Adaptation and Validation of the Hooked on Nicotine Checklist (HONC) with Spanish Adolescents.

INTRODUCTION: The expansion of new tobacco consumption formats and electronic vapor products threatens to reverse the trend of declining smoking rates that had been observed among younger people in recent decades. Early detection in the health sector requires screening tools that have been adapted and validated in our context. This study aims to translate, culturally adapt, pilot and empirically validate the Hooked on Nicotine Checklist (HONC) with Spanish adolescents. METHODS: The process of translation and cultural adaptation included the following stages: direct translation, synthesis of translations, back translation, consolidation with a committee of experts and pre-test, along with a cognitive interview, which served as pilot testing. Empirical validation was conducted with a sample of 1027 adolescents aged between 12 and 18 (M=15.40; SD=1.638). RESULTS: The results obtained confirm that the HONC is a brief, clear and easy-to-understand tool, with appropriate psychometric properties. A Cronbach's alpha value of 0.90 was obtained. Sensitivity, specificity, PPV and NPV indices reached values of 0.56, 0.94, 0.79 and 0.83, respectively. Cut-off point 1 is the one reaching the best balance between the two values. CFA showed a model good overall fit. CONCLUSION: This study makes the Spanish version of the HONC available to researchers and clinicians, so that it can be used with sufficient psychometric guarantees.

Global producer responsibility for plastic pollution.

Brand names can be used to hold plastic companies accountable for their items found polluting the environment. We used data from a 5-year (2018-2022) worldwide (84 countries) program to identify brands found on plastic items in the environment through 1576 audit events. We found that 50% of items were unbranded, calling for mandated producer reporting. The top five brands globally were The Coca-Cola Company (11%), PepsiCo (5%), Nestlé (3%), Danone (3%), and Altria (2%), accounting for 24% of the total branded count, and 56 companies accounted for more than 50%. There was a clear and strong log-log linear relationship production (%) = pollution (%) between companies' annual production of plastic and their branded plastic pollution, with food and beverage companies being disproportionately large polluters. Phasing out single-use and short-lived plastic products by the largest polluters would greatly reduce global plastic pollution.

Exploring the Combined Action of Adding Pertuzumab to Branded Trastuzumab versus Trastuzumab Biosimilars for Treating HER2+ Breast Cancer.

The binding activity of various trastuzumab biosimilars versus the branded trastuzumab towards the glycosylated extracellular domain of the human epidermal growth factor receptor 2 (HER2) target in the presence of pertuzumab was investigated. We employed size exclusion chromatography with tetra-detection methodology to simultaneously determine absolute molecular weight, concentration, molecular size, and intrinsic viscosity. All trastuzumab molecules in solution exhibit analogous behavior in their binary action towards HER2 regardless of the order of addition of trastuzumab/pertuzumab. This analogous behavior of all trastuzumab molecules, including biosimilars, highlights the robustness and consistency of their binding activity towards HER2. Furthermore, the addition of HER2 to a mixture of trastuzumab and pertuzumab leads to increased formation of high-order HER2 complexes, up to concentrations of one order of magnitude higher than in the case of sequential addition. The observed increase suggests a potential synergistic effect between these antibodies, which could enhance their therapeutic efficacy in HER2-positive cancers. These findings underscore the importance of understanding the complex interplay between therapeutic antibodies and their target antigens, providing valuable insights for the development of more effective treatment strategies.

Characteristics and Outcomes of Atrial Fibrillation in Chronic Heart Failure Patients: A Comprehensive Analysis of the Colombian Heart Failure Registry.

