Genetic targeting of Card19 is linked to disrupted NINJ1 expression, impaired cell lysis, and increased susceptibility to Yersinia infection.

Cell death plays a critical role in inflammatory responses. During pyroptosis, inflammatory caspases cleave Gasdermin D (GSDMD) to release an N-terminal fragment that generates plasma membrane pores that mediate cell lysis and IL-1 cytokine release. Terminal cell lysis and IL-1ß release following caspase activation can be uncoupled in certain cell types or in response to particular stimuli, a state termed hyperactivation. However, the factors and mechanisms that regulate terminal cell lysis downstream of GSDMD cleavage remain poorly understood. In the course of studies to define regulation of pyroptosis during Yersinia infection, we identified a line of Card19-deficient mice (Card19lxcn) whose macrophages were protected from cell lysis and showed reduced apoptosis and pyroptosis, yet had wild-type levels of caspase activation, IL-1 secretion, and GSDMD cleavage. Unexpectedly, CARD19, a mitochondrial CARD-containing protein, was not directly responsible for this, as an independently-generated CRISPR/Cas9 Card19 knockout mouse line (Card19Null) showed no defect in macrophage cell lysis. Notably, Card19 is located on chromosome 13, immediately adjacent to Ninj1, which was recently found to regulate cell lysis downstream of GSDMD activation. RNA-seq and western blotting revealed that Card19lxcn BMDMs have significantly reduced NINJ1 expression, and reconstitution of Ninj1 in Card19lxcn immortalized BMDMs restored their ability to undergo cell lysis in response to caspase-dependent cell death stimuli. Card19lxcn mice exhibited increased susceptibility to Yersinia infection, whereas independently-generated Card19Null mice did not, demonstrating that cell lysis itself plays a key role in protection against bacterial infection, and that the increased infection susceptibility of Card19lxcn mice is attributable to loss of NINJ1. Our findings identify genetic targeting of Card19 being responsible for off-target effects on the adjacent gene Ninj1, disrupting the ability of macrophages to undergo plasma membrane rupture downstream of gasdermin cleavage and impacting host survival and bacterial control during Yersinia infection.

Prevalencia de anemia en la población mexicana: análisis de la Ensanut Continua 2022.

OBJETIVO: Describir la magnitud de la prevalencia de anemia en la población mexicana participante en la Encuesta Nacional de Salud y Nutrición Continua 2022 (Ensanut Continua 2022). Material y métodos. La Ensanut 2022 es probabilística. Mediante sangre venosa y Hemocué (201+) se midió hemoglobina (Hb) y se ajustó por altitud. Se definió anemia según criterios de la Organización Mundial de la Salud (OMS). Considerando el diseño muestral de la encuesta, se obtuvieron prevalencias e IC95%. RESULTADOS: Las prevalencias de anemia fueron 6.8% en niños de 1-4 años, 3.8% en niños de 5-11 años, 10.1% en adolescentes (12-19 años), 15.8% en mujeres (20-49 años) y 10.3% en adultos mayores (≥60 años). CONCLUSIONES: La anemia afectó principalmente a las mujeres adultas. Resulta necesario identificar sus causas para focalizar acciones y evitar el ciclo intergeneracional del riesgo de anemia.

A Comparative and Critical Analysis for In Vitro Cytotoxic Evaluation of Magneto-Crystalline Zinc Ferrite Nanoparticles Using MTT, Crystal Violet, LDH, and Apoptosis Assay.

Zinc ferrite nanoparticles (ZFO NPs) are a promising magneto-crystalline platform for nanomedicine-based cancer theranostics. ZFO NPs synthesized using co-precipitation method are characterized using different techniques. UV-visible spectroscopy exhibits absorption peaks specific for ZFO. Raman spectroscopy identifies Raman active, infrared active, and silent vibrational modes while Fourier transforms infrared spectroscopic (FTIR) spectra display IR active modes that confirm the presence of ZFO. X-ray diffraction pattern (XRD) exhibits the crystalline planes of single-phase ZFO with a face-centered cubic structure that coincides with the selected area electron diffraction pattern (SAED). The average particle size according to high-resolution transmission electron microscopy (HR-TEM) is 5.6 nm. X-ray photoelectron spectroscopy (XPS) signals confirm the chemical states of Fe, Zn, and O. A superconducting quantum interference device (SQUID) displays the magnetic response of ZFO NPs, showing a magnetic moment of 45.5 emu/gm at 70 kOe. These ZFO NPs were then employed for comparative cytotoxicity evaluation using MTT, crystal violet, and LDH assays on breast adenocarcinoma epithelial cell (MCF-7), triple-negative breast cancer lines (MDA-MB 231), and human embryonic kidney cell lines (HEK-293). Flow cytometric analysis of all the three cell lines were performed in various concentrations of ZFO NPs for automated cell counting and sorting based on live cells, cells entering in early or late apoptotic phase, as well as in the necrotic phase. This analysis confirmed that ZFO NPs are more cytotoxic towards triple-negative breast cancer cells (MDA-MB-231) as compared to breast adenocarcinoma cells (MCF-7) and normal cell lines (HEK-293), thus corroborating that ZFO can be exploited for cancer therapeutics.

