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Zebra mussels, Dreissena polymorpha, have recently invaded Central Texas. More information is needed to predict their spread in this region and inform management decisions. In this study, we examined riverine zebra mussel dispersal from, and settlement downstream of, a recently invaded reservoir, Lake Belton. Veliger samples and settlement of juveniles on artificial substrata were monitored at sites within Lake Belton and 0.4 to 54.7 river kilometers (rkm) downstream from the lake outlet. Veliger density varied greatly across space and time with peak densities of live veligers found in both early summer (May-June) and fall (October). High juvenile settlement occurred consistently at 2.5 and 6.0 rkm downstream. Juvenile settlement was not observed = 13 rkm downstream until the spring of 2016 after a period of prolonged increased river discharge. Our findings suggest that mussels were dispersal limited in 2015, and prolonged periods of increased river discharge may have facilitated their dispersal further downstream in 2016. [ABSTRACT FROM AUTHOR]

The Gram-positive model bacterium Bacillus subtilis is used for many biotechnological applications, including the large-scale production of vitamins. For vitamin B5, a precursor for coenzyme A synthesis, there is so far no established fermentation process available, and the metabolic pathways that involve this vitamin are only partially understood. In this study, we have elucidated the complete pathways for the biosynthesis of pantothenate and coenzyme A in B. subtilis . Pantothenate can not only be synthesized but also be taken up from the medium. We have identified the enzymes and the transporter involved in the pantothenate biosynthesis and uptake. High-affinity vitamin B5 uptake in B. subtilis requires an ATP-driven energy coupling factor transporter with PanU (previously YhfU) as the substrate-specific subunit. Moreover, we have identified a salvage pathway for coenzyme A acquisition that acts on complex medium even in the absence of pantothenate synthesis. This pathway requires rewiring of sulfur metabolism resulting in the increased expression of a cysteine transporter. In the salvage pathway, the bacteria import cysteinopantetheine, a novel naturally occurring metabolite, using the cystine transport system TcyJKLMN. This work lays the foundation for the development of effective processes for vitamin B5 and coenzyme A production using B. subtilis ., Importance: Vitamins are essential components of the diet of animals and humans. Vitamins are thus important targets for biotechnological production. While efficient fermentation processes have been developed for several vitamins, this is not the case for vitamin B5 (pantothenate), the precursor of coenzyme A. We have elucidated the complete pathway for coenzyme A biosynthesis in the biotechnological workhorse Bacillus subtilis . Moreover, a salvage pathway for coenzyme A synthesis was found in this study. Normally, this pathway depends on pantetheine; however, we observed activity of the salvage pathway on complex medium in mutants lacking the pantothenate biosynthesis pathway even in the absence of supplemented pantetheine. This required rewiring of metabolism by expressing a cystine transporter due to acquisition of mutations affecting the regulation of cysteine metabolism. This shows how the hidden "underground metabolism" can give rise to the rapid formation of novel metabolic pathways., Competing Interests: The authors declare no conflict of interest.

Background and Aims: Steatotic liver disease (SLD) is generally considered to represent a hepatic manifestation of metabolic syndrome and includes a disease spectrum comprising isolated steatosis, metabolic dysfunction-associated steatohepatitis, liver fibrosis and ultimately cirrhosis. A better understanding of the detailed underlying pathogenic mechanisms of this transition is crucial for the design of new and efficient therapeutic interventions. Thymocyte differentiation antigen (Thy-1, also known as CD90) expression on fibroblasts controls central functions relevant to fibrogenesis, including proliferation, apoptosis, cytokine responsiveness, and myofibroblast differentiation., Methods: The impact of Thy-1 on the development of SLD and progression to fibrosis was investigated in high-fat diet (HFD)-induced SLD wild-type and Thy-1-deficient mice. In addition, the serum soluble Thy-1 (sThy-1) concentration was analysed in patients with metabolic dysfunction-associated SLD stratified according to steatosis, inflammation, or liver fibrosis using noninvasive markers., Results: We demonstrated that Thy-1 attenuates the development of fatty liver and the expression of profibrogenic genes in the livers of HFD-induced SLD mice. Mechanistically, Thy-1 directly inhibits the profibrotic activation of nonparenchymal liver cells. In addition, Thy-1 prevents palmitic acid-mediated amplification of the inflammatory response of myeloid cells, which might indirectly contribute to the pronounced development of liver fibrosis in Thy-1-deficient mice. Serum analysis of patients with metabolically associated steatotic liver disease syndrome revealed that sThy-1 expression is correlated with liver fibrosis status, as assessed by liver stiffness, the Fib4 score, and the NAFLD fibrosis score., Conclusion: Our data strongly suggest that Thy-1 may function as a fibrosis-protective factor in mouse and human SLD., (© 2024 The Authors. Liver International published by John Wiley & Sons Ltd.)

Background: The pain analgesia hypothesis suggests that reduced pain sensitivity (PS) is a specific risk factor for the engagement in non-suicidal self-injury (NSSI). Consistent with this, several studies found reduced PS in adults as well as adolescents with NSSI. Cross-sectional studies in adults with borderline personality disorder (BPD) suggest that PS may (partially) normalize after remission or reduction of BPD symptoms. The objective of the present study was to investigate the development of PS over 1 year in a sample of adolescents with NSSI and to investigate whether PS at baseline predicts longitudinal change in NSSI., Methods: N = 66 adolescents who underwent specialized treatment for NSSI disorder participated in baseline and 1-year follow-up assessments, including heat pain stimulation for the measurement of pain threshold and tolerance. Associations between PS and NSSI as well as BPD and depressive symptoms were examined using negative binomial, logistic, and linear regression analyses., Results: We found that a decrease in pain threshold over time was associated with reduced NSSI (incident rate ratio = 2.04, p = 0.047) and that higher pain tolerance at baseline predicted lower probability for NSSI (odds ratio = 0.42, p = 0.016) 1 year later. However, the latter effect did not survive Holm correction ( p = 0.059). No associations between PS and BPD or depressive symptoms were observed., Conclusion: Our findings suggest that pain threshold might normalize with a decrease in NSSI frequency and could thus serve as a state marker for NSSI.

