Implementing Strategies to Recruit and Retain a Diverse Sample of Heart Failure Patients.

Introduction: The increased prevalence, severity, and mortality of heart disease and specifically heart failure among Hispanic and Black populations are a concern for clinicians and researchers. Additionally, patients of poor socioeconomic status also have worse outcomes for cardiovascular disease. To address disparities, it is necessary to address the persistent lack of representation in clinical research of diverse populations, including the Hispanic and Black populations and individuals who are of low socioeconomic status. Method: This study was a pilot randomized trial of a medication adherence intervention for heart failure patients conducted at a safety net hospital and affiliated pharmacy with a diverse patient population. Using an evidence-based multifactorial approach, this investigation implemented and adapted best practices to support the inclusion of Hispanic, Black, and socioeconomically diverse participants. Results: A total of 40 participants were recruited, 58% were Hispanic, 38% Black, and 5% White. A total of 40% reported the need for socioeconomic assistance. At 30 days after discharge, follow-up data were obtained for 37 of 40 (93%) of participants either by interview, electronic record, or both. Conclusion: Findings suggest that a combination of strategies used in this trial can be applied to recruit and retain ethnically and socioeconomically diverse participants.

Immediate Postpartum Breastfeeding Following Pregnancy with Cardiac Disease.

OBJECTIVE: This study aimed to identify predictors of immediate postpartum breastfeeding among women with maternal cardiac disease (MCD). STUDY DESIGN: This study included all gravidas with MCD who delivered at a single institution from 2012 to 2018. Charts were abstracted for maternal demographics, obstetrical outcome, cardiac diagnoses, cardiac risk stratification scores, and prepregnancy echocardiogram findings. Kruskal-Wallis and Fisher's exact tests were used to compare the breastfeeding (BF) group versus the nonbreastfeeding (NBF) group. Logistic regression was used to obtain odds ratios (ORs) with 95% confidence intervals (CIs). RESULTS: Among 211 gravidas with MCD, 12% were not breastfeeding at the time of postpartum hospital discharge. Compared with the BF group, the NBF group had a significantly higher proportion of women with cardiomyopathy (21% NBF vs. 7% BF, OR 3.44, 95% CI 1.12-10.71), with modified World Health Organization (WHO) classification ≥III (33 vs. 14%, OR 3.16, 95% CI 1.22-8.15), and with prepregnancy ejection fraction (EF) < 50% (55 vs. 14%, OR 7.20, 95% CI 1.92-27.06). There were otherwise no differences between the two groups with regards to other cardiac diagnoses or cardiac risk scores. CONCLUSION: In women with MCD, cardiomyopathy, modified WHO class ≥III, and a prepregnancy EF < 50% were associated with NBF in the immediate postpartum period. These findings may guide providers in identifying a subset of women with MCD who can benefit from increased breastfeeding counseling and support. KEY POINTS: · Eighty-two percent of patients with cardiac disease are breastfeeding at the time of postpartum discharge.. · Cardiomyopathy is associated with an increased odds of not breastfeeding at postpartum discharge.. · Rationale for not breastfeeding is infrequently documented in the medical record..

Microbial divergence and evolution. The case of anammox bacteria.

Species differentiation and the appearance of novel diversity on Earth is a major issue to understand the past and future of microbial evolution. Herein, we propose the analysis of a singular evolutive example, the case of microorganisms carrying out the process of anammox (anaerobic ammonium oxidation). Anammox represents a singular physiology active on Earth from ancient times and, at present, this group is still represented by a relatively limited number of species carrying out a specific metabolism within the Phylum Planctomycetota. The key enzyme on the anammox pathway is hydrazine dehydrogenase (HDH) which has been used as a model in this study. HDH and rRNA (16S subunit) phylogenies are in agreement suggesting a monophyletic origin. The diversity of this singular phylogenetic group is represented by a few enriched bacterial consortia awaiting to be cultured as monospecific taxa. The apparent evolution of the HDH genes in these anammox bacteria is highly related to the diversification of the anammox clades and their genomes as pointed by phylogenomics, their GC content and codon usage profile. This study represents a clear case where bacterial evolution presents a paralleled genome, gene and species diversification through time from a common ancestor; a scenario that most times is masked by a web-like phylogeny and the huge complexity within the prokaryotes. Besides, this contribution suggests that microbial evolution of the anammox bacteria has followed an ordered, vertical diversification through Earth history and will present a potentially similar speciation fate in the future.

