Non-invasive detection of slow conduction with cardiac magnetic resonance imaging for ventricular tachycardia ablation.

AIMS: Non-invasive myocardial scar characterization with cardiac magnetic resonance (CMR) has been shown to accurately identify conduction channels and can be an important aid for ventricular tachycardia (VT) ablation. A new mapping method based on targeting deceleration zones (DZs) has become one of the most commonly used strategies for VT ablation procedures. The aim of the study was to analyse the capability of CMR to identify DZs and to find predictors of arrhythmogenicity in CMR channels. METHODS AND RESULTS: Forty-four consecutive patients with structural heart disease and VT undergoing ablation after CMR at a single centre (October 2018 to July 2021) were included (mean age, 64.8 ± 11.6 years; 95.5% male; 70.5% with ischaemic heart disease; a mean ejection fraction of 32.3 ± 7.8%). The characteristics of CMR channels were analysed, and correlations with DZs detected during isochronal late activation mapping in both baseline maps and remaps were determined. Overall, 109 automatically detected CMR channels were analysed (2.48 ± 1.15 per patient; length, 57.91 ± 63.07 mm; conducting channel mass, 2.06 ± 2.67 g; protectedness, 21.44 ± 25.39 mm). Overall, 76.1% of CMR channels were associated with a DZ. A univariate analysis showed that channels associated with DZs were longer [67.81 ± 68.45 vs. 26.31 ± 21.25 mm, odds ratio (OR) 1.03, P = 0.010], with a higher border zone (BZ) mass (2.41 ± 2.91 vs. 0.87 ± 0.86 g, OR 2.46, P = 0.011) and greater protectedness (24.97 ± 27.72 vs. 10.19 ± 9.52 mm, OR 1.08, P = 0.021). CONCLUSION: Non-invasive detection of targets for VT ablation is possible with CMR. Deceleration zones found during electroanatomical mapping accurately correlate with CMR channels, especially those with increased length, BZ mass, and protectedness.

Same-day discharge after atrial fibrillation ablation under a nurse-coordinated standardized protocol.

AIMS: Same-day discharge (SDD) after atrial fibrillation (AF) ablation is an effective means to spare healthcare resources. However, safety remains a concern, and besides structural adaptations, SDD requires more efficient logistics and coordination. Therefore, in this study, we implement a streamlined, nurse-coordinated SDD programme following a standardized protocol. METHODS AND RESULTS: As a dedicated SDD coordinator, a nurse specialized in ambulatory cardiac interventions was in charge of the full SDD protocol, including eligibility, patient flow, in-hospital logistics, patient education, and discharge as well as early post-discharge follow-up by smartphone-based virtual visits. Patients planned for AF ablation were considered eligible if they had a left ventricular ejection fraction (LVEF) ≥35%, with basic support at home and accessibility of the hospital within 60 min also forming a part of the eligibility criteria. A total of 420 consecutive patients were screened by the SDD coordinator, of whom 331 were eligible for SDD. The reasons for exclusion were living remotely (29, 6.9%), lack of support at home (19, 4.5%), or LVEF <35% (17, 4.0%). Of the eligible patients, 300 (91%) were successfully discharged the same day. There were no major post-SDD complications. Rates of unplanned medical attention (19, 6.3%) and 30-day readmission (5, 1.6%) were extremely low and driven by femoral access-site complications. These were significantly reduced upon the introduction of compulsory ultrasound-guided punctures after the initial 150 SDD patients (P = 0.0145). Standardized SDD coordination resulted in efficient workflows and reduced the total workload of the medical staff. CONCLUSION: Same-day discharge after AF ablation following a nurse-coordinated standardized protocol is safe and efficient. The concept of ambulatory cardiac intervention nurses functioning as dedicated coordinators may be key in the future transition of hospitals to SDD. Ultrasound-guided femoral puncture virtually eliminated relevant femoral access-site complications in our cohort and should therefore be a prerequisite for SDD.

Catheter Ablation of Ventricular Tachycardia in Ischemic Heart Disease: What Is Known and New Perspectives.

