Orthopedics Hyperguide Review | Dr Hutaif General Ortho -...

I. Important facts concerning FGFR3 physiology and disorders
A. Gain in function mutation results in achondroplasia
1/. Point mutation
2/. Homogenous (single, constant amino acid change)
3/. Receptor is active even without ligand binding
4/. Autosomal dominant
B. Regulates cell growth, proliferation, and differentiation
C . Ligand binding results in phosphorylation of the tyrosine kinase domain
D. Activation of the receptor limits enchondral ossification
E. Deficiency of the receptor results in elongation of the vertebral column and long bones (knockout mice) Correct Answe Autosomal recessive inheritance

I. Important facts concerning FGFR3 physiology and disorders
A. Gain in function mutation results in achondroplasia
1/. Point mutation
2/. Homogenous (single, constant amino acid change)
3/. Receptor is active even without ligand binding
4/. Autosomal dominant
B. Regulates cell growth, proliferation, and differentiation
C . Ligand binding results in phosphorylation of the tyrosine kinase domain
D. Activation of the receptor limits enchondral ossification
E. Deficiency of the receptor results in elongation of the vertebral column and long bones (knockout mice) Correct Answe Receptor is active even without ligand binding

I. Important facts concerning FGFR3 physiology and disorders
A. Gain in function mutation results in achondroplasia
1/. Point mutation
2/. Homogenous (single, constant amino acid change)
3/. Receptor is active even without ligand binding
4/. Autosomal dominant
B. Regulates cell growth, proliferation, and differentiation
C . Ligand binding results in phosphorylation of the tyrosine kinase domain
D. Activation of the receptor limits enchondral ossification
E. Deficiency of the receptor results in elongation of the vertebral column and long bones (knockout mice) Correct Answe Gain of function mutation

I. Important facts concerning FGFR3 physiology and disorders
A. Gain in function mutation results in achondroplasia
1/. Point mutation
2/. Homogenous (single, constant amino acid change)
3/. Receptor is active even without ligand binding
4/. Autosomal dominant
B. Regulates cell growth, proliferation, and differentiation
C . Ligand binding results in phosphorylation of the tyrosine kinase domain
D. Activation of the receptor limits enchondral ossification
E. Deficiency of the receptor results in elongation of the vertebral column and long bones (knockout mice) Correct Answe Receptor activation enhances enchondral ossification

I. Important facts concerning FGFR3 physiology and disorders
A. Gain in function mutation results in achondroplasia
1/. Point mutation
2/. Homogenous (single, constant amino acid change)
3/. Receptor is active even without ligand binding
4/. Autosomal dominant
B. Regulates cell growth, proliferation, and differentiation
C . Ligand binding results in phosphorylation of the tyrosine kinase domain
D. Activation of the receptor limits enchondral ossification
E. Deficiency of the receptor results in elongation of the vertebral column and long bones (knockout mice) Correct Answe Loss in function mutations

II. Achondroplasia is the most homogeneous disorder in regard to the point mutation (single amino acid point mutation – arginine to glycine)
A. The defect is a gain in function of the FGFR3
B. FGFR3 regulates bone growth by limiting enchondral ossification
C . The phenotype of achondroplasia is:
1/. Varus knee deformity
2/. Spinal stenosis
3/. Atlantoaxial instability
C orrect Answer: Achondroplasia

Fibroblast growth factor receptor 3 regulates bone growth by limiting enchondral ossification. The other responses refer to:
C artilage oligomeric matrix protein (C OMP): C artilage cell proliferation and migration (through calcium-dependent proteoglycan binding)
Diastrophic dysplasia sulfate transporter gene (DTDST): Transport of sulfate into cells; needed for proteoglycan production
Fibrillin (FBN1): Formation of structural glycoprotein (fibrillin) for elastin-containing micro-fibrils
Neurofibromin (NF-1) - tumor suppressor gene to control cell growth and differentiation; negatively regulates the gene RAS
o RAS causes cell proliferation
C orrect Answer: Regulates bone growth by limiting enchondral ossification