Neonatal Survival After Serial Amnioinfusions for Bilateral Renal Agenesis: The Renal Anhydramnios Fetal Therapy Trial.

Importance: Early anhydramnios during pregnancy, resulting from fetal bilateral renal agenesis, causes lethal pulmonary hypoplasia in neonates. Restoring amniotic fluid via serial amnioinfusions may promote lung development, enabling survival. Objective: To assess neonatal outcomes of serial amnioinfusions initiated before 26 weeks' gestation to mitigate lethal pulmonary hypoplasia. Design, Setting, and Participants: Prospective, nonrandomized clinical trial conducted at 9 US fetal therapy centers between December 2018 and July 2022. Outcomes are reported for 21 maternal-fetal pairs with confirmed anhydramnios due to isolated fetal bilateral renal agenesis without other identified congenital anomalies. Exposure: Enrolled participants initiated ultrasound-guided percutaneous amnioinfusions of isotonic fluid before 26 weeks' gestation, with frequency of infusions individualized to maintain normal amniotic fluid levels for gestational age. Main Outcomes and Measures: The primary end point was postnatal infant survival to 14 days of life or longer with dialysis access placement. Results: The trial was stopped early based on an interim analysis of 18 maternal-fetal pairs given concern about neonatal morbidity and mortality beyond the primary end point despite demonstration of the efficacy of the intervention. There were 17 live births (94%), with a median gestational age at delivery of 32 weeks, 4 days (IQR, 32-34 weeks). All participants delivered prior to 37 weeks' gestation. The primary outcome was achieved in 14 (82%) of 17 live-born infants (95% CI, 44%-99%). Factors associated with survival to the primary outcome included a higher number of amnioinfusions (P = .01), gestational age greater than 32 weeks (P = .005), and higher birth weight (P = .03). Only 6 (35%) of the 17 neonates born alive survived to hospital discharge while receiving peritoneal dialysis at a median age of 24 weeks of life (range, 12-32 weeks). Conclusions and Relevance: Serial amnioinfusions mitigated lethal pulmonary hypoplasia but were associated with preterm delivery. The lower rate of survival to discharge highlights the additional mortality burden independent of lung function. Additional long-term data are needed to fully characterize the outcomes in surviving neonates and assess the morbidity and mortality burden. Trial Registration: ClinicalTrials.gov Identifier: NCT03101891.

Machine Learning Algorithms Applied to Predict Autism Spectrum Disorder Based on Gut Microbiome Composition.

