New Discovery on Causes of Dementia

Researchers at bio-tech firm Neuro-Bio, based in Oxford, have made a significant discovery about the causes of dementia. Almost 900,000 people in the UK suffer from dementia, and nearly 70,000 die from it every year. The number of suffers has been projected to rise to 1.6 million by 2040.

Research to date has focused on developing drugs to destroy amyloid plaques (protein deposits) that build up in the brain, affecting memory and cognitive function. However, recent studies show no improvement in symptoms after taking these drugs. 

Research by a team led by Dr Susan Greenfield's on the causes of Alzheimer's dementia has led to the hypothesis that something else could be the initial cause and that amyloid plaques build up well after brain degeneration has begun.

New studies have shown that cells at the centre of the brain, in the isodendritic core, are the first to begin dying in the brain of someone with Alzheimer's disease (the most common form of dementia) often ten to 15 years before they experience symptoms. When these cells die, it sets off a snowball effect, causing more and more cells to die.

While scientists are still unsure why this process begins, Neuro-Bio claims to have found a molecule responsible for causing the damage, called T14. They have developed a drug to limit the cell damage caused by T14 and initial trials on mice show this is effective. 

Human trials are expected to follow, to investigate whether it is safe and effective in humans. The treatment is given as a nasal spray. 

T14 can also be measured in blood and Neuro-Bio is also developing this biomarker as a companion diagnostic.

Source: Oxford scientists hail major breakthrough which could provide relief to 900,000 Britons with dementia by Ethan Ennals, Daily Mail, 2nd April 2022.

Air Pollution and Cancer

 Researchers at the Francis Crick Institute in London have shown that air pollution does not cause cell damage directly but 'wakes up' old damaged cells. This transforms our understanding of how tumours develop and it may now be possible to develop drugs that stop cancers forming.

The classical view of cancer is that it starts with a healthy cell, which over time acquires more and more mutations in its genetic code, or DNA, until it reaches a point where is becomes a cancer and grows uncontrollably. However it is also known that cancerous mutations are also found in seemingly healthy tissue, and many substances known to cause cancer, including air pollution, don't seem to damage people's DNA.

Research has now produced evidence of a different idea. The damage is already there in our cell's DNA, as we grow and age, but there needs to be a trigger to make it cancerous. The research focused on exploring why non-smokers get lung cancer. While the vast majority of lung cancers are caused by smoking, one in ten cases is due to air pollution.

Focusing on a form of pollution called particulate matter 2.5 (known as PM2.5), which of far smaller than the diameter of a human hair, they carried out a series of detailed human and animal experiments which showed the following.

• Places with higher levels of air pollution had more lung cancers not caused by smoking.
• Breathing in PM2.5 leads to the release of a chemical alarm (interleukin-1-beta) in the lungs.
• This causes inflammation and activates cells in the lungs to help repair any damage.
• But around one in every 600,000 cells in the lungs of a 50-year-old already contains potentially cancerous mutations.
• These are acquired as we age but appear completely healthy until they are activated by the chemical alarm and become cancerous.

And crucially, the researchers were able to stop cancers forming in mice exposed to air pollution by using a drug that blocks the alarm signal.

People who had never smoked but developed lung cancer often had no idea why. To give them clues about how this might work is important, since 99% of people in the world live in places where air pollution exceeds the WHO guidelines, so it impacts everyone.

The results also showed that mutations alone are not always enough to cause cancer. It can need another element. We even need to rethink how smoking causes cancer - is it just the known DNA damage caused by the chemicals in tobacco or is the smoke causing inflammation too? The idea that mutated DNA is not enough to cause cancers and that they need another trigger to grow was first proposed by Isaac Berenblaum in 1947.

Source: Air pollution cancer breakthrough will rewrite the rules. By James Gallagher, Health and science correspondent, BBC News. https://www.bbc.co.uk/news/health-62797777 

Galleri screening test for cancer trial by NHS

On the 13th September 2021 the NHS began the world's largest trial of a revolutionary new blood test that can detect more than 50 types of cancer before symptoms appear.

Patients whose cancer is found early at stage one or two typically have a broader range of treatment options available, which can be curative and are often less aggressive. Diagnosis at the earliest stage has typically between five and ten times the survival rate with those found at stage four.

