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Over 12,000 genetic variations that determine a person’s height have been found by researchers.

The 12,111 variations that cluster around areas of the genome involved with skeletal development provide a strong genetic predictor of height. The discovered variations account for 40% of the variance in height for persons of European ancestry and 10-20% for those of non-European ancestry.

Adult height is mostly determined by the information encoded in our DNA — children from tall parents tend to be taller and those from short parents are shorter, but these estimates aren’t perfect. Growth from a small baby into an adult, and the role genetics play in this, have traditionally been a complex and poorly understood area of human biology. Previously, the largest genome-wide association study looking at height used a sample size of up to 700,000 individuals, the current sample is about seven times more than previous studies.

The unprecedented scale of the research provides new levels of detail and biological insight as to why people are tall or short, with heritability being linked to various specific genomic regions. The findings show that genetic variants associated with height are concentrated in regions covering just over 20% of the genome.

The findings of the study might assist doctors discover patients who are unable to achieve their genetically projected height, which could then aid in the detection of hidden diseases or ailments that are stunting their growth or negatively influencing their health. The study also provides a significant model for how genome-wide investigations may be used to determine a disease’s biology and, ultimately, its genetic components.

While this study has a large number of participants from non-European ancestries compared to previous studies, the researchers emphasise the need for more diversity in genomic research.

Most of the genetic data available is from people of European ancestry, so genome-wide studies don’t capture the wide range of ancestral diversity across the globe. Increasing the size of genome-wide studies in non-European ancestry populations is essential to achieve the same level of saturation and close the gap in prediction accuracy in different populations.

Dr Eirini Marouli, co-first author of the study and Senior Lecturer in Computational Biology at Queen Mary University of London, said:

“We have accomplished a feat in studying the DNA of over 5 million people that was broadly considered impossible until recently.

“Genomic studies are revolutionary and might hold the key to solving many global health challenges — their potential is tremendously exciting. If we can get a clear picture of a trait such as height at a genomic level, we may then have the model to better diagnose and treat gene-influenced conditions like heart disease or schizophrenia, for example.

“If we can map specific parts of the genome to certain traits, it opens the door to widespread targeted, personalised treatments further down the line that could benefit people everywhere.”

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Anxiety and despair have been on the rise internationally for decades, a trend exacerbated by the COVID-19 epidemic. A recent study demonstrated how researchers discovered novel remedies to aid in the alleviation of this global mental health burden.

The findings of a research done by Frank Schroeder of the Boyce Thompson Institute were published in Nature Chemical Biology. Serotonin, first identified in the 1930s, is a neurotransmitter generated in many animals that affects a variety of activities including eating, sleep, mood, and cognition. Serotonin-altering drugs are the primary treatment for psychological diseases such as anxiety and depression, as well as eating disorders.

As a simple model for neurobiology research, the microscopic roundworm Caenorhabditis elegans has been used extensively to study serotonin’s role in regulating behavior and food intake. For many years, researchers thought that serotonin was made in C. elegans by one specific molecular pathway, and that serotonin was then quickly degraded.

Schroeder’s team and colleagues at Columbia University now demonstrated that both of those assumptions were not quite correct.

“We discovered a second, parallel biosynthetic pathway that accounts for about half of the total serotonin produced in our model system,” said Schroeder.

The work began about three years ago, when the researchers unexpectedly discovered an enzyme that converts serotonin into derivative compounds.

“Most people in the field thought serotonin is made and then quickly broken down, but we found that, instead, it is used as a building block for other compounds that are responsible for some of serotonin’s activity,” explained Schroeder. “So, we decided to start at the beginning and see how serotonin is made, and once it is made then how is it converted into these new molecules.”

Jingfang Yu, a graduate student in Schroeder’s lab and first author on the paper, further showed that the new serotonin derivatives affect feeding behavior.

“When the worms lack endogenous serotonin, they tend to move quickly across the bacteria food lawn on an agar plate, and turn infrequently to explore the food,” Yu said. “We found this behavior can be alleviated by treating the worms with serotonin derivatives, suggesting these newly identified compounds contribute to effects previously attributed to serotonin.”

