Additive and Emergent Catalytic Properties of Dimeric Unnatural Amino Acid Derivatives: Aldol and Conjugate Additions

Different densely substituted L- and D-proline esters were prepared by asymmetric (3+2) cycloaddition reactions catalyzed by conveniently selected EhuPhos chiral ligands. The γ-nitro-2-alkoxycarbonyl pyrrolidines thus obtained in either their endo or exo forms were functionalized and coupled to yield the corresponding γ-dipeptides. The catalytic properties of these latter dimers were examined using aldol and conjugate additions as case studies. When aldol reactions were analyzed, an additive behavior in terms of stereocontrol was observed on going from the monomers to the dimers. In contrast, in the case of the conjugate additions between ketones and nitroalkenes, the monomers did not catalyze this reaction, whereas the different γ-dipeptides promoted the formation of the corresponding Michael adducts. Therefore, in this latter case emergent catalytic properties were observed for these novel γ-dipeptides based on unnatural proline derivatives. Under certain conditions stoichiometric amounts of ketone, acid and nitroalkene), formation of N-acyloxy-2-oxooctahydro-1H-indoles was observed.Financial support for this work was provided by the Spanish Ministerio de Ciencia e Innovación (MICINN-FEDER, Grants PID2019-104772GB-100 and RED2018-102387-T) and the Gobierno Vasco/Eusko Jaurlaritza (GV/EJ, Grant IT-1346-19). A.R.-O. thanks the Ministerio de Ciencia, Innovación y Universidades for her Ph.D. grant. M.d.G.R thanks the DIPC and UPV/EHU for her postdoctoral contract

Finding Nature in Your Neighborhood: A Field Mapping Protocol for Community Based Assessment of Greenspace Access

The Audubon Society of Portland and PSU Capstone students developed the Greenspace Access Point Field Mapping Protocol during the summer of 2013. The protocol was developed as a tool for a community-based approach to inventorying open space access points and to generate more accurate information on open space access in the Portland-Metro region

Applications of OralCDx ® methodology in the diagnosis of oral leukoplakia

Objective: We aim to evaluate the effectiveness of the brush biopsy technique using OralCDx ® (OralScan Laboratories Inc., Suffern, NY) as a new method for early diagnosis and control of a 'potentially malignant disorder' such as oral leukoplakia. Design of the study: We performed a study in which samples were taken using OralCDx ® on 24 patients who visited the Master of Oral Medicine, Oral Surgery and Implantology of the University of Santiago de Compostela between February 2009 and May 2010. These patients presented clinical and histological lesions that were consistent with oral leukoplakia. We evaluated the relationship between the keratinization degree of the lesions and cell representation; the diagnosis obtained through OralCDx ® and biopsies; and sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV). Results: 50% of patients were men and 50% women with an average age of 62.38 years. The Kappa coefficient relating keratinization of lesions and cell representation was 0.33, the OralCDx ® - biopsy diagnostic rate reached a Kappa value of 0.66, recording 72.7%, sensitivity and 92.3% specificity, PPV was 88.8%, while NPV reached 80%. Conclusions: cytology sampling with OralCDx ® showed high sensitivity and specificity values, which make it a good tool for monitoring oral leukoplakia, but nowadays the most reliable method that allows us to confirm the exact diagnosis of the lesions and their anatomical and pathological characteristics still is conventional biopsy using a surgical scalpel. © Medicina Oral S. L

Importance of the vaporization margin during CO2 laser treatment of oral leukoplakia: a survival study

Objectives: the main purpose of this study was to assess the response of oral leukoplakia to CO2 laser vaporization treatment, as well as determining possible factors that may affect recurrence of lesions. Materials and methods: a retrospective study was conducted, in which the medical records of patients who had been clinically and histologically diagnosed with oral leukoplakia and treated with CO2 laser between 1996 and 2019 at the Oral Medicine Teaching Unit of the Faculty of Dentistry of the University of Santiago de Compostela were reviewed. Results: fifty-eight patients were included: 36 female and 22 male subjects, with a mean age of 63.7 years old (SD ±13.1). The average follow-up time was 57.5 months (SD ±57.9). A relapse rate of 52.6% was determined. Of all the studied variables, the margin was the only one for which a statistically significant association with recurrence of lesions was demonstrated (p < 0.05). Conclusion: the vaporization of lesions using CO2 laser with a safety margin of at least 3 mm from the clinical limits of OL is a key factor in preventing recurrenceS

Impact of intermittent preventive treatment of malaria in pregnancy with dihydroartemisinin-piperaquine versus sulfadoxine-pyrimethamine on the incidence of malaria in infancy: a randomized controlled trial.

