Marker Of Vulnerability Research Articles

Inflammation and emotion regulation: a narrative review of evidence and mechanisms in emotion dysregulation disorders.

Emotion dysregulation (ED) describes a difficulty with the modulation of which emotions are felt, as well as when and how these emotions are experienced or expressed. It is a focal overarching symptom in many severe and prevalent neuropsychiatric diseases, including bipolar disorders (BD), attention deficit/hyperactivity disorder (ADHD), and borderline personality disorder (BPD). In all these disorders, ED can manifest through symptoms of depression, anxiety, or affective lability. Considering the many symptomatic similarities between BD, ADHD, and BPD, a transdiagnostic approach is a promising lens of investigation. Mounting evidence supports the role of peripheral inflammatory markers and stress in the multifactorial aetiology and physiopathology of BD, ADHD, and BPD. Of note, neural circuits that regulate emotions appear particularly vulnerable to inflammatory insults and peripheral inflammation, which can impact the neuroimmune milieu of the central nervous system. Thus far, few studies have examined the link between ED and inflammation in BD, ADHD, and BPD. To our knowledge, no specific work has provided a critical comparison of the results from these disorders. To fill this gap in the literature, we review the known associations and mechanisms linking ED and inflammation in general, and clinically, in BD, ADHD, and BD. Our narrative review begins with an examination of the routes linking ED and inflammation, followed by a discussion of disorder-specific results accounting for methodological limitations and relevant confounding factors. Finally, we critically discuss both correspondences and discrepancies in the results and comment on potential vulnerability markers and promising therapeutic interventions.

Is the association between blood pressure and cognition in the oldest-old modified by physical, vascular or brain pathology markers? The EMIF-AD 90 + Study

BackgroundPrior studies suggest a changing association between blood pressure (BP) and cognition with aging, however work in the oldest-old has yielded ambiguous results. Potentially, these mixed results can be explained by modifying factors. The aim of this study was to establish whether physical, vascular or brain pathology markers that describe a state of increased vulnerability, affect the association between BP and cognition in the oldest-old. Results may influence clinicians’ decisions regarding the use of antihypertensives in this age group.MethodsWe included 122 individuals (84 without cognitive impairment and 38 with cognitive impairment) from the EMIF-AD 90 + Study (mean age 92.4 years). First, we tested cross-sectional associations of systolic and diastolic BP with a cognitive composite score. Second, we tested whether these associations were modified by physical markers (waist circumference, muscle mass, gait speed and handgrip strength), vascular markers (history of cardiac disease, carotid intima media thickness as a proxy for atherosclerosis and carotid distensibility coefficient as a proxy for arterial stiffness) or brain pathology markers (white matter hyperintensities and cortical thickness).ResultsIn the total sample, there was no association between BP and cognition, however, waist circumference modified this association (p-value for interaction with systolic BP: 0.03, with diastolic BP: 0.01). In individuals with a high waist circumference, higher systolic and diastolic BP tended to be associated with worse cognition, while in individuals with a low waist circumference, higher systolic BP was associated with better cognition. The others physical, vascular and brain pathology markers did not modify the association between BP and cognition.ConclusionsWhen examining various markers for physical, vascular and brain vulnerability, only waist circumference affected the association between BP and cognition. This warrants further research to evaluate whether waist circumference may be a marker in clinical practice influencing the use of antihypertensives in the oldest-old.

Severe periodontal disease is associated with a high-risk phenotype of coronary plaques and a higher severity of coronary atherosclerosis, as assessed by Coronary Computed Tomography Angiography

