Nuclear compensatory evolution driven by mito-nuclear incompatibilities.

Mitochondrial function relies on the coordinated expression of mitochondrial and nuclear genes, exhibiting remarkable resilience despite high mitochondrial mutation rates. The nuclear compensation mechanism suggests deleterious mitochondrial alleles drive compensatory nuclear mutations to preserve mito-nuclear compatibility. However, prevalence and factors conditioning this phenomenon remain debated due to its conflicting evidence. Here, we investigate how mito-nuclear incompatibilities impact substitutions in a model for species radiation. Mating success depends on genetic compatibility (nuclear DNA) and spatial proximity. Populations evolve from partially compatible mito-nuclear states, simulating mitochondrial DNA (mtDNA) introgression. Mutations do not confer advantages nor disadvantages, but individual fecundity declines with increasing incompatibilities, selecting for mito-nuclear coordination. We find that selection for mito-nuclear compatibility affects each genome differently based on their initial state. In compatible gene pairs, selection reduces substitutions in both genomes, while in incompatible nuclear genes, it consistently promotes compensation, facilitated by more mismatches. Interestingly, high mitochondrial mutation rates can reduce nuclear compensation by increasing mtDNA rectification, while substitutions in initially compatible nuclear gene are boosted. Finally, the presence of incompatibilities accelerates species radiation, but equilibrium richness is not directly correlated to substitution rates, revealing the complex dynamics triggered by mitochondrial introgression and mito-nuclear coevolution. Our study provides a perspective on nuclear compensation and the role of mito-nuclear incompatibilities in speciation by exploring extreme scenarios and identifying trends that empirical data alone cannot reveal. We emphasize the challenges in detecting these dynamics and propose analyzing specific genomic signatures could shed light on this evolutionary process.

Introduction of a hexavalent vaccine containing acellular pertussis into the national immunization program for infants in Peru: a cost-consequence analysis of vaccination coverage.

BACKGROUND: Infant vaccination coverage rates in Peru have declined in recent years, exacerbated by the COVID-19 pandemic. Introduction of the fully-liquid diphtheria, tetanus, and acellular pertussis (DTaP)-inactivated polio vaccine (IPV)-hepatitis B (HB)-Haemophilus influenzae type B (Hib) hexavalent vaccine (DTaP-IPV-HB-Hib) in Peru's infant National Immunization Program may help improve coverage. We evaluated costs and healthcare outcomes, including coverage, of switching from a pentavalent vaccine containing whole-cell pertussis component (DTwP-HB-Hib) plus IPV/oral polio vaccine (IPV/OPV) to the hexavalent vaccine for the primary vaccination scheme (2, 4 and 6 months). METHODS: The analysis was performed over a 5-year period on a cohort of children born in Peru in 2020 (N = 494,595). Four scenarios were considered: the pentavalent plus IPV/OPV scheme (S1); replacing the pentavalent plus IPV/OPV scheme with the hexavalent scheme (S2); expanded delivery of the pentavalent plus IPV/OPV scheme (S3); expanded delivery of the hexavalent scheme (S4). Vaccine coverage and incidence of adverse reactions (ARs) were estimated using Monte Carlo simulations and previous estimates from the literature. Cases of vaccine-preventable diseases were estimated using a Markov model. Logistical and healthcare costs associated with these outcomes were estimated. Impact of key variables (including coverage rates, incidence of ARs and vaccine prices) on costs was evaluated in sensitivity analyses. RESULTS: The overall cost from a public health payer perspective associated with the pentavalent plus IPV/OPV vaccine scheme (S1) was estimated at $56,719,350, increasing to $61,324,263 (+ 8.1%), $59,121,545 (+ 4.2%) and $64,872,734 (+ 14.4%) in scenarios S2, S3 and S4, respectively. Compared with the status quo (S1), coverage rates were estimated to increase by 3.1% points with expanded delivery alone, and by 9.4 and 14.3% points, if the hexavalent vaccine is deployed (S2 and S4, respectively). In both scenarios with the hexavalent vaccine (S2 and S4), pertussis cases would also be 5.7% and 8.7% lower, and AR rates would decrease by 32%. The cost per protected child would be reduced when the hexavalent vaccine scheme. Incidence of ARs was an important driver of cost variability in the sensitivity analysis. CONCLUSIONS: Implementation of the hexavalent vaccine in Peru's National Immunization Program has a positive public health cost consequence.

