Reaction monitoring via benchtop nuclear magnetic resonance spectroscopy: A practical comparison of on-line stopped-flow and continuous-flow sampling methods

The ability for nuclear magnetic resonance (NMR) spectroscopy to provide quantitative, structurally rich information makes this spectroscopic technique an attractive reaction monitoring tool. The practicality of NMR for this type of analysis has only increased in the recent years with the influx of commercially available benchtop NMR instruments and compatible flow systems. In this study, we aim to compare 19F NMR reaction profiles acquired under both on-line continuous-flow and stopped-flow sampling methods, with modern benchtop NMR instrumentation, and two reaction systems: a homogeneous imination reaction and a biphasic activation of a carboxylic acid to acyl fluoride. Reaction trends with higher data density can be acquired with on-line continuous-flow analyses, and this work highlights that representative reaction trends can be acquired without any correction when monitoring resonances with a shorter spin–lattice relaxation time (T1), and with the used flow conditions. On-line stopped-flow analyses resulted in representative reaction trends in all cases, including the monitoring of resonances with a long T1, without the need of any correction factors. The benefit of easier data analysis, however, comes with the cost of time, as the fresh reaction solution must be flowed into the NMR system, halted, and time must be provided for spins to become polarized in the instrument's external magnetic field prior to spectral measurement. Results for one of the reactions were additionally compared with the use of a high-field NMR.publishedVersio

Understanding the conservation-genetics gap in Latin America: challenges and opportunities to integrate genetics into conservation practices

Introduction: Integrating genetic data into conservation management decisions is a challenging task that requires strong partnerships between researchers and managers. Conservation in Latin America is of crucial relevance worldwide given the high biodiversity levels and the presence of hotspots in this region.Methods: We conducted a survey across Latin America to identify gaps and opportunities between genetic researchers and conservation managers. We aimed to better understand conservation managers’ points of view and how genetic research could help conservation practitioners to achieve their goals, by implementing genetic assessments that could effectively inform conservation practices. We distributed an online survey via four regional collaborating organizations and 32 focal points based in 20 Latin American countries. The target respondents were conservation managers of species or areas in Latin America.Results: We collected a total of 468 answered questionnaires from 21 Latin American countries. Most respondents (44%) were from an academic or research institution while non-academics were mainly from non-governmental institutions (30%) and government agencies (25%). Most respondents (65%) have performed or used genetic assessments in their managed area or species, either alone, in partnership, contracting someone else or using published results. For the majority of this group, the genetic results were relevant to their conservation management goals, helping to inform management decisions. Respondents that had not performed genetic assessments (35%) were mainly from the non-academic group, and their main barriers were limited access to funds, genetic lab facilities, and trained personnel to design studies and conduct lab work.Discussion: From the findings, we describe the current situation and provide a general diagnosis of the conservation-genetics gap in Latin America. We describe the gender gap, academic-practitioner co-development of conservation questions and projects, and the nationality and residency of Latin American conservation managers in relation to the countries where they work. We discuss opportunities to co-create research questions and co-develop studies based on conservation practitioners’ needs. We offer recommendations for overcoming barriers to integrate genetic information into conservation actions, and advance agendas that fit the needs and realities of the highly heterogeneous, biodiverse and challenging Latin American region

Preeclampsia and COVID-19: results from the INTERCOVID prospective longitudinal study