The worm C. elegans is an excellent model for studying serotonin because the compound’s molecular signaling pathways are highly conserved across species, including in humans. For example, the researchers showed that in C. elegans a large portion of serotonin is made in the gut, which is also the case in humans.

Schroeder said there are hints that human serotonin is converted into metabolites similar to the ones identified in C. elegans.

“This research opens up the door for many more avenues of research in humans,” said Schroeder, who is also a professor in the Department of Chemistry and Chemical Biology in the college of Arts and Sciences at Cornell University.

“Are the analogous metabolites important in humans? What is the role of one manufacturing pathway versus the other? How are these manufacturing pathways and metabolites important for human behaviors, like mental health and feeding behaviors?” he asked.

The researchers are currently exploring how the new serotonin derivatives affect behavior in C. elegans and whether similar serotonin metabolites exist in humans.

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The criteria for success for the roughly 8.5 million Americans with peripheral artery disease (PAD, pronounced P-A-D), which is characterised by narrowed or clogged arteries in the legs, should be driven by their symptoms, according to a new American Heart Association scientific statement published today in the Association’s premier, peer-reviewed journal Circulation.

The American Heart Association’s scientific statement is a professional assessment of current results that may impact future practise recommendations.

Managing peripheral artery disease (PAD) based on a person’s experience of symptoms can result in more patient-centred care and outcomes, with a focus on high-value care, compared to relying on clinical measures like the rate of blood flow to the legs or artery diameter. This is highlighted in the statement, “Advancing peripheral artery disease quality of care and outcomes through patient-reported health status assessment.”

“The person living with peripheral artery disease is the authority on its impact on their daily life. Our treatment must be grounded in their lived experiences and go beyond the clinical measures of how well blood flows through the arteries,” said Vice Chair and lead author of the statement writing group Kim G. Smolderen, PhD, a clinical psychologist and an associate professor of medicine and psychiatry and co-director of the Vascular Medicine Outcomes Research (VAMOS) lab at Yale University in New Haven, Connecticut.

“We have spent years developing and validating standardized instruments to capture people’s experiences in a reliable and sensitive way. We are now at a point where we can start integrating this information into real-world care, through pilot programs that can develop quality benchmarks for different phenotypes of patients with PAD and the types of treatments they undergo, as seen from their perspective.”

Painful Legs and Other Patient Experiences

Although those who have peripheral artery disease (PAD) tend to be older than 40, it can also affect younger people. People with PAD have blockages in the arteries that carry blood to their legs and feet, which frequently results in pain, cramping, or weakness when they walk, necessitating a brief break to ease the discomfort. Although some people have no symptoms, many patients may only have no pain because they restrict their activities.

Their functionality and health status are also impaired, according to studies. People who have critical limb ischemia, or highly restricted blood supply to the legs, may endure discomfort even while at rest, have wounds that do not heal or develop gangrene that could result in an amputation. Another risk factor for heart attack or stroke is PAD.

The everyday functioning and quality of life of patients are significantly impacted by all of these manifestations, with the impact growing as the disease’s severity rises. Other medical diseases like Type 2 diabetes, coronary artery disease, kidney dysfunction, or mental health issues like depression or stress-related illnesses that are frequent in persons with PAD can have an impact on outcomes, according to Smolderen.

Patient-led Treatment

Coordination of care for risk factors and patient concerns is prioritised when the healthcare team is more aware of the impact of disease on quality of life. The statement urges gathering feedback from patients’ therapy experiences to enhance and personalise care for those with obstructed leg arteries.

Patient-reported outcomes measures (PROMs) are a systematic and proven approach of directly asking patients to rate how their symptoms, physical, social, and emotional functioning, and quality of life are affected by their disease. PROM feedback can be used to more accurately and impartially evaluate the quality of care provided to PAD patients.

The use of PROMs has several key benefits, including improving patient comprehension of the patient’s lived experience with PAD, improving patient self-management of symptoms and medical needs, standardising quality performance benchmarks for practises that treat patients with PAD, and providing pertinent feedback to identify treatment changes or needs.

It may be possible for physicians to consider beyond a specific intervention by calling more attention to quality-of-life issues or cardiovascular risk factors when patients are included as the expert on their own experiences. This viewpoint could spark discussions that change the course of therapy or introduce patients to additional treatments like behavioural health services, wound care, or smoking cessation. Self-management and joint decision-making between patients and physicians may be improved by patient-centred care.