The application of machine learning (ML) techniques stands as a reliable method for aiding in the diagnosis of complex diseases. Recent studies have related the composition of the gut microbiota to the presence of autism spectrum disorder (ASD), but until now, the results have been mostly contradictory. This work proposes using machine learning to study the gut microbiome composition and its role in the early diagnosis of ASD. We applied support vector machines (SVMs), artificial neural networks (ANNs), and random forest (RF) algorithms to classify subjects as neurotypical (NT) or having ASD, using published data on gut microbiome composition. Naive Bayes, k-nearest neighbors, ensemble learning, logistic regression, linear regression, and decision trees were also trained and validated; however, the ones presented showed the best performance and interpretability. All the ML methods were developed using the SAS Viya software platform. The microbiome's composition was determined using 16S rRNA sequencing technology. The application of ML yielded a classification accuracy as high as 90%, with a sensitivity of 96.97% and specificity reaching 85.29%. In the case of the ANN model, no errors occurred when classifying NT subjects from the first dataset, indicating a significant classification outcome compared to traditional tests and data-based approaches. This approach was repeated with two datasets, one from the USA and the other from China, resulting in similar findings. The main predictors in the obtained models differ between the analyzed datasets. The most important predictors identified from the analyzed datasets are Bacteroides, Lachnospira, Anaerobutyricum, and Ruminococcus torques. Notably, among the predictors in each model, there is the presence of bacteria that are usually considered insignificant in the microbiome's composition due to their low relative abundance. This outcome reinforces the conventional understanding of the microbiome's influence on ASD development, where an imbalance in the composition of the microbiota can lead to disrupted host-microbiota homeostasis. Considering that several previous studies focused on the most abundant genera and neglected smaller (and frequently not statistically significant) microbial communities, the impact of such communities has been poorly analyzed. The ML-based models suggest that more research should focus on these less abundant microbes. A novel hypothesis explains the contradictory results in this field and advocates for more in-depth research to be conducted on variables that may not exhibit statistical significance. The obtained results seem to contribute to an explanation of the contradictory findings regarding ASD and its relation with gut microbiota composition. While some research correlates higher ratios of Bacillota/Bacteroidota, others find the opposite. These discrepancies are closely linked to the minority organisms in the microbiome's composition, which may differ between populations but share similar metabolic functions. Therefore, the ratios of Bacillota/Bacteroidota regarding ASD may not be determinants in the manifestation of ASD.

Extremophiles: the species that evolve and survive under hostile conditions.

Extremophiles possess unique cellular and molecular mechanisms to assist, tolerate, and sustain their lives in extreme habitats. These habitats are dominated by one or more extreme physical or chemical parameters that shape existing microbial communities and their cellular and genomic features. The diversity of extremophiles reflects a long list of adaptations over millions of years. Growing research on extremophiles has considerably uncovered and increased our understanding of life and its limits on our planet. Many extremophiles have been greatly explored for their application in various industrial processes. In this review, we focused on the characteristics that microorganisms have acquired to optimally thrive in extreme environments. We have discussed cellular and molecular mechanisms involved in stability at respective extreme conditions like thermophiles, psychrophiles, acidophiles, barophiles, etc., which highlight evolutionary aspects and the significance of extremophiles for the benefit of mankind.

Microbial Growth under Limiting Conditions-Future Perspectives.

Microorganisms rule the functioning of our planet and each one of the individual macroscopic living creature. Nevertheless, microbial activity and growth status have always been challenging tasks to determine both in situ and in vivo. Microbial activity is generally related to growth, and the growth rate is a result of the availability of nutrients under adequate or adverse conditions faced by microbial cells in a changing environment. Most studies on microorganisms have been carried out under optimum or near-optimum growth conditions, but scarce information is available about microorganisms at slow-growing states (i.e., near-zero growth and maintenance metabolism). This study aims to better understand microorganisms under growth-limiting conditions. This is expected to provide new perspectives on the functions and relevance of the microbial world. This is because (i) microorganisms in nature frequently face conditions of severe growth limitation, (ii) microorganisms activate singular pathways (mostly genes remaining to be functionally annotated), resulting in a broad range of secondary metabolites, and (iii) the response of microorganisms to slow-growth conditions remains to be understood, including persistence strategies, gene expression, and cell differentiation both within clonal populations and due to the complexity of the environment.

Soil Thermophiles and Their Extracellular Enzymes: A Set of Capabilities Able to Provide Significant Services and Risks.

