Problems Affecting Labor

Much experimental work has been devoted in comparing the folding behavior of proteins sharing the same fold but different sequence. The recent design of proteins displaying very high sequence identities but different 3D structure allows the unique opportunity to address the protein-folding problem from a complementary perspective. Here we explored by ℙ-value analysis the pathways of folding of three different heteromorphic pairs, displaying increasingly high-sequence identity (namely, 30%, 77%, and 88%), but different structures called G A (a 3-α helix fold) and G B (an α/β fold). The analysis, based on 132 site-directed mutants, is fully consistent with the idea that protein topology is committed very early along the pathway of folding. Furthermore, data reveals that when folding approaches a perfect two-state scenario, as in the case of the G A domains, the structural features of the transition state appear very robust to changes in sequence composition. On the other hand, when folding is more complex and multistate, as for the G Bs, there are alternative nuclei or accessible pathways that can be alternatively stabilized by altering the primary structure. The implications of our results in the light of previous work on the folding of different members belonging to the same protein family are discussed

Haemoglobin Engineering: For fun and money

AbstractThe recent transplantation of an unusual allosteric effect from crocodile to human haemoglobin has implications for both molecular evolution and the engineering of artificial blood substitutes

The reaction of Pseudomonas nitrite reductase and nitrite. A stopped-flow and EPR study.

The reaction between reduced Pseudomonas nitrite reductase and nitrite has been studied by stopped-flow and rapid-freezing EPR spectroscopy. The interpretation of the kinetics at pH 8.0 is consistent with the following reaction mechanism (where k1 and k3 much greater than k2). [formula: see text] The bimolecular step (Step 1) is very fast, being lost in the dead time of a rapid mixing apparatus; the stoichiometry of the complex has been estimated to correspond to one NO2- molecule/heme d1. The final species is the fully reduced enzyme with NO bound to heme d1; and at all concentrations of nitrite, there is no evidence for dissociation of NO or for further reduction of NO to N2O. Step 2 is assigned to an internal electron transfer from heme c to reduced NO-bound heme d1 occurring with a rate constant of 1 s-1; this rate is comparable to the rate of internal electron transfer previously determined when reducing the oxidized enzyme with azurin or cytochrome c551. When heme d1 is NO-bound, the rate at which heme c can accept electrons from ascorbate is remarkably increased as compared to the oxidized enzyme, suggesting an increase in the redox potential of the latter heme

Long-term prediction of adherence to continuous positive air pressure therapy for the treatment of moderate/severe obstructive sleep apnea syndrome

BACKGROUND: Continuous positive airway pressure (CPAP) therapy is a highly effective treatment for obstructive sleep apnea syndrome (OSAS). However, poor adherence is a limiting factor, and a significant proportion of patients are unable to tolerate CPAP. The aim of this study was to determine predictors of long-term non-compliance with CPAP. METHODS: CPAP treatment was prescribed to all consecutive patients with moderate or severe OSAS (AHI ≥15 events/h) (n = 295) who underwent a full-night CPAP titration study at home between February 1, 2002 and December 1, 2016. Adherence was defined as CPAP use for at least 4 h per night and five days per week. Subjects had periodical follow-up visits including clinical and biochemical evaluation and assessment of adherence to CPAP. RESULTS: Median follow-up observation was 74.8 (24.2/110.9) months. The percentage of OSAS patients adhering to CPAP was 41.4% (42.3% in males and 37.0% in females), and prevalence was significantly higher in severe OSAS than in moderate (51.8% vs. 22.1%; p < 0.001; respectively). At multivariate analysis, lower severity of OSAS (HR = 0.66; CI 95 0.46-0.94) p < 0.023), cigarette smoking (HR = 1.72; CI 95 1.13-2.61); p = 0.011), and previous cardiovascular events (HR = 1.95; CI 95 1.03-3.70; p = 0.04) were the only independent predictors of long-term non-adherence to CPAP after controlling for age, gender, and metabolic syndrome. CONCLUSIONS: In our cohort of patients with moderate/severe OSAS who were prescribed CPAP therapy, long-term compliance to treatment was present in less than half of the patients. Adherence was positively associated with OSAS severity and negatively associated with cigarette smoking and previous cardiovascular events at baseline

Kinetics of Reduction of Cytochrome \u3ci\u3ec\u3c/i\u3e Oxidase by Dithionite and the Effect of Hydrogen Peroxide

