Development of a therapeutic anti-HtrA1 antibody and the identification of DKK3 as a pharmacodynamic biomarker in geographic atrophy.

Genetic polymorphisms in the region of the trimeric serine hydrolase high-temperature requirement 1 (HTRA1) are associated with increased risk of age-related macular degeneration (AMD) and disease progression, but the precise biological function of HtrA1 in the eye and its contribution to disease etiologies remain undefined. In this study, we have developed an HtrA1-blocking Fab fragment to test the therapeutic hypothesis that HtrA1 protease activity is involved in the progression of AMD. Next, we generated an activity-based small-molecule probe (ABP) to track target engagement in vivo. In addition, we used N-terminomic proteomic profiling in preclinical models to elucidate the in vivo repertoire of HtrA1-specific substrates, and identified substrates that can serve as robust pharmacodynamic biomarkers of HtrA1 activity. One of these HtrA1 substrates, Dickkopf-related protein 3 (DKK3), was successfully used as a biomarker to demonstrate the inhibition of HtrA1 activity in patients with AMD who were treated with the HtrA1-blocking Fab fragment. This pharmacodynamic biomarker provides important information on HtrA1 activity and pharmacological inhibition within the ocular compartment.

Suicide in Later Life in Uruguay: A Suicide Note Analysis.

Suicide is a significant public health challenge worldwide, with inconsistent behavioral patterns. This study examined the psychological processes underlying 191 suicide notes left by older adults in Uruguay, a country doubling global and regional suicide rates, with the highest prevalence among those aged 60+. Uruguay highlights in the region as a high-income country. Through content analysis with an inter-judge strategy, the notes revealed that loneliness, loss of interest, and loss of meaning for life, were prevalent. Financial hardship was not a primary reason for suicide. Social connectedness was highlighted as a factor for reducing suicide risk in older adults, particularly those with ill health and physical impairment. The study sheds light on the need to expand social services aimed at reducing loneliness and the need to combat ageism and social prejudice towards suicide in Uruguay, providing valuable insights into suicide prevention strategies for older adults in diverse social settings.

Use of Coffee Bean Bagasse Extracts in the Brewing of Craft Beers: Optimization and Antioxidant Capacity.

Coffee bean bagasse is one of the main by-products generated by industrial coffee production. This by-product is rich in bioactive compounds such as caffeine, caffeic and chlorogenic acid, and other phenols. The aims of this work are to optimize the extraction conditions of phenolic compounds present in coffee bean bagasse and incorporate them into stout-style craft beers, as well as to determine their effect on the phenol content and antioxidant capacity. The optimal conditions for extraction were 30% ethanol, 30 °C temperature, 17.5 mL of solvent per gram of dry sample, and 30 min of sonication time. These conditions presented a total phenol content of 115.42 ± 1.04 mg GAE/g dry weight (DW), in addition to an antioxidant capacity of 39.64 ± 2.65 µMol TE/g DW in DPPH• and 55.51 ± 6.66 µMol TE/g DW for FRAP. Caffeine, caffeic and chlorogenic acids, and other minor compounds were quantified using HPLC-DAD. The coffee bean bagasse extracts were added to the stout craft beer and increased the concentration of phenolic compounds and antioxidant capacity of the beer. This work is the first report of the use of this by-product added to beers.

Anti-Lymphocyte Antigen 6 Complex, Locus E-Seco-Cyclopropabenzindol-4-One-Dimer Antibody-Drug Conjugate That Forms Adduct with α1-Microglobulin Demonstrates Slower Systemic Antibody Clearance and Reduced Tumor Distribution in Animals.

