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Background: The effect of non-pulsatile, normothermic cardiopulmonary-bypass (CPB) on the splanchnic blood-flow and oxygen-transport, the hepatic function and the gastrointestinal barrier were observed in a prospective observational study in 31 adults undergoing cardiac valve replacement surgery.Methods: The splanchnic (i.e. hepatic) blood-flow (HBF) was measured by the constant infusion of indocyanine-green (ICG) using a hepatic-venous catheter. Liver function was examined by calculation of lactate uptake, ICG extraction and the monoethylglycinexylidide (MEGX) test. A day before and after surgery the gastrioduodenal and intestinal permeability was measured by determination of sucrose and lactulose/mannitol excretion.Results: Splanchnic blood flow and oxygen delivery did not decrease during and after surgery while splanchnic oxygen consumption (P < 0.0125) and arterial lactate concentrations increased. The splanchnic lactate uptake paralleled the lactate concentration. After but not during CPB an increase of systemic oxygen consumption was observed. The MEGX test values decreased on the first day after surgery. The ICG extraction was attenuated during the operation. The gastroduodenal and the intestinal permeability increased significantly postoperatively (P < 0.002, respectively, P < 0.001). There was no correlation between these findings and the duration of CPB. There was a significant correlation of the intestinal permeability but not of the gastroduodenal permeability between the prior and after surgery values (P < 0.001).Conclusion: Increased oxygen consumption during CPB may indicate an inflammatory reaction due to the pump beginning in the splanchnic area or a redistribution of the splanchinc blood flow during the CPB. Normothermic CPB does not lead to a significant or prolonged reduction of liver function. Normothermic CPB causes an increase of gastrointestinal permeability. The intestinal barrier function prior to surgery was accountable for the degree of loss of intestinal barrier function following surgery. [ABSTRACT FROM AUTHOR]

Experience has shown that better quality CPR leads to a greater chance of a patient surviving a cardiac arrest. Simple CPR techniques, such as using only chest compressions, lead to better skill retention and greater willingness to attempt resuscitation on strangers. However, it is not clear from clinical or experimental studies whether such techniques offer any physiological benefit over more usual 5:1 or 15:2 compression:ventilation ratios. Computer simulations of blood flow and gas exchange during CPR showed that continuous chest compressions produced much greater blood flow (1.39 l/min) than 5:1 (0.73 l/min), 15:2 (0.86 l/min) or 50:5 (0.94 l/min) ratios. However, the ratio of 5:1 produced the highest arterial oxygen levels, with continuous chest compressions the lowest. The most appropriate measure of CPR efficiency appears to be the amount of oxygen delivered to the body during CPR. The ratios of 15:2 and 50:5 produced significantly greater oxygen delivery to the body than 5:1, the greater blood flow with these techniques offsetting the slightly lower arterial oxygen levels. The best oxygen delivery was provided by continuous chest compression in the early stages of CPR. After 3–4 min however, hypoxia meant that continuous compressions became worse than the other techniques. Spontaneous gasping by the patient during CPR was able to extend the effectiveness of chest compression only CPR for much longer. [Copyright &y& Elsevier]

Purpose: Since many drug targets and metabolizing enzymes are developmentally regulated, we investigated a potential comparable regulation of inosine 5'-monophosphate dehydrogenase (IMPDH) activity that has recently been advocated as a pharmacodynamic biomarker of mycophenolic acid (MPA) effects in the paediatric population. Since the field of pharmacodynamic monitoring of MPA is evolving, we also analyzed the response of IMPDH activity on MPA in children vs adolescents after renal transplantation. Methods: We analyzed IMPDH activity in peripheral blood mononuclear cells (PBMCs) in 79 healthy children aged 2.0-17.9 years in comparison to 106 healthy adults. Pharmacokinetic/pharmacodynamic profiles of MPA and IMPDH over 6 or 12 h after mycophenolate mofetil dosing were performed in 17 paediatric renal transplant recipients. IMPDH activity was measured by HPLC and normalized to the adenosine monophosphate (AMP) content of the cells, MPA plasma concentrations were measured by HPLC. Results: Inosine 5'-monophosphate dehydrogenase activity displayed a high inter-individual variability (coefficient of variation 40.2%) throughout the entire age range studied. Median IMPDH did not differ significantly in healthy pre-school children (82 [range, 42-184] μmol/s/mol AMP), school-age children (61 [30-153]), adolescents (83 [43-154]) and healthy adults (83 [26-215]). Similar to adults, IMPDH activity in children and adolescents was inversely correlated with MPA plasma concentration. Conclusions: In conclusion, our data do not show a pronounced developmental regulation of IMPDH activity in PBMCs in the paediatric population and there is a comparable inhibition of IMPDH activity by MPA in children and adolescents after renal transplantation. [ABSTRACT FROM AUTHOR]

Objectives: The present study was designed to investigate early proteome and phosphoproteome changes during inhibition of lymphocyte proliferation induced by sirolimus (SRL). Materials and methods: Proliferation assays were conducted using human CCRF-CEM T lymphoblasts under different SRL concentrations. Total protein lysates after SRL treatment were used to identify significantly regulated proteins and phosphorylated proteins by 2-DE and Q-TOF Ultima Global mass spectrometer. Results and conclusions: Incubation with 2.5 μmol/l SRL resulted in a ∼ 70% inhibition of cell proliferation. Cells incubated with 2.5 μmol/l for 30 min showed a differential phosphorylation pattern with one higher (TCPQ) and six lower phosphorylation signals (TBA1B, VIME, HNRPD, ENPL, SEPT9, PLSL). On investigating the differential protein expression, five proteins were found to be up-regulated (ECHB, PSB3, MTDC, LDHB and NDKA) and four were down-regulated (EHD1, AATC, LMNB1 and MDHC). Nine of these differentially regulated proteins/phosphoproteins (TCPQ, TBA1B, VIME, HNRPD, ENPL, ECHB, PSB3, LDHB and LMNB1) showed significant interaction potential, through binding protein YWHAZ using MINT software. Conclusions: We report for the first time the simultaneous early influence of SRL on phosphorylation status and on protein expression in the total proteome of CCRF-CEM T lymphoblasts and predict that 56% of the proteins interact with each other, highlighting significance of these results. [ABSTRACT FROM AUTHOR]

