Recent data suggest that subclinical atherosclerosis is more related to visceral adipose tissue distribution than to overall fat mass. Both perirenal fat and epicardial fat are visceral fat depots surrounding the kidneys and the myocardium, respectively, which can be easily assessed by ultrasound. Their clinical relevance in children is largely unknown. This review describes studies relating perirenal and epicardial fat to cardiovascular disease or carotid intima-media thickness (cIMT), a well-established surrogate for subclinical atherosclerosis, and discusses this in context with our own data from children. In adults, both perirenal and epicardial fat are useful biological markers of visceral obesity. The former has been related to hypertension in overweight subjects and with atherosclerosis in patients with human immunodeficiency virus. The latter was associated with several metabolic syndrome components and with calcification of the carotid artery. In healthy prepubertal children, both epicardial and perirenal fat thickness, rather than total body fat mass, were related to cIMT. Ultrasonography measures of perirenal and epicardial fat are related to atherosclerosis in adults and may be convenient tools for the assessment of cardiometabolic risk in children.
Adipose Tissue ; Adult ; Atherosclerosis ; Biomarkers ; Body Fat Distribution ; Cardiovascular Diseases ; Carotid Arteries ; Carotid Intima-Media Thickness ; Child ; HIV ; Humans ; Hypertension ; Intra-Abdominal Fat ; Kidney ; Myocardium ; Obesity, Abdominal ; Overweight ; Ultrasonography

OBJECTIVES: In Spain, there has been a recent increase in the mortality rate for chronic obstructive pulmonary disease (COPD) in younger women. This study aimed to analyze trends in the COPD mortality rate in Spain from 1980 to 2020, evaluating any differences between genders and age groups. METHODS: Death certificates and mid-year population data were obtained from the Spanish National Institute of Statistics. For both genders, age group-specific and standardized (overall and truncated) rates were calculated by the direct method using the world standard population. The data were analyzed using the joinpoint regression method. RESULTS: In both men and women, the number of COPD deaths increased from 1980 to 1999 (average annual increase of 7% in men and 4% in women), while from 1999 onwards, deaths decreased by -1.0% per year in both genders. In women, there was a significant final period of increase in the 55-59 to 70-74 age groups and a slowing of the decline in the over 75 age group. Additionally, an increase in mortality for the truncated rates was observed for women between 2006 and 2020. In men under 70 years of age, there was an initial period in which death rates remained stable or significantly increased, followed by a period in which they decreased significantly. CONCLUSIONS Our study shows age and gender differences in COPD mortality trends in Spain. Although the data show a downward trend, we have identified a worrying increase in the truncated rates in women for the last few years.

Objective: Agitation in patients diagnosed with personality disorders (PD) is one of the most frequent crises in emergency departments (ED). Although many medications have been tested, their effectiveness has been small or non-significant, and no specific drugs are supported by the available evidence. This study aimed to evaluate the efficacy of Inhaled loxapine (IL) as a therapeutic option for agitated patients with PD. Methods: A naturalistic, unicentric, prospective study was carried out. Thirty subjects diagnosed with PD and attending the ED with episodes of agitation were recruited most of whom were women diagnosed with Borderline Personality Disorder. Subjects were treated with a single dose of IL (9.1 mg). Efficacy was assessed with the Clinical Global Impression scale, the Excited Component of the Positive and Negative Syndrome Scale (PANSS-EC) and the Agitation-Calmness Evaluation Scale (ACES). Patients were followed 60 minutes after administration to measure IL effect and its duration. Results: IL exhibited an overall efficacy in managing mild to severe agitation, with a quick onset of effect and persistence. ‘Effect of time’, where IL efficacy is maintained over time, is more marked in higher-severity agitation. No additional treatments were needed to improve agitation during the follow-up time. Conclusion Results suggest that IL could be a safe and effective option to manage agitation in PD.