Anti-Ly6E-seco-cyclopropabenzindol-4-one dimer antibody-drug conjugate (ADC) has been reported to form an adduct with α1-microglobulin (A1M) in animal plasma, but with unknown impact on ADC PK and tissue distribution. In this study, we compared the PK and tissue distribution of anti-Ly6E ADC with unconjugated anti-Ly6E mAb in rodents and monkeys. For PK studies, animals received an intravenous administration of anti-Ly6E ADC or unconjugated anti-Ly6E mAb. Plasma samples were analyzed for total antibody (Tab) levels and A1M adduct formation. PK parameters were generated from dose-normalized plasma concentrations. Tissue distribution was determined in tumor-bearing mice after a single intravenous dosing of radiolabeled ADC or mAb. Tissue radioactivity levels were analyzed using a gamma counter. The impact of A1M adduct formation on target cell binding was assessed in an in vitro cell binding assay. The results show that ADC Tab clearance was slower than that of mAb in mice and rats but faster than mAb in monkeys. Correspondingly, the formation of A1M adduct appeared to be faster and higher in mice, followed by rats, and slowest in monkeys. Although ADC tended to show an overall lower distribution to normal tissues, it had a strikingly reduced distribution to tumors compared with mAb, likely due to A1M adduct formation interfering with target binding, as demonstrated by the in vitro cell binding assay. Together, these data 1) demonstrate that anti-Ly6E ADC that forms A1M adduct had slower systemic clearance with strikingly reduced tumor distribution and 2) highlight the importance of selecting an appropriate linker-drug for successful ADC development. SIGNIFICANCE STATEMENT: Anti-lymphocyte antigen 6 complex, locus E, ADC with seco-cyclopropabenzindol-4-one-dimer payload formed adduct with A1M, which led to a decrease in systemic clearance but also attenuated tumor distribution. These findings demonstrate the importance of selecting an appropriate linker-drug for ADC development and also highlight the value of a mechanistic understanding of ADC biotransformation, which could provide insight into ADC molecule design, optimization, and selection.

Antibody-Drug Conjugates Derived from Cytotoxic seco-CBI-Dimer Payloads Are Highly Efficacious in Xenograft Models and Form Protein Adducts In Vivo.

This work discloses the first examples of antibody-drug conjugates (ADCs) that are constructed from linker-drugs bearing dimeric seco-CBI payloads (duocarmycin analogs). Several homogeneous, CD22-targeting THIOMAB antibody-drug conjugates (TDCs) containing the dimeric seco-CBI entities are shown to be highly efficacious in the WSU-DLCL2 and BJAB mouse xenograft models. Surprisingly, the seco-CBI-containing conjugates are also observed to undergo significant biotransformation in vivo in mice, rats, and monkeys and thereby form 1:1 adducts with the Alpha-1-Microglobulin (A1M) plasma protein from these species. Variation of both the payload mAb attachment site and length of the linker-drug is shown to alter the rates of adduct formation. Subsequent experiments demonstrated that adduct formation attenuates the in vitro antiproliferation activity of the affected seco-CBI-dimer TDCs, but does not significantly impact the in vivo efficacy of the conjugates. In vitro assays employing phosphatase-treated whole blood suggest that A1M adduct formation is likely to occur if the seco-CBI-dimer TDCs are administered to humans. Importantly, protein adduct formation leads to the underestimation of total antibody (Tab) concentrations using an ELISA assay but does not affect Tab values determined via an orthogonal LC-MS/MS method. Several recommendations regarding bioanalysis of future in vivo studies involving related seco-CBI-containing ADCs are provided based on these collective findings.

Development of Anti-CD74 Antibody-Drug Conjugates to Target Glucocorticoids to Immune Cells.

Glucocorticoids (GCs) are excellent anti-inflammatory drugs but are dose-limited by on-target toxicity. We sought to solve this problem by delivering GCs to immune cells with antibody-drug conjugates (ADCs) using antibodies containing site-specific incorporation of a non-natural amino acid, novel linker chemistry for in vitro and in vivo stability, and existing and novel glucocorticoid receptor (GR) agonists as payloads. We directed fluticasone propionate to human antigen-presenting immune cells to afford GR activation that was dependent on the targeted antigen. However, mechanism of action studies pointed to accumulation of free payload in the tissue culture supernatant as the dominant driver of activity and indeed administration of the ADC to human CD74 transgenic mice failed to activate GR target genes in splenic B cells. Suspecting dissipation of released payload, we designed an ADC bearing a novel GR agonist payload with reduced permeability which afforded cell-intrinsic activity in human B cells. Our work shows that antibody-targeting offers significant potential for rescuing existing and new dose-limited drugs outside the field of oncology.

Exploration of Pyrrolobenzodiazepine (PBD)-Dimers Containing Disulfide-Based Prodrugs as Payloads for Antibody-Drug Conjugates.