Resting-state electroencephalography (EEG) microstates are brief periods (60-120 ms) of quasi-stable scalp field potentials, indicating simultaneous activity of large-scale networks. Microstates are assumed to reflect basic neuronal information processing. A common finding in psychosis spectrum disorders is that microstates classes C and D are altered. Whereas evidence in adults with schizophrenia is substantial, little is known about effects in underage patients, particularly in those at clinical high risk for psychosis (CHR) and first-episode psychosis (FEP). The present study used 74-channel EEG to investigate microstate effects in a large sample of patients with CHR (n = 100) and FEP (n = 33), clinical controls (CC, n = 18), as well as age-matched healthy controls (HC, n = 68). Subjects span an age range from 9 to 35 years, thus, covering underage patients as well as the most vulnerable period for the emergence of psychosis and its prodrome. Four EEG microstates classes were analyzed (A-D). In class D, CHR and FEP patients showed a decrease compared to HC, and CHR patients also to CC. An increase in class C was found in CHR and FEP compared to HC but not to CC. Results were independent of age and no differences were found between the psychosis spectrum groups. The findings suggest an age-independent decrease of microstate class D to be specific to the psychosis spectrum, whereas the increase in class C seems to reflect unspecific psychopathology. Overall, present data strengthens the role of microstate D as potential biomarker for psychosis, as early as in adolescence and already in CHR status., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Non-suicidal self-injury (NSSI) is a transdiagnostic psychiatric symptom with high prevalence and relevance in child and adolescent psychiatry. Therefore, it is of great interest to identify a biological phenotype associated with NSSI. The aim of the present study was to cross-sectionally investigate patterns of biological markers underlying NSSI and associated psychopathology in a sample of female patients and healthy controls. Comprehensive clinical data, saliva and blood samples, heart rate variability and pain sensitivity, were collected in n = 149 patients with NSSI and n = 40 healthy participants. Using machine-based learning, we tested the extent to which oxytocin, dehydroepiandrosterone (DHEA), beta-endorphin, free triiodothyronine (fT3), leukocytes, heart rate variability and pain sensitivity were able to classify participants regarding their clinical outcomes in NSSI, depression and borderline personality disorder symptomatology. We evaluated the predictive performance of several models (linear and logistic regression, elastic net regression, random forests, gradient boosted trees) using repeated cross-validation. With NSSI as an outcome variable, both logistic regression and machine learning models showed moderate predictive performance (Area under the Receiver Operating Characteristic Curve between 0.67 and 0.69). Predictors with the highest predictive power were low oxytocin (OR = 0.55; p = 0.002), low pain sensitivity (OR = 1.15; p = 0.021), and high leukocytes (OR = 1.67; p = 0.015). For the psychopathological outcome variables, i.e., depression and borderline personality disorder symptomatology, models including the biological variables performed not better than the null model. A combination of hormonal and inflammatory markers, as well as pain sensitivity, were able to discriminate between participants with and without NSSI disorder. Based on this dataset, however, complex machine learning models were not able to detect non-linear patterns of associations between the biological markers. These findings need replication and future research will reveal the extent to which the respective biomarkers are useful for longitudinal prediction of clinical outcomes or treatment response., (© 2024. The Author(s).)

Proton-dependent oligopeptide transporters (POTs) are promiscuous transporters of the major facilitator superfamily that constitute the main route of entry for a wide range of dietary peptides and orally administrated peptidomimetic drugs. Given their clinical and pathophysiological relevance, several POT homologs have been studied extensively at the structural and molecular level. However, the molecular basis of recognition and transport of diverse peptide substrates has remained elusive. We present 14 X-ray structures of the bacterial POT DtpB in complex with chemically diverse di- and tripeptides, providing novel insights into the plasticity of the conserved central binding cavity. We analyzed binding affinities for more than 80 peptides and monitored uptake by a fluorescence-based transport assay. To probe whether all 8400 natural di- and tripeptides can bind to DtpB, we employed state-of-the-art molecular docking and machine learning and conclude that peptides with compact hydrophobic residues are the best DtpB binders., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Objectives: We carried out this work with the aim of assessing the effectiveness of a set of interventions over time for the administration of antibiotics., Design: Prospective observational study., Setting: Patients admitted to the emergency room and ICU of the hospital where the study was conducted are evaluated daily for some sociodemographic and clinical variables. Among them are some quality indicators, such as the time between the diagnosis of sepsis or septic shock until the start of the infusion of antibiotics. This indicator reflects several aspects related to a set of assistance measures (adequacy of antibiotic dispensation, rapid response team (RRT), sepsis care quality improvement program, antimicrobial management program, improvements in emergency department assistance)., Patients or Participants: Patients with sepsis or septic shock were admitted to the ICU of a university and public hospital in southern Brazil., Main Variables of Interest: The time between the diagnosis of sepsis or septic shock and the beginning of the infusion of antibiotics., Results: Between 2013 and 2018, 1676 patients were evaluated. The mean time for antibiotic infusion decreased from 6.1 ± 8.6 hours to 1.7 ± 2.9 hours ( p < 0.001). The percentage of patients who received antibiotics in the first hour increased from 20.7 to 59.0% ( p < 0.001)., Conclusion: In this study, we demonstrated that a set of actions adopted in a large tertiary hospital was associated with decreased time to start antibiotic therapy in septic patients., How to Cite This Article: Moraes RB, Haas JS, Vidart J, Nicolaidis R, Deutschendorf C, Moretti MMS, et al . A Coordinated and Multidisciplinary Strategy can Reduce the Time for Antibiotics in Septic Patients at a University Hospital. Indian J Crit Care Med 2023;27(7):465-469., Competing Interests: Source of support: Nil Conflict of interest: None, (Copyright © 2023; The Author(s).)