No matter the patient’s literacy level, language obstacles, or cultural norms, all of these advantages are attainable as long as the patient-reported outcome measures are evaluated using methods that the patient is able to grasp. It’s also crucial that PROMs are carried out by professionals who are qualified and knowledgeable enough to use the tools, interpret the results, and connect patients with further resources. The claim gives examples of PROMs that assess depressive symptoms, general health status, PAD-specific health status, and leg pain and functioning (including walking limitation).

Performance Measures to Improve Quality of Care

PROMs might potentially be used to evaluate whether programmes are offering persons with PAD high-quality care. PROMs are increasingly being incorporated into definitions of what it means to give patient-centred, high-quality clinical care, and PROMs scores may have a direct impact on reimbursement, according to the Centers for Medicare and Medicaid Services and the National Quality Forum. PROMs are converted into Patient-Reported Outcomes Performance Measures for programme evaluation (PRO-PMs).

The use of PRO-PMs has the potential to:

a. offer quantifiable goals for programmes to improve their quality of care;

b. encourage the development of training and expertise for health systems to administer, interpret, and use PRO-PMs in an ethical manner to improve patient care;

c. lessen disparities in care and promote health equity;

d. assist in the development of national standards for quality care.

“This roadmap highlights a paradigm shift that places the patient experience front and centre, which is a departure from the status quo. It is provocative to now place the lived experience with the disease at the forefront, engaging people with PAD to provide information that holds health systems and practitioners accountable as to whether high-quality care was delivered, in addition to assessing the safe and effective delivery of current evidence-based treatments,” said Smolderen.

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Every year on October 10, World Mental Health day is observed. In 1992, the World Federation for Mental Health observed the day for the first time.

The objective behind observing this day is to raise awareness about mental health concerns and mobilise support for mental health. The World Health Organization’s (WHO) official website stated that “The Day provides an opportunity for all stakeholders working on mental health issues to discuss their work, and what more needs to be done to make mental health care a reality for people worldwide.”

Significance

The main objectives of World Mental Health Day are to raise public awareness of mental health concerns around the world and to motivate people to support mental health. The day makes sure that the topic of mental health is brought up and continues to be on people’s minds. The day offers an opportunity for mental health care professionals to exchange ideas and discover new strategies for ensuring that mental health treatment is available to everyone worldwide.

History

A non-governmental organisation called the World Federation for Mental Health (WFMH) was established in 1948. On October 10, 1992, Richard Hunter, who was the deputy secretary general of the WFMH at the time, declared the first World Mental Health Day. Every year since 1994, a unique theme has been chosen for the international celebration.

2022 Theme

‘Make mental health & well-being for all a global priority’ is the theme for World Mental Health Day 2022.
According to the World Health Organization (WHO), prior to the COVID-19 pandemic, one in eight people globally experienced mental health problems. But there wasn’t enough financial and infrastructural support for mental health.
The pandemic raised mental stress across the globe.

More than 7 lakh individuals commit suicide each year as a result of stress or depression, according to the WHO. On World Mental Health Day, it is highlighted how stigma and discrimination harm individuals who are afflicted. It advocates for social inclusion and everyone’s entitlement to high-quality medical treatment.

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A doctor has voiced optimism for the recovery of the mentally ill lady who was chained for 36 years and rescued by a non-government organisation in Firozabad, Uttar Pradesh, noting that the procedure might take several weeks.

Under the leadership of Bharatiya Janata Party MLA Anjula Mahour, the NGO Seva Bharati rescued a mentally ill lady who had been chained by her family members for the last 36 years in Firozabad’s Tundla, Uttar Pradesh. The woman has been taken to an Agra psychiatric hospital for treatment.

The woman was chained at the age of 17 years and turned 53 when she was freed and admitted to the hospital.

Speaking to ANI, Dr Dinesh Rathore, Medical Superintendent, Agra mental institute said, “A woman aged 53 years hailing from Firozabad was rescued and brought here. She was kept shackled in chains in a room by her family for 36 years, who believed that she was mentally ill”.