Background: It is unclear whether the suggested link between COVID-19 during pregnancy and preeclampsia is an independent association or if these are caused by common risk factors. Objective: This study aimed to quantify any independent association between COVID-19 during pregnancy and preeclampsia and to determine the effect of these variables on maternal and neonatal morbidity and mortality. Study Design: This was a large, longitudinal, prospective, unmatched diagnosed and not-diagnosed observational study assessing the effect of COVID-19 during pregnancy on mothers and neonates. Two consecutive not-diagnosed women were concomitantly enrolled immediately after each diagnosed woman was identified, at any stage during pregnancy or delivery, and at the same level of care to minimize bias. Women and neonates were followed until hospital discharge using the standardized INTERGROWTH-21st protocols and electronic data management system. A total of 43 institutions in 18 countries contributed to the study sample. The independent association between the 2 entities was quantified with the risk factors known to be associated with preeclampsia analyzed in each group. The outcomes were compared among women with COVID-19 alone, preeclampsia alone, both conditions, and those without either of the 2 conditions. Results: We enrolled 2184 pregnant women; of these, 725 (33.2%) were enrolled in the COVID-19 diagnosed and 1459 (66.8%) in the COVID-19 not-diagnosed groups. Of these women, 123 had preeclampsia of which 59 of 725 (8.1%) were in the COVID-19 diagnosed group and 64 of 1459 (4.4%) were in the not-diagnosed group (risk ratio, 1.86; 95% confidence interval, 1.32–2.61). After adjustment for sociodemographic factors and conditions associated with both COVID-19 and preeclampsia, the risk ratio for preeclampsia remained significant among all women (risk ratio, 1.77; 95% confidence interval, 1.25–2.52) and nulliparous women specifically (risk ratio, 1.89; 95% confidence interval, 1.17–3.05). There was a trend but no statistical significance among parous women (risk ratio, 1.64; 95% confidence interval, 0.99–2.73). The risk ratio for preterm birth for all women diagnosed with COVID-19 and preeclampsia was 4.05 (95% confidence interval, 2.99–5.49) and 6.26 (95% confidence interval, 4.35–9.00) for nulliparous women. Compared with women with neither condition diagnosed, the composite adverse perinatal outcome showed a stepwise increase in the risk ratio for COVID-19 without preeclampsia, preeclampsia without COVID-19, and COVID-19 with preeclampsia (risk ratio, 2.16; 95% confidence interval, 1.63–2.86; risk ratio, 2.53; 95% confidence interval, 1.44–4.45; and risk ratio, 2.84; 95% confidence interval, 1.67–4.82, respectively). Similar findings were found for the composite adverse maternal outcome with risk ratios of 1.76 (95% confidence interval, 1.32–2.35), 2.07 (95% confidence interval, 1.20–3.57), and 2.77 (95% confidence interval, 1.66–4.63). The association between COVID-19 and gestational hypertension and the direction of the effects on preterm birth and adverse perinatal and maternal outcomes, were similar to preeclampsia, but confined to nulliparous women with lower risk ratios. Conclusion: COVID-19 during pregnancy is strongly associated with preeclampsia, especially among nulliparous women. This association is independent of any risk factors and preexisting conditions. COVID-19 severity does not seem to be a factor in this association. Both conditions are associated independently of and in an additive fashion with preterm birth, severe perinatal morbidity and mortality, and adverse maternal outcomes. Women with preeclampsia should be considered a particularly vulnerable group with regard to the risks posed by COVID-19

The satisfactory growth and development at 2 years of age of the INTERGROWTH-21st Fetal Growth Standards cohort support its appropriateness for constructing international standards.