The phenotype of achondroplasia includes: Varus knee deformity
Spinal stenosis
Atlantoaxial instability
The other responses:
Neurofibromatosis: C afé au lait spots, pseudoarthrosis of tibia and scoliosis C harcot-Marie-Tooth disease: C avovarus feet, areflexia, and distal motor wasting Duchenne muscular dystrophy: Proximal muscle weakness and calf hypertrophy Marfanâs syndrome: Dolichostenomelia and scoliosis
C orrect Answer: Knee varus and spinal stenosis

I. Important facts concerning fibroblast growth factor receptor 3 (FGFR3) physiology and disorders
A. Gain in function mutation results in achondroplasia
1/. Point mutation
2/. Homogenous (single, constant amino acid change)
3/. Receptor is active even without ligand binding
4/. Autosomal dominant
B. Regulates cell growth, proliferation, and differentiation
C . Ligand binding results in phosphorylation of the tyrosine kinase domain
D. Activation of the receptor limits enchondral ossification
E. Deficiency of the receptor results in elongation of the vertebral column and long bones (knockout mice) II. The other responses
A. Runx2 (C baf1) deficiency: C leidocranial dysplasia, absent clavicles
B. Diastrophic dysplasia sulfate transporter gene (DTDST): Transport of sulfate into cells; needed for proteoglycan production
C . Hoxd-13 deficiency: Defects in development and patterning limb, results in synpolydactyly
C orrect Answer: Increased vertebral height and long bone length

One should remember the important mutations that occur in musculoskeletal conditions: A. FGFR3 mutation: Achondroplasia
B. Type IX collagen mutation: Multiple epiphyseal dysplasia (MED)
C . WISP3 mutation: Spondyloepiphyseal dysplasia with progressive osteoarthropathy
D. Type II collagen mutation: Stickler syndrome
E. Sulfate transporter gene mutation: Diastrophic dysplasia
F. Fibrillin gene mutation: Marfanâs syndrome
G. Type V collagen mutation: Ehlers-Danlos syndrome
H. Type I collagen mutation: Osteogenesis imperfecta
C orrect Answer: Mutation in fibroblast growth factor receptor 3 gene

One should remember the important mutations that occur in musculoskeletal conditions: FGFR3 mutation: Achondroplasia
Type IX collagen mutation: Multiple epiphyseal dysplasia (MED)
WISP3 mutation: Spondyloepiphyseal dysplasia with progressive osteoarthropathy
Type II collagen mutation: Stickler syndrome
Sulfate transporter gene mutation: Diastrophic dysplasia
Fibrillin gene mutation: Marfanâs syndrome
Type V collagen mutation: Ehlers-Danlos syndrome
Type I collagen mutation: Osteogenesis imperfecta
C orrect Answer: Type V collagen mutation

One should remember the important mutations that occur in musculoskeletal conditions: FGFR3 mutation: Achondroplasia
Type IX collagen mutation: Multiple epiphyseal dysplasia (MED)
WISP3 mutation: Spondyloepiphyseal dysplasia with progressive osteoarthropathy
Type II collagen mutation: Stickler syndrome
Sulfate transporter gene mutation: Diastrophic dysplasia
Fibrillin gene mutation: Marfanâs syndrome
Type V collagen mutation: Ehlers-Danlos syndrome
Type I collagen mutation: Osteogenesis imperfecta
C orrect Answer: Sulfate transporter gene mutation

One should remember the important mutations that occur in musculoskeletal conditions: FGFR3 mutation: Achondroplasia
Type IX collagen mutation: Multiple epiphyseal dysplasia (MED)
WISP3 mutation: Spondyloepiphyseal dysplasia with progressive osteoarthropathy
Type II collagen mutation: Stickler syndrome
Sulfate transporter gene mutation: Diastrophic dysplasia
Fibrillin gene mutation: Marfanâs syndrome
Type V collagen mutation: Ehlers-Danlos syndrome
Type I collagen mutation: Osteogenesis imperfecta
C orrect Answer: WISP3 mutation

One should remember the important mutations that occur in musculoskeletal conditions: FGFR3 mutation: Achondroplasia
Type IX collagen mutation: Multiple epiphyseal dysplasia (MED)
WISP3 mutation: Spondyloepiphyseal dysplasia with progressive osteoarthropathy
Type II collagen mutation: Stickler syndrome
Sulfate transporter gene mutation: Diastrophic dysplasia
Fibrillin gene mutation: Marfanâs syndrome
Type V collagen mutation: Ehlers-Danlos syndrome
Type I collagen mutation: Osteogenesis imperfecta
C orrect Answer: Type II collagen mutation