The impact of extremely brief meditation and brief mindfulness interventions on assisted reproductive technologies success rates: A randomised controlled trial.

OBJECTIVE: To investigate the effect of extremely brief meditation (EBMI) or brief mindfulness interventions (Brief MI) on pregnancy rate in women undergoing Assisted Reproductive Technology (ART). METHODS: This is a prospective, three-armed, randomized controlled trial with women undergoing ART cycle, age ranging from 18 to 50 years. In the day of embryo transfer, the patients randomized to Brief MI group received a 15-minute audio of mindfulness. They were instructed to practice it daily, starting from the day of embryo transfer to the day of the pregnancy test, leading to a total of 180-210 minutes. Women randomized to EBMI met once a week during the waiting time between the embryo transfer and pregnancy test day in the same virtual room with a meditator instructor for 40 minutes, totalizing two sessions (80 minutes). The pregnancy rate was assessed via a blood test to measure hCG performed 2 weeks after embryo transfer. RESULTS: A total of 68 women aged 37.5 ± 4.3y were included (EBMI, n = 24; Brief MI, n = 22 and CG, n = 22). Pearson's Chi-square test and Student's t-test for independent samples showed no significant differences between intervention and control groups. Both EBMI and Brief MI had no significant effect on pregnancy rate in women undergoing ART. CONCLUSION: This randomized control trial revealed that the extremely brief meditation (EBMI) or self-managed brief mindfulness intervention (Brief MI) had no significant effect on pregnancy rates in infertile women undergoing ART cycles. TRIAL REGISTRATION NUMBER: NCT04058262.

The effect of single dose of gonadotropin-releasing hormone agonist injection in frozen-thawed embryo transfer on pregnancy outcomes: A systematic review and meta-analysis.

This systematic review and meta-analysis of randomized controlled trials aimed to evaluate the effect of a single-dose gonadotropin-releasing hormone agonist administration in the frozen-thawed embryo transfer cycle on pregnancy outcomes. A literature search was strategically conducted using PubMed, EMBASE, and the Cochrane Controlled Trials Register. The primary outcome was the clinical pregnancy rate. The secondary outcomes combined chemical pregnancy rate, implantation rate, ongoing pregnancy rate, live birth rate, miscarriage rate, and extrauterine pregnancy rate. Out of the 1594 citations that were found, only six met the criteria for being included in the meta-analysis. The clinical pregnancy rate was higher in the treatment group than in the control group (52.05% vs. 47.29%; p=0.04; RR=1.09; 95% CI=1.00-1.18). According to subgroup analysis based on the natural cycle, the clinical pregnancy rate with the agonist administration is significantly higher (43.75% vs. 27.35%; p=0.01; RR=1.6; 95% CI=1.10-2.32). However, there was no difference between the groups in terms of artificial cycles (p=0.80; 95% CI=0.96-1.20). The secondary outcomes did not show significant differences. We concluded that supplementing with a single dose of gonadotrophin-releasing hormone agonist can marginally increase the clinical pregnancy rate, particularly in the natural cycle. Other pregnancy outcomes do not improve with the treatment.

An Aphid Pest Superclone Benefits From a Facultative Bacterial Endosymbiont in a Host-Dependent Manner, Leading to Reproductive and Proteomic Changes.