A number of cytotoxic pyrrolobenzodiazepine (PBD) monomers containing various disulfide-based prodrugs were evaluated for their ability to undergo activation (disulfide cleavage) in vitro in the presence of either glutathione (GSH) or cysteine (Cys). A good correlation was observed between in vitro GSH stability and in vitro cytotoxicity toward tumor cell lines. The prodrug-containing compounds were typically more potent against cells with relatively high intracellular GSH levels (e.g., KPL-4 cells). Several antibody-drug conjugates (ADCs) were subsequently constructed from PBD dimers that incorporated selected disulfide-based prodrugs. Such HER2 conjugates exhibited potent antiproliferation activity against KPL-4 cells in vitro in an antigen-dependent manner. However, the disulfide prodrugs contained in the majority of such entities were surprisingly unstable toward whole blood from various species. One HER2-targeting conjugate that contained a thiophenol-derived disulfide prodrug was an exception to this stability trend. It exhibited potent activity in a KPL-4 in vivo efficacy model that was approximately three-fold weaker than that displayed by the corresponding parent ADC. The same prodrug-containing conjugate demonstrated a three-fold improvement in mouse tolerability properties in vivo relative to the parent ADC, which did not contain the prodrug.

Discovery of Pyrophosphate Diesters as Tunable, Soluble, and Bioorthogonal Linkers for Site-Specific Antibody-Drug Conjugates.

As part of an effort to examine the utility of antibody-drug conjugates (ADCs) beyond oncology indications, a novel pyrophosphate ester linker was discovered to enable the targeted delivery of glucocorticoids. As small molecules, these highly soluble phosphate ester drug linkers were found to have ideal orthogonal properties: robust plasma stability coupled with rapid release of payload in a lysosomal environment. Building upon these findings, site-specific ADCs were made between this drug linker combination and an antibody against human CD70, a receptor specifically expressed in immune cells but also found aberrantly expressed in multiple human carcinomas. Full characterization of these ADCs enabled procession to in vitro proof of concept, wherein ADCs 1-22 and 1-37 were demonstrated to afford potent, targeted delivery of glucocorticoids to a representative cell line, as measured by changes in glucocorticoid receptor-mediated gene mRNA levels. These activities were found to be antibody-, linker-, and payload-dependent. Preliminary mechanistic studies support the notion that lysosomal trafficking and enzymatic linker cleavage are required for activity and that the utility for the pyrophosphate linker may be general for internalizing ADCs as well as other targeted delivery platforms.

[Follow-up of the patient with pacemakers: Interrogation and basic programming]. / Seguimiento del paciente con marcapasos: interrogatorio y programación básica.

Permanent pacemakers are a frequently used therapeutic modality. Its use has had a great impact on the morbidity and mortality and quality of life of patients with heart rhythm disturbances, with an exponential increase observed in recent decades. The use of this strategy presents different phases, in which follow-up throughout the useful life of the device is a fundamental and determinant pillar of the efficacy and safety of this therapeutic modality. This review seeks to provide a clear and structured update of the fundamental aspects to consider in the follow-up of all patients with pacemakers. The follow-up of the patient with a pacemaker must follow a complete, systematic and periodic protocol, evaluating aspects and parameters related to the patient and the pacemaker, in order to ensure the proper and safe operation of the device adapted to the person.

Los marcapasos permanentes son una modalidad terapéutica de uso frecuente. Su empleo ha tenido un gran impacto en la morbimortalidad y calidad de vida de los pacientes con alteraciones del ritmo cardiaco, observándose en las últimas décadas un incremento exponencial. El empleo de esta estrategia presenta diferentes fases, que inician con la indicación de la estimulación, la selección del sistema de marcapaso apropiado, el procedimiento de implantación, la programación inicial y el seguimiento posterior, en la cual el seguimiento a lo largo de la vida útil del dispositivo es un pilar fundamental y determinante de la eficacia y seguridad de esta modalidad terapéutica. La presente revisión busca proporcionar una actualización clara y estructurada de los aspectos fundamentales a considerar en el seguimiento de todo paciente portador de marcapasos. El seguimiento del paciente con marcapasos debe seguir un protocolo completo, sistemático y periódico, evaluando aspectos y parámetros relacionado con el paciente y el marcapaso, con la finalidad de garantizar un funcionamiento adecuado y seguro del dispositivo adaptado a la persona.