Background: Heart failure (HF) and atrial fibrillation (AF) represent conditions that commonly coexist. The impact of AF in HF has yet to be well studied in Latin America. This study aimed to characterize the sociodemographic and clinical features, along with patients' outcomes with AF and HF from the Colombian Heart Failure Registry (RECOLFACA). Methods: Patients with ambulatory HF and AF were included in RECOLFACA, mainly with persistent or permanent AF. A 6-month follow-up was performed. Primary outcome was all-cause mortality. To assess the impact of AF on mortality, we used a logistic regression model. A P value of < 0.05 was considered significant. All statistical tests were two-tailed. Results: Of 2,528 patients with HF in the registry, 2,514 records included information regarding AF diagnosis. Five hundred sixty (22.3%) were in AF (mean age 73 ± 11, 56% men), while 1,954 had no AF (mean age 66 ± 14 years, 58% men). Patients with AF were significantly older and had a different profile of comorbidities and implanted devices compared to non-AF patients. Moreover, AF diagnosis was associated with lower quality of life score (EuroQol-5D), mainly in mobility, personal care, and daily activity. AF was prevalent in patients with preserved ejection fraction (EF), while no significant differences in N-terminal prohormone of brain natriuretic peptide (NT-proBNP) levels were observed. Although higher mortality was observed in the AF group compared to individuals without AF (8.9% vs. 6.1%, respectively; P = 0.016), this association lost statistical significance after adjusting by age in a multivariate regression model (odds ratio (OR): 1.35; 95% confidence interval (CI): 0.95 - 1.92). Conclusions: AF is more prevalent in HF patients with higher EF, lower quality of life and different clinical profiles. Similar HF severity and non-independent association with mortality were observed in our cohort. These results emphasize the need for an improved understanding of the AF and HF coexistence phenomenon.

Evaluation of Sample Size Influence on Chemical Characterization and In Vitro Antioxidant Properties of Flours Obtained from Mushroom Stems Coproducts.

The mushroom industry generates large amounts of stem co-product. This is generated after mushroom harvest; stems are attached to the growth substratum, and their only use has traditionally been as compost. In this study, we investigated extensively for the first time this co-product and the influence of sample size (L->0.510 mm; LI-0.510-0.315 mm; SI-0.315-0.180 mm; S-<0.180 mm) on the characterization and antioxidant activity of flours obtained from stem co-products of Agaricus bisporus (ABSF) and Pleurotus ostreatus (POSF). ABSF was rich in protein (14 g/100 g), calcium (428.23-700.77 mg/100 g), and sorbitol (22.57-26.60 g/100 g), while POSF was rich in ß-glucans (36.62-40.34 g/100 g) and linoleic acid (20.57-39.86 g/100 g of lipid). Both species were flush in amino acids and had an umami flavour. ABSF showed more elevated values for emulsifying activity than POSF. The S sizes were highlighted for their yield, hydration properties, and oil holding capacity. Furthermore, ABSF-S exhibited heightened antioxidant capacity in vitro, in consonance with the total phenolic compounds observed (0.91 mg/g). However, the antioxidant assays in POSF presented a positive correlation with ß-glucan content. Our study suggests that these co-products could have several food-related applications, such as potential for use as an emulsifier, sweetener, or fortifier in the development of functional food, owing to their rich concentrations of fibre, protein, sorbitol, and ß-glucans. Nevertheless, it is necessary to understand the interactions of the flours with the potential food matrix prior to proceeding further with food-related applications.

Coxsackievirus infection induces direct pancreatic ß cell killing but poor antiviral CD8+ T cell responses.

Coxsackievirus B (CVB) infection of pancreatic ß cells is associated with ß cell autoimmunity and type 1 diabetes. We investigated how CVB affects human ß cells and anti-CVB T cell responses. ß cells were efficiently infected by CVB in vitro, down-regulated human leukocyte antigen (HLA) class I, and presented few, selected HLA-bound viral peptides. Circulating CD8+ T cells from CVB-seropositive individuals recognized a fraction of these peptides; only another subfraction was targeted by effector/memory T cells that expressed exhaustion marker PD-1. T cells recognizing a CVB epitope cross-reacted with ß cell antigen GAD. Infected ß cells, which formed filopodia to propagate infection, were more efficiently killed by CVB than by CVB-reactive T cells. Our in vitro and ex vivo data highlight limited CD8+ T cell responses to CVB, supporting the rationale for CVB vaccination trials for type 1 diabetes prevention. CD8+ T cells recognizing structural and nonstructural CVB epitopes provide biomarkers to differentially follow response to infection and vaccination.

Effectiveness of Capacity-Building and Quality Improvement Interventions to Improve Day-of-Birth Care in Kinshasa, Democratic Republic of the Congo.