The English grain aphid, Sitobion avenae, is a significant agricultural pest affecting wheat, barley, and oats. In Chile, the most prevalent and persistent clone (superclone) of S. avenae harbors the facultative endosymbiont bacterium Regiella insecticola. To determine the role of this bacterium in the reproductive success of this superclone, the presence of R. insecticola was manipulated to assess its impact on (1) the reproductive performance of this clone on two host plant species (wheat and barley), (2) the production of winged morphs, (3) changes in the insects' proteomic profiles, and (4) the root/shoot ratio of plant. It was found that the reproductive performance of this S. avenae superclone varied across host plants, depending on the presence of the facultative bacterial endosymbiont. Aphids infected with R. insecticola showed higher reproductive success on wheat, while the opposite effect was observed on barley. Aphid biomass was greater when infected with R. insecticola, particularly on barley. Additionally, aphids harboring R. insecticola exhibited a higher proportion of winged individuals on both host plants. Protein regulation in aphids on wheat was lower compared to those on barley. A higher root/shoot biomass ratio was observed in wheat plants compared to barley when infested by R. insecticola-infected aphid. Thus, R. insecticola significantly influences the reproductive performance and proteomic profile of a S. avenae superclone, with these effects shaped by the host plant. This suggests that the interaction between the host plant and the facultative endosymbiont contributes to the ecological success of this superclone.

Impact of neonatal hyperoxia on adult cardiac autonomic function in rats: Role of angiotensin II type 1 receptor activation.

Individuals born preterm present altered cardiac autonomic function, a risk factor to heart diseases. Neonatal renin-angiotensin-system activation contributes to adult cardiomyopathy in rats exposed to neonatal hyperoxia, a well-established model of preterm birth-related conditions. Central angiotensin II receptor activation is a key modulator of the autonomic drive to the heart. Whether neonatal hyperoxia leads to alteration of the cardiac autonomic function through activation of the angiotensin II receptor type 1 (AT1) is unknown and was examined in the present study. Sprague-Dawley pups were exposed to hyperoxia or room air from postnatal days 3-10. AT1 antagonist losartan or water was given orally postnatal days 8-10. Blood pressure, autonomic function, left ventricular sympathetic innervation, ß-adrenergic-receptors expression, and AT1 expression in the solitary-tract-nucleus were examined in adult rats. Neonatal hyperoxia led to loss of day-night blood pressure variation, decreased heart rate variability, increased sympathovagal balance, increased AT1 expression in the solitary-tract, decreased left ventricle sympathetic innervation, and increased ß1-adrenergic-receptor protein expression. Losartan prevented the autonomic changes and AT1 expression in the solitary-tract but did not impact the loss of circadian blood pressure variation nor the changes in sympathetic innervation and in ß1-adrenergic-receptor expression. In conclusion, neonatal hyperoxia leads to both central autonomic and cardiac sympathetic changes, partly programmed by neonatal activation of the renin-angiotensin system.

How did coronavirus disease 2019 affect autonomic balance in young individuals? Analysis by heart rate variability

SUMMARY OBJECTIVE: The aim of this study was to demonstrate the effect of coronavirus disease 2019 on the cardiovascular autonomic system using heart rate variability in young individuals. METHODS: The study was designed retrospectively by scanning the 24-h Holter electrocardiography records of patients who applied to the Ankara Abdurrahman Yurtaslan Oncology Education and Research Hospital Cardiology outpatient clinic. The study group consisted of 492 patients under the age of 40 years, who did not have additional comorbidities or medication use and had prolonged symptoms after coronavirus disease 2019 during the pandemic. The control group, including 401 patients, was determined during the pre-pandemic period (before December 2019). Heart rate variability parameters were evaluated by scanning the 24-h Holter electrocardiography records of the patients and compared with the non-coronavirus disease 2019 group. RESULTS: The median age of participants was 30 years. Standard deviation of normal RR intervals (SDNN) ≤100 ms was more prevalent in the study group (27 (6.7%) vs 73 (14.8%), p<0.001). In univariate logistic regression analysis, the presence of coronavirus disease 2019 [(OR 2.41, 95%CI 1.52-3.83), p<0.001] and age [(OR 1.04, 95%CI 1.01-1.07), p=0.016] had a significant effect on the probability of SDNN≤100. In multivariate logistic regression analysis, the presence of coronavirus disease 2019 [(OR 2.42, 95%CI 1.52-3.85), p<0.001] and age [(OR 2.42, 95%CI 1.52-3.85), p=0.016] had a significant effect on the probability of SDNN≤100. Frequency domain measures such as, high-frequency values were significantly higher in the study group (p=0.029). The study group's low-frequency/high frequency ratio was significantly lower (p=0.019). The low-frequency/high-frequency ratio's cut-off value was ≤2.77. for determining the differentiation between coronavirus disease 2019 positive and negative cases in the receiver operating characteristic analysis. The sensitivity rate was 80.7%. The area under the curve value is 0.546 (p=0.019). CONCLUSION: This study showed that coronavirus disease 2019 causes reduced heart rate variability and increased parasympathetic activity in young patients. This may explain the prolonged symptoms after coronavirus disease 2019 infection.

