A new research has found that the drugs used to treat HIV/AIDS patients could be used to treat patients diagnosed with the most common form of primary brain tumour. The breakthrough, co-funded by the charity Brain Tumour Research, is significant because, if further research is conclusive, the anti-retroviral drugs could be prescribed for patients diagnosed with meningioma and acoustic neuroma brain tumours (also known as schwannoma).
More effective approaches are urgently needed as there are very few treatment options for these tumour types which frequently return following surgery and radiotherapy. Meningioma is the most common form of primary brain tumour. Mostly low-grade, it can become cancerous over time and develops from cells located in the meninges which protect the brain and spinal cord. Acoustic neuroma is a different type of low-grade, or non-cancerous brain tumour, which develops in nerve-protecting cells called Schwann cells. Both tumours may occur spontaneously, usually in adulthood, or in the hereditary disease Neurofibromatosis type 2 (NF2) in childhood/early adolescence.
Researchers at the Brain Tumour Research Centre at the University of Plymouth showed previously that a tumour suppressor, named Merlin, contributed to the development of meningioma, acoustic neuroma and ependymoma tumours. It can also contribute to neurofibromatosis type 2 (NF2). Tumour suppressor genes play important roles in normal cells by controlling division or repairing errors in DNA. However, when tumour suppressors do not work properly or are absent, cells can grow out of control, leading to cancer.
In this latest study, Dr Sylwia Ammoun, Senior Research Fellow, and her collaborator, Dr Robert Belshaw investigated the role that specific sections of our DNA play in tumour development. Named ‘endogenous retrovirus HERV-K’, these sections of DNA are relics of ancient infections that affected our primate ancestors, which have become stable elements of human DNA. Dr Ammoun said, “High levels of proteins produced by HERV-K DNA have previously been linked to the development of different tumours. In this study, the team showed that high levels of HERV-K proteins were present in meningioma and schwannoma cells obtained from patients. The team was also able to identify molecular events that may enable HERV-K proteins to stimulate the growth of these tumours. Furthermore, several drugs have identified that target these proteins, reducing the growth of schwannoma and grade I meningioma cells in the laboratory.”
Professor Oliver Hanemann, Director of the Brain Tumour Research Centre of Excellence, added, “Significantly, these drugs – the retroviral protease inhibitors ritonavir, atazanavir, and lopinavir – have already been approved by them for use in the treatment of HIV/AIDS in the USA and are also available in the UK.
These results revealed HERV-K proteins to be critical regulators of growth in tumours that are deficient in Merlin.” Hugh Adams, the spokesman for Brain Tumour Research, said, “These findings are extremely significant as drug repurposing is a valuable way to accelerate the testing of new approaches into clinical trials which, if successful, could reach patients sooner.
“This is particularly critical for patients with brain tumours as many of them do not have the luxury of time,” he added. The Study has been published in Cancer research Journal.
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SOCIALLY ISOLATED OLDER ADULTS MAY HAVE FEWER TEETH: STUDY
Researchers have found that older people who are socially isolated tend to lose their teeth more quickly than those with more social interaction.
The study involved observing older Chinese adults and was led by researchers at NYU Rory Meyers College of Nursing. The findings were published in ‘Community Dentistry and Oral Epidemiology.
“Our study suggests that maintaining and improving social connections may benefit the oral health of older adults,” said Xiang Qi, a PhD student at NYU Meyers and the study’s first author. “The findings align with previous studies demonstrating that structural indicators of social disconnection can have powerful effects on indicators of health and well-being,” he said.
Social isolation and loneliness in older adults have been major public health concerns around the world and are risk factors for heart disease, mental health disorders, cognitive decline, and premature death. In some countries, including the United States and China, up to one in three older adults were lonely, according to the World Health Organization. The COVID-19 pandemic had exacerbated these issues among older adults, as many in-person interactions had been interrupted to protect older adults from infection.
Social isolation and loneliness are related but different. Social isolation has been defined as having few social relationships or infrequent social contact with others, while loneliness referred to the feeling created by a lack of social connection.
“While social isolation and loneliness often go hand in hand, it’s possible to live alone and be socially isolated but to not feel lonely, or to be surrounded by people but still feel lonely,” said Bei Wu, Dean’s Professor in Global Health at NYU Meyers and the study’s senior author.