Abstract Introduction Although incompletely understood, the relationship between coronary heart disease (CHD) and periodontal disease (PD) is well known. A variety of indices can be used to identify periodontal disease. The lack of strict criteria in defining PD represents a challenge in studying the link with CHD. Data from the literature regarding the relationship between different periodontal indices and CHD are extremely limited. Purpose To investigate the link between the PD indices, coronary calcifications and plaque features in patients with CHD who underwent coronary computed tomography angiography (CCTA). Methods The study included 52 patients with PD in whom (CCTA) revealed CHD. All patients underwent a complex oral examination of the periodontal status and the following indices were assessed: gingival index (GI), plaque index (PqI), calculus index (CI), furcation defects (FI), papillary bleeding index (PBI), tooth mobility, clinical attachment loss (CAL) and probing pocket depth (PPD). The indices were determined for the tooth’s 1.6, 2.1, 2.4, 3.6, 4.1, 4.4 and the final score for each index was obtained by summing the values from the six teeth. The association between the periodontal indices and CCTA features (total coronary artery calcium and vulnerability markers) was evaluated using Graph Pad InStat 3.10 software. The p value was set at 0.05 for statistical significance. Results The mean age of the study population was 54.48 ± 12.83 years old with a male to female ratio of 2.46. At the CCTA examination, mean total coronary artery calcium score was 284.20 ± 418.00. An association between the total coronary artery calcium score and GI (r2=0.12, p=0.01), PqI (r2=0.07, p=0.04), CI (r2=0.10, p=0.01), PBI (r2=0.12, p=0.01), PPD (r2=0.08, p=0.03) was found. Assessment of CCTA features of vulnerability at the level of atherosclerotic plaques indicated a strong association between periodontal indexes and plaque vulnerability: p<0.01 for association between CAL and spotty calcification, positive remodeling and napkin ring sign, p=0.009 for association between PPD and spotty calcification, and p=0.01 for association between tooth mobility and positive remodeling. Conclusions In patients with concomitant PD and CHD, the severity of periodontal disease seems to be associated with severity of atherosclerotic disease, assessed by the total coronary artery calcium score. At the same time, severity of PD is associated with a more expressed vulnerability of coronary plaques, indicating a high-risk phenotype of atheromatous plaques in patients with concomitant PD, and systemic inflammation is most likely the link between the two conditions.

National routine data for low birthweight and preterm births: Systematic data quality assessment for United Nations member states (2000-2020).

Low birthweight (<2500 g) and preterm birth (<37 weeks) are markers of newborn vulnerability. To facilitate informed decisions about investments in prevention and care, it is imperative to enhance data quality and use. Hence, the objective of this study is to systematically assess the quality of data concerning low birthweight and preterm births within routine administrative data sources. Systematic data quality assessment by adopting the WHO Data Quality Framework. National routine data system from UN member states. Livebirths. National routine administrative data on low birthweight and preterm births for 195 countries from 2000 to 2020 were systematically collated, totalling >700 million live births. The WHO data quality framework was adapted to undertake standardised data quality assessments. Availability, reporting quality, internal and external consistency of low birthweight and preterm data. Most United States Member States (64%: 124/195) had national data on low birthweight and (40%: 82/195) had data on preterm birth. Routine data system reporting was highest in North America, Australasia and Europe, where more than 95% live births had data on low birthweight and over 75% had data preterm births. In contrast,data reporting was lowest in sub-Saharan Africa (13% for low birthweight, 8% for preterm births) and Southern Asia (16% for low birthweight, 5% for preterm births). Most countries collect individual-level data; but, aggregate data reporting from hospital-based systems remain common in sub-Saharan Africa and Southern Asia. While data quality was generally high in North America, Australasia and Europe, gaps remain in the availability of gestational age metadata. Consistency between low birthweight and preterm rates were poor in Southern Asia and sub-Saharan Africa regions across time. There was high external consistency between low birthweight rates obtained from routine administrative data compared with low birthweight rates obtained from survey data for countries with highdata quality. Sub-Saharan Africa and South Asia countries have data gaps but also opportunities for rapid progress. Most births occure in facilities, electronic health information systems already include low birthweight, and adding accurate gestational age including with ultrasound assessment is becoming increasingly attainable. Moving toward the collection of individual level data would enable monitoring of quality of care and longer-term outcomes. This is crucial for every child and family and essential for measuring progress towards relevant sustainable development goals. The assessment will inform countries' actions for data quality improvement at national level and use of data for impact.

Machine learning-directed electrical impedance tomography to predict metabolically vulnerable plaques.