He said that when she was in a bad condition at the time when she was brought to the hospital.

“We found her in a very bad condition. She was wearing filthy clothes with dirt all over. NGO members bathed her and got her some clean clothes. Her medical tests are being conducted. We are hopeful that she will recover soon, maybe within a few weeks,” said Dr Rathore.

According to the villagers, she was fed by the family through a crack in the door and was provided with water for her bathing through the window.

The treatment of the woman is underway.

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According to a new study, a Mediterranean diet heavy in fibre, monounsaturated fatty acids, and polyphenols is associated with higher immunotherapy response rates and progression-free survival in patients with advanced melanoma.

Experts believe that nutrition will play a significant part in the effectiveness of immunotherapy, and trials are being broadened to explore outcomes for other tumour types, including gut malignancies.

A Mediterranean diet, containing mono-and polyunsaturated fats from olive oil, nuts and fish, polyphenols and fibre from vegetables, fruit, and wholegrains, was significantly associated with an improved response to immunotherapy drugs called Immune Checkpoint Inhibitors (ICIs). ICIs, which have been highly successful in treating melanoma, work by blocking immune system checkpoints, which then force the body’s own T-cells to attack cancers.

The new multi-centre study by researchers from the UK and the Netherlands, recorded the dietary intake of 91 patients with advanced melanoma, who were treated with ICI drugs and monitored their progress with regular radiographic response check-ups.

As well as having a significant association with overall response rate, a Mediterranean diet was significantly associated with progression-free survival at 12 months.

Laura Bolte, author of the study and PhD candidate under supervision of Prof. Rinse Weersma from the University Medical Center Groningen, Netherlands, commented, “ICI has helped to revolutionise the treatment of different types of advanced cancers. Our study underlines the importance of dietary assessment in cancer patients starting ICI treatment and supports a role for dietary strategies to improve patient outcomes and survival.”

The study also found that eating wholegrains and legumes reduced the likelihood of developing drug induced immune-related side effects, such as colitis. In contrast, red and processed meat was associated with a higher probability of immune-related side effects.

“The relationship of ICI response with diet and the gut microbiome opens a promising and exciting future to enhance treatment responses. Clinical trials investigating the effect of a high fibre diet, ketogenic diet and supplementation of omega-3 are underway. Since ICI therapy is being expanded to various tumour types, including digestive cancers, these studies could unlock treatment benefits for a large group of cancer patients in the future,” added Laura Bolte.

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According to a research, a novel treatment that combines the use of two ultrasound technologies may provide an alternative for moving moving kidney stones out of the ureter with minimal discomfort and no anaesthetic.

The new study’s findings were published in The Journal of Urology. The physician directs ultrasonic waves towards the stone using a portable transducer put on the skin during the treatment. The ultrasound can then be used to shift and rearrange the stones to facilitate passage, a procedure known as ultrasonic propulsion, or to break up the stone, a procedure known as burst wave lithotripsy (BWL).

Unlike shock wave lithotripsy, which is the standard procedure now in use and requires sedation, this technology doesn’t hurt, said lead author Dr. M. Kennedy Hall, a UW Medicine emergency medicine doctor. “It’s nearly painless, and you can do it while the patient is awake, and without sedation, which is critical.”

The research team hopes that, with this new technology, the procedure of moving or breaking up the stones could eventually be performed in a clinic or emergency room setting, Hall added.

Stones in the ureter, which leads from the kidney to the bladder, can cause severe pain and are a common reason for emergency department visits. Most patients with ureteral stones are advised to wait to see if the stone will pass on its own.

However, this observation period can last for weeks, with nearly one-fourth of patients eventually requiring surgery, Hall noted.

One in 11 Americans will have a urinary stone over the course of their lifetime. The incidence appears to be increasing, according to one UW Medicine study looking at this same technology. Up to 50% of patients with a stone event will recur within five years, the study noted.

Hall and colleagues evaluated the new technique to meet the need for a way to treat stones without surgery.
The study was designed to test the feasibility of using the ultrasonic propulsion or using BWL to break up stones in awake, unanaesthetized patients, Hall said.

Twenty-nine patients participated in the study. Sixteen were treated with propulsion alone and 13 with propulsion and burst wave lithotripsy. In 19 patients, the stones moved. In two cases, the stones moved out of the ureter and into the bladder.