Older adults are also at risk for another health concern: losing teeth. In China, older adults aged 65 to 74 had fewer than 23 teeth on average (adults typically have 32 teeth, or 28 if wisdom teeth have been removed) and 4.5 per cent of this age group had lost all of their teeth.
Gum disease, smoking, lack of access to dental care, and chronic illnesses like diabetes and heart disease increase the risks of tooth loss. Missing teeth could have a significant impact on one’s quality of life, affecting nutrition, speech, and self-esteem.
To understand the relationship between social isolation, loneliness, and tooth loss in older adults in China, the researchers used the Chinese Longitudinal Healthy Longevity Survey to analyse data from 4,268 adults aged 65 and up. The participants completed surveys at three different time points (2011-12, 2014, and 2018), which captured measures of social isolation and loneliness, how many teeth people had and lost over the 7-year study, and other factors. More than a quarter (27.5 per cent) of the study participants were socially isolated, and 26.5 per cent reported feeling lonely.
The researchers found that higher levels of social isolation were associated with having fewer teeth and losing teeth more quickly over time, even when controlling for other factors such as oral hygiene, health status, smoking and drinking, and loneliness. Older adults who were socially isolated had, on average, 2.1 fewer natural teeth and 1.4 times the rate of losing their teeth than those with stronger social ties.
“Socially isolated older adults tend to be less engaged in social and health-promoting behaviours like physical activity, which could have a negative impact on their overall functioning and oral hygiene, as well as increase their risk for systemic inflammation,” said Wu. “This functional impairment seems to be a major pathway linking social isolation to tooth loss.”
Surprisingly, loneliness was not associated with the number of remaining teeth, nor with the rate of tooth loss.
“While social isolation can result in a lack of support that can affect health behaviours, for older adults who feel lonely, it’s possible that their social networks are still in place and can help them to keep up healthy behaviours,” said Qi.
The findings highlighted the importance of developing interventions to reduce social isolation.
Breakthrough COVID-19 infections spur strong antibody responses: Study
In view of the spike in COVID-19 infections globally, a recent study shed light on the strength, durability, and breadth of neutralising antibody responses generated by breakthrough infections in individuals vaccinated against SARS-CoV-2.
Alexandra Walls and David Veesler in the Department of Biochemistry at the University of Washington in Seattle led the project.
Characteristics of the Delta and Omicron coronavirus variants of concern included enhanced transmissibility and immune evasion even in non-immunologically naive individuals, compared to the ancestral pandemic coronavirus.
These characteristics, and the waning of immunity from vaccines, have led to breakthrough infections in vaccinated individuals. For the most part, otherwise healthy people who were vaccinated against the SARS-CoV-2 usually did not have severe symptoms if they did end up contracting the virus.
The researchers wanted to understand what effect catching the virus after being vaccinated had on neutralizing antibodies, and to see how durable and broad these responses were. Their hope was that advancing such knowledge would help guide vaccination policies and pandemic mitigation strategies.
Through their project the researchers learned that the degree of antibody response depended on whether a person has had one, two, three, or four exposures to the spike protein through infection, vaccination, or a mixture of the two. The scientists also checked antibody responses in groups of individuals who had been vaccinated after having COVID-19, those who were previously vaccinated and experienced a breakthrough infection, those who were vaccinated only, and those who were boosted and therefore vaccinated three times.
Among their study subjects, those who had completed a three-vaccination protocol, and those who had been vaccinated after recovering from COVID-19, and those with a breakthrough infection after vaccination launched almost comparable neutralizing antibody responses, in terms of magnitude and breadth. Their serum binding and antibody neutralizing responses to the spike protein in the current pandemic coronavirus variants were much more potent and lasting than those generated by people who had received only two doses of COVID-19 vaccine or who had a previous infection not followed by vaccination.
This observation suggested that the increased number of exposures to SARS-CoV-2 antigens, either through infection and vaccination or triple vaccination, enhanced the quality of antibody responses.
The researchers also looked at how broad the elicited antibodies could be. They investigated neutralization of the divergent Omicron SARS-CoV-2 variant of concern, currently responsible for the majority of cases in the United States. Their findings showed that boosted individuals (or those that have a mixture of infection and double vaccination) have neutralizing antibodies at similar levels to subjects vaccinated twice against the original ancestral strain. This suggested a large amount of immune evasion, but that vaccine boosters could help close the neutralizing antibody gap caused by Omicron.