[Nutritional state and shortcoming of micronutrients on schooled youth's diet on the metropolitan zone of Guadalajara Jalisco]. / Estado nutricional y carencias de micronutrientes en la dieta de adolescentes escolarizados de la Zona Metropolitana de Guadalajara, Jalisco.

The adolescence is a stage of high nutritional risk due to the increased requirements, changes in eating habits and potential risk. There are documented evidence of micronutrient deficiency among the population of Mexico. To evaluate the nutritional status and micronutrient deficiencies in the diet of adolescents. The sample consisted of 307 adolescents. We analyzed the body composition by using anthropometric indicators. To determine the intake of micronutrients, the 24 hours reminder and software Mexfoods were used. The percentages that indicate adequate intake were classified according to the following breakpoints: Below minimum requirements, when intake was < 50%; minimum requirements covered > or = 50% and < 75%; and exceed minimum requirements when it was > or = 75%. The BMI indicated that 21.8% of students of both sexes showed malnutrition and the prevalence of overweight and obesity was 27.9%. The micronutrient intake results indicated significant deficiencies in iron (p = 0.002), zinc (p = 0.000) and calcium (p = 0.002). The B-complex vitamins were those that had lower failure rates. We identified that the diet of adolescents has significant micronutrient deficiencies and that adolescent girls resulted with the major deficiencies. It is urgent to develop strategies, to reduce the problems of food deficit in adolescents.

Antibody Conjugation of a Chimeric BET Degrader Enables in†vivo Activity.

The ability to selectively degrade proteins with bifunctional small molecules has the potential to fundamentally alter therapy in a variety of diseases. However, the relatively large size of these chimeric molecules often results in challenging physico-chemical properties (e. g., low aqueous solubility) and poor pharmacokinetics which may complicate their in vivo applications. We recently discovered an exquisitely potent chimeric BET degrader (GNE-987) which exhibited picomolar cell potencies but also demonstrated low in vivo exposures. In an effort to improve the pharmacokinetic properties of this molecule, we discovered the first degrader-antibody conjugate by attaching GNE-987 to an anti-CLL1 antibody via a novel linker. A single IV dose of the conjugate afforded sustained in vivo exposures that resulted in antigen-specific tumor regressions. Enhancement of a chimeric protein degrader with poor in vivo properties through antibody conjugation thereby expands the utility of directed protein degradation as both a biological tool and a therapeutic possibility.

Diagnóstico y manejo de la congestión en insuficiencia cardíaca aguda / Diagnosis and management of congestion in acute heart failure / Diagnóstico e tratamento da congestão na insuficiência cardíaca aguda

La congestión en pacientes con insuficiencia cardíaca representa una manifestación de diversos procesos estructurales y funcionales cardiovasculares, asociada a alta morbimortalidad y reducción de calidad de vida, se considera la principal causa de ingreso a hospitalización y reingreso por insuficiencia cardíaca. Durante las últimas décadas, se ha logrado un mejor entendimiento de los diversos eventos fisiopatológicos desencadenantes, lo cual ha mejorado su pronóstico, diagnóstico y tratamiento. Por estos constantes avances, es necesaria su frecuente revisión y análisis. La atención del paciente con insuficiencia cardíaca y episodios de congestión es compleja y crucial. Su abordaje inicia con el reconocimiento temprano de las manifestaciones clínicas, uso de métodos no invasivos diagnósticos, delimitación del perfil de congestión; consecuentemente, es necesario brindar un manejo oportuno, intensivo y eficaz que contemple el empleo temprano de diuréticos intravenosos, la evaluación de metas de descongestión y, en casos específicos, terapia diurética combinada e incluso medicamentos vasoactivos o ultrafiltración continua.