One should remember the genetic findings in patients with osteoarthritis: Siblings have a 27% risk compared to spouses
Twice as common in monozygotic twins compared to dizygotic twins Precocious osteoarthritis is associated with type V collagen mutation Does not occur universally in aging hip joints
Distal interphalangeal joint arthritis linked to a region of chromosome 2q
C orrect Answer: Siblings have a 27% risk compared to spouses

There are a set of disorders with a sex-linked inheritance pattern that are most likely caused by a point mutation in the short stature homeobox gene. These disorders include:
Turnerâs syndrome
Langer mesomelic dysplasia
Leri-Weill dyschondrosteosis
The other responses refer to common disorders with well-documented genetic abnormalities:
Achondroplasia: FGFR3
Diastrophic dysplasia: DTDST (sulfate transporter gene) C leidocranial dysplasia: C BFA1
Multiple epiphyseal dysplasia: C OMP
C orrect Answer: Turnerâs syndrome

P63 is an important factor in normal limb outgrowth patterning. The other factors are involved with common disorders:
C BFA1: C leidocranial dysplasia
C OMP: Multiple epiphyseal dysplasia
C OL1A1: Osteogenesis imperfecta (easy to remember type I collagen) VDR3: Osteoporosis (easy to remember vitamin D receptor)
C orrect Answer: P63

A large prospective, randomized study showed a reduction in vertebral and nonvertebral fractures when patients were treated with intravenous (IV) zoledronic acid within 90 days of a hip fracture, followed up with annual treatment.
Important points to remember about this study:
Study: Zoledronic acid (5 mg, IV) within 90 days of hip fracture and then annually (1,000 patients in each group) New fractures: 8.6% vs 13.9% (absolute risk reduction, 5.3%; relative risk reduction, 35%)
New fractures
  o   Vertebral: 1.7% vs 3.8% (P = .02)
  o   Nonvertebral: 7.6% vs 10.7% (P = .03)
  o   Hip: 2.0% vs 3.5% (relative risk 30%, not significant)   o   Divergence of fracture-free survival at 12 months BMD
  o   12 month: 2.6% vs -1.0%   o   24 month: 4.7% vs -0.7%   o   36 month: 5.5% vs -0.9% Death
  o   Hazard ratio: -0.72 (0.56 to 0.93 C I, P = .01) Adverse advents
  o   Pyrexia: 8.7% vs 3.1%   o   Myalgia: 4.9% vs 2.7%
  o   Bone pain: 3.2% vs 1.0%
C orrect Answer: Reduction in vertebral and nonvertebral fractures

A large prospective, randomized study showed a reduction in vertebral and nonvertebral fractures when patients were treated with intravenous (IV) zoledronic acid within 90 days of a hip fracture, followed up with annual treatment.
Important points to remember about this study:
Study: Zoledronic acid (5 mg, IV) within 90 days of hip fracture and then annually (1,000 patients in each group) New fractures: 8.6% vs 13.9% (absolute risk reduction, 5.3%; relative risk reduction, 35%)
New fractures
  o   Vertebral: 1.7% vs 3.8% (P = .02)
  o   Nonvertebral: 7.6% vs 10.7% (P = .03)
  o   Hip: 2.0% vs 3.5% (relative risk 30%, not significant)   o   Divergence of fracture-free survival at 12 months BMD
  o   12 month: 2.6% vs -1.0%   o   24 month: 4.7% vs -0.7%   o   36 month: 5.5% vs -0.9% Death
  o   Hazard ratio: -0.72 (0.56 to 0.93 C I, P = .01) Adverse advents
  o   Pyrexia: 8.7% vs 3.1%   o   Myalgia: 4.9% vs 2.7%
  o   Bone pain: 3.2% vs 1.0%
C orrect Answer: Decrease in new fractures; survival advantage

