Stereoselective Synthesis of Densely Substituted Pyrrolidines via a [3 + 2] Cycloaddition Reaction between Chiral N-tert-Butanesulfinylazadienes and Azomethine Ylides

The N-tert-butanesulfinylimine group behaves as a suitable electron-withdrawing group in 1-azadienes, allowing the diastereoselective synthesis of densely substituted pyrrolidines by 1,3-dipolar cycloadditions (1,3-DCs) with azomethylene ylides. The use of Ag2CO3 as catalyst has allowed one to obtain a wide variety of proline derivatives with high regio- and diastereoselectivities. Subsequent efficient transformations provide valuable proline derivatives, some of which can be used as organocatalysts. The influence of the N-tert-butanesulfinyl group on the diastereoselectivity was studied by computational methods.We gratefully acknowledge financial support from the Spanish Ministerio de Ciencia, Innovación y Universidades (project RED2018-102387-T), the Spanish Ministerio de Economía, Industria y Competitividad, Agencia Estatal de Investigación (AEI) and Fondo Europeo de Desarrollo Regional (FEDER, EU) (projects CTQ2017-82935-P and PID2019-107268GB-I00), the Generalitat Valenciana (IDIFEDER/2021/013, GVA-COVID19/2021/079, CIDEGENT/2020/058, CIAPOT/2022/11, and APOTIP/2021/020), Medalchemy S. L. (Medalchemy-18T), and the University of Alicante (VIGROB-068, UAUSTI21-05)

Architectural characterization of a delta-front reservoir analogue combining Ground Penetrating Radar and Electrical Resistivity Tomography : Roda Sandstone (Lower Eocene, Graus-Tremp basin, Spain)

Three-dimensional reconstruction of reservoir analogues can be improved combining data from different geophysical methods. Ground Penetrating Radar (GPR) and Electrical Resistivity Tomography (ERT) data are valuable tools, since they provide subsurface information from internal architecture and facies distribution of sedimentary rock bodies, enabling the upgrading of depositional models and heterogeneity reconstruction. The Lower Eocene Roda Sandstone is a well-known deltaic complex widely studied as a reservoir analogue that displays a series of sandstone wedges with a general NE to SW progradational trend. To provide a better understanding of internal heterogeneity of a 10m-thick progradational delta-front sandstone unit, 3D GPR data were acquired. In addition, common midpoints (CMP) to measure the sandstone subsoil velocity, test profiles with different frequency antennas (25, 50 and 100MHz) and topographic data for subsequent correction in the geophysical data were also obtained. Three ERT profiles were also acquired to further constrain GPR analysis. These geophysical results illustrate the geometry of reservoir analogue heterogeneities both depositional and diagenetic in nature, improving and complementing previous outcrop-derived data. GPR interpretation using radar stratigraphy principles and attributes analysis provided: 1) tridimensional geometry of major stratigraphic surfaces that define four units in the GPR Prism, 2) image the internal architecture of the units and their statistical study of azimuth and dips, useful for a quick determination of paleocurrent directions. These results were used to define the depositional architecture of the progradational sandbody that shows an arrangement in very-high-frequency sequences characterized by clockwise paleocurrent variations and decrease of the sedimentary flow, similar to those observed at a greater scale in the same system. This high-frequency sequential arrangement has been attributed to the autocyclic dynamics of a supply-dominated delta-front where fluvial and tidal currents are in competition. The resistivity models enhanced the viewing of reservoir quality associated with cement distribution caused by depositional and early diagenetic processes related to the development of transgressive and regressive systems tracts in high-frequency sequences

Cutaneous, genital and oral lichen planus : a descriptive study of 274 patients

Lichen planus (LP) is a chronic autoimmune disease that affects the oral mucosa as well as the skin, genital mucosa and other sites. Objective: to evaluate the correlation between oral, genital and cutaneous lichen planus, in a sample of LP patients. This descriptive study reviewed 274 clinical histories of patients, who all presented histological confirmation of lichen planus verified by a pathologist, attending research centers in Barcelona. A total of 40 LP patients (14.59%) presented genital lesions. Of 131 patients with cutaneous LP (47.8%), the most commonly affected zones were the body?s flexor surfaces, representing 60.1% of cases. 24% of patients (n=55) related the start of the lesions with previous stress events. Of the 131 subjects with cutaneous lesions, 19% (n=25) also presented oral lichen planus (OLP). Of the total sample, 53.6% (n=147) of patients presented oral lesions. The systemic diseases most commonly associated with this patient sample were psychological problems such as stress, anxiety and depression (48%), hypertension (27%), gastric problems (12%), and diabetes (9.7%). A family history of lichen planus was found in only 2 cases (0,72%) out of the total of 274. Any patient with OLP should undergo a thorough history and examination to investigate potential extraoral manifestations. The fact that 37 patients with OLP in this patient series were identified with simultaneous involvement at more than one site highlights the need for thorough evaluation and multidisciplinary approaches to this disease

