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This analysis compared microvascular and cardiac outcomes from women in the Treatment Options for Type 2 Diabetes in Adolescents and Youth (TODAY) study, originally diagnosed with youth-onset Type 2 diabetes between the ages of 10-17 yrs, who experienced a pregnancy lasting 20 wks during the course of the study vs. those without. Pregnancy information was obtained prospectively by self-report followed by medical record review. Neuropathy and nephropathy were assessed annually. Retinopathy, echocardiography, and arterial stiffness were assessed twice during the study. Women with a history of pregnancy prior to the initial assessment were excluded. Of the 4women in TODAY, 116 reported a pregnancy lasting ≥ 20 weeks, with 67 having a single pregnancy and 49 with multiple pregnancies. The mean age at first pregnancy was 21.6 yrs. and mean diabetes duration 8 yrs. At study entry, women who reported a pregnancy during the trial were older (14 yrs. vs. 13.6 yrs., p=0.05) with lower household income (51.5% vs. 37.8% below $25,000, p=0.002) . Primary study outcome, defined as HbA1c >8% or inability to wean from insulin, was similar between the two groups. In Cox regression models adjusted for participant characteristics from study entry including age, race/ethnicity, household income, diabetes duration, HbA1c (>6%) , and BMI, women with a pregnancy had an increased risk of hyperfiltration, 2.76 (1.38-5.49) , p=0.0vs. those without a pregnancy. No differences were observed in rates of retinopathy, neuropathy, or macro- and microalbuminuria in women with vs. without a history of pregnancy. In fully adjusted models, history of pregnancy did not impact echocardiographic measures or arterial stiffness obtained prior to the reported pregnancy versus the measures after the pregnancy. These results suggest that pregnancy increases the risk of hyperfiltration in women with youth-onset T2D, but not other micro or macrovascular complications. Disclosure J.B.Tryggestad: None. M.M.Kelsey: Other Relationship; Boehringer Ingelheim International GmbH, Janssen Pharmaceuticals, Inc., Rhythm Pharmaceuticals, Inc. S.A.Arslanian: Advisory Panel; Eli Lilly and Company, Novo Nordisk, Other Relationship; AstraZeneca, Research Support; Eli Lilly and Company, Novo Nordisk. S.Chernausek: None. K.Drews: None. E.N.Escaname: None. M.Geffner: Advisory Panel; Novo Nordisk, Pfizer Inc., Research Support; Novo Nordisk. E.M.Isganaitis: Research Support; AstraZeneca, Dexcom, Inc., Insulet Corporation. Funding U01-DK61212, U01-DK61230, U01-DK61239, U01-DK61242, and U01-DK61254

Introduction: High sensitivity troponin T (hsTnT) is a strong predictor of adverse outcome during SARS-CoV-2 infection. However, its determinants remain partially unknown. We aimed to assess the relationship between severity of inflammatory response/coagulation abnormalities and hsTnT in Coronavirus Disease 2019 (COVID-19). We then explored the relevance of these pathways in defining mortality and complications risk and the potential effects of the treatments to attenuate such risk.Methods: In this single-center, prospective, observational study we enrolled 266 consecutive patients hospitalized for SARS-CoV-2 pneumonia. Primary endpoint was in-hospital COVID-19 mortality. Results: hsTnT, even after adjustment for confounders, was associated with mortality. D-dimer and CRP presented stronger associations with hsTnT than PaO2. Changes of hsTnT, D-dimer and CRP were related but only D-dimer was associated with mortality. Moreover, low molecular weight heparin showed attenuation of the mortality in the whole population, particularly in subjects with higher hsTnT.Conclusions: D-dimer possessed a strong relationship with hsTnT and mortality. Anticoagulation treatment showed greater benefits with regard to mortality. These findings suggest a major role of SARS-CoV-2 coagulopathy in hsTnT elevation and its related mortality in COVID-19. A better understanding of the mechanisms related to COVID-19 might pave the way to therapy tailoring in these high-risk individuals.