During this century, a number of reports have described the potential roles of thermophiles in the upper soil layers during high-temperature periods. This study evaluates the capabilities of these microorganisms and proposes some potential consequences and risks associated with the activity of soil thermophiles. They are active in organic matter mineralization, releasing inorganic nutrients (C, S, N, P) that otherwise remain trapped in the organic complexity of soil. To process complex organic compounds in soils, these thermophiles require extracellular enzymes to break down large polymers into simple compounds, which can be incorporated into the cells and processed. Soil thermophiles are able to adapt their extracellular enzyme activities to environmental conditions. These enzymes can present optimum activity under high temperatures and reduced water content. Consequently, these microorganisms have been shown to actively process and decompose substances (including pollutants) under extreme conditions (i.e., desiccation and heat) in soils. While nutrient cycling is a highly beneficial process to maintain soil service quality, progressive warming can lead to excessive activity of soil thermophiles and their extracellular enzymes. If this activity is too high, it may lead to reduction in soil organic matter, nutrient impoverishment and to an increased risk of aridity. This is a clear example of a potential effect of future predicted climate warming directly caused by soil microorganisms with major consequences for our understanding of ecosystem functioning, soil health and the risk of soil aridity.

In vitro ovicidal effect of p-coumaric acid from Acacia bilimekii aerial parts against Haemonchus contortus.

Acacia bilimekii is a plant with a high content of protein, fibre, and condensed tannins, making it an excellent feed for small ruminants with anthelmintic potential. This study aimed to evaluate the ovicidal activity of a hydroalcoholic extract (Ab-HA) and fractions from A. bilimekii aerial parts on Haemonchus contortus. The ovicidal activity of the Ab-HA extract and its fractions obtained by chromatographic fractionation were evaluated through the egg hatching inhibition (EHI) test. The results showed that the Ab-HA extract had 91% EHI at 20,000 µg/mL with a mean effective concentration (EC50) of 9260 µg/mL. After liquid-liquid fractionation of Ab-HA extract, the aqueous fraction (Ab-Aq) did not show ovicidal activity, whereas the organic fraction (Ab-EtOAc) showed a better EHI than the Ab-HA extract (98.9% at 2500 µg/mL). Then, the chemical fractionation of Ab-EtOAc allowed obtaining six bioactive fractions (AbR12-17) with an EHI greater than 90% at 1500 µg/mL. The best treatment was AbR15 (98.7% EHI at 750 µg/mL). Chemical analysis by HPLC-PDA of AbR15 indicated the presence of p-coumaric acid and the flavone luteolin as major compounds. Additionally, the commercial p-coumaric acid standard was evaluated in the EHI assay and showed an EHI of 97% at 62.5 µg/mL. Meanwhile, the confocal laser scanning microscopy analysis demonstrated a colocalization effect between p-coumaric acid and the H. contortus embryonated eggs. These results indicate that due to their major chemical compounds (including p-coumaric acid), the aerial parts of the plant A. bilimekii, could be considered as natural potential tool for controlling haemonchosis in small ruminants.

Maternal cardiac disease and perinatal outcomes in a single tertiary care center.

OBJECTIVE: Maternal mortality in the U.S. has increased, with a substantial contribution from maternal cardiac disease. As a result of improved childhood survival, more women with congenital heart disease are reaching reproductive age leading to a growing high-risk obstetric population. We sought to determine the obstetrical and neonatal outcomes of women with maternal cardiac disease, including acquired cardiovascular disease and congenital heart disease. METHODS: We studied a retrospective cohort study of women that delivered from 2008 to 2013 (N = 9026). Singleton pregnancies without preexisting conditions were established as the unexposed group for this study. Maternal and neonatal outcomes were compared between the unexposed group (N = 7277) and women exposed to maternal (acquired or congenital) cardiac disease (N = 139) as well as only congenital heart disease (N = 85). Statistical comparisons used univariate/multivariable logistic and linear regression analysis controlling for confounders with p < .05 and 95% confidence intervals indicating statistical significance. RESULTS: Pregnancies complicated by maternal cardiac disease were associated with increased odds of preterm birth (<34 weeks, <37 weeks), intrauterine growth restriction (IUGR), need for assisted vaginal delivery, maternal ICU admission, and prolonged maternal hospitalization (>7 d). Neonatal outcomes including small for gestational age and Apgar score <7 at 5 min were increased in the pregnancies complicated by maternal cardiac disease. When pregnancies complicated by congenital heart disease were analyzed as a sub-group of the cohort, the results were similar. There were increased odds of preterm birth (<37 weeks), early-term delivery, need for assisted vaginal delivery, and prolonged hospitalization. Neonatal outcomes were only significant for small for gestational age. CONCLUSION: We observed that in a select cohort of pregnancies complicated by maternal cardiac diseases (acquired or congenital), there were significant increases of adverse perinatal outcomes. Therefore, a multidisciplinary approach including maternal-fetal medicine specialists, cardiologists, obstetric anesthesia, and dedicated ancillary support is imperative for optimal care of this high-risk obstetrics population.

