Fetal magnetocardiographic recordings with a prototype bed-based array system of optically-pumped magnetometers.

OBJECTIVE: To record and extract features of fetal cardiac activities with a semi-rigid prototype optically-pumped magnetometers (OPM) sensor array. METHODS: Fetal magnetocardiography (fMCG) data were collected from 15 pregnant women between 28 and 40 weeks gestation. Mothers were lying flat in a customized bed with sensors touching their abdomen from below using a prototype grid. fMCG was extracted to perform standard fetal heart rate variability (FHRV) analysis. RESULTS: fMCG was observed in 13 of the 15 pregnant women. OPM FHRV indicators were in the range of previous SQUID studies. CONCLUSION: Semi-rigid prototype OPM system has the ability to record quality fMCG. fMCG is capable of identifying lethal cardiac rhythm disturbances in the fetus. Our novel application of OPM technology may lower costs and increase maternal comfort, thus expanding fMCG's generalizability.

Function and expression of N-acetyltransferases 1 and 2 are altered in lymphocytes in type 2 diabetes and obesity.

The cytosolic enzymes N-Acetyl Transferases 1 and 2 (NATs) transfer an acetyl group from acetyl-CoA to a xenobiotic substrate. NATs are regulated at the genetic and epigenetic levels by deacetylase enzymes such as sirtuins. The enzymatic expression of NAT1, NAT2, and SIRT1 was evaluated by flow cytometry, as well as the enzymatic activity of NATs by cell culture and HPLC analysis. Six SNPs were determined through genotyping. T2D patients (n = 29) and healthy subjects (n = 25) with a median age of 57 and 50, respectively, were recruited. An increased enzyme expression and a diminished NAT2 enzymatic activity were found in cells of T2D patients compared to the control group, while NAT1 was negatively correlated with body fat percentage and BMI. In contrast, Sirtuin inhibition increased NAT2 activity, while Sirtuin agonism decreased its activity in both groups. The analysis of NAT2 SNPs showed a higher frequency of rapid acetylation haplotypes in T2D patients compared to the control group, possibly associated as a risk factor for diabetes. The enzymatic expression of CD3+NAT2+ cells was higher in the rapid acetylators group compared to the slow acetylators group. The levels and activity of NAT1 were associated with total cholesterol and triglycerides. Meanwhile, CD3+NAT2+ cells and NAT2 activity levels were associated with HbA1c and glucose levels. The results indicate that NAT2 could be involved in metabolic processes related to the development of T2D, due to its association with glucose levels, HbA1c, and the altered SIRT-NAT axis. NAT1 may be involved with dyslipidaemias in people who are overweight or obese.

Correlation of fetal heart rate dynamics to inflammatory markers and brain-derived neurotrophic factor during pregnancy.

OBJECTIVES: This study aims to show the relation between biomarkers in maternal and cord-blood samples and fetal heart rate variability (fHRV) metrics through a non-invasive fetal magnetocardiography (fMCG) technique. METHODS: Twenty-three women were enrolled for collection of maternal serum and fMCG tracings immediately prior to their scheduled cesarean delivery. The umbilical cord blood was collected for measurement of biomarker levels. The fMCG metrics were then correlated to the biomarker levels from the maternal serum and cord blood. RESULTS: Brain-derived neurotrophic factor (BDNF) had a moderate correlation with fetal parasympathetic activity (0.416) and fetal sympathovagal ratios (-0.309; -0.356). Interleukin (IL)-6 also had moderate-sized correlations but with an inverse relationship as compared to BDNF. These correlations were primarily in cord-blood samples and not in the maternal blood. CONCLUSIONS: In this small sample-sized exploratory study, we observed a moderate correlation between fHRV and cord-blood BDNF and IL-6 immediately preceding scheduled cesarean delivery at term. These findings need to be validated in a larger population.

Use of an airway bundle to reduce unplanned extubations in a neonatal intensive care unit.

BACKGROUND: Following the opening of an infant cardiac neonatal intensive care unit, our aim was to determine a baseline UE rate and implement initiatives to target a goal less than 0.5 UEs/100 ventilator days. METHODS: We utilized the Model for Improvement. Key stakeholders included neonatal providers, nurses, and respiratory therapists. We focused on the creation of an airway bundle that addressed securement methods, communication and education. RESULTS: From October 2017 to January 2018, our baseline UE rate was 0.92 UEs/100 ventilator days. Subsequent to the implementation of an airway bundle with high compliance, we observed a significant change in the centerline (0.45 to 0.02 UEs/100 ventilator days) during the spring of 2021, followed by a period of 480 days with no UEs. CONCLUSION: In a unit where UEs were infrequent events, high compliance with an airway bundle led to a significantly sustained decrease in our UE rates.