Human epidemiological studies have indicated that low birth weight associated with an adverse intrauterine environment is related to a greater incidence of cardiovascular disorders in later life. In the foetus, endogenous glucocorticoids generally increase if there is intrauterine nutrient deficiency. The consequent glucocorticoid hyperexposure has been hypothesised to cause in utero programming of atherogenic genes. We investigated the effect of oral treatment with the synthetic glucocorticoid dexamethasone during early or late pregnancy in marmoset monkeys on oxidative and antioxidant status in the offspring. Urinary concentrations of F2-isoprostanes were quantified as markers for in vivo oxidative stress. Expression of the mRNAs for the antioxidant enzymes cytosolic glutathione peroxidase (GPx-1), phospholipid hydroperoxide glutathione peroxidase (GPx-4), cytosolic Cu,Zn-superoxide dismutase (SOD1), mitochondrial Mn-superoxide dismutase (SOD2), glutathione reductase (GSR), modifier subunit of glutamate-cysteine ligase (GCLM) and catalase were determined in the aorta. Three groups of pregnant marmosets (10 animals per group) were treated orally for one week with vehicle, or with dexamethasone (5 mg/kg daily) during two gestation windows: early dexamethasone group, pregnancy day 42-48, and late dexamethasone group, pregnancy day 90-96. In one male sibling of each litter (10 males per group), aortas were taken at 2 years of age. In the late dexamethasone group a higher aortic mRNA expression for GPx-1 (p < 0.023), MnSOD (p < 0.016), GCLM (p < 0.019) and GSR (p < 0.014) in comparison to the controls was observed. Aortic expression in the early dexamethasone group was statistically significantly higher only for GSR mRNA (p < 0.038). No significant changes in urinary F2-isoprostane concentrations between controls, early and late dexamethasone groups at 2 years of age were observed. Hence, prenatal exposure to dexamethasone in the third trimester leads to increased mRNA expression of several aortic antioxidant enzymes in the offspring. This expression pattern was not temporally related to oxidative stress, and it may reflect in utero re-programming of aortic antioxidant gene expression during prenatal glucocorticoid exposure. [ABSTRACT FROM AUTHOR]

Objective: Oxidative stress has been implicated in the side-effects caused by haemodialysis (HD) treatment.Design: In the present study we have investigated whether gene expression of the enzymatic defence system provided by cellular glutathione peroxidase (GPx-1), phospholipid glutathione peroxidase (GPx-4), glutathione reductase (GSSG-R), glutathione synthethase (GSH-S), Cu/Zn-superoxide dismutase (SOD-1) and catalase (CAT) is affected by HD. The GPx-1, GPx-4, GSSG-R, GSH-S, SOD-1 and CAT mRNA were determined in white blood cells by quantitative reverse transcriptase-polymerase chain reaction with the LightCycler instrument and transcription elongation factor-2 as reference gene at the start (SD) and immediately after (ED) dialysis treatment (n = 36). In a subgroup (n = 10), messenger RNA (mRNA) expression was determined hourly during a 5 h HD.Results: The expression of GPx-1, GPx-4, GSSG-R, GSH-S, SOD-1 and CAT mRNA was not affected by a single HD treatment. All mRNAs were significantly (P < 0.05) increased in HD patients [median (16. percentiles (perc.); 84. perc.)]: GPx-1: 2.18 (0.89; 3.23); GPx-4: 0.41 (0.26; 0.74); GSSG-R: 0.04 (0.02; 0.10); GSH-S: 0.04 (0.02; 0.08); SOD-1: 0.32 (0.20; 0.62); CAT: 0.12 (0.06; 0.18) when compared with healthy blood donors (GPx-1: 0.91 (0.60; 1.44); GPx-4: 0.27 (0.16; 0.43); GSSG-R: 0.02 (0.01; 0.02); GSH-S: 0.02 (0.02; 0.04); SOD-1: 0.15 (0.10; 0.18); CAT: 0.07 (0.04; 0.16).Conclusions: These results show that the HD procedure does not acutely affect the antioxidant defence system on the gene level but suggest that the chronic stress caused by uraemia and/or HD may cause gene induction of the enzymatic defence system. [ABSTRACT FROM AUTHOR]

The effects of fluvastatin and bezafibrate on lipids, lipoproteins, and apoproteins (apo) were investigated in a multicenter randomized, double-blind, parallel-group study. After 8 weeks of strictly controlled (computer-based assessment) dietary stabilization, patients with primary hypercholesterolemia (low-density lipoprotein cholesterol [LDL-C] > or = 160 mg/dL; triglycerides < or = 300 mg/dL) were enrolled into a 6-week placebo phase. Altogether, 131 patients were randomized to receive either fluvastatin at 40 mg once daily (n = 64; mean age 53 years) or bezafibrate at 400 mg once daily (n = 67; mean age 52 years) for 12 weeks. Compliance with the diet was monitored (3-day food records) after 6 and 12 weeks. Fluvastatin led to significant reductions in LDL-C (-23%), total cholesterol (-17%), LDL-C/high-density lipoprotein cholesterol (HDL-C) (-24%) and apo B (-19%). Fluvastatin significantly increased LpA-I (+8%) and apo E (+20%). Bezafibrate produced significant reductions in LDL-C (-17%), total cholesterol (-13%), LDL-C/HDL-C (-24%), triglycerides (-28%), apo B (-15%), and LpA-I (-10%) and significantly increased HDL-C (+12%), apo A-I (+9%), apo A-II (+30%), apo E (+14%), and Lp(a) (+3%). No clinically notable increases in levels of liver enzymes or creatine phosphokinase were observed with either treatment. Both treatments were well tolerated. There was a low incidence of adverse events that tended to be mild and included headache, muscular pain, angina, and dyspepsia. The frequency of adverse events was similar in both treatment groups, and no significant differences in dietary behavior were observed. In conclusion, fluvastatin is a well tolerated 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitor for the treatment of primary hypercholesterolemia. Effects of fluvastatin on LpA-I occur irrespective of changes in HDL-C. [ABSTRACT FROM AUTHOR]

