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PURPOSEBreast cancer mortality rates in Latin America (LA) are higher than those in the United States, possibly because of advanced disease presentation, health care disparities, or unfavorable molecular subtypes. The Latin American Cancer Research Network was established to address these challenges and to promote collaborative clinical research. The Molecular Profiling of Breast Cancer Study (MPBCS) aimed to evaluate the clinical characteristics and treatment outcomes of LA participants with locally advanced breast cancer (LABC).PATIENTS AND METHODSThe MPBCS enrolled 1,449 participants from Argentina, Brazil, Chile, Mexico, and Uruguay. Through harmonized procedures and quality assurance measures, this study evaluated clinicopathologic characteristics, neoadjuvant chemotherapy response, and survival outcomes according to residual cancer burden (RCB) and the type of surgery.RESULTSOverall, 711 and 480 participants in the primary surgery and neoadjuvant arms, respectively, completed the 5-year follow-up period. Overall survival was independently associated with RCB (worse survival for RCBIII-adjusted hazard ratio, 8.19, P < .001, and RCBII [adjusted hazard ratio, 3.69, P < .008] compared with RCB0 [pathologic complete response or pCR]) and type of surgery (worse survival in mastectomy than in breast-conserving surgery [BCS], adjusted hazard ratio, 2.97, P = .001). The hormone receptor–negative-human epidermal growth factor receptor 2–positive group had the highest proportion of pCR (48.9%). The analysis of the ASCO Quality Oncology Practice Initiative breast module revealed high compliance with pathologic standards but lower adherence to treatment administration standards. Notably, compliance with trastuzumab administration varied widely among countries (33.3%-88.7%).CONCLUSIONIn LABC, we demonstrated the survival benefit of BCS and the prognostic effect of the response to available neoadjuvant treatments despite an important variability in access to key treatments. The MPBCS represents a significant step forward in understanding the real-world implementation of oncologic procedures in LA.

Abstract Objective Although 82% of American adults have a body mass index (BMI) of over 25, individuals with elevated BMI are considered difficult to recruit for studies. Effective participant identification and recruitment are crucial to minimize the likelihood of sampling bias. One understudied factor that could lead to sampling bias is the study information presented in recruitment materials. In the context of weight research, potential participants with higher weight may avoid studies that advertise weight‐related procedures. Thus, this study experimentally manipulated the phrasing of weight‐related information included in recruitment materials and examined its impact on participants' characteristics. Methods Two visually similar flyers, either weight‐salient or neutral, were randomly posted throughout a university campus to recruit participants (N = 300) for a short survey, assessing their internalized weight bias, anticipated and experienced stigmatizing experiences, eating habits, and general demographic characteristics. Results Although the weight‐salient (vs. neutral) flyer took 18.5 days longer to recruit the target sample size, there were no between flyer differences in respondents' internalized weight bias, anticipated/experienced weight stigma, disordered eating behaviors, BMI, or perceived weight. Absolute levels of these variables, however, were low overall. Conclusion Providing detailed information about study procedures allows participants to have more autonomy over their participation without differentially affecting participant characteristics.

