Wednesday 22 March 2023

Parkinson Disease

Parkinson disease (PD) is one of the most common neurologic disorders, affecting approximately 1% of individuals older than 60 years and causing progressive disability that can be slowed, but not halted, by treatment. The 2 major neuropathologic findings in Parkinson disease are loss of pigmented dopaminergic neurons of the substantia nigra pars compacta and the presence of Lewy bodies and Lewy neurites.

Signs and symptoms

Initial clinical symptoms of Parkinson disease include the following:

  • Tremor
  • Subtle decrease in dexterity
  • Decreased arm swing on the first-involved side
  • Soft voice
  • Decreased facial expression
  • Sleep disturbances
  • Rapid eye movement (REM) behavior disorder (RBD; a loss of normal atonia during REM sleep)
  • Decreased sense of smell
  • Symptoms of autonomic dysfunction (eg, constipation, sweating abnormalities, sexual dysfunction, seborrheic dermatitis)
  • A general feeling of weakness, malaise, or lassitude
  • Depression or anhedonia
  • Slowness in thinkin

Onset of motor signs include the following:

  • Typically asymmetric
  • The most common initial finding is a resting tremor in an upper extremity
  • Over time, patients experience progressive bradykinesia, rigidity, and gait difficulty
  • Axial posture becomes progressively flexed and strides become shorter
  • Postural instability (balance impairment) is a late phenomenon

Nonmotor symptoms

Nonmotor symptoms are common in early Parkinson disease. Recognition of the combination of nonmotor and motor symptoms can promote early diagnosis and thus early intervention, which often results in a better quality of life.


Parkinson disease is a clinical diagnosis. No laboratory biomarkers exist for the condition, and findings on routine magnetic resonance imaging and computed tomography scans are unremarkable.

Clinical diagnosis requires the presence of 2 of 3 cardinal signs:

  • Resting tremor
  • Rigidity
  • Bradykinesia


The goal of medical management of Parkinson disease is to provide control of signs and symptoms for as long as possible while minimizing adverse effects.

Symptomatic drug therapy

  • Usually provides good control of motor signs of Parkinson disease for 4-6 years
  • Levodopa/carbidopa: The gold standard of symptomatic treatment
  • Monoamine oxidase (MAO)–B inhibitors: Can be considered for initial treatment of early disease
  • Other dopamine agonists (eg, ropinirole, pramipexole): Monotherapy in early disease and adjunctive therapy in moderate to advanced disease
  • Anticholinergic agents (eg, trihexyphenidyl, benztropine): Second-line drugs for tremor only

Treatment for nonmotor symptoms

  • Sildenafil citrate (Viagra): For erectile dysfunction
  • Polyethylene glycol: For constipation
  • Modafinil: For excessive daytime somnolence
  • Methylphenidate: For fatigue (potential for abuse and addiction)

Deep brain stimulation

  • Surgical procedure of choice for Parkinson disease
  • Does not involve destruction of brain tissue
  • Reversible
  • Can be adjusted as the disease progresses or adverse events occur
  • Bilateral procedures can be performed without a significant increase in adverse events


Before the introduction of levodopa, Parkinson disease caused severe disability or death in 25% of patients within 5 years of onset, 65% within 10 years, and 89% within 15 years. The mortality rate from Parkinson disease was 3 times that of the general population matched for age, sex, and racial origin. With the introduction of levodopa, the mortality rate dropped approximately 50%, and longevity was extended by many years. This is thought to be due to the symptomatic effects of levodopa, as no clear evidence suggests that levodopa stems the progressive nature of the disease.