In sub-Saharan African settings like the Democratic Republic of the Congo, high-quality care during childbirth and the immediate postpartum period is lacking in public facilities, necessitating multipronged interventions to improve care. We used a pre-post design to examine the effectiveness of a low-dose, high-frequency capacity-building and quality improvement (QI) intervention to improve care for women and newborns around the day of birth in 16 health facilities in Kinshasa, Democratic Republic of the Congo. Effectiveness was assessed based on changes in provider skills, key health indicators, and beneficiary satisfaction. To assess changes in the competency of the 188 providers participating in the intervention, we conducted objective structured clinical examinations on care for mothers and newborns on the day of birth, immediate postpartum family planning (PPFP) counseling and method provision, and postabortion care before and after implementation of training and at 6 and 12 months after training. Interrupted time series (ITS) analysis techniques were used to analyze routine health service data for changes in select maternal, newborn, and postpartum outcomes before and after the intervention. To assess changes in clients' perceptions of care, 2 rounds of telephone surveys were administered. Before the intervention, less than 2% of participating providers demonstrated competency in skills. Immediately after training, more than 80% demonstrated competency, and 70% retained competency after 12 months. ITS analyses show the risk of early neonatal death declined significantly by 9% (95% confidence interval [CI]=4%, 13%, P<.001), and likelihood of immediate PPFP uptake increased significantly by 72% (95% CI=53%, 92%, P<.001). Client satisfaction improved by 58% over the life of the project. These findings build on previous studies documenting the effectiveness of clinical capacity-building and QI approaches. If implemented at scale, this approach has the potential to substantively contribute to improving maternal and perinatal health in similar settings.

Pain as a disease in the new International Classification of Diseases (ICD-11): Latin American expert consensus.

Aims: Pain diagnoses in the 10th version of the International Classification of Diseases (ICD-10) did not adequately support the current management of pain. Therefore, we aimed to review the new 11th revision (ICD-11) in order to analyze its usefulness for the management, coding, research and education of chronic pain from a Latin American perspective. Methods: The Latin American Federation of Associations for the Study of Pain convened a meeting of pain experts in Lima, Peru. Pain specialists from 14 Latin American countries attended the consensus meeting. Results: In ICD-11, chronic pain is defined as pain that persists or recurs longer than 3 months and is subdivided into seven categories: chronic primary pain and six types of chronic secondary pain. Chronic primary pain is now considered a disease in itself, and not a mere symptom of an underlying disease. Conclusion: The novel definition and classification of chronic pain in ICD-11 is helpful for better medical care, research and health statistics. ICD-11 will improve chronic pain management in Latin American countries, for both the pain specialist and the primary care physician.

Chronic pain is one of the most frequent reasons for medical consultation in Latin America. In the tenth revision of the International Classification of Diseases and Related Health Problems (ICD-10), chronic pain was not adequately defined and individual pain diagnoses were poorly defined. For the first time in Latin America, a meeting of pain experts analyzed and reviewed the 11th version of the International Classification of Diseases (ICD-11), when the Latin America Federation of Associations for the Study of Pain organized a meeting of experts from 14 Latin American countries. In ICD-11, chronic pain is recognized as a biopsychosocial phenomenon and defined as pain that continues or returns for more than 3 months. It is split into seven types: chronic primary pain and six types of chronic secondary pain. In ICD-11, chronic primary pain is now considered a disease in itself, not a mere manifestation of other disease. Our article is the first to address the problems, challenges and benefits of using ICD-11 from a Latin American perspective. It will help to facilitate and disseminate the use of this new classification of chronic pain. This will improve chronic pain treatment, statistics, research and development of better health strategies for pain management in Latin America.

Pediatric Plexiform Fibromyxoma: A Case Report.

The plexiform fibromyxoma is a rare mesenchymal tumor in adults that generally originates in the antrum of stomach, being its occurrence in pediatric patients exceptional. It was classified as a distinct entity by World Health Organization in 2010. No recurrences and metastases have been documented in many of the reported patients to date, being the surgical treatment curative. We report the case of a 3-month-old infant who presented to the emergency department with an episode of intestinal subocclusion requiring an emergent surgery. During the surgical intervention, a mass was identified in the jejunum, causing partial occlusion of its lumen. The surgical pathology report revealed an infiltrative tumor composed of spindle-shaped cells disposed in a stroma with a plexiform pattern alternating myxoid areas. These findings and the immunohistochemical characteristics of the neoplastic cells led to classify the tumor as a plexiform fibromyxoma. A description of the immunophenotype of this tumor is made and differential diagnosis with other gastrointestinal tumors is also discussed.

