El historiador-científico y/ o el historiador-escritor: límites y transgresiones de la tarea cognitivo-literaria de escribir la historia

La pregunta acerca del estatus epistémico de la narración histórica ha sido formulada de manera tal que el espectro de respuestas posibles se reduce al delimitado por una alternativa excluyente; o bien la narración histórica es valorada positivamente como un discurso "científico", o bien es menospreciada como una rama de la literatura. En este contexto, pensar en apelar a la teoría literaria como recurso relevante para elaborar una teoría de la historia genera desconfianza, dado que se asume que tal asociación no puede sino redundar en una mirada debilitadora de la tarea del historiador

El concepto de campo histórico como construcción lingüístico-ficcional-hipotética en Hayden White

Nuestro articulo, en primer lugar, remontará el afán crítico de White hacia una de sus fuentes teóricas; el estructuralismo. En segundo lugar, reconstruirá los aspectos más positivos de la perspectiva whiteana ligados a la postulación del concepto de "campo histórico" como central para entender la dinámica epistémica de la obra histórica. Finalmente, destacaremos cómo en el concepto de "ficción" o ''ficcionalización" puede evidenciarse esta doble mirada crítico-positiva del autor. Deberemos recordar que White presenta una teoría que se propone explicar cómo comprendemos el pasado, a partir del modo en que los historiadores ofrecen explicaciones históricas en forma de textos

The effects of verbal information on children's fear beliefs about social situations

Two experiments explored the role of verbal information in changing children’s fearrelated beliefs about social situations. In Experiment 1, 118 6- to 8- and 12- to 13-year-olds heard positive, negative, or no information about individuals’ experiences of three social situations. Fear beliefs regarding each situation were assessed before and after this manipulation. Verbal information had no significant influence on children’s fear beliefs. In Experiment 2, the same paradigm was used with 80 12- to 13-year-olds, but the information took the form of multiple attitude statements about the situations expressed by groups of peers, older children, or adults. An affective priming task of implicit attitudes was used to complement the explicit questions about fear beliefs. Negative information influenced both explicit and implicit fear beliefs. The source of information and the child’s own social anxiety did not moderate these effects. Implications for our understanding of the socialisation of childhood fears are discussed

Globalizing Hayden White

This conversation originated in a plenary session organized by Ewa Domańska and María Inés La Greca under the same title of ‘Globalizing Hayden White’ at the III International Network for Theory of History Conference ‘Place and Displacement: The Spacing of History’ held at Södertörn University, Stockholm, in August 2018. In order to pay homage to Hayden White’s life work 5 months after his passing we knew that what was needed–and what he himself would have wanted–was a vibrant intellectual exchange. Our ‘celebration by discussion’ contains elaborated and revised versions of the presentations by scholars from China (Xin Chen), Latin America (María Inés La Greca, Veronica Tozzi Thompson), United States (Paul Roth), Western (Kalle Pihlainen) and East-Central Europe (Ewa Domańska). We took this opportunity of gathering scholars who represent different parts of the world, different cultures and approaches to reflect on White’s ideas in a global context. Our interest was in discussing how his work has been read and used (or even misread and misused) and how it has influenced theoretical discussions in different parts of the globe. Rather than just offering an account as experts, we mainly wanted to reflect on the current state of our field and the ways that White’s inheritance might and should be carried forward in the future.Fil: Domanska, Ewa. Adam Mickiewicz University in Poznań; PoloniaFil: la Greca, María Inés. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Tres de Febrero. Departamento de Metodología, Estadística y Matemáticas; Argentina. Universidad de Buenos Aires. Facultad de Filosofía y Letras. Departamento de Filosofía; ArgentinaFil: Roth, Paul A.. University of California at Santa Cruz; Estados UnidosFil: Chen, Xin. Zhejiang University; ChinaFil: Tozzi, María Verónica. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Tres de Febrero. Departamento de Metodología, Estadística y Matemáticas; Argentina. Universidad de Buenos Aires. Facultad de Filosofía y Letras. Departamento de Filosofía; ArgentinaFil: Pihlainen, Kalle. Tallinn University; Estoni

Polymorphisms in metabolic genes, their combination and interaction with tobacco smoke and alcohol consumption and risk of gastric cancer: a case-control study in an Italian population.