Background: Balkan endemic nephropathy (BEN) is a slow progressive nephropathy with frequent occurrence of uroepithelial tumors in the upper urinary tract. Genetic factors involved in xenobiotic detoxification mechanisms may cause genetic predisposition to BEN and influence the risk for this disease. Polymorphic MDR1 variants with decreased P-glycoprotein (P-gp) activity modulate the risk for renal neoplasm. We have therefore investigated the impact of MDR1 polymorphisms on BEN manifestation. Methods: The constitutional genotype frequencies of two SNPs (C3435T and G2677T) in the MDR1 gene in 112 healthy control subjects were investigated and compared with those of 96 patients with BEN. Identification of the SNPs was done with rapid cycle real-time PCR and melting curve analysis with allele-specific probes. Results: The frequency of mutant alleles was comparable in both groups. Significant differences were revealed when the MDR1 haplotypes were analyzed. Individuals with a predicted haplotype 12 (2677G/3435T) were less frequent in BEN cases (frequency 7.3%) than in controls (16.1%, p = 0.006). We found that carriers of the haplotype 12 had a decreased risk for BEN (OR = 0.411; 0.21–0.78). Conclusions: The data suggest that haplotype 12 is protective against BEN. There is no clear molecular explanation of the MDR1 haplotype effects on the protein activity, which can explain the modified effect of the haplotype 12 on BEN risk. Copyright © 2004 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

The physiological basis of cognitive decline remains largely uncharacterized. We identified a protein panel signature, in living humans, that correlates to improvement in neurocognition over a period of 5 years. Our signature is composed of complement proteins, coagulation cascade, and extracellular matrix regulators. In our cohort, SERPINF1 is associated with greater maximal oxygen uptake after an aerobic exercise intervention. Sleep quality is also a key factor in relation to inter-alpha-trypsin inhibitor heavy chain H2, which was associated with greater sleep efficiency. Additionally, we validate that the coagulation profile of decliners' plasma contains procoagulant agonists, leading to greater platelet activation. ANN NEUROL 2025., (© 2025 The Author(s). Annals of Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association.)

Advancements in neoadjuvant regimens for esophageal adenocarcinoma have enabled some patients to achieve complete pathologic response at time of esophagectomy. There are currently limited data detailing this trend or the implications of complete pathologic response on survival. The National Cancer Database was used to identify 16,169 patients with esophageal adenocarcinoma that received trimodal therapy including esophagectomy between 2006 and 2020. Of these, 11.4% had complete pathologic response at esophagectomy. Patient factors, staging characteristics, and survival trends were evaluated. In patients diagnosed between 2016 and 2020, the rate of complete pathologic response was 17.5%. Female sex (OR 1.295, 95% CI 1.134-1.481, p = 0.0001), Black race (OR 1.729, 95% CI 1.362-2.196, p = 0.0002), Hispanic ethnicity (OR 1.418, 95% CI 1.073-1.875, p = 0.0141), and later era of diagnosis (2016-2020 OR 2.898, 95% CI 2.508-3.349, p < 0.0001) were independent predictors of complete pathologic response. Clinical stage II disease was associated with an increased probability of complete pathologic response (OR 1.492, 95% CI 1.19-1.871) while clinical stage III disease had a decreased probability of complete pathologic response (OR 0.762, 95% CI 0.621-0.936, p < 0.0001). Complete pathologic response conveyed a strong survival benefit, with a median survival of 86.4 months (95% CI 73.9-102.1) versus 30.7 months (95% CI 29.8-31.7, p < 0.0001) in those without complete pathologic response. Four-year median survival was also higher in those with complete pathologic response (63.3%, 95% CI 60.8-66.0% vs. 39.2%, 95% CI 38.4-40.1%, p < 0.0001). In summary, complete pathologic response is associated with a profound survival advantage in patients with esophageal adenocarcinoma. Such knowledge carries implications for patient counseling, prognostication, and surveillance and demonstrates a need for improved identification of complete clinical response prior to esophagectomy., (© The Author(s) 2024. Published by Oxford University Press on behalf of International Society for Diseases of the Esophagus. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: The significance of lymphovascular invasion (LVI) in esophageal adenocarcinoma (EAC) has not yet been described. Potential utility as an adjunct to current staging guidelines remains unknown., Methods: The National Cancer Database was queried from 2006 to 2020. Univariate and multivariable models, Kaplan Meier method, and log-rank test were used. Subgroup analyses by pN stage were conducted., Results: Of 9,689 patients, 23.2% had LVI. LVI was an independent prognostic factor (hazard ratio [HR] 1.401, 95% confidence interval [CI] 1.307-1.502, p < 0.0001) with reduction in median survival to 20.0 months (95% CI 18.9-21.4) from 39.7 months (95% CI 37.8-42.3, p < 0.0001). Multivariable survival analysis adjusted on pN and pT stage found that patients with LVI had decreased survival in a given pN stage (p < 0.001). pN0/LVI+ patients had a similar prognosis to the higher staged pN1/LVI- (28.6 months), although pN1/LVI- patients did slightly worse (p = 0.0135). Additionally, patients with pN1/LVI+ had equivalent survival compared with pN2/LVI- (p = 0.178) as did pN2/LVI+ patients compared with pN3/LVI- (p = 0.995)., Conclusions: In these data, LVI is an independent negative prognostic factor in EAC. LVI was associated with a survival reduction similar to an upstaged nodal status irrespective of T stage. Patients with LVI may be better classified at a higher pN stage., (© 2024. The Author(s).)