The American Academy of Neurology notes that the following clinical features may help predict the rate of progression of Parkinson disease :
Older age at onset and initial rigidity/hypokinesia can be used to predict (1) a more rapid rate of motor progression in those with newly diagnosed Parkinson disease and (2) earlier development of cognitive decline and dementia; however, initially presenting with tremor may predict a more benign disease course and longer therapeutic benefit from levodopa
A faster rate of motor progression may also be predicted if the patient is male, has associated comorbidities, and has postural instability/gait difficulty (PIGD)
Older age at onset, dementia, and decreased responsiveness to dopaminergic therapy may predict earlier nursing home placement and decreased survival
Patient Education

Patients with Parkinson disease should be encouraged to participate in decision making regarding their condition. In addition, individuals and their caregivers should be provided with information that is appropriate for their disease state and expected or ongoing challenges. Psychosocial support and concerns should be addressed and/or referred to a social worker or psychologist as needed.

Prevention of falls should be discussed. The UK National Institute for Health and Clinical Excellence has several guidance documents including those for patients and caregivers.

Other issues that commonly need to be addressed at appropriate times in the disease course include cognitive decline, personality changes, depression, dysphagia, sleepiness and fatigue, and impulse control disorders. Additional information is also often needed for financial planning, insurance issues, disability application, and placement (assisted living facility, nursing home).

Tuesday 21 March 2023

55 countries facing serious health worker shortages – World Health Organisation

The World Health Organisation has said that no less than 55 countries are struggling with serious health worker shortages as they continue to seek better-paid opportunities in wealthier nations.

They continue to seek better-paid opportunities in wealthier nations that have stepped up efforts to recruit them amid the COVID-19 pandemic.

According to WHO, African nations have been worst hit by the phenomenon, with 37 countries on the continent facing health worker shortages.

“Health workers shortage have threatened their chances of achieving universal health care by 2030 – a key Sustainable Development Goals pledge.’’

The actions of wealthy countries that belong to the Organisation for Economic Cooperation and Development come under scrutiny in the WHO alert, among other regions.

“Within Africa, it’s a very vibrant economy that is creating new opportunities,” Dr Jim Campbell, the Director responsible for health worker policy at WHO, said in a statement on Tuesday.

“The Gulf States have traditionally been reliant on international personnel and then some of the OECD high-income countries have really accelerated their recruitment and employment to respond to the pandemic and respond to the loss of lives, the infections, the absences of workers during the pandemic”.

To help countries protect their vulnerable healthcare systems, WHO has issued an updated health workforce support and safeguards list, which highlights nations with low numbers of qualified healthcare staff.

“These countries require priority support for health workforce development and health system strengthening, along with additional safeguards that limit active international recruitment,” the WHO insisted.

Supporting the call for universal healthcare for all countries in line with the SDGs, WHO Director-General, Dr Tedros Ghebreyesus, called on all countries to respect the provisions in the WHO health workforce support and safeguards list.

“Health workers are the backbone of every health system, and yet 55 countries with some of the world’s most fragile health systems, do not have enough and many are losing their health workers to international migration,” he added.

Although many countries do respect existing WHO guidelines on the recruitment of health care workers, the principle is not accepted wholesale, WHO warned.

“What we are seeing is that the majority of countries are respecting those provisions by not actively recruiting from these (vulnerable) countries,” Campbell said.

“But there is also a private recruitment market that does exist and we’re looking to them to also reach some of the global standards that are anticipated in terms of their practice and behaviour.”

Mechanisms also exist for governments or other individuals to notify WHO if they are “worried” about the behaviour of recruiters, the WHO official said.

The WHO health workforce support and safeguard list does not prohibit international recruitment but recommends that governments involved in such programmes are informed about the impact on the health system in countries where they source qualified health professionals.

Intermittent fasting may change how your DNA is expressed

A new study found that a time-restricted diet reshaped nearly 80 per cent of all gene expression in mice — leading to reductions in obesity, health improvements and more.
A new study found that a time-restricted diet reshaped nearly 80 per cent of all gene expression in mice — leading to reductions in obesity, health improvements and more.

Mice who only ate at specific times of the day experienced “profound” changes in genetic expression, leading to health benefits like reduced risk of obesity and inflammation, new research found.

To an extent, it’s not about  what you eat as much as when you eat it — so says recent research that sheds new light on the benefits of intermittent fasting. 