"The change was as big as night and day": Experiences of professors teaching students with intellectual disabilities.

Since the inception of the Higher Education Opportunity Act in 2008, there has been an increase in the number of post-secondary education institutions in the United States that have established inclusive postsecondary programs for individuals with intellectual disabilities to attend college and achieve higher levels of employment. Previous studies have investigated the development and outcomes of these programs, however, less has been explored related to professors' experiences and perceptions regarding this unique student population, particularly within Hispanic Serving Institutions (HSI). The current study focused on professors teaching inclusive courses within a new Comprehensive Transition and Postsecondary Program at a HSI and aimed to identify their perceptions and experiences related to instructing students with intellectual disabilities. Six professors participated in pre- and post-semester in-depth interviews. Findings from applied thematic analysis included: (a) barriers to success; (b) academic supports and strategies; (c) successful outcomes and (d) considerations for future, related programming.

Inhibition of Stearoyl-CoA Desaturase by Sterculic Oil Reduces Proliferation and Induces Apoptosis in Prostate Cancer Cell Lines.

Prostate cancer (PCa) is a common type of cancer affecting male population. PCa treatments have side effects and are temporarily effective, so new therapeutic options are being investigated. Due to the high demand of energy for cell proliferation, an increase in the expression and activity of lipogenic enzymes such as the stearoyl-CoA desaturase (SCD) have been observed in PCa. Sterculic acid, contained in the seed's oil of Malvales, is a natural inhibitor of SCD. The objective of our investigation was to evaluate the effects of sterculic oil (SO) from Sterculia apetala seeds on proliferation, cell cycle and apoptosis in prostate cancer cells. SO was administered to PC3 and LNCaP cells, and to prostate normal cells; cell viability, cell cycle, apoptosis, SCD gene and protein expression and enzymatic activity were analyzed. SO administration (4 mM sterculic acid) diminished cell viability in LNCaP and PC3 cells, arrested cell cycle in G2 and promoted apoptosis. SO diminished SCD enzymatic activity with no effects on gene nor protein expression. Our results suggest that SO might offer benefits as an adjuvant in hormonal and chemotherapy prostate cancer treatments. This is the first study to analyze the effect of SO on cancer cells.

Hydrodynamic interactions hinder transport of flow-driven colloidal particles.

The flow-driven transport of interacting micron-sized particles occurs in many soft matter systems spanning from the translocation of proteins to moving emulsions in microfluidic devices. Here we combine experiments and theory to investigate the collective transport properties of colloidal particles along a rotating ring of optical traps. In the corotating reference frame, the particles are driven by a vortex flow of the surrounding fluid. When increasing the depth of the optical potential, we observe a jamming behavior that manifests itself in a strong reduction of the current with increasing particle density. We show that this jamming is caused by hydrodynamic interactions that enhance the energetic barriers between the optical traps. This leads to a transition from an over- to an under-critical tilting of the potential in the corotating frame. Based on analytical considerations, the enhancement effect is estimated to increase with increasing particle size or decreasing radius of the ring of traps. Measurements for different ring radii and Stokesian dynamics simulations for corresponding particle sizes confirm this. The enhancement of potential barriers in the flow-driven system is contrasted to the reduction of barriers in a force-driven one. This diverse behavior demonstrates that hydrodynamic interactions can have a very different impact on the collective dynamics of many-body systems. Applications to soft matter and biological systems require careful consideration of the driving mechanism and of the role of hydrodynamic interactions.