Microbial components have a range of direct effects on the fetal brain. However, little is known about the cellular targets and molecular mechanisms that mediate these effects. Neural progenitor cells (NPCs) control the size and architecture of the brain and understanding the mechanisms regulating NPCs is crucial to understanding brain developmental disorders. We identify ventricular radial glia (vRG), the primary NPC, as the target of bacterial cell wall (BCW) generated during the antibiotic treatment of maternal pneumonia. BCW enhanced proliferative potential of vRGs by shortening the cell cycle and increasing self-renewal. Expanded vRGs propagated to increase neuronal output in all cortical layers. Remarkably, Toll-like receptor 2 (TLR2), which recognizes BCW, localized at the base of primary cilia in vRGs and the BCW-TLR2 interaction suppressed ciliogenesis leading to derepression of Hedgehog (HH) signaling and expansion of vRGs. We also show that TLR6 is an essential partner of TLR2 in this process. Surprisingly, TLR6 alone was required to set the number of cortical neurons under healthy conditions. These findings suggest that an endogenous signal from TLRs suppresses cortical expansion during normal development of the neocortex and that BCW antagonizes that signal through the TLR2/cilia/HH signaling axis changing brain structure and function. IMPORTANCE Fetal brain development in early gestation can be impacted by transplacental infection, altered metabolites from the maternal microbiome, or maternal immune activation. It is less well understood how maternal microbial subcomponents that cross the placenta, such as bacterial cell wall (BCW), directly interact with fetal neural progenitors and neurons and affect development. This scenario plays out in the clinic when BCW debris released during antibiotic therapy of maternal infection traffics to the fetal brain. This study identifies the direct interaction of BCW with TLR2/6 present on the primary cilium, the signaling hub on fetal neural progenitor cells (NPCs). NPCs control the size and architecture of the brain and understanding the mechanisms regulating NPCs is crucial to understanding brain developmental disorders. Within a window of vulnerability before the appearance of fetal immune cells, the BCW-TLR2/6 interaction results in the inhibition of ciliogenesis, derepression of Sonic Hedgehog signaling, excess proliferation of neural progenitors, and abnormal cortical architecture. In the first example of TLR signaling linked to Sonic Hedgehog, BCW/TLR2/6 appears to act during fetal brain morphogenesis to play a role in setting the total cell number in the neocortex., Competing Interests: The authors declare a conflict of interest. PT serves on the SAB for Immunoscape and Cytoagents and has received travel support from 10X Genomics and honorarium and travel support from Illumina. The remaining authors have no conflicts of interest to disclose.

Transjugular intrahepatic portosystemic shunt (TIPS) creation is effective in treating the sequelae of decompensated liver cirrhosis-including medically refractory ascites and variceal bleeding-by decompressing the portal venous system through a manmade portosystemic conduit within the liver. However, the altered physiology in which splenomesenteric blood bypasses intrahepatic portal venous perfusion can precipitate varying degrees of hepatic encephalopathy (HE). While the majority of post-TIPS HE cases can be treated medically, some require escalated management strategies, including endovascular interventions to modify the indwelling TIPS and/or occlude competitive physiologic spontaneous portosystemic shunts. This review article details the epidemiology, risk factors, diagnosis, classification, and treatment of post-TIPS HE., (Thieme. All rights reserved.)

Background: Non-suicidal self-injury (NSSI) is highly prevalent among adolescents and predicts future psychopathology including suicide. To improve therapeutic decisions and clinical outcome of patients engaging in NSSI, it seems beneficial to determine neurobiological markers associated with treatment response. The present study investigated whether resting-state functional brain connectivity (RSFC) served to predict clinical improvements following treatment in adolescents engaging in NSSI., Methods: N = 27 female adolescents with NSSI took part in a baseline MRI exam and clinical outcome was assessed at follow-ups one, two and three years after baseline. During the follow-up period, patients received in- and/or outpatient treatment. Mixed-effects linear regression models were calculated to examine whether RSFC was associated with clinical improvement., Results: Patients' clinical outcome improved across time. Lower baseline RSFC between left paracentral gyrus and right anterior cingulate gyrus was associated with clinical improvement from baseline to one-year and from two-year to three-year follow-up. Lower and higher baseline RSFC in several inter- and intrahemispheric cortico-cortical and cortico-subcortical connections of interest were associated with clinical symptomatology and its severity, independent from time., Limitations: A relatively small sample size constrains the generalizability of our findings. Further, no control group not receiving treatment was recruited, therefore clinical changes across time cannot solely be attributed to treatment., Conclusions: While there was some evidence that RSFC was associated with clinical improvement following treatment, our findings suggest that functional connectivity is more predictive of severity of psychopathology and global functioning independent of time and treatment. We thereby add to the limited research on neurobiological markers as predictors of clinical outcome after treatment., Competing Interests: Conflict of interest The authors have no conflict of interest to declare. Disclosures The study was funded by the Dres. Majic/Majic-Schelz-Foundation and the Dietmar Hopp Foundation [23011121]. The foundations were not involved in the collection, analysis or interpretation of data, in the writing of the manuscript or the decision to submit the article for publication., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Low T3 syndrome occurs frequently in patients with sepsis. Type 3 deiodinase (DIO3) is present in immune cells, but there is no description of its presence in patients with sepsis. Here, we aimed to determine the prognostic impact of thyroid hormones levels (TH), measured on ICU admission, on mortality and evolution to chronic critical illness (CCI) and the presence of DIO3 in white cells. We used a prospective cohort study with a follow-up for 28 days or deceased. Low T3 levels at admission were present in 86.5% of the patients. DIO3 was induced by 55% of blood immune cells. The cutoff value of 60 pg/mL for T3 displayed a sensitivity of 81% and specificity of 64% for predicting death, with an odds ratio of 4.89. Lower T3 yielded an area under the receiver operating characteristic curve of 0.76 for mortality and 0.75 for evolution to CCI, thus displaying better performance than commonly used prognostic scores. The high expression of DIO3 in white cells provides a novel mechanism to explain the reduction in T3 levels in sepsis patients. Further, low T3 levels independently predict progression to CCI and mortality within 28 days for sepsis and septic shock patients.

Introduction: The "Cutting Down Programme" (CDP), a brief psychotherapeutic intervention for treating nonsuicidal self-injury (NSSI) in adolescents, was comparable to high-quality treatment as usual (TAU) in a previous randomized controlled trial (RCT)., Objective: The aim of the study was to evaluate the long-term outcomes of the CDP over up to 4 years., Methods: Assessments of NSSI, suicide attempts, borderline personality disorder (BPD), depression, and quality of life took place 2 to 4 years (T3) after enrollment in a RCT. The evolution of NSSI, suicide attempts, depression, and quality of life was analyzed using (generalized) linear mixed-effects models. Ordered logistic regression was used for analyzing BPD diagnoses. Data from T0, T2, and T3 are reported., Results: Out of 74 patients, 70 (95%) were included in the T3 assessment. The frequency of NSSI events alongside with suicide attempts and depression further decreased between T2 and T3 and BPD between T0 and T3 in both groups. Quality of life remained stable in both groups between T2 and T3. Both groups received substantial but comparable additional treatment between T2 and T3. More treatment sessions during the follow-up period were linked to larger improvements of NSSI., Conclusions: The CDP was found to be as effective as TAU in promoting recovery from NSSI and comorbid symptoms in the long term. Results suggest that treatment effects from a brief psychotherapeutic intervention may endure and even further improve after completion of the program. However, additional treatment seems to improve chances for recovery independent from CDP versus TAU., (© 2023 S. Karger AG, Basel.)

