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Depression: Gene-activating drug reverses symptoms in mice

Monitoring Desk

WASHINGTON: New research shows that activating a gene that, in turn, boosts the activity of certain neurons involved in depression can reverse symptoms of the condition in male mice.

Depression is “the leading cause of disability worldwide,” as more than 300 million people across the globe are living with the condition.

In the United States, major depressive disorder affects 6.7 percent of the population, including over 16 million adults.

Recently, more and more studies have been shedding light on the genetic and neurological mechanisms at play behind depression.

For instance, a pioneering study has uncovered 44 genetic locations that the researchers showed to have a link to a higher risk of the condition. Other studies have found that brain areas scientists link with reward and memory processing are different in those living with depression.

Zooming in on a single gene, a genome-wide association study appearing in 2015 found that a variant of a protein-encoding gene known as Sirtuin1 (SIRT1) correlates with a much higher risk of depression.

Now, new research finds that direct activation of this gene in the prefrontal cortex — a brain area we associate with complex thinking and planning of socially-appropriate responses — can reverse symptoms of depression in male mice.

Molecular behavioral neuroscientist and pharmacologist Xin-Yun Lu, Ph.D., is the corresponding author of the latest study. The researcher is also a professor in the Department of Neuroscience and Regenerative Medicine at the Medical College of Georgia at Augusta University.

Prof. Lu and her colleagues published their research in the journal Molecular Psychiatry.

To test the impact of a SIRT1-activating drug in depressed mice, Prof. Lu and team knocked out the SIRT1 gene in male rodents and examined their reaction to a sweet drink that they would usually strongly prefer.

The researchers found that knocking out the gene reduced the number of mitochondria in excitatory neurons and decreased their excitation. Mitochondria are the so-called powerhouses of the cell, that is, tiny organelles inside cells that turn nutrients into energy.

Excitatory neurons, explain the researchers, are underactive in depression and do not communicate with each other correctly. These neurons seem to be “disconnected” in depression, says Prof. Lu.

The researchers depressed the rodents by subjecting them to “chronic unpredictable stress.” They did so by restraining the mice for 2 hours, pinching their tails for 15 minutes, subjecting them to constant light for 24 hours, keeping them in wet bedding for 24 hours, or tilting their cages. They also subjected the mice to 10-minute small electric shocks and social isolation.

As a result of the chronic stress, the male rodents that had the SIRT1 gene knocked out lost their interest in the sweet solution they usually preferred — a symptom scientists consider to be the equivalent of anhedonia in depressed humans. These rodents also exhibited signs of “behavioral despair” in the forced swim test.

However, when the researchers injected the prefrontal cortex of the male rodents with a SIRT1 activator they call SRT2104, they reversed these symptoms. The drug had an “antidepressant-like” effect, according to Prof. Lu. She and her colleagues conclude:

“These results suggest that SIRT1 in [medial prefrontal cortex] excitatory neurons is required for normal neuronal excitability and synaptic transmission and regulates depression-related behaviors in a sex-specific manner.”

Prof. Lu now plans to examine existing drugs and see if any of them affect SIRT1 in a similar way to the activator they used in this research. The scientists theorize that we may one day use SIRT1 activators as an effective treatment for major depression.

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Female brain is a few years younger than a male: Study

Monitoring Desk

WASHINGTON: Scientists revealed that healthy women have a metabolic brain age that is persistently four years younger than men’s of the same age.

“Brain metabolism changes with age but what we noticed is that a good deal of the variation we see is down to sex differences,” said Marcus Raichle, a neurobiologist at Washington University school of medicine in St Louis. “If you look at how brain metabolism predicts a person’s age, women come out looking about four years younger than they are.”

Mani Goyal at the University’s Mallinckrodt Institute of Radiology and lead author on the paper said men’s brains were not aging faster than women’s. “They start adulthood about three years older than women and that persists throughout life,” he said. “What we don’t know is what it means. I think this could mean that the reason women don’t experience as much cognitive decline in later years is because their brains are effectively younger.”

The study was based on metabolism rather than the birth date found an average 3.8-year difference between men and women.

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Congo virus claims another life in Karachi

F.P. Report

KARACHI: Congo virus claimed another life here on Sunday after which toll due the disease mounted to two. Director Jinnah Hospital Dr. Seemi Jamali said that Tazeem Faizan 70, was shifted to hospital two days earlier, where he was found affected with Congo virus. After detection of Congo virus, Tazeem was under treatment at a private hospital where he breathed his last on Sunday raising death toll due to virus to two. A couple of days earlier, 35-year-old lady had died of Congo virus in Orangi Town.

