Mortality Due to Acute Respiratory Distress Syndrome in Latin America.

OBJECTIVES: Mortality due to acute respiratory distress syndrome (ARDS) is a major global health problem. Knowledge of epidemiological data on ARDS is crucial to design management, treatment strategies, and optimize resources. There is ample data regarding mortality of ARDS from high-income countries; in this review, we evaluated mortality due to ARDS in Latin America. DATA SOURCES: We searched in PubMed, Cochrane Central Register of Controlled Trials, Web of Science, and Latin American and Caribbean Health Science Literature databases from 1967 to March 2023. STUDY SELECTION: We searched prospective or retrospective observational studies and randomized controlled trials conducted in Latin American countries reporting ARDS mortality. DATA EXTRACTION: Three pairs of independent reviewers checked all studies for eligibility based on their titles and abstracts. We performed meta-analysis of proportions using a random-effects model. We performed sensitivity analyses including studies with low risk of bias and with diagnosis using the Berlin definition. Subgroup analysis comparing different study designs, time of publication (up to 2000 and from 2001 to present), and studies in which the diagnosis of ARDS was made using Pa o2 /F io2 less than or equal to 200 and regional variations. Subsequently, we performed meta-regression analyses. Finally, we graded the certainty of the evidence (Grading of Recommendations Assessment, Development, and Evaluation). DATA SYNTHESIS: Of 3315 articles identified, 32 were included (3627 patients). Mortality was 52% in the pooled group (low certainty of evidence). In the sensitivity analysis (according to the Berlin definition), mortality was 46% (moderate certainty of evidence). In the subgroup analysis mortality was 53% (randomized controlled trials), 51% (observational studies), 66% (studies published up to 2000), 50% (studies after 2000), 44% (studies with Pa o2 /F io2 ≤ 200), 56% (studies from Argentina/Brazil), and 40% (others countries). No variables were associated with mortality in the meta-regression. CONCLUSIONS: ARDS mortality in Latin America remains high, as in other regions. These results should constitute the basis for action planning to improve the prognosis of patients with ARDS (PROSPERO [CRD42022354035]).

Plasmid permissiveness of wastewater microbiomes can be predicted from 16S rRNA sequences by machine learning.

MOTIVATION: Wastewater treatment plants (WWTPs) harbor a dense and diverse microbial community. They constantly receive antimicrobial residues and resistant strains, and therefore provide conditions for horizontal gene transfer (HGT) of antimicrobial resistance (AMR) determinants. This facilitates the transmission of clinically important genes between, e.g. enteric and environmental bacteria, and vice versa. Despite the clinical importance, tools for predicting HGT remain underdeveloped. RESULTS: In this study, we examined to which extent water cycle microbial community composition, as inferred by partial 16S rRNA gene sequences, can predict plasmid permissiveness, i.e. the ability of cells to receive a plasmid through conjugation, based on data from standardized filter mating assays using fluorescent bio-reporter plasmids. We leveraged a range of machine learning models for predicting the permissiveness for each taxon in the community, representing the range of hosts a plasmid is able to transfer to, for three broad host-range resistance IncP plasmids (pKJK5, pB10, and RP4). Our results indicate that the predicted permissiveness from the best performing model (random forest) showed a moderate-to-strong average correlation of 0.49 for pB10 [95% confidence interval (CI): 0.44-0.55], 0.43 for pKJK5 (0.95% CI: 0.41-0.49), and 0.53 for RP4 (0.95% CI: 0.48-0.57) with the experimental permissiveness in the unseen test dataset. Predictive phylogenetic signals occurred despite the broad host-range nature of these plasmids. Our results provide a framework that contributes to the assessment of the risk of AMR pollution in wastewater systems. AVAILABILITY AND IMPLEMENTATION: The predictive tool is available as an application at https://github.com/DaneshMoradigaravand/PlasmidPerm.

Artificial intelligence cloud platform improves arrhythmia detection from insertable cardiac monitors to 25 cardiac rhythm patterns through multi-label classification.