Revealing alterations in heart rate fluctuations during the progression of Chagas disease.

Introduction: The heart rate variability (HRV) continually evolves throughout life, reflecting modifications in the architecture of the sinoatrial node (SAN) and in the regulation of heart rate by the autonomic nervous system (ANS). Both can be considerably affected by Chagas disease, causing important changes in the complex nature of HRV. We aim to evaluate the ability of an index based on the false nearest neighbors method (FN10) to reflect these changes during disease progression. Methods: We perform a retrospective, descriptive, and cross-sectional study analyzing HRV time series of participants with Chagas disease. We determine the dependence of FN10 on age and sex in a healthy population, and then evaluate FN10 in individuals with Chagas disease. Results and discussion: In the healthy population, FN10 has a scaling behavior with age, which is independent of sex. In Chagas disease, some individuals show FN10 values significantly above those seen in the healthy population. We relate the findings to the pathophysiological mechanisms that determine the progression of the disease. The results indicate that FN10 may be a candidate prognostic biomarker for heart disease.

Influence of biological maturation on cardiac autonomic recovery in female volleyball players during & after repeated sprints training: An experimental trial.

Previously, it was suggested that biological maturation (BM) could be linked to cardiac autonomic recovery (CAR) in the pediatric population. However, this influence hasn't been confirmed yet. Our aim was to investigate the impact of BM on CAR in female volleyball players. Experimental study with a sample of 38 volleyball players, comprising 20 girls (age: [11.6 â€‹± â€‹2.1] years) and 18 women (age: [24.5 â€‹± â€‹5.5] years), we analyzed BM, comparing maturing subjects (girls) with mature subjects (women). Additionally, we assessed peak height velocity (PHV) in girls. We conducted a training session involving repeated sprints (3 rounds of 6 sprints interspersed by 5 â€‹min [min] of passive rest). Using short-range radio telemetry, we analyzed CAR during (at the end of the 1st and 2nd rounds) and after (following the 3rd round) the training session of repeated sprints by applying the 60-s to 300-s heart rate recovery index (HRR-Index). Girls exhibited superior CAR compared to women (round 2: 60-s, 120-s, 240-s, and 300-s, p â€‹< â€‹0.005). Subgroup analyses of BM indicated that individuals in the Late-PHV stage demonstrated superior CAR compared to those in the Early-PHV and During-PHV groups. (60-s to 300-s, η 2 p â€‹> â€‹0.4, p â€‹< â€‹0.05). Subjects in the During-PHV stage were superior to those in the Early-PHV stage (240-s á 300-s, η 2 p â€‹> â€‹0.4, p â€‹< â€‹0.05). We have concluded that biological maturation has a significant impact on cardiac autonomic recovery.

Cardiac autonomic regulation during submaximal exercise in women with fibromyalgia.

Fibromyalgia (FM) patients present impaired cardiac autonomic regulation during maximal exercise; however, it is unknown whether these alterations also manifest during submaximal exercise. The aim of this study was to compare the on-transient heart rate (HR) response and HR variability during a constant-load submaximal cycling exercise between FM and control (CON) women. Ten women with FM (age: 45.2±9.3 years) and 10 age-matched CON women (age: 48.4±6.1 years) performed a 15-min cycling exercise, with the work rate fixed at 50% of the individual peak power output attained in a maximal graded exercise test. The time intervals between consecutive heartbeats were recorded regularly during the exercise for subsequent analysis of on-transient HR response and HR variability indices. The on-transient HR time constant was similar (P=0.83) between the FM (41.0±14.1 sec) and CON (42.2±10.4 sec). During the 5-10 and 10-15 min of exercise, HR variability indices indicating sympathetic and parasympathetic activities were similar (P>0.05) between FM and CON groups. In conclusion, women with FM presented a normal cardiac autonomic response to submaximal cycling exercise. These findings have clinical relevance, as submaximal exercises are commonly prescribed for FM patients.