PURPOSE OF THE REVIEW: This review aims to evaluate current evidence regarding ventricular tachycardia ablation in patients with ischemic heart disease and explore novel approaches currently developing to improve procedural and long-term outcomes. RECENT FINDINGS: Recently published trials (PARTITA, PAUSE-SCD, and SURVIVE-VT) have demonstrated the prognostic benefit of prophylactic ventricular tachycardia ablation compared to current clinical practice. Advanced cardiac imaging provides a valuable pre-procedural evaluation of the arrhythmogenic substrate, identifying ablation targets non-invasively. Advanced cardiac mapping techniques allow to better characterize arrhythmogenic substrate during ablation procedure. Emerging technologies like pulsed field ablation and ultra-low temperature cryoablation show promise in ventricular tachycardia ablation. Advancements in mapping techniques, ablation technologies, and pre-procedural cardiac imaging offer promise for improving ventricular tachycardia ablation outcomes in ischemic heart disease.

Scar conducting channel characterization to predict arrhythmogenicity during ventricular tachycardia ablation.

AIMS: Heterogeneous tissue channels (HTCs) detected by late gadolinium enhancement cardiac magnetic resonance (LGE-CMR) are related to ventricular arrhythmias, but there are few published data about their arrhythmogenic characteristics. METHODS AND RESULTS: We enrolled 34 consecutive patients with ischaemic and non-ischaemic cardiomyopathy who were referred for ventricular tachycardia (VT) ablation. LGE-CMR was performed prior to ablation, and the HTCs were analyzed. Arrhythmogenic HTCs linked to induced VT were identified during the VT ablation procedure. The characteristics of arrhythmogenic HTCs were compared with those of non-arrhythmogenic HTCs. Three patients were excluded due to low-quality LGE-CMR images. A total of 87 HTCs were identified on LGE-CMR in 31 patients (age:63.8 ± 12.3 years; 96.8% male; left ventricular ejection fraction: 36.1 ± 10.7%). Of the 87 HTCs, only 31 were considered arrhythmogenic because of their relation to a VT isthmus. The HTCs related to a VT isthmus were longer [64.6 ± 49.4 vs. 32.9 ± 26.6 mm; OR: 1.02; 95% CI: (1.01-1.04); P < 0.001] and had greater mass [2.5 ± 2.2 vs. 1.2 ± 1.2 grams; OR: 1.62; 95% CI: (1.18-2.21); P < 0.001], a higher degree of protectedness [26.19 ± 19.2 vs. 10.74 ± 8.4; OR 1.09; 95% CI: (1.04-1.14); P < 0.001], higher transmurality [number of wall layers with CCs: 3.8 ± 2.4 vs. 2.4 ± 2.0; OR: 1.31; 95% CI: (1.07-1.60); P = 0.008] and more ramifications [3.8 ± 2.0 vs. 2.7 ± 1.1; OR: 1.59; 95% CI: (1.15-2.19); P = 0.002] than non-arrhythmogenic HTCs. Multivariate logistic regression analysis revealed that protectedness was the strongest predictor of arrhythmogenicity. CONCLUSION: The protectedness of an HTC identified by LGE-CMR is strongly related to its arrhythmogenicity during VT ablation.

Stepwise application of ECG and electrogram-based criteria to ensure electrical resynchronization with left bundle branch pacing.

AIMS: To define a stepwise application of left bundle branch pacing (LBBP) criteria that will simplify implantation and guarantee electrical resynchronization. Left bundle branch pacing has emerged as an alternative to biventricular pacing. However, a systematic stepwise criterion to ensure electrical resynchronization is lacking. METHODS AND RESULTS: A cohort of 24 patients from the LEVEL-AT trial (NCT04054895) who received LBBP and had electrocardiographic imaging (ECGI) at 45 days post-implant were included. The usefulness of ECG- and electrogram-based criteria to predict accurate electrical resynchronization with LBBP were analyzed. A two-step approach was developed. The gold standard used to confirm resynchronization was the change in ventricular activation pattern and shortening in left ventricular activation time, assessed by ECGI. Twenty-two (91.6%) patients showed electrical resynchronization on ECGI. All patients fulfilled pre-screwing requisites: lead in septal position in left-oblique projection and W paced morphology in V1. In the first step, presence of either right bundle branch conduction delay pattern (qR or rSR in V1) or left bundle branch capture Plus (QRS ≤120 ms) resulted in 95% sensitivity and 100% specificity to predict LBBP resynchronization, with an accuracy of 95.8%. In the second step, the presence of selective capture (100% specificity, only 41% sensitivity) or a spike-R <80 ms in non-selective capture (100% specificity, sensitivity 46%) ensured 100% accuracy to predict resynchronization with LBBP. CONCLUSION: Stepwise application of ECG and electrogram criteria may provide an accurate assessment of electrical resynchronization with LBBP (Graphical abstract).

