Long-Term Outcomes of Biological Therapy in Crohn's Disease Complicated With Internal Fistulizing Disease: BIOSCOPE Study From GETECCU.

INTRODUCTION: The prevalence of penetrating complications in Crohn's disease (CD) increases progressively over time, but evidence on the medical treatment in this setting is limited. The aim of this study was to evaluate the effectiveness of biologic agents in CD complicated with internal fistulizing disease. METHODS: Adult patients with CD-related fistulae who received at least 1 biologic agent for this condition from the prospectively maintained ENEIDA registry were included. Exclusion criteria involved those receiving biologics for perianal disease, enterocutaneous, rectovaginal, anastomotic, or peristomal fistulae. The primary end point was fistula-related surgery. Predictive factors associated with surgery and fistula closure were evaluated by multivariate logistic regression and survival analyses. RESULTS: A total of 760 patients from 53 hospitals (673 receiving anti-tumor necrosis factors, 69 ustekinumab, and 18 vedolizumab) were included. After a median follow-up of 56 months (interquartile range, 26-102 months), 240 patients required surgery, with surgery rates of 32%, 41%, and 24% among those under anti-tumor necrosis factor, vedolizumab, or ustekinumab, respectively. Fistula closure was observed in 24% of patients. Older patients, ileocolonic disease, entero-urinary fistulae, or an intestinal stricture distal to the origin of the fistula were associated with a higher risk of surgery, whereas nonsmokers and combination therapy with an immunomodulator reduced this risk. DISCUSSION: Biologic therapy is beneficial in approximately three-quarters of patients with fistulizing CD, achieving fistula closure in 24%. However, around one-third still undergo surgery due to refractory disease. Some patient- and lesion-related factors can identify patients who will obtain more benefit from these drugs.

Analysis of the electronic delocalization in some isoelectronic analogues of B12 doped with beryllium and/or carbon.

In the current work, a new family of isoelectronic analogues to B12 is reported. The construction of this family was performed through the isoelectronic substitution principle to generate species such as B11C+, B11Be-, B10BeC, B10C22+, B10Be22- B9Be2C-, and B9BeC2+. The search for the global minimum was realized by utilizing genetic algorithms, while the induced magnetic field, electronic localization function, magnetic current densities, and multicenter aromaticity criteria were calculated to understand their electronic delocalization. Our results show that, in general, C atoms avoid hypercoordination, whereas we have found species with Be atoms located in hypercoordinated positions that are relatively stable. Our analysis of aromaticity indicates that B12 has double σ and π disk aromaticity. Mono, double or triple substitution of B by C+ or Be- reduces somewhat the aromaticity of the clusters, but less in the case of Be- substitution.

Differences in the need for adalimumab dose optimization between Crohn's disease and ulcerative colitis.

AIM: to compare the need for and time to adalimumab dose escalation and de-escalation between patients with Crohn's disease (CD) and ulcerative colitis (UC). METHODS: this observational cohort study included patients with luminal CD or patients with UC treated with adalimumab. Adalimumab dose optimization was decided based on the Harvey-Bradshaw index (CD) or the partial Mayo score (UC). The co-primary endpoints were the differences in the rate of dose escalation and the cumulative probability of escalation-free survival between cohorts. We also evaluated the rates of de-escalation and predictors of adalimumab dose escalation and de-escalation. RESULTS: twenty-four of 43 CD patients (56%) and 28 of 43 UC patients (65%) required adalimumab dose escalation. UC patients had a higher adjusted rate of dose escalation (hazard ratio [HR] 2.33, 95% confidence interval [CI] 1.19-4.56; p = 0.013) than CD patients. The median time to dose escalation was significantly shorter for UC than CD patients (3.2 months, interquartile range [IQR]: 2.0-10.3 vs 12.2 months, IQR: 6.1-35.7; p = 0.001). Survival curves showed that UC patients had an increased probability of dose escalation (p < 0.001). Prior anti-TNF therapy was associated with dose escalation (HR 2.13, 95% CI 1.05-4.34; p = 0.037). Adalimumab dose de-escalation was attempted in 32% of UC patients and 50% of CD patients. Survival curves showed that CD patients had an increased probability of dose de-escalation (p = 0.030). CONCLUSION: UC patients more frequently required adalimumab dose escalation than CD patients. UC patients required optimization earlier than CD patients. More CD patients than UC patients can be dose de-escalated later on during treatment.