BackgroundIrritable bowel syndrome (IBS) is a disorder of the gut-brain interaction that is associated with abdominal pain, altered bowel patterns, and reduced quality of life. Up to 50% of patients with IBS also report anxiety or depressive symptoms. Although effective self-management interventions exist for individuals with IBS, few have been effectively implemented, and most do not consider the unique needs of patients with comorbid IBS and anxiety or depression. ObjectiveThis study aimed to determine the anticipated acceptability, appropriateness, feasibility, and usability of a comprehensive self-management intervention using an implementation science and human-centered design approach among individuals with comorbid IBS and anxiety or depression and health care providers. MethodsA convergent mixed methods design was used to elicit feedback on the comprehensive self-management intervention outline and content to identify refinement needs before testing. Patients with IBS and moderate to severe anxiety or depression and health care providers were purposefully sampled from primary care and gastroenterology settings. Participants completed semistructured interviews and surveys on anticipated acceptability, appropriateness, feasibility, and usability. ResultsPatient participants (n=12) were on average 36.8 (SD 12.2) years of age, and 42% (5/12) were currently receiving psychological therapy. Health care providers (n=14) were from primary care (n=7) and gastroenterology (n=7) settings. The mean usability scores (out of 100) were 52.5 (SD 14.5) for patients and 45.6 (SD 11.6) for providers. For patients and providers, qualitative data expanded the quantitative findings for acceptability and appropriateness. Acceptability findings were the comprehensive nature of the intervention and discussion of the gut-brain interaction. For appropriateness, participants reported that the intervention provided structure, accountability, and support. Feasibility was confirmed for patients, but there was a divergence of findings between quantitative and qualitative measures for providers. Patients focused on intervention feasibility, while providers focused on implementation feasibility in the clinic. Identified usability issues to address before implementation included the intervention delivery format, length, and lack of integration into health care settings that, if not addressed, may limit the reach of the intervention. ConclusionsPatients and health care providers found the intervention acceptable and appropriate. Several feasibility and usability issues were identified, including intervention delivery methods, length of intervention, and the best methods to implement in the clinic setting. The next steps are to refine the intervention to address the identified issues and test in a pilot study whether addressing usability issues leads to the anticipated improvements in implementation and uptake.

The taiep rat is a tubulin mutant with an early hypomyelination followed by progressive demyelination of the central nervous system due to a point mutation in the Tubb4a gene. It shows clinical, radiological, and pathological signs like those of the human leukodystrophy hypomyelination with atrophy of the basal ganglia and cerebellum (H-ABC). Taiep rats had tremor, ataxia, immobility episodes, epilepsy, and paralysis; the acronym of these signs given the name to this autosomal recessive trait. The aim of this study was to analyze the characteristics of somatosensory evoked potentials (SSEPs) and motor evoked potentials (MEPs) in adult taiep rats and in a patient suffering from H-ABC. Additionally, we evaluated the effects of 4-aminopyridine (4-AP) on sensory responses and locomotion and finally, we compared myelin loss in the spinal cord of adult taiep and wild type (WT) rats using immunostaining. Our results showed delayed SSEPs in the upper and the absence of them in the lower extremities in a human patient. In taiep rats SSEPs had a delayed second negative evoked responses and were more susceptible to delayed responses with iterative stimulation with respect to WT. MEPs were produced by bipolar stimulation of the primary motor cortex generating a direct wave in WT rats followed by several indirect waves, but taiep rats had fused MEPs. Importantly, taiep SSEPs improved after systemic administration of 4-AP, a potassium channel blocker, and this drug induced an increase in the horizontal displacement measured in a novelty-induced locomotor test. In taiep subjects have a significant decrease in the immunostaining of myelin in the anterior and ventral funiculi of the lumbar spinal cord with respect to WT rats. In conclusion, evoked potentials are useful to evaluate myelin alterations in a leukodystrophy, which improved after systemic administration of 4-AP. Our results have a translational value because our findings have implications in future medical trials for H-ABC patients or with other leukodystrophies.

Abstract Background Awareness about hereditary breast cancer and the preventative steps to minimize disease risk is lower in Hispanic/Latina individuals than non-Hispanic White women in the United States. For this reason, we developed a promotor-based hereditary breast cancer education and risk identification program for self-identified Hispanic/Latina women, which included training promotores in basic genetics and hereditary breast cancer. This study explored promotores’ experiences receiving training and participating in virtual practice sessions as well as changes in knowledge about hereditary breast cancer. Methods A total of ten promotores underwent a two-week basic training led by the promotores organization and an eight-hour in person hereditary breast cancer training workshop. Demographic information along with pre- and post-training surveys were completed by ten promotores who participated in the training workshop. Surveys were given to determine changes in knowledge of hereditary breast cancer and genetics. Of the ten promotores, two were selected to lead community education sessions and participated in 6 semi-structured interviews. All interviews and practice sessions were conducted using a virtual platform. Results The data revealed that after the 8-h workshop and practice sessions, promotores felt confident about their ability to conduct virtual education sessions with the community. Interviews identified key facilitators to success such as a supportive environment, practice presentations, and personal motivation. Learning the online platform was considered the biggest challenge by the promotores, as opposed to learning complex genetics topics. Conclusions These results provide further evidence supporting promotores’ willingness and ability to provide health education on relatively complex topics. It also offers insight into the challenges of presenting information to vulnerable populations using an online platform and the additional support that is required to ensure a positive outcome.