Congestion in patients with heart failure represents a manifestation of various cardiovascular structural and functional processes, associated with high morbidity and mortality and reduced quality of life, being considered the main cause of hospitalization and readmission due to heart failure. During the last decades, a better understanding of the various triggering pathophysiological events has been achieved, modifying their prognosis, diagnosis, and treatment. Due to these constant advances, its frequent review and analysis is necessary. The care of patients with heart failure and episodes of congestion is complex and crucial. Its approach begins with early recognition of clinical manifestations, use of non-invasive diagnostic methods, delimitation of the congestion profile; followed by timely, intensive, and effective management that contemplates the early use of intravenous diuretics, evaluation of decongestion goals and, in specific cases, combined diuretic therapy, and even vasoactive medications or continuous ultrafiltration.

A congestão em pacientes com insuficiência cardíaca representa manifestação de diversos processos cardiovasculares estruturais e funcionais, associada a elevada morbidade e mortalidade e redução da qualidade de vida, é considerada a principal causa de internação e reinternação por insuficiência cardíaca. Durante as últimas décadas, conseguiu-se uma melhor compreensão dos vários eventos fisiopatológicos desencadeantes, o que melhorou o seu prognóstico, diagnóstico e tratamento. Devido a esses constantes avanços, sua revisão e análise frequente se fazem necessárias. O cuidado de pacientes com insuficiência cardíaca e episódios de congestão é complexo e crucial. Sua abordagem inicia-se com reconhecimento precoce das manifestações clínicas, utilização de métodos diagnósticos não invasivos, delimitação do perfil de congestão. Consequentemente, é necessário proporcionar manejo oportuno, intensivo e eficaz que inclua o uso precoce de diuréticos intravenosos, a avaliação das metas de descongestão e, em casos específicos, terapia diurética combinada e até mesmo medicações vasoativas ou ultrafiltração contínua.

Prediction of non-linear pharmacokinetics in humans of an antibody-drug conjugate (ADC) when evaluation of higher doses in animals is limited by tolerability: Case study with an anti-CD33 ADC.

For antibody-drug conjugates (ADCs) that carry a cytotoxic drug, doses that can be administered in preclinical studies are typically limited by tolerability, leading to a narrow dose range that can be tested. For molecules with non-linear pharmacokinetics (PK), this limited dose range may be insufficient to fully characterize the PK of the ADC and limits translation to humans. Mathematical PK models are frequently used for molecule selection during preclinical drug development and for translational predictions to guide clinical study design. Here, we present a practical approach that uses limited PK and receptor occupancy (RO) data of the corresponding unconjugated antibody to predict ADC PK when conjugation does not alter the non-specific clearance or the antibody-target interaction. We used a 2-compartment model incorporating non-specific and specific (target mediated) clearances, where the latter is a function of RO, to describe the PK of anti-CD33 ADC with dose-limiting neutropenia in cynomolgus monkeys. We tested our model by comparing PK predictions based on the unconjugated antibody to observed ADC PK data that was not utilized for model development. Prospective prediction of human PK was performed by incorporating in vitro binding affinity differences between species for varying levels of CD33 target expression. Additionally, this approach was used to predict human PK of other previously tested anti-CD33 molecules with published clinical data. The findings showed that, for a cytotoxic ADC with non-linear PK and limited preclinical PK data, incorporating RO in the PK model and using data from the corresponding unconjugated antibody at higher doses allowed the identification of parameters to characterize monkey PK and enabled human PK predictions.

Tissue Physiology of Cynomolgus Monkeys: Cross-Species Comparison and Implications for Translational Pharmacology.

We previously performed a comparative assessment of tissue-level vascular physiological parameters in mice and rats, two of the most commonly utilized species in translational drug development. The present work extends this effort to non-human primates by measuring tissue- and organ-level vascular volumes (Vv), interstitial volumes (Vi), and blood flow rates (Q) in cynomolgus monkeys. These measurements were accomplished by red blood cell labeling, extracellular marker infusion, and rubidium chloride bolus distribution, respectively, the same methods used in previous rodent measurements. In addition, whole-body blood volumes (BV) were determined across species. The results demonstrate that Vv, Vi, and Q, measured using our methods scale approximately by body weight across mouse, rat, and monkey in the tissues considered here, where allometric analysis allowed extrapolation to human parameters. Significant differences were observed between the values determined in this study and those reported in the literature, including Vv in muscle, brain, and skin and Q in muscle, adipose, heart, thymus, and spleen. The impact of these differences for selected tissues was evaluated via sensitivity analysis using a physiologically based pharmacokinetic model. The blood-brain barrier in monkeys was shown to be more impervious to an infused radioactive tracer, indium-111-pentetate, than in mice or rats. The body weight-normalized total BV measured in monkey agreed well with previously measured value in rats but was lower than that in mice. These findings have important implications for the common practice of scaling physiological parameters from rodents to primates in translational pharmacology.