An Overview of the Rotational Behavior of Metal--Poor Stars

The present paper describes the behavior of the rotational velocity in metal--poor stars ([Fe/H]<-0.5 dex) in different evolutionary stages, based on Vsini values from the literature. Our sample is comprised of stars in the field and some Galactic globular clusters, including stars on the main sequence, the red giant branch (RGB), and the horizontal branch (HB). The metal--poor stars are, mainly, slow rotators, and their Vsini distribution along the HR diagram is quite homogeneous. Nevertheless, a few moderate to high values of Vsini are found in stars located on the main sequence and on the HB. We show that the overall distribution of Vsini values is basically independent of metallicity for the stars in our sample. In particular, the fast-rotating main sequence stars in our sample present similar rotation rates as their metal-rich counterparts, suggesting that some of them may actually be fairly young, in spite of their low metallicity, or else that at least some of them would be better classified as blue straggler stars. We do not find significant evidence of evolution in Vsini values as a function of position on the RGB; in particular, we do not confirm previous suggestions that stars close to the RGB tip rotate faster than their less evolved counterparts. While the presence of fast rotators among moderately cool blue HB stars has been suggested to be due to angular momentum transport from a stellar core that has retained significant angular momentum during its prior evolution, we find that any such transport mechanisms must likely operate very fast as the star arrives on the zero-age HB (ZAHB), since we do not find a link between evolution off the ZAHB and Vsini values. We present an extensive tabulation of all quantities discussed in this paper, including rotation velocities, temperatures, gravitieComment: 22 pages, 10 figure

Women's attitudes towards mechanisms of action of family planning methods: survey in primary health centres in Pamplona, Spain

Background: Informed consent in family planning includes knowledge of mechanism of action. Some methods of family planning occasionally work after fertilization. Knowing about postfertilization effects may be important to some women before choosing a certain family planning method. The objective of this survey is to explore women's attitudes towards postfertilization effects of family planning methods, and beliefs and characteristics possibly associated with those attitudes. Methods: Cross-sectional survey in a sample of 755 potentially fertile women, aged 18–49, from Primary Care Health Centres in Pamplona, Spain. Participants were given a 30-item, selfadministered, anonymous questionnaire about family planning methods and medical and surgical abortion. Logistic regression was used to identify variables associated with women's attitudes towards postfertilization effects. Results: The response rate was 80%. The majority of women were married, held an academic degree and had no children. Forty percent of women would not consider using a method that may work after fertilization but before implantation and 57% would not consider using one that may work after implantation. While 35.3% of the sample would stop using a method if they learned that it sometimes works after fertilization, this percentage increased to 56.3% when referring to a method that sometimes works after implantation. Women who believe that human life begins at fertilization and those who consider it is important to distinguish between natural and induced embryo loss were less likely to consider the use of a method with postfertilization effects. Conclusion: Information about potential postfertilization effects of family planning methods may influence women's acceptance and choice of a particular family planning method. Additional studies in other populations are necessary to evaluate whether these beliefs are important to those populations

Safety and Efficacy of a New Synthetic Material Based on Monetite, Silica Gel, PS-Wallastonite, and a Hydroxyapatite Calcium Deficient: A Randomized Comparative Clinic Trial

Background and Objectives: Maxillary bone defects related to post-extraction alveolar ridge resorption are usual. These defects may lead to failure in further surgical implant phases given the lack of bone volume to perform the dental implant. The objective of this clinical assay was to evaluate the safety and efficacy of an experimental synthetic bone substitute in the preservation of post-extraction maxillary alveoli. Materials and Methods: 33 voluntary patients who had at least one maxillary premolar tooth that was a candidate for exodontia (n = 39) and subsequent implant rehabilitation participated. The regenerated alveoli were monitored by means of periodic clinical examinations (days 9 ± 1, 21 ± 4, 42 ± 6, and 84 ± 6), measuring the height and width of the alveolar crest (days 0 and 180 ± 5), measurement of radiodensity using tomographic techniques (days 0–5 and 175 ± 5), and histological examination of biopsies collected at 180 ± 5 days. Results: No significant differences were observed during the entire follow-up period between the two groups with respect to the safety variables studied. A variation in width of −0.9 ± 1.3 mm and −0.6 ± 1.5 mm, and a variation in height of −0.1 ± 0.9 mm and −0.3 ± 0.7 mm was observed for experimental material Sil-Oss® and Bio-Oss®, respectively. The radiodensity of the alveoli regenerated with the experimental material was significantly lower than that corresponding to Bio-Oss®. However, the histological study showed greater osteoid matrix and replacement of the material with newformed bone in the implanted beds with the experimental material. Conclusions: Both materials can be used safely and proved equally effective in maintaining alveolar flange dimensions, they are also histologically biocompatible, bioactive and osteoconductive. The experimental material showed the advantage of being resorbable and replaced with newformed bone, in addition to promoting bone regeneration