Adalimumab for Induction of Histological Remission in Moderately to Severely Active Ulcerative Colitis.

BACKGROUND: Histological remission represents a target distinct from endoscopic healing in ulcerative colitis (UC) and seems a better predictor of clinical outcomes. AIMS: The aim of this study was to assess the ability of adalimumab to achieve histological remission in UC patients. METHODS: Single-center, retrospective, open-label study of patients treated with adalimumab. Eligible patients were anti-TNF naïve adults with moderately to severely active UC. The Mayo score including endoscopy was performed at baseline and weeks 8 and 52. Histological activity was scored using the Geboes Index. The primary endpoint was histological remission, defined as a Geboes grade ≤ 3.0, at week 52. RESULTS: We included 34 patients. At week 8, 6 of 34 patients (17.6%) achieved histological remission. At week 52, 9 patients (26.5%, intention to treat; 31%, per protocol) had histological remission. Patients had a significant and progressive reduction in the most severe subgrades of Geboes Index from baseline at weeks 8 and 52. At weeks 8 and 52, 50 and 61.8% of patients achieved mucosal healing (Mayo endoscopic subscore 0-1). All patients who achieved histological remission also had mucosal healing. At week 8, 85.3 and 20.6% of patients achieved clinical response (decrease in Mayo score ≤ 3 points) or remission (Mayo score ≤ 2), respectively. At week 52, the corresponding values were 67.6 and 52.9%, respectively. At week 52, agreement between histological remission and mucosal healing was fair (kappa 0.293). Agreement between histological remission and Mayo endoscopic subscore 0 was good (kappa 0.71). CONCLUSIONS: Adalimumab was able to achieve histological remission in anti-TNF naïve patients with moderately to severely active UC.

Adalimumab Maintenance Treatment in Ulcerative Colitis: Outcomes by Prior Anti-TNF Use and Efficacy of Dose Escalation.

BACKGROUND: The impact of prior anti-TNF use on "real-life" outcomes of adalimumab therapy in ulcerative colitis (UC) is not well known. AIM: To compare the influence of prior anti-TNF use on the outcomes of adalimumab maintenance treatment in UC patients. We also assessed the effectiveness of adalimumab dose escalation. METHODS: This retrospective multicenter cohort study included consecutive UC who advanced to an adalimumab maintenance regimen. Patients in whom adalimumab was discontinued prior to week eight of treatment were excluded. The co-primary efficacy endpoints were the cumulative probabilities of adalimumab failure-free survival and colectomy-free survival. We also assessed the need for and the effectiveness of adalimumab dose escalation. RESULTS: Of 184 UC on maintenance treatment with adalimumab, 116 (63%) had previous anti-TNF use. After a median follow-up of 23 months (interquartile range 13-49), 112 patients (60%) maintained corticosteroid-free clinical response. Sixty-nine patients (37%) had adalimumab failure, and 22 (12%) needed colectomy. Anti-TNF-naïve patients had significantly lower adjusted rates of adalimumab failure (hazard ratio [HR] 0.65; p < 0.001), adalimumab dose escalation (HR 0.35; p = 0.002), and need for colectomy (HR 0.26; p < 0.004). Seventy-six patients (41%) needed dose escalation after secondary loss of response, and 47% of these regained response after escalation. Short-term response after escalation was identified as a significant predictor of colectomy avoidance (HR 0.53; p = 0.007). CONCLUSIONS: In this "real-life" cohort of UC patients on maintenance treatment with adalimumab, anti-TNF-naïve patients had significantly better long-term outcomes. Adalimumab dose escalation enabled recovery of response in nearly half of patients.