The reduction of cytochrome c oxidase by dithionite was reinvestigated with a flow-flash technique and with varied enzyme preparations. Since cytochrome a3 may be defined as the heme in oxidase which can form a photolabile CO adduct in the reduced state, it is possible to follow the time course of cytochrome a3 reduction by monitoring the onset of photosensitivity. The onset of photosensitivity and the overall rate of heme reduction were compared for Yonetani and Hartzell-Beinert preparations of cytochrome c oxidase and for the enzyme isolated from blue marlin and hammer-head shark. For all of these preparations the faster phase of heme reduction, which is dithionite concentration-dependent, is almost completed when the fraction of photosensitive material is still small. We conclude that cytochrome a3 in the resting enzyme is consistently reduced by an intramolecular electron transfer mechanism. To determine if this is true also for the pulsed enzyme, we examined the time course of dithionite reduction of the peroxide complex of the pulsed enzyme. It has been previously shown that pulsed cytochrome c oxidase can interact with H2O2 and form a stable room temperature peroxide adduct (Bickar, D., Bonaventura, J., and Bonaventura, C. (1982) Biochemistry 21, 2661-2666). Rather complex kinetics of heme reduction are observed when dithionite is added to enzyme preparations that contain H2O2. The time courses observed provide unequivocal evidence that H2O2 can, under these conditions, be used by cytochrome c oxidase as an electron acceptor. Experiments carried out in the presence of CO show that a direct dithionite reduction of cytochrome a3 in the peroxide complex of the pulsed enzyme does not occur

Aspectos de la biología y el control de Eleusine indica y Eleusine tristachya en barbechos y en el cultivo de soja