Background: This study aimed to evaluate the influence of maternal diabetes in the risk of neurodevelopmental disorders in offspring in the prenatal and postnatal periods. Methods: This cohort study included singleton gestational diabetes mellitus (GDM) pregnancies >22 weeks’ gestation with live newborns between 1991 and 2008. The control group was randomly selected and matched (1:2) for maternal age, weeks of gestation and birth year. Cox regression models estimated the effect of GDM on the risk of attention-deficit/hyperactivity disorder (ADHD), autism spectrum disorder (ASD), and maternal type 2 diabetes mellitus (T2DM). Moreover, interaction between maternal T2DM and GDM-ADHD relationship was evaluated. Results: Children (n=3,123) were included (1,073 GDM; 2,050 control group). The median follow-up was 18.2 years (interquartile range, 14.2 to 22.3) (n=323 with ADHD, n=36 with ASD, and n=275 from women who developed T2DM). GDM exposure was associated with ADHD (hazard ratio [HR]crude, 1.67; 95% confidence interval [CI], 1.33 to 2.07) (HRadjusted, 1.64; 95% CI, 1.31 to 2.05). This association remained significant regardless of the treatment (diet or insulin) and diagnosis after 26 weeks of gestation. Children of mothers who developed T2DM presented higher rates of ADHD (14.2 vs. 10%, P=0.029). However, no interaction was found when T2DM was included in the GDM and ADHD models (P>0.05). GDM was not associated with an increased risk of ASD (HRadjusted, 1.46; 95% CI, 0.74 to 2.84). Conclusion Prenatal exposure to GDM increases the risk of ADHD in offspring, regardless of GDM treatment complexity. However, postnatal exposure to maternal T2DM was not related to the development of ADHD.

We describe the development of quinolylnitrones (QNs) as multifunctional ligands inhibiting cholinesterases (ChEs: acetylcholinesterase and butyrylcholinesterase-hBChE) and monoamine oxidases (hMAO-A/B) for the therapy of neurodegenerative diseases. We identified QN 19, a simple, low molecular weight nitrone, that is readily synthesized from commercially available 8-hydroxyquinoline-2-carbaldehyde. Quinolylnitrone 19 has no typical pharmacophoric element to suggest ChE or MAO inhibition, yet unexpectedly showed potent inhibition of hBChE (IC₅₀ = 1.06 ± 0.31 nmol/L) and hMAO-B (IC₅₀ = 4.46 ± 0.18 μmol/L). The crystal structures of 19 with hBChE and hMAO-B provided the structural basis for potent binding, which was further studied by enzyme kinetics. Compound 19 acted as a free radical scavenger and biometal chelator, crossed the blood-brain barrier, was not cytotoxic, and showed neuroprotective properties in a 6-hydroxydopamine cell model of Parkinson's disease. In addition, in vivo studies showed the anti-amnesic effect of 19 in the scopolamine-induced mouse model of AD without adverse effects on motoric function and coordination. Importantly, chronic treatment of double transgenic APPswe-PS1δE9 mice with 19 reduced amyloid plaque load in the hippocampus and cortex of female mice, underscoring the disease-modifying effect of QN 19.

Background: and Purpose Recent studies suggested an increased incidence of cerebral venous thrombosis (CVT) during the coronavirus disease 2019 (COVID-19) pandemic. We evaluated the volume of CVT hospitalization and in-hospital mortality during the 1st year of the COVID-19 pandemic compared to the preceding year. Methods: We conducted a cross-sectional retrospective study of 171 stroke centers from 49 countries. We recorded COVID-19 admission volumes, CVT hospitalization, and CVT in-hospital mortality from January 1, 2019, to May 31, 2021. CVT diagnoses were identified by International Classification of Disease-10 (ICD-10) codes or stroke databases. We additionally sought to compare the same metrics in the first 5 months of 2021 compared to the corresponding months in 2019 and 2020 (ClinicalTrials.gov Identifier: NCT04934020). Results: There were 2,313 CVT admissions across the 1-year pre-pandemic (2019) and pandemic year (2020); no differences in CVT volume or CVT mortality were observed. During the first 5 months of 2021, there was an increase in CVT volumes compared to 2019 (27.5%; 95% confidence interval [CI], 24.2 to 32.0; P<0.0001) and 2020 (41.4%; 95% CI, 37.0 to 46.0; P<0.0001). A COVID-19 diagnosis was present in 7.6% (132/1,738) of CVT hospitalizations. CVT was present in 0.04% (103/292,080) of COVID-19 hospitalizations. During the first pandemic year, CVT mortality was higher in patients who were COVID positive compared to COVID negative patients (8/53 [15.0%] vs. 41/910 [4.5%], P=0.004). There was an increase in CVT mortality during the first 5 months of pandemic years 2020 and 2021 compared to the first 5 months of the pre-pandemic year 2019 (2019 vs. 2020: 2.26% vs. 4.74%, P=0.05; 2019 vs. 2021: 2.26% vs. 4.99%, P=0.03). In the first 5 months of 2021, there were 26 cases of vaccine-induced immune thrombotic thrombocytopenia (VITT), resulting in six deaths. Conclusions During the 1st year of the COVID-19 pandemic, CVT hospitalization volume and CVT in-hospital mortality did not change compared to the prior year. COVID-19 diagnosis was associated with higher CVT in-hospital mortality. During the first 5 months of 2021, there was an increase in CVT hospitalization volume and increase in CVT-related mortality, partially attributable to VITT.