BACKGROUND: The World Health Organization recommends that human growth should be monitored with the use of international standards. However, in obstetric practice, we continue to monitor fetal growth using numerous local charts or equations that are based on different populations for each body structure. Consistent with World Health Organization recommendations, the INTERGROWTH-21st Project has produced the first set of international standards to date pregnancies; to monitor fetal growth, estimated fetal weight, Doppler measures, and brain structures; to measure uterine growth, maternal nutrition, newborn infant size, and body composition; and to assess the postnatal growth of preterm babies. All these standards are based on the same healthy pregnancy cohort. Recognizing the importance of demonstrating that, postnatally, this cohort still adhered to the World Health Organization prescriptive approach, we followed their growth and development to the key milestone of 2 years of age. OBJECTIVE: The purpose of this study was to determine whether the babies in the INTERGROWTH-21st Project maintained optimal growth and development in childhood. STUDY DESIGN: In the Infant Follow-up Study of the INTERGROWTH-21st Project, we evaluated postnatal growth, nutrition, morbidity, and motor development up to 2 years of age in the children who contributed data to the construction of the international fetal growth, newborn infant size and body composition at birth, and preterm postnatal growth standards. Clinical care, feeding practices, anthropometric measures, and assessment of morbidity were standardized across study sites and documented at 1 and 2 years of age. Weight, length, and head circumference age- and sex-specific z-scores and percentiles and motor development milestones were estimated with the use of the World Health Organization Child Growth Standards and World Health Organization milestone distributions, respectively. For the preterm infants, corrected age was used. Variance components analysis was used to estimate the percentage variability among individuals within a study site compared with that among study sites. RESULTS: There were 3711 eligible singleton live births; 3042 children (82%) were evaluated at 2 years of age. There were no substantive differences between the included group and the lost-to-follow up group. Infant mortality rate was 3 per 1000; neonatal mortality rate was 1.6 per 1000. At the 2-year visit, the children included in the INTERGROWTH-21st Fetal Growth Standards were at the 49th percentile for length, 50th percentile for head circumference, and 58th percentile for weight of the World Health Organization Child Growth Standards. Similar results were seen for the preterm subgroup that was included in the INTERGROWTH-21st Preterm Postnatal Growth Standards. The cohort overlapped between the 3rd and 97th percentiles of the World Health Organization motor development milestones. We estimated that the variance among study sites explains only 5.5% of the total variability in the length of the children between birth and 2 years of age, although the variance among individuals within a study site explains 42.9% (ie, 8 times the amount explained by the variation among sites). An increase of 8.9 cm in adult height over mean parental height is estimated to occur in the cohort from low-middle income countries, provided that children continue to have adequate health, environmental, and nutritional conditions. CONCLUSION: The cohort enrolled in the INTERGROWTH-21st standards remained healthy with adequate growth and motor development up to 2 years of age, which supports its appropriateness for the construction of international fetal and preterm postnatal growth standards

Ten golden rules for optimal antibiotic use in hospital settings: the WARNING call to action

Antibiotics are recognized widely for their benefits when used appropriately. However, they are often used inappropriately despite the importance of responsible use within good clinical practice. Effective antibiotic treatment is an essential component of universal healthcare, and it is a global responsibility to ensure appropriate use. Currently, pharmaceutical companies have little incentive to develop new antibiotics due to scientific, regulatory, and financial barriers, further emphasizing the importance of appropriate antibiotic use. To address this issue, the Global Alliance for Infections in Surgery established an international multidisciplinary task force of 295 experts from 115 countries with different backgrounds. The task force developed a position statement called WARNING (Worldwide Antimicrobial Resistance National/International Network Group) aimed at raising awareness of antimicrobial resistance and improving antibiotic prescribing practices worldwide. The statement outlined is 10 axioms, or “golden rules,” for the appropriate use of antibiotics that all healthcare workers should consistently adhere in clinical practice

Marine Macrolides: Blue Biotechnology Against Cancer

Chemical study of marine organisms has revealed them as a rich source of natural products with unique structural characteristics and outstanding biological activities. Marine macrolides are a unique group of natural products that frequently include a highly oxygenated polyene backbone and a macrocyclic lactone as a conformational constraint. Many of them have shown unparalleled cell growth antiproliferative properties, making them valuable molecular probes for the discovery of new biochemical pathways or as promising lead compounds in the development route to new antitumor chemotherapeutic agents. This bibliographic review has been focussed on marine macrolides with strong cytotoxic activity and potential in cancer research and therapy, as well as those macrolides either in the market or currently in clinical trials and/or preclinical development.Peer reviewe

Corozalic Acid: A Key Okadaic Acid Biosynthetic Precursor with Phosphatase Inhibition Activity

Toxin precursors : Corozalic acid, a new Ser/Thr protein phosphatase 1 and 2A inhibitor that turned out to be a key metabolic intermediate, was isolated from cultures of the marine dinoflagellate Prorocentrum belizeanum. Detailed spectroscopic analysis and extensive computational calculations revealed its structure and conformational behavior. In addition, a comprehensive picture of the interactions of corozalic acid with PP1 and PP2A is proposed (see figure) on the basis of ab initio, docking and molecular dynamics calculations.Peer reviewe