BACKGROUND: Intermittent preventive treatment of malaria during pregnancy (IPTp) with dihydroartemisinin-piperaquine (DP) significantly reduces the burden of malaria during pregnancy compared to sulfadoxine-pyrimethamine (SP), the current standard of care, but its impact on the incidence of malaria during infancy is unknown. METHODS: We conducted a double-blind randomized trial to compare the incidence of malaria during infancy among infants born to HIV-uninfected pregnant women who were randomized to monthly IPTp with either DP or SP. Infants were followed for all their medical care in a dedicated study clinic, and routine assessments were conducted every 4 weeks. At all visits, infants with fever and a positive thick blood smear were diagnosed and treated for malaria. The primary outcome was malaria incidence during the first 12 months of life. All analyses were done by modified intention to treat. RESULTS: Of the 782 women enrolled, 687 were followed through delivery from December 9, 2016, to December 5, 2017, resulting in 678 live births: 339 born to mothers randomized to SP and 339 born to those randomized to DP. Of these, 581 infants (85.7%) were followed up to 12 months of age. Overall, the incidence of malaria was lower among infants born to mothers randomized to DP compared to SP, but the difference was not statistically significant (1.71 vs 1.98 episodes per person-year, incidence rate ratio (IRR) 0.87, 95% confidence interval (CI) 0.73-1.03, p = 0.11). Stratifying by infant sex, IPTp with DP was associated with a lower incidence of malaria among male infants (IRR 0.75, 95% CI 0.58-0.98, p = 0.03) but not female infants (IRR 0.99, 95% CI 0.79-1.24, p = 0.93). CONCLUSION: Despite the superiority of DP for IPTp, there was no evidence of a difference in malaria incidence during infancy in infants born to mothers who received DP compared to those born to mothers who received SP. Only male infants appeared to benefit from IPTp-DP suggesting that IPTp-DP may provide additional benefits beyond birth. Further research is needed to further explore the benefits of DP versus SP for IPTp on the health outcomes of infants. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02793622 . Registered on June 8, 2016

Aplicativo para madres “Mom”

En el siguiente trabajo de investigación, se desarrolla la validación de la idea de negocio del aplicativo MOM. Se trata de una plataforma que ofrece el servicio de agenda para madres de familia, dentro de ella podrán encontrar diversos servicios como: niñeras, pediatras, psicólogos, tutores y establecimientos cercanos de salud. También, podrán encontrar recomendaciones para el cuidado de su menor hijo según su edad. Este proyecto está dirigido a las madres con hijos de 0 a 16 años, residentes de Lima Metropolitana y pertenecientes a los niveles socioeconómicos A y B. Se estableció la tendencia de crecimiento de servicios relacionados con madres de familia como marco de referencia para determinar el valor del modelo de negocio. Después del análisis de fuentes primarias y secundarias, se pudo determinar que el mercado de agendas online presenta un desarrollo significativo que debe ser aprovechado por el aplicativo mencionado, ya que hay competidores con la misma propuesta que el aplicativo que se presentará. La propuesta de valor del modelo de negocio ha demostrado viabilidad en el mercado y satisface las necesidades de nuevos consumidores. Por último, se desarrolló el plan financiero del proyecto con el objetivo de evaluar si el proyecto es viable. Se estableció la inversión inicial, los gastos administrativos y ventas, los costos operativos, también se definió una estimación de las ventas basada en el concierge. Finalmente, como resultado se tuvo que el proyecto es viable, debido a que, se obtuvo un VAN positivo, una TIR mayor a la tasa de descuento.In the following research work, the validation of the business idea of the MOM application is developed. It is a platform that offers an agenda service for mothers, where they can find different services such as babysitters, pediatricians, psychologists, tutors and nearby health facilities. Also, they will be able to find recommendations for the care of their youngest child according to their age. This project is aimed at mothers with children from 0 to 16 years old, residents of Metropolitan Lima and belonging to the A and B socioeconomic levels. The growth trend of services related to mothers was established as a frame of reference to determine the value of the business model. After the analysis of primary and secondary sources, it was determined that the online agendas market presents a significant development that should be taken advantage of by the mentioned application, since there aren't competitors with the same proposal as the application to be presented. The value proposition of the business model has demonstrated viability in the market and satisfies the needs of new consumers. Finally, the project's financial plan was developed in order to evaluate whether the project is viable. The initial investment, administrative and sales expenses, and operating costs were established, as well as an estimate of sales based on the concierge. Finally, as a result, the project was found to be viable, due to the fact that a positive NPV and an IRR higher than the discount rate were obtained.Trabajo de investigació

Antiretroviral agents and prevention of malaria in HIV-infected Ugandan children.