Looking outside of the SARS-CoV-2 family showed a similar pattern, where repeated and multiple exposures improved the otherwise weak neutralizing antibody response to SARS-CoV. Finally, the authors did not identify improvements in antibody binding to common cold causing coronavirus spike proteins like OC43 or HKU1.
This suggested that repeated SARS-CoV-2 exposure does not improve spike reactivity to more divergent coronaviruses. These findings supported the development of broader sarbecovirus or coronavirus vaccines to be prepared in the event of a future spillover event.
The study groups consisted of about 15 people, from the Hospitalized or Ambulatory Adults with Respiratory Viral Infections, or HAARVI, project at the UW in Seattle. HAARVI, led by UW Medicine infectious disease physician Helen Chu, looked at recovered COVID-19 patients to study immune responses over time, to understand the long-term consequences of the infection, and to compare immune responses from vaccines and natural infections.
The findings were published in ‘Cell’, one of the scientific journals of Cell Press.
FERTILITY TREATMENT DURING PANDEMIC
The COVID-19 pandemic caused fertility clinic closures worldwide. These closures were abrupt and sudden, patients undergoing treatment lost access to services during the first phase of the pandemic, the cycles that were in progress were abandoned which led to the freezing of all embryos in an IVF cycle without a fresh embryo transfer.
The COVID-19 pandemic has claimed the lives of over one million people worldwide and has affected all aspects of healthcare worldwide including the delivery of care to patients with fertility-related diagnoses.
Subsequently, only emergency medical services were functioning and all the assisted reproductive technology (ART) clinics were shut down which had an enormous impact on the patients already undergoing infertility treatment economically as well as mentally. But, as the ongoing coronavirus pandemic situation is stabilising, it becomes essential to resume the ART services in a gradual manner. However, strict vigilance and a stepwise approach to the treatment are being adhered to, to minimise the risks related to COVID-19 infection to patients and healthcare staff.
• Patients are fully informed about the nature of the Covid-19 pandemic and its effect on their treatment and future pregnancy outcome(s).
• Patients acknowledge all the facts and give informed consent for the fertility treatment at this particular time.
• The ART clinics modified their layout and working practices in accordance with National and local guidelines for Covid-19.
Couples are strongly advised to take an RT-PCR test before commencing treatment. This must be repeated before any ART procedure that is considered invasive and requires regional or general anaesthesia such as egg retrieval, HCG trigger or embryo transfer. It is advised that the test is done less than three days prior to the procedure. To avoid getting infected, patients are strongly recommended, partners and potential donors are advised to self-isolate from the beginning of ovarian stimulation until the procedure is finished.
When the pandemic first hit, there was a fear about the safety to conceive or even visiting the clinic for consultations. But people are more informed now.
In recent weeks, the highly contagious Omicron variant of COVID-19 has resulted in a surge of new cases across India and other countries. Mostly, all ART Clinics have additional protective measures in place, Staff members who cannot maintain a 2m distance from patients are required to wear an isolation gown, N95 mask, eye protection, and gloves to minimise transmission. Clinics are conducting regular Rapid Antigen tests on all their clinic staff members.
In addition to the existing precautions and safety measures a vaccine policy for all of our team members is being implemented, all staff must complete COVID-19 screening forms daily before entering the clinic.
The additional protocols followed by the clinics will ensure safety and will continue to offer all fertility services while maintaining a safe clinic environment for patients and staff.
For patients currently undergoing treatment, Self-monitoring for COVID-19 symptoms and completing pre-screening forms before appointments is mandatory. Patients are advised not to visit the clinic if experiencing any symptoms or are feeling unwell.
Patients are advised of getting fully vaccinated now to decrease the risk of developing a severe COVID-19 infection and to further reduce the risk of transmission. Recent public health initiatives have expanded vaccine eligibility, and all of our patients (whether they are trying to get pregnant or are already pregnant) are advised and encouraged to book appointments to receive their 1st, 2nd or booster dose when available.
In compliance with public health guidelines, ART Clinics continue to carefully minimise the number of people inside the clinics at any given time. To mitigate the risks of exposure for everyone, a no visitor policy is enforced.