Las malezas son plantas que interfieren con la actividad productiva agrícola, están adaptadas a los ambientes modificados por el hombre y constituyen una de las principales causas de pérdida de rendimientos de los cultivos. En Argentina se ha incrementado el problema de malezas gramíneas de difícil control con glifosato y graminicidas en el barbecho y en el cultivo de soja. Es necesario generar conocimientos en la región sojera núcleo sobre las malezas de gran difusión como E. indica y especialmente de especies problemáticas de reciente aparición como E. tristachya de la que no se dispone de información a nivel mundial. Los objetivos de esta tesis fueron estudiar la bioecología y el control de E. indica y E. tristachya en el barbecho y en el cultivo de soja, abordando i) la caracterización de la sensibilidad de biotipos a glifosato y graminicidas en distintos estados de crecimiento; ii) la competencia entre las malezas y el cultivo de soja a través del análisis de la complementariedad de recursos (RYT) y la habilidad competitiva (IA) mediante la biomasa y producción de semillas; y de la altura y la tasa de crecimiento relativo (RGR) y producción de biomasa (TDM); iii) la dinámica poblacional con y sin herbicidas, la emergencia y mortalidad por cohortes, la producción de biomasa, la producción y longevidad de semillas; iv) el estudio de factores que afectan la absorción de estos herbicidas en dos estados de crecimiento de las malezas. Los siguientes estudios se realizaron en el campo experimental de la Facultad de Cs. Agrarias UNR en Zavalla, Santa Fe: Se determinó entre 2016 y 2018, el efecto de los herbicidas (glifosato, haloxifop-metil y cletodim) en el corto plazo (biomasa 30 días después de la aplicación-DDA-) y en el largo plazo (número de macollos, altura y producción de semilla - rebrote 330 DDA) – utilizando un diseño factorial en macetas con tres biotipos de E. tristachya y un biotipo de E. indica y se les aplicó 10 dosis de herbicidas en el estado de plántula, vegetativo y reproductivo. Los datos de biomasa fueron ajustados a un modelo log-logístico. El control de E. indica en el estado de plántula y de los biotipos de E. tristachya en los estados de plántula y vegetativo en el corto plazo se logró con ED50 y ED90 menores o iguales a las recomendadas para todos herbicidas. En cambio, E. indica en los estados vegetativo y reproductivo y E. tristachya en el estado reproductivo requirió mayores dosis con los tres herbicidas. El control a largo plazo de E. tristachya a la dosis recomendada o inferior no es aceptable en el estado reproductivo ya que se observó rebrote con todos los herbicidas. Se estableció un banco artificial de semillas a partir del cual se identificaron tres cohortes diferentes todos los años. En E. indica y E. tristachya en 2016 no hubo diferencias en el número de plantas con y sin herbicida y la segunda cohorte presentó el mayor número de emergencias. En 2017 en ambas especies hubo mayor número de plantas sin herbicidas. La tercera cohorte produjo menos plantas que las dos primeras. Sin aplicación de herbicida en la primera cohorte, la mortalidad de E. indica en 2016 fue menor que en E. tristachya. En 2017 no hubo diferencias. En la segunda y tercera cohorte la mortalidad fue del 100 %, lo que se atribuye a la competencia ejercida por el canopeo, ya que en el momento de emergencia de la segunda cohorte, la soja se encontraba en el estado V3-V4. El estudio de la competencia se realizó en macetas a la intemperie durante 2016 y 2017 mediante un diseño aditivo. La cantidad de semillas producidas por planta fue superior para E. indica vs E. tristachya. Ambos años, RYTbiomasa y RYTsemillas entre malezas no fue significativamente diferente de 1, indicando competencia completa o ausencia de complementariedad de recursos. La biomasa de E. indica en presencia de E. tristachya en relación con su monocultura creció 80 %, mientras que E. tristachya en presencia de E. indica aumentó 26 %. Por lo tanto, la reducción del crecimiento debido a la competencia fue menor para E. indica. En los estadíos R3 y R5 de la soja, E. indica presentó mayor altura que el cultivo y que E. tristachya. RGR entre ambas especies de Eleusine no difirió, excepto a los 7 días después de la emergencia (DDE) y en los momentos de RGR máximo para cada especie (0,37 a 42 DDE en E. indica y 0,32 a 49 DDE en E. tristachya). Estos resultados también señalan que E. indica alcanzó su máximo RGR antes que E. tristachya. La TDM al final del ciclo de crecimiento en E. indica es 90 g superior que la de E. tristachya. En la Facultad de Cs. Agrarias UNL en Esperanza se realizó la caracterización morfológica y anatómica foliar de Eleusine indica (Zavalla) y de tres biotipos de Eleusine tristachya (Aranguren, Crespo y Zavalla) en estado vegetativo y reproductivo, a través de la cuantificación de tricomas, estomas, y la cantidad de ceras epicuticulares; y de la evaluación del daño anatómico foliar a las 96 h post aplicación de glifosato y graminicidas. La densidad estomática aumentó en todos los casos en el estado reproductivo en relación al estado vegetativo. La cantidad de ceras epicuticulares en estado vegetativo y reproductivo fue mayor para los biotipos de E. tristachya Aranguren y Crespo. No se hallaron diferencias entre estados de crecimiento para cada especie y biotipo. Todos los herbicidas produjeron cambios en la anatomía foliar de las malezas, principalmente en el espesor de los tejidos de la hoja. La integración de los conocimientos generados sobre la bioecología y control de Eleusine indica y Eleusine tristachya suscitará el diseño de estrategias y tácticas de control que de manera integrada permitan un abordaje sustentable de los agroecosistemas de la región pampeana.Weeds are plants that interfere with agricultural productive activity, are adapted to man modified environments and constitute one of the main causes of loss of crop yields. In Argentina, concern about grassy annual weeds control with glyphosate and graminicides in fallow and soybean cultivation has increased lately. It is necessary to generate knowledge in the central soybean region about widespread weeds such as E. indica and especially of problematic species of recent appearance such as E. tristachya for which there is no information available worldwide. The objectives of this thesis were to study the bioecology and control of E. indica and E. tristachya in the fallow and in soybean, addressing i) the characterization of the biotypes sensitivity to glyphosate and graminicide in different growth stages; ii) competition between weeds and soybean through the analysis of resource complementarity (RYT), competitive ability (AI), and biomass and seed production; and height and relative growth rate (RGR) and biomass production determined by total dry matter (TDM); iii) population dynamics with and without herbicides, emergence and mortality in each cohort, biomass and seed production and seed longevity; iv) the study of factors that affect the absorption of glyphosate and graminicides in two stages of weed growth. The following studies were conducted in the experimental field of the Facultad Cs. Agrarias UNR at Zavalla, Santa Fe: Between 2016 and 2018, the effect of herbicides (glyphosate, haloxyfop-methyl and cletodim) was determined in the short term (biomass 30 days after application-DDA-) and in the long term (number of tillers, height and production of seed - regrowth 330 DDA) - using a factorial design in pots with three biotypes of E. tristachya and a biotype of E. indica and 10 doses of herbicides were applied in the seedling, vegetative and reproductive stage. The biomass data were adjusted to a log-logistic model. The control of E. indica at the seedling stage and of the biotypes of E. tristachya at the seedling and vegetative stages in the short term was achieved with ED50 and ED90 less than or equal to those recommended for all herbicides. In contrast, E. indica at the vegetative and reproductive stages and E. tristachya at the reproductive stage required higher doses with the three herbicides. Long-term control of E. tristachya at the recommended or lower dose is not acceptable in the reproductive stage since regrowth was observed with all herbicides. An artificial seed bank was established, and three different cohorts were identified every year. For E. indica and E. tristachya in 2016 there were no differences in the number of plants with and without herbicide and the second cohort showed the highest emergence. In 2017 in both species density was higher without herbicides. The third cohort produced fewer plants than the first two. Without herbicide application in the first cohort, the mortality of E. indica in 2016 was lower than for E. tristachya. In 2017 there were no differences. In the second and third cohort the mortality was 100%, which is attributed to the competition exerted by the canopy, since at the time of emergence of the second cohort, soybean were in the V3-V4 stages. The study of the competition was carried out outdoors in pots during 2016 and 2017 using an additive design. The quantity of seeds produced per plant was higher for E. indica vs. E. tristachya. Both years, RYTbiomass and RYTseeds among weeds was not significantly different from 1, indicating complete competition or lack of resource complementarity. The biomass of E. indica in the presence of E. tristachya in relation to its monoculture was 80%, while E. tristachya in the presence of E. indica was 26%. Therefore, the reduction in growth due to competition was lower for E. indica. In R3- R5 of soybean stages, E. indica showed greater height than the crop and than E. tristachya. RGR did not differ between both species of Eleusine, except at 7 days after emergence (DAE) and at periods of maximum RGR for each species (0.37 to 42 DDE in E. indica and 0.32 to 49 DDE in E. tristachya). These results also indicate that E. indica reached its maximum RGR before E. tristachya. TDM at the end of the growing season was 90 g higher for E. indica than for E. tristachya. At Facultad Cs. Agrarias UNL at Esperanza, the morphological and anatomical characterization of Eleusine indica (Zavalla) and three biotypes of Eleusine tristachya (Aranguren, Crespo and Zavalla) were carried out in a vegetative and reproductive stages, through the quantification of trichomes, stomata, and amount of epicuticular waxes; and the evaluation of the anatomical damage foliar at 96 h post application of glyphosate and graminicides. Stomatic density increased in all cases in the reproductive relative to the vegetative stage. The amount of epicuticular waxes in the vegetative and the reproductive stages were higher for the biotypes of E. tristachya Aranguren and Crespo. No differences were found between growth stages for each species and biotype. All herbicides produced changes in the leaf anatomy of the weeds, mainly in the thickness of the leaf tissues. Integration of the results obtained about the bioecology and control of Eleusine indica and Eleusine tristachya will contribute to the design of control strategies and tactics so as to allow a sustainable management of the agroecosystems of the soybean central region.Fil: Apellido, Nombre. Universidad Nacional de Rosario. Facultad de Ciencias Agrarias; ArgentinaFil: Brunori, Alejandro M.. Universidad Nacional de Rosario. Facultad de Ciencias Agrarias; Argentin