Exploring the Influence of Fetal Sex on Heart Rate Dynamics Using Fetal Magnetocardiographic Recordings.

Fetal sex has been associated with different development trajectories that cause structural and functional differences between the sexes throughout gestation. Fetal magnetocardiography (fMCG) recordings from 123 participants (64 females and 59 males; one recording/participant) from a database consisting of low-risk pregnant women were analyzed to explore and compare fetal development trajectories of both sexes. The gestational age of the recordings ranged from 28 to 38 weeks. Linear metrics in both the time and frequency domains were applied to study fetal heart rate variability (fHRV) measures that reveal the dynamics of short- and long-term variability. Rates of linear change with GA in these metrics were analyzed using general linear model regressions with assessments for significantly different variances and GA regression slopes between the sexes. The fetal sexes were well balanced for GA and sleep state. None of the fHRV measures analyzed exhibited significant variance heterogeneity between the sexes, and none of them exhibited a significant sex-by-GA interaction. The absence of a statistically significant sex-by-GA interaction on all parameters resulted in none of the regression slope estimates being significantly different between the sexes. With high-precision fMCG recordings, we were able to explore the variation in fHRV parameters as it relates to fetal sex. The fMCG-based fHRV parameters did not show any significant difference in rates of change with gestational age between sexes. This study provides a framework for understanding normal development of the fetal autonomic nervous system, especially in the context of fetal sex.

A Comparative Study on Graft and Overall Survival Rates Between Diabetic and Nondiabetic Kidney Transplant Patients Through Survival Analysis.

Background: Patients with diabetes mellitus (DM) have worse graft and overall survival, but recent evidence suggests that the difference is no longer significant. Objective: To compare the outcomes between patients with end-stage kidney disease due to DM (ESKD-DM) and ESKD due to nondiabetic etiology (ESKD-non-DM) who underwent kidney transplantation (KT) up to 10 years of follow-up. Design: Survival analysis of a retrospective cohort. Setting and Patients: All patients who underwent KT at the Hospital Universitario San Ignacio, Colombia, between 2004 and 2022. Measurements: Overall and graft survival in ESKD-DM and ESKD-non-DM who received KT. Patients who died with functional graft were censored for the calculation of kidney graft survival. Methods: Log-rank test, Cox proportional hazards model, and competing risk analysis were used to compare overall and graft survival in patients with ESKD-DM and ESKD-non-DM who underwent KT. Results: A total of 375 patients were included: 60 (16%) with ESKD-DM and 315 (84%) with ESKD-non-DM. Median follow-up was 83.3 months. Overall survival was lower in patients with ESKD-DM at 5 (75.0% vs 90.8%, P < .001) and 10 years (55.0% vs 86.7%, P < .001). Cardiovascular death was higher in patients with diabetes (27.3% vs 8.2%, P = .021). Death-censored graft survival was similar in both groups (96.7% vs 93.3% at 5 years, P = .324). On multivariate analysis, the factors associated with global survival were DM (hazard ratio [HR] = 2.11, 95% confidence interval [CI] = 1.23-3.60, P = .006), recipient age (HR = 1.05, 95% CI = 1.02-1.08, P < .001), delayed graft function (HR = 2.07, 95% CI = 1.24-3.46, P = .005), and donor age (HR = 1.03, 95% CI = 1.01-1.05, P = .002). In the competing risk analysis, DM was associated with mortality only in the cardiovascular death group (sub-hazard ratio [SHR] = 6.06, 95% CI = 1.01-36.4, P = .049). Limitations: Change in diabetes treatment received over time and adherence to glycemic targets were not considered. The sample size is relatively small, which limits the precision of our estimates. The Kidney Donor Profile Index and the occurrence of treated acute rejection were not included in the regression models. Conclusion: Overall survival is lower in patients with diabetes, possibly due to older age and cardiovascular comorbidities. Therefore, patients with diabetes should be followed more closely to control cardiovascular risk factors. However, there is no difference in graft survival.

