The immunological changes in HIV include depletion in CD4+ T cell, cytokine dysregulation and immune dysfunction. The dominant immunologic feature of HIV infection is progressive depletion of the helper T cell (CD4+ T cell), which reverses the normal CD4:CD8 ratio and subsequently lead to immunodeficiency. Other imuunological changes include:
increased B2-microglobulin
decreased IL-2 production
polyclonal B-cell activation
decreased NK cell function
reduced delayed hypersensitivity responses

Achondroplasia is a common cause of dwarfism. It is caused by a mutation in fibroblast growth factor receptor 3 (FGFR3). In normal development FGFR3 has a negative regulatory effect on bone growth. In achondroplasia, the mutated form of the receptor is constitutively active and this leads to severely shortened bones. The effect is genetically dominant, with one mutant copy of the FGFR3 gene being sufficient to cause achondroplasia, while two copies of the mutant gene are invariably fatal. A person with achondroplasia thus has a 50% chance of passing dwarfism to each of their offspring. People with achondroplasia can be born to parents that do not have the condition due to spontaneous mutation. It occurs as a sporadic mutation in approximately 80% of cases (associated with advanced paternal age) or it may be inherited as an autosomal dominant genetic disorder.
People with achondroplasia have short stature, with an average adult height of 131 centimeters (52 inches) for males and 123 centimeters (48 inches) for females.

To describe how often a disease or another health event occurs in a population, different measures of disease frequency can be used. The prevalence reflects the number of existing cases of a disease. In contrast to the prevalence, the incidence reflects the number of new cases of disease and can be reported as a risk or as an incidence rate. Prevalence and incidence are used for different purposes and to answer different research questions.

Prostacyclin (PGI2) generated by the vascular wall is a potent vasodilator, and the most potent endogenous inhibitor of platelet aggregation so far discovered. Prostacyclin inhibits platelet aggregation by increasing cyclic AMP levels. Prostacyclin is a circulating hormone continually released by the lungs into the arterial circulation. Circulating platelets are, therefore, subjected constantly to prostacyclin stimulation and it is via this mechanism that platelet aggregability in vivo is controlled.

Myc is a family of regulator genes and proto-oncogenes that code for transcription factors.

A tumor suppressor gene, or antioncogene, is a gene that protects a cell from one step on the path to cancer. When this gene mutates to cause a loss or reduction in its function, the cell can progress to cancer, usually in combination with other genetic changes. Tumor suppressor genes can be grouped into categories including caretaker genes, gatekeeper genes, and landscaper genes; the classification schemes are continually evolving.
Examples include:
Gene Associated cancers
p53 Common to many cancers, Li-Fraumeni syndrome
APC Colorectal cancer
BRCA1 Breast and ovarian cancer
BRCA2 Breast and ovarian cancer
NF1 Neurofibromatosis
Rb Retinoblastoma
WT1 Wilm’s tumour

Northern blotting’s purpose is to measure the size and amount of RNA transcribed from a specific gene of interest.

The SEM is dependent on the variation in the population and the number of the extracted samples. A large variation in the population causes a large difference in the sample means, ultimately resulting in a larger SEM. However, as more samples are extracted from the population, the sample means move closer to the population mean, which results in a smaller SEM. In short, the SEM is an indicator of how close the sample mean is to the population mean. Standard error of the mean = standard deviation / square root (number of patients)
The standard error of the mean is calculated by the standard deviation / square root (number of patients)

= 12 / square root (64) = 12 / 8 = 1.5

A t test is a type of statistical test that is used to compare the means of two groups. It is one of the most widely used statistical hypothesis tests in pain studies. There are two types of statistical inferences: parametric and nonparametric methods. Parametric methods refer to a statistical technique in which one defines the probability distribution of probability variables and makes inferences about the parameters of the distribution. In cases in which the probability distribution cannot be defined, nonparametric methods are employed. T tests are a type of parametric method; they can be used when the samples satisfy the conditions of normality, equal variance, and independence. In this case the data is parametric, comparing two independent samples from the same population.

Specificity (negative in health)
The ability of a test to correctly classify an individual as disease- free is called the test′s specificity. [Table 2]

Specificity = d / b+d

= d (true negative) / b+d (true negative + false positive)

= Probability of being test negative when disease absent.

Example: One hundred persons with normal angles (diagnosed by ′gold standard′: gonioscopy) are examined by peripheral angle chamber depth examination. Eighty-five persons had normal peripheral angle chamber depth [Table 3]. The specificity of the peripheral angle chamber depth examination to PACG is therefore –

85 / 100 = 85%.

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)

Lysosomal hydrolases are synthesized in the rough endoplasmic reticulum and specifically transported through the Golgi apparatus to the trans-Golgi network, from which transport vesicles bud to deliver them to the endosomal/lysosomal compartment. The explanation of how the lysosomal enzymes are accurately recognized and selected over many other proteins in the trans-Golgi network relies on them being tagged with a unique marker: the mannose-6-phosphate (M6P) group, which is added exclusively to the N-linked oligosaccharides of lysosomal soluble hydrolases, as they pass through the cis-Golgi network. Generation of the M6P recognition marker depends on a reaction involving two different enzymes: UDP-N-acetylglucosamine 1-phosphotransferase and α-N-acetylglucosamine-1-phosphodiester α-N-acetylglucosaminidase.

Reverse transcription polymerase chain reaction is a laboratory technique combining reverse transcription of RNA into DNA and amplification of specific DNA targets using polymerase chain reaction. It is primarily used to measure the amount of a specific RNA. The main advantage of PCR is its sensitivity: only one strand of sample DNA is needed to detect a particular DNA sequence. It now has many uses including prenatal diagnosis, detection of mutated oncogenes and diagnosis of infections.

Molluscum contagiosum (MC), is a viral infection of the skin that results in small, raised, pink lesions with a dimple in the center with little to no surrounding erythema. They may occasionally be itchy or sore. They may occur singularly or in groups. Any area of the skin may be affected, with abdomen, legs, arms, neck, genital area, and face being most common. Onset of the lesions is around 7 weeks after infection. It usually goes away within a year without scarring.
Chickenpox lesions in the early stages may be mistaken for molluscum. However, the presence of associated macules and later vesicles and pustules help to differentiate them.

