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Infection01:20

Infection

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When a pathogen enters the body and reproduces, it can cause an infection, damage body cells, and cause illness symptoms that eventually lead to disease. Therefore, its prevention requires breaking the chain of infection.
The chain begins with pathogens: bacteria, viruses, fungi, prions, or parasites such as protozoa helminths. These can be present on the skin as transient or resident flora, or they can be acquired from the environment. Identifying and treating the type of infection and...
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Urinary Tract Infection II: Pathophysiology01:25

Urinary Tract Infection II: Pathophysiology

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The pathophysiology of urinary tract infections (UTIs) encompasses several progressive stages, beginning with bacterial colonization and culminating in potential systemic complications if untreated. UTIs are primarily initiated by bacteria, such as Escherichia coli, which often originate from the gastrointestinal tract and migrate to the urinary system through the periurethral area. This migration can occur via several routes, including improper hygiene practices, sexual activity, or...
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Cystic Fibrosis: Pathogenesis01:23

Cystic Fibrosis: Pathogenesis

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Cystic fibrosis (CF), an autosomal recessive disorder, significantly affects the function of exocrine glands. This genetically inherited disease is characterized by the production of thick and sticky mucus, which can severely affect various organs and systems in the body.
CF is primarily caused by a genetic mutation in a chromosome 7 gene coding for the cystic fibrosis transmembrane conductance regulator (CFTR) protein. The most common gene mutation leading to CF is the ΔF508 mutation,...
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Pneumonia II: Pathophysiology01:29

Pneumonia II: Pathophysiology

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The pathophysiology of pneumonia involves the following steps:
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Stages of Infection01:26

Stages of Infection

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Stages of infection describe what happens to a susceptible host once a pathogen invades the human body. The stages of infection are incubation, prodromal, illness, stage of decline, and convalescence. The incubation stage is the period from exposure to a pathogen until symptoms start. The infected person is unaware of impending illness as the pathogens grow and multiply within the body. The duration may vary depending on the type of infection. The incubation period of measles averages ten to...
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Defense Against Bacterial Pathogens01:31

Defense Against Bacterial Pathogens

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The human immune system is a complex network of cells, tissues, and organs that work together to defend the body against bacterial infections. It consists of various immune cells, each playing a specific role in the defense mechanism.
Phagocytes
Phagocytes are the frontline soldiers of the immune system. They include neutrophils and macrophages. Neutrophils are the most abundant type of white blood cell and are quickly mobilized to the site of infection. Macrophages are larger cells that patrol...
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Video Experimental Relacionado

Updated: Jan 7, 2026

Mouse Footpad Inoculation Model to Study Viral-Induced Neuroinflammatory Responses
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Ciencia básica y patogénesis

Ricky Lali1, Shihong Mao2, Basilio Cieza3

  • 1Department of Pathology and Molecular Medicine, McMaster University, Hamilton, ON, Canada.

Alzheimer's & dementia : the journal of the Alzheimer's Association
|December 25, 2025
PubMed
Resumen
Este resumen es generado por máquina.

Este estudio presenta la primera puntuación de riesgo poligénico de variantes raras para la enfermedad de Alzheimer de inicio tardío (LOAD), demostrando su eficacia en la predicción del riesgo de LOAD en diversas poblaciones. La nueva puntuación, rvPRS-AD, utiliza variantes genéticas raras para mejorar la estratificación del riesgo.

Palabras clave:
enfermedad de Alzheimer de inicio tardíopuntuación de riesgo poligénico de variantes rarasrvPRS-ADpredicción del riesgo genéticoestratificación del riesgodiversidad poblacionalvariantes genéticas rarasABCA7APOEε4

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Área de la Ciencia:

  • Genética
  • Neurociencia
  • Biología Computacional

Sus antecedentes:

  • La enfermedad de Alzheimer de inicio tardío (LOAD) representa un desafío significativo para la salud mundial, y se proyecta que los casos se tripliquen para 2050.
  • Los factores genéticos contribuyen a más del 60% de la variación de LOAD, sin embargo, las puntuaciones de riesgo tradicionales que utilizan variantes comunes tienen un poder predictivo limitado en diversas poblaciones.
  • El potencial predictivo de las variantes dañinas raras en un marco poligénico para LOAD no se ha evaluado previamente.

Objetivo del estudio:

  • Desarrollar la primera puntuación de riesgo poligénico de variantes raras para LOAD (rvPRS-AD).
  • Evaluar el poder predictivo transancestral de rvPRS-AD.
  • Evaluar la independencia de rvPRS-AD de los predictores de variantes comunes y del estado de APOEε4.

Principales métodos:

  • Se desarrolló rvPRS-AD utilizando un método RV-EXCALIBER adaptado al genoma completo para pruebas de carga de variantes raras.
  • Se utilizaron casos europeos de LOAD y datos de control de gnomAD para identificar genes que confieren riesgo.
  • Se construyó rvPRS-AD en participantes hispanos ponderando la carga de variantes dañinas raras por gen.

Principales resultados:

  • Se identificó ABCA7 como el gen con la asociación más fuerte con LOAD (OR = 1.40, p=1×10⁻⁴).
  • rvPRS-AD mostró un poder predictivo transancestral significativo, aumentando las probabilidades de LOAD en un 38% en hispanos (aumento de 1 DE).
  • La puntuación se mantuvo predictiva independientemente del estado de APOEε4 e identificó a individuos con riesgo extremo (≥2 veces las probabilidades aumentadas).

Conclusiones:

  • rvPRS-AD es el primer instrumento genético que aprovecha las variantes raras en un marco poligénico para la predicción del riesgo de LOAD.
  • Este enfoque ofrece una predicción mejorada en poblaciones ancestralmente diversas.
  • rvPRS-AD proporciona una herramienta novedosa para la estratificación del riesgo de LOAD independientemente de las variantes comunes.