Survival Analysis in Adult Heart Transplantation: Experience from a Brazilian Single Center.

INTRODUCTION: Heart transplantation is the gold standard for advanced heart failure treatment. This study examines the survival rates and risk factors for early mortality in adult heart transplant recipients at a Brazilian center. METHODS: This retrospective cohort study involved 255 adult heart transplant patients from a single center in Brazil. Data were collected from medical records and databases including three defined periods (2012-2015, 2016-2019, and 2020-2022). Statistical analysis employed Kaplan-Meier survival curves, Cox proportional hazards analysis for 30-day mortality risk factors, and Log-rank tests. RESULTS: The recipients were mostly male (74.9%), and the mean age was 46.6 years. Main causes of heart failure were idiopathic dilated cardiomyopathy (33.9%), Chagas cardiomyopathy (18%), and ischemic cardiomyopathy (14.3%). The study revealed an overall survival of 68.1% at one year, 58% at five years, and 40.8% at 10 years after heart transplantation. Survivalimproved significantly over time, combining the most recent periods (2016 to 2022) it was 73.2% in the first year and 63% in five years. The main risk factors for 30-day mortality were longer time on cardiopulmonary bypass, the initial period of transplants (2012 to 2015), older age of the donor, and nutritional status of the donor (overweight or obese). The main causes of death within 30 days post-transplant were infection and primary graft dysfunction. CONCLUSION: The survival analysis by period demonstrated that the increased surgical volume, coupled with the team's experience and modifications to the immunosuppression protocol, contributed to the improved early and mid-term outcomes.

Octocoral growth rate and mortality along a eutrophication gradient in Cuban reefs.

Octocorals are showing resilience to local and global stressors, while the decline in zooxanthellate corals continues. One of the processes that helps explain this ecological succession is the vertical growth of octocorals, which allows colonies to avoid stressors occurring at the substrate level. However, the growth and survival of octocorals could be affected by eutrophication, similar to what has happened with zooxanthellate corals. For this reason, the growth rate, mortality and survival of two octocoral species were determined along a eutrophication gradient in Cuba. A permanent band transect (250 × 2 m) was established on seven frontal reefs, and marked colonies were monitored for one year. The growth rates in height, width and colony area of Eunicea flexuosa and Plexaura kükenthali were significantly greater in the reefs near the polluted river basins. The eutrophication gradient, water visibility, and sediment accumulation on the bottom explained 36-78% of the variability in the growth of both species. The positive and significant correlations between the growth rate and stable nitrogen isotopes in both species and the microbiological variables, suggest that the contributions of dissolved inorganic nitrogen and organic matter from sewage discharge favor the growth of colonies. The eutrophication gradient did not explain the variability in mortality of either species in the short term, while hydrodynamic stress did. The results of this research highlight the resilience of both species and their ability to grow more rapidly in areas with eutrophic conditions, low water visibility, and greater sediment accumulation on the bottom, which may help explain the abundance of octocorals in the western tropical Atlantic.

Pricing drinking water testing in northern Haiti: Financial sensitivity to operating costs, user demand, and economic conditions.

Safe drinking water availability is a concern in Haiti. Public systems have limited coverage and reliability. Private wells and local water sources are often of unknown or poor quality. Public health events, such as the 2010 cholera outbreak, demonstrate vulnerability to water contamination. To address these concerns, a drinking water laboratory was established at the Campus Henri Christophe in Limonade, a branch of the State University of Haiti, to meet water testing demands from local clients such as for-profit kiosks, institutions, industries, and municipal water systems. This study assessed the financial viability of a university-based drinking water laboratory in Haiti by calculating Internal Rate of Return and Net Present Value. Sensitivity analysis was used to identify the range of conditions under which laboratory revenues would cover operating costs. To achieve an acceptable profitability level, the laboratory must perform microbiological testing for routine monitoring samples and test an average of five samples per day. Price-based incentives for new clients have relatively small impacts on profitability. Finally, international and Haitian inflation cause some variation in profitability. These economic factors will be among the key drivers of laboratory operation costs. The results underscore the main factors that must be considered to make the laboratory successful and the importance of strategic marketing for laboratory managers to encourage clients to regularly test drinking water and emphasize microbiological testing.

