Increased brain fractional perfusion in obesity using intravoxel incoherent motion (IVIM) MRI metrics.

OBJECTIVE: This research seeks to shed light on the associations between brain perfusion, cognitive function, and mental health in individuals with and without obesity. METHODS: In this study, we employed the noninvasive intravoxel incoherent motion (IVIM) magnetic resonance imaging (MRI) technique to examine brain fractional perfusion (FP) in two groups: individuals with obesity (N = 72) and healthy controls (N = 66). Additionally, we investigated potential associations between FP, cognitive function, and depressive symptoms in the participants with and without obesity. Finally, artificial intelligence algorithms (Boruta analysis) were also used. RESULTS: Participants with obesity exhibited increased FP within dopaminergic brain circuits, particularly involving prefrontal cortex areas, anterior and posterior sections of the cingulate cortex, the right striatum, and the midbrain. Additionally, these individuals demonstrated lower working memory and higher depressive symptoms compared to the control group. Notably, higher FP in the inferior temporal and occipital cortices correlated with greater depressive symptoms, whereas increased FP in the right ventral caudate and the midbrain was associated with better working memory performance. A link between inflammatory and metabolic variables, with a particular emphasis on monocytes, and FP in obesity was also evidenced by Boruta analysis. CONCLUSIONS: Increased brain perfusion in individuals with obesity is associated with cognitive function and mental health through interaction with metabolic and inflammatory factors.

Lower serum ferritin levels are associated with worse cognitive performance in aging.

OBJECTIVES: Iron is important for neurogenesis, synaptic development, and neurotransmitter synthesis. Serum ferritin (SF) is a reliable marker for assessing iron stores. Therefore, we evaluated the cognitive function associated with SF levels. We also assessed brain iron content using R2* Magnetic Resonance Imaging (MRI) and its association with SF levels. DESIGN: Data from three cross-sectional observational studies were used. Aging Imageomics (n = 1030) was conducted on aged subjects. Health Imageomics (n = 971) and IR0NMET (n = 175) were conducted in middle-aged subjects. SETTING AND PARTICIPANTS: Participants were enrolled at Dr. Josep Trueta University Hospital facilities. The three cohorts included a total of 2176 subjects (mean age, 52 years; 48% men). MEASUREMENTS: SF levels were measured by standard laboratory methods. Total Digits Span (TDS), and Phonemic Verbal Fluency (PVF) were used to assess executive function. Language function was assessed by semantic verbal fluency (SVF), attention by the Symbol Digit Modalities Test, and memory by the Memory Binding Tests - Total Free Recall and Total Delayed Free Recall. MRI was used to assess the iron content of the brain by R2*. RESULTS: In subjects aged 65 years or older, SF levels were associated with increased TDS (ß = 0.003, p = 0.02), PVF (ß = 0.004, p = 0.01), and SVF (ß = 0.004, p = 0.002) scores. After stratification by sex, these findings were significant only in men, where SF was associated with increased TDS (ß = 0.003, p = 0.01), PVF (ß = 0.004, p = 0.03), and SVF (ß = 0.004, p = 0.009) scores. In middle-aged subjects, SF was also associated with increased SVF scores (ß = 0.005, p = 0.011). Lastly, in men, SF levels were negatively associated with R2*, a surrogate marker of brain iron content, in both the left frontal inferior opercular area (r = -0.41, p = 0.005) and the right frontal inferior opercular area (r = -0.44, p = 0.002). CONCLUSIONS: SF is significantly and positively associated with cognition. In older people with low SF levels, iron supplementation may be a promising therapy to improve cognition.

Unraveling the gut-brain connection: The association of microbiota-linked structural brain biomarkers with behavior and mental health.

AIM: The gut microbiota can influence human behavior. However, due to the massive multiple-testing problem, research into the relationship between microbiome ecosystems and the human brain faces drawbacks. This problem arises when attempting to correlate thousands of gut bacteria with thousands of brain voxels. METHODS: We performed brain magnetic resonance imaging (MRI) scans on 133 participants and applied machine-learning algorithms (Ridge regressions) combined with permutation tests. Using this approach, we were able to correlate specific gut bacterial families with brain MRI signals, circumventing the difficulties of massive multiple testing while considering sex, age, and body mass index as confounding factors. RESULTS: The relative abundance (RA) of the Selenomonadaceae, Clostridiaceae, and Veillonellaceae families in the gut was associated with altered cerebellar, visual, and frontal T2-mapping and diffusion tensor imaging measures. Conversely, decreased relative abundance of the Eubacteriaceae family was also linked to T2-mapping values in the cerebellum. Significantly, the brain regions associated with the gut microbiome were also correlated with depressive symptoms and attentional deficits. CONCLUSIONS: Our analytical strategy offers a promising approach for identifying potential brain biomarkers influenced by gut microbiota. By gathering a deeper understanding of the microbiota-brain connection, we can gain insights into the underlying mechanisms and potentially develop targeted interventions to mitigate the detrimental effects of dysbiosis on brain function and mental health.