Model-based recursive partitioning to estimate unfair health inequalities in the United Kingdom Household Longitudinal Study

We measure unfair health inequality in the UK using a novel data- driven empirical approach. We explain health variability as the result of circumstances beyond individual control and health-related behaviours. We do this using model-based recursive partitioning, a supervised machine learning algorithm. Unlike usual tree-based algorithms, model-based recursive partitioning does identify social groups with different expected levels of health but also unveils the heterogeneity of the relationship linking behaviors and health outcomes across groups. The empirical application is conducted using the UK Household Longitudinal Study. We show that unfair inequality is a substantial fraction of the total explained health variability. This finding holds no matter which exact definition of fairness is adopted: using both the fairness gap and direct unfairness measures, each evaluated at different reference values for circumstances or effort

An unusual Erdheim-Chester disease with orbital involvement: A case report

Erdheim-Chester disease is a rare non-Langerhans cell histiocytosis with multiorgan involvement and a specific tropism for perivascular and fatty connective tissue, of unclear origin, with poor response to therapy. Its identification is difficult because of the variable clinical presentation and its lack of knowledge. We report the case of a 63-years-old woman, with a history of bilateral orbital pseudotumor, who comes to our attention because of progressively worsening asthenia, vomiting and systemic inflammation. Total body computerized tomography scan showed a volumetric increase of choroid plexus of the temporal horn of the left lateral ventricle, presence of solid retrobulbar tissue at the level of both maxillary sinuses, lung fibrosis, and retroperitoneal and peri-aortic infiltration. The association of these signs addressed to a diagnosis of Erdheim-Chester disease. Thus, although extremely rare, the diagnosis of Erdheim-Chester disease must be considered in the case of bilateral retro-orbital tumors and multisystemic involvement

Practical indications for the prevention and management of SARS-CoV-2 in ambulatory dialysis patients : lessons from the first phase of the epidemics in Lombardy

Confronting the SARS-CoV-2 outbreak has allowed us to appreciate how efficiently highly-resourced settings can respond to crises. However even such settings are not prepared to deal with the situation, and lessons are only slowly being learnt. There is still an urgent need to accelerate protocols that lead to the implementation of rapid point-of-care diagnostic testing and effective antiviral therapies. In some high-risk populations, such as dialysis patients, where several individuals are treated at the same time in a limited space and overcrowded areas, our objective must be to ensure protection to patients, the healthcare team and the dialysis ward. The difficult Italian experience may help other countries to face the challenges. The experience of the Lombardy underlines the need for gathering and sharing our data to increase our knowledge and support common, initially experience-based, and as soon as possible evidence-based position to face this overwhelming crisis