Il grembo fra le parole: Cio’ che ci unisce e ci trasforma in relazione. Storie di donne rifugiate ordinarie-straordinarie e la mia

Màster en Estudis de la Diferència Sexual, Universitat de Barcelona. DUODA, Centre de recerca de dones, curs: 2016-2017, Tutora: María Milagros Rivera Garreta

Correction: The Endocytic Adaptor Eps15 Controls Marginal Zone B Cell Numbers.

Eps15 is an endocytic adaptor protein involved in clathrin and non-clathrin mediated endocytosis. In Caenorhabditis elegans and Drosophila melanogaster lack of Eps15 leads to defects in synaptic vesicle recycling and synapse formation. We generated Eps15-KO mice to investigate its function in mammals. Eps15-KO mice are born at the expected Mendelian ratio and are fertile. Using a large-scale phenotype screen covering more than 300 parameters correlated to human disease, we found that Eps15-KO mice did not show any sign of disease or neural deficits. Instead, altered blood parameters pointed to an immunological defect. By competitive bone marrow transplantation we demonstrated that Eps15-KO hematopoietic precursor cells were more efficient than the WT counterparts in repopulating B220⁺ bone marrow cells, CD19⁻ thymocytes and splenic marginal zone (MZ) B cells. Eps15-KO mice showed a 2-fold increase in MZ B cell numbers when compared with controls. Using reverse bone marrow transplantation, we found that Eps15 regulates MZ B cell numbers in a cell autonomous manner. FACS analysis showed that although MZ B cells were increased in Eps15-KO mice, transitional and pre-MZ B cell numbers were unaffected. The increase in MZ B cell numbers in Eps15 KO mice was not dependent on altered BCR signaling or Notch activity. In conclusion, in mammals, the endocytic adaptor protein Eps15 is a regulator of B-cell lymphopoiesis

Sexual violence and eclampsia: analysis of data from Demographic and Health Surveys from seven low- and middle-income countries.

BACKGROUND: Scientific literature has provided clear evidence of the profound impact of sexual violence on women's health, such as somatic disorders and mental adverse outcomes. However, consequences related to obstetric complications are not yet completely clarified. This study aimed to assess the association of lifetime exposure to intimate partner sexual violence with eclampsia. METHODS: We considered all the seven Demographic and Health Surveys (DHS) that included data on sexual violence and on signs and symptoms suggestive of eclampsia for women of reproductive age (15-49 years). We computed unadjusted and adjusted odds ratios (OR) to evaluate the risk of suggestive eclampsia by ever subjected to sexual violence. A sensitivity analysis was conducted restricting the study population to women who had their last live birth over the 12 months before the interview. RESULTS: Self-reported experience of sexual violence ranged from 3.7% in Mali to 9.2% in India while prevalence of women reporting signs and symptoms compatible with eclampsia ranged from 14.3% in Afghanistan to 0.7% in the Philippines. Reported sexual violence was associated with a 2-fold increased odd of signs and symptoms suggestive of eclampsia in the pooled analysis. The sensitivity analysis confirmed the strength of the association between sexual violence and eclampsia in Afghanistan and in India. CONCLUSIONS: Women and girls in low-and-middle-income countries are at high risk of sexual violence, which may represent a risk factor for hypertensive obstetric complication. Accurate counseling by health care providers during antenatal care consultations may represent an important opportunity to prevent adverse outcomes during pregnancy

Conversion to secondary progressive multiple sclerosis: patient awareness and needs. results from an online survey in Italy and Germany