Effects of the acceptor unit in dyes with acceptor-bridge-donor architecture on the electron photo-injection mechanism and aggregation in DSSCs.

Dye-sensitized solar cells (DSSCs) are devices that convert light to electrical energy. Nowadays, researchers have focused on the understanding of the performance of dyes in solar cells. In this way, new efficient dyes have been obtained which can act as efficient light-harvesting compounds where the combination and the balance of acceptor(A)-bridge-donor(D) architectures confer suitable attributes and properties to the dye. Herein, we have carried out a DFT study on the optical and electronic properties of eight different A motifs and their influence on the electron photo-injection (PI) mechanisms through type I (indirect) or type II (direct) pathways in A-bridge-D dyes in DSSCs. The models consisted of thiophene as a bridge and triphenylamine as a D anchored to a TiO2 anatase cluster. All geometry optimizations were calculated using the B3LYP, CAM-B3LYP and BHandHLYP functionals combined with the 6-31G(d,p) basis set for C, H, N, O and S and the LANL2DZ pseudopotential for Ti atoms. Most of the A dyes display optoelectronic properties consistent with a type-I (indirect) mechanism except for the A5 dye where the results suggest a type-II (direct) PI pathway. In addition, molecular dynamics (MD) simulations have been carried out in order to describe the formation of dye dimers and analyze the stability of the aggregates due to intermolecular interactions. The observed trends indicate that dyes with A2 and A5 anchoring groups have less tendency to dimerize due to weaker intermolecular interactions resulting in less stable dimer complexes. Specifically, we found that the A motif influences the PI by a dye and the dimerization profiles.

Infliximab Dose Escalation as an Effective Strategy for Managing Secondary Loss of Response in Ulcerative Colitis.

BACKGROUND: The outcomes of infliximab dose escalation in ulcerative colitis (UC) have not been well evaluated. AIMS: To assess the short- and long-term outcomes of infliximab dose escalation in a cohort of patients with UC. METHODS: This was a multicenter, retrospective, cohort study. All consecutive UC patients who had lost response to infliximab maintenance infusions and who underwent infliximab dose escalation were included. Post-escalation short-term clinical response and remission were evaluated. In the long term, the cumulative probabilities of infliximab failure-free survival and colectomy-free survival were calculated. Predictors of short-term response and event-free survival were estimated using logistic regression analysis and Cox proportional hazard regression analysis. RESULTS: Seventy-nine patients were included. Fifty-four patients (68.4%) achieved short-term clinical response and 41 patients (51.9%) entered in clinical remission. After a median follow-up of 15 months [interquartile range (IQR) 8-26], 33 patients (41.8%) had infliximab failure. Patients with short-term response had a significantly lower adjusted rate of infliximab failure [hazard ratio (HR) 0.24, 95% confidence interval (CI) 0.12-0.49; p < 0.001]. During a median follow-up of 24 months (IQR 13-34), 9 patients (11.4%) needed colectomy. Short-term response was identified as a predictor of colectomy avoidance (HR 0.14; 95% CI 0.03-0.69; p < 0.007). CONCLUSIONS: In UC patients who lost response to infliximab during maintenance, infliximab dose escalation enabled recovery of short-term response in nearly 70% of patients. In the long term, 58% of patients maintained sustained clinical benefit, and 9 of 10 avoided colectomy. Short-term response was associated with an 86% reduction in the relative risk of colectomy.

Large differences in global transcriptional regulatory programs of normal and tumor colon cells.