BACKGROUND: Human immunodeficiency virus (HIV) protease inhibitors show activity against Plasmodium falciparum in vitro. We hypothesized that the incidence of malaria in HIV-infected children would be lower among children receiving lopinavir-ritonavir-based antiretroviral therapy (ART) than among those receiving nonnucleoside reverse-transcriptase inhibitor (NNRTI)-based ART. METHODS: We conducted an open-label trial in which HIV-infected children 2 months to 5 years of age who were eligible for ART or were currently receiving NNRTI-based ART were randomly assigned to either lopinavir-ritonavir-based ART or NNRTI-based ART and were followed for 6 months to 2 years. Cases of uncomplicated malaria were treated with artemether-lumefantrine. The primary end point was the incidence of malaria. RESULTS: We enrolled 176 children, of whom 170 received the study regimen: 86 received NNRTI-based ART, and 84 lopinavir-ritonavir-based ART. The incidence of malaria was lower among children receiving the lopinavir-ritonavir-based regimen than among those receiving the NNRTI-based regimen (1.32 vs. 2.25 episodes per person-year; incidence-rate ratio, 0.59; 95% confidence interval [CI], 0.36 to 0.97; P=0.04), as was the risk of a recurrence of malaria after treatment with artemether-lumefantrine (28.1% vs. 54.2%; hazard ratio, 0.41; 95% CI, 0.22 to 0.76; P=0.004). The median lumefantrine level on day 7 after treatment for malaria was significantly higher in the lopinavir-ritonavir group than in the NNRTI group. In the lopinavir-ritonavir group, lumefantrine levels exceeding 300 ng per milliliter on day 7 were associated with a reduction of more than 85% in the 63-day risk of recurrent malaria. A greater number of serious adverse events occurred in the lopinavir-ritonavir group than in the NNRTI group (5.6% vs. 2.3%, P=0.16). Pruritus occurred significantly more frequently in the lopinavir-ritonavir group, and elevated alanine aminotransferase levels significantly more frequently in the NNRTI group. CONCLUSIONS: Lopinavir-ritonavir-based ART as compared with NNRTI-based ART reduced the incidence of malaria by 41%, with the lower incidence attributable largely to a significant reduction in the recurrence of malaria after treatment with artemether-lumefantrine. Lopinavir-ritonavir-based ART was accompanied by an increase in serious adverse events. (Funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development; ClinicalTrials.gov number, NCT00978068.)

Infant sex modifies associations between placental malaria and risk of malaria in infancy.

BACKGROUND: Placental malaria (PM) has been associated with a higher risk of malaria during infancy. However, it is unclear whether this association is causal, and is modified by infant sex, and whether intermittent preventive treatment in pregnancy (IPTp) can reduce infant malaria by preventing PM. METHODS: Data from a birth cohort of 656 infants born to HIV-uninfected mothers randomised to IPTp with dihydroartemisinin-piperaquine (DP) or Sulfadoxine-pyrimethamine (SP) was analysed. PM was categorized as no PM, active PM (presence of parasites), mild-moderate past PM (> 0-20% high powered fields [HPFs] with pigment), or severe past PM (> 20% HPFs with pigment). The association between PM and incidence of malaria in infants stratified by infant sex was examined. Causal mediation analysis was used to test whether IPTp can impact infant malaria incidence via preventing PM. RESULTS: There were 1088 malaria episodes diagnosed among infants during 596.6 person years of follow-up. Compared to infants born to mothers with no PM, the incidence of malaria was higher among infants born to mothers with active PM (adjusted incidence rate ratio [aIRR] 1.30, 95% CI 1.00-1.71, p = 0.05) and those born to mothers with severe past PM (aIRR 1.28, 95% CI 0.89-1.83, p = 0.18), but the differences were not statistically significant. However, when stratifying by infant sex, compared to no PM, severe past PM was associated a higher malaria incidence in male (aIRR 2.17, 95% CI 1.45-3.25, p < 0.001), but not female infants (aIRR 0.74, 95% CI 0.46-1.20, p = 0.22). There were no significant associations between active PM or mild-moderate past PM and malaria incidence in male or female infants. Male infants born to mothers given IPTp with DP had significantly less malaria in infancy than males born to mothers given SP, and 89.7% of this effect was mediated through prevention of PM. CONCLUSION: PM may have more severe consequences for male infants, and interventions which reduce PM could mitigate these sex-specific adverse outcomes. More research is needed to better understand this sex-bias between PM and infant malaria risk. Trial registration ClinicalTrials.gov, NCT02793622. Registered 8 June 2016, https://clinicaltrials.gov/ct2/show/NCT02793622