Background: Few studies have investigated the experiences of patients around the conversion to secondary progressive multiple sclerosis (SPMS). ManTra is a mixed-method, co-production research project conducted in Italy and Germany to develop an intervention for newly-diagnosed SPMS patients. In previous project actions, we identified the needs and experiences of patients converting to SPMS via literature review and qualitative research which involved key stakeholders.Aims: The online patient survey aimed to assess, on a larger and independent sample of recently-diagnosed SPMS patients: (a) the characteristics associated to patient awareness of SPMS conversion; (b) the experience of conversion; (c) importance and prioritization of the needs previously identified.Methods: Participants were consenting adults with SPMS since <= 5 years. The survey consisted of three sections: on general and clinical characteristics; on experience of SPMS diagnosis disclosure (aware participants only); and on importance and prioritization of 33 pre-specified needs.Results: Of 215 participants, those aware of their SPMS diagnosis were 57% in Italy vs. 77% in Germany (p = 0.004). In both countries, over 80% of aware participants received a SPMS diagnosis from the neurologist; satisfaction with SPMS disclosure was moderate to high. Nevertheless, 28-35% obtained second opinions, and 48-56% reported they did not receive any information on SPMS. Participants actively seeking further information were 63% in Germany vs. 31% in Italy (p < 0.001).Variables independently associated to patient awareness were geographic area (odds ratio, OR 0.32, 95% CI 0.13-0.78 for Central Italy; OR 0.21, 95% CI 0.08-0.58 for Southern Italy [vs. Germany]) and activity limitations (OR 7.80, 95% CI 1.47-41.37 for dependent vs. autonomous patients).All pre-specified needs were scored a lot or extremely important, and two prioritized needs were shared by Italian and German patients: "physiotherapy" and "active patient care involvement." The other two differed across countries: "an individualized health care plan" and "information on social rights and policies" in Italy, and "psychological support" and "cognitive rehabilitation" in Germany.Conclusions: Around 40% of SPMS patients were not aware of their disease form indicating a need to improve patient-physician communication. Physiotherapy and active patient care involvement were prioritized in both countries

Expression of Mutant or Cytosolic PrP in Transgenic Mice and Cells Is Not Associated with Endoplasmic Reticulum Stress or Proteasome Dysfunction

The cellular pathways activated by mutant prion protein (PrP) in genetic prion diseases, ultimately leading to neuronal dysfunction and degeneration, are not known. Several mutant PrPs misfold in the early secretory pathway and reside longer in the endoplasmic reticulum (ER) possibly stimulating ER stress-related pathogenic mechanisms. To investigate whether mutant PrP induced maladaptive responses, we checked key elements of the unfolded protein response (UPR) in transgenic mice, primary neurons and transfected cells expressing two different mutant PrPs. Because ER stress favors the formation of untranslocated PrP that might aggregate in the cytosol and impair proteasome function, we also measured the activity of the ubiquitin proteasome system (UPS). Molecular, biochemical and immunohistochemical analyses found no increase in the expression of UPR-regulated genes, such as Grp78/Bip, CHOP/GADD153, or ER stress-dependent splicing of the mRNA encoding the X-box-binding protein 1. No alterations in UPS activity were detected in mutant mouse brains and primary neurons using the UbG76V-GFP reporter and a new fluorogenic peptide for monitoring proteasomal proteolytic activity in vivo. Finally, there was no loss of proteasome function in neurons in which endogenous PrP was forced to accumulate in the cytosol by inhibiting cotranslational translocation. These results indicate that neither ER stress, nor perturbation of proteasome activity plays a major pathogenic role in prion diseases