Contexte: Les patients diabétiques (DB) sont ceux qui présentent les pires résultats de greffe et de survie globale, mais des données récentes suggèrent que la différence n'est désormais plus significative. Objectif: Comparer les résultats des patients atteints d'insuffisance rénale terminale causée par le DB (IRT-DB) et ceux des patients non-diabétiques (IRT-nonDB) pour une période de 10 ans après une transplantation rénale (TR). Conception: Analyse de la survie d'une cohorte rétrospective. Sujets et cadre de l'étude: Tous les patients qui ont subi une TR à l'Hôpital Universitario San Ignacio (Colombie) entre 2004 et 2022. Mesures: La survie globale et la survie du greffon chez les patients IRT-DB et IRT-nonDB après une TR. Les patients décédés avec un greffon fonctionnel ont été censurés pour le calcul de la survie du greffon. Méthodologie: Le test logarithmique par rangs, un modèle de régression à effet proportionnel de Cox et une analyse des risques concurrents ont été utilisés pour comparer la survie globale et la survie du greffon des patients atteints d'IRT-DB et d'IRT-nonDB après une TR. Résultats: Au total, 375 patients ont été inclus à l'étude, soit 60 patients (16 %) atteints d'IRT-DB et 315 (84 %) atteints d'IRT-nonDB. La durée médiane du suivi était de 83,3 mois. La survie globale était plus faible chez les patients atteints d'IRT-DB à 5 ans (75,0 c. 90,8 %; p<0,001) et à 10 ans (55,0 % c. 86,7 %; p<0,001). Les décès de causes cardiovasculaires ont été plus nombreux chez les patients diabétiques (27,3 % c. 8,2 %; p=0,021). La survie du greffon censurée pour le décès était similaire pour les deux groupes (96,7 % c. 93,3 % à 5 ans, p=0,324). Dans l'analyse multivariée, les facteurs associés à la survie globale étaient le DB (RR=2,11; IC95 : 1,23-3,60; p=0,006), l'âge du receveur (RR=1,05; IC95 : 1,02-1,08; p<0,001), le retard de fonction du greffon (RR = 2,07; IC95 : 1,24-3,46; p = 0,005) et l'âge du donneur (RR = 1,03; IC95 : 1,01-1,05; p=0,002). Dans l'analyse des risques concurrents, le DB a été associé à la mortalité uniquement dans le groupe de patients décédés de causes cardiovasculaires (RRS=6,06; IC95 : 1,01-36,4; p=0,049). Limites: Les modifications dans le traitement du diabète au fil du temps et l'observance des cibles glycémiques n'ont pas été prises en compte. La taille de l'échantillon est relativement faible, ce qui limite la précision des estimations. L'indice de profil du donneur (Kidney Donor Profile Index­KDPI) et la survenue d'un rejet aigu traité n'ont pas été inclus dans les modèles de régression. Conclusion: La survie globale est plus faible chez les patients diabétiques, peut-être en raison de l'âge avancé et des comorbidités cardiovasculaires de ces patients. Les patients diabétiques devraient par conséquent faire l'objet d'un suivi plus rapproché afin de surveiller les facteurs de risque cardiovasculaire. Aucune différence n'a cependant été observée pour la survie du greffon.

Assessing uterine electrophysiology prior to elective term induction of labor.

Objective: The purpose of this study was to determine if uterine electrophysiological signals gathered from 151 non-invasive biomagnetic sensors spread over the abdomen were associated with successful induction of labor (IOL). Study design: Uterine magnetomyogram (MMG) signals were collected using the SARA (SQUID Array for Reproductive Assessment) device from 33 subjects between 37 and 42 weeks gestational age. The signals were post-processed, uterine contractile related MMG bursts were detected, and parameters in the time and frequency domain were extracted. The modified Bishop score calculated at admission was used to determine the method of IOL. Wilcoxon's rank-sum test was used to compare IOL successes and failures for differences in gestational age (GA), parity, modified Bishop's score, maximum oxytocin, and electrophysiological parameters extracted from MMG. Results: The average parity was three times (3x) higher (1.53 versus 0.50; p = 0.039), and the average modified Bishop score was 2x higher (3.32 versus 1.63; p = 0.032) amongst IOL successes than failures, while the average GA and maximum oxytocin showed a small difference. For the MMG parameters, successful IOLs had, on average, 3.5x greater mean power during bursts (0.246 versus 0.070; p = 0.034) and approximately 1.2x greater mean number of bursts (2.05 versus 1.68; p = 0.036) compared to the failed IOLs, but non-significant differences were observed in mean peak frequency, mean burst duration, and mean duration between bursts. Conclusion: The study showed that inductions of labor that took less than 24 h to deliver have a higher mean power in the baseline electrophysiological activity of the uterus when recorded prior to planned induction. The results are indicative that baseline electrophysiological activity measured prior to induction is associated with successful induction.