BACKGROUND: Dysregulation of transcriptional programs leads to cell malfunctioning and can have an impact in cancer development. Our study aims to characterize global differences between transcriptional regulatory programs of normal and tumor cells of the colon. METHODS: Affymetrix Human Genome U219 expression arrays were used to assess gene expression in 100 samples of colon tumor and their paired adjacent normal mucosa. Transcriptional networks were reconstructed using ARACNe algorithm using 1,000 bootstrap replicates consolidated into a consensus network. Networks were compared regarding topology parameters and identified well-connected clusters. Functional enrichment was performed with SIGORA method. ENCODE ChIP-Seq data curated in the hmChIP database was used for in silico validation of the most prominent transcription factors. RESULTS: The normal network contained 1,177 transcription factors, 5,466 target genes and 61,226 transcriptional interactions. A large loss of transcriptional interactions in the tumor network was observed (11,585; 81% reduction), which also contained fewer transcription factors (621; 47% reduction) and target genes (2,190; 60% reduction) than the normal network. Gene silencing was not a main determinant of this loss of regulatory activity, since the average gene expression was essentially conserved. Also, 91 transcription factors increased their connectivity in the tumor network. These genes revealed a tumor-specific emergent transcriptional regulatory program with significant functional enrichment related to colorectal cancer pathway. In addition, the analysis of clusters again identified subnetworks in the tumors enriched for cancer related pathways (immune response, Wnt signaling, DNA replication, cell adherence, apoptosis, DNA repair, among others). Also multiple metabolism pathways show differential clustering between the tumor and normal network. CONCLUSIONS: These findings will allow a better understanding of the transcriptional regulatory programs altered in colon cancer and could be an invaluable methodology to identify potential hubs with a relevant role in the field of cancer diagnosis, prognosis and therapy.

In Silico Analysis of the Aromaticity of Some Carbo-Metallabenzenes and Carbo-Dimetallabenzenes (Carbo-mers Proposed from Metallabenzenes).

In the current work, we introduce a novel class of molecules termed carbo-metallabenzenes, and their aromaticity has been comprehensively analyzed. The molecules were strategically designed with the insertion of acetylene (C≡C or C2) units in some selected metallabenzenes. Furthermore, if a second metallic unit is inserted (replacing a sp2 carbon) in the carbo-metallabenzenes rings, a new family of carbo-mers is generated, and this second group has been named as carbo-dimetallabenzenes. The primary objective of this work is to ascertain, through various methodologies, whether these newly proposed molecules retain the aromatic characteristics observed in carbo-benzene. The methodologies employed for bond analysis and aromaticity exploration include the analysis of the molecular orbitals, energy decomposition analysis, electron density of delocalized bonds, magnetically induced current density, and the induced magnetic field (Bind). This study sheds light on that the insertion of the metallic centers reduces the electronic delocalization and their aromaticity is, in some cases, comparable with the electronic delocalization of the inorganic iminobora-borazine and also provides valuable insights into their electronic structure through a multifaceted analysis.

Meta-analysis: Real-world effectiveness and safety of ustekinumab in patients with ulcerative colitis.

BACKGROUND: Evidence on real-world outcomes of ustekinumab for ulcerative colitis (UC) patients is needed. AIMS: To summarise evidence on the real-world outcomes of ustekinumab for UC and conduct a meta-analysis of effectiveness and safety data. METHODS: A systematic search was conducted through September 2022 in electronic databases for observational studies evaluating ustekinumab for UC. A random-effects meta-analysis model was used to calculate the pooled effect sizes (percentages or incidence rates [IRs]) of effectiveness and safety outcomes. RESULTS: In all, 19 studies were included with 3786 patients. More than 92% of patients were previously treated with any biologic, 61.1% with both anti-TNF and vedolizumab and 16.4% with any biologic and tofacitinib. Clinical remission was achieved in 45.4% at week 8 (95% CI: 30.1%-60.6%), 43.8% (38.4%-49.2%) at weeks 12-16, 44.6% (35.9%-53.3%) at month 6, and 50.6% (36.3%-64.8%) at month 12. Response was achieved in 61.2%, 59.4%, 65.2% and 76.8% at weeks 8, 12-16, month 6 and 12, respectively. CS-free remission was achieved in 18.7%, 36.8%, 34.5% and 39% at weeks 8, 12-16, month 6 and 12, respectively. Overall, 58.2% of patients had endoscopic improvement at month 12. Almost 30% of the patients needed dose escalation, which was effective in 40% of these patients. The IRs of colectomy, adverse events (AEs), serious AEs and serious infections were 4.8, 7.9, 0.8 and 0.3 per 100 patient-years, respectively. CONCLUSIONS: This meta-analysis confirms the effectiveness and safety of ustekinumab in a highly treatment-refractory population of UC patients.