The Galleri test

This simple blood test looks for the earliest signs of cancer, especially those that are usually difficult to identify early or for which there are no NHS screening programmes, such as lung, pancreas and stomach cancers. The test was developed by the firm of Grail, California and is is already in use in the USA.

The test works by finding chemical changes in fragments of genetic code (cell-free DNA or cfDNA) that leak from tumours into the bloodstream. Finding these changes does not mean someone actually has cancer, just that they might have cancer and will need follow up tests.

The Trial

The NHS aims to recruit 140,000 volunteers in eight areas of England to see how well the test works. Participants must not have already had a cancer diagnosis in the last three years.The first people to take part will have blood samples taken at mobile testing clinics in retail parks and other convenient community locations. They will then be invited back to give further samples after 12 months and again at 2 years.

The study is a randomised control trial (RCT). Half the participants will have their blood screened with the test immediately. The other half will have their sample stored and may be tested in the future. This will allow scientists to compare the stage at which cancer is detected between the two groups.

People will only know if they are in the test group if they are among the small minority whose test detects potential signs of cancer in their blood. They will be contacted by a trial nurse and referred to an NHS hospital for further tests. All participants will be advised to continue with their standard NHS screening appointments, and contact their GP if they notice any new or unusual symptoms.

Initial results of the study are expected by 2023 and, if successful, NHS England plans to extend the testing to a further one million people in 2024 and 2025.

Source: Various news sites in 2021.

The Queen has died - Long live the King

Queen Elizabeth II died on the 8th September 2022, but what happens next?

Succession

Her eldest son, Charles, became king immediately. The new monarch chooses the name they will be known as - in this case Charles III.

An Accession Council, by custom held at St James's Palace, is usually convened within 24 hours of the death of the monarch and the accession of the successor to the throne. The Council should be held before Parliament meets, and Parliament should meet as soon as practicable after the death.

The Accession Council comprises certain Privy Counsellors, Great Officers of State, the Lord High Mayor and High Sheriffs of the City of London, Realm High Commissioners, some senior civil servants and certain others invited to attend, but without the new Sovereign. This meeting formally announces the death of the monarch and proclaims the succession of the new sovereign. The Accession Proclamation is signed by those members of the Royal Family who are Privy Councellors, the Archbishop of Canterbury, the Lord Chancellor, the Archbishop of York, the Prime Minister, the Lord Privy Seal, the Lord Great Chamberlain, the Earl Marshall and the Lord President of the Council

Following this the Sovereign holds their first Privy Council, which is attended by Privy Counsellors only.

Funeral

The funeral will be held at Westminster Abbey on Monday 19th Sept. King Charles III has approved a bank holiday on the day of the funeral.

The Queen's coffin was first laid to rest in the ballroom at Balmoral to allow the Royal Household to pay their respects. On Saturday 10th Sept. her coffin will then be driven via Ballater, Aberdeen, Dundee and Perth to the Palace of Holyroodhouse in Edinburgh. On Monday a procession will march up the Royal Mile St Giles' Cathedral in Edinburgh, where a Vigil of the Princes is expected to take place with members of the Royal Family. The public may be able to file past her coffin while she lies in state. On Tuesday she will be flown to London, and be driven from Buckingham Palace to Westminster Hall, where people will be allowed to file past over a period of four days' lying in state. Her coffin will be draped with the Royal Standard and once in Westminster Hall it will be topped with the Imperial State Crown, orb and sceptre.

The Queen's coffin will then be taken to Westminster Abbey for the funeral service. Following the funeral service, her coffin will be drawn in a walking processions from the abbey to Wellington Arch, at London's Hyde Park Corner before heading to Windsor by hearse. The Queen's coffin will make its final journey that afternoon to St George's Chapel in Windsor Castle for the committal service. Her coffin will be lowered into the Royal Vault, before being interred in the King George VI memorial chapel, located inside St George's Chapel.

Mourning

A period of national mourning is now in place and will last until the day of the state funeral.

The period of Royal Mourning by the Queen's family will continue for seven days after the funeral.

Other events

The union flag will be flown at half mast on government buildings until the morning after the funeral. Flags will return to full mast for a 24-hour period beginning at 13:00 BST on Saturday to mark the proclamation of Charles as King, before returning to half mast.