Management of Ventricular Arrhythmias in Heart Failure.

PURPOSE OF REVIEW: Despite substantial progress in medical and device-based heart failure (HF) therapy, ventricular arrhythmias (VA) and sudden cardiac death (SCD) remain a major challenge. Here we review contemporary management of VA in the context of HF with one particular focus on recent advances in imaging and catheter ablation. RECENT FINDINGS: Besides limited efficacy of antiarrhythmic drugs (AADs), their potentially life-threatening side effects are increasingly acknowledged. On the other hand, with tremendous advances in catheter technology, electroanatomical mapping, imaging, and understanding of arrhythmia mechanisms, catheter ablation has evolved into a safe, efficacious therapy. In fact, recent randomized trials support early catheter ablation, demonstrating superiority over AAD. Importantly, CMR imaging with gadolinium contrast has emerged as a central tool for the management of VA complicating HF: CMR is not only essential for an accurate diagnosis of the underlying entity and subsequent treatment decisions, but also improves risk stratification for SCD prevention and patient selection for ICD therapy. Finally, 3-dimensional characterization of arrhythmogenic substrate by CMR and imaging-guided ablation approaches substantially enhance procedural safety and efficacy. VA management in HF patients is highly complex and should be addressed in a multidisciplinary approach, preferably at specialized centers. While recent evidence supports early catheter ablation of VA, an impact on mortality remains to be demonstrated. Moreover, risk stratification for ICD therapy may have to be reconsidered, taking into account imaging, genetic testing, and other parameters beyond left ventricular function.

Development of a Predictive Model for the Diagnosis of Lower Urinary Tract Obstruction in Men.

PURPOSE: We sought to develop and validate a bladder outlet obstruction predictive model for men with nonneurogenic lower urinary tract symptoms. MATERIALS AND METHODS: We retrospectively included 1,148 patients who underwent a urodynamic study in the Urology Service of the Burgos University Hospital from January 2007 to December 2019. Obstruction was defined using the Abrams-Griffiths number. A multivariable logistic regression analysis was conducted to determine the predictors of bladder outlet obstruction. We transferred these data to a model to calculate the individual probability of obstruction. RESULTS: A first group with 563 patients randomly divided was selected for the design of the predictive risk model and a second group of 585 patients for the validation. A total of 331 patients (58.8%) in the development group and 381 (65.1%) in the validation group had a diagnosis of obstruction. A multivariable logistic regression model showed that age, history of previous surgical intervention, presence of voiding symptoms, preserved anal tone, maximum urinary flow rate and voiding efficiency were significant for predicting obstruction. The model had an area under the receiver operating characteristic curve of 0.78 (95% CI 0.75-0.82) and a model validation of 0.78 (0.72-0.83). CONCLUSIONS: Our proposed model based on clinical and noninvasive urodynamics parameters allows us to predict the risk of presenting bladder outlet obstruction in patients with lower urinary tract symptoms.

The potential role of yeasts in the mitigation of health issues related to beer consumption.

Food consumption of healthier products has become an essential trend in the food sector. This is also the case in beer, a biochemical process of transformation performed by yeast cells. More and more studies proclaim the need to reduce ethanol content in alcoholic drinks, certainly the most important health issue of beer consumption. In this review we gather key health issues related to beer consumption and the last advances regarding the use of yeast to attenuate those health problems. Furthermore, we have included the latest findings about the general positive impact of yeast in health as a consequence of its ability to biotransform polyphenolic compounds present in the wort, producing healthy compounds as hydroxytyrosol or melatonin, and its ability to perform as a probiotic driver. Besides, a group of population with chronic diseases as diabetes or celiac disease could take advantage of low carbohydrate or gluten-free beers, respectively. The role of yeast in beer production has been traditionally associated to its fermentative power. But here we have found a change in this dogma in the last years toward yeasts being a main driver to enhance healthy aspects of beer. The key findings are discussed and possible future directions are proposed.