A large prospective, randomized study showed a reduction in vertebral and nonvertebral fractures when patients were treated with intravenous (IV) zoledronic acid within 90 days of a hip fracture, followed up with annual treatment.
Important points to remember about this study:
Study: Zoledronic acid (5 mg, IV) within 90 days of hip fracture and then annually (1,000 patients in each group) New fractures: 8.6% vs 13.9% (absolute risk reduction, 5.3%; relative risk reduction, 35%)
New fractures
  o   Vertebral: 1.7% vs 3.8% (P = .02)
  o   Nonvertebral: 7.6% vs 10.7% (P = .03)
  o   Hip: 2.0% vs 3.5% (relative risk 30%, not significant)   o   Divergence of fracture-free survival at 12 months BMD
  o   12 month: 2.6% vs -1.0%   o   24 month: 4.7% vs -0.7%   o   36 month: 5.5% vs -0.9% Death
  o   Hazard ratio: -0.72 (0.56 to 0.93 C I, P = .01) Adverse advents
  o   Pyrexia: 8.7% vs 3.1%   o   Myalgia: 4.9% vs 2.7%
  o   Bone pain: 3.2% vs 1.0%
C orrect Answer: Decreased vertebral fractures, decreased nonvertebral fracture, and improved survival

A large prospective, randomized study showed a reduction in vertebral and nonvertebral fractures when patients were treated with intravenous (IV) zoledronic acid within 90 days of a hip fracture, followed up with annual treatment.
Important points to remember about this study:
Study: Zoledronic acid (5 mg, IV) within 90 days of hip fracture and then annually (1,000 patients in each group) New fractures: 8.6% vs 13.9% (absolute risk reduction, 5.3%; relative risk reduction, 35%)
New fractures
  o   Vertebral: 1.7% vs 3.8% (P = .02)
  o   Nonvertebral: 7.6% vs 10.7% (P = .03)
  o   Hip: 2.0% vs 3.5% (relative risk 30%, not significant)   o   Divergence of fracture-free survival at 12 months BMD
  o   12 month: 2.6% vs -1.0%   o   24 month: 4.7% vs -0.7%   o   36 month: 5.5% vs -0.9% Death
  o   Hazard ratio: -0.72 (0.56 to 0.93 C I, P = .01) Adverse advents
  o   Pyrexia: 8.7% vs 3.1%   o   Myalgia: 4.9% vs 2.7%
  o   Bone pain: 3.2% vs 1.0% Correct Answe Pyrexia and myalgia

This patient has a new fracture. Because the fracture occurred following minor trauma, the physician should assume that this patient has an insufficiency fracture related to her osteoporosis.
Patients who sustain an osteoporotic hip fracture should be treated with antiresorptive therapy to lower the risk of a subsequent hip or vertebral fracture. A recent randomized trial showed the following:
A large prospective, randomized study showed a reduction in vertebral and nonvertebral fractures when patients were treated with intravenous (IV) zoledronic acid within 90 days of a hip fracture, followed up with annual treatment.
Important points to remember about this study:
Study: Zoledronic acid (5 mg, IV) within 90 days of hip fracture and then annually (1,000 patients in each group) New fractures: 8.6% vs 13.9% (absolute risk reduction, 5.3%; relative risk reduction, 35%)
New fractures
  o   Vertebral: 1.7% vs 3.8% (P = .02)
  o   Nonvertebral: 7.6% vs 10.7% (P = .03)
  o   Hip: 2.0% vs 3.5% (relative risk 30%, not significant)   o   Divergence of fracture-free survival at 12 months
C orrect Answer: Antiresorptive therapy

Biocompatibility refers to materials that can be implanted into the body without causing major adverse reactions. Some materials, such as cobalt chromium alloys, are essentially inert; these materials cause no reaction from the body.
Other materials might be biocompatible, but they are not inert: Porous tantalum is a metal material that grows into bone.
Autologous chondrocytes are grown in vitro and then used as filler for cartilage defects.
Biodegradable polymeric scaffolds are resorbed and new tissues are laid down upon them.
C alcium sulfate pellets are quickly resorbed over a 4- to 6-week period and new bone formation occurs either completely or incompletely.
C orrect Answer: C obalt-chromium alloys

Ultra-high molecular weight polyethylene is inert in bulk form but may cause severe bone loss when found in a particulate form. Wear debris that is generated at a polyethylene metal articulation is ingested by macrophages and an inflammatory response is generated. Bone resorption often results with aseptic loosening of the involved component.
C orrect Answer: Ultra-high molecular weight polyethylene

