On the occasion of the centennial of the Nobel Prize in Physiology or Medicine, 1923: Nicolae C. Paulescu-between scientific creativity and political fanatism

Altres ajuts: acords transformatius de la UABSince the Nobel Prize in Physiology or Medicine was awarded in 1923 to FG Banting and JJR Macleod, many voices have been raised against this decision. The bitterest protest was that of the Romanian scientist Nicolae C. Paulescu. In 2002, The Romanian Academy of Sciences, the European Association for the Study of Diabetes (EASD) and the International Diabetes Federation (IDF) planned to hold a series of academic events the following year in Paris to acknowledge Paulescu's scientific merits in the discovery of the antidiabetic hormone. However, the initiative was cancelled in August 2003, when the European Center of the Simon Wiesenthal Foundation (SWC) accused Paulescu of being antisemitic. The authors of this manuscript have decided to approach "the Paulescu case" from its double aspect, scientific and sociopolitical, to analyze the circumstances surrounding the discovery of the antidiabetic hormone, and Paulescu's alleged antisemitic past in the historical context of the Romanian nation in the interwar period. We contacted the SWC and people related to the 2003 events in Paris. We performed a comparative review of the documents published by the Toronto group and by Paulescu and analyzed the correspondence and articles generated by international experts from the scientific community interested in the controversy. We carried out an exhaustive bibliographic search through several online catalogs (INDEXCAT, NLM Gateway, EUREKA, MEDHIST). We travelled to Bucharest, where we visited Paulescu's house-museum, interviewed a former student of the Romanian professor, and a prominent medical historian who was knowledgeable about Paulescu's scientific and political biography. Dan Angelescu†, son of Dr. Constantin Angelescu (1904-1990), Paulescu's nephew and collaborator, provided us with a copy of all the available documentation from Paulescu's personal archive. It constitutes an essential source for understanding Paulescu's personal, political and academic biography. Archives consulted: Românǎ Academy (Bucharest). Personal Archive of Paulescu, House -Museum (Bucharest)*. Romanian Jewish Heritage (Bucharest). http://romanianjewish.org/ **. Simon Wiesenthal Center (Los Angeles, CA) http://www.wiesenthal.com **. Romanian Patent Office. Oficiul de Stat pentru Invenții şi Mǎrci (OSIM) (Bucharest)***. Nobel Archives (Stockholm) https://www.nobelprize.org . Internet Archive (San Francisco, CA) https://archive.org **. Wellcome Library (London) https://wellcomelibrary.org **. The European Library https://www.theeuropeanlibrary.org/ **. US National Library of Medicine, NLM historical collections http://www.nlm.nih.gov/hmd/index.html **. US. Holocaust Memorial Museum http://www.ushmm.org/ (*: archive consulted on site; **: material found in the online catalog of the archive; ***: archivists sent us digitized copies of archival material). Books consulted for information on the history of Romania and antisemitism: "Nationalist ideology and antisemitism. The case of Romanian intellectuals in the 1930s", by Leon Volovici; "The mystique of ultranationalism: History of the Iron Guard, Romania, 1919-1941" by Francisco Vega; "Romania 1866-1947", by Keith Hitchins; "History of Romania. Compendium", by Ioan-Aurel Pop and Joan Bolovan; "The Holocaust in Romania. The destruction of Jews and Gypsies under the Antonescu regime, 1940-1944", by Radu Ioanid; "The Jews of East Central Europe between the World Wars", by Ezra Mendelson; "Cultural Politics in Greater Romania. Regionalism, Nation Building and Ethnic Struggle, 1918-1930", by Irina Livezeanu, and "Judeophobia. How and when it is born, where and why it survives", by Gustavo Daniel Perednik. Articles are referenced in the bibliography section at the end of the manuscript. A-Nicolae Paulescu developed an intense long-term research activity, which included complete pancreatectomy and preparation of a pancreatic extract (PE) containing the antidiabetic hormone he called pancreina. Parenteral administration of the PE achieved excellent results in the treatment of experimental diabetes in dogs and induction of hypoglycemia in the healthy animal. This work was initiated before 1916 and published at least eight months antedating the publication of the first article by Banting and Best (February 1922), who were acquainted with Paulescu's results, but misinterpreted them. The pancreatic extract of the two Canadian researchers, -iletin/insulin-, only achieved similar results to that of the Romanian scientist once they abandoned the use of the "degenerated pancreas" extract (ligation of the ductal system), replacing it with the pancreas of adult or fetal bovine. Pancreina and insulin were very similar. The award of the Nobel Prize in Physiology or Medicine to FG Banting and JJR Macleod in October 1923 honored the successful clinical use of insulin in patients with diabetes mellitus. Paulescu's achievements were ignored. B-Nicolae Paulescu publicly manifested his Judeophobic ideology on multiple occasions in academic and political interventions and in publications and participated with other figures from the Romanian intellectual sphere in the founding of the Uniunea Național Crestinǎ (UNC, National Christian Union) in 1922 and of the Liga Apǎrǎrii Național Cresține (LANC, League for Christian National Defense) in 1923, antisemitic far-right political parties, associated with an irrational Christian orthodoxy and hatred of Jews. Paulescu played a pivotal role in the spread of antisemitism. A-The Romanian scientist NC Paulescu started an intense research program aimed at the isolation of the antidiabetic hormone before 1916, including an original procedure of pancreatectomy in the dog and the elaboration of a pancreatic extract that achieved excellent results in the treatment of experimental diabetes, demonstrating its beneficial effects on the metabolism of carbohydrates, proteins and fats and reducing both glycosuria and glycemia and the urinary excretion of ketone bodies of depancreatized dogs toward normality. The results of these investigations were published in 1920 and 1921, predating the first report published by FG ​​Banting and CH Best in February 1922. It has been sufficiently demonstrated that Canadian researchers were aware of Paulescu's excellent results, mentioning them only in passing, albeit erroneously misrepresenting key results of the Romanian scientist's publication in the aforementioned seminal Canadian article. Expert historians and international scientists have recognized that the pancreatic extract that Paulescu called pancreina and that obtained by Banting and Best, insulin, were very similar. The October 1923 award of the Nobel Prize in Physiology or Medicine to FG Banting and JJR Macleod ignored Paulescu's scientific achievements in the treatment of experimental diabetes and rewarded the extraordinary advance of insulin treatment in human diabetes. B-At the end of August 2003, a few days before the date of the celebration at the Hôtel Dieu in Paris of the scheduled program of tribute to the scientific merits of NC Paulescu and his important contribution to the discovery of the antidiabetic hormone, convened by the Romanian Academy and the International Diabetes Federation, the Wiesenthal Foundation publicly accused the Romanian scientist of being an antisemite, an act that determined the cancellation of the announced events. The exhaustive investigation of the personal convictions and antisemitic behavior of Nicolae C. Paulescu has undoubtedly documented the Judeophobic ideology of the Romanian scientist, linked to his orthodox religious radicalism, manifested in multiple documents (mostly pamphlets) and interventions in collaboration with other relevant personalities of the Romanian intelligentsia of his time. Furthermore, Paulescu participated in the creation of political organizations of the most radical extreme right that played a fundamental role in the spread of antisemitism amongst the Romanian population and the university community