There will be a remembrance service at St Paul's Cathedral on Friday (9th Sept.?) attended by the prime minister and other senior ministers.

On Friday 9th Sept. bells will toll in tribute to the Queen at Westminster Abbey, St Paul's Cathedral and Windsor Castle. Around the country parish churches with bells will also be tolled in tribute. Gun salutes of 96 rounds to mark each year of her life will be fired in Hyde Park and elsewhere.

Many sporting fixtures have largely been cancelled, as have the final three of the BBC Proms concerts. Theatre performances are expected to continue, observing a minute's silence. Strikes for industrial disputes have also been cancelled.

Changes of title

The Duke and Duchess of Cambridge automatically became Duke and Duchess of Cornwall and Cambridge. The title of Prince of Wales is the gift of the sovereign and is not automatically passed on. However, King Charles has bestowed the title of Prince of Wales on Prince William and his wife Catherine becomes Princess of Wales.

The children of the Duke and Duchess of Sussex could now be titled Prince Archie and Princess Lilibet as on the death of the Queen they are now the children of sons of the sovereign. It is not known whether Harry and Meghan will use the titles for their children. The Duke of Sussex is now 5th in line for the succession, with his brother William 1st in line and then William and Kate's children George (2nd), Charlotte (3rd) and Louis (4th).

Currency, stamps and passports - and more

The money and coins currently in circulation will be replaced with the face of King Charles III. A new portrait of Charles will be commissioned, from which millions of pounds worth of new currency will be printed by the Royal Mint and distributed across the UK. The old currency featuring the Queen's face will be gradually fazed out.

As with coins, new stamps featuring Charles will simply be slowly brought into circulation. Any current stamps you own with the Queen on will still be eligible for use.

All British passports are issued in the name of Her Majesty, and are still valid for travel. The wording in the inside of the front cover of new passports will be updated to His Majesty.

When a monarch dies, royal warrants they issued become void and a company has two years to stop using the royal arms. The warrants Charles issued as Prince of Wales will continue because they go with the household, not the title.

Police forces in England and Wales will have to change the royal cypher of Queen Elizabeth II in the centre of helmet plates.

Leading barristers have become King's Counsel (KC) instead of Queen's Counsel (QC).

END

Human Sexes, Gender and Transgender

 At the present time - 2022 - there is much in the media about the issues of gender and sex. These are also topics that generate a lot of (sometimes heated) discussion. So this post aims to clarify some of this area.

Sex (Definition): Either of the two major forms of individuals that occur in many species and that are distinguished respectively as female or male especially on the basis of their reproductive organs and structures. (Merriam-Webster Dictionary)

Sexual Orientation (Definition): An enduring pattern of romantic or sexual attraction (or a combination of these) to persons of the opposite sex or gender (heterosexual), the same sex or gender (homosexual), or to both sexes and more than one gender (bisexual). The lack of sexual attraction to others (asexuality) is sometimes defined as a fourth category. (Wikipedia)

Sex: Your birth certificate is the document that records the sex (male or female) of a child born in the UK. This information is given to the local Registrar by the person registering the birth, usually one of the parents, along with the forenames that have been chosen for the child. 

For the vast majority of births, the physical sex of the child is obvious as either male or female. For a very rare number, the sex of the child is indeterminate or where there are intersex traits. It is estimated that this occurs once in every 1,500 births, In these cases the General Register Office advice is that registration is deferred until medical investigations are complete. 

Tests typically include testing chromosomes, hormones and internal organs. Test results do not always indicate male or female, but can be on a sliding scale between the two. Ultimately the sex chosen for an intersex baby is the one doctors and their family believe they will grow up to identify with best. In past years, surgery was typically the first thing to do, but many now feel this should be delayed. 

To further complicate matters, some Disorders of Sex Development (DSD) are not obvious from external appearance and are only identified later when a child needs surgery (e.g. for a hernia) or hormone testing for other reasons. 

Sexual orientation: It is only possible to estimate the proportions of a population that identify as lesbian, gay or bisexual by using the statistics from national surveys and censuses. In the UK in 2019, an estimated 1.4 million people aged 16 or over identified as LGB; this was around 2.7% of a population of c. 67.1 million.