The study, published Tuesday in journal Cell Metabolism, found that mice fed only during certain blocks of time experienced “profound” changes in gene expression. Nearly 80 per cent of all genes were impacted in some way, the paper reads.

The changes resulted in a plethora of health benefits, the authors wrote, including: improved blood sugar regulation, decreased risk of obesity and even a reversal of certain hallmarks of ageing.
You can think of a gene as the blueprint for a specific protein, written in DNA. When a gene is expressed, the blueprint is converted into its protein product by cellular machinery. Because proteins are responsible for most cellular functions from fat metabolism to immune response, even slight changes in gene expression could leave a massive impact.

According to the research, restricting when mice could eat reshaped when and to what extent certain genes were expressed — for example, some organs learned to switch on the genes for regulating blood sugar when it came feeding time, and to repress them when it was time to fast.

The researchers say their findings opened the door for further research into how dietary interventions might impact our genes and what this means for those suffering from issues like diabetes, heart disease and cancer.

What is time-restricted eating?

Shaunak Deota, first author of the study and a post-doctoral fellow at the Salk Institute for Biological Studies in San Diego, explained time-restricted eating as “eating consistently in a narrow window of 8 to 10 hours” when one is most active and fasting the remainder of the day. Intermittent fasting is a form of this practice, he said.

By feeding and fasting at the same time every day, we are reinforcing a biological rhythm in our bodies, Deota said: “Our body is getting the food at the same time every day, so all our organ systems know when the food is going to come and they’re prepared for it.”

Previous studies have shown that time-restricted eating may reduce the risk of obesity and diabetes, help to improve cardiovascular health, provide benefits for gut function and cardiovascular health and more.

Deota’s research now contributes, to his knowledge, the first “holistic” look at how time-restricted eating impacts the body as a system.

To achieve their results, the researchers put two groups of mice on the same high-calorie diet. One group was only allowed to eat during a nine-hour window when they were most active. The other could feed whenever they wanted.

After seven weeks, the mice on a time-restricted diet gained less weight than their counterparts, despite eating the same amount of food. 

The researchers then killed 48 of the mice — 24 from each group — to investigate the diet’s impact on the body. They sacrificed two mice from each group every two hours over a 24-hour period, noting how their organ systems changed over time.

How time-restricted eating changes the body

After studying the mouse organs, Deota and his team made a “pretty surprising” discovery; mice on the time-restricted diet had synchronized their gene expression with their feeding schedules.

“That is important because these genes will get translated into proteins,” Deota said. “Those proteins are helping our body to anticipate that there is food coming.”

According to their paper, roughly 70 per cent of all mouse genes fell into rhythm with the feeding schedule. Come mealtime, individual organs could promote genes in charge of nutrient metabolism while suppressing those responsible for inflammatory signalling and immune activation.

Moreover, the scientists found the diet reversed several hallmarks of aging, leading to reduced inflammation, increased cellular housekeeping, improved RNA and protein balance and more.

“Molecularly speaking, we saw a lot of pathways which are activated by (the time-restricted diet) in multiple organ systems. And a lot of these pathways actually have been implicated in improving health and leading to a longer, healthy life,” Deota said.

The limitations

All that being said, we need to remember these results were seen in mice, not humans — we’re still a long way off from demonstrating the same phenomenon happens in people, said Dani Renouf, a registered dietitian at St. Paul’s Hospital in Vancouver. For now, these results represent a “wonderful start to a conversation.”

“We’re just prototyping at this point because we’re using animal models and looking at things on a cellular level,” she said. “In order to now make conclusions in human beings, we need to take several steps before we can definitively do that with time restricted-eating.”

Renouf also noted the experiments took place in a tightly controlled environment. Real life is messy and chaotic, she said, and will likely influence results.

On the flip side, Deota believes “most of these benefits can be translated to humans” because his lab’s findings line up with what clinical studies into time-restricted eating have discovered.

Saturday 18 March 2023


Space Goth Grand Slam

In an effort to understand the origin of our galaxies, astronomers have spotted an insane, galactic showdown for the ages: four giant black holes in dwarf galaxies destined to collide, though not all in the same place. But boy, did they score a grand slam of astronomy firsts.