Hydrodynamic Interactions Can Induce Jamming in Flow-Driven Systems.

Hydrodynamic interactions between fluid-dispersed particles are ubiquitous in soft matter and biological systems and they give rise to intriguing collective phenomena. While it was reported that these interactions can facilitate force-driven particle motion over energetic barriers, here we show the opposite effect in a flow-driven system, i.e., that hydrodynamic interactions hinder transport across barriers. We demonstrate this result by combining experiments and theory. In the experiments, we drive colloidal particles using rotating optical traps, thus creating a vortex flow in the corotating reference frame. We observe a jamminglike decrease of particle currents with density for large barriers between traps. The theoretical model shows that this jamming arises from hydrodynamic interactions between the particles. The impact of hydrodynamic interactions is reversed compared to force-driven motion, suggesting that our findings are a generic feature of flow-driven transport.

Peripheral markers of allergen-specific immune activation predict clinical allergy in eosinophilic esophagitis.

BACKGROUND: Eosinophilic esophagitis (EoE) is a T-cell-mediated disease that is caused by specific foods and results in esophageal dysfunction. Existing allergy testing modalities are not helpful when attempting to identify EoE-causal foods necessitating empiric food elimination and recurrent endoscopy. The goal of this study was to identify and compare allergen-specific immune features that can be assayed in a minimally invasive manner to predict clinical food allergy in EoE. METHODS: We obtained blood samples from control subjects (n = 17), subjects with clinical EoE milk allergy (n = 17), and subjects with immunoglobulin E-mediated milk allergy (n = 9). We measured total and milk-specific plasma immunoglobulin G (IgG)4 levels and peripheral memory CD4+ T helper (TH ) cell proliferation and cytokine production after stimulation with endotoxin-depleted milk proteins. Sensitivity and specificity for predicting clinical EoE milk allergy were calculated and compared between approaches. RESULTS: Total and milk-specific IgG4 levels were not significantly different between control subjects and subjects with clinical EoE milk allergy. Stimulation with milk proteins caused TH lymphocytes from subjects with clinical EoE milk allergy to proliferate more (%P1 of 38.3 ± 4.6 vs. 12.7 ± 2.8, p < 0.0001), and produce more type 2 cytokines (%IL-4+ of 33.7 ± 2.8 vs. 6.9 ± 1.6, p < 0.0001) than cells from control subjects. Milk-dependent memory TH -cell proliferation (sensitivity and specificity of 88% and 82%, respectively) and interleukin 4 (IL-4) production (sensitivity and specificity of 100%) most strongly predicted clinical EoE milk allergy. CONCLUSIONS: Peripheral markers of allergen-specific immune activation may be useful in identifying EoE-causal foods. Assaying milk-dependent IL-4 production by circulating memory TH lymphocytes most accurately predicts clinical EoE milk allergy.

The Autotransporter IcsA Promotes Shigella flexneri Biofilm Formation in the Presence of Bile Salts.

Shigella flexneri is an intracellular bacterial pathogen that invades epithelial cells in the colonic mucosa, leading to bloody diarrhea. A previous study showed that S. flexneri forms biofilms in the presence of bile salts, through an unknown mechanism. Here, we investigated the potential role of adhesin-like autotransporter proteins in S. flexneri biofilm formation. BLAST search analysis revealed that the S. flexneri 2457T genome harbors 4 genes, S1242, S1289, S2406, and icsA, encoding adhesin-like autotransporter proteins. Deletion mutants of the S1242, S1289, S2406 and icsA genes were generated and tested for biofilm formation. Phenotypic analysis of the mutant strains revealed that disruption of icsA abolished bile salt-induced biofilm formation. IcsA is an outer membrane protein secreted at the bacterial pole that is required for S. flexneri actin-based motility during intracellular infection. In extracellular biofilms, IcsA was also secreted at the bacterial pole and mediated bacterial cell-cell contacts and aggregative growth in the presence of bile salts. Dissecting individual roles of bile salts showed that deoxycholate is a robust biofilm inducer compared to cholate. The release of the extracellular domain of IcsA through IcsP-mediated cleavage was greater in the presence of cholate, suggesting that the robustness of biofilm formation was inversely correlated with IcsA processing. Accordingly, deletion of icsP abrogated IcsA processing in biofilms and enhanced biofilm formation.

A sub-Mercury-sized exoplanet.