Development of an analytical method for antimony speciation in vegetables by HPLC-hydride generation-atomic fluorescence spectrometry.

A new method for antimony speciation in terrestrial edible vegetables (spinach, onions, and carrots) was developed using HPLC with hydride generation-atomic fluorescence spectrometry. Mechanical agitation and ultrasound were tested as extraction techniques. Different extraction reagents were evaluated and optimal conditions were determined using experimental design methodology, where EDTA (10 mmol/L, pH 2.5) was selected because this chelate solution produced the highest extraction yield and exhibited the best compatibility with the mobile phase. The results demonstrated that EDTA prevents oxidation of Sb(III) to Sb(V) and maintains the stability of antimony species during the entire analytical process. The LOD and precision (RSD values obtained) for Sb(V), Sb(III), and trimethyl Sb(V) were 0.08, 0.07, and 0.9 microg/L and 5.0, 5.2, and 4.7%, respectively, for a 100 microL sample volume. The application of this method to real samples allowed extraction of 50% of total antimony content from spinach, while antimony extracted from carrots and onion samples ranged between 50 and 60 and 54 and 70%, respectively. Only Sb(V) was detected in three roots (onion and spinach) that represented 60-70% of the total antimony in the extracts.

Real-World Effectiveness and Safety of Tofacitinib in Patients With Ulcerative Colitis: Systematic Review With Meta-Analysis.

BACKGROUND: Knowledge of the real-world effectiveness and safety of tofacitinib for ulcerative colitis (UC) is relevant to confirm the benefit observed in clinical trials. METHODS: This systematic review and meta-analysis evaluated the real-world effectiveness of tofacitinib for moderate to severely active UC. The primary outcome was clinical remission evaluated at week 8, weeks 12 to 16, and month 6. Secondary outcomes were response, corticosteroid-free remission, mucosal healing, colectomy, and safety. RESULTS: Seventeen studies with a total of 1162 patients with UC were included. Remission (11 studies) was achieved in 34.7% of patients at week 8 (95% confidence interval [CI], 24.4%-45.1%), 47% at weeks 12 to 16 (95% CI, 40.3%-53.6%), and 38.3% at month 6 (95% CI, 29.2%-47.5%) at month 6 duplicated. Response was achieved in 62.1%, 64.2%, 50.8%, and 41.8% of patients at week 8, weeks 12 to 16, month 6, and month 12, respectively. Corticosteroid-free remission (5 studies) was achieved in 38.4%, 44.3%, 33.6%, and 31% of patients at week 8, weeks 12 to 16, month 6, and month 12, respectively. Mucosal healing was achieved in 48.3% and 45.3% of patients at week 8 and weeks 12 to 16, respectively. Patients who were biologic-naïve (11.6%) had a significantly higher rate of response at week 8 (1.38; 95% CI, 1.03-1.84). The incidence rates of serious adverse events and herpes zoster was 8.9 and 6.9 per 100 patient-years, respectively. CONCLUSIONS: This meta-analysis of real-world studies confirms the effectiveness of tofacitinib in a highly refractory population of patients with moderate to severely active UC. Tofacitinib showed an acceptable safety profile. These findings were consistent with clinical trials and further support the use of tofacitinib in UC.

Association of golimumab trough concentrations during maintenance with clinical, biological, endoscopic and histologic remission in patients with ulcerative colitis.