Meningiomas are the most common benign tumours of the brain. Their name is derived from the fact that they arise from the dura mater which together with the pia matter and arachnoid mater form the meninges. The chances that a meningioma is benign are almost 98%. They are non-invasive and well delineated, causing sign and symptoms of brain compression.

The human immunodeficiency virus (HIV) is grouped to the genus Lentivirus within the family of Retroviridae, subfamily Orthoretrovirinae. The HIV genome consists of two identical single-stranded RNA molecules that are enclosed within the core of the virus particle. The genome of the HIV provirus, also known as proviral DNA, is generated by the reverse transcription of the viral RNA genome into DNA, degradation of the RNA and integration of the double-stranded HIV DNA into the human genome.

Secretin is a peptide hormone produced in the S cells of the duodenum, which are located in the intestinal glands. In humans, the secretin peptide is encoded by the SCT gene.
Secretin helps regulate the pH of the duodenum by
1) inhibiting the secretion of gastric acid from the parietal cells of the stomach and
(2) stimulating the production of bicarbonate from the ductal cells of the pancreas.
G cells in the antrum of the stomach release gastrin
I cells in upper small intestine release CCK
D cells in the pancreas & stomach secrete somatostatin
K cells secrete gastric inhibitory peptide, an incretin, which also promotes triglyceride storage.

The walls of the ascending limb of the loop of Henle are not permeable to water. The tubular fluid thus becomes increasingly dilute as it ascends toward the cortex, whereas the interstitial fluid around the loops of Henle in the medulla becomes increasingly more concentrated.

The ascending limb actively reabsorbs NaCl but has an extremely low transepithelial osmotic water permeability, even in the presence of vasopressin. This combination of NaCl reabsorption without water reabsorption serves two vital functions: it provides NaCl to increase the osmolality of the medullary interstitium, tubules, vasculature, and collecting ducts; and it dilutes the luminal fluid within the thick ascending limb.

Hypocalcaemia occurs in patients with impaired function of the parathyroid glands. This is most common after thyroid or parathyroid surgery, but it can be idiopathic—mostly in young adults and less often as part of a genetic syndrome, such as autoimmune polyglandular syndrome type 1. Usually, the first and most useful test to perform in such cases is the measurement of the parathyroid hormone.

Burkitt lymphoma is a germinal centre B-cell-derived cancer that was instrumental in the identification of MYC as an important human oncogene more than three decades ago. Recently, new genomics technologies have uncovered several additional oncogenic mechanisms that cooperate with MYC to create this highly aggressive cancer.

NPV = TN / FN+TN

= TN (true negative) / FN+TN (false negative + true negative)

= Probability (patient not having disease when test is negative)

Troponin T is a 37 ku protein that binds to tropomyosin, thereby attaching the troponin complex to the thin filament.

The foramen rotundum is one of the several circular apertures (the foramina) located in the base of the skull, in the anterior and medial part of the sphenoid bone. The maxillary branch (V2) of the trigeminal nerve (CN V) passes through and exits the skull via the pterygopalatine fossa and the foramen rotundum.

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.

The SEM is an indicator of how close the sample mean is to the population mean. In reality, however, only one sample is extracted from the population. Therefore, the SEM is estimated using the standard deviation (SD) and a sample size (Estimated SEM). The SEM computed by a statistical program is an estimated value calculated via this process.

Estimated Standard Error of the Mean (SEM)=SDn√

Positive predictive value is the probability that subjects with a positive screening test truly have the disease.

Positive predictive value = true positive / ( true positive + false positive)

CD8+ T cells recognize antigens in the form of short peptide fragments bound to major histocompatibility complex class I (MHCI) molecules on the target cell surface.1 Specific engagement of peptide-MHCI (pMHCI) complexes via the clonotypically expressed αβ T-cell receptor (TCR) triggers a range of effector functions that play a critical role in protective immunity against intracellular infections and various malignancies.

Positive predictive value = TP (true positives) / [TP + FP (false positives)] = 40 / (40 + 20) = 0.66

When statistically comparing data sets, researchers estimate the population of each sample and examine them to see whether they are identical. The standard error of the mean (SEM) – not the standard deviation (SD), which represents the variation in the sample – is used to estimate the population mean. Via this process, researchers conclude that the sample used in their studies appropriately represents the population within the error range specified by the pre-set significance level.
The SEM is smaller than the SD, as the SEM is estimated usually with the SD divided by the square root of the sample size. For this reason, researchers are tempted to use the SEM when describing their samples. It is acceptable to use either the SEM or SD to compare two different groups if the sample sizes of the two groups are equal; however, the sample size must be stated in order to deliver accurate information. For example, when a population has a large amount of variation, the SD of an extracted sample from this population must be large. However, the SEM will be small if the sample size is deliberately increased.

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.

The Hyperlipidaemia Effect: Pseudohyponatremia in Pancreatic Cancer; Patients who have disorders of cholestasis commonly present with volume depletion due to vomiting and poor oral intake, which, in turn, often leads to hypovolemic hyponatremia. It is less well known that disorders of cholestasis, including tumours of the hepatobiliary system, can be accompanied by hyperlipidaemia.

Current guidelines recommend the use of ambrisentan, Bosentan (recommendation I, level of evidence A) and macitentan (I, B) in patients with PAH and WHO functional class II and III. In WHO functional class IV, the first-line drug is Epoprostenol and the recommendation for Endothelin receptor antagonists is weaker (IIb, C).

The Smooth endoplasmic reticulum (ER) is the major site at which membrane lipids are synthesized in eukaryotic cells. Because they are extremely hydrophobic, lipids are synthesized in association with already existing cellular membranes rather than in the aqueous environment of the cytosol. Although some lipids are synthesized in association with other membranes, most are synthesized in the ER. They are then transported from the ER to their ultimate destinations either in vesicles or by carrier proteins.

Cholecystokinin (CCK) was discovered in 1928 in jejunal extracts as a gallbladder contraction factor. It was later shown to be member of a peptide family, which are all ligands for the CCK1 and CCK2 receptors. CCK peptides are known to be synthetized in the small intestinal endocrine I-cells and cerebral neurons.

