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Gender violence is a human rights violation and a serious public health problem that should be addressed with an inter-sector and interdisciplinary focus. Collaboration and coordination between sectors, including the health sector, is essential for guaranteeing such approach. The study aimed to learn which actors address gender violence in the communities and to study the communities' opinions concerning the public health system's role in (and approach to) this problem. A qualitative action-research project was conducted with local community self-diagnosis workshops, using various qualitative techniques and thematic analysis. The results pointed to various local actors that address the problem and showed that primary healthcare plays a relevant role, due mainly to its proximity to the population and interdisciplinary approach. The obstacles identified by the communities for the health system approach mainly involved the biomedical model of care, decentralization, and lack of resources, training, and integrated policies. In conclusion, the workshops facilitated the development of collective knowledge on the local reality, underlining the role of primary healthcare and the need to link action and approaches between sectors and communities.

Background: Although surgical resection is the only potentially curative treatment for pancreatic cancer (PC), long-term outcomes of this treatment remain poor. The aim of this study is to describe the feasibility of a neoadjuvant treatment with induction polychemotherapy (IPCT) followed by chemoradiation (CRT) in resectable PC, and to develop a machine-learning algorithm to predict risk of relapse., Methods: Forty patients with resectable PC treated in our institution with IPCT (based on mFOLFOXIRI, GEMOX or GEMOXEL) followed by CRT (50 Gy and concurrent Capecitabine) were retrospectively analyzed. Additionally, clinical, pathological and analytical data were collected in order to perform a 2-year relapse-risk predictive population model using machine-learning techniques., Results: A R0 resection was achieved in 90% of the patients. After a median follow-up of 33.5 months, median progression-free survival (PFS) was 18 months and median overall survival (OS) was 39 months. The 3 and 5-year actuarial PFS were 43.8% and 32.3%, respectively. The 3 and 5-year actuarial OS were 51.5% and 34.8%, respectively. Forty-percent of grade 3-4 IPCT toxicity, and 29.7% of grade 3 CRT toxicity were reported. Considering the use of granulocyte colony-stimulating factors, the number of resected lymph nodes, the presence of perineural invasion and the surgical margin status, a logistic regression algorithm predicted the individual 2-year relapse-risk with an accuracy of 0.71 (95% confidence interval [CI] 0.56-0.84, p = 0.005). The model-predicted outcome matched 64% of the observed outcomes in an external dataset., Conclusion: An intensified multimodal neoadjuvant approach (IPCT + CRT) in resectable PC is feasible, with an encouraging long-term outcome. Machine-learning algorithms might be a useful tool to predict individual risk of relapse. A small sample size and therapy heterogeneity remain as potential limitations.

One of the main difficulties with blood substitutes based on hemoglobin (Hb) solutions is the auto-oxidation of the hemes, a problem aggravated by the dimerization of Hb tetramers. We have employed a method to study the oxyHb tetramer-dimer equilibrium based on the rate of auto-oxidation as a function of protein concentration. The 16-fold difference in dimer and tetramer auto-oxidation rates (in 20 mM phosphate buffer at pH 7.0, 37 degrees C) was exploited to determine the fraction dimer. The results show a transition of the auto-oxidation rate from low to high protein concentrations, allowing the determination of the tetramer-dimer dissociation coefficient K4,2 = [Dimer] 2/[Tetramer]. A 14-fold increase in K4,2 was observed for addition of 10 mM of the allosteric effector inositol hexaphosphate (IHP). Recombinant hemoglobins (rHb) were genetically engineered to obtain Hb with a lower oxygen affinity than native Hb (Hb A). The rHb alpha2beta2 [(C7) F41Y/(G4) N102Y] shows a fivefold increase in K4,2 at pH 7.0, 37 degrees C. An atmosphere of pure oxygen is necessary in this case to insure fully oxygenated Hb. When this condition is satisfied, this method provides an efficient technique to characterize both the tetramer-dimer equilibrium and the auto-oxidation rates of various oxyHb. For low oxygen affinity Hb equilibrated under air, the presence of deoxy subunits accelerates the auto-oxidation. Although a full analysis is complicated, the auto-oxidation studies for air equilibrated samples are more relevant to the development of a blood substitute based on Hb solutions. The double mutants, rHb alpha2beta2 [(C7) F41Y/(G4) N102A] and rHb alpha2beta2 [(C7) F41Y/(E10) K66T], show a lower oxygen affinity and a higher rate of oxidation than Hb A. Simulations of the auto-oxidation rate versus Hb concentration indicate that very high protein concentrations are required to observe the tetramer auto-oxidation rate. Because the dimers oxidize much more rapidly, even a small fraction dimer will influence the observed oxidation rate.

We have engineered alpha2beta2 [Phe63]hemoglobin by changing the highly conserved distal histidine of the beta chains to a phenylalanine. The mutant tetramer binds four high-affinity ligands, such as CO or NO, to the ferrous form, or CN to the oxidized iron; however, it binds only two low-affinity ligands, oxygen and azide. The absorption spectrum of the ferrous deoxy or ferric forms are not normal, displaying an enhanced absorption of the visible band near 560 nm. Half of the autooxidation process, attributed to the mutated beta subunits, is over 1000-fold faster than for Hb A. The mutant Hb exhibits non-cooperative binding of two oxygens with an affinity about fivefold lower than those of HbA valency hybrids (alpha met beta)2. Functional properties of this mutant Hb resemble those of Hb Saskatoon ([Tyr63]Hb) [Suzuki, T., Hayashi, A., Shimizu, A. & Yamamura, Y. (1966) Biochim. Biophys. Acta 127, 280-282]. Flash-photolysis experiments also indicate non-cooperative behaviour: the CO-recombination kinetics were independent of the fraction dissociated. Furthermore, the amplitude of the CO bimolecular phase was the same for the (alpha(CO)metbeta)2 valency hybrid or the (alphaCO betaCO)2 form, suggesting mainly geminate CO-recombination kinetics to the beta chains. EPR and Resonance Raman spectra did not show evidence for a hemichrome, normally considered as a six-coordinated iron with low-spin character. The EPR and resonance Raman spectra for the mutated beta subunits demonstrate the presence of a high-spin compound in the ferric and deoxy ferrous forms. In particular, the ferrous mutated beta subunits are penta-coordinated. The abnormal absorption spectra are possibly due to an interaction between the porphyrin and the phenyl ring in the distal position rather than to direct binding to the iron.