Type 1 Diabetes Screening and Diagnosis.

Those with concerning signs or symptoms should be evaluated for type 1 diabetes (T1D). Those with first-degree relatives with T1D or based on the presence of high-risk genes are at increased risk and benefit from screening. Universal screening should be considered in light of new potential therapies to delay disease progression. Although oral glucose tolerance test is the gold standard for T1D staging, there are multiple tools available when oral glucose tolerance test is not feasible. Risk score calculations increase the ability to predict disease progression. Testing should be repeated when symptoms of overt diabetes mellitus are not present.

Use of Supervision Data to Improve Quality of Care for Malaria in Pregnancy: Experience in Six African Countries.

Malaria in pregnancy (MiP) intervention coverage, especially intermittent preventive treatment in pregnancy (IPTp), lags behind other global malaria indicators. In 2020, across Africa, only 32% of eligible pregnant women received at least three IPTp doses, despite high antenatal care attendance. We conducted a secondary analysis of data collected during Outreach Training and Supportive Supervision visits from 2019 to 2020 to assess quality of care and explore factors contributing to providers' competence in providing IPTp, insecticide-treated nets, malaria case management, and respectful maternity care. Data were collected during observations of provider-patient interactions in six countries (Cameroon, Cote d'Ivoire, Ghana, Kenya, Mali, and Niger). Competency scores (i.e., composite scores of supervisory checklist observations) were calculated across three domains: MiP prevention, MiP treatment, and respectful maternity care. Scores are used to understand drivers of competency, rather than to assess individual health worker performance. Country-specific multilinear regressions were used to assess how competency score was influenced by commodity availability, training, provider gender and cadre, job aid availability, and facility type. Average competency scores varied across countries: prevention (44-90%), treatment (78-90%), and respectful maternity care (53-93%). The relative association of each factor with competency score varied. Commodity availability, training, and access to job aids correlated positively with competency in multiple countries. To improve MiP service quality, equitable access to training opportunities for different cadres, targeted training, and access to job aids and guidelines should be available for providers. Collection and analysis of routine supervision data can support tailored actions to improve quality MiP services.

Persistent Hypoglycemia and Hyperinsulinism in a Patient With KMT2D-Associated Kabuki Syndrome.

We report a 3-year-old girl with persistent hypoglycemia and hyperinsulinism secondary to KMT2D-associated Kabuki syndrome (KS). During the neonatal period, the patient had multiple complications, including gastroesophageal reflux disease, failure to thrive, G-tube dependence, congenital heart disease, and persistent hypoglycemia. The initial workup at 2 weeks of age was suggestive of hyperinsulinism. She was treated with intravenous glucose infusion and diazoxide. She was discharged from the NICU on diazoxide, chlorothiazide, and enteral feeds. Diazoxide was discontinued at 2 months old secondary to adverse effects. Hyperinsulinemic hypoglycemia was ultimately confirmed with a glucagon stimulation test at 5 months of age. At 11 months of age, when the enteral feeds were attempted to be spaced, she presented to our outpatient clinic with persistent hypoglycemia. Review of prior outside records confirmed a negative congenital hyperinsulinism genetic panel. She was treated with maltodextrin, enteral feeds, and close glucose monitoring. We noted that she had dysmorphic features that were suggestive of KS. At 2 years of age, a whole exome sequence confirmed a pathogenic mutation in KMT2D. Persistent hypoglycemia beyond the neonatal period is a rare finding in KS. In addition, it is a more common finding in KS type 2 (KDM6A).

MicroRNAs Associated with Disability Progression and Clinical Activity in Multiple Sclerosis Patients Treated with Glatiramer Acetate.