Site-specific conjugation allows modulation of click reaction stoichiometry for pretargeted SPECT imaging.

Antibody pretargeting is a promising strategy for improving molecular imaging, wherein the separation in time of antibody targeting and radiolabeling can lead to rapid attainment of high contrast, potentially increased sensitivity, and reduced patient radiation exposure. The inverse electron demand Diels-Alder 'click' reaction between trans-cyclooctene (TCO) conjugated antibodies and radiolabeled tetrazines presents an ideal platform for pretargeted imaging due to rapid reaction kinetics, bioorthogonality, and potential for optimization of both slow and fast clearing components. Herein, we evaluated a series of anti-human epidermal growth factor receptor 2 (HER2) pretargeting antibodies containing distinct molar ratios of site-specifically incorporated TCO. The effect of stoichiometry on tissue distribution was assessed for pretargeting TCO-modified antibodies (monitored by 125I) and subsequent accumulation of an 111In-labeled tetrazine in a therapeutically relevant HER2+tumor-bearing mouse model. Single photon emission computed tomography (SPECT) imaging was also employed to assess tumor imaging at various TCO-to-monoclonal antibody (mAb) ratios. Increasing TCO-to-mAb molar ratios correlated with increased in vivo click reaction efficiency evident by increased tumor distribution and systemic exposure of 111In-labeled tetrazines. The pharmacokinetics of TCO-modified antibodies did not vary with stoichiometry. Pretargeted SPECT imaging of HER2-expressing tumors using 111In-labeled tetrazine demonstrated robust click reaction with circulating antibody at ~2 hours and good tumor delineation for both the 2 and 6 TCO-to-mAb ratio variants at 24 hours, consistent with a limited cell-surface pool of pretargeted antibody and benefit from further distribution and internalization. To our knowledge, this represents the first reported systematic analysis of how pretargeted imaging is affected solely by variation in click reaction stoichiometry through site-specific conjugation chemistry.

Preclinical pharmacokinetics and pharmacodynamics of DCLL9718A: An antibody-drug conjugate for the treatment of acute myeloid leukemia.

Few treatment options are available for acute myeloid leukemia (AML) patients. DCLL9718A is an antibody-drug conjugate that targets C-type lectin-like molecule-1 (CLL-1). This receptor is prevalent on monocytes, neutrophils, and AML blast cells, and unlike CD33, is not expressed on hematopoietic stem cells, thus providing possible hematopoietic recovery. DCLL9718A comprises an anti-CLL-1 IgG1 antibody (MCLL0517A) linked to a pyrrolobenzodiazepine (PBD) dimer payload, via a cleavable disulfide-labile linker. Here, we characterize the in vitro and in vivo stability, the pharmacokinetics (PK) and pharmacodynamics (PD) of DCLL9718A and MCLL0517A in rodents and cynomolgus monkeys. Three key PK analytes were measured in these studies: total antibody, antibody-conjugated PBD dimer and unconjugated PBD dimer. In vitro, DCLL9718A, was stable with most (> 80%) of the PBD dimer payload remaining conjugated to the antibody over 96 hours. This was recapitulated in vivo with antibody-conjugated PBD dimer clearance estimates similar to DCLL9718A total antibody clearance. Both DCLL9718A and MCLL0517A showed linear PK in the non-binding rodent species, and non-linear PK in cynomolgus monkeys, a binding species. The PK data indicated minimal impact of conjugation on the disposition of DCLL9718A total antibody. Finally, in cynomolgus monkey, MCLL0517A showed target engagement at all doses tested (0.5 and 20 mg/kg) as measured by receptor occupancy, and DCLL9718A (at doses of 0.05, 0.1 and 0.2 mg/kg) showed strong PD activity as evidenced by notable reduction in monocytes and neutrophils.

Suicidal Ideation, Depressive Symptomatology, and Self-Concept: A Comparison Between Mexican Institutionalized and Noninstitutionalized Children.