Delivery of ubiquitinated substrates to the proteasome.
Ubiquitinated proteins are delivered to the proteasome by various routes and the complete picture of how these pathways fit together has yet to emerge, reviewed in. Some substrates bind directly to the proteasome by interacting with the 19S regulatory particle subunits Rpn1028 or Rpn1329, and probably Rpt530. Alternatively, ubiquitinated substrates can be brought to the proteasome by adaptors that bind both the proteasome and the ubiquitin chain on the substrate to deliver it for degradation.

Relative Risk = (Probability of event in exposed group) / (Probability of event in not exposed group)
Experimental event rate, EER = 10 / 200 = 0.05

Control event rate, CER = 12 / 600 = 0.02

Therefore the relative risk = EER / CER = 0.05 / 0.02 = 2.5

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.

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.

1B: Individual Randomised Control Trial (with narrow confidence intervals)

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.

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

Soluble guanylyl cyclase (GC-1) is the primary receptor of nitric oxide (NO) in smooth muscle cells and maintains vascular function by inducing vasorelaxation in nearby blood vessels. GC-1 converts guanosine 5′-triphosphate (GTP) into cyclic guanosine 3′,5′-monophosphate (cGMP), which acts as a second messenger to improve blood flow.

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

The patient seems to be conscious about his decision, which should be respected. According to Mental Capacity Act 2005, a person who makes an unwise decision should not be treated as unable to make a decision.

The definition of negative predictive value is the probability that the individuals with truly negative screening test don’t have Chlamydia. The equation is the following: Negative predictive value = Truly negative/(truly negative + false negative) = 172 / (172 + 5) = 172 / 177

Interleukin-4 (IL-4), IL-5 and IL-13, the signature cytokines that are produced during type 2 immune responses, are critical for protective immunity against infections of extracellular parasites and are responsible for asthma and many other allergic inflammatory diseases. Although many immune cell types within the myeloid lineage compartment including basophils, eosinophils and mast cells are capable of producing at least one of these cytokines, the production of these “type 2 immune response-related” cytokines by lymphoid lineages, CD4 T helper 2 (Th2) cells and type 2 innate lymphoid cells (ILC2s) in particular, are the central events during type 2 immune responses.

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.

According to the updated GMC guidelines, patient safety is more important than anything else, thus the correct thing to do is inform your colleague’s employing body.

Beef liver is one of the best sources of folic acid, amongst others like green vegetables and nuts.

One of the questions the therapist poses himself while informing a patient is: whom shall I inform about the diagnosis, treatment and prognosis? If we unconditionally accepted the view that information belongs to the patient from an ethical and legal standpoint, we would automatically exclude the partner and the family. Therefore, the therapist should raise another question: what is the benefit to the patient? To answer the question and the resulting dilemma, we have to leverage the long experience of family therapy and tailor it to the cases we are dealing with. It should be taken into consideration that patient and family are a dynamic system which was balanced before the onset of the disease, but is now disrupted, entering into crisis. Therefore, the denial mechanisms and personality characteristics we have previously elaborated on, and communication among members play a crucial role in determining the information strategy and the way family should be approached. In this particular case, the most appropriate person to inform the patient is the consultant, meaning the one currently responsible for the patient’s care. The patient most probably has already developed some form of close and trustful relationship with his consultant.

Fc Receptors include the IgG receptors (FcγR), high-affinity IgE receptor (FcεRI), IgA and IgA/IgM receptors, and neonatal Fc receptor for IgG (FcRn). In particular, the FcγRs have been well known to play an important role in many biologic processes including those associated with the response to infection and cancer as well as in the pathogenesis of immune-mediated diseases. Fc receptors, the receptors for the Fc region of immunoglobulins, play an essential role in antibody-dependent immune responses. Fc receptors are detected on many types of hematopoietic cells including macrophages, neutrophils, dendritic cells, eosinophils, basophils, mast cells, and NK cells. Plasma cells produce five classes of antibodies, IgA, IgD, IgE, IgG and IgM. Fc receptors with an Ig superfamily related structure exist that correspond to each of these classes of immunoglobulins.

Interleukin 1 alpha and interleukin 1 beta (IL1 alpha and IL1 beta) are cytokines that participate in the regulation of immune responses, inflammatory reactions, and hematopoiesis. It is secreted mainly by macrophages and monocytes and acts as a costimulator of T cell and B cell proliferation.

Adverse effects due to IFN-alpha have been described in almost every organ system. Many side-effects are clearly dose-dependent. Taken together, occurrence of flu-like symptoms, haematological toxicity, elevated transaminases, nausea, fatigue, and psychiatric sequelae are the most frequently encountered side effects.

Nerve conduction velocity is an important aspect of nerve conduction studies. It is the speed at which an electrochemical impulse propagates down a neural pathway. Ultimately, conduction velocities are specific to each individual and depend largely on an axon’s diameter and the degree to which that axon is myelinated.
The cardiac action potential is a brief change in voltage (membrane potential) across the cell membrane of heart cells. Conduction speed varies:
Atrial conduction spreads along ordinary atrial myocardial fibres at 1 m/sec
AV node conduction 0.05 m/sec
Ventricular conduction Purkinje fibres are of large diameter and achieve velocities of 2-4 m/sec (this allows a rapid and coordinated contraction of the ventricles.

Dopamine (DA) holds a predominant role in the regulation of prolactin (PRL) secretion. Through a direct effect on anterior pituitary lactotrophs, DA inhibits the basally high-secretory tone of the cell. It accomplishes this by binding to D2 receptors expressed on the cell membrane of the lactotroph, activation of which results in a reduction of PRL exocytosis and gene expression by a variety of intracellular signalling mechanisms.

People aged 16 or over are entitled to consent to their own treatment. This can only be overruled in exceptional circumstances. Children under the age of 16 can consent to their own treatment if they’re believed to have enough intelligence, competence and understanding to fully appreciate what’s involved in their treatment. This is known as being Gillick competent.