Mode of delivery and neonatal outcomes with early preterm severe preeclampsia: does fetal growth restriction matter?

OBJECTIVE: Severe preeclampsia diagnosed at or prior to 34 weeks is an indication for preterm delivery. Many patients with severe preeclampsia develop fetal growth restriction as a result of the placental dysfunction associated with both conditions. The ideal mode of delivery in cases of preterm severe preeclampsia with fetal growth restriction remains controversial, with providers often proceeding directly to cesarean delivery rather than attempting a trial of labor due to theoretic concerns about the harms of labor in the face of placental dysfunction. There are limited data supporting this approach. This study evaluates whether the presence of fetal growth restriction affects the ultimate mode of delivery or neonatal outcomes among pregnancies with severe preeclampsia undergoing induction of labor at or before 34 weeks. METHODS: This was a retrospective cohort study of singletons with severe preeclampsia undergoing induction of labor ≤ 34 weeks at a single center between January 2015 and April 2022. The primary predictor was fetal growth restriction, defined as estimated fetal weight < 10th percentile for gestational age on ultrasound. Mode of delivery and neonatal outcomes were compared between those with and without fetal growth restriction using Fisher's exact and Kruskal-Wallis tests, and multivariate logistic regression was used to obtain adjusted odds ratios. RESULTS: 159 patients were included (N = 117 without fetal growth restriction, N = 42 with fetal growth restriction). There was no difference in vaginal delivery between the groups (70% vs 67%, p = .70). While those with fetal growth restriction had a higher incidence of respiratory distress syndrome and longer neonatal hospital stay, these differences were not statistically significant after adjusting for gestational age at delivery. There were no significant differences in other neonatal outcomes, including Apgar score, cord blood gases, intraventricular hemorrhage, necrotizing enterocolitis, neonatal sepsis, and neonatal demise. CONCLUSION: For pregnancies complicated by severe preeclampsia that require delivery ≤ 34 weeks, the likelihood of successful vaginal delivery following induction of labor does not differ based on presence of fetal growth restriction. Furthermore, fetal growth restriction is not an independent risk factor for adverse neonatal outcomes in this population. Induction of labor should be considered a reasonable approach and should be routinely offered to patients with concurrent preterm severe preeclampsia and fetal growth restriction.

Impact of a Digital Atopic Dermatitis Educational Intervention on Hispanic Patients and Family Members.

With the increasing incidence of atopic dermatitis (AD) in the U.S., the highest prevalence of AD being found in Hispanic countries, and the rising Hispanic-American population, educational resources on eczema focused on Spanish-speaking populations are needed more than ever. As such, the primary goal of this project was to assess the beneficial impact of an educational intervention conducted through a virtual platform for Hispanic individuals living with atopic dermatitis. Utilizing WhatsApp, the study enrolled 55 participants diagnosed with AD and/or parents of children diagnosed with AD. Participants were enrolled in a seven-day educational module with daily topics on AD health knowledge. A health knowledge survey was administered before the educational program, upon completion of the program, and one month after completion. The program found a 14% increase in AD health knowledge upon completion of the program (p < 0.001). Most importantly, there was no significant difference found between the health knowledge survey submitted at program completion and one month after completion, signaling that health knowledge taught through the course was successfully retained by participants (p = 0.29). Qualitative themes involving atopic disease were additionally explored through group discussions, including mental health and peer stigma. This study is the first of its kind in dermatology utilizing the WhatsApp format. The success of retained health knowledge regarding AD demonstrates that future virtual endeavors can be effective and accessible methods of patient education overall for populations that might not have ease of access to major medical centers.

