The prion protein has two forms: the normal form (PrPc) and the infectious form (PrPSc). The normal form can be broken down by proteases, while the infectious form is resistant to proteases.

Prion Protein and its Role in Disease

Prion protein is a type of infective agent that is composed of protein. It is made up of proteins called PrP, which exist in two forms: a normal form (PrPC) and an abnormal form (PrPSc). The abnormal form is resistant to protease, which means it cannot be broken down in the body. This abnormal form can change adjacent normal PrPC into the abnormal form, which is how the infection spreads.

PrPC is a normal component of cell membranes and has an alpha-helical structure. However, in PrPSc, much of the alpha-helical structure is replaced by a beta-sheet structure. This change in structure causes PrPSc to aggregate into plaques in the extracellular space of the central nervous system, disrupting normal tissue structure.

Prions cause disease by this disruption of normal tissue structure, leading to neurological symptoms and ultimately death. Understanding the structure and behavior of prion proteins is crucial in developing treatments and preventative measures for prion diseases.

Multiculturalism is the coexistence of various cultural of ethnic groups within a shared social and political framework. Acculturation is the process of cultural and psychological change that occurs when different cultural groups come into contact with each other. Canadian psychologist John Berry identified four paths to acculturation: assimilation, integration, separation, and marginalization. Assimilation involves giving up one’s home culture and adopting the dominant culture, while integration involves maintaining one’s home culture while also embracing the dominant culture. Separation involves maintaining one’s home culture while being isolated from the dominant culture, and marginalization involves giving up one’s home culture and failing to related properly to the dominant culture. There is a cultural debate regarding assimilation and multiculturalism, with two forms of assimilation recognized: total assimilation, which involves the obliteration of the non-dominant culture, and melting pot assimilation, which refers to a less extreme version where a new form of the dominant culture emerges. Laissez-faire multiculturalism refers to multiculturalism that occurs without planning, such as the existence of Chinatowns in most cities.

Alzheimer’s disease often results in the shrinkage of the hippocampus, which is a component of the limbic system and is responsible for the formation and retention of long-term memories.

Alzheimer’s disease is characterized by both macroscopic and microscopic changes in the brain. Macroscopic changes include cortical atrophy, ventricular dilation, and depigmentation of the locus coeruleus. Microscopic changes include the presence of senile plaques, neurofibrillary tangles, gliosis, degeneration of the nucleus of Meynert, and Hirano bodies. Senile plaques are extracellular deposits of beta amyloid in the gray matter of the brain, while neurofibrillary tangles are intracellular inclusion bodies that consist primarily of hyperphosphorylated tau. Gliosis is marked by increases in activated microglia and reactive astrocytes near the sites of amyloid plaques. The nucleus of Meynert degenerates in Alzheimer’s, resulting in a decrease in acetylcholine in the brain. Hirano bodies are actin-rich, eosinophilic intracytoplasmic inclusions which have a highly characteristic crystalloid fine structure and are regarded as a nonspecific manifestation of neuronal degeneration. These changes in the brain contribute to the cognitive decline and memory loss seen in Alzheimer’s disease.

In the given example, Mark is using sublimation as a defence mechanism to express his internal impulses in a socially acceptable way. It is not an example of aggression. Similarly, playing tennis cannot be considered as constructive gratifying service to others, which is a characteristic of altruism. Instead, it is an example of displacement, where Mark is transferring his emotional response to a situation that carries less emotional risk. Mark is externalizing his feelings through sublimation, rather than turning them into self-harm.

Valproate can pass through the placenta, increasing the likelihood of birth defects. The extent of risk during pregnancy is not fully understood, but it is believed to be influenced by the dosage. Children who were exposed to valproate in the womb may have a lower IQ, with those aged 6 showing an average decrease of 7-10 points compared to those exposed to other antiepileptic medications.

Valproate: Forms, Doses, and Adverse Effects

Valproate comes in three forms: semi-sodium valproate, valproic acid, and sodium valproate. Semi-sodium valproate is a mix of sodium valproate and valproic acid and is licensed for acute mania associated with bipolar disorder. Valproic acid is also licensed for acute mania, but this is not consistent with the Maudsley Guidelines. Sodium valproate is licensed for epilepsy. It is important to note that doses of sodium valproate and semi-sodium valproate are not the same, with a slightly higher dose required for sodium valproate.