The Nobel Prize of Physiology or Medicine, 1923: controversies on the discovery of the antidiabetic hormone

Altres ajuts: acords transformatius de la UABTo analyze the main contributions to the discovery of the antidiabetic hormone in the period between 1889, the year in which Oskar Minkowski demonstrated that complete pancreatectomy in dogs caused diabetes, and the year 1923, the date in which the clinical use of insulin was consolidated. A main objective has been to review the controversies that followed the Nobel Prize and to outline the role of the priority rule in Science. We have considered the priority rule defined by Robert Merton in 1957, which takes into account the date of acceptance of the report of a discovery in an accredited scientific journal and/or the granting of a patent, complemented by the criteria set out by Ronald Vale and Anthony Hyman (2016) regarding the transfer of information to the scientific community and its validation by it. The awarding of the Nobel Prize in Physiology or Medicine in October 1923 has represented a frame of reference. The claims and disputes regarding the prioritization of the contributions of the main researchers in the organotherapy of diabetes have been analyzed through the study of their scientific production and the debate generated in academic institutions. According to the criteria of Merton, Vale and Hyman, the priority of the discovery of the antidiabetic hormone corresponds to the investigations developed in Europe by E. Gley (1900), GL Zülzer (1908) and NC Paulescu (1920). (2) The active principle of the pancreatic extracts developed by Zülzer (acomatol), Paulescu (pancreina) and Banting and Best (insulin) was the same. (3) JB Collip succeeded in isolating the active ingredient from the pancreatic extract in January 1922, eliminating impurities to the point of enabling its use in the clinic. (4) In 1972, the Nobel Foundation modified the purpose of the 1923 Physiology or Medicine award to Banting and Macleod by introducing a new wording: "the credit for having produced the pancreatic hormone in a practical available form" (instead of "for the discovery of insulin")