According to health experts, symptoms of Congo virus include backache, joints pain, pain in abdomen, high fever and bleeding from any part of body.

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3 days polio campaign Kicks-off in KP and merged districts from today

F.P. Report

PESHAWAR: Due to continuous virus circulation in the environment and reporting of two new polio cases from Bannu and Bajaur, Emergency Operations Center Khyber Pakhtunkhwa has decided to launch case response in 21 districts of the province along with exclusive Inactivated Polio Vaccination (IPV) campaign in the provincial capital from February 18, next.

This was decided at a high level meeting held here with Coordinator EOC Capt( R) Kamran Afridi in the chair.  Director EPI Dr Akram Shah, Technical Focal Person Dr Imtiaz Ali Shah and technical heads of WHO, UNICEF and N Stop were also present on the occasion.

The meeting decided to start a special IPV campaign in the provincial capital from February 18, next wherein children from four months up to five years of age will be vaccinated with injectable polio vaccine while OPV will be administered to children from zero to five years.

The case response campaign will be carried out in Peshawar, Charsadda, Nowshera, Mardan, Swabi, Malakand, Kohat, Karak, Hangu, Lakki Marwat, Tank, Bannu, Dera Ismail Khan and Lower Dir, Bajaur, Khyber, Kurram, Mohmand, Orakzai, South Waziristan and North Waziristan.

Total target of oral polio vaccine stands at 4.745 million children under the age of five in for which 16532 teams have been constituted for OPV campaign out of which 14377 were mobile teams, 1230 fixed, 802 Transit and 123 roaming teams whereas 3832 area supervisors will ensure quality campaign.  

Likewise, 691575 children will receive injectable polio vaccine in the eight days campaign in Peshawar where over 1082 trained teams will be vaccinating children at outreach sites.

Speaking on the occasion, Capt (R) Kamran Afridi said that two drops of oral polio vaccine was the only remedy for polio eradication as the entire world including Muslim countries have wiped out polio from their regions for good through OPV.

He requested all parents to cooperate with the teams in vaccination of their children to help protect them from lifelong disability and urged media to sensitize community on the significance of OPV and IPV vaccination for the health of their children.

He said that IPV was an additional boost that build blood immunity whereas OPV strengthens both gut and blood immunity and together they provide complete safety against the crippling disease of polio which is not curable and can even kill children when their immunity is compromised. 

EPI Director Dr Akram Shah said that IPV is one of the safest vaccines in use and no serious systemic adverse reactions have been shown to follow vaccination with IPV, whether used alone or in combination with other vaccines.

He said that minor local reactions, such as redness and tenderness, may occur following IPV and can be treated with paracetamol adding that IPV can be safely administered to sick children or children with immune-deficiencies.

It is perfectly safe to vaccinate children with IPV multiple times, and each additional dose of polio vaccine will further strengthen a child’s immunity level against polio, he added.

It  merits mentioning here that four polio cases have been reported from the country in 2019 so far out of which one each from Bajaur, Bannu, Hangue and Lahore has been recorded.

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Flu virus kills 56 in Greek

Monitoring Desk

ATHENS: Greek health authorities have become increasingly concerned over the past several weeks as fifty-six people have died of flu complications so far this year, the Center for Disease Control and Prevention (KEELPNO) said on Thursday.

The particular flu virus strain H1N1, which has hit this winter, seems to be especially lethal for the elderly, as most of the victims in Greece were seniors.

Epidemiologists and other experts urge the Greek population, especially patients suffering from chronic illnesses, to get vaccinated early, before the beginning of the flu season, and not leave it until the last minute.

Authorities also advise the public to take necessary precautionary measures to avoid spreading the virus, for example by staying home when they realize that they are suffering from flu symptoms such as fever, cough and sore throat.

KEELPNO has recorded eighteen deaths from influenza this week, with a total of sixty-one people suffering from influenza admitted into intensive care units across the country.

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Reducing diabetes risk with a personalized diet

Lauren Sharkey      

WASHINGTON: Keeping blood glucose at a healthy level reduces the risk of developing diabetes. But until now, reducing high glucose levels has focused on limiting carb and calorie intake, rather than on how individuals respond to different foods.