Competing Interests: Disclosures The authors have no conflict of interest.

The obesity pandemic is presumed to be accelerated by endocrine disruptors such as phthalate-plasticizers, which interfere with adipose tissue function. With the restriction of the plasticizer di-(2-ethylhexyl)-phthalate (DEHP), the search for safe substitutes gained importance. Focusing on the master regulator of adipogenesis and adipose tissue functionality, the peroxisome proliferator-activated receptor gamma (PPARγ), we evaluated 20 alternative plasticizers as well as their metabolites for binding to and activation of PPARγ and assessed effects on adipocyte lipid accumulation. Among several compounds that showed interaction with PPARγ, the metabolites MINCH, MHINP, and OH-MPHP of the plasticizers DINCH, DINP, and DPHP exerted the highest adipogenic potential in human adipocytes. These metabolites and their parent plasticizers were further analyzed in human preadipocytes and mature adipocytes using cellular assays and global proteomics. In preadipocytes, the plasticizer metabolites significantly increased lipid accumulation, enhanced leptin and adipsin secretion, and upregulated adipogenesis-associated markers and pathways, in a similar pattern to the PPARγ agonist rosiglitazone. Proteomics of mature adipocytes revealed that both, the plasticizers and their metabolites, induced oxidative stress, disturbed lipid storage, impaired metabolic homeostasis, and led to proinflammatory and insulin resistance promoting adipokine secretion. In conclusion, the plasticizer metabolites enhanced preadipocyte differentiation, at least partly mediated by PPARγ activation and, together with their parent plasticizers, affected the functionality of mature adipocytes similar to reported effects of a high-fat diet. This highlights the need to further investigate the currently used plasticizer alternatives for potential associations with obesity and the metabolic syndrome., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Organoid evolution models complemented with integrated single-cell sequencing technology provide a powerful platform to characterize intra-tumor heterogeneity (ITH) and tumor evolution. Here, we conduct a parallel evolution experiment to mimic the tumor evolution process by evolving a colon cancer organoid model over 100 generations, spanning 6 months in time. We use single-cell whole-genome sequencing (WGS) in combination with viral lineage tracing at 12 time points to simultaneously monitor clone size, CNV states, SNV states, and viral lineage barcodes for 1,641 single cells. We integrate these measurements to construct clonal evolution trees with high resolution. We characterize the order of events in which chromosomal aberrations occur and identify aberrations that recur multiple times within the same tumor sub-population. We observe recurrent sequential loss of chromosome 4 after loss of chromosome 18 in four unique tumor clones. SNVs and CNVs identified in our organoid experiments are also frequently reported in colorectal carcinoma samples, and out of 334 patients with chromosome 18 loss in a Memorial Sloan Kettering colorectal cancer cohort, 99 (29.6%) also harbor chromosome 4 loss. Our study reconstructs tumor evolution in a colon cancer organoid model at high resolution, demonstrating an approach to identify potentially clinically relevant genomic aberrations in tumor evolution., Competing Interests: The authors declare no competing financial interests. J.d.R. is founder of Cyclomics B.V., (© 2022 The Authors.)

We performed a systematic review and meta-analysis to comprehensively determine the prevalence and the prognostic role of non-thyroidal illness syndrome (NTIS) in critically ill patients. We included studies that assessed thyroid function by measuring the serum thyroid hormone (TH) level and in-hospital mortality in adult septic patients. Reviews, case reports, editorials, letters, animal studies, duplicate studies, and studies with irrelevant populations and inappropriate controls were excluded. A total of 6869 patients from 25 studies were included. The median prevalence rate of NTIS was 58% (IQR 33.2-63.7). In univariate analysis, triiodothyronine (T3) and free T3 (FT3) levels in non-survivors were relatively lower than that of survivors (8 studies for T3; standardized mean difference (SMD) 1.16; 95% CI, 0.41-1.92; I2 = 97%; P < 0.01). Free thyroxine (FT4) levels in non-survivors were also lower than that of survivors (12 studies; SMD 0.54; 95% CI, 0.31-0.78; I2 = 83%; P < 0.01). There were no statistically significant differences in thyrotropin levels between non-survivors and survivors. NTIS was independently associated with increased risk of mortality in critically ill patients (odds ratio (OR) = 2.21, 95% CI, 1.64-2.97, I2 = 65% P < 0.01). The results favor the concept that decreased thyroid function might be associated with a worse outcome in critically ill patients. Hence, the measurement of TH could provide prognostic information on mortality in adult patients admitted to ICU.

Introduction: Aggressive behavior in reaction to threats, frustration, or provocation is prevalent in borderline personality disorder (BPD). This study investigated aggressive behavior and its biological correlates in adolescents with BPD., Methods: Twenty-one female adolescents with a DSM-IV BPD diagnosis and 25 sex- and age-matched healthy controls participated in the Taylor Aggression Paradigm (TAP), a laboratory-based experiment measuring aggressive behavior in the interpersonal context. Heart rate was measured and saliva samples were taken throughout the experiment., Results: Multilevel mixed-effects linear regression analyses revealed no significant group difference in aggressive behavior induced by the TAP. Additionally, the two groups did not differ in cortisol, testosterone, and heart rate responses to the aggression induction. The BPD group showed a significant cortisol increase in the time preceding the start of the TAP in contrast to the healthy control group, in whom a significant heart rate increase from baseline to the first block of the TAP was observed., Discussion: There was no evidence, either at the phenomenological or the biological level, of increased task-induced aggression in adolescents with BPD. The results may indicate that adolescents with BPD experienced fearful stress in anticipation of the experimental task in contrast to healthy controls who showed an adaptive response of the autonomic nervous system necessary to deal with the upcoming demand., (© 2021 The Author(s) Published by S. Karger AG, Basel.)