The characterization of atherosclerotic plaques to predict their vulnerability to rupture remains a diagnostic challenge. Despite existing imaging modalities, none have proven their abilities to identify metabolically active oxidized low-density lipoprotein (oxLDL), a marker of plaque vulnerability. To this end, we developed a machine learning-directed electrochemical impedance spectroscopy (EIS) platform to analyze oxLDL-rich plaques, with immunohistology serving as the ground truth. We fabricated the EIS sensor by affixing a six-point microelectrode configuration onto a silicone balloon catheter and electroplating the surface with platinum black (PtB) to improve the charge transfer efficiency at the electrochemical interface. To demonstrate clinical translation, we deployed the EIS sensor to the coronary arteries of an explanted human heart from a patient undergoing heart transplant and interrogated the atherosclerotic lesions to reconstruct the 3D EIS profiles of oxLDL-rich atherosclerotic plaques in both right coronary and left descending coronary arteries. To establish effective generalization of our methods, we repeated the reconstruction and training process on the common carotid arteries of an unembalmed human cadaver specimen. Our findings indicated that our DenseNet model achieves the most reliable predictions for metabolically vulnerable plaque, yielding an accuracy of 92.59% after 100 epochs of training.

Association of polygenic risk for bipolar disorder with grey matter structure and white matter integrity in youth

There is a gap in knowledge regarding the polygenic underpinnings of brain anomalies observed in youth bipolar disorder (BD). This study examined the association of a polygenic risk score for BD (BD-PRS) with grey matter structure and white matter integrity in youth with and without BD. 113 participants were included in the analyses, including 78 participants with both T1-weighted and diffusion-weighted MRI images, 32 participants with T1-weighted images only, and 3 participants with diffusion-weighted images only. BD-PRS was calculated using PRS-CS-auto and was based on independent adult genome-wide summary statistics. Vertex- and voxel-wise analyses examined the associations of BD-PRS with grey matter metrics (cortical volume [CV], cortical surface area [CSA], cortical thickness [CTh]) and fractional anisotropy [FA] in the combined sample, and separately in BD and HC. In the combined sample of participants with T1-weighted images (n = 110, 66 BD, 44 HC), higher BD-PRS was associated with smaller grey matter metrics in frontal and temporal regions. In within-group analyses, higher BD-PRS was associated with lower CTh of frontal, temporal, and fusiform gyrus in BD, and with lower CV and CSA of superior frontal gyrus in HC. In the combined sample of participants with diffusion-weighted images (n = 81, 49 BD, 32 HC), higher BD-PRS was associated with lower FA in widespread white matter regions. In summary, BD-PRS calculated based on adult genetic data was negatively associated with grey matter structure and FA in youth in regions implicated in BD, which may suggest neuroimaging markers of vulnerability to BD. Future longitudinal studies are needed to examine whether BD-PRS predicts neurodevelopmental changes in BD vs. HC and its interaction with course of illness and long-term medication use.

An observational treatment study of metacognition in anxious-depression

Prior studies have found metacognitive biases are linked to a transdiagnostic dimension of anxious-depression, manifesting as reduced confidence in performance. However, previous work has been cross-sectional and so it is unclear if under-confidence is a trait-like marker of anxious-depression vulnerability, or if it resolves when anxious-depression improves. Data were collected as part of a large-scale transdiagnostic, four-week observational study of individuals initiating internet-based cognitive behavioural therapy (iCBT) or antidepressant medication. Self-reported clinical questionnaires and perceptual task performance were gathered to assess anxious-depression and metacognitive bias at baseline and 4-week follow-up. Primary analyses were conducted for individuals who received iCBT (n=649), with comparisons between smaller samples that received antidepressant medication (n=82) and a control group receiving no intervention (n=88). Prior to receiving treatment, anxious-depression severity was associated with under-confidence in performance in the iCBT arm, replicating previous work. From baseline to follow-up, levels of anxious-depression were significantly reduced, and this was accompanied by a significant increase in metacognitive confidence in the iCBT arm (β=0.17, SE=0.02, p&lt;0.001). These changes were correlated (r(647)=-0.12, p=0.002); those with the greatest reductions in anxious-depression levels had the largest increase in confidence. While the three-way interaction effect of group and time on confidence was not significant (F(2, 1632)=0.60, p=0.550), confidence increased in the antidepressant group (β=0.31, SE = 0.08, p&lt;0.001), but not among controls (β=0.11, SE = 0.07, p=0.103). Metacognitive biases in anxious-depression are state-dependent; when symptoms improve with treatment, so does confidence in performance. Our results suggest this is not specific to the type of intervention.