Health meal together

The number of people in the United States who receive a diagnosis of diabetes continues to rise.

According to the Centers for Disease Control and Prevention (CDC), 9.4 percent of the U.S. population had diabetes in 2015.

Some sources estimate that about 40 percent of U.S. adults have prediabetes. This condition is characterized by higher than normal blood sugar levels and may lead to type 2 diabetes, heart disease, and stroke.

Experts are always looking for ways to prevent the onset of the condition. Reducing blood sugar — or blood glucose — levels is the primary method.

Typically, this involves controlling diet with a specific focus on lowering calorie and carbohydrate intake. Not only can this prevent diabetes, but it can also reduce a person’s risk of obesity and heart or kidney disease.

However, new research has shown that taking a more individualized approach may produce better results. “The current models of predicting blood glucose levels perform well, but they tend to bucket everything, like fats and carbohydrates, into one category,” says Purna Kashyap, co-director of the Mayo Clinic Center for Individualized Medicine Microbiome Program, in Rochester, MN.

“As a clinician, I have seen that my patients do not respond to the same foods the same way — just like not all weight-loss diets work for all people the same,” adds study co-author Dr. Heidi Nelson.

The influence of the microbiome

The research team worked to find a model that could predict how blood sugar levels would react after a person ate specific foods.

The team took individual features into account. These included age, diet, and physical activity. They also considered the gut microbiome — the trillions of bacteria living in the intestines.

In total, 327 people living in either Minnesota or Florida took part in the study. Each participant gave a stool sample, which allowed researchers to examine each person’s unique gut microbiome. The team followed the participants for 6 days.

For breakfast, the volunteers ate bagels and cream cheese. The participants were then free to choose their diet for the rest of the day. The researchers asked them to record everything they ate, along with any exercise and rest periods. A blood glucose monitor also tracked blood sugar levels every 5 minutes.

The results are available in the JAMA Network Open journal. The article reports that the newly developed model accurately predicted how blood sugar responded to food 62 percent of the time.

Researchers noted that this was a significant improvement compared to the accuracy based on just carbohydrates (40 percent) or calories (32 percent).

Additionally, the team was able to see why certain foods resulted in tiredness for some people but gave others more energy.

“For people who want to manage their blood glucose levels, we have a new model that predicts their unique response to foods.”

Strengthening the case

Many studies on the topic tend to rely on self-reported data. This can be a problem if a person does not report elements of their day-to-day life accurately.

However, in this particular study, the researchers provided the participants with a food-logging app that allowed them to log meals instantly and privately, reducing the chance of forgetfulness.

It is not the only study to promote a different take on managing blood sugar levels. A 2015 study conducted at Israel’s Weizmann Institute of Science demonstrated similar findings.

The research team believes that comparable findings from two different countries strengthen the case for the individualized model.

“The similarity of results across Israel and the United States suggests that the individualized model works across diverse populations, despite personal traits and microbiomes that tend to vary due to different geographic locations, genetics, and behaviors.”

Courtesy: (medicalnewstoday)

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100 children die in DR Congo measles outbreak

 DR CONGO (AFP): More than a hundred children in Democratic Republic of Congo have died of measles since the start of the year, an outbreak that has added to deadly epidemics of cholera and Ebola, the UN said on Wednesday.

Health officials in the southeast provinces of Lualaba and Lomami recorded 7,175 cases of measles in January, “at least 137 of which were fatal,” the UN’s MONUSCO peacekeeping mission said.

More than 80 percent of the fatalities were children aged under five, it said.

Experts have blamed lack of vaccination, poor medical facilities and malnutrition among the young.

Monusco added that 1,936 cases of cholera had been recorded since the start of the year in Katanga, Lomami and Tanganyika.

Lack of clean drinking water, sanitation and medical care were hampering the fight against the disease, it said.

“We don’t speak about these two epidemics very much” yet they are “also very worrying and deadly,” said the report.

Last weekend, the government said more than 500 people had died from Ebola since last August in North Kivu and Ituri, in the troubled east of the country.

Poor security in the region, where armed rebels have terrorised the population for years, has complicated efforts to roll back the outbreak.

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Timely diagnosis of cancer can save a kid’s life

F.P. Report

ISLAMABAD: International Childhood Cancer Day (ICCD) is celebrated around the world each year on February 15th. This year’s campaign focuses on ‘No More Pain and No More Loss’ for children with cancer and their families.