BACKGROUND: The distribution and the potential gene-gene and gene-environment interaction of selected metabolic genetic polymorphisms was investigated in relation to gastric cancer risk in an Italian population. METHODS: One hundred and seven cases and 254 hospital controls, matched by age and gender, were genotyped for CYP1A1, CYP2E1, mEH, GSTM1, GSTT1, NAT2 and SULT1A1 polymorphisms. Haplotype analysis was performed for EPHX1 exons 3 and 4, as well as CYP2E1 RsaI (*5 alleles) and CYP2E1 DraI (*5A or *6 alleles). The effect modification by alcohol and cigarette smoking was tested with the heterogeneity test, while the attributable proportion (AP) was used to measure the biological interaction from the gene-gene interaction analysis. RESULTS: Gastric cancer risk was found to be associated with the inheritance of GSTT1 null genotype (OR = 2.10, 95%CI: 1.27-3.44) and the SULT1A1 His/His genotype (OR = 2.46, 95%CI: 1.03-5.90). No differences were observed for the haplotype distributions among cases and controls. For the first time an increased risk was detected among individuals carrying the *6 variant allele of CYP2E1 if ever-drinkers (OR = 3.70; 95%CI: 1.45-9.37) with respect to never-drinkers (OR = 0.18; 95% CI: 0.22-1.46) (p value of heterogeneity among the two estimates = 0.001). Similarly, the effect of SULT1A1 variant genotype resulted restricted to ever-smokers, with an OR of 2.58 (95%CI: 1.27-5.25) for the carriers of His allele among smokers, and an OR of 0.86 (95%CI: 0.45-1.64) among never-smokers (p value of heterogeneity among the two estimates = 0.03). The gene-gene interaction analyses demonstrated that individuals with combined GSTT1 null and NAT2 slow acetylators had an additional increased risk of gastric cancer, with an OR of 3.00 (95%CI: 1.52-5.93) and an AP of 52%. CONCLUSION: GSTT1, SULT1A1 and NAT2 polymorphisms appear to modulate individual's susceptibility to gastric cancer in this Italian population, particularly when more than one unfavourable genotype is present, or when combined with cigarette smoke. The increased risk for the carriers of CYP2E1*5A or *6 alleles among drinkers need to be confirmed by larger prospective studies

Implementing Enhanced Perioperative Care in Emergency General Surgery: A Prospective Multicenter Observational Study

Introduction: ERAS pathway has been proposed as the standard of care in elective abdominal surgery. Guidelines on ERAS in emergency surgery have been recently published; however, few evidences are still available in the literature. The aim of this study was to evaluate the feasibility of an enhanced recovery protocol in a large cohort of patients undergoing emergency surgery and to identify possible factors impacting postoperative protocol compliance. Methods: This is a prospective multicenter observational study including patients who underwent major emergency general surgery for either intra-abdominal infection or intestinal obstruction. The primary endpoint of the study is the adherence to ERAS postoperative protocol. Secondary endpoints are 30-day mortality and morbidity rates, and length of hospital stay. Results: A total of 589 patients were enrolled in the study, 256 (43.5%) of them underwent intestinal resection with anastomosis. Major complications occurred in 92 (15.6%) patients and 30-day mortality was 6.3%. Median adherence occurred on postoperative day (POD) 1 for naso-gastric tube removal, on POD 2 for mobilization and urinary catheter removal, and on POD 3 for oral intake and i.v. fluid suspension. Laparoscopy was significantly associated with adherence to postoperative protocol, whereas operative fluid infusion > 12 mL/Kg/h, preoperative hyperglycemia, presence of a drain, duration of surgery and major complications showed a negative association. Conclusions: The present study supports that an enhanced recovery protocol in emergency surgery is feasible and safe. Laparoscopy was associated with an earlier recovery, whereas preoperative hyperglycemia, fluid overload, and abdominal drain were associated with a delayed recovery