There are differences in age groups. While 2.7% of those aged 16 and over identify as LGB, the proportion of all 16 to 24 year old's identifying as LGB is around  6.6%. Possible reasons for this pattern are that younger people could be more likely to explore their sexuality, combined with more social acceptance of different sexual identities and the expression of these today. However, for the first time, older people (aged 65 years and over) also showed an increase in those identifying as LGB (from 0.7% in 2018 up to 1.0% in 2019).

Source: UK Office for National Statistics. NB: Since these figures have not been collected in the past, it is not clear what proportion of those aged 16-24 will continue to identify as LGB as they progress through adolescence.)  

Gender (Definition): Gender is the range of characteristics pertaining to femininity and masculinity and differentiating between them. Depending on the context, this may include sex-based social structures and gender identity. Most cultures use a gender binary, having two genders; those who exist outside these groups may fall under the umbrella term 'non-binary'. (Wikipedia)

Transgender (Definition): Transgender people have a gender identity or expression that differs from the sex they were assigned at birth. The term may also be used to refer to people who are non-binary or genderqueer, and to cross-dressers. Being transgender is distinct from sexual orientation. (Wikipedia) Some transgender people undergo surgery hormone treatment and lifelong hormone treatment to 'become' the other gender. However, genetically their body cells will remain female or male, which may have other health implications.

Transsexual (Definition): People who desire medical assistance (hormone treatment and surgery) to transition to the physical characteristics of another sex. (Wikipedia)

Human Biology

Genetics and DNA have revealed that humans are not just born male and female. There are at least six biological sexes that can result in fairly normal lifespans. (In addition there are other 'sexes' that result in spontaneous abortion as the body identifies the foetus as non-viable.)

Even today, people think of someone as a 'man' if they look masculine and as a 'woman' if they look feminine. This can lead to some significant misunderstandings of how the world actually works.

• Mokgadi Caster Semenya: An intersex woman, assigned female at birth and has always lived as a woman, with XY chromosomes and naturally elevated testosterone levels. However as a runner, other competitors felt her higher testosterone levels gave her an unfair advantage over XX women. 2018: The international athletics federation, announced new rules to apply only to those with the 46,XY karyotype, who are now required to lower their testosterone levels in order to compete in the female classification. The medication taken can have side effects.
• Transgender male to female competing in women's events. More and more male-to-female athletes are competing in women's competitions, creating a dilemma for all involved. Such athletes have been allowed to compete in women's Olympic events since 2012 on condition that this is after castration and two years of hormone therapy. However, others feel that they still have an advantage of the benefit of more androgen for their first 20 years of growth, with a male type skeleton and musculature. It is also likely that a male athlete will have a male brain, since developing foetuses have male imprinting of the brain, which does not go away after androgen  supression and sex change surgery.

The sex of a baby is determined by its sex chromosomes, with XX being female and XY male, but is typically identified by its genitalia or visible sex organs (penis and vagina). However, some babies with the genetic variants listed below can appear to be females or males but actually have other sex chromosome combinations. A study in Great Britain showed that 97 out of 100 people who were actually XXY thought they were a normal XY male, and had few signs that this was not the case.

• XX = Most common form of Female
• XY  = Most common form of Male
• X  = Turner's syndrome (roughly 1 in 2,000 to 1 in 5,000 births). This chromosome variation happens randomly when the baby is conceived. It is not linked to the mother's age. These females tend to be shorter than average, and have under-developed ovaries. Most likely to be diagnosed between the ages of 8 to 14.
• XXY = Kleinfelter syndrome (roughly 1 in 500 or 1 in 1,000 births). Males are born with an extra X chromosome. Many of them are unaware they have the extra chromosome. Infertility tends to be the main problem.
• XYY = Jacob's syndrome (roughly 1 in 1,000 births). Affected individuals are usually very tall. Many experience severe acne during adolescence, and other symptoms may include learning disabilities and behavioural problems such as impulsivity.
• XXXY = (roughly 1 in 18,000 to 1 in 50,000 births). Characterized by the presence of 2 extra X chomosomes in males. Sometimes referred to as a variant of Klinefelter syndrome, but differs from that and is more severe. Signs and symptoms vary but include learning difficulties, intellectual disability, low muscle tone, delayed growth, distinctive facial features and various birth defects that may affect the genital and musculoskeletal systems. Many have poorly developed social skills and delayed language development. The condition is not inherited and likely results from a random error in cell division.

END