Conduction system pacing vs. biventricular pacing in patients with ventricular dysfunction and AV block.

BACKGROUND: It is unknown whether His-Purkinje conduction system pacing (HPCSP), as either His bundle or left bundle branch pacing, could be an alternative to cardiac resynchronization therapy (BiVCRT) for patients with left ventricular dysfunction needing ventricular pacing due to atrioventricular block. The aim of the study is to compare the echocardiographic response and clinical improvement between HPCSP and BiVCRT. METHODS: Consecutive patients who successfully received HPCSP were compared with a historical cohort of BiVCRT patients. Patients were 1:1 matched by age, LVEF, atrial fibrillation, renal function and cardiomyopathy type. Responders were defined as patients who survived, did not require heart transplantation and increased LVEF ≥5 points at 6-month follow-up. RESULTS: HPCSP was successfully achieved in 92.5% (25/27) of patients. During follow-up, 8% (2/25) of HPCSP patients died and 4% (1/25) received a heart transplant, whereas 4% (1/25) of those in the BiVCRT cohort died. LVEF improvement was 10% ± 8% HPCSP versus 7% ± 5% BiVCRT (p = .24), and the percentage of responders was 76% (19/25) HPCSP versus 64% (16/25) BiVCRT (p = .33). Among survivors, the percentage of patients who improved from baseline II-IV mitral regurgitation (MR) to 0-I MR was 9/11 (82%) versus 2/8 (25%) (p = .02). Compared to those with BiVCRT, patients with HPCSP achieved better NYHA improvement: 1 point versus 0.5 (OR 0.34; p = .02). CONCLUSION: HPCSP in patients with LVEF ≤45% and atrioventricular block improved the LVEF and induced a response similar to that of BiVCRT. HPCSP significantly improved MR and NYHA functional class. HPCSP may be an alternative to BiVCRT in these patients. (Figure 1. Central Illustration). [Figure: see text].

Polymorphisms in the oxytocin receptor and their association with apathy and impaired social cognition in Huntington's disease.

BACKGROUND: Huntington's disease (HD) is a neurodegenerative disorder characterized by cognitive, motor, and neuropsychiatric manifestations. Oxytocin is a neuropeptide studied for its role as a neuromodulator regulating multiple behaviors linked to social cognition. Genetic variation of oxytocin receptor (OXTR) might interact in the etiology and development of several impaired social behaviors. Our aim was to study OXTR polymorphisms and their relationship with apathy and social cognition in HD. METHODS: OXTR was sequenced in 21 cases and 22 controls. We assessed apathy, anxiety, depression, and irritability (Hospital Anxiety and Depression Scale-Snaith Irritability scale, HADS-SIS) and social cognition (Ekman 60 faces test), motor symptoms and functionality with the total functional capacity (TFC), and the Unified HD rating Scale (UHDRS). RESULTS: We identified ten variants in OXTR. Three variants were classified as possibly damaging (p.Arg40Gly) or probably damaging (p.Leu46Pro, p.Thr102Asn). Subjects carrying the wild-type genotype of the synonymous variant p.Val45 showed a significantly lower score in the HADS-SIS scale, related to lower irritability (p = 0.013). The only subject carrying the heterozygous genotype of the synonymous variant p.Leu62 showed a significantly higher score on Ekman scale, compared to wild-type (p = 0.049); however, this finding was not confirmed after bootstrapping. CONCLUSION: Variations in OXTR could have a relevant role in the correct development of social and cognitive functions. Future approaches will include the molecular study of p.Arg40Gly, p.Leu46Pro, and p.Thr102Asn to confirm their pathogenicity, as well as the validation of the influence of p.Val45 and p.Leu62 variants for their involvement in irritability and social cognition in HD.