Gut microbiota links to serum ferritin and cognition.

Iron is required for the replication and growth of almost all bacterial species and in the production of myelin and neurotransmitters. Increasing clinical studies evidence that the gut microbiota plays a critical role in iron metabolism and cognition. However, the understanding of the complex iron-microbiome-cognition crosstalk remains elusive. In a recent study in the Aging Imageomics cohort (n = 1,030), we identified a positive association of serum ferritin (SF) with executive function (EF) as inferred from the semantic verbal fluency (SVF,) the total digit span (TDS) and the phonemic verbal fluency tests (PVF). Here, we explored the potential mechanisms by analyzing the gut microbiome and plasma metabolome using shotgun metagenomics and HPLC-ESI-MS/MS, respectively. Different bacterial species belonging to the Proteobacteria phylum (Klebsiella pneumoniae, Klebsiella michiganensis, Unclassified Escherichia) were negatively associated both with SF and executive function. At the functional level, an enrichment of microbial pathways involved in phenylalanine, arginine, and proline metabolism was identified. Consistently, phenylacetylglutamine, a metabolite derived from microbial catabolism of phenylalanine, was negatively associated with SF, EF, and semantic memory. Other metabolites such as ureidobutyric acid and 19,20-DiHDPA, a DHA-derived oxylipin, were also consistently and negatively associated with SF, EF, and semantic memory, while plasma eicosapentaenoic acid was positively associated. The associations of SF with cognition could be mediated by the gut microbiome through microbial-derived metabolites.

Adipose tissue coregulates cognitive function.

Obesity is associated with cognitive decline. Recent observations in mice propose an adipose tissue (AT)-brain axis. We identified 188 genes from RNA sequencing of AT in three cohorts that were associated with performance in different cognitive domains. These genes were mostly involved in synaptic function, phosphatidylinositol metabolism, the complement cascade, anti-inflammatory signaling, and vitamin metabolism. These findings were translated into the plasma metabolome. The circulating blood expression levels of most of these genes were also associated with several cognitive domains in a cohort of 816 participants. Targeted misexpression of candidate gene ortholog in the Drosophila fat body significantly altered flies memory and learning. Among them, down-regulation of the neurotransmitter release cycle-associated gene SLC18A2 improved cognitive abilities in Drosophila and in mice. Up-regulation of RIMS1 in Drosophila fat body enhanced cognitive abilities. Current results show previously unidentified connections between AT transcriptome and brain function in humans, providing unprecedented diagnostic/therapeutic targets in AT.

Drug Allergy Alert System in a Spanish University Hospital: Description and Dynamics of Use.

INTRODUCTION: The drug allergy alert system reduces the frequency of adverse drug events, although it is subjected to collateral effects, since 80-90% of alerts are not real, and a large percentage of alerts are overridden (46.2-96.2%). We reviewed how the alert system is used at University Hospital Fundación Alcorcon (HUFA). METHODS: Data were obtained from the drug allergy alert and the alert overriding notification forms (both in the period 2011-20). We also recorded drug allergy diagnoses at HUFA, drug consumption in primary care in 2016. We calculated the incidence of drug allergy alert activation, temporal trends in use, and correlations between the number of drugs in several datasets. RESULTS: We collected 15,535 alerts. NSAIDs and penicillins were the drugs with the highest number of drug allergy alerts (36.55% and 26.91%, respectively). A correlation was found between the number of drug alerts and the type of drug allergy in HUFA in 2016. Only 6.83% of the alerts were removed, and, of these, 21.77% were reactivated. Approximately 100 overrides were recorded per year from 2016 (6.8% of 8,434 activated alerts during 2014-2020). CONCLUSIONS: The number of drug allergy alerts recorded via the drug allergy alert system of HUFA correlates with the distribution of drug allergy diagnoses in the hospital, although many of the alerts could be false positives (as per current published evidence). We detected a very low frequency of removed alerts (6.83%), a relevant frequency of reactivations (one quarter), and a very low frequency of overrides (6.8%).

Consumption of ultra-processed foods is associated with depression, mesocorticolimbic volume, and inflammation.

