Universidad de la República

This study aims to identify the social and healthcare needs of patients with rare diseases (RD) and their physicians within a Universal Health Care System. It seeks to provide valuable insights for policymakers, patient organizations, and healthcare professionals while informing about these diseases, raising awareness, and designing strategies to improve access to quality, timely medical care, including therapies and medication at a local and regional level. Two semi-structured surveys were conducted between May 2023 and August 2024, targeting family members of patients with RD (N = 64) and physicians (N = 56) in Uruguay. Surveys were self-administered via email or conducted by an interviewer, and were disseminated through healthcare professionals, RD associations, and social media, using "snowball" methodology and word-of-mouth references. Uruguay faces significant deficiencies in access to diagnosis and treatment for rare diseases, leading to a prolonged "diagnostic odyssey" for families and multiple barriers for physicians, ranging from lack of training to limited access to specialized tools. The low reporting rate to the National Registry of Congenital Defects and Rare Diseases and the lack of updates to the Comprehensive Health Care Plan exacerbate inequities in access to diagnosis and treatment. A key finding is inequality in access to whole-exome sequencing (WES), despite its proven effectiveness in reducing diagnostic times and improving accuracy. Its use remains restricted due to high costs and lack of universal coverage, highlighting the need for a national genomic medicine strategy and medical training in molecular diagnosis. The survey results indicate that RDs have a significant physical, emotional, and economic impact on patients and families. The main concerns raised include diagnostic delays, partly due to difficulties accessing specific tests and treatments. The medical community also acknowledges these issues. The healthcare system needs to update its coverage to include genomic diagnostics, improve medical training, strengthen coordination, and ensure equitable treatment access. These results mimic what is seen in other countries in Latin America and the Southern Cone. They call for a comprehensive, formalized framework for diagnosis, treatment, and care of rare diseases at local and regional levels, accounting for family experiences and prioritizing family wellbeing.

Heme is an essential molecule for most organisms, yet some parasites, like Trypanosoma cruzi, the causative agent of Chagas disease, cannot synthesize it. These parasites must acquire heme from their hosts, making this process critical for their survival. In the midgut of the insect vector, T. cruzi epimastigotes are exposed to both hemoglobin (Hb) and free heme resulting from its degradation. Despite the importance of this nutrient, how different heme sources influence parasite gene expression remains poorly understood.Here, we showed that heme restitution either as hemin or Hb to heme-starved parasites induces an early and distinct transcriptional response in T. cruzi epimastigotes. Using RNA sequencing at 4- and 24-hours post-supplementation, we identified gene subsets commonly or uniquely regulated by each heme source, including genes putatively linked to heme acquisition and metabolism. The study includes the first focused characterization of CRAL/TRIO domain-containing protein (TcCRAL/TRIO), a novel heme-responsive hemoprotein. Our results provide a more detailed picture of T. cruzi biology and highlights heme acquisition as a promising point of vulnerability to control parasite proliferation.

Abstract Quantile regression is one of the most important methods to estimate heterogeneous effects on a variable of interest. In many applications there is a subset of covariates of interest, while the rest operate as controls in the regression equation. This work presents a straightforward empirical strategy for situations in which the control variables have a homogeneous effect on the conditional distribution. We develop the asymptotic theory for the proposed estimator and the corresponding inference procedures. An application using environmental pollution data illustrates the method by estimating the Environmental Kuznets Curve.

Abstract Cortical states shape sensory processing, decision-making, and behavior, and are characterized by distinct patterns of neuronal oscillatory activity. Pharmacological agents can modulate these states and their underlying electrophysiological signatures. Modafinil is a widely used wake-promoting agent and cognitive enhancer, but its effects on cortical oscillations are not fully understood. In this study, we evaluated the effect of modafinil on cortical activity during wakefulness and subsequent sleep. Ten male Wistar rats were implanted with electrocorticographic electrodes and recorded following oral administration of modafinil or its vehicle. Our results show that modafinil increased wakefulness in a dose-dependent manner, with doses of 200 and 300 mg/kg producing prolonged wake episodes and reducing hypnogram complexity. During wakefulness, modafinil enhanced gamma-band power in anterior cortices, an effect primarily driven by increases in the aperiodic rather than oscillatory components. Although no sleep rebound was observed, subsequent NREM sleep exhibited increased delta power, particularly in anterior regions, indicating heightened sleep pressure. In conclusion, our findings demonstrate that modafinil-induced wakefulness is associated with an enhanced aperiodic gamma band component at the anterior cortices in the EEG. Furthermore, modafinil modulates sleep homeostasis by enhancing NREM sleep intensity rather than extending its duration.

ABSTRACT This paper analyzes the evolution of Latin American social protection systems during the inclusionary period from the beginning of the 2000s to the mid-2010s. Using microdata from household surveys across 17 countries, we build a traditional composite measure that provides a macro-level valuation of social protection (the Social Protection Aggregate Index, SPAI). We also propose an innovative index at the individual level (social protection deprivation index, SPDI) that measures deprivation in social protection using Alkire and Foster’s method. Both measures reveal significant improvements in social protection – through aggregate coverage and declines in individual deprivations – in all countries between 2002 and 2016. The change is mostly concentrated between 2002 and 2012. The most significant variations occurred in countries classified as intermediate in terms of social protection system development, whereas changes in countries from the least advantaged group were minimal. By providing quantitative comparative evidence through SPAI and SPDI, we contribute to improving our understanding of how aggregate-level changes in social protection affected individual experiences. They also provide a more nuanced assessment of how different groups of countries experienced the inclusionary period in such a heterogeneous region.