Survival in Restless Legs Syndrome: An 11-Year Surveillance, Community-Based Population Study.

BACKGROUND: A growing body of evidence relates restless legs syndrome (RLS) to an increased risk of mortality attributable to both cerebrovascular and cardiovascular events. The aim was to investigate survival in patients with RLS. METHODS: This was an observational, retrospective longitudinal study of a cohort of patients followed up for 11 years. RLS was diagnosed by a physician using the International RLS Study Group criteria. Mortality was analyzed using age-standardized mortality ratios (SMR: observed/expected deaths) and Cox regression analysis. RESULTS: Vital status was studied in a cohort of 232 patients: 181 women (78%), 96 with RLS (41.4%) with a mean age at baseline of 49.8 ± 15.0 years and a mean RLS duration of 14.1 ± 1.9 years, and 136 non-RLS (58.6%) with a mean age of 51.3 ± 14.9 years. This RLS cohort was followed up for a period of 10.4 ± 2.0 years. As of September 2019, 17 (7.3%) patients died (6 with RLS, 6.3%), and the most frequent cause was oncological (66.7%). A total of 944 person-years of observations were available for survival analysis. RLS was not associated with increased mortality in adjusted Cox regression analysis (HR = 1.12, 95% CI: 0.40-3.15), and survival was similar to that expected for the general population (SMR = 0.61, 95% CI: 0.27-1.36). CONCLUSIONS: RLS seems not to be associated with increased mortality compared to the general population. Still, studies with prospective data collection with large samples are needed to study the long-term mortality risk factors in RLS cohorts.

Deciphering the melatonin metabolism in Saccharomyces cerevisiae by the bioconversion of related metabolites.

Melatonin (Mel), originally considered a neurohormone, has been detected in beverages and food-fermented products in which yeast metabolism is highly important. This indolamine is synthesized from serotonin, with L-tryptophan being the initial substrate of both. Regarding Mel metabolism, the biosynthetic pathway in mammals consists in four-step reactions. However, six genes are implicated in the synthesis of Mel in plants, which suggest the presence of many pathways. The aim of this study was to provide new empirical data on the production of Mel and other indole-related compounds in the yeast Saccharomyces cerevisiae (S. cerevisiae). To this end, we performed the addition of the pathway intermediates in S. cerevisiae cells in different growth stages (exponential and arrested cells) to follow the bioconversion and new indolic compound production from them. The different bioconverted indolic compounds tested (L-tryptophan, 5-hydroxytryptophan, tryptamine, serotonin, N-acetylserotonin, 5-methoxytryptamine, and Mel) were analyzed by UHPLC-MS/MS from the extra- and intracellular contents. Our results showed that serotonin, in yeast, was prevalently formed via tryptophan decarboxylation, followed by tryptamine hydroxylation as in plants. Mel production from serotonin can be achieved by either N-acetylation, followed by O-methylation or O-methylation, in turn followed by N-acetylation. Accordingly, the classic pathway of Mel synthesis in vertebrates does not seems prevalent in yeast.

Identification of novel mouse and rat CB1R isoforms and in silico modeling of human CB1R for peripheral cannabinoid therapeutics.

Targeting peripheral CB1R is desirable for the treatment of metabolic syndromes without adverse neuropsychiatric effects. We previously reported a human hCB1b isoform that is selectively enriched in pancreatic beta-cells and hepatocytes, providing a potential peripheral therapeutic hCB1R target. It is unknown whether there are peripherally enriched mouse and rat CB1R (mCB1 and rCB1, respectively) isoforms. In this study, we found no evidence of peripherally enriched rodent CB1 isoforms; however, some mCB1R isoforms are absent in peripheral tissues. We show that the mouse Cnr1 gene contains six exons that are transcribed from a single promoter. We found that mCB1A is a spliced variant of extended exon 1 and protein-coding exon 6; mCB1B is a novel spliced variant containing unspliced exon 1, intron 1, and exon 2, which is then spliced to exon 6; and mCB1C is a spliced variant including all 6 exons. Using RNAscope in situ hybridization, we show that the isoforms mCB1A and mCB1B are expressed at a cellular level and colocalized in GABAergic neurons in the hippocampus and cortex. RT-qPCR reveals that mCB1A and mCB1B are enriched in the brain, while mCB1B is not expressed in the pancreas or the liver. Rat rCB1R isoforms are differentially expressed in primary cultured neurons, astrocytes, and microglia. We also investigated modulation of Cnr1 expression by insulin in vivo and carried out in silico modeling of CB1R with JD5037, a peripherally restricted CB1R inverse agonist, using the published crystal structure of hCB1R. The results provide models for future CB1R peripheral targeting.