BACKGROUND: The consumption of ultra-processed foods and drinks (UPF) has been associated with depression and inflammation and preclinical studies showed that some UPF components disrupt the amygdala-hippocampal complex. We combine diet, clinical and brain imaging data to investigate the relationship between the UPF consumption, depressive symptoms, and brain volumes in humans, considering interactions with obesity, and the mediation effect of inflammation biomarkers. METHODS: One-hundred fifty-two adults underwent diet, depressive symptoms, anatomic magnetic resonance imaging assessments and laboratory tests. Relationships between the % of UPF consumption (in grams) of the total diet, depressive symptoms, and gray matter brain volumes were explored using several adjusted regression models, and in interaction with the presence of obesity. Whether inflammatory biomarkers (i.e., white blood cell count, lipopolysaccharide-binding protein, c-reactive protein) mediate the previous associations was investigated using R mediation package. RESULTS: High UPF consumption was associated with higher depressive symptoms in all participants (ß = 0.178, CI = 0.008-0.261) and in those with obesity (ß = 0.214, CI = -0.004-0.333). Higher consumption was also associated with lower volumes in the posterior cingulate cortex and the left amygdala, which in the participants with obesity also encompassed the left ventral putamen and the dorsal frontal cortex. White blood count levels mediated the association between UPF consumption and depressive symptoms (p = 0.022). LIMITATIONS: The present study precludes any causal conclusions. CONCLUSIONS: UPF consumption is associated with depressive symptoms and lower volumes within the mesocorticolimbic brain network implicated in reward processes and conflict monitoring. Associations were partially dependent on obesity and white blood cell count.

The Longitudinal Changes in Subcutaneous Abdominal Tissue and Visceral Adipose Tissue Volumetries Are Associated with Iron Status.

Excess iron is known to trigger adipose tissue dysfunction and insulin resistance. Circulating markers of iron status have been associated with obesity and adipose tissue in cross-sectional studies. We aimed to evaluate whether iron status is linked to changes in abdominal adipose tissue longitudinally. Subcutaneous abdominal tissue (SAT) and visceral adipose tissue (VAT) and its quotient (pSAT) were assessed using magnetic resonance imaging (MRI), at baseline and after one year of follow-up, in 131 (79 in follow-up) apparently healthy subjects, with and without obesity. Insulin sensitivity (euglycemic- hyperinsulinemic clamp) and markers of iron status were also evaluated. Baseline serum hepcidin (p = 0.005 and p = 0.002) and ferritin (p = 0.02 and p = 0.01)) were associated with an increase in VAT and SAT over one year in all subjects, while serum transferrin (p = 0.01 and p = 0.03) and total iron-binding capacity (p = 0.02 and p = 0.04) were negatively associated. These associations were mainly observed in women and in subjects without obesity, and were independent of insulin sensitivity. After controlling for age and sex, serum hepcidin was significantly associated with changes in subcutaneous abdominal tissue index (iSAT) (ß = 0.406, p = 0.007) and visceral adipose tissue index (iVAT) (ß = 0.306, p = 0.04), while changes in insulin sensitivity (ß = 0.287, p = 0.03) and fasting triglycerides (ß = -0.285, p = 0.03) were associated with changes in pSAT. These data indicated that serum hepcidin are associated with longitudinal changes in SAT and VAT, independently of insulin sensitivity. This would be the first prospective study evaluating the redistribution of fat according to iron status and chronic inflammation.

Long-Term Hearing Outcomes following Stapedotomy in Patients with Otosclerosis and Preoperative Small Air-Bone Gap.

OBJECTIVES: To assess the long-term effectiveness of stapedotomies performed on patients with otosclerosis and preoperative small air-bone gaps (ABGs). METHODS: Retrospective study comparing the 10-year postoperative hearing outcomes after primary stapedotomies in patients with small (≤20 dB) and large ABGs (> 20 dB). Ninety out of 175 stapedotomies (22 and 68 in the small and large ABG groups, respectively) were monitored with long-term follow-ups. RESULTS: Ten years after the operation, hearing measurements were similar for both groups, although a significant decline of bone conduction thresholds was evident (p = 0.007 and p < 0.001, respectively). An improvement of ≥10 dB in the postoperative ABG (clinical improvement) was achieved only in the large ABG group. CONCLUSIONS: Even though long-term hearing levels will evolve similarly in patients with ≤20 and > 20 dB preoperative ABGs, the lack of clinical improvement found in the small ABG group is not in favor of an early surgery.

Adaptation and validation of the Spanish version of the Nasal Obstruction Symptom Evaluation (NOSE) Scale.