Neuromodulation interventions, such as Deep Brain Stimulation (DBS) and repeated transcranial magnetic stimulation (rTMS), are proposed as possible new complementary therapies to treat substance use disorders (SUD) such as alcohol use disorder (AUD). It is hypothesized that neuromodulation may induce neural plasticity in the reward and frontostriatal systems via electrical field induction, possibly reducing symptoms. Preclinical self-administration rodent models of AUD may help us gain insight into the effects of neuromodulation therapies on different pathology, as well as the neural mechanisms behind the positive effects. DBS, or any type of brain stimulation using intracranial electrodes in rodents, would benefit from the use of magnetic resonance imaging (MRI) to study the longitudinal effects and mechanisms of stimulation as well as novel targets, as it is a non-invasive technique that allows the analysis of structural and functional changes in the brain. To do this, there is a need for MRI-compatible electrodes that allow for MRI acquisition with minimal distortion of the magnetic field. In this protocol, we present a method for the construction and surgery of chronically implantable monopolar carbon electrodes for use in rats. Unlike conventional electrodes, carbon electrodes are resistant to high temperatures, flexible, and generate fewer artifacts in MRI compared to conventional ones. We validated its use by using a focal electrical stimulation high-frequency (20 Hz) protocol that lasted ∼10 sessions. We propose that this technique can also be used for the research of the neurophysiological bases of the neuromodulatory treatment in other preclinical substance use disorders (SUD) models.

La personalidad de marca es una percepción ampliada que tiene el consumidor hacia las marcas, lo que involucra una relación con este y se fundamenta en aspectos relacionados en la compra como el precio, la calidad o el sabor; pero asociar características de personalidad y emocionalidad a la marca genera una percepción interesante que define el mismo consumidor. Por ello este artículo tiene como objetivo identificar la personalidad de marca percibida hacia las marcas de alimento para mascotas, perros y gatos, por parte de sus dueños en la ciudad de Bogotá. Para esto se llevó a cabo un estudio descriptivo y de corte transversal, a través de la aplicación de un instrumento a 388 personas dueñas de mascotas perros y gatos. Entre los resultados se destacó el reconocimiento como uno de los principales rasgos de personalidad que identifican a estas marcas de alimentos, ya que es un factor que sí influye en la decisión de compra y si el consumidor es de un nivel socioeconómico menor, logra percibir o identificar más fácil los rasgos de personalidad en las marcas.

Learning gain can be defined as the difference between students’ language competences demonstrated at two different points in time. In this article, we reported on a small-scale study aimed at measuring learning gains and piloting the methods chosen. Fourteen students of English as a foreign language participated in the study. We employed a student self-report survey, an oral performance assessment task and a standardised test for data gathering, and we applied them at three different moments during the eight-month study. Our data analysis includes the comparison of percentages rendered by test scores, the estimation of means for oral task scores and grouping and coding for qualitative data in the survey. Results show the gradual pattern of language improvement and the suitability of methods. These results can help stakeholders or policymakers in selecting relevant evidence to improve accountability in decision-making. We have provided conclusions and recommendations below for a larger scale study.