Observational study of newborn infant parasympathetic evaluation as a comfort system in awake patients admitted to a pediatric intensive care unit.

To compare the newborn infant parasympathetic evaluation system (NIPE) scores with a validated clinical scale using two different nebulizers in children with bronchiolitis admitted to a PICU. Comfort was evaluated using the COMFORT-behavior scale (CBS) before (T1), during (T2) and after (T3) each nebulization. In order to compare NIPE and CBS values during the whole T1 to T3 period, the variable Dif-CBS was defined as the difference between maximal and minimal CBS scores, and Dif-NIPE as the difference between 75th and 25th percentile NIPE values. Analyses were carried out, firstly for the total of nebulizations and secondly comparing two different nebulization systems: a jet nebulizer (JN) and a nebulizer integrated in high flow nasal cannulas (NHF). 84 nebulizations were recorded on 14 patients with a median [25th-75th percentile] age of 6 months (3.1-9.5). A Dif-CBS of 4 points (2-7), as well as changes in CBS scores between T1 and T2, defined the nebulization as a discomfort stimulus. The NIPE system, represented as the Dif-NIPE, showed a median variation of 9 points (7-10), and was poorly correlated to Dif-CBS [rs 0.162 (P = 0.142)]. Discomfort during nebulization, assessed by CBS was greater with the JN system compared to NHF: 17 (13-22) vs 13 (9-15) (P = 0.001). NIPE monitoring detected no significant differences between both nebulization systems (P = 0.706). NIPE monitoring showed a variation in comfort during nebulization in the patient with bronchiolitis, though correlation with CBS was poor. Further research is required before NIPE can be suggested as a comfort monitoring system for the awake infant.

Absence of cannabinoid 1 receptor in beta cells protects against high-fat/high-sugar diet-induced beta cell dysfunction and inflammation in murine islets.

AIMS/HYPOTHESIS: The cannabinoid 1 receptor (CB1R) regulates insulin sensitivity and glucose metabolism in peripheral tissues. CB1R is expressed on pancreatic beta cells and is coupled to the G protein Gαi, suggesting a negative regulation of endogenous signalling in the beta cell. Deciphering the exact function of CB1R in beta cells has been confounded by the expression of this receptor on multiple tissues involved in regulating metabolism. Thus, in models of global genetic or pharmacological CB1R blockade, it is difficult to distinguish the indirect effects of improved insulin sensitivity in peripheral tissues from the direct effects of inhibiting CB1R in beta cells per se. To assess the direct contribution of beta cell CB1R to metabolism, we designed a mouse model that allows us to determine the role of CB1R specifically in beta cells in the context of whole-body metabolism. METHODS: We generated a beta cell specific Cnr1 (CB1R) knockout mouse (ß-CB1R-/-) to study the long-term consequences of CB1R ablation on beta cell function in adult mice. We measured beta cell function, proliferation and viability in these mice in response to a high-fat/high-sugar diet and induction of acute insulin resistance with the insulin receptor antagonist S961. RESULTS: ß-CB1R-/- mice had increased fasting (153 ± 23% increase at 10 weeks of age) and stimulated insulin secretion and increased intra-islet cAMP levels (217 ± 33% increase at 10 weeks of age), resulting in primary hyperinsulinaemia, as well as increased beta cell viability, proliferation and islet area (1.9-fold increase at 10 weeks of age). Hyperinsulinaemia led to insulin resistance, which was aggravated by a high-fat/high-sugar diet and weight gain, although beta cells maintained their insulin secretory capacity in response to glucose. Strikingly, islets from ß-CB1R-/- mice were protected from diet-induced inflammation. Mechanistically, we show that this is a consequence of curtailment of oxidative stress and reduced activation of the NLRP3 inflammasome in beta cells. CONCLUSIONS/INTERPRETATION: Our data demonstrate CB1R to be a negative regulator of beta cell function and a mediator of islet inflammation under conditions of metabolic stress. Our findings point to beta cell CB1R as a therapeutic target, and broaden its potential to include anti-inflammatory effects in both major forms of diabetes. DATA AVAILABILITY: Microarray data have been deposited at GEO (GSE102027).