Literature examining emotional regulation in infants with autism spectrum disorder (ASD) has focused on parent report. We examined behavioral and physiological responses during an emotion-evoking task designed to elicit emotional states in infants. Infants at an increased likelihood for ASD (IL; have an older sibling with ASD; 96 not classified; 29 classified with ASD at age two) and low likelihood (LL; no family history of ASD; n = 61) completed the task at 6, 12, and 18 months. The main findings were (1) the IL-ASD group displayed higher levels of negative affect during toy removal and negative tasks compared to the IL non-ASD and LL groups, respectively, (2) the IL-ASD group spent more time looking at the baseline task compared to the other two groups, and (3) the IL-ASD group showed a greater increase in heart rate from baseline during the toy removal and negative tasks compared to the LL group. These results suggest that IL children who are classified as ASD at 24 months show differences in affect, gaze, and heart rate during an emotion-evoking task, with potential implications for understanding mechanisms related to emerging ASD.

Background: Behavioral symptom trajectories are informative of the development of young children at increased likelihood for autism spectrum disorder (ASD)., Methods: Developmental trajectories of early signs were examined in a cohort of siblings of children diagnosed with ASD (n = 502) from 6 to 18 months using the Autism Observation Scale for Infants (AOSI), and from 18 months to 5-7 years using the Autism Diagnostic Observation Schedule (ADOS). Diagnostic outcomes for ASD at age 3 confirmed diagnosis for 137 children. We further analyzed the conditional probability of a switch from a trajectory measured with the AOSI to a trajectory measured with the ADOS as well as predictors from age 6 months., Results: We derived three early trajectories of behavioral signs ("Low," "Intermediate," and "Increasing") from 6 to 18 months using the AOSI. We then derived three similar, distinct trajectories for the evolution of symptom severity between 18 and 60-84 months of age (Low, Intermediate, Increasing) using the ADOS. Globally, the Low trajectory included children showing fewer ASD signs or symptoms and the Increasing trajectory included children showing more severe symptoms. We also found that most children in the Low AOSI trajectory stayed in the corresponding ADOS trajectory, whereas children in an Increasing AOSI trajectory tended to transition to an Intermediate or Increasing ADOS trajectory. Developmental measures taken at 6 months (early signs of ASD, Fine Motor, and Visual Reception skills) were predictive of trajectory membership., Conclusions: Results confirm substantial heterogeneity in the early emergence of ASD signs in children at increased likelihood for ASD. Moreover, we showed that the way those early behavioral signs emerge in infants is predictive of later symptomatology. Results yield clear clinical implications, supporting the need to repeatedly assess infants at increased likelihood for ASD as this can be highly indicative of their later development and behavior., (© 2022 Association for Child and Adolescent Mental Health.)

Background: Despite the significant clinical consequences and socioeconomic costs of gunshot wounds to the head (GSWH), studies examining prehospital risk factors, geospatial patterns, and economic cost are lacking., Methods: A retrospective analysis was performed for patients with GSWH (single or multiple injuries) presenting to the level one Ryder Trauma Center (hospital patients) as well as the Miami-Dade County Medical Examiner (ME) Department, from October 2013 to October 2015. In addition, ME data were queried from the previous decade (2008-2017) to analyze longitudinal trends., Results: A total of 402 consecutive patients met the inclusion criteria: 297 (74%) presented to the ME and 105 (26%) presented to the hospital. GSWH in our cohort had a case fatality rate of 89%, predominantly affecting males, whites, and individuals who committed suicide, with a mean age of 41.9 ± 20.6 years. Hospital patients were more likely to be black males from low socioeconomic status (SES) regions involved in assault. Older white males were overrepresented in patients attempting and completing suicide and thus comprised a higher percentage of ME cases. Geospatial analysis of hospital patient injury zip codes shows that GSWH are significantly clustered in low-income urban centers with greater poverty rates. In Miami-Dade County, the economic burden of GSWH, as measured by total health care costs and lifetime productivity losses, was estimated to be $11,867,415 and $246,179,498, respectively., Conclusions: In the first analysis of GSWH with the inclusion of both hospital and ME data in a representative urban setting, our findings show prehospital risk factors and the unequal distribution of the significant economic costs of GSWH., (Copyright © 2023 Elsevier Inc. All rights reserved.)

North Carolina implemented a rapid statewide COVID-19 vaccine strategy that focused on vaccinating people quickly and equitably. We describe the sociodemographic factors associated with COVID-19 vaccine uptake in North Carolina and how these factors were considered in communication as well as community and health care provider engagement in the COVID-19 response., (©2022 by the North Carolina Institute of Medicine and The Duke Endowment. All rights reserved.)

Delays in motor development are not considered a core feature of autism spectrum disorder (ASD). Yet, recent studies of infant siblings of children with ASD suggest that early delays in motor skills may be associated with later delays in developmental areas considered to be core features of an ASD diagnosis. While these studies demonstrate the longitudinal association between core features and motor delays observed at single time points, there is considerable interest in studying the trajectories of motor development over the first 3 years of life. To accomplish this, we investigated early trajectories of motor development in a cohort of 499 infant siblings of children with ASD and 176 children with no family history of ASD. Data for the current study were drawn from the prospective, multi-site, Canadian Infant Sibling Study. We evaluated trajectories of fine and gross motor development over the first 3 years using group-based trajectory modeling. Our results show that membership for both fine and gross motor trajectory groups was related to expressive language skills, receptive language skills, ASD symptom severity scores, and diagnostic classification at age 3. These results provide evidence that the trajectory of a child's early motor development may have important prognostic implications in ASD., (© 2021 International Society for Autism Research and Wiley Periodicals LLC.)