Modeling Substitution Rate Evolution across Lineages and Relaxing the Molecular Clock.

Relaxing the molecular clock using models of how substitution rates change across lineages has become essential for addressing evolutionary problems. The diversity of rate evolution models and their implementations are substantial, and studies have demonstrated their impact on divergence time estimates can be as significant as that of calibration information. In this review, we trace the development of rate evolution models from the proposal of the molecular clock concept to the development of sophisticated Bayesian and non-Bayesian methods that handle rate variation in phylogenies. We discuss the various approaches to modeling rate evolution, provide a comprehensive list of available software, and examine the challenges and advancements of the prevalent Bayesian framework, contrasting them to faster non-Bayesian methods. Lastly, we offer insights into potential advancements in the field in the era of big data.

The Impact of Stimulation Parameters on Cardiovascular Outcomes in Chronic Stroke Patients Following Transcranial Direct Current Stimulation-A Pilot Controlled, Randomized, Double-Blind Crossover Trial.

BACKGROUND: Stroke survivors often experience autonomic nervous system (ANS) dysfunction. While Transcranial Direct Current Stimulation (tDCS) has been shown to modulate the ANS when applied to the left hemisphere, its effects on the right hemisphere remain unexplored. OBJECTIVE: We aimed to compare the effects of tDCS applied to both the injured and the contralateral hemispheres on heart rate variability (HRV) and functional capacity in individuals post-stroke. METHODS: Twenty individuals with cerebral hemisphere lesions (ten with right-hemisphere lesions and ten with left-hemisphere lesions) were randomized into four groups: anodal and sham tDCS on the left temporal cortex (T3) and anodal and sham tDCS on the right temporal cortex (T4). HRV was assessed before the intervention, after the six-minute walk test (6MWT), and following tDCS. HRV data were categorized into frequency ranges: low frequency (LF), high frequency (HF), and sympathovagal balance. The 6MWT (meters) was conducted both pre- and post-tDCS. RESULTS: In individuals with right-hemisphere lesions, a higher global LF value was observed (right side: 71.4 ± 16.8 nu vs. left side: 65.7 ± 17.3 nu; p = 0.008), as well as lower values of the HF component (right side: 29.5 ± 18.9 nu vs. left side: 34.0 ± 17.4 nu; p = 0.047), consequently exhibiting higher global values of the low/high-frequency ratio (right side: 3.9 ± 2.8 vs. left side: 2.9 ± 2.4). Regarding the stimulation site, tDCS over T3 led to a lower overall value of the low/high-frequency ratio (left hemisphere: 3.0 ± 2.2 vs. right hemisphere: 3.7 ± 2.9; p = 0.040) regardless of the lesion location. A significant increase in the distance covered in the 6MWT was observed for individuals with lesions in both hemispheres after tDCS at T3. CONCLUSIONS: Participants with right-hemisphere lesions exhibited superior global sympathetic autonomic nervous system activity. When the tDCS was applied on the left hemisphere, it maintained lower sympathovagal balance values and improved functional capacity regardless of the hemisphere affected by the stroke.

Drug Nanocrystals in Oral Absorption: Factors That Influence Pharmacokinetics.

Despite the safety and convenience of oral administration, poorly water-soluble drugs compromise absorption and bioavailability. These drugs can exhibit low dissolution rates, variability between fed and fasted states, difficulty permeating the mucus layer, and P-glycoprotein efflux. Drug nanocrystals offer a promising strategy to address these challenges. This review focuses on the opportunities to develop orally administered nanocrystals based on pharmacokinetic outcomes. The impacts of the drug particle size, morphology, dissolution rate, crystalline state on oral bioavailability are discussed. The potential of the improved dissolution rate to eliminate food effects during absorption is also addressed. This review also explores whether permeation or dissolution drives nanocrystal absorption. Additionally, it addresses the functional roles of stabilizers. Drug nanocrystals may result in prolonged concentrations in the bloodstream in some cases. Therefore, nanocrystals represent a promising strategy to overcome the challenges of poorly water-soluble drugs, thus encouraging further investigation into unclear mechanisms during oral administration.