PurposesMost molecular-based published studies on breast cancer do not adequately represent the unique and diverse genetic admixture of the Latin American population. Searching for similarities and differences in molecular pathways associated with these tumors and evaluating its impact on prognosis may help to select better therapeutic approaches.Patients and MethodsWe collected clinical, pathological, and transcriptomic data of a multi-country Latin American cohort of 1,071 stage II-III breast cancer patients of the Molecular Profile of Breast Cancer Study (MPBCS) cohort. The 5-year prognostic ability of intrinsic (transcriptomic-based) PAM50 and immunohistochemical classifications, both at the cancer-specific (OSC) and disease-free survival (DFS) stages, was compared. Pathway analyses (GSEA, GSVA and MetaCore) were performed to explore differences among intrinsic subtypes.ResultsPAM50 classification of the MPBCS cohort defined 42·6% of tumors as LumA, 21·3% as LumB, 13·3% as HER2E and 16·6% as Basal. Both OSC and DFS for LumA tumors were significantly better than for other subtypes, while Basal tumors had the worst prognosis. While the prognostic power of traditional subtypes calculated with hormone receptors (HR), HER2 and Ki67 determinations showed an acceptable performance, PAM50-derived risk of recurrence best discriminated low, intermediate and high-risk groups. Transcriptomic pathway analysis showed high proliferation (i.e. cell cycle control and DNA damage repair) associated with LumB, HER2E and Basal tumors, and a strong dependency on the estrogen pathway for LumA. Terms related to both innate and adaptive immune responses were seen predominantly upregulated in Basal tumors, and, to a lesser extent, in HER2E, with respect to LumA and B tumors.ConclusionsThis is the first study that assesses molecular features at the transcriptomic level in a multicountry Latin American breast cancer patient cohort. Hormone-related and proliferation pathways that predominate in PAM50 and other breast cancer molecular classifications are also the main tumor-driving mechanisms in this cohort and have prognostic power. The immune-related features seen in the most aggressive subtypes may pave the way for therapeutic approaches not yet disseminated in Latin America.Clinical Trial RegistrationClinicalTrials.gov (Identifier: NCT02326857).

Molecular profile of breast cancer in Latin-American women was studied in five countries: Argentina, Brazil, Chile, Mexico, and Uruguay. Data about socioeconomic characteristics, risk factors, prognostic factors, and molecular subtypes were described, and the 60-month overall cumulative survival probabilities (OS) were estimated. From 2011 to 2013, 1,300 eligible Latin-American women 18 years or older, with a diagnosis of breast cancer in clinical stage II or III, and performance status ≦̸1 were invited to participate in a prospective cohort study. Face-to-face interviews were conducted, and clinical and outcome data, including death, were extracted from medical records. Unadjusted associations were evaluated by Chi-squared and Fisher’s exact tests and the OS by Kaplan–Meier method. Log-rank test was used to determine differences between cumulative probability curves. Multivariable adjustment was carried out by entering potential confounders in the Cox regression model. The OS at 60 months was 83.9%. Multivariable-adjusted death hazard differences were found for women living in Argentina (2.27), Chile (1.95), and Uruguay (2.42) compared with Mexican women, for older (≥60 years) (1.84) compared with younger (≤40 years) women, for basal-like subtype (5.8), luminal B (2.43), and HER2-enriched (2.52) compared with luminal A subtype, and for tumor clinical stages IIB (1.91), IIIA (3.54), and IIIB (3.94) compared with stage IIA women. OS was associated with country of residence, PAM50 intrinsic subtype, age, and tumor stage at diagnosis. While the latter is known to be influenced by access to care, including cancer screening, timely diagnosis and treatment, including access to more effective treatment protocols, it may also influence epigenetic changes that, potentially, impact molecular subtypes. Data derived from heretofore understudied populations with unique geographic ancestry and sociocultural experiences are critical to furthering our understanding of this complexity.

El nivel de capacidades tecnológicas que logra desarrollar una organización es de gran relevancia para generar ventajas competitivas. El estudio de las capacidades tecnológicas se ha centrado en analizar su relación con el desempeño empresarial, el aprendizaje, la internacionalización, las estrategias de cooperación, entre otros. Este estudio se enfoca en el análisis de la orientación emprendedora, el enfoque estratégico de la organización y la experiencia, y su impacto en el desarrollo de capacidades tecnológicas de las empresas del sector automotriz de la región centro de México. Los resultados muestran que las empresas que quieran mejorar su nivel de capacidades tecnológicas deben establecer una filosofía empresarial enfocada en la innovación, lo que conlleva a tomar decisiones de manera proactiva, escaneando continuamente el entorno y gestionar el conocimiento organizacional para aprender de las experiencias.