Special Issue: "New Methods in Microbial Research 2.0": Editorial.

Today, it is definitively accepted that microorganisms play a central role in the functioning and maintenance of our planet and the organisms thriving on it [...].

Antibiofilm and antimicrobial activity of curcumin-chitosan nanocomplexes and trimethoprim-sulfamethoxazole on Achromobacter, Burkholderia, and Stenotrophomonas isolates.

BACKGROUND: Non-fermenting Gram-negative Achromobacter xylosoxidans, Burkholderia cepacia complex, and Stenotrophomonas maltophilia species cause healthcare-associated infections, often showing resistance to first-line drugs such as trimethoprim-sulfamethoxazole (TMP-SXT). The aim of this study was to determine the effect of curcumin-chitosan nanocomplexes on biofilm-producing clinical isolates of non-fermenting Gram-negative bacilli. METHODS: A. xylosoxidans, B. cepacia complex, and S. maltophilia clinical isolates were identified by MALDI-TOF mass spectrometry. Antimicrobial susceptibility was determined by broth microdilution. Curcumin (Cur), chitosan (Chi), and sodium tripolyphosphate (TPP) were encapsulated by ionotropic gelation in magnetic nanoparticles (MNP) and were assessed by scanning electron microscopy (SEM) and Fourier-transform infrared (FTIR). Biofilm inhibition and eradication by Cur-Chi-TPP-MNP with TMP-SXT was assessed. RESULTS: Cur-Chi-TPP-MNP in combination with TMP-SXT showed biofilm inhibition activity in A. xylosoxidans (37.5 µg/mL), B. cepacia (18.75 µg/mL), and S. maltophilia (4.69-18.75 µg/mL) and low biofilm eradication activity in all three strains (150 - 300 µg/mL). CONCLUSIONS: Cur-Chi-TPP-MNP in combination with TMP-SXT was able to inhibit biofilm and in lower effect to eradicate established biofilms of clinical isolates of A. xylosoxidans, B. cepacia complex, and S. maltophilia species. Our results highlight the need to assess these potential treatment options to be used clinically in biofilm-associated infections.

Risk factors for functional dyspepsia, erosive and non-erosive gastroesophageal reflux disease: A cross-sectional study.

BACKGROUND: Conflicting data exists regarding risk factors associated with Gastroesophageal Reflux Disease (GERD) and Functional Dyspepsia (FD). Few studies examine anxiety/depression in relation to GERD phenotypes (Esophagitis/EE, and Non-Erosive Reflux Disease/NERD), FD, and Rome-IV syndromes. Our aim was to evaluate the association between epidemiological factors and comorbidities with GERD phenotypes, FD, and Rome-IV syndromes, as well as their relationship with anxiety/depression. METHODS: 338 subjects were selected from 357 patients referred to three tertiary-centers for endoscopic evaluation. Every subject was interviewed individually to administer three validated questionnaires: GERD-Q, Rome-IV and HADS. RESULTS: 45/338 patients were controls, 198/58.6% classified as GERD, 81/24.0% EE (49/14.5% symptomatic, and 32/9.5% asymptomatic), 117/34.6% NERD, 176/52.1% FD (43/12.7% epigastric pain syndrome, 36/10.7% postprandial distress syndrome, and 97/28.7% overlapping syndrome). 81 patients were mixed GERD-FD. Multivariate analysis found significant independent associations: age in NERD and FD; sex in EE, asymptomatic EE and FD; body mass index in NERD and FD; alcohol in EE; anxiety/depression in FD; use of calcium channel antagonists in EE; and inhalers in FD. We compared controls vs different groups/subgroups finding significantly more anxiety in NERD, FD, all Rome-IV syndromes, and mixed GERD-FD; more depression in FD, overlapping syndrome, and mixed GERD-FD; and higher levels of anxiety+depression in NERD, FD, overlapping syndrome, and mixed GERD-FD. CONCLUSIONS: NERD and FD share demographic and psychopathological risk factors which suggests that they may form part of the same pathophysiological spectrum. Regarding NERD anxiety was predominant, and in FD anxiety+depression, suggesting that both processes may require complementary psychological therapy.

