USMLE | General Principles of Foundational Science

Biochemistry and molecular biology

• Gene expression: DNA structure, replication, exchange, and epigenetics (eg, imprinting, X-
• activation, DNA methylation) Gene expression: transcription
• Gene expression: translation, post-translational processing, modifications, and disposition of proteins (degradation), including protein/glycoprotein synthesis, intra-extracellular sorting, and processes/functions related to Golgi complex and rough endoplasmic reticulum
• Structure and function of proteins and enzymes (eg, enzyme kinetics and structural/regulatory proteins)
• Energy metabolism (eg, ATP generation, transport chain)

Biology of cells

• Adaptive cell responses and cellular homeostasis (eg, hypertrophy)
• Mechanisms of injury and necrosis, including pathologic processes (eg, liquefactive necrosis, free radical formation)
  • Apoptosis
• Cell cycle and cell cycle regulation (eg, mitosis) Mechanisms of dysregulation
  • cell biology of cancer (eg, role of p53, proto-oncogenes)
  • general principles of invasion and metastasis, including cancer staging
• Cell/tissue structure, regulation, and function, including cytoskeleton, organelles, glycolipids, channels, gap junctions, extracellular matrix, and receptors

Human development and genetics

• Principles of pedigree analysis
  • inheritance patterns
  • occurrence and recurrence risk determination
• Population genetics:  Hardy-Weinberg law, founder effects, mutation-selection equilibrium
• Principles of gene therapy
• Genetic testing and counseling
• Genetic mechanisms (eg, penetrance, genetic heterogeneity)

Biology of tissue response to disease

• Acute inflammatory responses (patterns of response)
  • acute inflammation and mediator systems (eg, histamine, prostaglandins, bradykinins, eosinophilic basic protein, nitric oxide)
  • vascular response to injury, including mediators
  • principles of cell adherence and migration (eg, ECAMs, selectins, leukocytic diapedesis, and rolling)
  • microbicidal mechanisms and tissue injury (eg, defensins)
  • clinical manifestations (eg, pain, fever, leukocytosis, leukemoid reaction, chills)
• Chronic inflammatory responses (eg, tumor necrosis factor)
• Reparative processes
  • wound healing, repair: thrombosis, granulation tissue, angiogenesis, fibrosis, scar/keloid formation
  • regenerative process

Pharmacodynamic and pharmacokinetic processes: general principles

• Pharmacokinetics: absorption, distribution, metabolism, excretion, dosage intervals Mechanisms of drug action, structure-activity relationships (eg, anticancer drugs)
• Concentration and dose-effect relationships (eg, efficacy, potency), types of agonists (eg, full, partial, inverse) and antagonists and their actions
• Individual factors altering pharmacokinetics and pharmacodynamics (eg, age, gender, disease, tolerance, compliance, body weight, metabolic proficiency, pharmacogenetics)
• Mechanisms of drug adverse effects, overdosage, toxicology
• Mechanisms of drug interactions
• Signal transduction, including structure/function of all components of signal transduction pathways such as receptors, ligands (eg, general principles of nitric oxide, autocrine and paracrine signaling)

Microbial biology

Microbial identification and classification, including principles, microorganism identification, and non-immunologic laboratory diagnosis

Bacteria

• • structure (eg, cell walls, composition, appendages, virulence factors, extracellular products, toxins, mechanism of action of toxins)
  • processes, replication, and genetics (eg, metabolism, growth, and regulation)
  • oncogenesis
  • antibacterial agents (eg, mechanisms of action on organism, toxicity to humans, and mechanisms of resistance)

Viruses

• • structure (eg, physical and chemical properties, virulence factors)
  • processes, replication, and genetics (eg, life cycles, location of virus in latent infection)
  • oncogenesis
  • antiviral agents (eg, mechanisms of action on virus, toxicity to humans, and mechanisms of resistance)

Fungi

• • structure (eg, cell wall, composition, appendages, virulence factors, extracellular products, toxins, mechanisms of action of toxins)
  • processes, replication, and genetics (eg, asexual vs. sexual, metabolism, growth)
  • antifungal agents (eg, mechanisms of action on fungus, toxicity to humans, and mechanisms of resistance)

Parasites

• • structure (eg, appendages, macroscopic features, and virulence factors) processes, replication, and genetics (eg, life cycles, metabolism, and growth) oncogenesis
  • antiparasitic agents (eg, mechanisms of action on parasite, toxicity to humans, and mechanisms of resistance)

Prions

Normal age-related findings and care of the well patient

Infancy and childhood (0-12 years)

Normal physical changes: linear growth, variations in linear growth, including constitutional delay; weight; head circumference; micturition, defecation, primary incontinence/bedwetting; normal physical examination; screening; sleep

Developmental stages: motor; speech; cognitive; psychosocial; anticipatory guidance

Lifestyle and routine preventive health care: nutrition; exercise (eg, benefits of exercise); preventive/travel medicine; risk factors and prevention (eg, guns, swimming, motor vehicles, car seats); routine vaccinations

Adolescence (13-17 years)

Normal physical changes: linear growth, variations in linear growth including constitutional delay; weight; puberty; normal physical examination; gynecomastia; autonomy/self-identity; sleep

Developmental stages: cognitive (eg, abstract thought); psychosocial (eg, autonomy, role confusion, sexual identity); anticipatory guidance

Lifestyle and routine preventive health care: nutrition; exercise (eg, benefits of exercise); preventive/travel medicine; risk factors and prevention (eg, risk-taking behavior, helmets, safe sex, motor vehicles, seat belts, distractions); routine vaccinations

Adulthood (18-64 years)

Normal physical changes: weight; normal physical examination; screening; sleep

Developmental stages: cognitive; intimacy vs isolation; anticipatory guidance

Lifestyle and routine preventive health care:  nutrition; exercise (eg, benefits of exercise); preventive/travel medicine; risk factors and prevention; routine vaccinations

Senescence (65 years and older)

Normal physical changes, including normal physical exam for age: weight, height (spinal compression), skin, bruising; normal physical examination; response to temperature; micturition, defecation; sleep

Developmental stages: motor; cognitive (eg, benign senescent forgetfulness); psychosocial; integrity vs despair; retrospection; anticipatory guidance

Lifestyle and routine preventive health care: nutrition; exercise (eg, benefits of exercise); preventive/travel medicine; risk factors and prevention (eg, falls, general medical condition; polypharmacy, driving, caregiver stress); routine vaccinations