Otherwise, someone with parental responsibility can consent for them.
This could be:
the child’s mother or father
the child’s legally appointed guardian
a person with a residence order concerning the child
a local authority designated to care for the child
a local authority or person with an emergency protection order for the child.
Giving the blood transfusion is therefore both clinically and ethically the right course of action.
Jehovah’s Witnesses frequently carry a signed and witnessed Advance Decision Document listing the blood products and autologous procedures that are, or are not, acceptable to them It is appropriate to have a frank, confidential discussion with the patient about the potential risks of their decision and the possible alternatives to transfusion, but the freely expressed wish of a competent adult must always be respected.

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

PCR is a simple, yet elegant, enzymatic assay, which allows for the amplification of a specific DNA fragment from a complex pool of DNA. PCR can be performed using source DNA from a variety of tissues and organisms, including peripheral blood, skin, hair, saliva, and microbes. Only trace amounts of DNA are needed for PCR to generate enough copies to be analysed using conventional laboratory methods. For this reason, PCR is a sensitive assay. Each PCR assay requires the presence of template DNA, primers, nucleotides, and DNA polymerase. The DNA polymerase is the key enzyme that links individual nucleotides together to form the PCR product. The above mentioned components are mixed in a test tube or 96-well plate and then placed in a machine that allows repeated cycles of DNA amplification to occur in three basic steps. The machine is essentially a thermal cycler. It has a thermal block with holes, into which the test tubes or plates holding the PCR reaction mixture are inserted. The machine raises and lowers the temperature of the block in discrete, precise and pre-programmed steps. The reaction solution is first heated above the melting point of the two complementary DNA strands of the target DNA, which allows the strands to separate, a process called denaturation. The temperature is then lowered to allow the specific primers to bind to the target DNA segments, a process known as hybridization or annealing. Annealing between primers and the target DNA occurs only if they are complementary in sequence (e.g. A binding to G). The temperature is raised again, at which time the DNA polymerase is able to extend the primers by adding nucleotides to the developing DNA strand. With each repetition of these three steps, the number of copied DNA molecules doubles.

Left ventricular ejection fraction = (stroke volume / end diastolic LV volume ) * 100%

Stroke volume = end diastolic LV volume – end systolic LV volume

Pulse pressure = Systolic Pressure – Diastolic Pressure

Polymerase chain reaction (PCR) is a method widely used in molecular biology to make several copies of a specific DNA segment. Using PCR, copies of DNA sequences are exponentially amplified to generate thousands to millions of more copies of that particular DNA segment.The main advantage of PCR is its sensitivity: only one strand of sample DNA is needed to detect a particular DNA sequence. It now has many uses including prenatal diagnosis, detection of mutated oncogenes and diagnosis of infections. PCR is also extensively used in forensics.

Vasopressin, also called antidiuretic hormone (ADH), regulates the tonicity of body fluids. It is released from the posterior pituitary in response to hypertonicity and promotes water reabsorption in the collecting ducts of the kidneys by the insertion of aquaporin-2 channels.. An incidental consequence of this renal reabsorption of water is concentrated urine and reduced urine volume. In high concentrations may also raise blood pressure by inducing moderate vasoconstriction.

Intestinal phosphate absorption is mediated by both transcellular and paracellular routes. The 1,25(OH)2D increases intestinal transcellular phosphate absorption at least in part by enhancing expression of type 2b sodium–phosphate cotransporter, thus increasing plasma phosphate.

Central chemoreception refers to the detection of changes in CO2/H+ within the brain and the associated effects on breathing. In the conscious animal the response of ventilation to changes in the brain’s interstitial fluid (ISF) pH is very sensitive. Note that a small change in cerebrospinal fluid (CSF) pH from 7.30 to 7.25 is associated with a doubling of alveolar ventilation; it is a very sensitive reflex response. Note also that the relationship of alveolar ventilation to ISF pH is essentially the same for both types of stimulation, metabolic acid-base disorders and primary CO2 stimulation.

Patients with compressive neuropathy of the ulnar nerve typically describe numbness and tingling of the ulnar-sided digits of the hand, classically in the small finger and ulnar aspect of the ring finger. Among the general population, symptoms usually begin intermittently and are often worse at night, particularly if the elbow is flexed while sleeping. As the disease progresses, paraesthesia may occur more frequently and during the daytime.

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.

Refeeding syndrome can be defined as the potentially fatal shifts in fluids and electrolytes that may occur in malnourished patients receiving artificial refeeding (whether enterally or parenterally). These shifts result from hormonal and metabolic changes and may cause serious clinical complications. The hallmark biochemical feature of refeeding syndrome is hypophosphatemia. However, the syndrome is complex and may also feature abnormal sodium and fluid balance; changes in glucose, protein, and fat metabolism; thiamine deficiency; hypokalaemia; and hypomagnesaemia.

Dermatitis herpetiformis (DH), or Duhring’s disease, is a chronic blistering skin condition,characterised by blisters filled with a watery fluid. Despite its name, it is neither related to nor caused by herpes virus: the name means that it is a skin inflammation having an appearance similar to herpes.
Dermatitis herpetiformis is characterized by intensely itchy, chronic papulovesicular eruptions, usually distributed symmetrically on extensor surfaces (buttocks, back of neck, scalp, elbows, knees, back, hairline, groin, or face)
Dermatitis herpetiformis is an autoimmune condition associated with HLA-DR3.
HLA-A3 is associated with haemochromatosis. HLA-B5 is most commonly associated with Behcet’s disease. HLA-DR4 is associated with both type 1 diabetes mellitus and rheumatoid arthritis. HLA-B27 is most commonly associated with several diseases, most commonly ankylosing spondylitis.

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.

The hazard ratio describes the relative risk of the complication based on comparison of event rates.

Hazard ratios have also been used to describe the outcome of therapeutic trials where the question is to what extent treatment can shorten the duration of the illness. However, the hazard ratio, a type of relative risk, does not always accurately portray the degree of abbreviation of the illness that occurred. In these circumstances, time-based parameters available from the time-to-event curve, such as the ratio of the median times of the placebo and drug groups, should be used to describe the magnitude of the benefit to the patient. The difference between hazard-based and time-based measures is analogous to the odds of winning a race and the margin of victory. The hazard ratio is the odds of a patient’s healing faster under treatment but does not convey any information about how much faster this event may occur.

