Discriminative capacity of volumetry by CT scan to identify autonomous cortisol secretion in incidental adrenal adenomas

Context Incidentally discovered adrenal adenomas are common. Assessment for possible autonomous cortisol excess (ACS) is warranted for all adrenal adenomas given the association with increased cardiometabolic disease. Objective To evaluate the discriminatory capacity of three-dimensional volumetry on computed tomography (CT) to identify ACS. Design, Setting, Patients Two radiologists, blinded to hormonal levels, prospectively analyzed CT images on 149 adult patients with unilateral, incidentally-discovered, adrenal adenomas. Main Outcome Measures Diameter and volumetry of the adenoma, volumetry of the contralateral adrenal gland, and the adenoma volume-to-contralateral gland volume (AV/CV) ratio were measured. ACS was defined as cortisol≥1.8 mcg/dL after 1mg dexamethasone suppression test (DST) and a morning ACTH ≤15 pg/mL. Results We observed that ACS was diagnosed in 35 (23.4%) patients. Cortisol post-DST was positively correlated with adenoma diameter and volume, and inversely correlated with contralateral adrenal gland volume. Cortisol post-DST was positively correlated with the AV/CV ratio (r=0.46, p<0.001) and ACTH was inversely correlated (r=-0.28, p<0.001). The AV/CV ratio displayed the highest Odds Ratio (1.40 CI 95% 1.18-1.65) and area under curve (0.91 CI 95% 0.86-0.96) for predicting ACS. An AV/CV ratio ≥1 (48% of the cohort) had a sensitivity of 97% and a specificity of 70% to identify ACS. Conclusions CT volumetry of adrenal adenomas and contralateral adrenal glands has a high discriminatory capacity to identify ACS. The combination of this simple and low-cost radiological phenotyping can supplement biochemical testing to substantially improve the identification of ACS.

Convergent Cerebrospinal Fluid Proteomes and Metabolic Ontologies in Humans and Animal Models of Rett Syndrome

MECP2 loss-of-function mutations cause Rett syndrome, a disorder that results from a disrupted brain transcriptome. How these transcriptional defects are decoded into a disease proteome remains unknown. We studied the proteome in Rett syndrome cerebrospinal fluid (CSF) across vertebrates. We identified a consensus proteome and ontological categories shared across Rett syndrome cerebrospinal fluid (CSF) from three species, including humans. Rett CSF proteomes enriched proteins annotated to HDL lipoproteins, complement, mitochondria, citrate/pyruvate metabolism, as well as synapse compartments. We used these prioritized and shared ontologies to select analytes for orthogonal quantification. These studies independently validated our proteome and ontologies. Ontologically selected CSF hits had genotypic discriminatory capacity as determined by Receiver Operating Characteristic (ROC) analysis and distinguished Rett from a related neurodevelopmental disorder, CDKL5 deficiency disorder. We propose that Mecp2 mutant CSF proteomes and ontologies inform novel putative mechanisms and biomarkers of disease. We suggest that Rett syndrome is a metabolic disorder impacting synapse function.

Análisis de la curva ROC en la evaluación de indicadores antropométricos

Evaluation of the Waist Weight-Circumference Index (WWCI) using Logistic Regression. Descriptive, prospective and cross-sectional study shows 1095 adults and older adults, aged between 20 and 96 years. Methods: variables: age, weight, size, Waist Circumference (WC), BMI, Waist-Size Index (WSI). Results: Similar BMI in both sexes; higher WC and WSI averages in a ≥ age of 65; major WWCI in group 20-59 years; WWCI risk rate (54.1%) higher in WC (44.7%) WSI (78.2%). WWSI significantly associated with BMI, WC and WSI (p<0.000); positive predictive value 0.92 and negative predictive value 0.70, indicate discriminatory capacity; Relative Risk, 1.92; Wald test statistic indicates statistical significance for the coefficients of risk probability equations; area under the ROC curve is 0.803 and 0.903 (P<0.000), high sensitivity and specificity. Conclusion: WWCI can be considered to evaluate overweight and obesity in adults, given its high discriminatory capacity.