All patients are encouraged to maintain social distancing, practice good hand hygiene and be diligent about social gatherings. All patients are required to wear a medical face mask at all times during their visit to the clinic. Nonetheless, this is a particularly challenging time for patients with infertility. Under the best of circumstances, infertility treatment is a time of uncertainty and emotional challenges; the coronavirus pandemic has intensified the distress many couples experience in this setting, while at the same time cutting off access to important sources of support, including family, friends, support groups, and professional mental health services.
Dr Rita Bakshi is the founder of RISAA IVF.
MORE THAN 5 HOURS’ EMERGENCY WAIT BEFORE ADMISSION LINKED TO INCREASED DEATH RISK: STUDY
A new study has found that waiting for more than five hours in emergency care before admission to the hospital is associated with a heightened risk of death from any cause within the next 30 days.
This can be measured and represented as a ‘number needed to harm metric’, of 1 extra death for every 82 patients delayed after 6-8 hours, concluded the researchers.
The 4-hour waiting time target before hospital discharge, admission, or transfer was introduced in 2004 in England, and shortly afterward in the other devolved nations of the UK, in a bid to tackle emergency department overcrowding.
Several other countries, including Canada and Australia, followed suit with similar measures. But in recent years, performance against this target has steadily declined amid rising patient demand.
Delays to timely admission from emergency departments have been linked to patient harm, and the researchers wanted to quantify the increased risk of death resulting from these delays.
They drew on Hospital Episode Statistics and Office of National Statistics data for England, covering every patient admitted to hospital from each major (type 1) emergency department in England between April 2016 and March 2018.
They compared recorded deaths from any cause within 30 days of admission with those that would be expected, allowing for a wide range of potentially influential factors.
These included sex, age, deprivation level, concurrent conditions, time of the day and month, previous attendances/emergency admissions, and crowding in the emergency department at the time.
Between April 2016 and March 2018, 26,738,514 people attended an emergency department in England: 5,249,891 of them were admitted to the hospital.
In all, 433,962 people died within 30 days during the study period. The overall unadjusted 30-day death rate was just under 9 per cent.
The average age of patients admitted was 55; the number of concurrent conditions rose in tandem with increasing age. Nearly twice as many patients came from areas of greatest deprivation as came from areas of least deprivation.
The most frequent time of arrival was between 12:00 and 17:59 hours, with the first 3 months of the year accounting for the biggest proportion of patients. The average wait in the emergency department was just under 5 hours; the breach rate of the 4-hour waiting time target averaged around 38 per cent
A statistically significant linear increase in the death rate emerged for waits longer than 5 hours in the emergency department.
After accounting for potentially influential risk factors, the death rate was 8 per cent higher than expected among those patients waiting between 6-8 hours before admission to hospital, and 10 per cent higher than expected for those waiting 8-12 hours, compared with patients moving on within 6 hours.
This can be measured and represented as a ‘number needed to harm metric’, of 1 extra death for every 82 patients delayed for 6-8 hours, said the researchers.
“The results from this study show that there is a ‘dose-dependent’ association between time in excess of 5 hours in the [emergency department] for admitted patients and their all-cause 30-day mortality,” they wrote.
“Moreover, 30-day mortality is a relatively crude metric that does not account for either increase in patient morbidity or for the inevitably worse patient experiences,” they added.
This is an observational study, and as such, can’t establish cause and effect.
But, said the researchers, “Despite limited supporting evidence, there are a number of clinically plausible reasons to accept that there is a temporal association between delayed admission to a hospital inpatient bed and poorer patient outcomes.”
Long stays in the emergency department are associated with exit block and crowding, which can delay access to vital treatments. And they are associated with an increase in subsequent hospital length of stay, especially for older patients, noted the researchers.
This, in turn, increases the risk of hospital-acquired infection and physiological and psychological deconditioning, they said.
Exit block is usually also related to bed occupancy levels, which are highest in the late afternoon and usually lower around midnight. A disproportionate number of delayed patients are therefore likely to be moved to a ward during the night when staffing levels are lowest, they added.
And they concluded, “This study confirms that healthcare policymakers should continue to mandate timely admission from the [emergency department] in order to protect patients from hospital-associated harm.”