From Mutation to Mechanism: an Approach to Understand Photoreceptors Function

Microbial rhodopsins and phytochromes are photoreceptors that use light to trigger biochemical processes. Upon light activation, they undergo a cyclic cascade of reactions leading to substrate transfer and/or conformational changes associated with the chromophore and protein. NmHR and UmRh1, two microbial rhodopsins, are a bacterial inward chloride pump and a fungal outward proton pump, respectively. While the role of NmHR from a marine bacterium is similar to that of the well-known archaeal inward chloride pump halorhodopsins (HsHR and NpHR), it shares a higher sequence homology with the bacterial outward sodium pump KR2. In addition, each rhodopsin contains a three-residue motif composed of amino acids involved in substrate transfer. The NTQ motif of NmHR is quite conserved in the sodium pump KR2 (NDQ), but is represented by a neutral TSA motif in archaebacterial halorhodopsins, suggesting a divergent evolution. A comprehensive mutational and spectroscopic analysis of residues known to be important for chloride transfer in archaeal halorhodopsins and for sodium transfer in KR2 revealed that chloride release and uptake in NmHR is different from that of archaeal halorhodopsins, but the architecture and residues involved in the process are more similar to KR2, despite the different charge and orientation of the transported ion. UmRh1 is a rhodopsin found in the pathogenic fungus Ustilago maydis, which causes corn smut disease. This fungal rhodopsin shares a high sequence similarity with the well-known archaeal outward proton pump bacteriorhodopsin (HsBR), especially at residues known to be important for the proton pathway of the latter. The DTD motif of HsBR is conserved in UmRh1 and is represented by a DTE motif. However, extensive mutagenesis and spectroscopy revealed that the protonation dynamics of UmRh1 are slightly different from those of HsBR, especially in the proton uptake reaction. Furthermore, the pump activity of UmRh1 is enhanced in the presence of auxins such as IAA (indole-3-acetic acid). Using time-resolved spectroscopy on UmRh1 variants in the presence and absence of IAA, a potential role for auxin was elucidated. It is involved in the enhancement of the reprotonation mechanism and the proton release reaction associated with its pathogenic role. Another aspect that has intrigued scientists over the years is the link between light and chromophore isomerization in photoreceptors, which leads to conformational changes in the protein. How does the signal propagate in the early stages of the photocycle after photon absorption? By introducing the noncanonical amino acid p-cyano-phenylalanine in NmHR and the phytochrome Agp2 into positions of conserved tryptophan residues known to be involved in conformational changes around the chromophore, preliminary results have been obtained that shed light on the protein-chromophore interaction.Mikrobielle Rhodopsine und Phytochrome sind Photorezeptoren, die Licht nutzen, um biochemische Prozesse auszulösen. Nach der Aktivierung durch Licht durchlaufen sie eine zyklische Reaktionskaskade, die zu einem Substrattransfer und/oder Konformationsänderungen im Zusammenhang mit dem Chromophor und dem Protein führt. Die hier untersuchten zwei mikrobiellen Rhodopsine sind NmHR, eine bakterielle nach innen gerichtete Chloridpumpe, und UmRh1, eine nach außen gerichtete pilzliche Protonenpumpe. Während die Rolle des aus einem Meeresbakterium stammenden NmHR derjenigen der bekannten Halorhodopsine (HsHR und NpHR) aus Archaeen ähnelt, weist es eine größere Sequenzhomologie mit der bakteriellen Natrium-Auswärtspumpe KR2 auf. Darüber hinaus enthält jedes Rhodopsin ein aus drei Aminosäuren bestehtes Motiv auf, das am Substrattransfer beteiligt ist. Das NTQ-Motiv von NmHR ist in der Natriumpumpe KR2 (NDQ) weitgehend konserviert, wird aber in archaebakteriellen Halorhodopsinen durch ein neutrales TSA-Motiv repräsentiert, was auf eine divergente Evolution hindeutet. Eine umfassende Mutationsanalyse mit nachfolgender spektroskopischer Untersuchung von Aminosäureresten, die für den Chlorid-Transfer in archaealen Halorhodopsinen und für den Natrium-Transfer in KR2 bekannt sind, ergab, dass sich in NmHR die Chloridfreisetzung und Aufnahme von der in archaealen Halorhodopsinen unterscheidet, dass aber die Architektur und die an dem Prozess beteiligten Aminosäuren dem KR2 ähnlicher sind, trotz der unterschiedlichen Ladung und Ausrichtung des transportierten Ions. UmRh1 ist ein Rhodopsin, welches in dem pathogenen Pilz Ustilago maydis vorkommt, der die Maisfleckenkrankheit verursacht. Dieses Pilzrhodopsin weist eine hohe Sequenzähnlichkeit mit der bekannten aus Archaeen stammenden Protonenpumpe Bakteriorhodopsin (HsBR) auf, vor allem an Stellen, die für den Protonenweg der letzteren wichtig sind. Das DTD-Motiv von HsBR ist in UmRh1 konserviert und wird durch ein DTE-Motiv dargestellt. Ausführliche Mutagenese und Spektroskopie zeigten jedoch, dass sich die Protonierungsdynamik von UmRh1 geringfügig von derjenigen von HsBR unterscheidet, insbesondere bei der Protonenaufnahmereaktion. Außerdem ist die Pumpaktivität von UmRh1 in Gegenwart von Auxinen wie IAA (Indol-3-Essigsäure) verstärkt. Durch zeitaufgelöste Spektroskopie an UmRh1-Varianten in Gegenwart und Abwesenheit von IAA wurde eine mögliche Rolle von Auxin aufgedeckt. Es ist wahrscheinlich an der Verstärkung des Reprotonierungsmechanismus und der Protonenfreisetzungsreaktion im Zusammenhang mit seiner pathogenen Rolle beteiligt. Ein weiterer Aspekt, der die Wissenschaftler im Laufe der Jahre fasziniert hat, ist die Verbindung zwischen Licht und der Isomerisierung des Chromophors in den Photorezeptoren, die zu Konformationsänderungen des Proteins führt. Wie wird das Signal in den frühen Stadien des Photozyklus nach der Photonenabsorption weitergeleitet? Durch die Einführung der nicht-kanonischen Aminosäure p-Cyano-Phenylalanin in NmHR und in Phytochrom Agp2 in Positionen von konservierten Tryptophanresten, von denen bekannt ist, dass sie an Konformationsänderungen um das Chromophor herum beteiligt sind, wurden erste Ergebnisse erzielt, die Licht auf die Protein-Chromophor-Interaktion werfen