Since the discovery of the first exoplanets, it has been known that other planetary systems can look quite unlike our own. Until fairly recently, we have been able to probe only the upper range of the planet size distribution, and, since last year, to detect planets that are the size of Earth or somewhat smaller. Hitherto, no planets have been found that are smaller than those we see in the Solar System. Here we report a planet significantly smaller than Mercury. This tiny planet is the innermost of three that orbit the Sun-like host star, which we have designated Kepler-37. Owing to its extremely small size, similar to that of the Moon, and highly irradiated surface, the planet, Kepler-37b, is probably rocky with no atmosphere or water, similar to Mercury.

Robust and Fast Scene Recognition in Robotics Through the Automatic Identification of Meaningful Images.

Scene recognition is still a very important topic in many fields, and that is definitely the case in robotics. Nevertheless, this task is view-dependent, which implies the existence of preferable directions when recognizing a particular scene. Both in human and computer vision-based classification, this actually often turns out to be biased. In our case, instead of trying to improve the generalization capability for different view directions, we have opted for the development of a system capable of filtering out noisy or meaningless images while, on the contrary, retaining those views from which is likely feasible that the correct identification of the scene can be made. Our proposal works with a heuristic metric based on the detection of key points in 3D meshes (Harris 3D). This metric is later used to build a model that combines a Minimum Spanning Tree and a Support Vector Machine (SVM). We have performed an extensive number of experiments through which we have addressed (a) the search for efficient visual descriptors, (b) the analysis of the extent to which our heuristic metric resembles the human criteria for relevance and, finally, (c) the experimental validation of our complete proposal. In the experiments, we have used both a public image database and images collected at our research center.

A closely packed system of low-mass, low-density planets transiting Kepler-11.

When an extrasolar planet passes in front of (transits) its star, its radius can be measured from the decrease in starlight and its orbital period from the time between transits. Multiple planets transiting the same star reveal much more: period ratios determine stability and dynamics, mutual gravitational interactions reflect planet masses and orbital shapes, and the fraction of transiting planets observed as multiples has implications for the planarity of planetary systems. But few stars have more than one known transiting planet, and none has more than three. Here we report Kepler spacecraft observations of a single Sun-like star, which we call Kepler-11, that reveal six transiting planets, five with orbital periods between 10 and 47 days and a sixth planet with a longer period. The five inner planets are among the smallest for which mass and size have both been measured, and these measurements imply substantial envelopes of light gases. The degree of coplanarity and proximity of the planetary orbits imply energy dissipation near the end of planet formation.

AtMYB7, a new player in the regulation of UV-sunscreens in Arabidopsis thaliana.

The phenylpropanoid metabolic pathway provides a wide variety of essential compounds for plants. Together with sinapate esters, in Brassicaceae species, flavonoids play an important role in protecting plants against UV irradiation. In this work we have characterized Arabidopsis thaliana AtMYB7, the closest homolog of AtMYB4 and AtMYB32, described as repressors of different branches of phenylpropanoid metabolism. The characterization of atmyb7 plants revealed an induction of several genes involved in flavonol biosynthesis and an increased amount of these compounds. In addition, AtMYB7 gene expression is repressed by AtMYB4. As a consequence, the atmyb4 mutant plants present a reduction of flavonol contents, indicating once more that AtMYB7 represses flavonol biosynthesis. Our results also show that AtMYB7 gene expression is induced by salt stress. Induction assays indicated that AtMYB7 represses several genes of the flavonoid pathway, DFR and UGT being early targets of this transcription factor. The results obtained indicate that AtMYB7 is a repressor of flavonol biosynthesis and also led us to propose AtMYB4 and AtMYB7 as part of the regulatory mechanism controlling the balance of the main A. thaliana UV-sunscreens.

A Systematic Review of MRI Studies and the "Emotional paiN and social Disconnect (END)" Brain Model of Suicidal Behavior in Youth.