BACKGROUND: The Nasal Obstruction Symptom Evaluation (NOSE) scale is a symptom-specific, self-completed questionnaire for assessing quality of life related to nasal obstruction or its treatment in patients with septal deviation. The aim of this study was to validate the Spanish adaptation of the NOSE, thus allowing comparison across studies and international multicenter projects. METHODOLOGY: Multicenter prospective instrument validation study. Guidelines for the cross-cultural adaptation process from the original English language scale into a Spanish language version were followed. The psychometric properties (reproducibility, reliability, validity, responsiveness) of the Spanish version ("NOSE-e" for "NOSE-espanol") were assessed in 58 consecutive patients undergoing septoplasty (both before and 3 months after surgery) and 58 matched asymptomatic controls. RESULTS: Test-retest reliability and internal consistency reliability were adequate. The NOSE-e demonstrated satisfactory construct validity. Positive correlations between the NOSE-e scores and the score of a visual analog scale measuring the subjective sensation of nasal obstruction were found. The instrument showed excellent between-groups discrimination and high response sensitivity to change. CONCLUSIONS: The Spanish version of the NOSE (NOSE-e) is a valid tool for measuring the subjective severity of nasal obstruction, and its use is recommended.

The cost associated with interstitial thermotherapy for tonsil reduction vs. standard tonsillectomy.

Given the high demand for tonsillectomies in children, the variety of techniques available, and the increasing need to control expenditures, it is important to analyse the costs associated with surgical procedures. The aim in the present study was to compare the cost of interstitial thermotherapy for tonsil volume reduction with conventional tonsillectomy. This was a nonrandomized, retrospective analysis at a public practice regional hospital between 2010 and 2012. Paediatric patients that underwent molecular resonance (MR)-induced tonsil thermal ablation (day case admission) were matched, according to age and concurrent surgery, to patients that underwent tonsillectomy by standard bipolar dissection (ordinary admission) during the same study period. Both groups were compared in economic terms based on operating room (OR) times, salaries, materials and hospitalization cost. Sixty-two patients were included (31 in each group). The mean ages of patients in the MR and tonsillectomy groups were 5.6 (2.7 SD) and 5.1 years (2.0 SD), respectively. A significantly lower mean surgery time (28.25 vs. 36.95 min), anaesthesia time (48.79 vs. 61.73 min), OR time (64.18 vs. 76.16 min), and OR cost (€166.60 vs. €199.58) were found in the MR group (P < 0.05). The mean cost-per-patient was significantly higher in the MR technique when the expenses of the single-use probe and the overnight stay were, respectively, added (€408.60 vs. €374.58, P = 0.007). The present study confirmed increased costs for interstitial thermotherapy for tonsil reduction compared to conventional tonsillectomy. Operation time and early discharge savings were eclipsed by the cost of the disposable probes.

[Prevalence of degenerative aortic valve stenosis in the elderly: results of a large community-based epidemiological study]. / Prevalenza della stenosi aortica degenerativa negli anziani: risultati di uno studio epidemiologico di comunità

BACKGROUND: There is a paucity of epidemiological data on the prevalence of degenerative aortic stenosis (AS) after the recent demographic changes and in the present therapeutic era. We sought to assess the prevalence of AS in an elderly population of an Italian urban area and to derive an epidemiological estimate of AS prevalence on a larger scale. METHODS: Elderly people (aged 75-95 years) of a 26 000 inhabitants town were clinically screened by general practitioners and classified into four groups: (1) no signs of AS; (2) known AS; (3) suspected AS (on the basis of the presence of a systolic murmur); (4) prior aortic valve replacement (AVR). Group 2 and 3 patients underwent physical examination and transthoracic echocardiography to confirm or rule out the diagnosis of AS, and to assess main comorbidities. RESULTS: Among the eligible patients, 2203 (93.7%) had no sign of AS; 49 (2.1%) had known AS; in 74 (3.1%) there was a systolic murmur suggesting AS, and 26 (1.1%) had previous AVR because of AS. Ten patients refused further screening, therefore 113 patients underwent transthoracic echocardiography. Among them, degenerative aortic disease without stenosis was observed in 22, and 63 had confirmed AS (severe in 21). Important comorbidities were frequently diagnosed in these patients. Including patients with previous AVR, AS was confirmed in 89/2350 patients (3.8%). On a regional scale, based on the demographics of this area, we estimated a prevalence of severe AS of 2248 cases per million inhabitants. CONCLUSIONS: The prevalence of AS in a population aged 75-95 years was 3.8%, and it was not previously diagnosed in a sizable proportion. More attention for early diagnosis of AS in the elderly is warranted.