Reduced osteoprotegerin expression by osteocytes may contribute to rebound resorption after denosumab discontinuation.

Denosumab is an anti-RANKL Ab that potently suppresses bone resorption, increases bone mass, and reduces fracture risk. Discontinuation of denosumab causes rapid rebound bone resorption and bone loss, but the molecular mechanisms are unclear. We generated humanized RANKL mice and treated them with denosumab to examine the cellular and molecular conditions associated with rebound resorption. Denosumab potently suppressed both osteoclast and osteoblast numbers in cancellous bone in humanized RANKL mice. The decrease in osteoclast number was not associated with changes in osteoclast progenitors in bone marrow. Long-term, but not short-term, denosumab administration reduced osteoprotegerin (OPG) mRNA in bone. Localization of OPG expression revealed that OPG mRNA is produced by a subpopulation of osteocytes. Long-term denosumab administration reduced osteocyte OPG mRNA, suggesting that OPG expression declines as osteocytes age. Consistent with this, osteocyte expression of OPG was more prevalent near the surface of cortical bone in humans and mice. These results suggest that new osteocytes are an important source of OPG in remodeling bone and that suppression of remodeling reduces OPG abundance by reducing new osteocyte formation. The lack of new osteocytes and the OPG they produce may contribute to rebound resorption after denosumab discontinuation.

Modified abaxial sesamoid nerve block provides enhanced proximal diffusion compared to basisesamoid block and lower proximal diffusion than traditional low plantar nerve block in equine hind limbs: ex vivo and in vivo study.

OBJECTIVE: To determine the proximal diffusion distance of radiopaque contrast medium and mepivacaine/methylene blue solution and incidence of inadvertent intrasynovial and intravascular injections of modified sesamoid nerve block (MASB) when compared with traditional plantar nerve analgesia techniques of the equine distal hind limb. SAMPLE: Ex vivo model: 18 hind limbs; and in vivo model: 5 horses in a crossover study. METHODS: In the ex vivo model, a mepivacaine/methylene blue solution was used to compare the diffusion distance between MASB, basisesamoid block (BSB), and traditional low plantar block (TLPB). Ten minutes after injection, skin was dissected and proximal diffusion distance of the dye patch was measured. In the in vivo model, both hind limbs were injected with radiopaque contrast medium with either MASB or TLPB. Ten minutes after injection, a radiograph was acquired and the proximal diffusion of the contrast medium patch was measured. RESULTS: In the ex vivo model, solution proximal diffusion distance for MASB was significantly longer than BSB (P < .050) and significantly shorter than TLPB (P < .050). Both techniques reached the proximal aspect of DFTS similarly (P = .289), and no difference in the incidence of intrasynovial or intravascular injections was observed (P = .292). In the in vivo model, contrast medium proximal diffusion of MASB was significantly shorter than TLPB (P < .050). The proportion of injections that diffused subcutaneously to the proximal aspect of the proximal pouch of the DFTS was not significantly different between techniques (P = .136). No difference in the incidence of DFTS intrasynovial or intravascular injections was observed (P = .305). CLINICAL RELEVANCE: MASB presented significantly more proximal diffusion than BSB and less proximal diffusion than TLPB, consistently reached the proximal aspect of DFTS, and presented a very low risk of intrasynovial and intravascular injections.

The water-energy-food nexus in biodiversity conservation: A systematic review around sustainability transitions of agricultural systems.

The Water Energy Food nexus is a powerful topic in agricultural systems to elucidate threats to biodiversity conservation and culture. This paper aimed to recapitulate nexus thinking research, focusing on social-ecological transitions of agriculture systems and biodiversity management within the Water-Energy-Food nexus. We developed a systematic review and a bibliometric analysis derived from 529 documents in the Scopus database. The ToS method identified a total of 81 relevant information in the sample of documents (529) categorised into roots (10), trunks (9) and leaves (62). This review paper situates types, focus, and highlights regarding biodiversity and prevalent thematic research areas such as "Food Nexus", "Environmental Flows", "Sustainability", "Transitions", and "Governance". Our results suggest that future research should focus on the nexus of "Water-Energy-Food-Biodiversity" and propose a transdisciplinary approach to elucidate the state of sustainability transitions in the agricultural systems at the landscape level. It could increase stakeholder interest in conservation, and sustainability management, to reverse biodiversity losses in ecosystems.