According to the World Health Organization (WHO) each year, more than 300,000 children, ages birth to 19 years are diagnosed with cancer around the world. Approximately 8 in 10 of these children live in low and middle-income countries where their survival rate is often poor.  These views were expressed by Dr. Saadiya Javed Khan, Consultant Pediatric Oncologist at Shaukat Khanum Memorial Cancer Hospital and Research Centre (SKMCH&RC), while talking to journalists on the occasion of World Childhood Cancer Day.

She added that, “cancer is a curable disease, if diagnosed and treated at an early stage under the supervision of qualified pediatric oncologists. In Pakistan, leukemia or blood cancer is the most common type found in children. Although it is nearly 90-95% curable in the west, survival in Pakistan is about 60-70%.  Factors leading to these poor outcomes include rampant malnutrition, infections, and late diagnosis.

Leukemia mostly affects kids between the ages of 3 to 5 and later adolescents.  The symptoms of leukemia are very identifiable. Some of its major symptoms include pallor, fatigue, easy bruising and frequent bone pains.  Besides leukemia, other common types of cancer seen in Pakistan include lymphomas, bone tumors, and retinoblastomas. As SKMCH&RC is a referral center, it receives patients from not only all provinces of Pakistan but also from Afghanistan as well.

Retinoblastoma, as it is hereditary should have genetic screening and family counselling once a child has been identified with the disease.”

Talking about precautionary measures, Dr. Saadiya said that, “a balanced diet is very important in the upbringing of a healthy child. A huge number of children are victims of malnutrition and avoidable infections if vaccinated appropriately. In our society, children are only being taken to doctors when they fall seriously ill. This practice should be avoided and regular medical checkups must be done after every six months to a year for well-child checks.”

She further added that, “in cancer treatment for children the role of trained pediatric oncologists is vital along with the availability of latest technology.” SKMCH&RC is providing state-of-the-art facilities in this regard. The most popular technology in the treatment of leukemia is cytogenetics and evaluation of minimal-residual disease (MRD) which is being provided to patients since the last couple of years. Cytogenetic helps in risk stratification and appropriate treatment plans. .  SKMCH&RC uses MRD technology to identify the effectiveness of treatment and modification in cases of residual disease.

For the treatment of retinoblastoma, intra-arterial chemotherapy technology  is being developed to help benefit our patients.  . Through this technology, chemotherapy can directly be injected into the tumor site which makes it possible to help prevent systemic side-effects of chemotherapy in young children.”

She informed the journalists, present at the occasion that “SKMCH&RC is also providing play therapy to pediatric patients. Painting, drawing, music and other play therapy strategies are a very effective method for controlling anger and mood swings of children. This helps to distract them and enables them to accommodate to the new changes in their lives.”

In her message on International Childhood Cancer Day, Dr. Saadiya Khan said that, “there is still a lot to do in treating child cancer patients and urged the government and individuals to work together in establishing children friendly hospitals on district and provincial levels. And also increase awareness about cancer in children in the community so that early diagnosis and referrals can help improve disease outcomes.”

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Researchers discover how sleep can fight infection

Monitoring Desk

BERLIN: Researchers in Germany have discovered why sleep can sometimes be the best medicine. Sleep improves the potential ability of some of the body’s immune cells to attach to their targets, according to a new study that will be published February 12 in the Journal of Experimental Medicine.

The study, led by Stoyan Dimitrov and Luciana Besedovsky at the University of Tübingen, helps explain how sleep can fight off an infection, whereas other conditions, such as chronic stress, can make the body more susceptible to illness.

T cells are a type of white blood cell that are critical to the body’s immune response. When T cells recognize a specific target, such as a cell infected with a virus, they activate sticky proteins known as integrins that allow them to attach to their target and, in the case of a virally infected cell, kill it. While much is known about the signals that activate integrins, signals that might dampen the ability of T cells to attach to their targets are less well understood.

Stoyan Dimitrov and colleagues at the University of Tübingen decided to investigate the effects of a diverse group of signaling molecules known as Gαs-coupled receptor agonists. Many of these molecules can suppress the immune system, but whether they inhibit the ability of T cells to activate their integrins and attach to target cells was unknown.