In a linked editorial, Derek Prentice, lay member for the Royal College of Emergency Medicine, insisted, “Let nobody be in doubt any longer, the NHS 4-hour operational target is, as many of us have always known, of key importance to patient safety.”
With sufficient funding for NHS beds and staff and social care provision, and prioritisation from NHS leaders, hospitals should be able to meet this target, he said. But these have been in short supply in recent years, he suggested. “Could there be better measures? Possibly, but until there are, and crucially, ones that have the support and trust of patients, the 4-hour target or one very close to this, must remain the gold standard. Those in doubt need look no further than the evidence provided by this excellent paper,” he asserted.
The Study has been published in the Emergency Medicine Journal ‘.
STUDY FINDS COVID-19 VACCINES OFFER LASTING PROTECTION
A new research has found that COVID-19 vaccination offers long-lasting protection from the worst outcomes of COVID-19.
The emergence of the delta and omicron variants had raised questions about whether breakthrough infections are caused by waning immunity or by the more transmissible variants.
Results of the study suggested that declining immunity is responsible for breakthrough infections, but vaccines maintained protection from hospitalization and severe disease nine months after getting the first shot.
“The primary takeaway message from our study is that unvaccinated people should get vaccinated right away,” said lead study author Danyu Lin, PhD, Dennis Gillings Distinguished Professor of Biostatistics at the UNC Gillings School of Global Public Health.
“The results of our study also underscore the importance of booster shots, especially for older adults,” Lin added.
The study, which is a collaboration between the UNC-Chapel Hill and the North Carolina Department of Health and Human Services, examined data on COVID-19 vaccination history and health outcomes for 10.6 million North Carolina residents between December 2020 and September 2021.
The study results were used by the Centres for Disease Control and Prevention to support the use of booster shots.
“This is an excellent example of the wonderful research partnership between the Gillings School and NCDHHS, who are working together to generate the evidence base needed to keep our communities safe,” said Penny Gordon-Larsen, PhD, Carla Smith Chamblee Distinguished Professor of Global Nutrition and associate dean for research at UNC Gillings School of Global Public Health
This data included outcomes from COVID-19 cases caused by the delta variant. However, data from this study were collected before the discovery of the omicron variant.
“By applying a novel methodology to the rich surveillance data, we were able to provide a precise and comprehensive characterization of the effectiveness over a nine-month period for the three vaccines employed in the U.S.,” Lin said.
“Unlike previous studies, we estimated the vaccine effectiveness in reducing the current risks of COVID-19, hospitalization, and death as a function of time elapsed since the first dose,” Lin continued.
“This information is critically important in determining the need for and the optimal timing of booster vaccination,” Lin added.
The study found that the effectiveness of the Pfizer and Moderna mRNA vaccines in reducing the risk of COVID-19 reached a peak of about 95 per cent two months after the first dose and then gradually declined. At seven months, the Pfizer vaccine dropped to 67 per cent effectiveness, compared to the Moderna vaccine, which maintained 80 per cent effectiveness.
Among early recipients of the two mRNA vaccines, effectiveness dropped dramatically from mid-June to mid-July, when the delta variant was surging.
Effectiveness for the Johnson & Johnson adenovirus vaccine was 75 per cent at one month after injection and fell to 60 per cent after five months. All three vaccines were effective at keeping people out of the hospital due to severe COVID-19. Effectiveness of the Pfizer vaccine reached a peak of 96 per cent at two months and remained around 90 per cent at seven months; effectiveness of the Moderna vaccine reached a peak of 97 per cent at two months and remained at 94 per cent at seven months. The effectiveness of the Johnson & Johnson vaccine reached a peak of 86 per cent at two months and was higher than 80 per cent through six months.
For all three vaccines, effectiveness against death was higher than that of hospitalization.
“Because the majority of the vaccines in the U.S. were administered more than seven months ago and only a small percentage of the population has received boosters, waning immunity is likely contributing to the breakthrough infections with the omicron variant,” Lin said.
Everyone age 5 and older are eligible for a COVID-19 vaccine. Those ages 18 and up should get a booster shot.
The research was led by Lin with major contributions from Yu Gu, a doctoral student in biostatistics, and Donglin Zeng, PhD, professor of biostatistics. NCDHHS epidemiologists Bradford Wheeler, Hayley Young, Shadia Khan Sunny, and Zack Moore participated in the research. Shannon Holloway from the North Carolina State Department of Statistics also contributed.