Mental health lived experience narratives are first-person accounts of people with experience of mental health problems. They have been published in journals, books and online, and used in healthcare interventions and anti-stigma campaigns. There are concerns about their potential misuse. A four-language systematic review was conducted of published literature characterizing uses and misuses of mental health lived experience narratives within healthcare and community settings. 6531 documents in four languages (English, Danish, Swedish, Norwegian) were screened and 78 documents from 11 countries were included. Twenty-seven uses were identified in five categories: political, societal, community, service level and individual. Eleven misuses were found, categorized as relating to the narrative (narratives may be co-opted, narratives may be used against the author, narratives may be used for different purpose than authorial intent, narratives may be reinterpreted by others, narratives may become patient porn, narratives may lack diversity), relating to the narrator (narrator may be subject to unethical editing practises, narrator may be subject to coercion, narrator may be harmed) and relating to the audience (audience may be triggered, audience may misunderstand). Four open questions were identified: does including a researcher's personal mental health narrative reduce the credibility of their research?: should the confidentiality of narrators be protected?; who should profit from narratives?; how reliable are narratives as evidence?)., (© The Author(s) 2021. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: Although early autism spectrum disorder (ASD) detection strategies tend to focus on differences at a point in time, behavioral symptom trajectories may also be informative., Methods: Developmental trajectories of early signs of ASD were examined in younger siblings of children diagnosed with ASD (n = 499) and infants with no family history of ASD (n = 177). Participants were assessed using the Autism Observation Scale for Infants (AOSI) from 6 to 18 months. Diagnostic outcomes were determined at age 3 years blind to previous assessments., Results: Semiparametric group-based modeling using AOSI scores identified three distinct trajectories: Group 1 ('Low', n = 435, 64.3%) was characterized by a low level and stable evolution of ASD signs, group 2 ('Intermediate', n = 180, 26.6%) had intermediate and stable levels, and group 3 ('Inclining', n = 61, 9.3%) had higher and progressively elevated levels of ASD signs. Among younger siblings, ASD rates at age 3 varied by trajectory of early signs and were highest in the Inclining group, membership in which was highly specific (94.5%) but poorly sensitive (28.5%) to ASD. Children with ASD assigned to the inclining trajectory had more severe symptoms at age 3, but developmental and adaptive functioning did not differ by trajectory membership., Conclusions: These prospective data emphasize variable early-onset patterns and the importance of a multipronged approach to early surveillance and screening for ASD., (© 2021 Association for Child and Adolescent Mental Health.)

A total of 12 compounds were synthesized from the natural sesquiterpene (-) drimenol (compounds 4 to 15). The synthesized compounds corresponded to N -phenyl-driman-9-carboxamide derivatives, similar to some fungicides that inhibit the electron-transport chain. Their structures were characterized and confirmed by 1 H NMR, 13 C NMR spectroscopy, and mass spectrometry. Compounds 5 to 15 corresponded to novel compounds. The effect of the compounds on the mycelial growth of Botrytis cinerea was evaluated. Methoxylated and chlorinated compounds in the aromatic ring (compounds 6, 7, 12, and 13) exhibited the highest antifungal activity with IC 50 values between 0.20 and 0.26 mM. On the other hand, the effect on conidial germination of B. cinerea of one methoxylated compound (6) and one chlorinated compound (7) was analyzed, and no inhibition was observed. Additionally, compound 7 decreased 36% the rate of oxygen consumption by germinating conidia., Competing Interests: The authors declare no conflicts of interest.

Background: The majority of research examining emotional difficulties in autism spectrum disorder (ASD) prior to age 2 relies on parent report., Methods: We examined behavioral responses (affect and gaze) during emotionally salient tasks designed to elicit mildly positive and negative emotional states in infants. At 12 and 18 months, infants at an increased likelihood for an ASD diagnosis (IL; have an older sibling with ASD; n = 60) and low likelihood (LL; no family history of ASD; n = 21) completed the Emotion-Evoking (EE) Task and parents completed the Infant Behavior Questionnaire-Revised (IBQ-R). All children received an Autism Diagnostic Observation Scale-second Edition assessment for ASD symptomatology at 24 months., Results: The main findings were (1) the IL group displayed higher rates of negative affect and spent less time looking at the task objects compared to the LL group, and (2) affect and gaze scores at 12 and 18 months, but not scores on the IBQ-R, predicted ASD symptoms at 24 months., Limitations: The data were drawn from an IL sample and may not be generalizable to the general ASD population, and the children were not followed to determine a diagnosis of ASD., Conclusion: These results suggest that behavioral responses can provide important information that complements parent reports of emotional regulation in IL infants as early as 12 months of age., (© 2021. The Author(s).)

Objective: The aim of this study was to investigate how curator goals influence the design of curation processes for collections of mental health lived experience narratives. The objectives were (1) to characterize the goals of a range of curators of existing collections, and (2) to identify specific working practices impacted by these goals., Research Design and Methods: Thirty semi-structured interviews were conducted with a purposive sample of curators of collections of lived experience narratives. Thematic analysis was conducted. Goals and impacts on working practice were tabulated, and narrative summaries were constructed to describe the relation between the two., Results: Curators interviewed were from seven countries (Brazil, Canada, Hong Kong, India, Italy, UK, USA), and 60% had lived experience of mental health service usage. Participants discussed eight goals that inspired their work: fighting stigma, campaigning for change in service provision, educating about mental health and recovery, supporting others in their recovery journey, critiquing psychiatry, influencing policy, marketing health services, and reframing mental illness. These goals influenced how decisions were made about inclusion of narratives, editing of narrative content, withdrawal rights, and anonymization., Conclusions: Our work will support the development of curatorship as a professional practice by shaping training for curators, helping curators reflect on the outcomes they would like to achieve, and helping individuals planning a collection to reflect on their motivations. We argue that transparency is an essential orientation for curators. Transparency allows narrators to make an informed choice about donating a narrative. It allows policy makers to understand the influences on a collection and hence treat it as a source of collective evidence., Competing Interests: There are no conflicts of interest to disclose.

