Instituto Nicaragüense de Cultura

Identifying new genes responsible for non-syndromic hearing loss remains a critical goal, as many individuals with hereditary deafness still lack a molecular diagnosis despite comprehensive genetic testing. The tectorial membrane (TM) is a specialized, collagen-rich, acellular matrix of the inner ear, essential for stimulating mechanosensitive hair cell bundles during sound transduction, and its structural integrity is critical for frequency tuning and auditory sensitivity. Although mutations in genes encoding a number of non-collagenous proteins found in the TM (TECTA, CEACAM16, OTOG, OTOGL) have been identified as deafness genes, definitive evidence implicating β-tectorin (TECTB) in human hearing loss has been lacking.Here, we present multiple lines of genetic and experimental evidence linking a missense variant in TECTB (c.674G>A, p.Cys225Tyr) to autosomal dominant, non-syndromic hearing loss in a multigenerational family. The variant alters one of eight highly conserved cysteines present within the zona pellucida (ZP) domain of TECTB and is predicted to disrupt protein folding and matrix assembly. Using a Tectb-C225Y knock-in mouse model, we show that homozygous animals exhibit severe hearing loss and profound disruption of TM morphology, while heterozygote animals display decreased matrix content within the TM and increased susceptibility to noise-induced hearing loss—despite normal auditory thresholds.These findings identify TECTB as a novel human deafness gene, further elucidate its structural role in maintaining TM integrity, and highlight its contribution to resilience against environmental and age-related auditory decline.

Much of the world's population has been infected with SARS-CoV-2. Thus, immunity from prior infection will play a critical role in future SARS-CoV-2 transmission. We investigated the impact of infection-induced immunity on viral shedding duration and viral load. We conducted a household cohort study in Managua, Nicaragua, with an embedded transmission study that closely monitors participants regardless of symptoms. Real-time reverse-transcription polymerase chain reaction (RT-PCR) and enzyme-linked immunosorbent assays (ELISAs) were used to measure infections and seropositivity, respectively. Blood samples were collected twice annually and surrounding household intensive monitoring periods. We used accelerated failure time models to compare shedding times. Participants vaccinated ≥14 days prior to infection were excluded from primary analyses. There were 600 RT-PCR-confirmed SARS-CoV-2 infections in unvaccinated participants between May 1, 2020, and March 10, 2022, with prior ELISA data. Prior infection was associated with 48% shorter shedding times (event time ratio [ETR] 0.52, 95% CI: 0.39-0.69, mean shedding: 13.7 vs. 26.4days). A fourfold higher anti-SARS-CoV-2 spike titer was associated with 17% shorter shedding (ETR 0.83, 95% CI: 0.78-0.90). Similarly, maximum viral loads (lowest cycle threshold [CT]) were lower for previously infected individuals (mean CT 29.8 vs. 28.0, p = 4.02 × 10-3 ), for adults and children ≥10years, but not for children 0-9years; there was little difference in CT levels for previously infected versus naïve adults aged above 60 years. Prior infection-induced immunity was associated with shorter viral shedding and lower viral loads, which may be important in the transition from pandemic to endemicity.

During the last two decades, law firms from Central America and the Dominican Republic have quickly adapted to globalization in response to economic growth in the region and important increases in the rate of foreign investment. The leading solo practitioners and traditional family firms have adopted the business models and structures of the corporate law firms from the United States, so they can compete in the market for high-end corporate legal services in the region. Shareholders in stock corporations are replacing the partner figure of the limited liability civil or commercial partnerships. This chapter analyzes the evolution of the Central American law firms that serve the high-end corporate sector and how they have responded to the modernizing forces and the challenges facing the globalization of legal practice. This chapter is based on a variety of sources including leading industry reports, scholarly works, international databases and in-depth interviews with the managing partners and other members of the leading corporate law firms of Costa Rica, Dominican Republic, El Salvador, Guatemala, Honduras, Nicaragua and Panama.