Objective: To assess pregnancy outcomes in young women with youth-onset type 2 diabetes followed in the TODAY study. Research Design and Methods: Pregnancy information (outcome, any maternal or fetal complications) was obtained from the female participants by self-report. Additionally, medical records for the pregnancy and the child’s neonatal course were obtained with data abstracted into standardized forms. Results: Over a maximum of 15 years, 260 pregnancies were reported by 141 women (age 21.5 years ± 3.2 years, BMI 35.6 ± 7.2 kg/m2, diabetes duration 8.1 ± 3.2 years). Contraception use prior to pregnancy reported by 13.5% of the women. Complications were reported by 65% of the women during their pregnancy. Pregnancy loss was observed in 25.3% and preterm birth in 32.6% of pregnancies. HbA1c ≥ 8% was observed in 31.9% of the pregnancies and 35% of the pregnancies were complicated by chronic hypertension. Nephropathy prior to pregnancy was observed in 25% of the women. In the offspring, 7.8% were classified as small for gestational age, 26.8% large for gestational age, and 17.9% in the macrosomic range. Conclusion: Based on observations from the TODAY cohort, young women with pre-gestational, youth-onset type 2 diabetes had very high rates of maternal complications stemming from significant socioeconomic disadvantage. The substantial maternal and infant complications seen in these young moms could potentially be avoided with improved contraception rates and reproductive planning.

The condensed nearest neighbor (CNN) classifier is one of the techniques used and known to perform recognition tasks. It has also proven to be one of the most interesting algorithms in the field of data mining despite its simplicity. However, CNN suffers from several drawbacks, such as high storage requirements and low noise tolerance. One of the characteristics of CNN is that it focuses on the selection of prototypes, which consists of reducing the set of training data. One of the goals of CNN seeks to achieve the reduction of information in such a way that the reduced information can represent large amounts of data to exercise decision-making on them. This paper mentions some of the most recent contributions to CNN-based unsupervised algorithms in a review that builds on the mathematical principles of condensed methods.

High sensitivity troponin T (hsTnT) is a strong predictor of adverse outcome during SARS-CoV-2 infection. However, its determinants remain partially unknown. We aimed to assess the relationship between severity of inflammatory response/coagulation abnormalities and hsTnT in Coronavirus Disease 2019 (COVID-19). We then explored the relevance of these pathways in defining mortality and complications risk and the potential effects of the treatments to attenuate such risk. In this single-center, prospective, observational study we enrolled 266 consecutive patients hospitalized for SARS-CoV-2 pneumonia. Primary endpoint was in-hospital COVID-19 mortality. hsTnT, even after adjustment for confounders, was associated with mortality. D-dimer and CRP presented stronger associations with hsTnT than PaO2. Changes of hsTnT, D-dimer and CRP were related; but only D-dimer was associated with mortality. Moreover, low molecular weight heparin showed attenuation of the mortality in the whole population, particularly in subjects with higher hsTnT. D-dimer possessed a strong relationship with hsTnT and mortality. Anticoagulation treatment showed greater benefits with regard to mortality. These findings suggest a major role of SARS-CoV-2 coagulopathy in hsTnT elevation and its related mortality in COVID-19. A better understanding of the mechanisms related to COVID-19 might pave the way to therapy tailoring in these high-risk individuals. © 2021, The Author(s).

Accurate risk stratification in COVID-19 patients consists a major clinical need to guide therapeutic strategies. We sought to evaluate the prognostic role of estimated pulse wave velocity (ePWV), a marker of arterial stiffness which reflects overall arterial integrity and aging, in risk stratification of hospitalized patients with COVID-19. This retrospective, longitudinal cohort study, analyzed a total population of 1671 subjects consisting of 737 hospitalized COVID-19 patients consecutively recruited from two tertiary centers (Newcastle cohort: n = 471 and Pisa cohort: n = 266) and a non-COVID control cohort (n = 934). Arterial stiffness was calculated using validated formulae for ePWV. ePWV progressively increased across the control group, COVID-19 survivors and deceased patients (adjusted mean increase per group 1.89 m/s, P p P P

Itaconic acid (IA) is an unsaturated diacid, a promising compound that might replace part of the petrochemical-based monomers, such as acrylic acid, as a building block for polymers. Recent developments in biotechnology allow the efficient production of IA through fermentation processes. However, further enhancements are necessary in the downstream (recovery) of the product. This investigation examined the separation of IA by adsorption from aqueous solutions, using two types of commercial, strongly basic ion-exchange resins: Purolite A-500P and PFA-300. To evaluate the separation process, the following parameters were tested: pH (from 3.03 to 6.33), temperature (from 10 to 50 °C), and IA concentration (from 0.41 to 6.50 g·L–1). The Freundlich and Langmuir isotherms were shown to be good fits to the experimental data, and the adsorption kinetics for IA was found to follow a pseudo-second-order (PSO) model. After batch tests, continuous adsorption experiments were carried out using a fixed bed column, and ...