High-Anxious People Generalize Costly Pain-Related Avoidance Behavior More to Novel Safe Contexts Compared to Low-Anxious People

Pain-related avoidance is adaptive when there is a bodily threat, but when it generalizes to safe movements/situations, it may become disabling. Both subclinical anxiety—a vulnerability marker for chronic pain—and chronic pain are associated with excessive fear generalization to safe stimuli/situations. Previous research focused mainly on passive fear correlates (psychophysiological arousal and self-reports) leaving avoidance behavior poorly understood. Therefore, we tested whether high-anxious individuals generalize their pain-related avoidance behavior more to novel, safe contexts than low-anxious people. In a robotic-arm-reaching task, both groups (low vs high trait anxiety) performed 1 of 3 movements to reach a target. In the threat context (black background), a painful stimulus could be partly/completely prevented by performing more effortful trajectories (longer and more force needed); in the safe context (white background), no pain occurred. Generalization of avoidance was tested in 2 novel contexts (light/dark gray backgrounds). We assessed pain expectancy, pain-related fear, startle eyeblink responses for all trajectories, and avoidance behavior (ie, maximal deviation from shortest trajectory). Results indicated that differential fear and expectancy selectively generalized to the novel context resembling the original threat context in both groups. Interestingly and in contrast with the verbal reports, high-anxious participants avoided more in the novel context resembling the original safe context, but not in the 1 resembling the threat context. No generalization emerged in the startle data. Because excessive pain-related avoidance specifically may cause withdrawal from daily life activities, these findings suggest that high-anxious individuals may be vulnerable to developing chronic pain disability. PerspectiveThis paper shows that high-anxious people do not overgeneralize pain-related fear and pain expectancy learned in a threat context more to novel, safe contexts than low-anxious individuals, but that they do avoid more in those contexts. These findings suggest that high-anxious individuals may be vulnerable to developing chronic pain disability.

The accumulation of erythrocytes quantified and visualized by Glycophorin C in carotid atherosclerotic plaque reflects intraplaque hemorrhage and pre-procedural neurological symptoms

The accumulation of erythrocyte membranes within an atherosclerotic plaque may contribute to the deposition of free cholesterol and thereby the enlargement of the necrotic core. Erythrocyte membranes can be visualized and quantified in the plaque by immunostaining for the erythrocyte marker glycophorin C. Hence, we theorized that the accumulation of erythrocytes quantified by glycophorin C could function as a marker for plaque vulnerability, possibly reflecting intraplaque hemorrhage (IPH), and offering predictive value for pre-procedural neurological symptoms. We employed the CellProfiler-integrated slideToolKit workflow to visualize and quantify glycophorin C, defined as the total plaque area that is positive for glycophorin C, in single slides of culprit lesions obtained from the Athero-Express Biobank of 1819 consecutive asymptomatic and symptomatic patients who underwent carotid endarterectomy. Our assessment included the evaluation of various parameters such as lipid core, calcifications, collagen content, SMC content, and macrophage burden. These parameters were evaluated using a semi-quantitative scoring method, and the resulting data was dichotomized as predefined criteria into categories of no/minor or moderate/heavy staining. In addition, the presence or absence of IPH was also scored. The prevalence of IPH and pre-procedural neurological symptoms were 62.4% and 87.1%, respectively. The amount of glycophorin staining was significantly higher in samples from men compared to samples of women (median 7.15 (IQR:3.37, 13.41) versus median 4.06 (IQR:1.98, 8.32), p < 0.001). Glycophorin C was associated with IPH adjusted for clinical confounders (OR 1.90; 95% CI 1.63, 2.21; p = < 0.001). Glycophorin C was significantly associated with ipsilateral pre-procedural neurological symptoms (OR:1.27, 95%CI:1.06–1.41, p = 0.005). Sex-stratified analysis, showed that this was also the case for men (OR 1.37; 95%CI 1.12, 1.69; p = 0.003), but not for women (OR 1.15; 95%CI 0.77, 1.73; p = 0.27). Glycophorin C was associated with classical features of a vulnerable plaque, such as a larger lipid core, a higher macrophage burden, less calcifications, a lower collagen and SMC content. There were marked sex differences, in men, glycophorin C was associated with calcifications and collagen while these associations were not found in women. To conclude, the accumulation of erythrocytes in atherosclerotic plaque quantified and visualized by glycophorin C was independently associated with the presence of IPH, preprocedural symptoms in men, and with a more vulnerable plaque composition in both men and women. These results strengthen the notion that the accumulation of erythrocytes quantified by glycophorin C can be used as a marker for plaque vulnerability.