Implementation of Rapid Genome Sequencing for Critically Ill Infants With Complex Congenital Heart Disease.

BACKGROUND: Rapid genome sequencing (rGS) has been shown to improve care of critically ill infants. Congenital heart disease (CHD) is a leading cause of infant mortality and is often caused by genetic disorders, yet the utility of rGS has not been prospectively studied in this population. METHODS: We conducted a prospective evaluation of rGS to improve the care of infants with complex CHD in our cardiac neonatal intensive care unit. RESULTS: In a cohort of 48 infants with complex CHD, rGS diagnosed 14 genetic disorders in 13 (27%) individuals and led to changes in clinical management in 8 (62%) cases with diagnostic results. These included 2 cases in whom genetic diagnoses helped avert intensive, futile interventions before cardiac neonatal intensive care unit discharge, and 3 cases in whom eye disease was diagnosed and treated in early childhood. CONCLUSIONS: Our study provides the first prospective evaluation of rGS for infants with complex CHD to our knowledge. We found that rGS diagnosed genetic disorders in 27% of cases and led to changes in management in 62% of cases with diagnostic results. Our model of care depended on coordination between neonatologists, cardiologists, surgeons, geneticists, and genetic counselors. These findings highlight the important role of rGS in CHD and demonstrate the need for expanded study of how to implement this resource to a broader population of infants with CHD.

Crucial role of iron in epigenetic rewriting during adipocyte differentiation mediated by JMJD1A and TET2 activity.

Iron metabolism is closely associated with the pathogenesis of obesity. However, the mechanism of the iron-dependent regulation of adipocyte differentiation remains unclear. Here, we show that iron is essential for rewriting of epigenetic marks during adipocyte differentiation. Iron supply through lysosome-mediated ferritinophagy was found to be crucial during the early stage of adipocyte differentiation, and iron deficiency during this period suppressed subsequent terminal differentiation. This was associated with demethylation of both repressive histone marks and DNA in the genomic regions of adipocyte differentiation-associated genes, 　including Pparg, which encodes PPARγ, the master regulator of adipocyte differentiation. In addition, we identified several epigenetic demethylases to be responsible for iron-dependent adipocyte differentiation, with the histone demethylase jumonji domain-containing 1A and the DNA demethylase ten-eleven translocation 2 as the major enzymes. The interrelationship between repressive histone marks and DNA methylation was indicated by an integrated genome-wide association analysis, and was also supported by the findings that both histone and DNA demethylation were suppressed by either the inhibition of lysosomal ferritin flux or the knockdown of iron chaperone poly(rC)-binding protein 2. In summary, epigenetic regulations through iron-dependent control of epigenetic enzyme activities play an important role in the organized gene expression mechanisms of adipogenesis.

Characterization of morphological and biological aspects of venomous caterpillars of the genus Lonomia Walker (Lepidoptera: Saturniidae) in Colombia.

The genus Lonomia Walker, 1855 (Lepidoptera: Saturniidae) is of particular interest to the medical community, since the scoli of these caterpillars harbor a venom that induces hemorrhaging in humans. In Colombia, deadly encounters with Lonomia achelous (Cramer, 1777), have been reported since 2000. There is little information on the main biological and ecological aspects of this genus to help better understand and develop prevention strategies. This study aimed to describe morphological and biological aspects (especially of immature stages) of four recently reported species of Lonomia in Colombia that pose a risk to humans. We collected caterpillars and adults from five localities and reared them under laboratory conditions. Specimens were identified using DNA barcoding and dissection of adult male genitalia. We provided the first description, to our knowledge, of part of the life cycles of Lonomia casanarensis Brechlin, 2017 and Lonomia orientoandensis Brechlin & Meister, 2011 and the complete life cycles of Lonomia columbiana Lemaire, 1972 and Lonomia orientocordillera Brechlin, Käch & Meister, 2013. We also present the first records of the parasitoids of L. orientocordillera, and L. casanarensis and new host plants. This information will guide not only their morphological recognition and the identification of their parasitoids and hosts, but also will guide rearing methods of these and other Lonomia species in new studies to prevent incidents with humans and create specific antivenoms.