BACKGROUND: Optimal golimumab concentration thresholds for important outcomes during maintenance are lacking. AIMS: To investigate the association of golimumab trough concentrations during maintenance with key outcomes, including endoscopic and histologic remission, and long-term event-free persistence with golimumab, in patients with UC. METHODS: This multi-centre, cross-sectional study included patients with UC on golimumab maintenance recruited either in remission or during a flare. Colonoscopy was scheduled, and study-specific rectocolonic biopsies were taken for blind central histologic reading. Samples for golimumab trough concentrations were collected close to colonoscopy. RESULTS: Fifty-two patients were included. Median golimumab trough concentrations (µg/ml) were significantly higher in patients who had clinical remission (2.01 vs. 0.72, p = 0.047), combined clinical-biochemical remission (PMS ≤2 + faecal calprotectin <250 µg/g) (2.21 vs. 1.47, p = 0.041), endoscopic healing (Mayo endoscopic subscore 0) (2.52 vs. 1.47, p = 0.003), histologic remission (Geboes index ≤2.0) (2.33 vs. 1.50, p = 0.02) and disease clearance (clinical remission endoscopic healing + histologic remission) (2.52 vs. 1.70, p = 0.009), compared with those not meeting these criteria. Golimumab concentrations were significantly higher in patients who avoided golimumab dose escalation/discontinuation during follow-up (2.24 vs. 0.98, p = 0.012). Receiver-operating characteristic analyses identified golimumab thresholds [area under the curve] of 0.85 [0.76], 1.90 [0.76], 2.29 [0.75], 1.79 [0.68], 2.29 [0.72] and 1.56 [0.71] µg/ml as associated with clinical remission, combined remission, endoscopic healing, histologic remission, disease clearance and long-term event-free persistence with golimumab, respectively. CONCLUSIONS: Golimumab trough concentrations during maintenance are associated with favourable treatment outcomes including endoscopic healing, histologic remission and long-term persistence on golimumab. We identified the optimal golimumab thresholds most closely associated with key outcomes.

Immigrant IBD Patients in Spain Are Younger, Have More Extraintestinal Manifestations and Use More Biologics Than Native Patients.

BACKGROUND: Previous studies comparing immigrant ethnic groups and native patients with IBD have yielded clinical and phenotypic differences. To date, no study has focused on the immigrant IBD population in Spain. METHODS: Prospective, observational, multicenter study comparing cohorts of IBD patients from ENEIDA-registry who were born outside Spain with a cohort of native patients. RESULTS: We included 13,524 patients (1,864 immigrant and 11,660 native). The immigrants were younger (45 ± 12 vs. 54 ± 16 years, p < 0.001), had been diagnosed younger (31 ± 12 vs. 36 ± 15 years, p < 0.001), and had a shorter disease duration (14 ± 7 vs. 18 ± 8 years, p < 0.001) than native patients. Family history of IBD (9 vs. 14%, p < 0.001) and smoking (30 vs. 40%, p < 0.001) were more frequent among native patients. The most prevalent ethnic groups among immigrants were Caucasian (41.5%), followed by Latin American (30.8%), Arab (18.3%), and Asian (6.7%). Extraintestinal manifestations, mainly musculoskeletal affections, were more frequent in immigrants (19 vs. 11%, p < 0.001). Use of biologics, mainly anti-TNF, was greater in immigrants (36 vs. 29%, p < 0.001). The risk of having extraintestinal manifestations [OR: 2.23 (1.92-2.58, p < 0.001)] and using biologics [OR: 1.13 (1.0-1.26, p = 0.042)] was independently associated with immigrant status in the multivariate analyses. CONCLUSIONS: Compared with native-born patients, first-generation-immigrant IBD patients in Spain were younger at disease onset and showed an increased risk of having extraintestinal manifestations and using biologics. Our study suggests a featured phenotype of immigrant IBD patients in Spain, and constitutes a new landmark in the epidemiological characterization of immigrant IBD populations in Southern Europe.

Innovation in IBD Care During the COVID-19 Pandemic: Results of a Cross-Sectional Survey on Patient-Reported Experience Measures.