The use of the plasticizer bis(2-ethylhexyl)phthalate (DEHP) and other plasticizers in the manufacture of plastic products has been restricted due to adverse health outcomes such as obesity, metabolic syndrome, and asthma, for which inflammation has been described to be a driving factor. The emerging alternative plasticizer 1,2-cyclohexanedioic acid diisononyl ester (DINCH) still lacks information regarding its potential effects on the immune system. Here, we investigated the effects of DINCH and its naturally occurring metabolite monoisononylcyclohexane-1,2-dicarboxylic acid ester (MINCH) on the innate immune response. Human THP-1 macrophages were exposed to 10 nM-10 μM DINCH or MINCH for 4 h, 16 h, and 24 h. To decipher the underlying mechanism of action, we applied an untargeted proteomic approach that revealed xenobiotic-induced activation of immune-related pathways such as the nuclear factor κB (NF-κB) signaling pathway. Key drivers were associated with oxidative stress, mitochondrial dysfunction, DNA damage repair, apoptosis, and autophagy. We verified increased reactive oxygen species (ROS) leading to cellular damage, NF-κB activation, and subsequent TNF and IL-1β release, even at low nM concentrations. Taken together, DINCH and MINCH induced cellular stress and pro-inflammatory effects in macrophages, which may lead to adverse health effects.

We investigated the metabolic profile, reactive species production, and inflammatory parameters in patients with epilepsy. Furthermore, we investigated whether there is any relationship between these parameters and seizure type. Patients with epilepsy (n=43) and healthy subjects (control group; n=41) were recruited to participate in the study. Initially, the participants were submitted to a clinical questionnaire and patients with epilepsy were classified according to seizure type. Metabolic markers and inflammatory and oxidative factors were also measured in specific blood samples. We compared these results with data from the control subjects. Statistical analyses showed that patients with epilepsy presented with higher levels of glycolipid, oxidative stress, and inflammatory parameters compared to the control subjects. Interestingly, patients with generalized seizures presented with higher MnSOD activity and metabolic parameters (total cholesterol, low-density lipoprotein, glucose and triglyceride levels) compared to the partial seizure and control groups. Furthermore, patients with generalized epilepsy demonstrated a significant correlation between TNF-α and caspase 8 (p<0.05), caspase 3 (p<0.05), and Picogreen (p<0.001). This study supports evidence that the levels of inflammatory, glycolipid, and oxidative factors are higher in epilepsy patients, especially those with generalized epilepsy.

Objective: The objective of the study was to evaluate the neurocognitive profile and its relation with Ala16ValMnSOD polymorphism in epilepsy and if these clinical parameters are linked to oxidative stress and inflammatory markers., Methods: Patients with epilepsy (n = 31) and healthy subjects (n = 42) were recruited. A neuropsychological evaluation was performed in both groups through a battery of cognitive tests. Oxidative stress, inflammatory markers, apoptotic factors, and deoxyribonucleic acid (DNA) damage were measured in blood samples., Results: Statistical analyses showed the association of MnSOD Ala16Val polymorphism with cognitive impairment, including praxis, perception, attention, language, executive functions, long-term semantic memory, short-term visual memory, and total memory in patients with epilepsy and Valine-Valine (VV) genotype compared with the control group. Compared with the controls and patients with epilepsy, Alanine-Alanine (AA), and Alanine-Valine (AV) genotype, the patients with epilepsy and VV genotype exhibited higher levels of tumor necrosis factor alpha (TNF-α), interleukin 1β (IL-1β), interleukin 6 (IL-6), activation of caspases 1 and 3 (CASP-1 and -3), and DNA damage. Our findings also showed higher carbonyl protein and thiobarbituric acid reactive substances (TBARS) levels as well as an increased superoxide dismutase (SOD) and acetylcholinesterase (AChE) activities in patients with epilepsy and VV genotype., Conclusion: This study supports the evidence of a distinct neuropsychological profile in patients with epilepsy, especially those with the VV genotype. Furthermore, our results suggest that oxidative and inflammatory pathways may be associated with genetic polymorphism and cognitive dysfunction in patients with epilepsy., Competing Interests: Declaration of competing interest None., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Objectives: This study aimed to investigate the clinical predictors of post-ictal headache (PIH) in patients with epilepsy in a tertiary center in Brazil., Methods: 302 individuals with adult-onset epilepsy were followed for 9.8 years in our Hospital. Structured questionnaires about headaches were applied. The presence of PIH was the primary outcome. We used multilevel linear modeling in our data analysis., Results: From the total, 46.3% had post-ictal headaches. Tension-type post-ictal headache was present in 55% (N = 77) of the subjects, migrainous in 32.1% (N = 45), and both types in 12.8% (N = 18). Family history of migraine (Odds ratio: 1.696; 95% CI: 1.372 to 2.096), diagnosis of drug-resistant epilepsy (Odds ratio: 1.169; 95% CI: 1.135 to 2.146), months since last visit (Odds ratio: 1.464; 95% CI: 1.243 to 2.888), and generalized seizure onset type of epilepsy (Odds ratio: 1.527; 95% CI: 1.114 to 1.668), were significant determinants of PIH on multilevel linear modeling., Discussion: PIH are associated with drug-resistant epilepsy, generalized seizures, and family history of migraine. The rates of pos-ictal headaches could be influenced by the use of antiepileptic drugs., (Copyright © 2020 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.)

Biotin, thiamine, and lipoic acid are industrially important molecules naturally synthesized by microorganisms via biosynthetic pathways requiring iron-sulfur (FeS) clusters. Current production is exclusively by chemistry because pathway complexity hinders development of fermentation processes. For biotin, the main bottleneck is biotin synthase, BioB, a S-adenosyl methionine-dependent radical enzyme that converts dethiobiotin (DTB) to biotin. BioB overexpression is toxic, though the mechanism remains unclear. We identified single mutations in the global regulator IscR that substantially improve cellular tolerance to BioB overexpression, increasing Escherichia coli DTB-to-biotin biocatalysis by more than 2.2-fold. Based on proteomics and targeted overexpression of FeS-cluster biosynthesis genes, FeS-cluster depletion is the main reason for toxicity. We demonstrate that IscR mutations significantly affect cell viability and improve cell factories for de novo biosynthesis of thiamine by 1.3-fold and lipoic acid by 1.8-fold. We illuminate a novel engineering target for enhancing biosynthesis of complex FeS-cluster-dependent molecules, paving the way for industrial fermentation processes., Competing Interests: Declaration of competing interest Biosyntia ApS has filed a patent application based on the results of this paper., (Copyright © 2020 The Author(s). Published by Elsevier Inc. All rights reserved.)