In this paper, we consider the problem of solving linear algebraic equations of the form $Ax=b$ among multi agents which seek a solution by using local information in presence of random communication topologies. The equation is solved by $m$ agents where each agent only knows a subset of rows of the partitioned matrix $[A,b]$. We formulate the problem such that this formulation does not need the distribution of random interconnection graphs. Therefore, this framework includes asynchronous updates or unreliable communication protocols without B-connectivity assumption. We apply the random Krasnoselskii-Mann iterative algorithm which converges almost surely and in mean square to a solution of the problem for any matrices $A$ and $b$ and any initial conditions of agents' states. We demonestrate that the limit point to which the agents' states converge is determined by the unique solution of a convex optimization problem regardless of the distribution of random communication graphs. Eventually, we show by two numerical examples that the rate of convergence of the algorithm cannot be guaranteed., Comment: 10 pages, 2 figures, a preliminary version of this paper appears without proofs in the Proceedings of the 57th IEEE Conference on Decision and Control, Miami Beach, FL, USA, December 17-19, 2018

Fundamento: la eliminación de la tuberculosis como problema de salud pública precisa el perfeccionamiento de las acciones preventivas sobre los casos de tuberculosis pulmonar con baciloscopia positiva.Objetivo: analizar la incidencia de tuberculosis pulmonar con baciloscopia positiva en el municipio Cienfuegos durante 1995-2013 y establecer pronóstico para el cuatrienio 2014- 2017.Métodos: estudio descriptivo retrospectivo que incluyó 133 casos de pacientes con baciloscopia positiva notificados. Se analizó: edad, sexo, área de salud, resultado de la baciloscopia, demora y lugar de diagnóstico. La predicción fue realizada con el modelo suavizado exponencial de Brown.Resultados: la baciloscopia positiva presentó una tendencia decreciente, representó el 56,1 % del total de casos de tuberculosis pulmonar. Predominaron los enfermos masculinos y el grupo de edades de 60 años y más. El 84,2 % de los casos presentó codificaciones altas en los exámenes microscópicos de esputo realizados. Menos del 52 % de los diagnósticos fueron realizados en la atención primaria de salud y solo el 50 % se enmarcó dentro del tiempo establecido por el programa como indicador operacional. Se predice que ocurrirá un discreto descenso de casos nuevos de pacientes con baciloscopia positiva en los próximos cuatro años. Conclusiones: eliminar la tuberculosis como problema sanitario es posible a mediano plazo en Cienfuegos; sin embargo el incumplimiento persistente de los indicadores que evalúan las acciones preventivas realizadas en los casos con baciloscopia positiva es y será un obstáculo serio para reducir la morbilidad y transmisibilidad de la enfermedad en la localidad.

A set of synthetic approaches was developed and applied to the synthesis of eight frame-shifted isoprenoid diphosphate analogues. These analogues were designed to increase or decrease the methylene units between the double bonds and/or the pyrophosphate moieties of the isoprenoid structure. Evaluation of mammalian GGTase-I and FTase revealed that small structural changes can result in substantial changes in substrate activity.

Protein prenylation is a type of post-translational modification that aids certain proteins in localizing to the plasma member where they activate cell signaling. To better understand the isoprenoid requirements and differences of FTase and GGTase-I, a series of saturated geranylgeranyl diphosphate analogs were synthesized and screened against both mammalian FTase and GGTase-I. Of our library of compounds, several analogs proved to be substrates of GGTase-I, with 11d having a krel = 0.95 when compared to GGPP (krel = 1.0).

Protein geranylgeranylation is a type of post-translational modification that aids in the localization of proteins to the plasma member where they elicit cellular signals. To better understand the isoprenoid requirements of GGTase-I, a series of aryl-modified geranylgeranyl diphosphate analogs were synthesized and screened against mammalian GGTase-I. Of our seven-member library of compounds, six analogs proved to be substrates of GGTase-I, with 6d having a krel = 1.93 when compared to GGPP (krel = 1.0).