Valproate is associated with many adverse effects, including nausea, tremor, liver injury, vomiting/diarrhea, gingival hyperplasia, memory impairment/confusional state, somnolence, weight gain, anaemia/thrombocytopenia, alopecia (with curly regrowth), severe liver damage, and pancreatitis. Increased liver enzymes are common, particularly at the beginning of therapy, and tend to be transient. Vomiting and diarrhea tend to occur at the start of treatment and remit after a few days. Severe liver damage is most likely to occur in the first six months of therapy, with the maximum risk being between two and twelve weeks. The risk also declines with advancing age.

Valproate is a teratogen and should not be initiated in women of childbearing potential. Approximately 10% of children exposed to valproate monotherapy during pregnancy suffer from congenital malformations, with the risk being dose-dependent. The most common malformations are neural tube defects, facial dysmorphism, cleft lip and palate, craniostenosis, cardiac, renal and urogenital defects, and limb defects. There is also a dose-dependent relationship between valproate and developmental delay, with approximately 30-40% of children exposed in utero experiencing delay in their early development, such as talking and walking later, lower intellectual abilities, poor language skills, and memory problems. There is also a thought to be a 3-fold increase of autism in children exposed in utero.

The symptoms described in the scenario are indicative of narcolepsy, specifically hypnopompic hallucinations and sleep paralysis. Narcolepsy is characterized by a set of symptoms including sleep attacks, cataplexy, sleep paralysis, and hypnagogic or hypnopompic hallucinations. Primary hypersomnia is excessive daytime sleepiness without the associated features of other sleep disorders of narcolepsy. REM sleep behavioral disorder (RBD) is characterized by complex behaviors during sleep, typically occurring during the longest periods of REM sleep and accompanied by vivid dream recall. Sleep terror disorder, also known as night terror, occurs during partial arousal from delta sleep and is typically amnestic. In contrast, the patient in the scenario was able to recall the episode of sleep paralysis. Schizophrenia cannot be diagnosed based on the symptoms described, as the criteria for hallucinations and an additional symptom from criterion A must be present for a significant portion of the time, and the symptoms can be attributed to narcolepsy.

Flashbulb Memory

Flashbulb memories are vivid and detailed recollections of the circumstances surrounding a significant event. These memories are typically episodic, meaning they are focused on the specific details of the event rather than just the facts. One example of a flashbulb memory might be recalling where you were and what you were doing when you first heard about the death of Princess Diana in 1997. What sets flashbulb memories apart from other types of memories is the high level of emotional arousal that accompanies them. This emotional intensity helps to cement the memory in the mind, making it more vivid and long-lasting.

To obtain an accurate measurement of the QT interval, it is recommended to measure it in lead II of leads V5-6. The Bazett formula may not provide accurate corrections for heart rates above 100 bpm of below 60 bpm, but it can be used to estimate the QT interval at a standard heart rate of 60 bpm through the corrected QT interval (QTc).

QTc Prolongation: Risks and Identification

The QT interval is a measure of the time it takes for the ventricles to repolarize and is calculated from the beginning of the QRS complex to the end of the T wave. However, the QT interval varies with the heart rate, making it difficult to use a single number as a cut-off for a prolonged QT. Instead, a corrected QT interval (QTc) is calculated for each heart rate using various formulas. A QTc over the 99th percentile is considered abnormally prolonged, with approximate values of 470 ms for males and 480 ms for females.

Prolonged QT intervals can lead to torsade de pointes (TdP), a polymorphic ventricular tachycardia that can be fatal if it degenerates into ventricular fibrillation. TdP is characterized by a twisting of the QRS complexes around an isoelectric line and is often asymptomatic but can also be associated with syncope and death. An accurate diagnosis requires an ECG to be recorded during the event. It is important to note that an increase in the QT interval due to a new conduction block should not be considered indicative of acquired LQTS and risk for TdP.

Hepatic encephalopathy is indicated by the presence of a distinctive ‘liver flap’.

Hepatomegaly

Chronic alcohol abuse can lead to hepatomegaly, which is an enlargement of the liver. This can be detected on physical examination by palpating the liver below the right ribcage. Hepatomegaly can also be associated with other signs of liver disease, such as jaundice, spider naevi, and caput medusa. It is important for psychiatrists to be aware of these physical findings in patients with alcohol use disorder, as they may indicate the need for further medical evaluation and treatment.

Cholecystokinin (CCK) is a hormone produced and released by the duodenum that stimulates the secretion of digestive enzymes and bile, while also acting as an appetite suppressant. corticotropin releasing hormone is secreted by the paraventricular nucleus of the hypothalamus and triggers the release of ACTH from the pituitary gland. Met- and Leu- encephalin are peptides that play a role in pain modulation. α-endorphin is one of several endorphins that can inhibit pain and induce a feeling of euphoria.

Source: https://www.ncbi.nlm.nih.gov/pubmed/16246215