The structural basis of odorant recognition in insect olfactory receptors

Olfactory systems must detect and discriminate amongst an enormous variety of odorants1. To contend with this challenge, diverse species have converged on a common strategy in which odorant identity is encoded through the combinatorial activation of large families of olfactory receptors1–3, thus allowing a finite number of receptors to detect a vast chemical world. Here we offer structural and mechanistic insight into how an individual olfactory receptor can flexibly recognize diverse odorants. We show that the olfactory receptor MhOR5 from the jumping bristletail4Machilis hrabei assembles as a homotetrameric odorant-gated ion channel with broad chemical tuning. Using cryo-electron microscopy, we elucidated the structure of MhOR5 in multiple gating states, alone and in complex with two of its agonists—the odorant eugenol and the insect repellent DEET. Both ligands are recognized through distributed hydrophobic interactions within the same geometrically simple binding pocket located in the transmembrane region of each subunit, suggesting a structural logic for the promiscuous chemical sensitivity of this receptor. Mutation of individual residues lining the binding pocket predictably altered the sensitivity of MhOR5 to eugenol and DEET and broadly reconfigured the receptor’s tuning. Together, our data support a model in which diverse odorants share the same structural determinants for binding, shedding light on the molecular recognition mechanisms that ultimately endow the olfactory system with its immense discriminatory capacity.

Polygener Risikoscore hilft bei der Diagnose der Spondylitis akylosans

<b>Objective:</b> We sought to test the hypothesis that Polygenic Risk Scores (PRSs) have strong capacity to discriminate cases of ankylosing spondylitis (AS) from healthy controls and individuals in the community with chronic back pain. <b>Methods:</b> PRSs were developed and validated in individuals of European and East Asian ethnicity, using data from genome-wide association studies in 15 585 AS cases and 20 452 controls. The discriminatory values of PRSs in these populations were compared with other widely used diagnostic tests, including C-reactive protein (CRP), HLA-B27 and sacroiliac MRI. <b>Results:</b> In people of European descent, PRS had high discriminatory capacity with area under the curve (AUC) in receiver operator characteristic analysis of 0.924. This was significantly better than for HLA-B27 testing alone (AUC = 0.869), MRI (AUC = 0.885) or C-reactive protein (AUC = 0.700). PRS developed and validated in individuals of East Asian descent performed similarly (AUC = 0.948). Assuming a prior probability of AS of 10% such as in patients with chronic back pain under 45 years of age, compared with HLA-B27 testing alone, PRS provides higher positive values for 35% of patients and negative predictive values for 67.5% of patients. For PRS, in people of European descent, the maximum positive predictive value was 78.2% and negative predictive value was 100%, whereas for HLA-B27, these values were 51.9% and 97.9%, respectively. <b>Conclusions:</b> PRS have higher discriminatory capacity for AS than CRP, sacroiliac MRI or HLA-B27 status alone. For optimal performance, PRS should be developed for use in the specific ethnic groups to which they are to be applied.

Better Identification of Cognitive Decline With Interleukin-2 Than With Amyloid and Tau Protein Biomarkers in Amnestic Mild Cognitive Impairment