Burst wave lithotripsy fragmented the stones in seven of the cases. At a two-week follow up, 18 of 21 patients (86%) whose stones were located lower in the ureter, closer to the bladder, had passed their stones. In this group, the average time to stone passage was about four days, the study noted.

One of these patients felt “immediate relief” when the stone was dislodged from the ureter, the study stated.

The next step for the researchers would be to perfom a clinical trial with a control group, which would not receive either BWL bursts or ultrasound propulsion, to evaluate the degree to which this new technology potentially aids stone passage, Hall said.

Development of this technology first started five years ago, when NASA funded a study to see if kidney stones could be moved or broken up, without anesthesia, on long space flights, such as the Mars missions.

The technology has worked so well that NASA has downgraded kidney stones as a key concern.

“We now have a potential solution for that problem,” Hall said.

This study began in 2018 and was conducted on patients at Harborview Medical Center, University of Washington Medical Center-Montlake and the Northwest Kidney Stone Center at University of Washington Medical Center-Northwest. It involved the University of Washington School of Medicine’s departments of emergency medicine, urology and radiology, and the UW Applied Physics Laboratory.

Other UW Medicine trials have looked at breaking apart kidney stones inside the kidneys. This is the first trial to look at moving the stones or breaking them apart in the ureter with BWL, Hall said.

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The cerebellum is most well-known for its function in motor control. According to Basel University experts, the cerebellum is also vital in retaining emotional memories.

The study’s findings were published in the journal PNAS. Positive and negative emotional events are particularly strongly remembered. This phenomena is critical to human existence since we must remember dangerous circumstances in order to avoid them in the future.

Previous studies have shown that a brain structure called the amygdala, which is important in the processing of emotions, plays a central role in this phenomenon. Emotions activate the amygdala, which in turn facilitates the storage of information in various areas of the cerebrum.

The current research, led by Professor Dominique de Quervain and Professor Andreas Papassotiropoulos at the University of Basel, investigates the role of the cerebellum in storing emotional experiences. In a large-scale study, the researchers showed 1,418 participants emotional and neutral images and recorded the subjects’ brain activity using magnetic resonance imaging.

In a memory test conducted later, the positive and negative images were remembered by the participants much better than the neutral images. The improved storage of emotional images was linked with an increase in brain activity in the areas of the cerebrum already known to play a part. However, the team also identified increased activity in the cerebellum.

The cerebellum in communication with the cerebrum

The researchers were also able to demonstrate that the cerebellum shows stronger communication with various areas of the cerebrum during the process of enhanced storage of the emotional images. It receives information from the cingulate gyrus – a region of the brain that is important in the perception and evaluation of feelings. Furthermore, the cerebellum sends out signals to various regions of the brain, including the amygdala and hippocampus. The latter plays a central role in memory storage.

“These results indicate that the cerebellum is an integral component of a network that is responsible for the improved storage of emotional information,” says de Quervain. Although an improved memory for emotional events is a crucial mechanism for survival, it does have its downsides: in the case of very negative experiences, it can lead to recurring anxiety. This means that the findings, which have now been released, may also be relevant in understanding psychiatric conditions such as post-traumatic stress disorder.

The current study forms part of a large-scale research project conducted by the Research Platform Molecular and Cognitive Neurosciences (MCN) at the University of Basel and the University Psychiatric Clinics (UPK) Basel. The aim of this project is to gain a better understanding of emotional and cognitive processes and to transfer results from basic research to clinical projects.

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According to a new mouse study, an epigenetics medicine presently being used to treat blood cancers and rare sarcomas can block the progression of bladder cancer by activating the immune system. The medicine is currently being evaluated in a national clinical trial for individuals with advanced bladder cancer.

It is the first time that a medicine formerly used to treat hematologic malignancies and uncommon sarcomas has been utilised to treat one of the most prevalent solid tumours.

The drug, tazemetostat, was originally developed to treat lymphoma. “We’ve discovered for the first time that the drug actually works by activating the immune system, not just by inhibiting the tumor,” said lead study author Dr. Joshua Meeks, an associate professor of urology and of biochemistry and molecular genetics at Northwestern University Feinberg School of Medicine and a Northwestern Medicine physician/scientist.