OBJECTIVES: To study whether systematic reviewers apply procedures to counter-balance some common forms of research malpractice such as not publishing completed research, duplicate publications, or selective reporting of outcomes, and to see whether they identify and report misconduct. DESIGN: Cross-sectional analysis of systematic reviews and survey of their authors. PARTICIPANTS: 118 systematic reviews published in four journals (Ann Int Med, BMJ, JAMA, Lancet), and the Cochrane Library, in 2013. MAIN OUTCOMES AND MEASURES: Number (%) of reviews that applied procedures to reduce the impact of: (1) publication bias (through searching of unpublished trials), (2) selective outcome reporting (by contacting the authors of the original studies), (3) duplicate publications, (4) sponsors' and (5) authors' conflicts of interest, on the conclusions of the review, and (6) looked for ethical approval of the studies. Number (%) of reviewers who suspected misconduct are reported. The procedures applied were compared across journals. RESULTS: 80 (68%) reviewers confirmed their data. 59 (50%) reviews applied three or more procedures; 11 (9%) applied none. Unpublished trials were searched in 79 (66%) reviews. Authors of original studies were contacted in 73 (62%). Duplicate publications were searched in 81 (69%). 27 reviews (23%) reported sponsors of the included studies; 6 (5%) analysed their impact on the conclusions of the review. Five reviews (4%) looked at conflicts of interest of study authors; none of them analysed their impact. Three reviews (2.5%) looked at ethical approval of the studies. Seven reviews (6%) suspected misconduct; only 2 (2%) reported it explicitly. Procedures applied differed across the journals. CONCLUSIONS: Only half of the systematic reviews applied three or more of the six procedures examined. Sponsors, conflicts of interest of authors and ethical approval remain overlooked. Research misconduct is sometimes identified, but rarely reported. Guidance on when, and how, to report suspected misconduct is needed.

El conocimiento es un recurso invaluable que se genera en las organizaciones y que se encuentra en los individuos que la integran. Este recurso se convierte en un “capital vivo” en la medida en que se reconoce, se valora y se aprovecha. Una organización que sabe gestionar el conocimiento es capaz de crear las condiciones para que éste germine, se fortalezca, crezca y se esparza como semilla fértil. En este trabajo se da cuenta de un proyecto de gestión del conocimiento que se llevó a cabo con la intención de indagar en lo que una institución educativa como el ITESO puede hacer para convertirse en una organización capaz de aprovechar el conocimiento que se produce en su interior, particularmente aquel que se genera en torno de los procesos de formación docente, y lo que puede aportar a la gestión del conocimiento para favorecer el desarrollo de acciones orientadas a la innovación de los escenarios de formación para profesores. Se presenta un planteamiento teórico sobre la formación docente en la educación superior, sus retos y desafíos. De ello se deriva el problema intervenido desde la gestión del conocimiento, en el contexto específico del Programa de Formación para la Docencia de la Coordinación de Desarrollo Educativo del ITESO y la propuesta metodológica diseñada para llevar a cabo el proyecto. Se ofrece una perspectiva teórica de los modelos de gestión del conocimiento que se revisaron para su construcción, seguido del plan de trabajo elaborado para el logro de los propósitos planteados. ITESO, A. C.

Protein prenylation is an important post-translational modification. Many G-proteins, such as Ras and Rho, are prenylated in order to anchor them to the cell membrane. Protein farnesyltransferase (...

Si presenta la ricostruzione storica della ricerca petrolifera nell'alta Val d'Agri (Basilicata, Italia meridionale), dove è ubicato il più vasto giacimento attualmente esistente in Europa a terra ferma, e degli accesi dibattiti scientifici che la caratterizzavano. Si racconta come da fine ottocento essa si sviluppa basandosi sulle manifestazioni superficiali di idrocarburi, che riveleranno la presenza del piccolo e poco profondo campo petrolifero di Tramutola, sfruttato durante gli anni trenta e quaranta dall'Agip. Si narra quindi la successiva importante scoperta nelle imponenti strutture della piattaforma carbonatica, sepolta sotto l'affascinante e complessa catena degli Appennini meridionali. L'analisi dà la possibilità di illustrare e rivelare come i fondamentali fattori socio-culturali, economici, scientifici e tecnologici continuamente interagiscono fra loro, evolvendosi nel corso della storia.

Protein post-translational modifications increase the functional diversity of the proteome by covalently adding chemical moieties onto proteins thereby changing their activation state, cellular localization, interacting partners, and life cycle. Lipidation is one such modification that enables membrane association of naturally cytosolic proteins. Protein prenyltransferases irreversibly install isoprenoid units of varying length via a thioether linkage onto proteins that exert their cellular activity at membranes. Substrates of prenyltransferases are involved in countless signaling pathways and processes within the cell. Identification of new prenylation substrates, prenylation pathway regulators, and dynamic trafficking of prenylated proteins are all avenues of intense, ongoing research that are challenging, exciting, and have the potential to significantly advance the field in the near future.