Evaluation of myocardial work and exercise capacity in patients recovered from the severe form of COVID-19.

Background: The impact of COVID-19 goes beyond its acute form and can lead to the persistence of symptoms and the emergence of systemic disorders, defined as long-term COVID. Methods: We performed a cross-sectional study that included patients over 18 years of age who recovered from the severe form of COVID-19 at least 60 days after their discharge. Patients and controls were enrolled to undergo transthoracic echocardiography (TTE) using a more sensitive tool, myocardial work, in combination with cardiopulmonary exercise testing (CPET). Results: A total of 52 patients and 31 controls were enrolled. Significant differences were observed in ejection fraction (LVEF; 62 ± 7 vs. 66 ± 6 %; p = 0.007), global longitudinal strain (LVGLS; -18.7 ± 2.6 vs. -20.4 ± 1.4 %; p = 0.001), myocardial wasted work (GWW; 152 ± 81 vs. 101 ± 54 mmHg; p = 0.003), and myocardial work efficiency (GWE; 93 ± 3 vs. 95 ± 2 %; p = 0.002). We found a significant difference in peak VO2 (24.4 ± 5.4 vs. 33.4 ± 8.8 mL/kg/min; p < 0.001), heart rate (160 ± 14 vs. 176 ± 11 bpm; p < 0.001), ventilation (84.6 ± 22.6 vs. 104.9 ± 27.0 L/min; p < 0.001), OUES% (89 ± 16 vs. 102 ± 22 %; p = 0.002), T ½ (120.3 ± 32 vs. 97.6 ± 27 s; p = 0.002) and HRR at 2 min (-36 ± 11 vs. -43 ± 13 bpm; p = 0.010). Conclusion: Our findings revealed an increased wasted work, with lower myocardial efficiency, significantly reduced aerobic exercise capacity, and abnormal heart rate response during recovery, which may be related to previously described late symptoms. The reduction in functional capacity during physical exercise is partly associated with a decrease in resting myocardial work efficiency. These findings strongly indicate the need to determine whether these manifestations persist in the long term and their impact on cardiovascular health and quality of life in COVID-19 survivors.

Reconstructing 90 years of anthropogenic activities in a subtropical reservoir: a chemometric and paleolimnological perspective.

Environmental reference conditions (RC) and historical trends are crucial for assessing the degree of freshwater impact and formulating restoration measures. This is particularly relevant for freshwater systems used as potable water sources. Using sediments from the Carlos Maggiolo reservoir (Minas, Uruguay), located in a watershed with a mining history, this study aimed to (1) establish metal (As, Cr, Cu, Ni, Pb, and Zn) RC using a predicted interval (PI) chemometric technique; (2) evaluate metal enrichment and toxicity over time and space; and (3) assess environmental changes examining geochemical proxies. Surface sediments from 29 stations were used to establish RC and a core from the dam area was sampled to infer past conditions. The sediments were submitted to partial digestion and analyzed by inductively coupled plasma optical emission spectrometry- ICP-OES. Enrichment factor (EF) calculated using both PI and bottom core values did not show significant differences over time. Over space and time, most metals primarily originated from natural sources (EF < 2). The PI in mg/kg was Cr: 23.74-37.32; Cu: 25.75-48.99; Ni: 16.29-25.55; Pb: 7.63-13.75; and Zn: 94.34-174.80. A stratigraphically constrained cluster analysis corroborated by a permutational multivariate analysis of variance categorized the reservoir into two zones: Zone I, before reservoir operation to ~ 1996, and Zone II from ~ 1997 to 2017. The average concentrations of the main metals of toxicological interest in zones I and II, respectively, were as follows: Cr 37.60 ± 1.59, 34.54 ± 1.49 mg/kg; Cu 49.76 ± 2.84, 44.55 ± 2.70 mg/kg; Ni 24.11 ± 0.67, 22.53 ± 1.22 mg/kg; Pb 12.40 ± 0.63, 13.52 ± 0.82 mg/kg; Zn 99.25 ± 3.12, 93.86 ± 4.42 mg/kg; Mn 1160.56 ± 68.88, 1441.61 ± 83.55 mg/kg; and P 1243.21 ± 271.56, 1128.42 ± 183.10 mg/kg. According to a principal component analysis, the period preceding reservoir operation until ~ 1985 was linked to mining activities and application of Cu2SO4, and the period from 1985s to 2000 was influenced by C and P concentrations due to increasing agricultural and afforestation activities in the watershed that consume P fertilizers. The most recent period, from 2000 to ~ 2017, was characterized by an increase in sedimentation rates mainly associated with erosion, particularly in the agricultural areas. This subsequent soil loss in the watershed could compromise the reservoir's useful life. This study contributes to a better understanding of metal geochemistry in subtropical reservoirs and aids in formulating effective recovery and restoration measures.