Using NASA's Chandra X-ray Observatory, the astronomers kept a close eye on two separate pairs of merging dwarf galaxies. One is in a cluster 760 million light-years away, the other, over 3.2 billion. Unfortunately, us humans are relegated to the nosebleeds for this one.

Still, we don't need to be close up to understand the significance of the findings, which were published as a study in The Astrophysical Journals. According to the researchers, it's the first evidence of large black holes in merging dwarf galaxies at all.

"Astronomers have found many examples of black holes on collision courses in large galaxies that are relatively close by," explained Marko Mićić, lead author of the study and an astrophysicists from the University of Alabama, in a press release."But searches for them in dwarf galaxies are much more challenging and until now had failed," he added.

Dwarfing Achievements

It's the dwarf galaxy angle that really makes this discovery significant. While they may not be as stunning in scope, dwarf galaxies are indispensable to understanding the evolution of galaxies as a whole.

The theories vary, but cosmologists generally believe that the initial dwarf galaxies, which formed hundreds of millions of years after the Big Bang, merged over time to form the large ones like our own that we're so familiar with.

"Most of the dwarf galaxies and black holes in the early universe are likely to have grown much larger by now, thanks to repeated mergers," said co-author Brenna Wells, an undergraduate researcher at UA, in the release.

"In some ways, dwarf galaxies are our galactic ancestors, which have evolved over billions of years to produce large galaxies like our own Milky Way."

All that goes to show why it's so frustrating that dwarf galaxies prove difficult to detect due to their lack of luminosity, and the fact they need to be observed at colossal distances.

Now that they've discovered not one, but four unique examples of them, the astronomers can return for followup observations — perhaps one of the best opportunities yet to understand the primeval galaxies of our universe.

Is the Nurses' Strike Over? RCN To Recommend New Pay Offer to Members

The Royal College of Nursing (RCN) has announced that they have received a new pay offer from NHS England, which it says it will recommend to members in a forthcoming vote. If accepted, this would bring an end to industrial action by nurses, 3 months after the strikes began.

The offer from the Government, which was made to all healthcare staff striking, including nurses, paramedics, 999 call handlers, midwives, security guards, and cleaners, includes a one-off payment for the 2022-23 financial year worth between £1655 and £3789, and a 5% consolidated pay increase for the 2023-24 financial year, according to the RCN.

New Pay Structure and Policy Framework on Safe Staffing

The deal also includes a new pay structure for nursing staff, which would come into force for 2024-2025. In addition, the Government had made a commitment – for the first time – to a national evidence-based policy framework on safe staffing, focusing on registered nurses, that "will draw on legislation in the rest of the UK and internationally", according to the RCN.

RCN General Secretary and Chief Executive Pat Cullen sees the deal as a win for nurses.

"The Government was forced into these negotiations and to reopen the pay award as a result of the historic pressure from nursing staff. Members took the hardest of decisions to go on strike and I believe they have been vindicated today," she said.

"It is not a panacea, but it is real tangible progress and the RCN's member leaders are asking fellow nursing staff to support what our negotiations have secured."

If Members Accept the Deal: 'No More Strikes'

The RCN's elected council met Thursday morning and decided that it will recommend that members vote to accept the offer in a forthcoming consultation. If members accept it, the dispute with Government and the NHS over pay will formally end. 

Negotiations with the RCN started 3 weeks ago, and all NHS unions took part in the last 10 days of talks. Aside from the RCN, UNISON, GMB, the Chartered Society of Physiotherapy, and the British Dietetic Association will also recommend the offer to their members in consultations that will be held over the coming weeks, according to the Department of Health and Social Care. Strike action will continue to be paused while they are consulted.
Prime Minister Rishi Sunak said of the deal: "It is right that we reward our hardworking NHS staff, who showed bravery and dedication throughout the pandemic and continue to make phenomenal progress to tackle waiting lists. Importantly this deal is also affordable for the taxpayer and continues to deliver on my promise to halve inflation.