BACKGROUND: Electrocardiogram (ECG) is the gold standard for the diagnosis of cardiac arrhythmias and other heart diseases. Insertable cardiac monitors (ICMs) have been developed to continuously monitor cardiac activity over long periods of time and to detect 4 cardiac patterns (atrial tachyarrhythmias, ventricular tachycardia, bradycardia, and pause). However, interpretation of ECG or ICM subcutaneous ECG (sECG) is time-consuming for clinicians. Artificial intelligence (AI) classifies ECG and sECG with high accuracy in short times. OBJECTIVE: To demonstrate whether an AI algorithm can expand ICM arrhythmia recognition from 4 to many cardiac patterns. METHODS: We performed an exploratory retrospective study with sECG raw data coming from 20 patients wearing a Confirm Rx™ (Abbott, Sylmar, USA) ICM. The sECG data were recorded in standard conditions and then analyzed by AI (Willem™, IDOVEN, Madrid, Spain) and cardiologists, in parallel. RESULTS: In nineteen patients, ICMs recorded 2261 sECGs in an average follow-up of 23 months. Within these 2261 sECG episodes, AI identified 7882 events and classified them according to 25 different cardiac rhythm patterns with a pondered global accuracy of 88%. Global positive predictive value, sensitivity, and F1-score were 86.77%, 83.89%, and 85.52% respectively. AI was especially sensitive for bradycardias, pauses, rS complexes, premature atrial contractions, and inverted T waves, reducing the median time spent to classify each sECG compared to cardiologists. CONCLUSION: AI can process sECG raw data coming from ICMs without previous training, extending the performance of these devices and saving cardiologists' time in reviewing cardiac rhythm patterns detection.

Median nerve somatosensory evoked potential alarm related to head and neck positioning for carotid surgery.

Head positioning in carotid surgery represents an often overlooked but sensitive period in the surgical plan. A 53-year-old male presented a significant decrement in median nerve somatosensory evoked potential (mSEP) following head and neck positioning for carotid pseudoaneurysm repair before skin incision.Neurophysiological monitoring was performed with mSEP and electroencephalography early during the patient's preparation and surgery. Within five minutes after rotation and extension of the head to properly expose the surgical field, the contralateral m-SEP significantly decreased in both cortical (N20/P25) and subcortical (P14/N18) components. Partial neck correction led to m-SEP improvement, allowing to proceed with the carotid repair. We discuss possible underlying pathophysiological mechanisms responsible for these changes and highlight the relevance of an early start on monitoring to avoid neurological deficits.

Unexpected median SEPs fluctuations during brain cavernous malformation resection with no post-operative deficit.

Median nerve somatosensory evoked potentials (SEPs) may present changes during cavernous malformation (CM) resection unrelated to new post-operative sensory deficits. We performed intraoperative neurophysiological monitoring of median SEPs (m-SEPs) in three patients who underwent CM resection (surgery) near the sensory-motor cortex. The only preoperative clinical manifestations in all patients were seizures. All patients presented m-SEPs alterations on the side of the lesion during the procedure. Two patients presented permanent changes in the cortical potentials. In the third patient, the cortical and subcortical components suffered temporal fluctuations to return to baselines at the end of the surgery. None of these patients developed new post-operative clinical deficits. During brain cavernous malformation resection, significant fluctuations in the amplitude of different components of m-SEPs may occur. These changes may be due to excitability variations on m-SEP generators and do not translate into new post-operative neurological deficits.

Neuromyelitis Optica Spectrum Disorders (NMOSD) and Connective Tissue Disease (CTD): an Update for the Rheumatologist.

PURPOSE OF REVIEW: To review the pathophysiology, presentation, and treatment of neuromyelitis optica spectrum disorder (NMOSD) and its association with systemic lupus erythematosus (SLE) and Sjogren's syndrome (SS). RECENT FINDINGS: NMOSD is an autoimmune disorder of the central nervous system that primarily targets astrocytes. Although the prevalence is unknown, the coexistence of NMOSD and SLE/SS is well-recognized. Patients with both NMOSD and SLE or SS require may require unique approaches to diagnosis and management. Coexistence of NMOSD and SLE/SS is important for the rheumatologist and neurologist to be able to recognize. For the rheumatologist, NMOSD and its neurologic symptoms represent a distinct disease process from neurologic complications of the patient's underlying connective tissue disease, and it requires distinct acute and chronic management. For the neurologist, the coexistence of SLE and SS can help to establish a diagnosis of NMOSD, or in some situations, the development of neurologic symptoms secondary to NMOSD can lead to the diagnosis of connective tissue disease.