L4 dermatome distribution includes the kneecaps.

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.

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.

When the aim of the randomized controlled trial (RCT) is to show that one treatment is superior to another, a statistical test is employed and the trial (test) is called a superiority trial (test).

Erythromycin is a bacteriostatic antibiotic. This means it stops the further growth of bacteria rather than directly destroying it. This is achieved by inhibiting protein synthesis. Erythromycin binds to the 23S ribosomal RNA molecule in the 50S subunit of the bacterial ribosome. This causes a blockage in the exiting of the peptide chain that is growing. Given that humans have 40S and 60S subunits, and do not have 50S subunits, erythromycin does not affect protein synthesis in human tissues.

This man has gingivostomatitis, a characteristic feature of primary herpes simplex virus infection. Herpetic gingivostomatitis is often the initial presentation during the first (primary) herpes simplex infection. It is of greater severity than herpes labialis (cold sores) which is often the subsequent presentations. Primary herpetic gingivostomatitis is the most common viral infection of the mouth.
Primary herpetic gingivostomatitis (PHGS) is caused predominantly by HSV-1 and affects mainly children. Prodromal symptoms, such as fever, anorexia, irritability, malaise and headache, may occur in advance of disease. Sub-mandibular lymphadenitis, halitosis and refusal to drink are usual concomitant findings.

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

NICE guidelines on hypercalcemia recommend that maintaining good hydration equals drinking 3-4 L of fluid/day, provided there are no contraindications. A low calcium diet is not necessary because intestinal absorption of calcium is reduced. The patient should avoid any other drugs or vitamins that could worsen the hypercalcemia. Mobilization is encouraged and any symptoms of hypercalcemia should be reported.

The somatostatin-secreting D-cells comprise ,5% of the cells of the pancreatic islets. The D-cells have a complex morphology and may, via cellular process, interact with many more islet cells than suggested by their low number. D-cells are equipped with ATP-sensitive potassium channels (KATP channels).

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.

This woman is receiving methotrexate, an immunosuppressant, to control her rheumatoid arthritis. In such immunocompromised patients, BNF suggests clarithromycin as first-line management.

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.

DIAGNOSIS:
A consensus definition for hemodynamically significant PDA is lacking. The diagnosis is often suspected clinically, when an infant demonstrates signs of excessive shunting from the arterial to pulmonary circulation. Continuous or a systolic murmur; note, a “silent” PDA may also occur when the ductus shunt is large enough that nonturbulent flow fails to generate a detectible murmur.
A low diastolic blood pressure (due to runoff into the ductus during diastole, more frequent in the most premature infants).
A wide pulse pressure (due to ductus runoff or steal)Hypotension (especially in the most premature infants)
Bounding pulses
Increased serum creatinine concentration or oliguria
Hepatomegaly

Over consumption of fluids, prolonged race duration and inadequate training all can predispose to acute hyponatraemia.
Mild symptoms include a decreased ability to think, headaches, nausea, and an increased risk of falls. Severe symptoms include confusion, seizures, and coma. Normal serum sodium levels are 135 – 145 mEq/liter (135 – 145 mmol/L). Hyponatremia is generally defined as a serum sodium level of less than 135 mEq/L and is considered severe when the level is below 120 mEq/L.
The correct treatment to give is hypertonic saline. Decompressive craniotomy would help alleviate raised intracranial pressure due to cerebral oedema however is not an appropriate first line treatment. Demeclocycline is used for SIADH and mannitol is more likely to be used in the context of traumatic brain injury.
Hyponatremia is corrected slowly, to lessen the risk of the development of central pontine myelinolysis (CPM), a severe neurological disease involving a breakdown of the myelin sheaths covering parts of nerve cells. During treatment of hyponatremia, the serum sodium (salt level in the blood) should not rise by more than 8 mmol/L over 24 hours.

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.

Primary rubella infection during pregnancy, particularly during the first trimester, can affect several organs and cause birth defects that are responsible for congenital rubella syndrome (CRS). The most common defects of CRS are hearing impairment (unilateral or bilateral sensorineural), eye defects (e.g., cataracts, congenital glaucoma, or pigmentary retinopathy), and cardiac defects (e.g., patent ductus arteriosus or peripheral pulmonic stenosis). Congenital hearing loss is the most common sequela, occurring in approximately 60% of cases, especially when infection occurs in the 4th month of pregnancy.

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.

A case-control study is designed to help determine if an exposure is associated with an outcome (i.e., disease or condition of interest). In theory, the case-control study can be described simply. Case-control studies have specific advantages compared to other study designs. They are comparatively quick, inexpensive, and easy. They are particularly appropriate for (1) investigating outbreaks, and (2) studying rare diseases or outcomes. Sudden infant death syndrome is a rare medical event, thus case-control study is the most suitable option.

Absolute risk reduction (ARR) – also called risk difference (RD) – is the most useful way of presenting research results to help your decision-making. In this example, the ARR is 8 per cent (20 per cent – 12 per cent = 8 per cent). This means that, if 100 children were treated, 8 would be prevented from developing bad outcomes. Another way of expressing this is the number needed to treat (NNT). If 8 children out of 100 benefit from treatment, the NNT for one child to benefit is about 13 (100 ÷ 8 = 12.5). CER = 20 / 400 = 1 / 20 = 0.05, EER = 10 / 400 = 0.025, ARR =CER – EER = 0.025

This patient has a poorly controlled T2DM with an underlying diabetic nephropathy. The histological findings are Kimmelstiel-Wilson lesions (nodular glomerulosclerosis) and hyaline arteriosclerosis. This is due to nonenzymatic glycosylation.

Diabetic nephropathy is the chronic loss of kidney function occurring in those with diabetes mellitus. Protein loss in the urine due to damage to the glomeruli may become massive, and cause a low serum albumin with resulting generalized body swelling (edema) and result in the nephrotic syndrome. Likewise, the estimated glomerular filtration rate (eGFR) may progressively fall from a normal of over 90 ml/min/1.73m2 to less than 15, at which point the patient is said to have end-stage kidney disease (ESKD). It usually is slowly progressive over years.

