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.

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

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.

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.

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.

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.

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.

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.

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.

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

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.

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.

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 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.

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.

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

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.

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

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.

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.

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.

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.

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√

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.

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.

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).

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.

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.

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.

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

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.

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.

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.

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.

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.

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.

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.

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

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

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

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.

L4 dermatome distribution includes the kneecaps.

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.

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.

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.

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.

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.

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.

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.

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.