High versus low positive end-expiratory pressure (PEEP) levels for mechanically ventilated adult patients with acute lung injury and acute respiratory distress syndrome.

BACKGROUND: In patients with acute lung injury (ALI) and acute respiratory distress syndrome (ARDS), mortality remains high. These patients require mechanical ventilation, which has been associated with ventilator-induced lung injury. High levels of positive end-expiratory pressure (PEEP) could reduce this condition and improve patient survival. This is an updated version of the review first published in 2013. OBJECTIVES: To assess the benefits and harms of high versus low levels of PEEP in adults with ALI and ARDS. SEARCH METHODS: For our previous review, we searched databases from inception until 2013. For this updated review, we searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, LILACS, and the Web of Science from inception until May 2020. We also searched for ongoing trials (www.trialscentral.org; www.clinicaltrial.gov; www.controlled-trials.com), and we screened the reference lists of included studies. SELECTION CRITERIA: We included randomised controlled trials that compared high versus low levels of PEEP in ALI and ARDS participants who were intubated and mechanically ventilated in intensive care for at least 24 hours. DATA COLLECTION AND ANALYSIS: Two review authors assessed risk of bias and extracted data independently. We contacted investigators to identify additional published and unpublished studies. We used standard methodological procedures expected by Cochrane. MAIN RESULTS: We included four new studies (1343 participants) in this review update. In total, we included 10 studies (3851 participants). We found evidence of risk of bias in six studies, and the remaining studies fulfilled all criteria for low risk of bias. In eight studies (3703 participants), a comparison was made between high and low levels of PEEP, with the same tidal volume in both groups. In the remaining two studies (148 participants), the tidal volume was different between high- and low-level groups. In the main analysis, we assessed mortality occurring before hospital discharge only in studies that compared high versus low PEEP, with the same tidal volume in both groups. Evidence suggests that high PEEP may result in little to no difference in mortality compared to low PEEP (risk ratio (RR) 0.97, 95% confidence interval (CI) 0.90 to 1.04; I² = 15%; 7 studies, 3640 participants; moderate-certainty evidence). In addition, high PEEP may result in little to no difference in barotrauma (RR 1.00, 95% CI 0.64 to 1.57; I² = 63%; 9 studies, 3791 participants; low-certainty evidence). High PEEP may improve oxygenation in patients up to the first and third days of mechanical ventilation (first day: mean difference (MD) 51.03, 95% CI 35.86 to 66.20; I² = 85%; 6 studies, 2594 participants; low-certainty evidence; third day: MD 50.32, 95% CI 34.92 to 65.72; I² = 83%; 6 studies, 2309 participants; low-certainty evidence) and probably improves oxygenation up to the seventh day (MD 28.52, 95% CI 20.82 to 36.21; I² = 0%; 5 studies, 1611 participants; moderate-certainty evidence). Evidence suggests that high PEEP results in little to no difference in the number of ventilator-free days (MD 0.45, 95% CI -2.02 to 2.92; I² = 81%; 3 studies, 1654 participants; low-certainty evidence). Available data were insufficient to pool the evidence for length of stay in the intensive care unit. AUTHORS' CONCLUSIONS: Moderate-certainty evidence shows that high levels compared to low levels of PEEP do not reduce mortality before hospital discharge. Low-certainty evidence suggests that high levels of PEEP result in little to no difference in the risk of barotrauma. Low-certainty evidence also suggests that high levels of PEEP improve oxygenation up to the first and third days of mechanical ventilation, and moderate-certainty evidence indicates that high levels of PEEP improve oxygenation up to the seventh day of mechanical ventilation. As in our previous review, we found clinical heterogeneity - mainly within participant characteristics and methods of titrating PEEP - that does not allow us to draw definitive conclusions regarding the use of high levels of PEEP in patients with ALI and ARDS. Further studies should aim to determine the appropriate method of using high levels of PEEP and the advantages and disadvantages associated with high levels of PEEP in different ARDS and ALI patient populations.

