Nondisjunction of chromosome 21 is the leading cause of Down syndrome. Two risk factors for maternal nondisjunction of chromosome 21 are increased maternal age and altered recombination.

A case–control study (also known as case–referent study) is a type of observational study in which two existing groups differing in outcome are identified and compared on the basis of some supposed causal attribute. Case–control studies are often used to identify factors that may contribute to a medical condition by comparing subjects who have that condition/disease (the cases) with patients who do not have the condition/disease but are otherwise similar (the controls).
An odds ratio (OR) is a statistic that quantifies the strength of the association between two events, A and B. The odds ratio is defined as the ratio of the odds of A in the presence of B and the odds of A in the absence of B or vice versa.

Hyperacute rejection appears in the first minutes following transplantation and occurs only in vascularized grafts. This very fast rejection is characterized by vessel thrombosis leading to graft necrosis. Hyperacute rejection is caused by the presence of antidonor antibodies existing in the recipient before transplantation. These antibodies induce both complement activation and stimulation of endothelial cells to secrete Von Willebrand procoagulant factor, resulting in platelet adhesion and aggregation. The result of these series of reactions is the generation of intravascular thrombosis leading to lesion formation and ultimately to graft loss. Today, this type of rejection is avoided in most cases by checking for ABO compatibility and by excluding the presence of antidonor human leukocyte antigen (HLA) antibodies by cross-match techniques between donor graft cells and recipient sera. This type of rejection is also observed in models of xenotransplantation of vascularized organs between phylogenetically distant species when no immunosuppressive treatment is given to the recipients.

Supravalvular aortic stenosis, is associated with a condition called William’s syndrome.
William’s syndrome is an inherited neurodevelopmental disorder caused by a microdeletion on chromosome 7. The most common symptoms of Williams syndrome are heart defects and unusual facial features. Other symptoms include failure to gain weight appropriately in infancy (failure to thrive) and low muscle tone. Individuals with Williams syndrome tend to have widely spaced teeth, a long philtrum, and a flattened nasal bridge.
Most individuals with Williams syndrome are highly verbal relative to their IQ, and are overly sociable, having what has been described as a cocktail party type personality.

The number needed to treat (NNT) is valuable information in treatment decisions. NNT is the inverse of the absolute risk reduction (1/ARR) between two treatment options. Control event rate = 10 / 50 = 0.2
Experimental event rate = 18 / 120 = 0.15

Absolute risk reduction = 0.2 – 0.15 = 0.05
Number needed to treat = 1 / 0.05 = 20

L4 dermatome distribution includes the kneecaps.

The type of significance test used depends on whether the data is parametric (can be measured, usually normally distributed) or non-parametric.
Parametric tests:
Student’s t-test – paired or unpaired*
Pearson’s product-moment coefficient – correlation

Non-parametric tests:
Mann-Whitney U test – unpaired data
Wilcoxon signed-rank test – compares two sets of observations on a single sample
chi-squared test – used to compare proportions or percentages
Spearman, Kendall rank – correlation.

The outcome measured is not normally distributed, i.e. it is non-parametric. This excludes the Student’s t-tests. We are not comparing percentages/proportions so the chi-squared test is excluded. The Mann–Whitney U test is a nonparametric test of the null hypothesis that it is equally likely that a randomly selected value from one sample will be less than or greater than a randomly selected value from a second sample.
This test can be used to investigate whether two independent samples were selected from populations having the same distribution.

An odds ratio (OR) is a measure of the association between an exposure and an outcome. The OR represents the odds that an outcome will occur given a particular exposure, compared to the odds of the outcome occurring in the absence of that exposure. Odds ratios are most commonly used in case-control studies, however they can also be used in cross-sectional and cohort study designs as well (with some modifications and/or assumptions). Where

a = Number of exposed cases

b = Number of exposed non-cases

c = Number of unexposed cases

d = Number of unexposed non-cases

OR=(a/c) / (b/d) = ad/bc

The most common cause of cervical radiculopathy is degenerative disease in the cervical spine. In 80–90% of patients with cervical radiculopathy, the C5/C6 or C6/C7 motion segments are affected by degenerative disease and the nearby C6 and/or C7 nerve roots are producing the symptoms. Patients with cervical radiculopathy complain of neck pain and radiating pain in the arm sometimes combined with sensory and motor disturbances in the arm and/or hand. These symptoms are accepted as being caused by the nerve root compression. Middle finger and palm of the hand are mostly rising the suspicion for C7 nerve root and median nerve involvement.