Electroencephalographic markers from routine sleep discriminate individuals who are vulnerable or resilient to sleep loss.

Sleep loss impairs cognition; however, individuals differ in their response to sleep loss. Current methods to identify an individual's vulnerability to sleep loss involve time-consuming sleep-loss challenges and neurobehavioural tests. Here, we sought to identify electroencephalographic markers of sleep-loss vulnerability obtained from routine night sleep. We retrospectively analysed four studies in which 50 healthy young adults (21 women) completed a laboratory baseline-sleep phase followed by a sleep-loss challenge. After classifying subjects as resilient or vulnerable to sleep loss, we extracted three electroencephalographic features from four channels during the baseline nights, evaluated the discriminatory power of these features using the first two studies (discovery), and assessed reproducibility of the results using the remaining two studies (reproducibility). In the discovery analysis, we found that, compared to resilient subjects, vulnerable subjects exhibited: (1) higher slow-wave activity power in channel O1 (p < 0.0042, corrected for multiple comparisons) and in channels O2 and C3 (p < 0.05, uncorrected); (2) higher slow-wave activity rise rate in channels O1 and O2 (p < 0.05, uncorrected); and (3) lower sleep spindle frequency in channels C3 and C4 (p < 0.05, uncorrected). Our reproducibility analysis confirmed the discovery results on slow-wave activity power and slow-wave activity rise rate, and for these two electroencephalographic features we observed consistent group-difference trends across all four channels in both analyses. The higher slow-wave activity power and slow-wave activity rise rate in vulnerable individuals suggest that they have a persistently higher sleep pressure under normal rested conditions.

Characterizing the spectrum of irritability in preadolescence: Dimensional and pragmatic applications.

Characterize the dimensional spectrum of preadolescent (PA) irritability, a robust transdiagnostic vulnerability marker, using the youth version of the Multidimensional Assessment Profiles Temper Loss (MAPS-TL-Youth) scale including common and with developmentally specific items. Based on this, derive and validate a clinically optimized irritability screener to flag psychopathology risk in preadolescents. The normal:abnormal irritability spectrum was modeled using MAPS-TL-Youth data from the Multidimensional Assessment of Preschoolers Study (MAPS) Study PA wave (n=340) via item response theory. Both cross-cutting core items from the MAPS scales and developmentally specific items were used to generate this dimension. Stepwise logistic regression was then used to optimize MAPS-TL-Youth irritability items in relation to Kiddie Schedule of Affective Disorders and Schizophrenia impairment to generate a clinically optimized irritability screener. Receiver operator characteristic analysis identified the irritability threshold for the screener. For the first time, youth self-report of their own irritability on the MAPS-TL was also modeled via the MAPS-TL-Youth-Self-Report (MAPS-TL-Youth-SR). Irritability was unidimensional and ranged from mild and common to severe and rare behaviors. Developmentally specific items allowed detection of more severe irritability. Items for the screener were identified in relation to concurrent impairment. These included low frustration tolerance and pathognomonic severe behaviors. The clinically optimized screener demonstrated very good sensitively (87%) and specificity (81%) in regard to concurrent irritability-related DSM disorders. Modeling of the MAPS-TL-Youth-SR yielded similar results. Characterizing the normal: abnormal spectrum of irritability in preadolescence advances application of Research Domain Criteria methods to this developmental period. This foundational work yielded two developmentally specified tools for irritability characterization in preadolescence: a nuanced dimensional scale to precisely characterize the full normal-abnormal irritability spectrum, and a pragmatic, clinically optimized screener suitable for real world use. Future application in mechanistic and clinical studies will be important for establishing validity and incremental utility.

Neural activations during cognitive and affective theory of mind processing in healthy adults with a family history of alcohol use disorder.

Social cognition impairments are a common feature of alcohol use disorders (AUD). However, it remains unclear whether these impairments are solely the consequence of chronic alcohol consumption or whether they could be a marker of vulnerability. The present study implemented a family history approach to address this question for a key process of social cognition: theory of mind (ToM). Thirty healthy adults with a family history of AUD (FH+) and 30 healthy adults with a negative family history of AUD (FH-), matched for age, sex, and education level, underwent an fMRI cartoon-vignette paradigm assessing cognitive and affective ToM. Participants also completed questionnaires evaluating anxiety, depressive symptoms, childhood trauma, and alexithymia. Results indicated that FH+ individuals differed from FH- individuals on affective but not cognitive ToM processing, at both the behavioral and neural levels. At the behavioral level, the FH+ group had lower response accuracy for affective ToM compared with the FH- group. At the neural level, the FH+ group had higher brain activations in the left insula and inferior frontal cortex during affective ToM processing. These activations remained significant when controlling for depressive symptoms, anxiety, and childhood trauma. These findings highlight difficulties during affective ToM processing among first-degree relatives of AUD patients, supporting the idea that some of the impairments exhibited by these patients may already be present before the onset of AUD and may be considered a marker of vulnerability.