The research has been published in the ‘New England Journal of Medicine ‘
NEW STUDY REVEALS BEING IN SPACE DESTROYS MORE RED BLOOD CELLS
A world-first study has revealed how space travel can cause lower red blood cell counts, known as space anemia.
Analysis of 14 astronauts showed their bodies destroyed 54 per cent more red blood cells in space than they normally would on Earth, according to a study published in ‘Nature Medicine’.
“Space anemia has consistently been reported when astronauts returned to Earth since the first space missions, but we didn’t know why,” said lead author Dr Guy Trudel, a rehabilitation physician and researcher at The Ottawa Hospital and professor at the University of Ottawa.
“Our study shows that upon arriving in space, more red blood cells are destroyed, and this continues for the entire duration of the astronaut’s mission,” added Dr Trudel.
Before this study, space anemia was thought to be a quick adaptation to fluids shifting into the astronaut’s upper body when they first arrived in space. Astronauts would lose 10 per cent of the liquid in their blood vessels this way. It was thought that astronauts rapidly destroyed 10 per cent of their red blood cells to restore the balance, and that red blood cell control came back to normal after 10 days in space.
Instead, Dr Trudel’s team found that the red blood cell destruction was a primary effect of being in space, not just caused by fluid shifts. They demonstrated this by directly measuring red blood cell destruction in 14 astronauts during their six-month space missions.
On Earth, our bodies create and destroy 2 million red blood cells every second. The researchers found that astronauts were destroying 54 per cent more red blood cells during the six months they were in space, or 3 million every second. These results were the same for both female and male astronauts.
Dr Trudel’s team made this discovery due to the techniques and methods they developed to accurately measure red blood cell destruction. These methods were then adapted to collect samples aboard the International Space Station.
At Dr Trudel’s lab at the University of Ottawa, they were able to precisely measure the tiny amounts of carbon monoxide in the breath samples from astronauts. One molecule of carbon monoxide was produced every time one molecule of heme, the deep-red pigment in red blood cells, was destroyed.
While the team didn’t measure red blood cell production directly, they assumed that the astronauts generated extra red blood cells to compensate for the cells they destroyed. Otherwise, the astronauts would end up with severe anemia, and would have had major health problems in space.
“Thankfully, having fewer red blood cells in space isn’t a problem when your body is weightless,” said Dr Trudel. “But when landing on Earth and potentially on other planets or moons, anemia affecting your energy, endurance, and strength can threaten mission objectives. The effects of anemia are only felt once you land, and must deal with gravity again,” he said.
In this study, five out of 13 astronauts were clinically anemic when they landed –one of the 14 astronauts did not have blood drawn on landing. The researchers saw that space-related anemia was reversible, with red blood cells levels progressively returning to normal three to four months after returning to Earth.
Interestingly, the team repeated the same measurements one year after astronauts returned to Earth, and found that red blood cell destruction was still 30 per cent above pre-flight levels. These results suggest that structural changes may have happened to the astronaut while they were in space that changed red blood cell control for up to a year after long-duration space missions.
The discovery that space travel increases red blood cell destruction had several implications. First, it supported the screening of astronauts or space tourists for existing blood or health conditions that are affected by anemia. Second, a recent study by Dr Trudel’s team found that the longer the space mission, the worse the anemia, which could impact long missions to the Moon and Mars. Third, increased red blood cell production would require an adapted diet for astronauts. And finally, it was unclear how long the body could maintain this higher rate of destruction and production of red blood cells.
These findings could also be applied to life on Earth. As a rehabilitation physician, most of Dr Trudel’s patients were anemic after being very ill for a long time with limited mobility, and anemia hindered their ability to exercise and recover. Bedrest had been shown to cause anemia, but how it did this was unknown.
“If we can find out exactly what’s causing this anemia, then there is a potential to treat it or prevent it, both for astronauts and for patients here on Earth,” said Dr Trudel.
He was further quoted saying, “This is the best description we have of red blood cell control in space and after return to Earth. These findings are spectacular, considering these measurements had never been made before and we had no idea if we were going to find anything. We were surprised and rewarded for our curiosity.”
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