Depending on the level of SCI, patients experience paraplegia or tetraplegia. Paraplegia is defined as the impairment of sensory or motor function in lower extremities. Patients with incomplete paraplegia generally have a good prognosis in regaining locomotor ability (,76% of patients) within a year. Complete paraplegic patients, however, experience limited recovery of lower limb function if their NLI is above T9. The spinothalamic tract is the one responsible for sensory information such as pain or temperature. However, it decussates at the same level the nerve root enters the spinal cord, meaning that the sensory loss will be contralateral. However, the dorsal column carries sensory fibres for fine touch and vibration and it decussates at the medulla which means that the sensory loss will be ipsilateral. The corticospinal tract is responsible for motor functions and it decussates at the medulla, meaning that the motor function loss will be ipsilateral.

Rifampicin specifically inhibits bacterial RNA polymerase, the enzyme responsible for DNA transcription, by forming a stable drug-enzyme complex with a binding constant of 10(-9) M at 37 C.

In adults, the most common symptom of meningitis is a severe headache, occurring in almost 90% of cases of bacterial meningitis, followed by nuchal rigidity (the inability to flex the neck forward passively due to increased neck muscle tone and stiffness). Other signs commonly associated with meningitis include photophobia (intolerance to bright light) and phonophobia (intolerance to loud noises).
In the United Kingdom empirical treatment consists of a third-generation cefalosporin such as cefotaxime or ceftriaxone. In the USA, where resistance to cefalosporins is increasingly found in streptococci, addition of vancomycin to the initial treatment is recommended. Penicillins, cephalosporins, carbapenems and monobactams all act via inhibition of cell wall synthesis.

In statistical hypothesis testing there are 2 types of errors:
– type I: the null hypothesis is rejected when it is true – i.e. Showing a difference between two groups when it doesn’t exist, a false positive.
– type II: the null hypothesis is accepted when it is false – i.e. Failing to spot a difference when one really exists, a false negative.

Relative Risk = (Probability of event in exposed group) / (Probability of event in not exposed group). The relative risk is mistaken by some, with the odds ratio and absolute risk. Relative risk is the ratio of the probability of an event occurring with an exposure versus the probability of the event occurring without the exposure. Thus to calculate the relative risk, we must know the exposure status of all individuals (either exposed or not exposed). This implies that relative risk is only appropriate for cases where the exposure status and incidence of disease can be accurately determined such as prospective cohort studies.

Nitric oxide, known as an endothelium-derived relaxing factor (EDRF), is biosynthesized endogenously from L-arginine, oxygen, and NADPH by various nitric oxide synthase (NOS) enzymes and is a signaling molecule in many physiological and pathological processes in humans.
One of the main enzymatic targets of nitric oxide is guanylyl cyclase. The binding of nitric oxide to the haem region of the enzyme leads to activation, in the presence of iron.

Atrial natriuretic peptide (ANP) is a 28-amino acid peptide that is synthesized, stored, and released by atrial myocytes in response to atrial distension, angiotensin II stimulation, endothelin, and sympathetic stimulation (beta-adrenoceptor mediated). ANP is synthesized and secreted by cardiac muscle cells in the walls of the atria in the heart. The main physiological actions of natriuretic peptides is to reduce arterial pressure by decreasing blood volume and systemic vascular resistance. It causes a reduction in expanded extracellular fluid (ECF) volume by increasing renal sodium excretion.

Gaucher’s disease is characterized by hepatosplenomegaly, cytopenia, sometimes severe bone involvement and, in certain forms, neurological impairment. The variability in the clinical presentations of GD may be explained by the continuum of phenotypes. However, three major phenotypic presentations can usually be distinguished. Type-1 GD is usually named non-neuronopathic GD; type-2 and type-3 are termed neuronopathic-GD. Gaucher disease (GD, ORPHA355) is a rare, autosomal recessive genetic disorder. It is caused by a deficiency of the lysosomal enzyme, glucocerebrosidase, which leads to an accumulation of its substrate, glucosylceramide, in macrophages.

The human cell has two type of DNA: Nuclear DNA and Mitochondrial DNA (MtDNA). A MtDNA copy is passed down entirely unchanged, through the maternal line. Males cannot pass their MtDNA to their offspring although they inherit a copy of it from their mother. There is poor genotype:phenotype correlation. Within a tissue or cell there can be different mitochondrial populations (this is known as heteroplasmy).
Examples of mitochondrial diseases include:
– Leber’s optic atrophy
– MELAS syndrome (mitochondrial encephalomyopathy lactic acidosis and stroke-like episodes)
– MERRF syndrome (myoclonus epilepsy with ragged-red fibres)
– Kearns-Sayre syndrome (more severe syndromic variant of chronic progressive external ophthalmoplegia, onset in patients < 20 years old)

Riboflavin, vitamin B2, is a water-soluble and heat-stable vitamin that the body uses to metabolize fats, protein, and carbohydrates into glucose for energy. Riboflavin deficiency can cause fatigue, swollen throat, blurred vision, and depression. It can affect the skin by causing skin cracks, itching, and dermatitis around the mouth. Hyperaemia and oedema around throat, liver degeneration, and hair loss can also occur along with reproductive issues. Usually, people with riboflavin deficiency also have deficiencies of other nutrients. In most cases, riboflavin deficiency can be reversed unless it has caused anatomical changes such as cataracts.