MicroRNAs (miRNAs) are promising biomarkers in multiple sclerosis (MS). This study aims to investigate the association between a preselected list of miRNAs in serum with therapeutic response to Glatiramer Acetate (GA) and with the clinical evolution of a cohort of relapsing-remitting MS (RRMS) patients. We conducted a longitudinal study for 5 years, with cut-off points at 2 and 5 years, including 26 RRMS patients treated with GA for at least 6 months. A total of 6 miRNAs from a previous study (miR-9.5p, miR-126.3p, mir-138.5p, miR-146a.5p, miR-200c.3p, and miR-223.3p) were selected for this analysis. Clinical relapse, MRI activity, confirmed disability progression (CDP), alone or in combination (No Evidence of Disease Activity-3) (NEDA-3), and Expanded Disability Status Scale (EDSS), were studied. After multivariate regression analysis, miR-9.5p was associated with EDSS progression at 2 years (ß = 0.23; 95% CI: 0.04-0.46; p = 0.047). Besides this, mean miR-138.5p values were lower in those patients with NEDA-3 at 2 years (p = 0.033), and miR-146a.5p and miR-126.3p were higher in patients with CDP progression at 2 years (p = 0.044 and p = 0.05 respectively. These results reinforce the use of microRNAs as potential biomarkers in multiple sclerosis. We will need more studies to corroborate these data and to better understand the role of microRNAs in the pathophysiology of this disease.

Coxsackievirus infection induces direct pancreatic ß-cell killing but poor anti-viral CD8+ T-cell responses.

Coxsackievirus B (CVB) infection of pancreatic ß cells is associated with ß-cell autoimmunity. We investigated how CVB impacts human ß cells and anti-CVB T-cell responses. ß cells were efficiently infected by CVB in vitro, downregulated HLA Class I and presented few, selected HLA-bound viral peptides. Circulating CD8+ T cells from CVB-seropositive individuals recognized only a fraction of these peptides, and only another sub-fraction was targeted by effector/memory T cells that expressed the exhaustion marker PD-1. T cells recognizing a CVB epitope cross-reacted with the ß-cell antigen GAD. Infected ß cells, which formed filopodia to propagate infection, were more efficiently killed by CVB than by CVB-reactive T cells. Thus, our in-vitro and ex-vivo data highlight limited T-cell responses to CVB, supporting the rationale for CVB vaccination trials for type 1 diabetes prevention. CD8+ T cells recognizing structural and non-structural CVB epitopes provide biomarkers to differentially follow response to infection and vaccination.

Radical Scavenging and Cellular Antioxidant Activity of the Cocoa Shell Phenolic Compounds after Simulated Digestion.

The cocoa industry generates a considerable quantity of cocoa shell, a by-product with high levels of methylxanthines and phenolic compounds. Nevertheless, the digestion process can extensively modify these compounds' bioaccessibility, bioavailability, and bioactivity as a consequence of their transformation. Hence, this work's objective was to assess the influence of simulated gastrointestinal digestion on the concentration of phenolic compounds found in the cocoa shell flour (CSF) and the cocoa shell extract (CSE), as well as to investigate their radical scavenging capacity and antioxidant activity in both intestinal epithelial (IEC-6) and hepatic (HepG2) cells. The CSF and the CSE exhibited a high amount of methylxanthines (theobromine and caffeine) and phenolic compounds, mainly gallic acid and (+)-catechin, which persisted through the course of the simulated digestion. Gastrointestinal digestion increased the antioxidant capacity of the CSF and the CSE, which also displayed free radical scavenging capacity during the simulated digestion. Neither the CSF nor the CSE exhibited cytotoxicity in intestinal epithelial (IEC-6) or hepatic (HepG2) cells. Moreover, they effectively counteracted oxidative stress triggered by tert-butyl hydroperoxide (t-BHP) while preventing the decline of glutathione, thiol groups, superoxide dismutase, and catalase activities in both cell lines. Our study suggests that the cocoa shell may serve as a functional food ingredient for promoting health, owing to its rich concentration of antioxidant compounds that could support combating the cellular oxidative stress associated with chronic disease development.

Prevalence, Clinical Characteristics, and Prognostic Impact of Kidney Disease on Heart Failure Patients: An Observational Study of the Colombian Heart Failure Registry.