The study will be published Oct. 5 in Science Advances.

“We think the specific mutations that may make the drug successful are found in almost 70% of bladder cancers,” said Meeks, also a member of the Robert H. Lurie Comprehensive Cancer Center of Northwestern University.

Bladder cancer affects more than 700,000 individuals in the U.S. It is the sixth most common cancer overall and the fourth most common among men. More than 80,000 people in the U.S. are diagnosed yearly with bladder cancer.

“Survival for advanced bladder cancer is extremely poor, and the drug works by mechanisms different than any other therapy,” Meeks said. “This is the first application of epigenetic therapy in bladder cancer.”

The drug is a pill that is well tolerated and could be added to other systemic therapies in bladder cancer, Meeks said. It is now being tested in a national clinical trial led by investigators at Northwestern for patients with late-stage bladder cancer.

Northwestern investigators showed that the medication, which targets the EZH2 gene — abundant in most tumors — can stop the growth of bladder cancer.

“EZH2 is commonly overexpressed in most solid tumors and works by ‘locking’ tumors in a state of growth,” Meeks said.

“We think it’s one of the main genes involved in cancer. We were interested in that gene because the most common mutations in bladder cancer may make EZH2 more active. When cells have higher levels of this gene activity, they proliferate.”

When scientists knocked out EZH2 in bladder cancers in mice, the tumors were much smaller and packed with immune cells.

“That was our clue the immune system may be suppressed by EZH2,” Meeks said. “Next, we gave a commercially available drug (tazemetostat) to inhibit the activity of this gene. It caused a lot of immune cells to pack the bladder.

Finally, when we used mice with no T cells, we found the drug was ineffective, confirming that the immune system was likely the primary pathway by which the drug works.

“We find that the treatment is potent immunotherapy in translational research. The drug changes the tumor to prime the immune system, activating CD4 helper cells that coordinate the immune response and recruit more T cells.”

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The length of daylight hours has been found to influence opioid receptor levels in brown fat by researchers. When the daylight hours shorten, receptor activity levels rise. A similar event occurs in the brain. Both phenomena aid in the adaptation of humans and animals to seasonal variations.

In a new study conducted at the Turku PET Centre in Finland, researchers discovered that shorter daylight hours affect opioid receptor signalling in animal brown fat.

When the amount of light diminishes, the opioid receptor levels increase. The observation was done in rats living in an artificial environment imitating seasonal daylight changes. “In the study, we observed that the number of mu-opioid receptors in brown fat was dependent on the length of daylight the rat was exposed to. This complements our previous findings that day length modulates opioid receptor levels in the brain emotional circuits in humans and rats,” says Senior Researcher Lihua Sun from the Turku PET Centre of the University of Turku.

He states that the opioid receptor activity of brown fat and brain are two separate phenomena. However, they share the same goal of helping a mammal, a person or an animal, adapt both physiologically and also emotionally to the change of seasons.

“Opioid receptor levels in the brain and brown fat might be interconnected, for example strengthening each other’s activity, but more research is needed to confirm this,” Sun emphasises.

Professor Anne Roivainen from the Turku PET Centre tells that this is the first time mu-opioid receptor levels have been assessed in peripheral regions using positron emission tomography (PET) imaging.

“The finding highlights that mu-opioid receptors affect the seasonality of brown fat activity. Future studies should further investigate whether mu-opioid receptors in brown fat are directly related to tissue energy consumption,” says Roivainen.

Opioid receptors are parts of the cell through which the opioid hormones can impact the cell. An example of such hormones is endorphin, which promotes pleasure and relieves pain in the body.

As a result, opioid receptor functions in the brain play an important part in both pain and mood and emotions. Receptor dysfunction has been linked to psychiatric diseases such as sadness and anxiety, as well as eating disorders. Seasonal affective changes, such as seasonal affective disorder, may potentially be influenced by opioid receptor levels. Winter blues and overeating are two of its symptoms.

More research is needed, according to Roivainen and Sun, to determine whether seasonal variations in mu-opioid receptor numbers in the brain and brown fat are underlying seasonal affective changes.

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