the entire pregnancy, including missing variables using imputation or controlling for month of enrollment, the observed associations were comparable.CONCLUSION: Diabetes mellitus and overweight or obesity were risk factors for COVID-19 diagnosis in pregnancy, and insulin-dependent gestational diabetes mellitus was associated with the disease. Therefore, it is essential that women with these comorbidities are vaccinated