Proteolytical processing of the growth factor VEGFC through the concerted activity of CCBE1 and ADAMTS3 is required for lymphatic development to occur. How these factors act together in time and space, and which cell types produce these factors is not understood. Here we assess the function of Adamts3 and the related protease Adamts14 during zebrafish lymphangiogenesis and show both proteins to be able to process Vegfc. Only the simultaneous loss of both protein functions results in lymphatic defects identical to vegfc loss-of-function situations. Cell transplantation experiments demonstrate neuronal structures and/or fibroblasts to constitute cellular sources not only for both proteases but also for Ccbe1 and Vegfc. We further show that this locally restricted Vegfc maturation is needed to trigger normal lymphatic sprouting and directional migration. Our data provide a single-cell resolution model for establishing secretion and processing hubs for Vegfc during developmental lymphangiogenesis.

Objective: To assess the relationship between time to focus clearance and hospital mortality in patients with sepsis and septic shock., Methods: This was an observational, single-center study with a retrospective analysis of the time to clearance of abdominal septic focus. Patients were classified according to the time to focus clearance into an early (≤ 12 hours) or delayed (> 12 hours) group., Results: A total of 135 patients were evaluated. There was no association between time to focus clearance and hospital mortality (≤ 12 hours versus > 12 hours): 52.3% versus 52.9%, with p = 0.137., Conclusion: There was no difference in hospital mortality among patients with sepsis or septic shock who had an infectious focus evacuated before or after 12 hours after the diagnosis of sepsis.

Background: Most of the epilepsy longitudinal studies have analyzed children. However, in endemic regions, such as Brazil, neurocysticercosis accounts for many adult-onset epilepsy cases. So, the main objective of this study was to identify the clinical predictors associated with drug-resistant adult-onset epilepsy in Brazil during a long-term follow-up., Methods: We followed 302 individuals with adult-onset epilepsy for 9.8 years in our University Hospital. Structured questionnaires about drug-resistant epilepsy were applied. The presence of drug-resistant epilepsy was the primary outcome. We used multilevel linear modeling in our data analysis., Results: Overall 47 (15.6%) individuals presented drug-resistant epilepsy and the etiology was structural in 70.2% of them, while infectious etiology was present in 8.5% of this group. Infectious etiology occurred in 25.9% (n = 66) of the patients from the nondrug-resistant group. Those with developmental delay were two times more likely to present seizures. Structural epilepsy etiology was associated with an increased chance of relapsing. Poor school performance and abnormal electroencephalogram were also associated with an increased chance of seizures., Conclusion: The course of epilepsy was favorable in the majority of our patients, and drug-resistant epilepsy rates were similar to those found in other studies, although we evaluated older individuals with higher levels of infectious etiology. Also, we found that neurocysticercosis was associated with well-controlled epilepsy, while structural epilepsy was directly related to the occurrence of seizures. We also hypothesized that the smaller size of lesions found in neurocysticercosis could contribute to better treatment response., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background and Purpose: Falls are the leading cause of unintentional deaths in older adults, with nearly one-third of adults older than 65 years falling annually. Previous work reveals that both medication status and gait changes are contributing factors to falls in older adults; however, it is unknown how these factors interact. Thus, the purpose of this investigation was to examine differences between gait biomechanics as a function of medication status in individuals older than 60 years with a self-reported history of falling. It was hypothesized that differences in gait mechanics would be observed as a function of the number of medications in these individuals., Methods: A total of 384 participants, age, mean (SD) = 73.2 (4.2) years; height, mean (SD) = 173.09 (16.4) cm; mass, mean (SD) = 65.45 (5.78) kg, were recruited from across the Southwest United States (Texas, New Mexico, Arizona, Nevada, and California) by the Electronic Caregiver Mobile Fall Risk Assessment Laboratory. Data for cadence, gait velocity, stride length, swing time, and double-support time were collected using a Walkway gait analysis system. Factor analysis was employed to determine whether the gait characteristics were similar to those observed in previous studies. A multivariate analysis with a follow-up univariate analysis was employed to determine group differences in gait factors and variables according to medication number (≥4 medications, n = 262 vs ≤3 medications, n = 122)., Results: Results of the factor analysis reveal that the data analyzed in the current study are similar to those observed in previous studies, with cadence (factor loading coefficient [FLC] = 0.745), gait velocity (FLC = 0.922), stride length (FLC = 0.789 for left and 0.790 for right) loading positively on a "pace" factor, swing time (FLC = 0.728 for right and 0.683 for left), and double-support time (FLC= 0.723) loading positively on a "rhythm" factor. The results of the multivariate analysis of variance revealed differences in gait factors across groups according to medication status. Univariate follow-up tests reveal that double-support time is longer and stride length is shorter in persons taking 4 or more medications as compared with those on 3 or fewer medications., Conclusion: The findings of this study indicate that certain abnormal gait parameters in participants with a history of falls are associated with taking 4 or more medications. Future studies should examine the extent to which gait changes and medications interact to predict falls.

The MnSOD Ala16Val single nucleotide polymorphism (SNP) has been associated with different diseases. However, there are scarcely studies relating this SNP in epilepsy, a neurologic disease that involves some interacting pathways, such as apoptotic and inflammatory factors. In this sense, we decided to investigate the relationship of MnSOD Ala16Val SNP with apoptotic markers in epilepsy and its relation with inflammatory pathway and seizure type. Ninety subjects were evaluated (47 epilepsies; 43 controls) by questionnaires and laboratorial exams. We observed a higher percentage of VV genotype in the epilepsy group when compared to the control group. IL-1 β , IL-6, caspase-1, and caspase-3 levels were increased in the epilepsy group (VV genotype). Furthermore, an important correlation between IL-1 β vs. caspase-1 and IL-6 vs. caspase-3 was observed in the epilepsy group (VV genotype). The epilepsy group which presented generalized seizures also demonstrated a positive correlation between IL-1 β vs. CASP1 and IL-6 vs. CASP3. Thus, it is a plausible propose that epilepsy patients with VV genotype and generalized seizures present a worse inflammatory and apoptotic status. Our findings suggest that the knowledge of MnSOD Ala16Val polymorphism existence is important to evaluate molecular mechanisms associated to seizure and improve the treatment of these patients., Competing Interests: The authors declare there are any potential conflicts of interest. The authors declare they have no actual or potential competing financial interests, (Copyright © 2020 Aline Kegler et al.)