BACKGROUND: The coronavirus 2019 (COVID-19) pandemic is a clinical situation that could be used as prototype for implementation of new systems of care. METHODS: This was a single-center, cross-sectional study. We evaluated the feasibility of a strategy based on the conversion of face-to-face visits to telephone consultations to manage IBD outpatients during the COVID-19 pandemic. A 4-item telephone survey (3 closed questions and a 100-point numeric description scale) was conducted to evaluate satisfaction of patients with telephone consultations. RESULTS: Between March 11 and April 8, 2020, 98% of the 216 scheduled face-to-face visits could be converted to telephone consultations, and we resolved an additional 162 urgent consultations by telephone. The rate of IBD-related hospitalization and visits to the emergency department decreased by 50% and 58%, respectively, compared with rates in the same period the previous year. The 4-item survey was conducted in 171 outpatients. In closed questions, patients reported a very high degree of satisfaction with telephone consultations, with no differences between scheduled (n = 123) and urgent consultations (n = 48; P = NS). The overall satisfaction rating with the telephone consultation evaluated with the numerical description scale was 94% and 93% for scheduled and urgent consultations, respectively (P < 0.82). Less than 20% of patients would have preferred a face-to-face visit to the telephone consultation at the time. CONCLUSIONS: A strategy based on the conversion of face-to-face visits to telephone consultations was able to guarantee a minimum standard quality of care during the COVID-19 pandemic. Patients reported a very high degree of satisfaction with telephone consultations.

Correction to "In Silico Analysis of the Electronic Delocalization in Some Double Fused-Ring Metallabenzenes".

[This corrects the article DOI: 10.1021/acsomega.1c00632.].

In Silico Analysis of the Electronic Delocalization in Some Double Fused-Ring Metallabenzenes.

In the current work, some metallabenzenes with one and several fused rings were analyzed in terms of their electronic delocalization. These fused-ring metallabenzenes are known as metallabenzenoids, and their aromatic character is not free of controversy. The systems of the current work were designed from crystallographic data of some synthesized molecules, and their electronic delocalization (aromaticity) was computationally examined in terms of the molecular orbital analysis (Hückel's rule), the induced magnetic field, and ring currents. The computational evidence allows us to understand if these molecules are or are not aromatic compounds.

Reception of Dietary and Other Health-Related Lifestyle Advice to Address Non-communicable Diseases in a Primary Care Context: A Mixed-Method Study in Central Argentina.

An effective way to address risk factors for non-communicable chronic diseases (NCD) and reduce healthcare costs is by using sound health-related advice (HRA) to promote healthy lifestyle habits. In Argentina, however, few studies have examined the context in which HRA is communicated and undertaken by patients at the primary care level. In this study, we assessed the reception of HRA using a mixed-method approach in a central area of Argentina. A total of 1,044 participants from the community were contacted and sociodemographic characteristics, health-related lifestyle factors, and medical history were collected. A calendar with health messages was provided to participants and its usage was assessed after 1 year. Additionally, semi-structured interviews were conducted with 34 patients attending a local primary healthcare center. The results show that HRA was given more frequently to individuals with higher mean age, lower educational level, and to females. Participants with a chronic health condition are at a higher chance of receiving advice to reduce salt intake and maintain a healthy weight. Dietary advice is offered along with other lifestyle recommendations. The use of alcohol and tobacco is usually addressed together. HRA was primarily received in the context of an NCD diagnosis and advice was directed, especially, to risky behaviors. The HRA to increase the intake of fruits and vegetables was mentioned less frequently. Patients at the healthcare center greatly appreciated receiving an HRA, especially when given in a tailored, written, and detailed form, and acknowledged its importance to prevent or control a chronic health condition as part of the medical treatment but showed concern regarding the ability to fully incorporate the advice. Lifestyle recommendations are highly appreciated by patients but are still underutilized since they are offered mostly in the context of illness. The health calendar was shown to be useful to complement health intervention programs at the community level. The findings of our study underscore the acknowledged value of HRA by participants to tackle the risk factors of chronic diseases. If properly used HRA constitutes a simple and highly valued tool to help address patient's needs to prevent and control NCD in Argentina.