"We have taken a reasonable approach throughout and this offer is good for NHS staff, it’s good for the taxpayer, and most importantly it is good news for patients whose care will no longer be disrupted by strike action."

Health and Social Care Secretary Steve Barclay said: "This offer will give nurses, paramedics, physiotherapists and other non-medical staff a fair pay rise while protecting our commitment to halve inflation."

Next Up: Junior Doctors

Responding to news that a pay deal has been reached in principle between the Government and unions, the Chief Executive of NHS Providers, Sir Julian Hartley said: "This is hugely positive development after months of strike action, which has seen NHS staff out on picket lines and widespread disruption to patient care, with tens of thousands of appointments postponed.
"We are very encouraged by the guarantee from the Government that there will be no impact on frontline services or the quality of care that patients receive as a result of this offer. We take this to mean that the deal is fully funded rather than relying on raids on NHS budgets, taking money away from key services. This is crucial to the success of the deal.

"It is also good to see that as a result of this deal all staff will be lifted above the real living wage, something we have long called for.

"We now need to see today's progress matched by urgent movement on talks between the Government and unions representing junior doctors. As trust leaders assess the full extent of the disruption caused by this week's 72-hour walkout, their message is loud and clear: Redouble your efforts to find a way through. No more strikes."

Can Particles in Dairy and Beef Cause Cancer and MS?

In our Western diet, dairy and beef are ubiquitous: Milk goes with coffee, melted cheese with pizza, and chili with rice. But what if dairy products and beef contained a new kind of pathogen that could infect you as a child and trigger cancer or multiple sclerosis (MS) 40-70 years later?

Researchers from the German Cancer Research Center(DKFZ) suspect that such zoonoses are possibly widespread and are therefore recommending that infants not be given dairy products until they are at least age 1 year. However, in two joint statements, the German Federal Institute for Risk Assessment (BfR) and the Max Rubner Institute (MRI) have rejected such theories.

In 2008, Harald zur Hausen, MD, DSc, received the Nobel Prize in Medicine for his discovery that human papillomaviruses cause cervical cancer. His starting point was the observation that sexually abstinent women, such as nuns, rarely develop this cancer. So it was possible to draw the conclusion that pathogens are transmitted during sexual intercourse, explain zur Hausen and his wife Ethel-Michele de Villiers, PhD, both of DKFZ Heidelberg.

Papillomaviruses, as well as human herpes and Epstein-Barr viruses (EBV), polyomaviruses, and retroviruses, cause cancer in a direct way: by inserting their genes into the DNA of human cells. With a latency of a few years to a few decades, the proteins formed through expression stimulate malignant growth by altering the regulating host gene.

Acid Radicals 

However, viruses — just like bacteria and parasites — can also indirectly trigger cancer. One mechanism for this triggering is the disruption of immune defenses, as shown by the sometimes drastically increased tumor incidence with AIDS or with immunosuppressants after transplants. Chronic inflammation is a second mechanism that generates acid radicals and thereby causes random mutations in replicating cells. Examples include stomach cancer caused by Helicobacter pyloriand liver cancer caused by Schistosoma, liver fluke, and hepatitis B and C viruses.

According to de Villiers and zur Hausen, there are good reasons to believe that other pathogens could cause chronic inflammation and thereby lead to cancer. Epidemiologic data suggest that dairy and meat products from European cows (Bos taurus) are a potential source. This is because colon cancer and breast cancer commonly occur in places where these foods are heavily consumed (ie, in North America, Argentina, Europe, and Australia). In contrast, the rate is low in India, where cows are revered as holy animals. Also noteworthy is that women with a lactose intolerance rarely develop breast cancer.

Viral Progeny 

In fact, the researchers found single-stranded DNA rings that originated in viruses, which they named bovine meat and milk factors (BMMF), in the intestines of patients with colon cancer. They reported, "This new class of pathogen deserves, in our opinion at least, to become the focus of cancer development and further chronic diseases." They also detected elevated levels of acid radicals in these areas (ie, oxidative stress), which is typical for chronic inflammation.