Profiles of disease progression and predictors of mortality in Colombian patients with amyotrophic lateral sclerosis: a comprehensive longitudinal study.

Objective: This study aimed to assess the prognostic value of the Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised (ALSFRS-R) in predicting mortality and characterizing disease progression patterns in ALS patients in Colombia. Methods: We conducted a retrospective longitudinal analysis of 537 ALS patients from the Roosevelt Institute Rehabilitation Service between October 2008 and October 2022. The study excluded nine patients due to incomplete data, resulting in 528 individuals in the analysis. ALS diagnoses were confirmed using the revised El Escorial and Gold Coast criteria. Disease progression was assessed using the ALSFRS-R, and mortality data were sourced from follow-up calls and a national database. Statistical analysis included Cox proportional hazards models to identify mortality predictors and Growth Mixture Modeling (GMM) to explore ALS progression trajectories. Results: The majority of the cohort (63.8%) deceased within the 84-month follow-up period. Survival analysis revealed that each point increase in the ALSFRS-R rate was associated with a 2.22-fold (95% CI =1.99-2.48, p < 0.001) increased risk of mortality. In the population with data from two clinical visits, the ALSFRS-R rate based on initial assessments predicted mortality more effectively over 36 months than the rate based on two evaluations. GMM identified three distinct progression trajectories: slow, intermediate, and rapid decliners. Conclusions: The ALSFRS-R rate, derived from self-reported symptom onset, significantly predicts mortality, underscoring its value in clinical assessments. This study highlights the heterogeneity in disease progression among Colombian ALS patients, indicating the necessity for personalized treatment approaches based on individual progression trajectories. Further studies are needed to refine these predictive models and improve patient management and outcomes.

A comprehensive meta-analysis of stem cell therapy for liver failure: Assessing treatment efficacy and modality.

INTRODUCTION AND OBJECTIVES: This meta-analysis aims to evaluate the efficacy of stem cell therapy (SCT) for liver failure. MATERIALS AND METHODS: The study adhered to the recommended guidelines of the PRISMA statement. Eligible studies published prior to May 13, 2023, were comprehensively searched in databases including PubMed, Web of Science, and Embase. Quality assessment was conducted using the Cochrane risk-of-bias tool, and the standard mean differences were calculated for the clinical parameters. The hazard ratios were determined by extracting individual patient data from the Kaplan-Meier curve. RESULTS: A total of 2,937 articles were retrieved, and eight studies were included in the final analysis. Most of the studies focused on HBV-related liver failure and were randomized controlled trials. All studies utilized mesenchymal stem cells (MSCs), with the majority (62.5%) being allogeneic. The analysis revealed that combining stem cell therapy with standard medical treatment or plasma exchange significantly enhanced patient survival and reduced MELD scores. Specifically, allogeneic stem cells showed superior efficacy in improving survival outcomes compared to autologous stem cells. Furthermore, deep vessel injection plus a single injection demonstrated better effectiveness than peripheral vessel injection plus multiple injections in reducing MELD scores. CONCLUSIONS: This comprehensive analysis underscores the potential of MSC therapy in significantly improving survival and clinical outcomes in patients with liver failure, highlighting the superior benefits of allogeneic MSCs and deep vessel plus single injection administration.