I‑European research, the cradle of the discovery of the antidiabetic hormone: the pioneer roles and the relevance of Oskar Minkowski and Eugène Gley

Acord transformatiu CRUE-CSICUTP en procés de revisióAims: The introduction of hormonal treatment in severe diabetes in 1922 represented a clinical and social impact similar to that of antibiotic therapy. In October 1923, the Assembly of the Karolinska Institute decided to award the Nobel Prize in Physiology or Medicine to the Canadian Frederick Grant Banting and the Scottish John James Rickard Macleod, researchers at the University of Toronto (UT), for "the discovery of insulin a year before". A few weeks later, European and American researchers protested the decision. The controversy remains to this day. Methods: We have conducted a comprehensive review of primary and critical sources focused on theorganotherapy of animal and human diabetes mellitus since 1889, when Oskar Minkowski demonstrated the induction of experimental diabetes by total pancreatectomy in the dog, until the spring of 1923, when the Nobel Foundation had already received all the nominations for the award in Physiology or Medicine. Results: The in-depth analysis of all these sources revealed that Europe was the cradle of the discovery of the antidiabetic hormone. The discovery involved multiple research steps headed by a long list of key investigators, mainly European. Conclusion: Marcel Eugène Émile Gley was the frst to demonstrate the presence of the "antidiabetic principle" in extracts from "sclerosed" pancreas. The French physiologist pioneered the successful reduction of glycosuria and diabetic symptoms by the parenteral administration of pancreatic extracts to depancreatized dogs in experiments developed between 1890 and 1905, antedating insulin in two decades

Los expedientes de depuración del franquismo en el Hospital de Sant Pau

El 26 de gener de 1939 la ciutat de Barcelona va caure en poder de les tropes franquistes. Les noves autoritats no van perdre el temps i el 9 de febrer de 1939 van signar la Llei de Responsabilitats polítiques. Al dia següent, 10 de febrer, van proclamar la Llei de Depuració de Funcionaris Públics. Aquest treball es basa en l’estudi dels 252 Expedients de Depuració als quals van ser sotmesos els metges de l’Hospital de la Santa Creu i Sant Pau.El 26 de enero de 1939 la ciudad de Barcelona cayó en poder de las tropas franquistas . Las nuevas autoridades no perdieron el tiempo y el 9 de febrero de 1939 se firmó la Ley de Responsabilidades políticas y el día siguiente, el 10 de febrero, la Ley de Depuración de Funcionarios Públicos . Este trabajo se basa en el estudio de los 252 Expedientes de Depuración a los que tuvieron que someterse los médicos del Hospital de la Santa Creu i Sant Pau

Calculation of direct and indirect excitons in GaAs/Ga1−xAlxAs coupled double quantum wells : the effects of in-plane magnetic fields and growth-direction electric fields

ABSTRACT: The variational procedure, in the effective-mass and parabolic-band approximations, is used in order to investigate the effects of crossed electric and magnetic fields on the exciton states in GaAs/Ga1−xAlxAs coupled double quantum wells. Calculations are performed for double quantum wells under applied magnetic fields parallel to the layers and electric fields in the growth direction. The exciton envelope wave function is obtained through a variational procedure using a hydrogenic 1s-like wave function and an expansion in a complete set of trigonometric functions for the electron and hole wave functions. We take into account intersubband mixing brought about by the Coulomb interaction of electron-hole pairs in double quantum wells and present a detailed analysis of the properties of direct and indirect exciton states in these systems. The present study clearly reveals anticrossing effects on the dispersion with applied voltage or growth-direction electric field of the photoluminescence peaks associated with direct and indirect excitons. Calculated results are found in good agreement with available experimental measurements on the photoluminescence peak position associated with direct and indirect excitons in GaAs-Ga1−xAlxAs double quantum wells under growthdirection applied electric fields or under applied in-plane magnetic fields