Advanced Therapy Medicinal Products: Availability, Access and Expenditure in Italy

Background: Advanced therapy medicinal products (ATMPs) are an innovative output of biomedical research, characterized by a high level of uncertainty on long-term efficacy and safety, elevated price tags and often complex administration. All these elements compounded make their European authorization, national price negotiation for reimbursement and subsequent dispensation and administration to the patient less straightforward and often less successful than for less innovative drugs. To assess if these hurdles have affected patient access and how are ATMPs used in Italy, we have analysed availability, access and expenditure of ATMPs in the period spanning from 2016 to 2023. Methods: We have analysed real world data on the duration of ATMP regulatory evaluations for authorisation and reimbursement, time to first patient access and expenditure for ATMPs through the Italian National Health System (INHS) expenditure data flow, as well as information on patient mobility and availability of health facilities specialized in administering ATMPs. Findings: Of the 18 ATMPs currently authorized in Europe, 9 are reimbursed by the INHS, but only 6 were actually used, generating a cumulative expenditure of roughly 300 Mln€ from 2016 to 2023, largely owing to CAR-T therapies. Time to patient access reaches an average of 340.6 days from the day publication in the official Gazette of the reimbursement decision to first patient treatment in one of the 107 health facilities authorized for ATMP administration, after an even longer evaluation time by regulatory agencies. Conclusion: Since the first reimbursement decision for an ATMP in Italy, back in 2016, these innovative drugs became progressively more and more available, both in terms of numbers and in terms of coverage across the country. Almost all Italian regions have at least one centre for ATMP administration and has performed a treatment in 2023. Notwithstanding their high per-treatment prices, ATMPs currently have a rather contained expenditure, however it is bound to keep growing in the next few years