Prevalence and risk of stillbirth according to biologic vulnerability phenotypes in the municipality of São Paulo, Brazil: A population-based cohort study.

To estimate the prevalence and risk of stillbirths by biologic vulnerability phenotypes in a cohort of pregnant women in the municipality of São Paulo, Brazil, 2017-2019. Retrospective population-based cohort study. Fetuses were assessed as small for gestational age (SGA), large for gestational age (LGA), adequate for gestational age (AGA), preterm (PT) as less than 37 weeks of gestation, non-PT (NPT) as 37 weeks of gestation or more, low birth weight (LBW) as less than 2500 g, and non-LBW (NLBW) as 2500 g or more. Relative risks (RR) with robust variance were estimated using Poisson regression. In all 442 782 pregnancies, including 2321 (0.5%) stillbirths, were included. About 85% (n = 1983) of stillbirths had at least one characteristic of vulnerability, compared with 21% (n = 92524) of live births. Fetuses with all three markers of vulnerability had the highest adjusted RR of stillbirth-SGA + LBW + PT (RR 155.00; 95% confidence interval [CI] 136.29-176.30) and LGA + LBW + PT (RR 262.04; 95% CI 206.10-333.16) when compared with AGA + NLBW + NPT. Our findings show that the simultaneous presence of prematurity, low birth weight, and abnormal intrauterine growth presented a higher risk of stillbirths. To accelerate progress towards reducing preventable stillbirths, one must identify the circumstances of greatest biologic vulnerability.

Association of polygenic risk for bipolar disorder with resting-state network functional connectivity in youth with and without bipolar disorder

Little is known regarding the polygenic underpinnings of anomalous resting-state functional connectivity (rsFC) in youth bipolar disorder (BD). The current study examined the association of polygenic risk for BD (BD-PRS) with whole-brain rsFC at the large-scale network level in youth with and without BD. 99 youth of European ancestry (56 BD, 43 healthy controls [HC]), ages 13–20 years, completed resting-state fMRI scans. BD-PRS was calculated using summary statistics from the latest adult BD genome-wide association study. Data-driven independent component analyses of the resting-state fMRI data were implemented to examine the association of BD-PRS with rsFC in the overall sample, and separately in BD and HC. In the overall sample, higher BD-PRS was associated with lower rsFC of the salience network and higher rsFC of the frontoparietal network with frontal and parietal regions. Within the BD group, higher BD-PRS was associated with higher rsFC of the default mode network with orbitofrontal cortex, and altered rsFC of the visual network with frontal and occipital regions. Within the HC group, higher BD-PRS was associated with altered rsFC of the frontoparietal network with frontal, temporal and occipital regions. In conclusion, the current study found that BD-PRS generated based on adult genetic data was associated with altered rsFC patterns of brain networks in youth. Our findings support the usefulness of BD-PRS to investigate genetically influenced neuroimaging markers of vulnerability to BD, which can be observed in youth with BD early in their course of illness as well as in healthy youth.

Congenital syphilis in Switzerland: a marker of inequality? A mini-review.

Syphilis remains a global public health problem, with growing incidence in most regions of the world, particularly among women of childbearing age. This alarming trend has led to an increase in cases of congenital syphilis, resulting in devastating consequences. While the implementation of measures by the World Health Organization (WHO) and various governments has contributed to a decline in the global incidence of congenital syphilis, many countries are facing an escalating crisis, as incidence continues to rise. This mini-review aims to provide an overview of the current state of this disease in different parts of the world, focusing on the most affected populations and highlighting congenital syphilis as a marker of vulnerability. It also focuses on Switzerland, a country with a robust economy, to identify shortcomings in the healthcare system that contribute to the persistence of congenital syphilis, even though the infection is easily detectable and treatable. In conclusion, this mini-review highlights the persistent risk of congenital syphilis worldwide, regardless of country prevalence or economic status, and underscores the need for sustained efforts to reach underserved women, emphasizing the vital role of comprehensive training for healthcare professionals.