Test-retest of the Subjective Visual Vertical Test performed using a mobile application with the smartphone anchored to a turntable.

PURPOSE: The alterations of the Subjective visual vertical test are related to vestibular pathology. Our previously validated method to distinguish between healthy and pathological individuals measures the deviation from the Subjective visual vertical using a mobile application installed on a smartphone fixed to a turntable anchored to the wall. The aim of this study was evaluating the intra-observer reliability of our method in individuals with or without vestibular pathology. METHODS: Participants were recruited consecutively. In each individual two measurements with an interval of 2 h were made. Both tests were performed by the same examiner. A total of 91 patients were included in this study, of which 25 were healthy and 66 diseased. Intra-observer reliability was evaluated using the intraclass correlation coefficient (ICC). To assess the clinical accuracy of the measurement, we calculated the standard error of the measurement (SEM) and the minimum detectable change (MDC) with a 95% confidence interval. RESULTS: Intra-observer reliability was excellent with an ICC 0.95 (0.92-0.97) in the whole sample, in healthy patients 0.91 (0.80-0.96) and in pathological patients 0.92 (0.87-0.95). The SEM was calculated to be 0.59 for the whole sample (0.26 in the "healthy" group, and 0.67 in the pathological group). Likewise, the sample's MDC was 1.16, being 0.52 and 1.36 for the healthy and the pathological group, respectively. CONCLUSIONS: Considering the results, our method presents an excellent intraobserver reliability. Furthermore, changes in deviation greater than 0.52 in healthy individuals and 1.36 in pathological individuals can be considered a real change in deviation.

Understanding Life at High Temperatures: Relationships of Molecular Channels in Enzymes of Methanogenic Archaea and Their Growth Temperatures.

Analyses of protein structures have shown the existence of molecular channels in enzymes from Prokaryotes. Those molecular channels suggest a critical role of spatial voids in proteins, above all, in those enzymes functioning under high temperature. It is expected that these spaces within the protein structure are required to access the active site and to maximize availability and thermal stability of their substrates and cofactors. Interestingly, numerous substrates and cofactors have been reported to be highly temperature-sensitive biomolecules. Methanogens represent a singular phylogenetic group of Archaea that performs anaerobic respiration producing methane during growth. Methanogens inhabit a variety of environments including the full range of temperatures for the known living forms. Herein, we carry out a dimensional analysis of molecular tunnels in key enzymes of the methanogenic pathway from methanogenic Archaea growing optimally over a broad temperature range. We aim to determine whether the dimensions of the molecular tunnels are critical for those enzymes from thermophiles. Results showed that at increasing growth temperature the dimensions of molecular tunnels in the enzymes methyl-coenzyme M reductase and heterodisulfide reductase become increasingly restrictive and present strict limits at the highest growth temperatures, i.e., for hyperthermophilic methanogens. However, growth at lower temperature allows a wide dimensional range for the molecular spaces in these enzymes. This is in agreement with previous suggestions on a potential major role of molecular tunnels to maintain biomolecule stability and activity of some enzymes in microorganisms growing at high temperatures. These results contribute to better understand archaeal growth at high temperatures. Furthermore, an optimization of the dimensions of molecular tunnels would represent an important adaptation required to maintain the activity of key enzymes of the methanogenic pathway for those methanogens growing optimally at high temperatures.