Galvanic corrosion is caused by an electrochemical potential that is created between two metals that are located in a conductive environment, such as body fluids.
Examples of galvanic corrosion include: Screw heads and a plate
Femoral head screw and barrel of a dynamic hip screw
Interlocking screws and an intramedullary nail
Galvanic corrosion can also occur within a metal if there are impurities (intergranular corrosion).
The other responses refer to:
Fretting corrosion: Between the femoral head and tapered neck
C revice corrosion: Screw head and countersunk region of the acetabular component
Oxidative degradation: Delamination of high-density polyethylene
Oxidative degradation: Irradiation of high-density polytheylene in an ambient environment
C orrect Answer: At the interface between a plate and the screw heads

Fretting corrosion occurs when micromotion exists between two metals in contact. One of the most common examples of fretting corrosion is micromotion between a modular femoral head and the tapered neck junction. Modular components, such as the S- ROM system (DePuy Orthopaedics Inc., Warsaw, Ind), are subject to fretting corrosion at each of the junctions.
Techniques to minimize fretting corrosion include:
Making sure the head-neck junctions are dry and clean
Eliminating micromotion but having an exact fit (ie, not mixing manufacturers)
The other responses refer to:
Galvanic corrosion: Impurities within a metal implant C revice corrosion: At a surface defect of an implant Galvanic corrosion: At sites of electrochemical gradients
Oxidative degradation: Irradiation of high-density polyethylene in an ambient environment
C orrect Answer: Relative micromotion under load

C revice corrosion occurs at the sites of a surface defect in a metal implant. At these defects, changes in pH and electrolyte concentrations cause corrosion.
C ommon examples of crevice corrosion include:
At the interface between an uncemented acetabular component and the cancellous screws (at the contact point where the head of the screw is countersunk into the acetabular shell)
At the interface between a screw head and the plate at the point where the screw head contacts the plate
The other responses refer to:
Galvanic corrosion: Impurities within a metal implant Galvanic corrosion: At sites of electrochemical gradients Fretting corrosion: Relative micromotion under load
Oxidative degradation: Free-radical generation during air sterilization
C orrect Answer: Differences in oxygen tension causing pH and electrolyte changes

One of the most important examples of corrosion is the breakdown of ultra-high density polyethylene. Wear particles result in osteolysis and bone loss. When UHMWPE is sterilized in air, free radicals are generated and lead to oxidative degradation of the UHMWPE.
The other responses refer to:
Ram extrusion: Manufacturing method for UHMWPE C ompression molding: Manufacturing method for UHMWPE Direct molding: Manufacturing method for UHMWPE Sterilization with ethylene oxide: Alternative
C orrect Answer: Sterilization in an ambient environment

The following are features of stress fractures:
A. Stress fractures most often occur from changes in an athleteâs training program.
1/. Increases in intensity
2/. Increases in duration
B. In military recruits, the rates are gender dependent.
1/. Men â 4%
2/. Women â 7%
C . Stress fractures occur in normal bone subjected to abnormal stresses.
D. Stress fractures occur in sites of bone resorption subjected to continued loading.
E. Important to know is the definition of insufficiency fractures â fractures in abnormal bone from normal stresses. Correct Answe Stress fractures occur in normal bone subjected to normal stresses.

There are a number of risk factors for stress factors:
A. Menstrual irregularity in women is perhaps the most significant risk factor.
1/. Remember the terrible triad in female patients:
a. Menstrual irregularity b. Eating disorders
c. Low bone mass
B. Increase in frequency and intensity of athletic training or activity
C . C hanges in athletic training are noted in 80% of athletes surveyed who have stress fractures. D. Decreased tibial width (smaller bone size)
E. Factors that have not been found to be statistically significant include:
1/. Testosterone levels in male athletes
2/. Age
a. Location by age is significant, but not etiology
3/. Training surfaces
4/. Flexibility
5/. Low calcium intake
C orrect Answer: Menstrual irregularity

There are a number of risk factors for stress fractures:
A. Menstrual irregularity in women is perhaps the most significant risk factor.
1/. Remember the terrible triad in female patients:
a. Menstrual irregularity b. Eating disorders
c. Low bone mass
B. Increase in frequency and intensity of athletic training or activity
C . C hanges in athletic training are noted in 80% of athletes surveyed who have stress fractures. D. Decreased tibial width (smaller bone size)
E. Factors that have not been found to be statistically significant include:
1/. Testosterone levels in male athletes
2/. Age
a. Location by age is significant, but not etiology
3/. Training surfaces
4/. Flexibility
5/. Low calcium intake
C orrect Answer: Increase in frequency and intensity of training