Effects of concurrent exercise training on muscle dysfunction and systemic oxidative stress in older people with COPD.

Oxidative stress is associated with disease severity and limb muscle dysfunction in COPD. Our main goal was to assess the effects of exercise training on systemic oxidative stress and limb muscle dysfunction in older people with COPD. Twenty-nine outpatients with COPD (66-90 years) were randomly assigned to a 12-week exercise training (ET; high-intensity interval training (HIIT) plus power training) or a control (CT; usual care) group. We evaluated mid-thigh muscle cross-sectional area (CSA; computed tomography); vastus lateralis (VL) muscle thickness, pennation angle, and fascicle length (ultrasonography); peak VO2 uptake (VO2peak ) and work rate (Wpeak ) (incremental cardiopulmonary exercise test); rate of force development (RFD); maximal muscle power (Pmax ; force-velocity testing); systemic oxidative stress (plasma protein carbonylation); and physical performance and quality of life. ET subjects experienced changes in mid-thigh muscle CSA (+4%), VL muscle thickness (+11%) and pennation angle (+19%), VO2peak (+14%), Wpeak (+37%), RFD (+32% to 65%), Pmax (+38% to 51%), sit-to-stand time (-24%), and self-reported health status (+20%) (all P < 0.05). No changes were noted in the CT group (P > 0.05). Protein carbonylation decreased among ET subjects (-27%; P < 0.05), but not in the CT group (P > 0.05). Changes in protein carbonylation were associated with changes in muscle size and pennation angle (r = -0.44 to -0.57), exercise capacity (r = -0.46), muscle strength (r = -0.45), and sit-to-stand performance (r = 0.60) (all P < 0.05). The combination of HIIT and power training improved systemic oxidative stress and limb muscle dysfunction in older people with COPD. Changes in oxidative stress were associated with exercise-induced structural and functional adaptations.

Minimum Action Path Theory Reveals the Details of Stochastic Transitions Out of Oscillatory States.

Cell state determination is the outcome of intrinsically stochastic biochemical reactions. Transitions between such states are studied as noise-driven escape problems in the chemical species space. Escape can occur via multiple possible multidimensional paths, with probabilities depending nonlocally on the noise. Here we characterize the escape from an oscillatory biochemical state by minimizing the Freidlin-Wentzell action, deriving from it the stochastic spiral exit path from the limit cycle. We also use the minimized action to infer the escape time probability density function.

Native V. californicum Alkaloid Combinations Induce Differential Inhibition of Sonic Hedgehog Signaling.

Veratrum californicum is a rich source of steroidal alkaloids such as cyclopamine, a known inhibitor of the Hedgehog (Hh) signaling pathway. Here we provide a detailed analysis of the alkaloid composition of V. californicum by plant part through quantitative analysis of cyclopamine, veratramine, muldamine and isorubijervine in the leaf, stem and root/rhizome of the plant. To determine whether additional alkaloids in the extracts contribute to Hh signaling inhibition, the concentrations of these four alkaloids present in extracts were replicated using commercially available standards, followed by comparison of extracts to alkaloid standard mixtures for inhibition of Hh signaling using Shh-Light II cells. Alkaloid combinations enhanced Hh signaling pathway antagonism compared to cyclopamine alone, and significant differences were observed in the Hh pathway inhibition between the stem and root/rhizome extracts and their corresponding alkaloid standard mixtures, indicating that additional alkaloids present in these extracts are capable of inhibiting Hh signaling.

Acute Respiratory Distress Syndrome: Mortality in a Single Center According to Different Definitions.