Age-related neurosensory deficit of the inner ear is mostly due to a loss of hair cells (HCs). Development of stem cell-based therapy requires a better understanding of factors and signals that drive stem cells into otic sensory progenitor cells (OSPCs) to replace lost HCs. Human induced pluripotent stem cells (hiPSCs) theoretically represent an unlimited supply for the generation of human OSPCs in vitro. In this study, we developed a monolayer-based differentiation system to generate an enriched population of OSPCs via a stepwise differentiation of hiPSCs. Gene and protein expression analyses revealed the efficient induction of a comprehensive panel of otic/placodal and late otic markers over the course of the differentiation. Furthermore, whole transcriptome analysis confirmed a developmental path of OSPC differentiation from hiPSCs. We found that modulation of WNT and transforming growth factor-β (TGF-β) signaling combined with fibroblast growth factor 3 (FGF3) and FGF10 treatment over a 6-day period drives the expression of early otic/placodal markers followed by late otic sensory markers within 13 days, indicative of a differentiation into embryonic-like HCs. In summary, we report a rapid and efficient strategy to generate an enriched population of OSPCs from hiPSCs, thereby establishing the value of this approach for disease modeling and cell-based therapies of the inner ear.

The inner ear represents a promising system to develop cell-based therapies from human induced pluripotent stem cells (hiPSCs). In the developing ear, Notch signaling plays multiple roles in otic region specification and for cell fate determination. Optimizing hiPSC induction for the generation of appropriate numbers of otic progenitors and derivatives, such as hair cells, may provide an unlimited supply of cells for research and cell-based therapy. In this study, we used monolayer cultures, otic-inducing agents, Notch modulation, and marker expression to track early and otic sensory lineages during hiPSC differentiation. Otic/placodal progenitors were derived from hiPSC cultures in medium supplemented with FGF3/FGF10 for 13 days. These progenitor cells were then treated for 7 days with retinoic acid (RA) and epidermal growth factor (EGF) or a Notch inhibitor. The differentiated cultures were analyzed in parallel by qPCR and immunocytochemistry. After the 13 day induction, hiPSC-derived cells displayed an upregulated expression of a panel of otic/placodal markers. Strikingly, a subset of these induced progenitor cells displayed key-otic sensory markers, the percentage of which was increased in cultures under Notch inhibition as compared to RA/EGF-treated cultures. Our results show that modulating Notch pathway during in vitro differentiation of hiPSC-derived otic/placodal progenitors is a valuable strategy to promote the expression of human otic sensory lineage genes.

El artículo ofrece un análisis sobre el papel de los/as profesionales de la salud en el acceso de las mujeres a los servicios de aborto legal y seguro en Uruguay. El creciente reconocimiento de los derechos sexuales y los reproductivos como derechos humanos en el escenario internacional –y en algunos contextos nacionales como el caso uruguayo– configuró, no sin controversias, un nuevo marco ético y normativo para las políticas públicas. La aprobación de la ley de interrupción voluntaria del embarazo en Uruguay (2012), tuvo lugar en un escenario de fuertes disputas morales, filosóficas y políticas sobre la autonomía de las mujeres. Las prácticas de los/as profesionales de la salud son un locus privilegiado de análisis de las posibilidades, resistencias y dificultades que se observan en la implementación de los servicios que la nueva ley establece para la atención del aborto legal.

Inhibitory factors have been implicated in the failure of remyelination in demyelinating diseases. Myelin associated inhibitors act through a common receptor called Nogo receptor (NgR) that plays critical inhibitory roles in CNS plasticity. Here we investigated the effects of abrogating NgR inhibition in a non-immune model of focal demyelination in adult mouse optic chiasm.A focal area of demyelination was induced in adult mouse optic chiasm by microinjection of lysolecithin. To knock down NgR levels, siRNAs against NgR were intracerebroventricularly administered via a permanent cannula over 14 days, Functional changes were monitored by electrophysiological recording of latency of visual evoked potentials (VEPs). Histological analysis was carried out 3, 7 and 14 days post demyelination lesion. To assess the effect of NgR inhibition on precursor cell repopulation, BrdU was administered to the animals prior to the demyelination induction. Inhibition of NgR significantly restored VEPs responses following optic chiasm demyelination. These findings were confirmed histologically by myelin specific staining. siNgR application resulted in a smaller lesion size compared to control. NgR inhibition significantly increased the numbers of BrdU+/Olig2+ progenitor cells in the lesioned area and in the neurogenic zone of the third ventricle. These progenitor cells (Olig2+ or GFAP+) migrated away from this area as a function of time.Our results show that inhibition of NgR facilitate myelin repair in the demyelinated chiasm, with enhanced recruitment of proliferating cells to the lesion site. Thus, antagonizing NgR function could have therapeutic potential for demyelinating disorders such as Multiple Sclerosis.