Introduction: Risk of suicidal ideation and suicidal behaviors greatly increases during adolescence, and rates have risen dramatically over the past two decades. However, few risk factors or biomarkers predictive of suicidal ideation or attempted suicide have been identified in adolescents. Neuroimaging correlates hold potential for early identification of adolescents at increased risk of suicidality and risk stratification for those at high risk of suicide attempt. Methods: In this systematic review, we evaluated neural regions and networks associated with suicidal ideation and suicide attempt in adolescents derived from magnetic resonance imaging (MRI) studies. A total of 28 articles were included in this review. Results: After descriptively synthesizing the literature, we propose the Emotional paiN and social Disconnect (END) model of adolescent suicidality and present two key neural circuits: (1) the emotional/mental pain circuit and (2) the social disconnect/distortion circuit. In the END model, the emotional pain circuit-consisting of the cerebellum, amygdala, and hippocampus-shows similar aberrations in adolescents with suicidal ideation as in those with a history of a suicide attempt (but to a smaller degree). The social disconnect circuit is unique to adolescent suicide attempters and includes the lateral orbitofrontal cortex (OFC), the temporal gyri, and the connections between them. Conclusion: Our proposed END brain model of suicidal behavior in youth, if confirmed by future prospective studies, can have implications for clinical goals of early detection, risk stratification, and intervention development. Treatments that target emotional pain and social disconnect may be ideal interventions for reducing suicidality in adolescents.

Triple Threat: Three Primary Malignancies Simultaneously Involving Three Genitourinary Organs.

Statistically, the chance of having concurrent renal cell carcinoma (RCC), urothelial carcinoma of the bladder (UC), and a neuroendocrine tumor (NET) of the renal parenchyma is less than one in a trillion. Herein, we describe an unusual case of a 67-year-old female who presented with bilateral flank pain and severe gross hematuria. Cross-sectional imaging revealed two large heterogeneous, endophytic renal masses with a single enlarged paracaval lymph node. Diagnostic cystoscopy was performed for completion of gross hematuria evaluation and revealed a concurrent papillary bladder tumor. Percutaneous biopsies of bilateral renal masses revealed clear cell RCC involving the left kidney and well-differentiated NET involving the right kidney, and transurethral resection of the bladder tumor revealed high-grade nonmuscle invasive urothelial carcinoma. The patient elected to undergo bilateral nephroureterectomy, radical cystectomy, and retroperitoneal and pelvic lymphadenectomy. Final pathology confirmed the presence of three different malignancies: noninvasive high-grade papillary UC of the bladder (pTaN0), left renal clear cell RCC (pT2bN0), right renal well-differentiated NET, and a single paracaval lymph nodes positive for metastatic NET (pT2aN1).

Overcrowding induces fast colloidal solitons in a slowly rotating potential landscape.

Collective particle transport across periodic energy landscapes is ubiquitously present in many condensed matter systems spanning from vortices in high-temperature superconductors, frictional atomic sliding, driven skyrmions to biological and active matter. Here we report the emergence of fast solitons propagating against a rotating optical landscape. These experimentally observed solitons are stable cluster waves that originate from a coordinated particle exchange process which occurs when the number of trapped microparticles exceeds the number of potential wells. The size and speed of individual solitons rapidly increase with the particle diameter as predicted by theory and confirmed by numerical simulations. We show that when several solitons coexist, an effective repulsive interaction can stabilize their propagation along the periodic potential. Our experiments demonstrate a generic mechanism for cluster-mediated transport with potential applications to condensed matter systems on different length scales.

Transplantation of Human-Fetal-Spinal-Cord-Derived NPCs Primed with a Polyglutamate-Conjugated Rho/Rock Inhibitor in Acute Spinal Cord Injury.

Neural precursor cell (NPC) transplantation represents a promising therapy for treating spinal cord injuries (SCIs); however, despite successful results obtained in preclinical models, the clinical translation of this approach remains challenging due, in part, to the lack of consensus on an optimal cell source for human neuronal cells. Depending on the cell source, additional limitations to NPC-based therapies include high tumorigenic potential, alongside poor graft survival and engraftment into host spinal tissue. We previously demonstrated that NPCs derived from rat fetal spinal cords primed with a polyglutamate (PGA)-conjugated form of the Rho/Rock inhibitor fasudil (PGA-SS-FAS) displayed enhanced neuronal differentiation and graft survival when compared to non-primed NPCs. We now conducted a similar study of human-fetal-spinal-cord-derived NPCs (hfNPCs) from legal gestational interruptions at the late gestational stage, at 19-21.6 weeks. In vitro, expanded hfNPCs retained neural features, multipotency, and self-renewal, which supported the development of a cell banking strategy. Before transplantation, we established a simple procedure to prime hfNPCs by overnight incubation with PGA-SS-FAS (at 50 µM FAS equiv.), which improved neuronal differentiation and overcame neurite-like retraction after lysophosphatidic-acid-induced Rho/Rock activation. The transplantation of primed hfNPCs into immune-deficient mice (NU(NCr)-Foxn1nu) immediately after the eighth thoracic segment compression prompted enhanced migration of grafted cells from the dorsal to the ventral spinal cord, increased preservation of GABAergic inhibitory Lbx1-expressing and glutamatergic excitatory Tlx3-expressing somatosensory interneurons, and elevated the numbers of preserved, c-Fos-expressing, activated neurons surrounding the injury epicenter, all in a low percentage. Overall, the priming procedure using PGA-SS-FAS could represent an alternative methodology to improve the capabilities of the hfNPC lines for a translational approach for acute SCI treatment.