INTRODUCTION: Chronic kidney disease (CKD) represents one of the most frequent comorbidities observed in heart failure (HF) patients and has been observed to increase this population's risk of adverse outcomes. Nevertheless, evidence analyzing kidney dysfunction in HF is scarce in Latin American populations. We aimed to analyze the prevalence of kidney dysfunction and assess its association with mortality in patients diagnosed with HF enrolled in the Colombian Heart Failure Registry (RECOLFACA). METHODS: RECOLFACA enrolled adult patients with HF diagnosis from 60 centers in Colombia during the period 2017-2019. The primary outcome was all-cause mortality. A Cox proportional-hazards regression model was used to assess the impact of the different categories of eGFR in mortality risk. A p value of <0.05 was considered significant. All statistical tests were two-tailed. RESULTS: From the total 2,514 evaluated patients, 1,501 (59.7%) patients had moderate kidney dysfunction (eGFR <60 mL/min/1.73 m2), while 221 (8.8%) patients were classified as having a severe kidney dysfunction (eGFR <30 mL/min/1.73 m2). Patients with lower kidney function were most commonly males, had higher median age, and reported a higher prevalence of cardiovascular comorbidities. Moreover, different patterns of medications prescription were observed when comparing CKD versus non-CKD patients. Finally, eGFR <30 mL/min/1.73 m2 was significantly associated with a higher mortality risk compared to eGFR >90 mL/min/1.73 m2 status (HR: 1.87; 95% CI, 1.10-3.18), even after an extensive adjustment by relevant covariates. CONCLUSION: CKD represents a prevalent condition in the setting of HF. Patients with CKD and HF present with multiple sociodemographic, clinical, and laboratory differences compared with those only diagnosed with HF and present a significantly higher risk of mortality. A timely diagnosis and optimal treatment and follow-up of CKD in the setting of HF may improve the prognosis of these patients and prevent adverse outcomes.

A growing plastic smog, now estimated to be over 170 trillion plastic particles afloat in the world's oceans-Urgent solutions required.

As global awareness, science, and policy interventions for plastic escalate, institutions around the world are seeking preventative strategies. Central to this is the need for precise global time series of plastic pollution with which we can assess whether implemented policies are effective, but at present we lack these data. To address this need, we used previously published and new data on floating ocean plastics (n = 11,777 stations) to create a global time-series that estimates the average counts and mass of small plastics in the ocean surface layer from 1979 to 2019. Today's global abundance is estimated at approximately 82-358 trillion plastic particles weighing 1.1-4.9 million tonnes. We observed no clear detectable trend until 1990, a fluctuating but stagnant trend from then until 2005, and a rapid increase until the present. This observed acceleration of plastic densities in the world's oceans, also reported for beaches around the globe, demands urgent international policy interventions.

Expanding the Phenotypic Spectrum of Alazami Syndrome: Two Unrelated Spanish Families.

Alazami syndrome is a rare disorder with an autosomal recessive inheritance caused by pathogenic biallelic variants in the LARP7 gene. Clinically, it is mainly characterized by short stature, intellectual disability, and dysmorphic facial features. However, the phenotype is not yet well-defined because less than 50 cases have been described to date. Here, we report three new patients from two unrelated Spanish families who, in addition to the defined features of Alazami syndrome, also exhibit unique features that broaden the phenotypic spectrum of the syndrome. Moreover, we describe the novel frameshift variant c.690_699delins27 in the LARP7 gene, in which loss of function is a known mechanism of Alazami syndrome.

New Cerebellar Ataxia, Neuropathy, Vestibular Areflexia Syndrome cases are caused by the presence of a nonsense variant in compound heterozygosity with the pathogenic repeat expansion in the RFC1 gene.

The biallelic pathogenic repeat (AAGGG)400-2000 intronic expansion in the RFC1 gene has been recently described as the cause of cerebellar ataxia, neuropathy, vestibular areflexia syndrome (CANVAS) and as a major cause of late-onset ataxia. Since then, many heterozygous carriers have been identified, with an estimated allele frequency of 0.7% to 4% in the healthy population. Here, we describe in two affected CANVAS sisters the presence of the nonsense c.724C > T p.(Arg242*) variant in compound heterozygosity with the pathogenic repeat expansion in the RFC1 gene. Further RNA analysis demonstrated a reduced expression of the p.Arg242* allele in patients confirming an efficient nonsense-mediated mRNA decay. We also highlight the importance of considering the sequencing of the RFC1 gene for the diagnosis, especially in patients with CANVAS diagnosis carriers of the AAGGG repeat expansion.