Chloride channels are involved in a diverse set of functions in normal physiology and acquired diseases. Additionally, there are genetic diseases caused by mutations in chloride channels (channelopathies) — the most common being cystic fibrosis, which has a prevalence of 1 in 2,000 Caucasians.

Normal distribution, also known as the Gaussian distribution, is a probability distribution that is symmetric about the mean. The normal distribution has the following properties:
– It is symmetric around the mode, the median and the mean of the distribution.
– It is unimodal
– The area under the curve and over the x-axis is unity (i.e. equal to one).
– Its density has two inflection points.
– Its density is log-concave.
The standard deviation (SD) is a measure of how much dispersion exists from the mean. SD = square root (variance)

The major endocrine functions of adrenal gland are to produce catecholamines and steroids. Catecholamine, synthesized by the adrenal medulla, is responsible for blood pressure and blood flow regulation whereas steroids produced by the cortex control energy and water homeostasis and immune responses. Glucocorticoids, a major group of adrenal steroids, have a stimulatory effect on catecholamine synthesis in the medulla.

The human cell has two type of DNA: Nuclear DNA and Mitochondrial DNA (MtDNA). A MtDNA copy is passed down entirely unchanged, through the maternal line. Males cannot pass their MtDNA to their offspring although they inherit a copy of it from their mother. Mitochondrial inheritance therefore has the following characteristics:
– Inheritance is only via the maternal line
– All children of affected males will not inherit the disease
– All children of affected females will inherit it

Leptin, a 167–amino acid hormone, was discovered in 1994 and is secreted mainly by adipocytes. Plasma leptin levels are significantly correlated with body mass index (BMI) and the total amount of body fat.

The number needed to treat (NNT) is an absolute effect measure that has been used to assess beneficial and harmful effects of medical interventions. In this case the NNT can be calculated as follows: NNT = 1/ Absolute risk reduction (ARR). ARR=(Control event rate expressed per 1000 patient years) – (Experimental event rate expressed per 1000 patient years) = 43.9-37.3 = 6.6/1000 patient years

NNT=(Patient years)/ARR = 1000/ 6.6 = 151.5. The closest to 151.5 is 150, thus it is the correct answer.

Pneumococcal meningitis is the most common and severe form of bacterial meningitis. Fatality rates are substantial, and long-term sequelae develop in about half of survivors. Disease outcome has been related to the severity of the proinflammatory response in the subarachnoid space. The complement system, which mediates key inflammatory processes, has been implicated as a modulator of pneumococcal meningitis disease severity in animal studies. C5 fragment levels in cerebrospinal fluid (CSF) of patients with bacterial meningitis correlated with several clinical indicators of poor prognosis. The common terminal pathway consists of complement components C5–C9, and activation forms the anaphylatoxin C5a, a strong proinflammatory mediator, and the membrane attack complex (MAC), which creates pores in the bacterial cell wall (12). Deficiencies in these late complement components have been recognized as a cause of recurrent and familial meningococcal infections.

Transposition of the great arteries results in a significant hypoxemic status that is observed clinically by central cyanosis. The bluish discoloration of the skin and mucous membranes is therefore the basic pattern of clinical presentation in transposition. Its onset and severity depend on anatomical and functional variants that influence the degree of mixing between the two circulations. Limited intercirculatory mixing, usually present if the ventricular septum is intact or the atrial septal defect is restrictive, is related to progressive and profound central cyanosis evident within the first hours of life. Tachypnoea, tachycardia, diaphoresis, poor weight gain, a gallop rhythm, and eventually hepatomegaly can be then detected later on during infancy. Heart murmurs associated with left outflow tract obstruction, due to a persistent arterial duct or a septal defect may be heard, but they are not a constant finding.

Absolute risk reduction (ARR) – also called risk difference (RD) – is the most useful way of presenting research results to help your decision-making. Absolute risk reduction = (Control event rate) – (Experimental event rate) = 0.05 = 5% reduction

Acute, symptomatic hypocalcaemia is treated with 10ml of 10% calcium gluconate over 10 minutes.

Distal renal tubular acidosis is due to defective proton secretion from the alpha intercalated cells of the distal tubule caused by dysfunction of the H+/K+ antiporter on the apical membrane. This leads to failure of H+ excretion thereby causing systemic acidosis and potassium depletion. Inability to lower the urine pH below 5.3 in the presence of systemic acidosis is the diagnostic hallmark of type I or distal renal tubular acidosis. Hypercalciuria, hypocitraturia and elevated urinary pH observed in distal renal tubular acidosis can lead to nephrocalcinosis and may cause renal calculi, obstructive uropathy and renal failure necessitating surgical or endoscopic stone extraction.