Chvostek and Trousseau signs can be elicited in patients with hypocalcaemia. Chvostek sign is the twitching of the upper lip with tapping on the cheek 2 cm anterior to the earlobe, below the zygomatic process overlying the facial nerve. Trousseau sign (a more reliable sign present in 94% of hypokalaemic individuals and only 1% to 4% of healthy people) is the presence of carpopedal spasm observed following application of an inflated blood pressure cuff over systolic pressure for 3 minutes in hypokalaemic patients.

The incidence rate is the number of new cases per population at risk in a given time period. For example, if a population initially contains 1,000 non-diseased persons and 28 develop a condition over two years of observation, the incidence proportion is 28 cases per 1,000 persons per two years, i.e. 2.8% per two years.
Prevalence is the proportion of a particular population found to be affected by a medical condition (typically a disease or a risk factor such as smoking or seat-belt use). It is derived by comparing the number of people found to have the condition with the total number of people studied, and is usually expressed as a fraction, as a percentage, or as the number of cases per 10,000 or 100,000 people.
Incidence should not be confused with prevalence, which is the proportion of cases in the population at a given time rather than rate of occurrence of new cases. Thus, incidence conveys information about the risk of contracting the disease, whereas prevalence indicates how widespread the disease is.

Hypovitaminosis B1, consistent with dry beriberi is crucially a treatable condition, although sometimes with incomplete recovery, but it is probably under-recognized yet increasingly common given increasing levels of alcohol abuse in the western world. Dry beriberi or ‘acute nutritional polyneuropathy’ is considered to be rare in the western world. Rapid deterioration can occur, typically with weakness, paraesthesia and neuropathic pain. Striking motor nerve involvement can occur, mimicking Guillain-Barré syndrome (GBS). In the context of increasing alcohol abuse in the western world, it is possible that alcoholic neuropathy associated with abrupt deterioration due to concomitant nutritional hypovitaminosis B1 may be seen increasingly often.

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.

Myasthenia gravis (MG) is an organ-specific autoimmune disease caused by an antibody-mediated assault on the muscle nicotinic acetylcholine receptor (AChR) at the neuromuscular junction. Binding of antibodies to the AChR leads to loss of functional AChRs and impairs the neuromuscular signal transmission, resulting in muscular weakness.

The CD15 antigen, also known as Lewis (hapten)X, serves as an immuno-phenotypic marker for Reed-Sternberg cells and its expression has diagnostic, but also prognostic significance in Hodgkin Lymphoma.

A t test is a type of statistical test that is used to compare the means of two groups. It is one of the most widely used statistical hypothesis tests in pain studies. There are two types of statistical inferences: parametric and nonparametric methods. Parametric methods refer to a statistical technique in which one defines the probability distribution of probability variables and makes inferences about the parameters of the distribution. In cases in which the probability distribution cannot be defined, nonparametric methods are employed. T tests are a type of parametric method; they can be used when the samples satisfy the conditions of normality, equal variance, and independence. In this case the data is parametric, and they belong to the same patients, so a paired t test should be used.

Normal distribution describes the spread of many biological and clinical measurements. Usually, 68.3% lies within 1 standard deviation (SD) of the mean, 95.4% lies within 2 SD of the mean and 99.7% lies within 3 SD of the mean.

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.

Hypogammaglobulinemia occurs due to a variety of underlying primary or secondary immunodeficient states, including HIV which is suspected in this case. The most commonly recognised clinical feature is recurrent infection.

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.

Funnel plots are graphical tools to assess and compare clinical performance of a group of care professionals or care institutions on a quality indicator against a benchmark. Incorrect construction of funnel plots may lead to erroneous assessment and incorrect decisions potentially with severe consequences.

Vincristine is part of the antimitotic agents, cell cycle specific (M phase). It binds to microtubules in the spindle apparatus and prevents their proper function, finally arresting mitosis.

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.

Steps required in performing the Wilcoxon signed rank test:

1 State the null hypothesis and, in particular, the hypothesized value for comparison
2 Rank all observations in increasing order of magnitude, ignoring their sign. Ignore any observations that are equal to the hypothesized value. If two observations have the same magnitude, regardless of sign, then they are given an average ranking
3 Allocate a sign (+ or -) to each observation according to whether it is greater or less than the hypothesized value (as in the sign test)
4 Calculate:
R+ = sum of all positive ranks
R- = sum of all negative ranks
R = smaller of R+ and R-
5 Calculate an appropriate P value What makes this test the most appropriate for this study is that the data is non-parametric, paired and comes from the same population.

Inherited metabolic disorders are often characterized by the lack of an essential enzyme and are currently treated by dietary restriction and other strategies to replace the substrates or products of the missing enzyme. Patients with homocystinuria lack the enzyme cystathionine β-synthase (CBS), and many of these individuals do not respond to current treatment protocols.

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.

Escherichia coli (also known as E. coli) is a gram-negative, facultatively anaerobic, rod-shaped bacterium commonly found in the lower intestine of warm-blooded organisms. Most E. coli strains are harmless, but some serotypes can cause serious food poisoning in their hosts, and are occasionally responsible for product recalls due to food contamination. The harmless strains are part of the normal flora of the gut, and can benefit their hosts by producing vitamin K2, and preventing colonization of the intestine with pathogenic bacteria. Virulent strains can cause gastroenteritis, urinary tract infections, and neonatal meningitis.
The most common causes of neonatal meningitis is bacterial infection of the blood, known as bacteremia (specifically Group B Streptococci (GBS; Streptococcus agalactiae), Escherichia coli, and Listeria monocytogenes). Although there is a low mortality rate in developed countries, there is a 50% prevalence rate of neurodevelopmental disabilities in E. coli and GBS meningitis

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.

Li-Fraumeni syndrome (LFS) is a cancer predisposition syndrome associated with the development of the following classic tumours: soft tissue sarcoma, osteosarcoma, pre-menopausal breast cancer, brain tumours, adrenocortical carcinoma (ACC), and leukaemia. LFS is diagnosed in individuals meeting established clinical criteria or in those who have a germline pathogenic variant in TP53 regardless of family cancer history.