The objectives were to characterize behavioral signs of autism spectrum disorder (ASD) in younger siblings of diagnosed children (high-risk; HR) and examine classification features of the Autism Observation Scale for Infants (AOSI). Participants (501 HR and 180 low-risk [LR]) were assessed between 6 and 18 months using the AOSI and at age 3 for ASD diagnoses. Total AOSI scores differentiated HR infants later diagnosed with ASD starting at 12 months. ROC analyses identified 12- and 18-month cutoff scores associated with 0.52 sensitivity and 0.74 specificity and 0.73 sensitivity and 0.65 specificity, respectively. Although classification accuracy does not support use as a standalone screen, the AOSI identifies features associated with ASD starting at 6 months and differentiates HR infants with ASD by 12 months., (© 2020 Society for Research in Child Development.)

Objectives: This article seeks to demonstrate the impact of distributing boxes of art resources and guided activities for vulnerable parents and infants to do together at home., Study Design: Designed in conjunction with the local arts centre and the psychology team at the University of Dundee, the art boxes were a response to planned face-to-face art interventions with families being cancelled due to COVID-19 restrictions. The aim of the art boxes is to encourage parents to make art together with their infants, fostering connection through playful, creative shared experiences. This research is currently being expanded to reach out to new families through referrals from health visitors, family nurses, and charity partners., Methods: Data is being collected on how the art boxes are experienced by families using a mixed-methods approach. Families complete feedback cards (online, or using the stamped addressed card included in the box) rating their experience on quantitative scales and providing open comments. Visual data are gathered through parents sharing images with us on social media. An initial sample of 10 participants has been interviewed using semistructured interviews, allowing more in-depth qualitative understanding of their experiences. These preliminary findings are discussed here., Results: The thematic analysis of initial interviews provided a rich picture of the disconnection families experienced during lockdown, why art boxes may be beneficial to parental well-being, and the mechanisms by which the boxes may help to develop connections for the parent and infant together., Conclusions: Preliminary findings show parents reporting feeling more confident and undertaking new activities which they plan to continue. This was of particular importance during lockdown where parents report opportunities for different experiences being more limited. Parent's describe positive playful interactions and reported improvements to their own well-being from doing creative activities together with their child. Analysis of these initial interviews gives a framework of barriers and supports to connection which highlights how art boxes can facilitate connectedness between dyads with the potential to strengthen attachments., (Copyright © 2021 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

The European Union's REACH Regulation requires determination of potential health and environmental effects of chemicals in commerce. The present case study examines the application of REACH guidance for health hazard assessments of three high production volume (HPV) aluminium (Al) substances: metallic aluminium, aluminium oxide, and aluminium hydroxide. Among the potential adverse health consequences of aluminium exposure, neurotoxicity is one of the most sensitive targets of Al toxicity and the most critical endpoint. This case study illustrates integration of data from multiple lines of evidence into REACH weight of evidence evaluations. This case study then explains how those results support regulatory decisions on classification and labelling. Challenges in the REACH appraisal of Al compounds include speciation, solubility and bioavailability, application of assessment factors, read-across rationale and differences with existing regulatory standards. Lessons learned from the present case study relate to identification and evaluation of toxicologic and epidemiologic data; assessing data relevance and reliability; development of derived no-effect levels (DNELs); addressing data gaps and preparation of chemical safety reports., (Copyright © 2020. Published by Elsevier B.V.)

New European legislation known as REACH (Registration, Evaluation, Authorization and Restriction of Chemicals) was introduced in 2007 to increase the speed at which the health and/or environmental risks of industrial chemicals were being assessed and managed (REACH (EC) No 1907/2006). REACH consolidated earlier chemicals-control statutes and placed the burden of assessing, and identifying the means to manage risks on industry. This paper details the REACH process for controlling and managing hazardous chemicals and challenges encountered in applying the provisions of REACH and the guidance documents available from European Chemical Agency. Special attention is paid to challenges in evaluating potential health risks of metals such as aluminum and aluminum compounds. Lessons learned from over a decade of experience with REACH legislation are also noted., (Copyright © 2020. Published by Elsevier B.V.)

Introduction: Emotion regulation, the ability to regulate emotional responses to environmental stimuli, develops in the first years of life and plays an important role in the development of personality, social competence, and behavior. Substantial literature suggests a relationship between emotion regulation and cardiac physiology; specifically, heart rate changes in response to positive or negative emotion-eliciting stimuli., Method: This systematic review and meta-analysis provide an in-depth examination of research that has measured physiological responding during emotional-evoking tasks in children from birth to 4 years of age., Results: The review had three main findings. First, meta-regressions resulted in an age-related decrease in baseline and task-related heart rate (HR) and increases in baseline and task-related respiratory sinus arrhythmia (RSA). Second, meta-analyses suggest task-related increases in HR and decreases in RSA and heart rate variability (HRV), regardless of emotional valence of the task. Third, associations between physiological responding and observed behavioral regulation are not consistently present in children aged 4 and younger. The review also provides a summary of the various methodology used to measure physiological reactions to emotional-evoking tasks, including number of sensors used and placement, various baseline and emotional-evoking tasks used, methods for extracting RSA, as well as percentage of loss and reasons for loss for each study., Conclusion: Characterizing the physiological reactivity of typically developing children is important to understanding the role emotional regulation plays in typical and atypical development., (© 2020 The Authors. Brain and Behavior published by Wiley Periodicals LLC.)