Previous research reports a significant prevalence of child depression worldwide and self-concept as a predictor of depression and suicide behavior. Although suicide in children is an increasing problem in Mexico, there are scarce studies reporting risk factors and none of children in foster care institutions. This was a comparative, ex post facto study whose aim was to analyze associations between suicidal ideation, depression, and self-concept in two paired samples of Mexican children (83 institutionalized and 83 noninstitutionalized). Results show 16% of the children reported suicidal ideation and statistically significant differences among variables in both samples. Suggestions are made to address this problem from early ages.

[Evaluation of two strategies for nutritional education using radio programs in Guadalajara, Mexico]. / Evaluación de dos estrategias de educación nutricional vía radio en Guadalajara, México.

Modifying knowledge and attitudes through persuasive communication in health via radio has produced encouraging results for public health planners. This study's objective was to measure the effect of an educational strategy on knowledge and attitudes towards nutrition in two marginalized communities in Guadalajara, Mexico. Two communities were randomly selected. In each community a group of individuals was invited to be exposed to radio broadcasts. Using a coded and structured instrument, knowledge and attitudes towards the contents of nutritional education for health were measured before and after the intervention in both groups. Group A (n = 37) was organized and exposed to the dynamics of the radio forum throughout the 4 months during which the project lasted. Group B (n = 33) was not organized, and listened to the radio program according to its own cultural dynamics. Median knowledge and attitudes (KA) for group A was 56.8 in the pre-test and 74.1 in the post-test (W: p = -0.05). In group B the KA results were 53.0 and 59.2, respectively (W: p = -0.05). The results emphasize the advantages of the radio forum as a health communications strategy for human nutrition.

Tentativa suicida y uso del tiempo libre en adolescentes escolarizados mexicanos / Suicide attempt and leisure in Mexican adolescents

Resumen El propósito del estudio fue identificar el uso del tiempo libre y su relación con la tentativa suicida en una muestra mexicana adolescente. Participaron 1290 estudiantes de nivel secundaria, entre 12 a 18 años (36 % varones, 64 % mujeres); el instrumento incluyó reactivos cerrados y formato libre. De las 11 categorías del tiempo libre obtenidas, la de relaciones fuera del ámbito familiar obtuvo el mayor puntaje (96 %) y el menor las actividades escolares (1,8 %). Se encontraron asociaciones estadísticamente significativas de riesgo suicida en las actividades pasivas, del hogar, relaciones familiares y cuidar el propio cuerpo; se encontraron actividades con efecto protector las relaciones sociales fuera del ámbito familiar y recreativas (artísticas, deportivas). Se presentan reflexiones sobre la producción y utilización creativa del tiempo libre en jóvenes y familias contemporáneas.

Abstract The aim of the present study was to identify leisure time and its association to suicide attempts in a sample of 1290 Mexican adolescents aged 12-18 (36 % male, 64 % female). The instrument included both, closed and open items. Out of 11 leisure categories, relationships outside their families were the most prevalent at 96 % while school-related activities were the least prevalent (at 1.8 %). Statistically significant differences were found for suicidal behavior and passive activities, home activities, family relationships, and body self-care. Recreation activities such as sports and arts, and relationships outside their families were found to be protective factors. Concluding considerations about the creative use of leisure for contemporary adolescents and families are included.

Resumo O objetivo deste estudo foi identificar a relação entre o uso do tempo livre e a tentativa de suicídio em uma amostra de adolescentes mexicanos. Participaram 1290 estudantes de ensino médio, entre 12 e 18 anos (36 % homens, 64 % mulheres). O instrumento de avaliação incluiu perguntas fechadas e abertas. Das 11 categorias estabelecidas para tempo livre, a que obteve maior pontuação (96 %) foi a de relações fora do âmbito familiar e a de menor pontuação (1.8 %) foi de atividades escolares. Foram encontradas associações estatísticas significativas entre o risco de suicídio e atividades passivas, tais como, atividades de casa, relações familiares e cuidados com o corpo próprio; atividades protetoras foram encontradas em relações sociais fora do âmbito familiar e de recreação (artísticas e esportivas). Apresenta-se reflexões sobre a produção e utilização criativa do tempo livre em jovens e famílias contemporâneas.