Relative risk reduction (RRR) tells you by how much the treatment reduced the risk of bad outcomes relative to the control group who did not have the treatment. In the previous example, the relative risk reduction of fever and rash in the group of the children on the intervention was 40 per cent (1 – 0.6 = 0.4 or 40 per cent). RRR = (EER -CER) / CER = (0.1 – 0.4) / 0.4 = -0.75 or 75% reduction.

In many Western countries and health plans in the United States, patients have a primary care physician who acts as a formal gatekeeper for medical specialist care and thereby determines together with the patient whether or not a patient requires medical specialist care. Ideally in such systems, patients are treated in primary care if possible, and referred to medical specialist care if necessary. For the gatekeeper system to be effective, it is vital that adequate decisions are made about when and who to refer. But it is also important that referred patients comply with the referral by consulting a medical specialist. In this case, the GP should discuss with the patient the reasons why she cannot follow the treatment plan. In other words, the GP should detect why the patient is being non-compliant.

Normal distribution describes the spread of many biological and clinical measurements. Usually, 68.3% lies within 1 standard deviation (SD) of the mean, 95.4% lies within 2 SD of the mean and 99.7% lies within 3 SD of the mean.

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)

Mitochondrial DNA (mtDNA) is a double-stranded molecule of 16.6 kb (Figure 1, lower panel). The two strands of mtDNA differ in their base composition, with one being rich in guanines, making it possible to separate a heavy (H) and a light (L) strand by density centrifugation in alkaline CsCl2 gradients.

Acquired asplenia or hyposlenia can occur following splenectomy. Hyposplenism is used to describe reduced (‘hypo-‘) splenic functioning and is associated with increased risk of sepsis from polysaccharide encapsulated bacteria. In particular, patients are at risk from Streptococcus pneumoniae, Haemophilus influenzae, and meningococcus. The risk is elevated as much as 350–fold.

Speaking to your consultant is the most appropriate first action to take in this scenario. They are best placed to be able to take action to try and amend the situation. The consultant is also ultimately responsible for patient care and hterefore have a right to know if you are struggling, as this may affect patient care.
Arriving early and taking time off sick do not address the problem.

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.

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.

The power of a test is defined as 1 − the probability of Type II error. The Type II error is concluding at no difference (the null is not rejected) when in fact there is a difference, and its probability is named β. Therefore, the power of a study reflects the probability of detecting a difference when this difference exists. It is also very important to medical research that studies are planned with an adequate power so that meaningful conclusions can be issued if no statistical difference has been shown between the treatments compared. More power means less risk for Type II errors and more chances to detect a difference when it exists.

An odds ratio (OR) is a measure of 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

Type I interferons (IFNs) form a network of homologous cytokines that bind to a shared, heterodimeric cell surface receptor and engage signalling pathways that activate innate and adaptive immune responses.

Serum vitamin D levels are influenced by sun exposure and diet. Cod liver oil is an important dietary vitamin D source in high-latitude countries like Norway where there is no sun-induced vitamin D production during the winter. 14 Norwegian Health Authorities have recommended 5 ml of cod liver oil daily (400 IU of vitamin D) for more than 60 years to prevent diseases like rickets, formerly more prevalent in areas with little access to vitamin D-rich fatty fish.

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 duration of these cell cycle phases varies considerably in different kinds of cells. For a typical rapidly proliferating human cell with a total cycle time of 24 hours, the G1 phase might last about 11 hours, S phase about 8 hours, G2 about 4 hours, and M about 1 hour. The proliferation of most animal cells is similarly regulated in the G1 phase of the cell cycle. In particular, a decision point in late G1, called the restriction point in animal cells, is the point at which the cell becomes committed to the cell cycle and after which extracellular proliferation stimulants are no longer required.. Although the proliferation of most cells is regulated primarily in G1, some cell cycles are instead controlled principally in G2.

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) = 0.15 = 15%

A cohort study is a particular form of longitudinal study that samples a cohort (a group of people who share a defining characteristic, typically those who experienced a common event in a selected period, such as birth or graduation), performing a cross-section at intervals through time.
The relative risk (RR) or risk ratio is the ratio of the probability of an outcome in an exposed group to the probability of an outcome in an unexposed group. Relative risk is used in the statistical analysis of the data of experimental, cohort and cross-sectional studies, to estimate the strength of the association between treatments or risk factors, and outcomes.

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.

Haemophilia is a X-linked recessive disorder. In X-linked recessive inheritance only males are affected. An exception to this seen in examinations are patients with Turner’s syndrome, who are affected due to only having one X chromosome. X-linked recessive disorders are transmitted by heterozygote females (carriers) and male-to-male transmission is not seen. Affected males can only have unaffected sons and carrier daughters.

In general, the aim is to keep the homocysteine (Hcy) concentration as close to normal as possible. In patients who are fully-responsive to pyridoxine, standard doses can lead to tHcy levels below 50 μmol/L (and sometimes within the normal range). Some patients who are partially-responsive to pyridoxine may be able to achieve a tHcy level below 50 μmol/L if they are also on a low-Met diet; for others it is not a realistic goal.

NICE guidelines on hypercalcemia recommend that maintaining good hydration equals drinking 3-4 L of fluid/day, provided there are no contraindications. A low calcium diet is not necessary because intestinal absorption of calcium is reduced. The patient should avoid any other drugs or vitamins that could worsen the hypercalcemia. Mobilization is encouraged and any symptoms of hypercalcemia should be reported.

An atheroma is an accumulation of degenerative material in the tunica intima (inner layer) of artery walls. The material consists of (mostly) macrophage cells, or debris, containing lipids (cholesterol and fatty acids), calcium and a variable amount of fibrous connective tissue.

Turner syndrome (TS) is one of the most common genetic disorders; occurs with an incidence of I: 2,500 female live births. It results from complete or partial chromosome X monosomy. TS is associated with abnormalities of the X chromosome and characteristic clinical features of short stature, gonadal dysgenesis, sexual developmental deficiencies, cardiac and/or renal defects, webbed neck, low-set ears, skeletal deformities including cubitus valgus, a propensity to ear infections and hearing deficits.