How Continuous Monitoring Changes the Interaction of Patients with a Mobile Telemedicine System

The use of continuous glucose monitor changes the way patients manage their diabetes, as observed in the increased number of daily insulin bolus, the increased number of daily BG measurements, and the differences in the distribution of BG measurements throughout the day. Continuous monitoring also increases the interaction of patients with the information system and modifies their patterns of use

Electronic Report Generation Web Service evaluated within a Telemedicine System

This work presents a generic tool based on a client-server architecture that generates electronic reports helping the evaluation process of any information system. For the specific evaluation of telemedicine systems the defined reports cover four dimensions: auditory of the system; evolution of clinical protocols; results from the questionnaires for user acceptance and quality of life; and surveillance of clinical variables. The use of a Web Service approach allows multiplatform use of the developed electronic report service and the modularity followed in the implementation enables easy system evolution and scalability

Vitamin D concentrations in familial combined hyperlipidemia: effects of lipid lowering treatment

BACKGROUND: Vitamin D deficiency has been linked to several cardiovascular risk factors but information regarding vitamin D concentrations in familial combined hyperlipidemia (FCHL) is lacking. Our objective was to examine vitamin D concentrations in patients with FCHL and to study the effects of lipid-lowering therapy. METHODS: We conducted a cross sectional study on 59 patients with FCHL and 48 healthy controls. We analyzed 25-hydroxyvitamin D (25(OH)D) concentrations and their association with lipid parameters, anthropometric measures, C-reactive protein and homeostasis model assessment (HOMA) index. Twenty-three patients with FCHL were also included in a longitudinal study conducted to analyze 25-hydroxyvitamin D concentrations before and after treatment for dyslipidemia. RESULTS: After adjustment for body mass index and seasonality, patients with FCHL had lower vitamin D concentrations than controls. Adjusted means (standard error of the mean (S.E.M)) for 25(OH)D according to the presence or absence of FCHL were 62.8 (3.6) nmol/L for patients with FCHL and 74.8 (4.1) nmol/L for controls (p = 0.021). In FCHL, hypovitaminosis D was associated with features of atherogenic dyslipidemia. After lipid-lowering therapy, vitamin D concentrations increased (51.0 ± 31.3 to 58.9 ± 24.6 nmol/L (P = 0.022)). However, changes in 25(OH)D concentrations did not correlate with changes in other parameters. CONCLUSIONS: Our findings suggest that FCHL is associated with decreased vitamin D concentrations and that treatment for dyslipidemia improves vitamin D status through an unknown mechanism. Further studies are needed to replicate these data in larger populations and to elucidate the mechanisms involved in this association

Hipovitaminosis D y obesidad. Relación con el grado de obesidad y el síndrome metabólico

En 343 sujetos con sobrepeso u obesidad demostramos la existencia de una relación inversa entre los niveles (r -0,403, p 40 Kg/m2. Asimismo, los pacientes con síndrome metabólico tenían niveles de calcidiol inferiores (43,35 ± 29,01 nmol/L y 55,26 ± 29,6 nmol/L) y presentaban una mayor prevalencia de hipovitaminosis D, independientemente del grado de obesidad. Estos datos sugieren, que como ocurre para otras comorbilidades asociadas con la obesidad, la distribución de la adiposidad parece desarrollar un papel en el estado de la vitamina D.En 343 subjectes amb sobrepès o obesitat demostrem l'existència d'una relació inversa entre els nivells (r -0,403, p 40 Kg/m2. A més a més, els pacients amb síndrome metabòlica tenien nivells de calcidiol inferiors (43,35 ± 29,01 nmol/L i 55,26 ± 29,6 nmol/L) i presentaven una major prevalença de d'hipovitaminosi D, independentment del grau d'obesitat. Aquestes dades suggereixen que, com succeeix amb altres comorbiditats associades a l'obesitat, la distribució del greix sembla jugar un paper en l'estat de la vitamina D