COVID-19 Severity in Multiple Sclerosis: Putting Data Into Context

Background and objectives: It is unclear how multiple sclerosis (MS) affects the severity of COVID-19. The aim of this study is to compare COVID-19-related outcomes collected in an Italian cohort of patients with MS with the outcomes expected in the age- and sex-matched Italian population. Methods: Hospitalization, intensive care unit (ICU) admission, and death after COVID-19 diagnosis of 1,362 patients with MS were compared with the age- and sex-matched Italian population in a retrospective observational case-cohort study with population-based control. The observed vs the expected events were compared in the whole MS cohort and in different subgroups (higher risk: Expanded Disability Status Scale [EDSS] score > 3 or at least 1 comorbidity, lower risk: EDSS score ≤ 3 and no comorbidities) by the χ2 test, and the risk excess was quantified by risk ratios (RRs). Results: The risk of severe events was about twice the risk in the age- and sex-matched Italian population: RR = 2.12 for hospitalization (p < 0.001), RR = 2.19 for ICU admission (p < 0.001), and RR = 2.43 for death (p < 0.001). The excess of risk was confined to the higher-risk group (n = 553). In lower-risk patients (n = 809), the rate of events was close to that of the Italian age- and sex-matched population (RR = 1.12 for hospitalization, RR = 1.52 for ICU admission, and RR = 1.19 for death). In the lower-risk group, an increased hospitalization risk was detected in patients on anti-CD20 (RR = 3.03, p = 0.005), whereas a decrease was detected in patients on interferon (0 observed vs 4 expected events, p = 0.04). Discussion: Overall, the MS cohort had a risk of severe events that is twice the risk than the age- and sex-matched Italian population. This excess of risk is mainly explained by the EDSS score and comorbidities, whereas a residual increase of hospitalization risk was observed in patients on anti-CD20 therapies and a decrease in people on interferon

DMTs and Covid-19 severity in MS: a pooled analysis from Italy and France

We evaluated the effect of DMTs on Covid-19 severity in patients with MS, with a pooled-analysis of two large cohorts from Italy and France. The association of baseline characteristics and DMTs with Covid-19 severity was assessed by multivariate ordinal-logistic models and pooled by a fixed-effect meta-analysis. 1066 patients with MS from Italy and 721 from France were included. In the multivariate model, anti-CD20 therapies were significantly associated (OR = 2.05, 95%CI = 1.39–3.02, p < 0.001) with Covid-19 severity, whereas interferon indicated a decreased risk (OR = 0.42, 95%CI = 0.18–0.99, p = 0.047). This pooled-analysis confirms an increased risk of severe Covid-19 in patients on anti-CD20 therapies and supports the protective role of interferon

Investigation of biological markers to evaluate the adaptation of the newborn Belgian Blue calf to the extrauterine life. A pilot study.

peer reviewedAdaptation to extrauterine life and immunity transfer at calving are more at stake when dealing with highly productive breeds such as the Belgian Blue Cattle Breed (BBCB). The purpose of the present pilot study was to evaluate different blood markers, from the birth to the first week of life in BBCB calves, in order to investigate fundamental aspects of the adaptation to the extrauterine life as passive immunity transfer and early energy metabolism. Eighty calves coming from 10 different farms located in Wallonia (Belgium) were enrolled. A clinical examination was performed to verify viability and maturity at birth. Blood samples were collected at birth, day 1 and day 3 to 7. Passive immunity transfer analysis included serum and colostrum immunoglobulin G (IgG) concentration, and plasmatic selenium concentration (Se). Glycemia, serum insulin and cortisol concentration have been considered for the energy metabolism analysis. The data collected were statistically analysed using logistic regression and unpaired t-test. All calves were born alive, viable and mature by caesarean section. Mortality rate was 0% at one week and 5% at three months. Only 33% of calves had an IgG concentration >16g/L after one week of age, while only 34% of colostra had an IgG concentration >70g/L. Glycemia and serum insulin concentration at birth were significantly lower than other breeds, and plasmatic selenium concentration were coherent with low supplemented dams. We compared calves across IgG concentration classes (>16 g/L vs <16g/L). The crosssectional analysis of the risk of FPT when given low IgG concentration colostra has shown a non significant odd ratio (OR 1,058 and 0,39116 g/L) (p<0,001). No significant difference has been shown between cortisol and glycemia (p=0,3) nor insulin and glycemia (p=0,2) at birth. These data suggest a significant difference in BBCB calves on several metabolic markers, but they also revealed that immunity transfer and micronutrition of pregnant hyper-productive dams remain a challenge in modern farms.GPS veaux mou