Incretin secretion in humans is under the influence of cannabinoid receptors.

The mechanisms regulating incretin secretion are not fully known. Human obesity is associated with altered incretin secretion and elevated endocannabinoid levels. Since cannabinoid receptors (CBRs) are expressed on incretin-secreting cells in rodents, we hypothesized that endocannabinoids are involved in the regulation of incretin secretion. We compared plasma glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) responses during oral glucose tolerance test (OGTT) in 20 lean and 20 obese participants from the Baltimore Longitudinal Study of Aging (BLSA). Next, we recruited 20 healthy men to evaluate GIP and GLP-1 responses during OGTT after administering placebo or nabilone (CBR agonist) in a randomized, double-blind, crossover fashion. Compared with the BLSA lean group, the BLSA obese group had significantly higher fasting and post-OGTT GIP levels, but similar fasting GLP-1 and significantly lower post-OGTT GLP-1 levels. In the nabilone vs. placebo study, when compared with placebo, nabilone resulted in significantly elevated post-dose fasting GIP levels and post-OGTT GIP levels, but no change in post-dose fasting GLP-1 levels together with significantly lower post-OGTT GLP-1 levels. Glucose levels were not different with both interventions. We conclude that elevated GIP levels in obesity are likely a consequence of increased endocannabinoid levels. CBRs exert tonic control over GIP secretion, which may have a homeostatic effect in suppressing GLP-1 secretion. This raises the possibility that gut hormones are influenced by endocannabinoids.

The Association of Poor Academic Performance with Tic Disorders: A Longitudinal, Mainstream School-Based Population Study.

BACKGROUND: Little is known about the academic performance of students with tic disorders (TD). Our aim was to investigate the association of TD and poor academic performance over time. METHODS: Longitudinal, observational study of mainstream schoolchildren comparing grade retention (GR) and learning disorders (LD) in students with vs. without TD between 2010 and 2014. Students with vs. without TD based on DSM-IV-TR criteria, or with vs. without GR and LD were compared in terms of comorbidities, school, and environmental characteristics. The association of TD with GR was analyzed using hazard ratios (HRs) with 95% CIs, and with LD using logistic regression analysis [Odds ratio (OR)]. RESULTS: Two hundred fifty-eight students were included (mean age 14.0 ± 1.71 years, 143 [55.4%] males). The incident rate for TD and GR was 2.6 and 3.3 per 100 persons-year, respectively. LD found in 21 (9.9%) students was associated with TD (OR 11.62, 95% CI 2.21-60.90, p = 0.004), and attention deficit hyperactivity disorder (ADHD; OR 6.63, 95% CI 1.55-28.37, p = 0.01). Low psychological support (HRs 12.79, 95% CI 3.39-48.17) and low sport participation (HRs 6.41, 95% CI 1.54-26.78) were risk factors for GR. CONCLUSIONS: TD was associated with academic difficulties, namely, LD in conjunction with ADHD but not GR. The diagnosis of TD and comorbidities, and the initiation of proper treatment could have a favorable impact on school performance, and consequently on social development.

Comparative imaging study of patients with persistent olfactory dysfunction due to mild COVID-19 using structural and functional MRI.