Plain radiographs have a high false-negative rate especially early in the clinical course of stress fracture.
Periosteal new bone formation is a hallmark finding.
Only 20% of bone scan positive foci correlate with positive radiographs. Positive radiographic findings include horizontal or linear patterns of sclerosis.
The âgray cortexâ may occur from increased osteoclastic resorption on the cortex. Correct Answe Plain radiographs have a low false-negative rate.

In 1995, Fredrickson and colleagues classified stress fractures into four grades based upon bone scans:
Grade 1Â Â Â Â Â Small ill-defined cortical area of mildly increased activity
Grade 2     Well-defined cortical area of moderately increased cortical activity
Grade 3Â Â Â Â Â Wide, cortical-medullary area of increased activity
Grade 4Â Â Â Â Â Transcortical area of intensely increased activity
In an early stress fracture (grade 1 bone scan criteria), a periosteal high signal on T2-weighted images and a normal marrow signal are present.C orrect Answer: Periosteal high signal on T2; normal marrow signal on T1- and T2-weighted images

In 1995, Fredrickson and colleagues classified stress fractures into four grades based upon bone scans:
Grade 1     Small ill-defined cortical area of mildly increased activity Grade 2     Well-defined cortical area of moderately increased cortical                     activity
Grade 3Â Â Â Â Â Wide, cortical-medullary area of increased activity
Grade 4Â Â Â Â Â Transcortical area of intensely increased activity
In a grade 4 stress fracture, the corresponding MRI will show: High periosteal signal on T2-weighted images
Low signal on T1-weighted images, often with a liner low signal line representing the fracture line
High signal on T2-weighted images, often with a liner low signal line representing the fracture line
C orrect Answer: High periosteal signal on T2; low marrow signal on T1; high marrow signal on T2

In 1995, Fredrickson and colleagues classified stress fractures into four grades based upon bone scans:
Grade 1     Small ill-defined cortical area of mildly increased activity Grade 2     Well-defined cortical area of moderately increased cortical                     activity
Grade 3Â Â Â Â Â Wide, cortical-medullary area of increased activity
Grade 4Â Â Â Â Â Transcortical area of intensely increased activity
C orrect Answer: High periosteal signal; normal marrow T1 signal; high marrow T2 signal

The majority of stress fractures are treated with rest and protected weight-bearing. When the patient rests, strain on the affected bone is reduced and formation exceeds resorption, leading to bone healing.
Electrical stimulation and ultrasound have not been shown to increase the rate of healing. For most stress fractures, surgery is not necessary.
C orrect Answer: Rest and protected weight-bearing

The majority of stress fractures are treated with rest and protected weight-bearing. When the patient rests, strain on the affected bone is reduced and formation exceeds resorption, leading to bone healing.
A tension-sided femoral neck stress fracture is most at risk for progression to a complete fracture and displacement. Correct Answe Tension-sided femoral neck

The majority of stress fractures are treated with rest and protected weight-bearing. When the patient rests, strain on the affected bone is reduced and formation exceeds resorption, leading to bone healing.
An anterior tibial tension stress fracture is most prone to not healing. This fracture typically occurs in the anterior cortex and appears as a horizontal lucency â the dreaded black line.
Many patients with this fracture will not heal nonoperatively and will require intramedullary rod fixation. Correct Answe Anterior tibial cortex tension

Repetitive stresses from jumping or leaping is a risk factor for anterior tibial cortex stress fractures. C orrect Answer: Repetitive jumping or leaping