The researchers assume that infants, whose immune system is not yet fully matured, ingest the BMMF as soon as they have dairy. Therefore, there is no need for adults to avoid dairy or beef because everyone is infected anyway, said zur Hausen in a speech.

'Breast Milk Is Healthy'

De Villiers and zur Hausen outlined more evidence of cancer-triggering pathogens. Mothers who have breastfed are less likely, especially after multiple pregnancies, to develop tumors in various organs or to have from MS and type 2 diabetes. The authors attribute the protective effect to oligosaccharides in breast milk, which begin to be formed midway through the pregnancy. They bind to lectin receptors and, in so doing, mask the terminal molecule onto which the viruses need to dock. As a result, their port of entry into the cells is blocked.

The oligosaccharides also protect the baby against life-threatening infections by blocking access by rotaviruses and noroviruses. In this way, especially if breastfeeding lasts a long time — around 1 year — the period of incomplete immunocompetence is bridged.

Colon Cancer 

To date, it has been assumed that around 20% of all cancerous diseases globally are caused by infections, said the researchers. But if the suspected BMMF cases are included, this figure rises to 50%, even to around 80%, for colon cancer. If the suspicion is confirmed, the consequences for prevention and therapy would be significant.

The voice of a Nobel prize winner undoubtedly carries weight, but at the time, zur Hausen still had to convince a host of skeptics with his discovery that a viral infection is a major cause of cervical cancer. Nonetheless, some indicators suggest that he and his wife have found a dead end this time.

Institutional Skepticism 

When his working group made the results public in February 2019, the DKFZ felt the need to give an all-clear signal in response to alarmed press reports. There is no reason to see dairy and meat consumption as something negative. Similarly, in their first joint statement, the BfR and the MRI judged the data to be insufficient and called for further studies. Multiple research teams began to focus on BMMF as a result. In what foods can they be found? Are they more common in patients with cancer than in healthy people? Are they infectious? Do they cause inflammation and cancer?

The findings presented in a second statement by the BfR and MRI at the end of November 2022 contradicted the claims made by the DKFZ scientists across the board. In no way do BMMF represent new pathogens. They are variants of already known DNA sequences. In addition, they are present in numerous animal-based and plant-based foods, including pork, fish, fruit, vegetables, and nuts.

BMMF do not possess the ability to infect human cells, the institutes said. The proof that they are damaging to one's health was also absent. It is true that the incidence of intestinal tumors correlates positively with the consumption of red and processed meat — which in no way signifies causality — but dairy products are linked to a reduced risk. On the other hand, breast cancer cannot be associated with the consumption of beef or dairy.

Therefore, both institutes recommend continuing to use these products as supplementary diet for infants due to their micronutrients. They further stated that the products are safe for people of all ages.

Association With MS? 

Unperturbed, de Villiers and zur Hausen went one step further in their current article. They posited that MS is also associated with the consumption of dairy products and beef. Here too geographic distribution prompted the idea to look for BMMF in the brain lesions of patients with MS. The researchers isolated ring-shaped DNA molecules that proved to be closely related to BMMF from dairy and cattle blood. "The result was electrifying for us."However, there are several other factors to consider, such as vitamin D3 deficiency. This is because the incidence of MS decreases the further you travel from the poles toward the equator (ie, as solar radiation increases). Also, the EBV clearly plays a role because patients with MS display increased titers of EBV antibodies. One study also showed that people in Antarctica excreted reactivated EBV in their saliva during winter and that vitamin D3 stopped the viral secretion.

Under these conditions, the researchers hypothesized that MS is caused by a double infection of brain cells by EBV and BMMF. EBV is reactivated by a lack of vitamin D3, and the BMMF multiply and are eventually converted into proteins. A focal immunoreaction causes the Schwann cells and oligodendrocytes to malfunction, which leads to the destruction of the myelin sheaths around the nerve fibers.