BACKGROUND: Mortality in acute lung injury (ALI) remains high, with outcome data arising mostly from multicenter studies. We undertook this investigation to determine hospital mortality in patients with ALI in a single center. METHODS: We studied patients admitted between 2005 and 2012 with ALI and acute respiratory distress syndrome (ARDS) according to the American European Consensus Conference (AECC) criteria and recorded clinical variables. Thereafter, patients were classified as subgroups according to the AECC and Berlin definition in order to compare the clinical characteristics and outcomes. RESULTS: In the 93 patients comprising the study, hospital mortality was 38%. Mortality at 28 days was 36%. Multivariate analysis associated hospital mortality with age and Pao2/Fio2 on day 1 ( P < .001). Differences resulted between the subgroups of AECC (ALI vs ARDS) and Berlin (mild vs moderate vs severe ARDS) in the lung injury score, Pao2/Fio2, Pao2/PAo2, PaCo2 on day 1, and hospital mortality. CONCLUSION: The overall hospital mortality (38%) was similar to that of other studies and according to the presence of ARDS (Pao2/Fio2 ≤ 200), we found significant differences between ALI and ARDS (AECC) and between mild and moderate or severe ARDS (Berlin) in baseline respiratory variables and mortality.

Religion in Motion: Continuities and Symbolic Affinities in Religion and Sport.

One of the major transformations in religion in contemporary societies has been the decline of church institutions and their reconstruction within a diverse network of associations, therapies, markets and other unconventional spiritual services. Based on extensive ethnographic fieldwork on religious behaviours and dynamics in sports contexts, and taking the similarities between sport and religion as the point of departure, this paper analyses, reflects on and theorises about the symbolic affinities of these two contemporary social institutions. The results show that symbolism converges in the religious element, tending to improve aspects related to sports ethics and establishing affective experiences among participants, with positive results for their physical and mental wellbeing. The findings indicate that a symbolic analysis of the various facets of sport is a useful approach for gaining a better understanding of this phenomenon, since besides being biological, diseases are also cultural and social, and thus, disease, religion and ritual are emotionally related.

Stochastic multi-scale models of competition within heterogeneous cellular populations: Simulation methods and mean-field analysis.

We propose a modelling framework to analyse the stochastic behaviour of heterogeneous, multi-scale cellular populations. We illustrate our methodology with a particular example in which we study a population with an oxygen-regulated proliferation rate. Our formulation is based on an age-dependent stochastic process. Cells within the population are characterised by their age (i.e. time elapsed since they were born). The age-dependent (oxygen-regulated) birth rate is given by a stochastic model of oxygen-dependent cell cycle progression. Once the birth rate is determined, we formulate an age-dependent birth-and-death process, which dictates the time evolution of the cell population. The population is under a feedback loop which controls its steady state size (carrying capacity): cells consume oxygen which in turn fuels cell proliferation. We show that our stochastic model of cell cycle progression allows for heterogeneity within the cell population induced by stochastic effects. Such heterogeneous behaviour is reflected in variations in the proliferation rate. Within this set-up, we have established three main results. First, we have shown that the age to the G1/S transition, which essentially determines the birth rate, exhibits a remarkably simple scaling behaviour. Besides the fact that this simple behaviour emerges from a rather complex model, this allows for a huge simplification of our numerical methodology. A further result is the observation that heterogeneous populations undergo an internal process of quasi-neutral competition. Finally, we investigated the effects of cell-cycle-phase dependent therapies (such as radiation therapy) on heterogeneous populations. In particular, we have studied the case in which the population contains a quiescent sub-population. Our mean-field analysis and numerical simulations confirm that, if the survival fraction of the therapy is too high, rescue of the quiescent population occurs. This gives rise to emergence of resistance to therapy since the rescued population is less sensitive to therapy.

Cyclopamine bioactivity by extraction method from Veratrum californicum.