Dimitrov and colleagues found that certain Gαs-coupled receptor agonists, including the hormones adrenaline and noradrenaline, the proinflammatory molecules prostaglandin E2 and D2, and the neuromodulator adenosine, prevented T cells from activating their integrins after recognizing their target. “The levels of these molecules needed to inhibit integrin activation are observed in many pathological conditions, such as tumor growth, malaria infection, hypoxia, and stress,” says Dimitrov. “This pathway may therefore contribute to the immune suppression associated with these pathologies.”

Adrenaline and prostaglandin levels dip while the body is asleep. Dimitrov and colleagues compared T cells taken from healthy volunteers while they slept or stayed awake all night. T cells taken from sleeping volunteers showed significantly higher levels of integrin activation than T cells taken from wakeful subjects. The researchers were able to confirm that the beneficial effect of sleep on T cell integrin activation was due to the decrease in Gαs-coupled receptor activation.

“Our findings show that sleep has the potential to enhance the efficiency of T cell responses, which is especially relevant in light of the high prevalence of sleep disorders and conditions characterized by impaired sleep, such as depression, chronic stress, aging, and shift work,” says last author Luciana Besedovsky.

In addition to helping explain the beneficial effects of sleep and the negative effects of conditions such as stress, Dimitrov and colleagues’ study could spur the development of new therapeutic strategies that improve the ability of T cells to attach to their targets. This could be useful, for example, for cancer immunotherapy, where T cells are prompted to attack and kill tumor cells.

The Journal of Experimental Medicine (JEM) features peer-reviewed research on immunology, cancer biology, stem cell biology, microbial pathogenesis, vascular biology, and neurobiology. All editorial decisions are made by research-active scientists in conjunction with in-house scientific editors. JEM makes all of its content free online no later than six months after publication.

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The time is now for mental health research

LONDON: One in four adults in the UK is directly affected by mental illness each year. This is a huge number of people experiencing conditions that can have very significant, very personal impacts on their day to day life, and yet we have so little in the way of explanation.

We have gaps in knowledge about why some people develop mental illness and some don’t. We don’t know the best treatment for each individual. And we don’t know enough about how to identify those most at risk so we can intervene earlier.

The sad truth today is that getting an accurate diagnosis can take years. Even then, a painful period of trial-and-error often follows until the most appropriate treatment is found. We simply don’t know enough to personalise treatments, both medicines and talking therapies, so that people get the right treatment at the right time.

The good news is that mental health is high on the agenda, like never before. The growing public dialogue around mental health has been exceptional. Members of the royal family have begun campaigning on the issue, successive governments have made mental health a priority, and powerful personal experiences are being shared globally. The days of unspoken conditions are, slowly but surely, giving way to an open and honest conversation about mental health. Providing people with space and the confidence to speak out and tackle stigma.

This is a fantastic first step in the journey of taking on mental illness. This is, however, just a first step. The key to real, lasting change is research.

We know that research has the power to transform lives, as seen so clearly when we look at physical health. Survival rates for cancer have been increased exponentially and HIV is no longer the death sentence it once was. A better understanding of an illness and the opportunity to explore treatments, and even cures, is only possible when we invest in research.

The potential to make this happen for mental health is real. The UK is a world leader in the mental health research field and technologies are providing a newer, faster way to make advances.

However, a lack of funding and prioritisation of research means that too many opportunities are being missed. Despite affecting 23% of the population, only 5.8% of UK health research is spent on mental health. At the moment, mental health research currently receives 22 times less funding than cancer research per person affected – a stark differential that lets down generations of people living with a mental illness.

At MQ, we’re working hard to change the picture. We support over 41 projects internationally, investigating a huge range of conditions: depression, anxiety, schizophrenia, bipolar disorder, eating disorders and more.

We’re an example of an organisation that is funding research to make an impact now and for future generations. We know that 75% of mental illness begins in young people, so we’re investing in a flagship programme to understand what puts young people at risk and identify new ways of intervening early.

By focusing on areas of huge potential, like data science, we are utilising a wealth of information to stimulate new answers to some of the most pressing challenges in mental health. And we’re connecting researchers internationally to share learnings and deepen understanding.

Critically, to deliver the long-term shift needed in mental health research, we’re also building an unprecedented movement of public support – working with people affected scientists, businesses, government and members of the public to make mental health research a national and international priority.

Progress won’t happen overnight. But the stories we hear every day about the challenges they face in getting the right help for their mental health demonstrates why the prize is worth fighting for. And with more and more people demanding better, now is the time for research to give hope in the future.

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