The effect of maternal pregestational diabetes on fetal autonomic nervous system.

Heart rate variability assessment of neonates of pregestational diabetic mothers have shown alterations in the autonomic nervous system (ANS). The objective was to study the effect of maternal pregestational diabetes on ANS at the fetal stage by combining cardiac and movement parameters using a non-invasive fetal magnetocardiography (fMCG) technique. This is an observational study with 40 participants where fetuses from a group of 9 Type 1, 19 Type 2 diabetic, and 12 non-diabetic pregnant women were included. Time and frequency domain fetal heart rate variability (fHRV) and coupling of movement and heart rate acceleration parameters related to fetal ANS were analyzed. Group differences were investigated using analysis of covariance to adjust for gestational age (GA). When compared to non-diabetics, the Type 1 diabetics had a 65% increase in average ratio of very low-frequency (VLF) to low-frequency (LF) bands and 63% average decrease in coupling index after adjusting for GA. Comparing Type 2 diabetics to non-diabetics, there was an average decrease in the VLF (50%) and LF bands (63%). Diabetics with poor glycemic control had a higher average VLF/LF (49%) than diabetics with good glycemic control. No significant changes at p < 0.05 were observed in high-frequency (HF) frequency domain parameters or their ratios, or in the time domain. Fetuses of pregestational diabetic mothers exhibited some differences in fHRV frequency domain and heart rate-movement coupling when compared to non-diabetics but the effect of fHRV related to fetal ANS and sympathovagal balance were not as conclusive as observed in the neonates of pregestational diabetic mothers.

Risk factors associated with acute kidney injury in a cohort of hospitalized patients with COVID-19.

BACKGROUND: Patients with COVID-19 have a high incidence of acute kidney injury (AKI), which is associated with mortality. The objective of the study was to determine the factors associated with AKI in patients with COVID-19. METHODOLOGY: A retrospective cohort was established in two university hospitals in Bogotá, Colombia. Adults hospitalized for more than 48 h from March 6, 2020, to March 31, 2021, with confirmed COVID-19 were included. The main outcome was to determine the factors associated with AKI in patients with COVID-19 and the secondary outcome was estimate the incidence of AKI during the 28 days following hospital admission. RESULTS: A total of 1584 patients were included: 60.4% were men, 738 (46.5%) developed AKI, 23.6% were classified as KDIGO 3, and 11.1% had renal replacement therapy. The risk factors for developing AKI during hospitalization were male sex (OR 2.28, 95% CI 1.73-2.99), age (OR 1.02, 95% CI 1.01-1.03), history of chronic kidney disease (CKD) (OR 3.61, 95% CI 2.03-6.42), High Blood Pressure (HBP) (OR 6.51, 95% CI 2.10-20.2), higher qSOFA score to the admission (OR 1.4, 95% CI 1.14-1.71), the use of vancomycin (OR 1.57, 95% CI 1.05-2.37), piperacillin/tazobactam (OR 1.67, 95% CI 1.2-2.31), and vasopressor support (CI 2.39, 95% CI 1.53-3.74). The gross hospital mortality for AKI was 45.5% versus 11.7% without AKI. CONCLUSIONS: This cohort showed that male sex, age, history of HBP and CKD, presentation with elevated qSOFA, in-hospital use of nephrotoxic drugs and the requirement for vasopressor support were the main risk factors for developing AKI in patients hospitalized for COVID-19.

Deadly and venomous Lonomia caterpillars are more than the two usual suspects.

Caterpillars of the Neotropical genus Lonomia (Lepidoptera: Saturniidae) are responsible for some fatal envenomation of humans in South America inducing hemostatic disturbances in patients upon skin contact with the caterpillars' spines. Currently, only two species have been reported to cause hemorrhagic syndromes in humans: Lonomia achelous and Lonomia obliqua. However, species identifications have remained largely unchallenged despite improved knowledge of venom diversity and growing evidence that the taxonomy used over past decades misrepresents and underestimates species diversity. Here, we revisit the taxonomic diversity and distribution of Lonomia species using the most extensive dataset assembled to date, combining DNA barcodes, morphological comparisons, and geographical information. Considering new evidence for seven undescribed species as well as three newly proposed nomenclatural changes, our integrative approach leads to the recognition of 60 species, of which seven are known or strongly suspected to cause severe envenomation in humans. From a newly compiled synthesis of epidemiological data, we also examine the consequences of our results for understanding Lonomia envenomation risks and call for further investigations of other species' venom activities. This is required and necessary to improve alertness in areas at risk, and to define adequate treatment strategies for envenomed patients, including performing species identification and assessing the efficacy of anti-Lonomia serums against a broader diversity of species.