Pilot Monitoring of Lead in Umbilical Cord Blood of Newborns Associated With the Use of Glazed Ceramics from Guanajuato, Mexico.

The use of lead-glazed pottery for cooking and storing food, a widespread practice in Mexico, represents a risk of exposure to lead from the human intrauterine stage. Therefore, a pilot study was carried out by means of the measurement of lead in umbilical cord blood by inductively coupled plasma mass spectrometry (ICP-MS) including 69 newborns from the Mexican state capital of Guanajuato, Guanajuato City, where the use of glazed clay is still widespread. Lifestyle and sociodemographic data were collected by interviewing the participating mothers. Hematological parameters and the anthropometry of the newborns and their mothers were analyzed; likewise, the G177C polymorphism in the ALAD gene was genotyped by PCR-RFLP as a marker of genetic vulnerability to lead. The geometric mean of lead in umbilical cord blood was 0.7µg/dL (< limit of detection = 0.01-28.22). Boys presented higher values than girls (p = 0.03). Only 5.8% of these were above the safety value of the US Centers for Disease Control and Prevention (CDC) of 3.5µg/dL. Correlations among lead concentrations, maternal age, weeks of gestation, newborn anthropometry, and hematological parameters were not found; however, the participating mothers who reported using glazed ceramics for cooking or storing food had the highest cord-blood lead concentrations (p = 0.04). Regarding genotyping, 97% had ALAD 1, while 3% had ALAD 1, 2; unfortunately, the sample size did not allow analysis of genetic vulnerability to lead. The preparation and conservation of food in handcrafted clay pottery increased the risk of having cord-blood lead values higher than those recommended by the CDC of 3.5µg/dL (OR = 5; 95% CI:1.3-23; p = 0.01). Our preliminary results suggest that there continues to be intrauterine exposure to lead in Guanajuato.

Coronary CT angiography for the assessment of atherosclerotic plaque inflammation: postmortem proof of concept with histological validation.

To evaluate the diagnostic utility of multiphase postmortem CT angiography (PMCTA) to detect plaque enhancement as a surrogate marker of inflammation, using fatal coronary plaques obtained from autopsies following sudden cardiac death. In this retrospective study, we included 35 cases (12 women, 34%; median [IQR] age, 52 [11] years), with autopsy-proven coronary thrombosis, histological examination, and multiphase PMCTA. Two radiologists blinded towards histological findings assessed PMCTA for plaque enhancement of the culprit lesion in consensus. Two forensic pathologists determined the culprit lesion and assessed histological samples in consensus. Cases with concomitant vasa vasorum density increase and intraplaque and periadventital inflammation were considered positive for plaque inflammation. Finally, we correlated radiology and pathology findings. All 35 cases had histological evidence of atherosclerotic plaque disruption and thrombosis; 30 (85.7%) had plaque inflammation. Plaque enhancement at multiphase PMCTA was reported in 21 (60%) and resulted in a PPV of 95.2% (77.3-99.2%) and an NPV of 28.6% (17-43.9%). Median histological ratings indicated higher intraplaque inflammation (p = .024) and vasa vasorum density (p = .032) in plaques with enhancement. We found no evidence of a difference in adventitial inflammation between CT-negative and CT-positive plaques (p = .211). Plaque enhancement was found in 2/3 of fatal atherothrombotic occlusions at coronary postmortem CT angiography. Furthermore, plaque enhancement correlated with histopathological plaque inflammation and increased vasa vasorum density. Plaque enhancement on multiphase CT angiography could potentially serve as a noninvasive marker of inflammation in high-risk populations. Phenotyping coronary plaque more comprehensively is one of the principal challenges cardiac imaging is facing. Translating our ex vivo findings of CT-based plaque inflammation assessment into clinical studies might help pave the way in defining high-risk plaque better. • Most thrombosed coronary plaques leading to fatality in our series had histological signs of inflammation. • Multiphase postmortem CT angiography can provide a noninvasive interrogation of plaque inflammation through contrast enhancement. • Atherosclerotic plaque enhancement at multiphase postmortem CT angiography correlated with histopathological signs of plaque inflammation and could potentially serve as an imaging biological marker of plaque vulnerability.