Rationale and Objectives: Peer learning is a case-based group-learning model intended to improve performance. In this descriptive paper, we describe multi-institutional, multi-subspecialty, web-based radiology case conferences and summarize the participants' experiences., Materials and Methods: A semi-structured, 27-question survey was administered to radiologists participating in abdominal, cardiothoracic, and musculoskeletal case conferences. Survey questions included demographics, perceived educational value and challenges experienced. Survey question formats were continuous, binary, five-point Likert scale or text-based. The measures of central tendencies, proportions of responses and patterns were tabulated., Results: From 57 responders, 12/57 (21.1%) were abdominal, 16/57 (28.1%) were cardiothoracic, and 29/57 (50.8%) were musculoskeletal conference participants; 50/56 (89.3%) represented academic practice. Median age was 45 years (range 35-74); 43/57 (75.4%) were male. Geographically, 16/52 (30.8%) of participants were from the East Coast, 16/52 (30.8%) Midwest, 18/52 (34.6%) West Coast, and 2/52 (3.8%) International. The median reported educational value was 5/5 (interquartile range 5-5). Benefits of the case conference included education (50/95, 52.6%) and networking (39/95, 41.1%). Participants reported presenting the following cases: "great call" 32/48 (66.7%), learning opportunity 32/48 (66.7%), new knowledge 41/49 (83.7%), "zebras" 46/49 (93.9%), and procedural-based 16/46 (34.8%). All 51/51 (100%) of responders reportedly gained new knowledge, 49/51 (96.1%) became more open to group discussion, 34/51 (66.7%) changed search patterns, and 50/51 (98%) would continue to participate. Reported challenges included time zone differences and support from departments for a protected time to participate., Conclusion: Peer learning through multi-institutional case conferences provides educational and networking opportunities. Current challenges and desires include having department-supported protected time and ability to receive continuing medical education credit., (Copyright © 2019 The Association of University Radiologists. Published by Elsevier Inc. All rights reserved.)

Understanding differences in social-emotional behavior can help identify atypical development. This study examined the differences in social-emotional development in children at increased risk of an autism spectrum disorder (ASD) diagnosis (infant siblings of children diagnosed with the disorder). Parents completed the Brief Infant-Toddler Social-Emotional Assessment (BITSEA) to determine its ability to flag children with later-diagnosed ASD in a high-risk (HR) sibling population. Parents of HR (n = 311) and low-risk (LR; no family history of ASD; n = 127) children completed the BITSEA when their children were 18 months old and all children underwent a diagnostic assessment for ASD at age 3 years. All six subscales of the BITSEA (Problems, Competence, ASD Problems, ASD Competence, Total ASD Score, and Red Flags) distinguished between those in the HR group who were diagnosed with ASD (n = 84) compared to non-ASD-diagnosed children (both HR-N and LR). One subscale (BITSEA Competence) differentiated between the HR children not diagnosed with ASD and the LR group. The results suggest that tracking early social-emotional development may have implications for all HR children, as they are at increased risk of ASD but also other developmental or mental health conditions.

Background: In recent years, there have been significant changes in the perception of valvular and vascular allograft transplants. Despite the constant evolution of the field of transplant and the involvement of multiple surgical specialties, there is not an official registry for administrative and clinical control. This study aims to design a registry of vascular and valvular allograft transplantation in Catalonia, Spain (ReVAC)., Materials and Methods: Three consecutive focal groups were designed. Focal groups established administrative, technical, and clinical requirements of ReVAC. ReVAC included patients with a transplanted cryopreserved vascular segment or cardiac valves that were distributed by Catalan tissue banks to public and private hospitals in Catalonia. Ten hospitals were involved in this study. Data were collected on 380 patients between January 1995 and November 2015., Results: The project resulted in the completion of a growing platform available online. ReVAC was divided into the following 3 levels: patient-related, surgery-related, and transplant-related data. Online access is available through the website of applications of the "Generalitat de Catalunya.", Conclusion: ReVAC has been useful for administrative and clinical control of transplants in Catalonia. Currently, data related to outcomes of arterial allografts are available, reinforcing the current guideline-supported indications, as well as opening a window for further analysis and guideline creation., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Introduction: There is a wide differential diagnosis for intraabdominal tumors. Surgical resection and microscopic analysis of tissue structure can identify tumor origin in most cases. Most rapidly growing invasive tumors are neoplastic. Inflammatory pseudotumors are a subcategory of intraabdominal tumors that are non-neoplastic and can be rapidly growing. Urachal cysts originate from the dome of the bladder; however they are typically not invasive. There is limited literature on the appropriate management of these tumors., Presentation: A 37-year-old female presenting with symptoms of abdominal pain was found to have a large intraabdominal mass invading multiple organs. Core biopsies demonstrated inflammation. The mass grew significantly over the course of a year and patient's abdominal pain worsened. The patient was taken to the operating room for resection. Final pathology revealed reactive fibrous tissue with acute and chronic inflammation invading bladder, urethra, abdominal wall, appendix, and ovary. Intraoperative frozen section demonstrated low grade spindle cells with concern for inflammatory pseudotumor but final pathology demonstrated inflammation., Discussion: Although benign, these tumors cause significant morbidity due to their size and level of organ invasion. Management should involve surgical resection as well as potential post-operative chemotherapy or NSAIDs based off clinical picture. We demonstrate the importance of close follow up for residual disease or recurrence of patients with inflammatory pseudotumors of the abdomen., Conclusion: This case highlights difficulties in diagnosis of a tumor that has potential to cause significant morbidity. There is need for further research to discover the best management after surgical resection of these tumors., Competing Interests: Declaration of Competing Interest N/A., (Copyright © 2020 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Introduction: Coat's plus syndrome is an extremely rare genetic syndrome that leads to a variety of symptoms. We are reporting a case of Coat's plus syndrome that had persistent GI bleeding and review of current literature., Presentation of Case: The patient is a female in her 40 s with a history of coat's disease and end stage renal failure on dialysis. The etiology of renal failure was not discovered, and the patient was being worked up for a kidney transplant. The patient required admission after deterioration of nutritional status with a BMI of 14.3. During admission the patient initially had intermittent GI bleeding requiring weekly blood transfusions. On work up of the GI bleed, no etiology was identified either. As a result persistent negative GI bleed work up, we pursued alternative diagnoses. The history of Coat's disease prompted us to work up the patient for Coat's plus syndrome. A genetic test confirmed the presence of CTC-1 gene mutation, which results in Coat's plus syndrome. With no treatment available as of yet, the patient continued to deteriorate into multi-organ failure., Discussion: We present an example of GI bleeding in Coat's plus syndrome, only identified thru genetic testing, that is very rare and complex in nature. Despite numerous workups, no specific etiology was identified for the GI bleeding., Conclusion: Previous reports have not investigated cause of GI bleeding, since it is extremely rare in the literature. Further investigation is warranted to understand cause and effects of GI bleeding in this rare genetic disease., Competing Interests: Declaration of Competing Interest No conflicts of interest., (Copyright © 2019. Published by Elsevier Ltd.)