Microbial cell factories offer new and sustainable production routes for high-value chemicals. However, identification of high producers within a library of clones remains a challenge. When product formation is coupled to growth, millions of metabolic variants can be effectively interrogated by growth selection, dramatically increasing the throughput of strain evaluation. While growth-coupled selections for cell factories have a long history of success based on metabolite auxotrophies and toxic antimetabolites, such methods are generally restricted to molecules native to their host metabolism. New synthetic biology tools offer the opportunity to rewire cellular metabolism to depend on specific and non-native products for growth., (Copyright © 2019 The Authors. Published by Elsevier Ltd.. All rights reserved.)

The MnSOD Ala16Val single nucleotide polymorphism (SNP) has shown to be associated to inflammatory pathways and many metabolic disorders, such as obesity and dyslipidemia. Metabolic syndrome (MetS) is an emergent problem among patients with epilepsy. However, little is known about interaction between MnSOD Ala16Val SNP and metabolic comorbities in epilepsy. Thus, we investigated the relationship between MnSOD Ala16Val SNP with epilepsy and its influence on MetS, inflammation, apoptosis and DNA damage parameters. Ninety subjects were evaluated (47 epilepsy patients and 43 healthy controls) by questionnaires and laboratorial exams. Levels of inflammatory, apoptotic and DNA damage markers, as well as MnSOD polymorphism were assessed. An increased proportion of VV genotype in epilepsy group when compared to control group was observed. Tumor Necrosis Factor-α (TNF-α), Acetylcholinesterase, caspase-8, and Picogreen levels were increased in VV epilepsy group. An important correlation between TNF-α vs caspase-8, and Cholesterol vs. Triglycerides was observed in the epilepsy group with VV genotype. Our findings suggest that the MnSOD Ala16Val SNP might have an important role in epilepsy, mainly in patients with generalized seizures and particularly with VV genotype. The metabolic parameters also presented significant results in epilepsy group with VV genotype, which applying attention in view of further consequences and disorders that could be developed., (Copyright © 2019. Published by Elsevier B.V.)

Recent research in the educational context has focused not only on academic achievement but also on subjective well-being (SWB) as both play a major role in students' lives. Whereas the determinants of academic achievement have been extensively investigated, little research has been conducted on school-related determinants of SWB in comparison with other students' characteristics. In the present cross-sectional study, we set out to investigate whether perceived school climate predicts school grades and SWB above and beyond other variables that are important for SWB and academic achievement. A sample of 767 8th and 9th grade students ( n = 361 female adolescents; age: M = 14.07 years, SD = 0.92) completed measures of SWB, perceived school climate, test anxiety, self-efficacy, and interest. Grade point average (GPA) indicated students' academic achievement. Data were analyzed with latent structural equation models in which GPA and SWB were regressed on the school climate variables and students' characteristics. Results indicated that a positive school climate as well as self-efficacy and the worry component of test anxiety predicted SWB and/or GPA after all other variables were controlled for. Directions for future research and the importance of school climate variables on adolescents' SWB and academic achievement are discussed.

Drug-induced kidney injury, largely caused by proximal tubular intoxicants, limits development and clinical use of new and approved drugs. Assessing preclinical nephrotoxicity relies on animal models that are frequently insensitive; thus, potentially novel techniques - including human microphysiological systems, or "organs on chips" - are proposed to accelerate drug development and predict safety. Polymyxins are potent antibiotics against multidrug-resistant microorganisms; however, clinical use remains restricted because of high risk of nephrotoxicity and limited understanding of toxicological mechanisms. To mitigate risks, structural analogs of polymyxins (NAB739 and NAB741) are currently in clinical development. Using a microphysiological system to model human kidney proximal tubule, we exposed cells to polymyxin B (PMB) and observed significant increases of injury signals, including kidney injury molecule-1 KIM-1and a panel of injury-associated miRNAs (each P < 0.001). Surprisingly, transcriptional profiling identified cholesterol biosynthesis as the primary cellular pathway induced by PMB (P = 1.22 ×10-16), and effluent cholesterol concentrations were significantly increased after exposure (P < 0.01). Additionally, we observed no upregulation of the nuclear factor (erythroid derived-2)-like 2 pathway, despite this being a common pathway upregulated in response to proximal tubule toxicants. In contrast with PMB exposure, minimal changes in gene expression, injury biomarkers, and cholesterol concentrations were observed in response to NAB739 and NAB741. Our findings demonstrate the preclinical safety of NAB739 and NAB741 and reveal cholesterol biosynthesis as a potentially novel pathway for PMB-induced injury. To our knowledge, this is the first demonstration of a human-on-chip platform used for simultaneous safety testing of new chemical entities and defining unique toxicological pathway responses of an FDA-approved molecule.

Cholesterol and cholesterol-derived oxysterols are critical for embryonic development, synapse formation and function, and myelination, among other biological functions. Indeed, alterations in levels of cholesterol, sterol precursors, and oxysterols result in a variety of developmental disorders, emphasizing the importance of cholesterol homeostasis. The ability of xenobiotics to reproduce similar phenotypes by altering cholesterol homeostasis has increasingly become of interest. Therefore, the ability to quantitatively assess alterations in cholesterol homeostasis resulting from exposure to xenobiotics is of value. This unit describes methods for the quantitative assessment of altered post-squalene cholesterol biosynthesis and subsequent oxysterol formation in various sample types using ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS). Understanding alterations in cholesterol homeostasis resulting from xenobiotic exposure can provide key insight into the toxicant's mechanism of action and resulting phenotype. © 2018 by John Wiley & Sons, Inc., (© 2018 John Wiley & Sons, Inc.)