Intra-operative electroencephalogram frontal alpha-band spectral analysis and postoperative delirium in cardiac surgery: A prospective cohort study.

Postoperative delirium (POD) remains a frequent complication after cardiac surgery, with pre-operative cognitive status being one of the main predisposing factors. However, performing complete pre-operative neuropsychological testing is challenging. The magnitude of frontal electroencephalographic (EEG) α oscillations during general anaesthesia has been related to pre-operative cognition and could constitute a functional marker for brain vulnerability. We hypothesised that features of intra-operative α-band activity could predict the occurrence of POD. Single-centre prospective observational study. University hospital, from 15 May 2019 to 15 December 2021. Adult patients undergoing elective cardiac surgery. Pre-operative cognitive status was assessed by neuropsychological tests and scored as a global z score. A 5-min EEG recording was obtained 30 min after induction of anaesthesia. Anaesthesia was maintained with sevoflurane. Power and peak frequency in the α-band were extracted from the frequency spectra. POD was assessed using the Confusion Assessment Method for Intensive Care Unit, the Confusion Assessment Method and a chart review. Sixty-five (29.5%) of 220 patients developed POD. Delirious patients were significantly older with median [IQR] ages of 74 [64 to 79] years vs. 67 [59 to 74] years; P < 0.001) and had lower pre-operative cognitive z scores (-0.52 ± 1.14 vs. 0.21 ± 0.84; P < 0.001). Mean α power (-14.03 ± 4.61 dB vs. -11.59 ± 3.37 dB; P < 0.001) and maximum α power (-11.36 ± 5.28 dB vs. -8.85 ± 3.90 dB; P < 0.001) were significantly lower in delirious patients. Intra-operative mean α power was significantly associated with the probability of developing POD (adjusted odds ratio, 0.88; 95% confidence interval (CI), 0.81 to 0.96; P = 0.007), independently of age and only whenever cognitive status was not considered. A lower intra-operative frontal α-band power is associated with a higher incidence of POD after cardiac surgery. Intra-operative measures of α power could constitute a means of identifying patients at risk of this complication. NCT03706989.

Correlation between new atherosclerotic plaque vulnerability markers and the carotid magnetic resonance images in hyperlipidemic patients treated with proprotein convertase subtilisin/kexin type 9 inhibitors

Correlation between new atherosclerotic plaque vulnerability markers and the carotid magnetic resonance images in hyperlipidemic patients treated with proprotein convertase subtilisin/kexin type 9 inhibitors

Analysis of polyunsaturated fatty acids in antipsychotic-free individuals with at-risk mental state and patients with first-episode schizophrenia.

Abnormalities in membrane phospholipids are considered one of the pathophysiological backgrounds for schizophrenia. This study, explores the fatty acid composition of erythrocyte membranes and its association with clinical characteristics in two groups: individuals with an at-risk mental state (ARMS) and patients experiencing their first-episode of schizophrenia (FES). This study measured erythrocyte membrane fatty acids in 72 antipsychotic-free individuals with ARMS, 18 antipsychotic-free patients with FES, and 39 healthy volunteers. Clinical symptoms and cognitive and social functions were assessed using the Positive and Negative Syndrome Scale (PANSS), Brief Assessment of Cognition in Schizophrenia (BACS), Schizophrenia Cognition Rating Scale (SCoRS), and Social and Occupational Functioning Assessment Scale (SOFAS). Eicosapentaenoic and docosapentaenoic acid levels were lower in the ARMS and FES groups than in the healthy control group. In contrast, nervonic acid (NA) levels were markedly higher in the ARMS and FES groups than in the controls, while only the FES group showed higher levels of arachidonic acid. Oleic acid and NA levels were significantly associated with PANSS scores in both the FES and ARMS groups, particularly for the negative and general subscores. However, the patient groups had no significant associations between the fatty acid composition and the BACS, SCoRS, and SOFAS scores. Furthermore, the baseline fatty acid composition did not differ between the ARMS individuals who later developed psychosis (N = 6) and those who were followed for more than 2 years without developing psychosis onset (N = 30). The findings suggest that abnormal fatty acid compositions may be shared in the early stages of schizophrenia and the clinical high-risk state for psychosis and may serve as vulnerability markers of psychopathology.