The rate of cognitive decline among patients with amnestic mild cognitive impairment (aMCI) varies, and it is thus crucial to accurately predict the probability of cognitive deterioration in patients with MCI. We compared the potential of cytokines with amyloid beta (Aβ) and tau biomarkers for predicting cognitive decline in patients with aMCI or Alzheimer’s disease (AD). All participants (controls, aMCI, and AD patients) underwent plasma biomarker examinations for Aβ1–40, Aβ1–42, total tau (t-tau), tau phosphorylated at threonine 181 [p-Tau181]), and 29 cytokines and baseline cognitive tests, including Mini-Mental State Examination (MMSE). The correlation between biomarker levels and annual MMSE change during the follow-up was examined. Receiver operating characteristic (ROC) curve analysis was performed to determine whether the statistically significant plasma biomarkers could identify cognitive decline. Higher baseline levels of IL-2, sCD40L, IL-8, and VEGF were associated with a lower annual cognitive decline in the aMCI group, and higher baseline levels of Aβ1–40, IFNγ, IL-5, IL-17A, IL-25, and FGF were associated with a rapid annual cognitive decline in the AD group. IL-2 had a high discriminatory capacity for identifying cognitive decline, with an area under curve (AUC) of 85.7% in the aMCI group, and the AUC was slightly increased when combining IL-2 with Aβ or tau biomarkers. However, none of the biomarkers had a satisfactory discriminatory capacity in the AD group. IL-2 may have a better discriminatory capacity for identifying cognitive decline than Aβ and tau biomarkers in patients with aMCI.

MMMELD-XI Score Is Associated With Short-Term Adverse Events in Patients With Heart Failure With Preserved Ejection Fraction

Aim: Accumulating evidence suggests that MELD-XI score holds the ability to predict the prognosis of congestive heart failure. However, most of the evidence is based on the end-stage heart failure population; thus, we aim to explore the association between the MELD-XI score and the prognosis in heart failure with preserved ejection fraction (HFpEF).Methods: A total of 30,096 patients hospitalized for HFpEF in Fujian Provincial Hospital between January 1, 2014 and July 17, 2020 with available measures of creatinine and liver function were enrolled. The primary endpoint was 60-day in-hospital all-cause mortality. Secondary endpoints were 60-day in-hospital cardiovascular mortality and 30-day rehospitalization for heart failure.Results: A total of 222 patients died within 60 days after admission, among which 75 deaths were considered cardiogenic. And 73 patients were readmitted for heart failure within 30 days after discharge. Generally, patients with an elevated MELD-XI score tended to have more comorbidities, higher NYHA class, and higher inflammatory biomarkers levels. Meanwhile, the MELD-XI score was positively correlated with NT-pro BNP, left atrial diameter, E/e' and negatively correlated with LVEF. After adjusting for conventional risk factors, the MELD-XI score was independently associated with 60-day in-hospital all-cause mortality [hazard ratio(HR) = 1.052, 95% confidential interval (CI) 1.022–1.083, P = 0.001], 60-day in-hospital cardiovascular mortality (HR = 1.064, 95% CI 1.013–1.118, P = 0.014), and 30-day readmission for heart failure (HR = 1.061, 95% CI 1.015–1.108, P = 0.009). Furthermore, the MELD-XI score added an incremental discriminatory capacity to risk stratification models developed based on this cohort.Conclusion: The MELD-XI score was associated with short-term adverse events and provided additional discriminatory capacity to risk stratification models in patients hospitalized for HFpEF.

Internal structure of Beck Hopelessness Scale: An analysis of method effects using the CT-C(M–1) model

The construct validity in relation to the dimensionality or factor structure of the Beck Hopelessness Scale (BHS) has long been debated in psychometrics. Irrelevant variance due to item wording (method effects) can distort the factor structure, and recent studies have examined the method factor’s role in the factor structure of the BHS. However, the models used to control the method effects have severe limitations, and new models are needed. One such model is the correlated trait-correlated method minus one (CT-C(M-1)), which is a powerful approach that gives the trait factor an unambiguous meaning and prevents the anomalous results associated with fully symmetrical bifactor modeling. The present work compares the fit and factor structure of the CT-C(M-1) model to bifactor models proposed in previous literature and evaluates the convergent validity of the CT-C(M-1) model and its discriminatory capacity by taking suicidal ideation as the criterion variable. This study used a large and heterogeneous open mode online sample of Argentinian people (N = 2,164). The results indicated that the CT-C(M-1) model with positive words as referenced items achieves the most adequate factor structure. The factorial scores derived from this model demonstrate good predictive and discriminating capabilities.