We present a novel mathematical formalism to predict the kinetics of DNA damage repair after exposure to both low- and high-LET radiation (X rays; 350 MeV/n 40Ar; 600 MeV/n 56Fe). Our method is based on monitoring DNA damage repair protein 53BP1 that forms radiation-induced foci (RIF) at locations of DNA double-strand breaks (DSB) in the nucleus and comparing its expression in primary skin fibroblasts isolated from 15 mice strains. We previously reported strong evidence for clustering of nearby DSB into single repair units as opposed to the classic "contact-first" model where DSB are considered immobile. Here we apply this clustering model to evaluate the number of remaining RIF over time. We also show that the newly introduced kinetic metrics can be used as surrogate biomarkers for in vivo radiation toxicity, with potential applications in radiotherapy and human space exploration. In particular, we observed an association between the characteristic time constant of RIF repair measured in vitro and survival levels of immune cells collected from irradiated mice. Moreover, the speed of DNA damage repair correlated not only with radiation-induced cellular survival in vivo, but also with spontaneous cancer incidence data collected from the Mouse Tumor Biology database, suggesting a relationship between the efficiency of DSB repair after irradiation and cancer risk.

The coronavirus disease 2019 (COVID-19) pandemic has challenged research capacities at global and national levels. The scientific community has played an important role in informing public policies for the management [...]

Abstract Lichen-forming fungi (LFF) are prolific producers of functionally and structurally diverse secondary metabolites, most of which are taxonomically exclusive and play lineage-specific roles. To date, widely distributed, evolutionarily conserved biosynthetic pathways in LFF are not known. However, this idea stems from polyketide derivatives, since most biochemical research on lichens has concentrated on polyketide synthases (PKSs). Here, we present the first systematic identification and comparison of terpene biosynthetic genes of LFF using all the available Lecanoromycete reference genomes and 22 de novo sequenced ones (111 in total, representing 60 genera and 23 families). We implemented genome mining and gene networking approaches to identify and group the biosynthetic gene clusters (BGCs) into networks of similar BGCs. Our large-scale analysis led to the identification of 724 terpene BGCs with varying degrees of pairwise similarity. Most BGCs in the dataset were unique with no similarity to a previously known fungal or bacterial BGC or among each other. Remarkably, we found two BGCs that were widely distributed in LFF. Interestingly, both conserved BGCs contain the same core gene, i.e., putatively a squalene/phytoene synthase (SQS), involved in sterol biosynthesis. This indicates that early gene duplications, followed by gene losses/gains and gene rearrangement are the major evolutionary factors shaping the composition of these widely distributed SQS BGCs across LFF. We provide an in-depth overview of these BGCs, including the transmembrane, conserved, variable and LFF-specific regions. Our study revealed that lichenized fungi do have a highly conserved BGC, providing the first evidence that a biosynthetic gene may constitute essential genes in lichens.

El ascenso de las nuevas derechas y la presencia de nuevas izquierdas ha transformado significativamente el panorama político global en el siglo XXI. El 22 de octubre de 2023, Argentina eligió como presidente a Javier Milei, un autoproclamado anarcocapitalista libertario que prometió desmantelar el Estado corrupto, derrotar a la casta y eliminar el peso como moneda nacional. Casi un año después, en noviembre de 2024, la reelección de Donald Trump marcó el regreso al poder de las derechas radicales en la primera potencia global y la consolidación del trumpismo, que desplazó a la derecha tradicional del Partido Republicano.