Initiation of joint attention is a critical developmental function related to further social communicative development in infancy. Joint attention appears to be impaired very early in life for children with autism spectrum disorder (ASD), well before a formal diagnosis is established. To observe the early development of joint attention, we prospectively followed infant siblings at high risk for ASD (HR) and low-risk (LR) infants. Initiations of joint attention behaviors were coded with respect to frequency, quality, and variety from videos taken during the administration of the Autism Observation Schedule for Infants. Participants were further stratified based on the presence of ASD (n = 17) or language delay (n = 19) at 3 years of age. Our results revealed that initiations of joint attention are impaired from 12 months of age in both children with ASD and those with language delay, especially for use of gestures (i.e., showing and pointing). At 18 months, fewer initiations of joint attention in all three dimensions distinguished infants with ASD, compared to infants with language delay and HR and LR infants without a diagnosis. Beyond the definition of initiation of joint attention as an early sign for ASD, clinical implications of these results concern the importance of intervening on frequency, quality, and variety of joint attention as early as possible in infants at heightened risk for ASD.

Seventy percent of cancer patients will have metastatic bone disease, most commonly in the vertebra. Prognosis of metastatic lung cancer is poor and treatment is mostly palliative. To-date, there is no systematic review on the ideal treatment for lung cancer with spinal metastases in regards to mortality. Literature searches were performed based on PRISMA guidelines for systematic review. Thirty-nine studies comprising 1925 patients treated for spinal metastases of lung cancer met inclusion criteria. All analyses were performed using SAS and SPSS. Data were analyzed for meaningful comparisons of baseline patient characteristics, primary cancer type, metastatic lesion characteristics, treatment modality, and clinical and radiologic outcomes. Significantly greater mean survival length was seen in the non-surgical group (8.5 months, SD 6.6, SEM 0.17) compared to the surgical group (7.5 months, SD 4.5, SEM 0.25; p = 0.013). There was no statistically significant survival difference between different types of primary lung cancer: NSCLC (8.3 months, SD 13.8, SEM 0.91) and SCLC (7.0 months, SD 4.6, SEM 0.46; p = 0.36). Number of vertebral levels involved per lesion also did not exhibit significant difference: single lesion (11.3 months, SD 6.8, SEM 2.2) and multiple lesions (13.8 months, SD 15.7, SEM 3.6; p = 0.64). For patients with symptomatic spinal metastases from lung cancer, non-operative approaches experience significantly better survival outcomes (p = 0.013). Future clinical studies are needed to determine the best treatment algorithm to help maximize outcomes and minimize mortality in metastatic lung cancer., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

OBJECTIVE Carotid body tumors (CBTs), extraadrenal paragangliomas, are extremely rare neoplasms in children that often require multimodal surgical treatment, including preoperative anesthesia workup, embolization, and resection. With only a few cases reported in the pediatric literature, treatment paradigms and surgical morbidity are loosely defined, especially when carotid artery infiltration is noted. Here, the authors report two cases of pediatric CBT and provide the results of a systematic review of the literature. METHODS The study was divided into two sections. First, the authors conducted a retrospective review of our series of pediatric CBT patients and screened for patients with evidence of a CBT over the last 10 years (2007–2017) at a single tertiary referral pediatric hospital. Second, they conducted a systematic review, according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, of all reported cases of pediatric CBTs to determine the characteristics (tumor size, vascularity, symptomatology), treatment paradigms, and complications. RESULTS In the systematic review (n = 21 patients [includes 19 cases found in the literature and 2 from the authors’ series]), the mean age at diagnosis was 11.8 years. The most common presenting symptoms were palpable neck mass (62%), cranial nerve palsies (33%), cough or dysphagia (14%), and neck pain (19%). Metastasis occurred only in 5% of patients, and 19% of cases were recurrent lesions. Only 10% of patients presented with elevated catecholamines and associated sympathetic involvement. Preoperative embolization was utilized in 24% of patients (external carotid artery in 4 and external carotid artery and vertebral artery in 1). Cranial nerve palsies (cranial nerve VII [n = 1], IX [n = 1], X [n = 4], XI [n = 1], and XII [n = 3]) were the most common cause of surgical morbidity (33% of cases). The patients in the authors’ illustrative cases underwent preoperative embolization and balloon test occlusion followed by resection, and both patients suffered from transient Horner’s syndrome after embolization. CONCLUSIONS Surgical management of CBTs requires an extensive preoperative workup, anesthesia, and multimodal surgical management. Due to a potentially high rate of surgical morbidity and vascularity, balloon test occlusion with embolization may be necessary in select patients prior to resection. Careful thorough preoperative counseling is vital to preparing families for the intensive management of these children. ABBREVIATIONS BTO = balloon test occlusion; CBT = carotid body tumor; CN = cranial nerve; ECA = external carotid artery; ICA = internal carotid artery; MIBG = iodine-123-meta-iodobenzylguanidine; PRISMA = Preferred Reporting Items for Systematic Reviews and Meta-Analyses.

Early communication impairment is among the most-reported first concerns in parents of young children with autism spectrum disorder (ASD). Using a parent-report questionnaire, we derived trajectory groups for early language and gesture acquisition in siblings at high risk for ASD and in children at low risk, during their first 2 years of life. Developmental skills at 6 months were associated with trajectory group membership representing growth in receptive language and gestures. Behavioral symptoms also predicted gesture development. All communication measures were strongly related to clinical and developmental outcomes. Trajectory groups further indicated slowest language/gesture acquisition in infants with later ASD diagnoses, in particular when associated with language delay. Overall, our results confirm considerable variability in communication development in high-risk infants.