Design and Protocol of the Renal Anhydramnios Fetal Therapy (RAFT) Trial.

PURPOSE: Anhydramnios secondary to anuria before 22 weeks of gestational age and congenital bilateral renal agenesis before 26 weeks of gestational age are collectively referred to as early-pregnancy renal anhydramnios. Early-pregnancy renal anhydramnios occurs in at least 1 in 2000 pregnancies and is considered universally fatal when left untreated because of severe pulmonary hypoplasia precluding ex utero survival The Renal Anhydramnios Fetal Therapy (RAFT) trial is a nonrandomized, nonblinded, multicenter clinical trial designed to assess the efficacy, safety, and feasibility of amnioinfusions for patients with pregnancies complicated by early-pregnancy renal anhydramnios. The primary objective of this study is to determine the proportion of neonates surviving to successful dialysis, defined as use of a dialysis catheter for ≥14 days. METHODS: A consortium of 9 North American Fetal Therapy Network (NAFTNet) centers was formed, and the RAFT protocol was refined in collaboration with the NAFTNet Scientific Committee. Enrollment in the trial began in April 2020. Participants may elect to receive amnioinfusions or to join the nonintervention observational expectant management group. Eligible pregnant women must be at least 18 years of age with a fetal diagnosis of isolated early-pregnancy renal anhydramnios. FINDINGS: In addition to the primary study objective stated above, secondary objectives include (1) to assess maternal safety and feasibility of the serial amnioinfusion intervention (2) to perform an exploratory study of the natural history of untreated early pregnancy renal anhydramnios (3) to examine correlations between prenatal imaging and lung specific factors in amniotic fluid as predictive of the efficacy of serial percutaneous amnioinfusions and (4) to determine short- and long-term outcomes and quality of life in surviving neonates and families enrolled in RAFT IMPLICATIONS: The RAFT trial is the first clinical trial to investigate the efficacy, safety, and feasibility of amnioinfusions to treat the survival-limiting pulmonary hypoplasia associated with anhydramnios. Although the intervention offers an opportunity to treat a condition known to be almost universally fatal in affected neonates, the potential burdens associated with end-stage kidney disease from birth must be acknowledged. CLINICALTRIALS: gov identifier: NCT03101891.

Mortality and life expectancy trends in Spain by pension income level for male pensioners in the general regime retiring at the statutory age, 2005-2018.

BACKGROUND: Research has generally found a significant inverse relationship in mortality risk across socioeconomic (SE) groups. This paper focuses on Spain, a country for which there continues to be very little evidence available concerning retirement pensioners. We draw on the Continuous Sample of Working Lives (CSWL) to investigate disparities in SE mortality among retired men aged 65 and above over the longest possible period covered by this data source: 2005-2018. We use the initial pension income (PI) level as our single indicator of the SE status of the retired population. METHODS: The mortality gradient by income is quantified in two ways: via an indicator referred to as "relative mortality", and by estimating changes in total life expectancy (LE) by PI level at ages 65 and 75 over time. We show that, should the information provided by the relative mortality ratio not be completely clear, a second indicator needs to be introduced to give a broad picture of the true extent of inequality in mortality. RESULTS: The first indicator reveals that, for the period covered and for all age groups, the differences in death rates across PI levels widens over time. At older age groups, these differences across PI levels diminish. The second indicator shows that disparities in LE at ages 65 and 75 between pensioners in the lowest and highest income groups are relatively small, although slightly higher than previously reported for Spain. This gap in LE widens over time, from 1.49 to 2.54 years and from 0.71 to 1.40 years respectively for pensioners aged 65 and 75. These differences are statistically significant. CONCLUSIONS: Along with other behavioral and structural aspects, a combination of factors such as the design of the pension system, the universality and quality of the health system, and high levels of family support could explain why LE inequalities for retired Spanish men are relatively small. To establish the reasons for this increased inequality in LE, more research needs to be carried out. An analysis of all Spanish social security records instead of just a sample would provide us with more information.