Important properties of articular cartilage include: Avascular (no blood vessels)
Aneural (no nerve fibers) Alymphatic (no lymphatic vessels)
Very low friction on cartilage on cartilage motion
Self-renewing (maintenance and restoration of extracellular matrix) With aging, loss of ability to maintain the extracellular matrix
C orrect Answer: Moderate friction on cartilage-on-cartilage motion
.v4b{border:2px solid #0984e3;background:#fff;color:#0984e3;padding:8px 20px;border-radius:25px;cursor:pointer;margin-right:10px;font-weight:bold;transition:0.3s;}
.v4b.active{background:#0984e3;color:#fff;}
.v4b:hover:not(.active){background:#e3f2fd;}
.mcq-v4-card{background:#fff;border-radius:15px;padding:35px;margin-bottom:40px;border:1px solid #e1e8ed;box-shadow:0 5px 15px rgba(0,0,0,0.04);}
.card-meta{color:#0984e3;font-weight:800;margin-bottom:20px;letter-spacing:1.5px;font-size:0.95rem;}
.q-stem{font-size:1.25rem;margin-bottom:30px;font-weight:500;line-height:1.7;color:#2d3436;}
.q-opt{display:flex;align-items:center;padding:15px;border:2px solid #f1f2f6;border-radius:12px;margin-bottom:15px;cursor:pointer;transition:all 0.2s ease-in-out;background:#fff;}
.q-opt:hover{border-color:#0984e3;background:#f0f7ff;transform:translateX(5px);}
.q-opt-circle{width:35px;height:35px;border:2px solid #ddd;border-radius:50%;display:flex;align-items:center;justify-content:center;margin-right:20px;font-weight:bold;background:#fafafa;flex-shrink:0;color:#636e72;}
.q-opt.correct{background:#e3fcef;border-color:#00b894;}
.q-opt.correct .q-opt-circle{background:#00b894;color:#fff;border-color:#00b894;}
.q-opt.wrong{background:#fff5f5;border-color:#ff7675;}
.q-opt.wrong .q-opt-circle{background:#ff7675;color:#fff;border-color:#ff7675;}
.q-opt.selected{border-color:#0984e3;background:#e3f2fd;}
.q-opt.selected .q-opt-circle{background:#0984e3;color:#fff;border-color:#0984e3;}
.q-feedback{margin-top:30px;padding:25px;background:#f8f9fa;border-left:6px solid #0984e3;border-radius:8px;}
.feedback-label{font-weight:bold;margin-bottom:15px;font-size:1.2rem;}
.explanation-text{line-height:1.7;color:#444;font-size:1.05rem;}

var v4E={
m:'study',r:new Map(),
setMode:function(m){this.m=m;document.getElementById('v4s').classList.toggle('active',m=='study');document.getElementById('v4e').classList.toggle('active',m=='exam');document.getElementById('v4xa').style.display=m=='exam'?'block':'none';this.reset();},
reset:function(){document.querySelectorAll('.q-opt').forEach(e=>{e.className='q-opt';e.style.pointerEvents='auto';});document.querySelectorAll('.q-feedback').forEach(e=>e.style.display='none');this.r.clear();this.up();},
up:function(){let s=0;this.r.forEach(v=>{if(v===true||v.s==v.c)s++;});const t=document.querySelectorAll('.mcq-v4-card').length;document.getElementById('v4sc').innerText=Math.round((s/t)*100)||0;},
reveal:function(c,s,k){const o=c.querySelectorAll('.q-opt');if(o[k-1])o[k-1].classList.add('correct');if(s!=k && o[s-1])o[s-1].classList.add('wrong');c.querySelector('.q-feedback').style.display='block';const fl=c.querySelector('.feedback-label');fl.innerHTML=s==k?' Correct Answer':' Incorrect';},
finish:function(){this.r.forEach((v,k)=>{this.reveal(document.getElementById('card-'+k),v.s,v.c);});document.querySelectorAll('.q-opt').forEach(e=>e.style.pointerEvents='none');window.scrollTo({top:0,behavior:'smooth'});}
};
document.querySelectorAll('.q-opt').forEach(el=>{
el.onclick=function(){
const q=this.dataset.q,k=this.dataset.correct,s=this.dataset.idx,p=this.closest('.mcq-v4-card');
if(v4E.m=='study') { if(v4E.r.has(q))return; v4E.r.set(q,s==k); p.querySelectorAll('.q-opt').forEach(o=>o.style.pointerEvents='none'); v4E.reveal(p,s,k); }
else { p.querySelectorAll('.q-opt').forEach(o=>o.classList.remove('selected')); this.classList.add('selected'); v4E.r.set(q,{s:s,c:k}); }
v4E.up();
};
});