Veratrum californicum, commonly referred to as corn lily or Californian false hellebore, grows in high mountain meadows and produces the steroidal alkaloid cyclopamine, a potent inhibitor of the Hedgehog (Hh) signaling pathway. The Hh pathway is a crucial regulator of many fundamental processes during vertebrate embryonic development. However, constitutive activation of the Hh pathway contributes to the progression of various cancers. In the present study, a direct correlation was made between the extraction efficiency for cyclopamine from root and rhizome by eight methods, and the associated biological activity in Shh-Light II cells using the Dual-Glo® Luciferase Assay System. Alkaloid recovery ranged from 0.39 to 8.03mg/g, with ethanol soak being determined to be the superior method for obtaining biologically active cyclopamine. Acidic ethanol and supercritical extractions yielded degraded or contaminated cyclopamine with lower antagonistic activity towards Hh signaling.

The effects of intrinsic noise on the behaviour of bistable cell regulatory systems under quasi-steady state conditions.

We analyse the effect of intrinsic fluctuations on the properties of bistable stochastic systems with time scale separation operating under quasi-steady state conditions. We first formulate a stochastic generalisation of the quasi-steady state approximation based on the semi-classical approximation of the partial differential equation for the generating function associated with the chemical master equation. Such approximation proceeds by optimising an action functional whose associated set of Euler-Lagrange (Hamilton) equations provides the most likely fluctuation path. We show that, under appropriate conditions granting time scale separation, the Hamiltonian can be re-scaled so that the set of Hamilton equations splits up into slow and fast variables, whereby the quasi-steady state approximation can be applied. We analyse two particular examples of systems whose mean-field limit has been shown to exhibit bi-stability: an enzyme-catalysed system of two mutually inhibitory proteins and a gene regulatory circuit with self-activation. Our theory establishes that the number of molecules of the conserved species is order parameters whose variation regulates bistable behaviour in the associated systems beyond the predictions of the mean-field theory. This prediction is fully confirmed by direct numerical simulations using the stochastic simulation algorithm. This result allows us to propose strategies whereby, by varying the number of molecules of the three conserved chemical species, cell properties associated to bistable behaviour (phenotype, cell-cycle status, etc.) can be controlled.

Purine nucleoside phosphorylase and xanthine oxidase activities in erythrocytes and plasma from marine, semiaquatic and terrestrial mammals.

Purine nucleoside phosphorylase (PNP) and xanthine oxidase (XO) are key enzymes involved in the purine salvage pathway. PNP metabolizes purine bases to synthetize purine nucleotides whereas XO catalyzes the oxidation of purines to uric acid. In humans, PNP activity is reported to be high in erythrocytes and XO activity to be low in plasma; however, XO activity increases after ischemic events. XO activity in plasma of northern elephant seals has been reported during prolonged fasting and rest and voluntary associated apneas. The objective of this study was to analyze circulating PNP and XO activities in marine mammals adapted to tolerate repeated cycles of ischemia/reperfusion associated with diving (bottlenose dolphin, northern elephant seal) in comparison with semiaquatic (river otter) and terrestrial mammals (human, pig). PNP activities in plasma and erythrocytes, as well as XO activity in plasma, from all species were quantified by spectrophotometry. No clear relationship in circulating PNP or XO activity could be established between marine, semiaquatic and terrestrial mammals. Erythrocytes from bottlenose dolphins and humans are highly permeable to nucleosides and glucose, intraerythrocyte PNP activity may be related to a release of purine nucleotides from the liver. High-energy costs will probably mean a higher ATP degradation rate in river otters, as compared to northern elephant seals or dolphins. Lower erythrocyte PNP activity and elevated plasma XO activity in northern elephant seal could be associated with fasting and/or sleep- and dive-associated apneas.

An assessment of the dynamic of religious ritualism in sporting environments.

The main focus of this study is the analysis of the link between sport, leisure and the behavior, and phenomenon of religion. From the qualitative point of view of social anthropology, fieldwork has been carried out with different informers from different sporting environments. Rather than directly show the fieldwork itself, we have decided to present an interpretation of it through an analysis of the environments, behaviors, attitudes, the discourse of leisure and sport and its relationship with market forces, advertising and the media. In this regard, we point out a reality which for some people is their conscience or reason for being, opening new directions of study and viewpoints in this area of sporting and health studies.