Hyperammonemia is a common finding in patients with methylmalonic acidemia. However, its contribution to methylmalonate (MMA)-induced neurotoxicity is poorly understood. The aim of this study was evaluate whether an acute metabolic damage to brain during the neonatal period may disrupt cerebral development, leading to neurodevelopmental disorders, as memory deficit. Mice received a single intracerebroventricular dose of MMA and/or NH 4 Cl, administered 12 hs after birth. The maze tests showed that MMA and NH 4 Cl injected animals (21 and 40 days old) exhibited deficit in the working memory test, but not in the reference memory test. Furthermore, MMA and NH 4 Cl increased the levels of 2',7'-dichlorofluorescein-diacetate (DCF), TNF-α, IL-1β in the cortex, hippocampus and striatum of mice. MMA and NH 4 Cl also increased glial proliferation in all structures. Since the treatment of MMA and ammonia increased cytokines levels, we suggested that it might be a consequence of the glial activation induced by the acid and ammonia, leading to delay in the developing brain and contributing to behavioral alterations. However, this hypothesis is speculative in nature and more studies are needed to clarify this possibility., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Purpose: The purpose of this study was to examine the cognitive function and depressive traits most frequently associated with the clinical assessment of patients with epilepsy and if these clinical parameters are linked to glycolipid levels and inflammatory and apoptotic markers., Methods: Patients with epilepsy (n = 32) and healthy subjects (n = 41) were recruited to participate in this study. Neuropsychological evaluation was performed in both groups through a battery of cognitive tests. Inflammatory markers, apoptotic factors, and deoxyribonucleic acid (DNA) damage were measured in blood samples. Additionally, the metabolic markers total cholesterol (CHO), low-density lipoprotein (LDL), high-density lipoprotein (HDL), triglyceride (TG), and glucose (GLU) levels were analyzed., Results: Statistical analyses showed that patients with epilepsy presented decreased scores in memory, attention, language, and executive function tests compared with the control group. Analysis revealed that there was negative correlation in epilepsy for seizure duration vs. oral language (R = -0.4484, p < 0.05) and seizure duration vs. problem solving (executive functions) (R = -0.3995, p < 0.05). This was also observed when comparing depression with temporal-spatial orientation (TSO) (R = -0.39, p < 0.05). Furthermore, we observed a higher depression score in patients with epilepsy than in the healthy ones. Statistical analyses showed higher acetylcholinesterase (AChE) (p < 0.05), interleukin 1β (IL-1β, p < 0.001), and tumor necrosis factor-alpha (TNF-α) (p < 0.001) levels compared with those in the control group. Moreover, patients with epilepsy had significantly higher serum levels of caspase 3 (CASP 3) (p < 0.001) and Picogreen (p < 0.001) compared with the control subjects. Regarding the metabolic markers, higher glycolipid levels were observed in the patients with epilepsy (CHO < 0.05*, LDL < 0.0001*, TG < 0.05*, GLU p < 0.05). High-density lipoprotein levels were not significant. The patients with epilepsy had significant correlation when comparing total language with TNF-α (R = -0.4, p < 0.05), praxes with CASP 3 (R = -0.52, p < 0.01), total CHO with total language (R = -0.48, p < 0.05), TG with semantic memory (R = -0.54, p < 0.05), TG with prospective memory (R = -0.2165, p < 0.02), TG with total memory (R = -0.53, p < 0.02), and GLU with total attention (R = -0.62, p < 0.002)., Conclusion: This study supports the evidence of a distinct neuropsychological profile between patients with epilepsy and healthy subjects. Furthermore, our findings suggest that inflammatory pathway, glycolipid profile, and depressive factors may be associated with cognitive dysfunction in patients with epilepsy., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background: Red blood cell distribution width (RDW) is a predictor of mortality in critically ill patients. Our objective was to investigate the association between the RDW at ICU discharge and the risk of ICU readmission or unexpected death in the ward., Methods: A secondary analysis of prospectively collected data study was conducted including patients discharged alive from the ICU to the ward. The target variable was the RDW collected at ICU discharge. Elevated RDW was defined as an RDW > 16%. Outcomes of interest included readmission to the ICU, unexpected death in the ward and in-hospital death. Variables with a p-value <0.1 in the univariate analysis or with biological plausibility for the occurrence of the outcome were included in the Cox proportional hazards model for adjustment., Results: We included 813 patients. A total of 138 readmissions to the ICU and 44 unexpected deaths in the ward occurred. Elevated RDW at ICU discharge was independently associated with readmission to the ICU or unexpected death in the ward after multivariable adjustment (HR: 1.901; 95% CI 1.357-2.662). Other variables associated with this outcome included age, tracheostomy and mean corpuscular volume (MCV) at ICU discharge. Similar results were obtained after the exclusion of unexpected deaths in the ward (HR 1.940; CI 1.312-2.871) and for in-hospital deaths (HR 1.716; 95% CI 1.141-2.580)., Conclusions: Elevated RDW at ICU discharge is independently associated with ICU readmission and in-hospital death., (Copyright © 2018 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.)

Segmentation of the axial skeleton in amniotes depends on the segmentation clock, which patterns the paraxial mesoderm and the sclerotome. While the segmentation clock clearly operates in teleosts, the role of the sclerotome in establishing the axial skeleton is unclear. We severely disrupt zebrafish paraxial segmentation, yet observe a largely normal segmentation process of the chordacentra. We demonstrate that axial entpd5+ notochord sheath cells are responsible for chordacentrum mineralization, and serve as a marker for axial segmentation. While autonomous within the notochord sheath, entpd5 expression and centrum formation show some plasticity and can respond to myotome pattern. These observations reveal for the first time the dynamics of notochord segmentation in a teleost, and are consistent with an autonomous patterning mechanism that is influenced, but not determined by adjacent paraxial mesoderm. This behavior is not consistent with a clock-type mechanism in the notochord., Competing Interests: LL, RN, LH, MV, AA, JP, IL, GV, LM, AO, SS No competing interests declared, (© 2018, Lleras Forero et al.)

Embryonic development is a crucial period in the life of a multicellular organism, during which limited sets of embryonic progenitors produce all cells in the adult body. Determining which fate these progenitors acquire in adult tissues requires the simultaneous measurement of clonal history and cell identity at single-cell resolution, which has been a major challenge. Clonal history has traditionally been investigated by microscopically tracking cells during development, monitoring the heritable expression of genetically encoded fluorescent proteins and, more recently, using next-generation sequencing technologies that exploit somatic mutations, microsatellite instability, transposon tagging, viral barcoding, CRISPR-Cas9 genome editing and Cre-loxP recombination. Single-cell transcriptomics provides a powerful platform for unbiased cell-type classification. Here we present ScarTrace, a single-cell sequencing strategy that enables the simultaneous quantification of clonal history and cell type for thousands of cells obtained from different organs of the adult zebrafish. Using ScarTrace, we show that a small set of multipotent embryonic progenitors generate all haematopoietic cells in the kidney marrow, and that many progenitors produce specific cell types in the eyes and brain. In addition, we study when embryonic progenitors commit to the left or right eye. ScarTrace reveals that epidermal and mesenchymal cells in the caudal fin arise from the same progenitors, and that osteoblast-restricted precursors can produce mesenchymal cells during regeneration. Furthermore, we identify resident immune cells in the fin with a distinct clonal origin from other blood cell types. We envision that similar approaches will have major applications in other experimental systems, in which the matching of embryonic clonal origin to adult cell type will ultimately allow reconstruction of how the adult body is built from a single cell.