Stereoselective Synthesis of Biheterocycles Containing Indole and 5,6-Dihydropyridin-2(1H)-one or α-Methylene-β-butyrolactam Scaffolds

Indium-mediated allylation of N-tert-butanesulfinyl imines derived from indole-2 and 3-carbaldehydes 3 and 5 with allylic bromides 6, proceed with high diastereoselectivity. Homoallylic amide derivatives 13 and 14 are transformed into dihydropyridinones 15 and 16, upon successive desulfinylation, N-acylation with acryloyl chloride and ring-closing-metathesis. Desulfinylation of amine ester derivatives 17 and 18, obtained when ethyl 2-(bromomethyl)acrylate (6 b) is used as the allylating reagent, lead to the corresponding α-methylene-γ-butyrolactams 19 and 20, in modest yields.We thank the continuous financial support from the Spanish Ministerio de Economía y Competitividad (MINECO; project CTQ2016-81797-REDC, CTQ2017-85093-P), Ministerio de Ciencia, Innovación y Universidades (RED2018-102387-T, PID2019-107268GB-100), FEDER, the Generalitat Valenciana (IDIFEDER/2021/013, CIDEGENT/2020/058, APOTIP/2021/020), the University of Alicante (VIGROB-068), and the Ministère de l’Enseignement Supérieur et de la Recherche Scientifique Algérienne; Direction de la Coopération et des Echanges Interuniversitaires; Programme de Formation Résidentielle à l’Étranger au titre de l’année universitaire 2019/2020: Programme National Exceptionnel (PNE)

Development of a thermosensitive hydrogel based on Polaxamer 407 and gellan gum with inclusion complexes (Sulfobutylated-β-cyclodextrin-Farnesol) as a local drug delivery system

This work proposes the development of a thermosensitive local drug release system based on Polaxamer 407, also known as Pluronic® F-127 (PF-127), Gellan Gum (GG) and the inclusion complex Sulfobutylated-β-cyclodextrin (CD) with Farnesol (FOH). Rheological properties of the hydrogels and their degradation were studied. According to the rheological results, a solution of 20% w/v of PF-127 forms a strong gel with a gelling temperature of about 25 °C (storage modulus of 15,000 Pa). The addition of the GG increased the storage modulus (optimal concentration of 0.5 % w/v) twofold without modifying the gelling temperature. Moreover, including 0.5% w/v of GG also increased 6 times the degradation time of the hydrogel. Regarding the inclusion complex, the addition of free CD decreased the viscosity and the gel strength since polymer chains were included in CD cavity without affecting the gelling temperature. Contrarily, the inclusion complex CD-FOH did not significantly modify any property of the formulation because the FOH was hosted in the CD. Furthermore, a mathematical model was developed to adjust the degradation time. This model highlights that the addition of the GG decreases the number of released chains from the polymeric network (which coincides with an increase in the storage modulus) and that the free CD reduces the degradation rate, protecting the polymeric chains. Finally, FOH release was quantified with a specific device, that was designed and printed for this type of system, observing a sustainable drug release (similar to FOH aqueous solubility, 8 μM) dependent on polymer degradation

Study protocol of cost-effectiveness and cost-utility of a biopsychosocial multidisciplinary intervention in the evolution of non-specific sub-acute low back pain in the working population: cluster randomised trial.

This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.Background: Low back pain (LBP), with high incidence and prevalence rate, is one of the most common reasons to consult the health system and is responsible for a significant amount of sick leave, leading to high health and social costs. The objective of the study is to assess the cost-effectiveness and cost-utility analysis of a multidisciplinary biopsychosocial educational group intervention (MBEGI) of non-specific sub-acute LBP in comparison with the usual care in the working population recruited in primary healthcare centres. Methods/design: The study design is a cost-effectiveness and cost-utility analysis of a MBEGI in comparison with the usual care of non-specific sub-acute LBP.Measures on effectiveness and costs of both interventions will be obtained from a cluster randomised controlled clinical trial carried out in 38 Catalan primary health care centres, enrolling 932 patients between 18 and 65 years old with a diagnosis of non-specific sub-acute LBP. Effectiveness measures are: pharmaceutical treatments, work sick leave (% and duration in days), Roland Morris disability, McGill pain intensity, Fear Avoidance Beliefs (FAB) and Golberg Questionnaires. Utility measures will be calculated from the SF-12. The analysis will be performed from a social perspective. The temporal horizon is at 3 months (change to chronic LBP) and 12 months (evaluate the outcomes at long term. Assessment of outcomes will be blinded and will follow the intention-to-treat principle. Discussion: We hope to demonstrate the cost-effectiveness and cost-utility of MBEGI, see an improvement in the patients' quality of life, achieve a reduction in the duration of episodes and the chronicity of non-specific low back pain, and be able to report a decrease in the social costs. If the intervention is cost-effectiveness and cost-utility, it could be applied to Primary Health Care Centres. Trial registration: ISRCTN: ISRCTN5871969