INTRODUCTION: Persistent post-COVID olfactory dysfunction continues to be studied due to the controversy in its pathophysiology and neuroimaging. MATERIALS AND METHODS: The patients had confirmed mild COVID-19 infection with olfactory dysfunction of more than one month of evolution and they were compared to controls with normal olfaction, assessed using the Sniffin' Sticks Olfactory Test and underwent brain, magnetic resonance imaging (MRI) of the olfactory bulb and olfactory function. RESULTS: A total of 8 patients and 2 controls participated. The average age of the patients was 34.5 years (SD 8.5), and that of the controls was 28.5 (SD 2.1). The average score in the patients' olfactory test was 7.9 points (SD 2.2). In brain and olfactory bulb MRI tests, no morphological differences were found. When evaluated by functional MRI, none of the patients activated the entorhinal area in comparison to the controls, who did show activation at this level. Activation of secondary olfactory areas in cases and controls were as follows: orbitofrontal (25% vs 100%), basal ganglia (25% vs 50%) and insula (38% vs 0%) respectively. CONCLUSIONS: There were no observed morphological changes in the brain MRI. Unlike the controls, none of the patients activated the entorhinal cortex in the olfactory functional MRI.

Validation of ActiGraph and Fitbit in the assessment of energy expenditure in Huntington's disease.

BACKGROUND: Consumer and research activity monitors have become popular because of their ability to quantify energy expenditure (EE) in free-living conditions. However, the accuracy of activity trackers in determining EE in people with Huntington's Disease (HD) is unknown. RESEARCH QUESTION: Can the ActiGraph wGT3X-B or the Fitbit Charge 4 accurately measure energy expenditure during physical activity, in people with HD compared to Indirect Calorimetry (IC) (Medisoft Ergo Card)? METHODS: We conducted a cross-sectional, observational study with fourteen participants with mild-moderate HD (mean age 55.7 ± 11.4 years). All participants wore an ActiGraph and Fitbit during an incremental test, running on a treadmill at 3.2 km/h and 5.2 km/h for three minutes at each speed. We analysed and compared the accuracy of EE estimates obtained by Fitbit and ActiGraph against the EE estimates obtained by a metabolic cart, using with Intra-class correlation (ICC), Bland-Altman analysis and correlation tests. RESULTS: A significant correlation and a moderate reliability was found between ActiGraph and IC for the incremental test (r = 0.667)(ICC=0.633). There was a significant correlation between Fitbit and IC during the incremental test (r = 0.701), but the reliability was poor at all tested speeds in the treadmill walk. Fitbit significantly overestimated EE, and ActiGraph underestimated EE compared to IC, but ActiGraph estimates were more accurate than Fitbit in all tests. SIGNIFICANCE: Compared to IC, Fitbit Charge 4 and ActiGraph wGT3X-BT have reduced accuracy in estimating EE at slower walking speeds. These findings highlight the need for population-specific algorithms and validation of activity trackers.

Fasting and Glucose Metabolism Differentially Impact Peripheral Inflammation in Human Type 2 Diabetes.

Cytokines produced by peripheral T-helper 1/17 cells disproportionately contribute to the inflammation (i.e., metaflammation) that fuels type 2 diabetes (T2D) pathogenesis. Shifts in the nutrient milieu could influence inflammation through changes in T-cell metabolism. We aimed to determine whether changes in glucose utilization alter cytokine profiles in T2D. Peripheral blood mononuclear cells (PBMCs), CD4+ T-cells, and CD4+CD25- T-effector (Teff) cells were isolated from age-matched humans classified by glycemic control and BMI. Cytokines secreted by CD3/CD28-stimulated PBMCs and Teff were measured in supernatants with multiplex cytokine assays and a FLEXMAP-3D. Metabolic activity of stimulated CD4+ T-cells was measured by a Seahorse XFe96 analyzer. In this study, we demonstrated that T-cell stimulated PBMCs from non-fasted people with T2D produced higher amounts of cytokines compared to fasting. Although dysglycemia characterizes T2D, cytokine production by PBMCs or CD4+ T-cells in T2D was unaltered by hyperglycemic media. Moreover, pharmacological suppression of mitochondrial glucose oxidation did not change T-cell metabolism in T2D, yet enhanced cytokine competency. In conclusion, fasting and glucose metabolism differentially impact peripheral inflammation in human T2D, suggesting that glucose, along with fatty acid metabolites per our previous work, partner to regulate metaflammation. These data expose a major disconnect in the use of glycemic control drugs to target T2D-associated metaflammation.