Changes in Hospital Outpatient Quality Reporting Program Brain CT Efficiency Performance, 2013 to 2018.

BACKGROUND AND PURPOSE: Inefficient imaging practices merit renewed attention in preparation for full implementation of the Appropriate Use Criteria Program. This study's purpose is to quantify changes in outpatient brain CT imaging efficiency from 2013 to 2018, including changes in relative efficiency by hospital category. MATERIALS AND METHODS: Imaging efficiency data were obtained from the Medicare Hospital Compare website. Summary statistics were calculated for rates of unnecessarily combined brain and sinus CT scans from 2013 to 2018. Relative performance was compared by hospital Medicare payment structure, type of ownership, and affiliation with a radiology residency program. The predictive value of these hospital characteristics on brain CT efficiency was determined using linear regression analysis. RESULTS: From 2013 to 2018, the mean frequency of unnecessarily combined brain and sinus CT scans decreased by 1.82% (95% confidence interval, 1.74%-1.90%). Proprietary and physician-owned hospitals exhibited a higher mean frequency of combined scans than other hospitals in 2013 (P < .001), and government-owned hospitals exhibited a lower mean frequency of combined scans than other hospitals in 2018 (P < .001). Radiology residency-affiliated hospitals exhibited no significant difference in 2013 but exhibited a higher mean frequency in 2018 (difference: 0.45%; 95% confidence interval, 0.29%-0.61%). Critical access hospital status and nonaffiliation with a radiology residency program were the strongest predictors of brain CT efficiency in the regression model. CONCLUSION: Recent changes in hospitals' relative brain CT efficiency suggest category-specific differences in responsiveness to quality improvement efforts and may foreshadow similar trends under forthcoming initiatives.

Adolescent Brain Development and Progressive Legal Responsibility in the Latin American Context.

In this article, we analyze the contributions of neuroscience to the development of the adolescent brain and shed additional light on the minimum age of criminal responsibility in the context of Latin America. In neurobiology, maturity is perceived to be complex because the brain's temporal development process is not uniform across all its regions. This has important consequences for adolescents' behavior; in their search for the acceptance of their peers, they are more vulnerable to pressure and more sensitive to stress than adults. Their affectivity is more unstable, and they show signs of low tolerance to frustration and important emotional reactivity, with a decrease in the capacity to self-regulate. Consequently, risky behavior presents itself more frequently during adolescence, and behaviors that transgress norms and social conventions typically peak between the ages of 17 and 19 years. However, only a small percentage of young offenders escalate their behavior to committing crimes during adulthood. In comparative law, there are considerable differences in Latin American countries' legal dispositions regarding the minimum age of criminal responsibility; Brazil, Costa Rica, and Ecuador regard the age of criminal responsibility to be 12 years, while Argentina accepts this to be 16 years. From a legal viewpoint, however, the debate about the minimum age of criminal responsibility is connected to other circumstances that, because they are still at a developmental stage, are attributed to adolescents' rights in their decision-making and understanding of autonomy (e.g., the minimum ages for voting, alcohol consumption, and medical consent). We argue that research on the development of the adolescent brain does not provide definitive answers about the exact age required for different juridical purposes. Nonetheless, the current state of knowledge does allow for reflection on the development and maturation of adolescents and the implications for considering them criminally responsible. It also validates demands for a system that provides adolescents with greater protection and that favors their healthy integral development. In any case, although a specific minimum age is not evident, this study is disposed not to recommend lowering the age of criminal responsibility, but rather increasing it.