Operative mortality after Society of Thoracic Surgeons-European Association for Cardio-Thoracic Surgery Mortality Category 1 to 3 procedures: Deficiencies and opportunities for quality improvement.

OBJECTIVES: We examined cases of operative mortality at a single quaternary academic center for patients undergoing relatively lower-risk (Society of Thoracic Surgeons-European Association for Cardio-Thoracic Surgery Mortality Category 1-3) procedures, as a means of identifying systemic weaknesses and opportunities for quality improvement. METHODS: A retrospective review of all operative mortality events for patients who underwent a Society of Thoracic Surgeons-European Association for Cardio-Thoracic Surgery Mortality Category 1, 2, or 3 index procedure (2009-2020) at our institution was performed. After a detailed chart review was performed by 2 independent faculty for each case, factors and system deficiencies that contributed to mortality were identified. RESULTS: A total of 42 mortalities were identified. A total of 37 patients (88%) had at least 1 Society of Thoracic Surgeons-designated risk factor, including prior cardiac operations (48%), extracardiac malformations (43%), and preoperative ventilation (33%). Eight patients (19%) had non-Society of Thoracic Surgeons-designated preoperative patient-level variables considered as at potential risk, including severe ventricular dysfunction, pulmonary hypertension, lung hypoplasia, and undiagnosed severe coronary abnormalities. Four patients (10%) had no identified preoperative risk factors. After detailed chart review, 5 broad categories were identified: patient-related factors (n = 33; 78%), postoperative infection (n = 13; 31%), postoperative residual lesions (n = 7; 17%), Fontan physiology failure (n = 4; 10%), and unexplained left ventricular failure after tetralogy of Fallot repair (n = 3; 7%). A total of 74% of patients had at least 1 preoperative, intraoperative, or postoperative system deficiency. A total of 50% of surgeries were urgent or emergency. CONCLUSIONS: Operative mortality after Society of Thoracic Surgeons-European Association for Cardio-Thoracic Surgery Mortality Category 1 to 3 procedures is related to the presence of multifactorial risk patterns (Society of Thoracic Surgeons and non-Society of Thoracic Surgeons-designated patient-level risk factors and variables, broad risk categories, system deficiencies, emergency surgery). A multidisciplinary approach to care, with early recognition and treatment of modifiable additional burdens, could reduce this risk.

Invasion of Toxoplasma gondii bradyzoites: Molecular dissection of the moving junction proteins and effective vaccination targets.

Toxoplasmosis is a neglected parasitic disease necessitating public health control. Host cell invasion by Toxoplasma occurs at different stages of the parasite's life cycle and is crucial for survival and establishment of infection. In tachyzoites, which are responsible for acute toxoplasmosis, invasion involves the formation of a molecular bridge between the parasite and host cell membranes, referred to as the moving junction (MJ). The MJ is shaped by the assembly of AMA1 and RON2, as part of a complex involving additional RONs. While this essential process is well characterized in tachyzoites, the invasion process remains unexplored in bradyzoites, which form cysts and are responsible for chronic toxoplasmosis and contribute to the dissemination of the parasite between hosts. Here, we show that bradyzoites invade host cells in an MJ-dependent fashion but differ in protein composition from the tachyzoite MJ, relying instead on the paralogs AMA2 and AMA4. Functional characterization of AMA4 reveals its key role for cysts burden during the onset of chronic infection, while being dispensable for the acute phase. Immunizations with AMA1 and AMA4, alone or in complex with their rhoptry neck respective partners RON2 and RON2L1, showed that the AMA1-RON2 pair induces strong protection against acute and chronic infection, while the AMA4-RON2L1 complex targets more selectively the chronic form. Our study provides important insights into the molecular players of bradyzoite invasion and indicates that invasion of cyst-forming bradyzoites contributes to cyst burden. Furthermore, we validate AMA-RON complexes as potential vaccine candidates to protect against toxoplasmosis.