Severe vitamin C deficiency results in scurvy, a disorder characterized by hemorrhagic manifestations and abnormal osteoid and dentin formation.
Vitamin C plays a role in collagen, carnitine, hormone, and amino acid formation. It is essential for bone and blood vessel health and wound healing and facilitates recovery from burns. Vitamin C is also an antioxidant, supports immune function, and facilitates the absorption of iron (see table Sources, Functions, and Effects of Vitamins).
Dietary sources of vitamin C include citrus fruits, tomatoes, potatoes, broccoli, strawberries, and sweet peppers. (See also Overview of Vitamins.)

The common congenital infections encountered are rubella, toxoplasmosis and cytomegalovirus. Cytomegalovirus is the most common congenital infection in the UK. Maternal infection is usually asymptomatic.
Congenital toxoplasmosis is associated with fetal death and abortion, and in infants, it is associated with neurologic deficits, neurocognitive deficits, and chorioretinitis.

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

Intracranial pressure (ICP) is a complex brain modality that determines cerebral perfusion pressure (CPP), which is the difference between arterial blood pressure (ABP), and ICP. Raised ICP reduces CPP and blood delivery to the brain. This jeopardizes cerebral function and organismal survival in many species. A massive rise in ICP is also known to produce an increase in ABP, bradycardia and respiratory irregularities termed Cushing response. This mechanism is generally considered to be an agonal and terminal event occurring in extreme condition of brainstem ischaemia leading to a sympatho-adrenal response.

Ebstein’s anomaly is characterised by apical displacement and adherence of the septal and posterior leaflets of the tricuspid valve to the underlying myocardium, thereby displacing the functional tricuspid orifice apically and dividing the right ventricle into two portions. The main haemodynamic abnormality leading to symptoms is tricuspid valve incompetence. The clinical spectrum is broad; patients may be asymptomatic or experience right-sided heart failure, cyanosis, arrhythmias and sudden cardiac death (SCD). Many Ebstein’s anomaly patients have an interatrial communication (secundum atrial septal defect (ASD II) or patent foramen ovale). Other structural anomalies may also be present, including a bicuspid aortic valve (BAV), ventricular septal defect (VSD), and pulmonary stenosis. The morphology of the tricuspid valve in Ebstein anomaly, and consequently the clinical presentation, is highly variable. The tricuspid valve leaflets demonstrate variable degrees of failed delamination (separation of the valve tissue from the myocardium) with fibrous attachments to the right ventricular endocardium.
The displacement of annular attachments of septal and posterior (inferior) leaflets into the right ventricle toward the apex and right ventricular outflow tract is the hallmark finding of Ebstein anomaly.

In the PCR, DNA amplification is performed by thermostable enzymes; invariably either family A DNA polymerases from thermophilic and hyperthermophilic Bacteria or family B DNA polymerases from hyperthermophilic Archaea. Family Y DNA polymerase from the hyperthermophilic archaeon Sulfolobus solfataricus, Sso-polY, is also an enzyme marketed for PCR, but with specialist applications. Each thermostable DNA polymerases has different characteristics and to achieve optimal results, the choice of a PCR enzyme depends on the application itself.

The C8 nerve forms part of the radial and ulnar nerves via the brachial plexus, and therefore has motor and sensory function in the upper limb. It originates from the spinal column from below the cervical vertebra 7 (C7).
The C8 nerve receives sensory afferents from the C8 dermatome. This consists of all the skin on the little finger, and continuing up slightly past the wrist on the palmar and dorsal aspects of the hand and forearm.
The other options available correspond to the C6 or C7 roots and these are unaffected as evidenced by normal elbow flexion and thumb sensation (C6) and normal sensation over the middle finger (C7). Elbow extension is weak as it has roots from both C7 and C8 and so cannot be used alone to decide between the two levels clinically.
The C8 nerve contributes to the motor innervation of many of the muscles in the trunk and upper limb. Its primary function is the flexion of the fingers, and this is used as the clinical test for C8 integrity, in conjunction with the finger jerk reflex.

Trunk:
– Pectoralis major – Medial and lateral pectoral nerves (C5, C6, C7, C8, T1)
– Pectoralis minor – Medial pectoral nerve (C5, C6, C7,C8, T1)
– Latissimus dorsi – Thoracodorsal nerve (C6, C7, C8)
Upper arm:
– Triceps brachii – Radial nerve (C6, C7,C8)
Forearm
– Flexor carpi ulnaris – Ulnar nerve (C7, C8, T1)
– Palmaris longus – Median nerve (C7,C8)
– Flexor digitorum superficialis – Median nerve (C8, T1)
– Flexor digitorum profundus – Median and Ulnar nerves (C8, T1)
– Flexor pollicis longus – Median nerve (C7,C8)
– Pronator quadratus – Median nerve (C7,C8)
– Extensor carpi radialis brevis – Deep branch of the radial nerve (C7,C8)
– Extensor digitorum – Posterior interosseous nerve (C7,C8)
– Extensor digiti minimi – Posterior interosseous nerve (C7,C8)
– Extensor carpi ulnaris – Posterior interosseous nerve (C7,C8)
– Anconeus – Radial nerve (C6, C7,C8)
– Abductor pollicis longus – Posterior interosseous nerve (C7,C8)
– Extensor pollicis brevis – Posterior interosseous nerve (C7,C8)
– Extensor pollicis longus – Posterior interosseous nerve (C7,C8)
– Extensor indicis – Posterior interosseous nerve (C7,C8)
Hand
– Palmaris brevis – Superficial branch of ulnar nerve (C8, T1)
– Dorsal interossei – Deep branch of ulnar nerve (C8, T1)
– Palmar interossei – Deep branch of ulnar nerve (C8, T1)
– Adductor pollicis – Deep branch of ulnar nerve (C8, T1)
– Lumbricals – Deep branch of ulnar, Digital branches of median nerve
– Opponens pollicis – Recurrent branch of median nerve (C8, T1)
– Abductor pollicis brevis – Recurrent branch of median nerve (C8, T1)
– Flexor pollicis brevis – Recurrent branch of median nerve (C8, T1)
– Opponens digiti minimi – Deep branch of ulnar nerve (C8, T1)
– Abductor digiti minimi – Deep branch of ulnar nerve (C8, T1)
– Flexor digiti minimi brevis – Deep branch of ulnar nerve (C8, T1)