Medically Speaking Team

According to new research, women who experienced substantial stress as a result of the COVID-19 epidemic were twice as likely to see changes in their menstrual cycle.
The study’s findings were published in Obstetrics & Gynecology by the University of Pittsburgh. According to the researchers, more than half of the study participants reported changes in menstrual cycle length, period duration, menstrual flow, or increased spotting, which might have economic and health ramifications for women.

“Early in the pandemic, it would come up anecdotally in talks with girlfriends and other women that ‘things have been kind of crazy with my period since the epidemic,'” said lead author Martina Anto-Ocrah, Ph.D., M.P.H., M.T. (A.S.C.P.). “We know that the epidemic has been a tremendously stressful period for many individuals, and we know that stress may appear in women’s bodies as alterations in menstruation function.”
Between March 2020 and May 2021, Anto-Ocrah and her colleagues created a two-part survey that contained a validated COVID-19 stress scale and self-reported menstrual cycle alterations.

The researchers collaborated with a market research firm to recruit a geographically and ethnically diverse set of participants to conduct the online survey in order to reach a varied population that was representative of the United States. They limited the sample to women between the ages of 18 and 45 who did not use chemical birth control.
10.5% of the 354 women who completed both portions of the poll expressed excessive stress.
After controlling for age, obesity, and other factors, the researchers discovered that women with high COVID-19 stress were more likely than their low-stress counterparts to report changes in menstrual cycle length, period duration, and spotting. In the high stress group, there was also a trend for higher menstrual flow, however this result was not statistically significant.

“Women’s responsibilities were reinterpreted throughout the epidemic, and as a society, we made steps back in terms of gender parity,” Anto-Ocrah explained. “Women frequently bore the burden of childcare and domestic responsibilities, and they perceived changes in daily activities and the risk of COVID-19 infection to be more stressful than males.”
Approximately 12% of subjects reported alterations in all four menstrual cycle aspects, which the researchers described as concerning.
“The menstrual cycle is an indicator of women’s general well-being,” Anto-Ocrah explained. “Menstrual cycle disruption and variable hormones can have an influence on fertility, mental health, cardiovascular disease, and other consequences. Finally, these issues can influence interpersonal dynamics, thereby adding strain to partnerships.”

Longer, more frequent, or heavier periods can also strain women’s budgets due to increased prices for feminine hygiene supplies.
“We know that the epidemic has had a detrimental economic impact on many individuals,” Anto-Ocrah added. “It’s a double whammy if modifications to your flow during a time of economic difficulty boost period-related charges – or the ‘tampon tax’ – economically.”
She believes that the findings will spur additional global research on COVID-19 stress and women’s health, including long-term implications on fertility, menopausal transition, and mental health.

An ultrasound scan can be used to diagnose prostate cancer, according to new study.

In a clinical experiment involving 370 men, researchers from Imperial College London, University College London, and Imperial College Healthcare NHS Trust discovered that a novel form of ultrasound scan may accurately detect most prostate cancer cases. When compared to magnetic resonance imaging (MRI) scans, ultrasound scans missed just 4.3 percent more clinically significant prostate cancer cases (cancer that should be treated rather than watched).

MRI scans are expensive and time-consuming. The team believes that an ultrasound scan should be used as a first test in a community healthcare setting and in low and middle-income countries which do not have easy access to high-quality MRI scans. They say it could be used in combination with current MRI scans to maximise cancer detection. The study is published in Lancet Oncology.

Professor Hashim Ahmed, lead author of the study and Chair of Urology at Imperial College London, said: “Prostate cancer is the most commonly diagnosed cancer in the UK. One in six men will be diagnosed with the disease in their lifetimes and that figure is expected to rise.

“MRI scans are one of the tests we use to diagnose prostate cancer. Although effective these scans are expensive, take up to 40 minutes to perform and are not easily available to all. Also, there are some patients who are unable to have MRI scans such as those with hip replacements or claustrophobia fears. As cancer waiting lists build as a result of the COVID-19 pandemic, there is a real need to find more efficient and cheaper tests to diagnose prostate cancer.

“Our study is the first to show that a special type of ultrasound scan can be used as a potential test to detect clinically significant cases of prostate cancer. The can detect most cases of prostate cancer with good accuracy, although MRI scans are slightly better.

“We believe that this test can be used in low and middle-income settings where access to expensive MRI equipment is difficult and cases of prostate cancer are growing.”

Prostate cancer is the most common cancer in men in the UK with around 52,300 new cases diagnosed each year. It develops when cells in the prostate grow in an uncontrolled way. Prostate cancer develops slowly and symptoms such as the blood in the urine do not appear until the disease has developed. It usually affects men over 50 and often men with a family history of the disease. Black men are disproportionately impacted by the disease and deaths from prostate cancer have now overtaken those from breast cancer.

One of the main methods to diagnose prostate cancer is a special type of magnetic resonance Imaging (MRI) scan called a multi-parametric MRI (mpMRI) scan, which helps doctors see if there is any cancer inside the prostate and how quickly the cancer is likely to grow. However, the scan takes 40 minutes and costs £350-450.

The new study looked at the use of a different kind of imaging called multiparametric ultrasound (mpUSS), which uses soundwaves to look at the prostate.

The test involves the use of a probe called a transducer to make the images of the prostate. It is placed into the rectum and it sends out sound waves that bounce off organs and other structures. These are then made into pictures of the organs.

The doctor doing the test also uses extra special types of ultrasound imaging that look at how stiff the tissue is and how much blood supply the tissue has. These are called elastography, doppler and contrast-enhancement with microbubbles. As cancers are more dense and have greater blood supply, they show up more clearly.

Although mpUSS is more widely available than mpMRI there has been no large-scale studies to validate its effectiveness as a test to detect prostate cancer cases.

In the new trial, called cancer diagnosis by multiparametric ultrasound of the prostate (CADMUS), the team recruited 370 men at risk of prostate cancer. They were identified following initial tests such as a prostate-specific antigen (PSA) test- a blood test to help detect prostate cancer — and/or an abnormal digital rectal examination — a test that examines a person’s lower rectum, pelvis, and lower belly.

The study took place at seven hospitals in the UK including lead site Charing Cross Hospital, part of Imperial College Healthcare NHS Trust, between March 2016-November 2019.

The men were given both mpUSS and mpMRI scans at separate visits. This was then followed by biopsies — which involves using thin needles to take small samples of tissue from the prostate to analyse under a microscope to check cancer — for 257 patients who had a positive mpUSS or mpMRI test result. The team then compared the results from the tests.
Cancer was detected in 133 men, with 83 men diagnosed with clinically significant cancer.

Individually, mpUSS detected 66 cases of clinically significant cancer compared to mpMRI which detected 77 cases.

Although mpUSS detected 4.3 per cent fewer clinically-important prostate cancers compared to mpMRI the researchers said this method would lead to 11.1 per cent more patients being biopsied. This was because the mpUSS sometimes showed up abnormal areas even though there was no cancer.

The researchers believe that the test can be used as an alternative to mpMRI as a first test for patients at risk of prostate cancer, particularly where mpMRI cannot be carried out. Both imaging tests missed clinically-important cancers detected by the other, so using both would increase the detection of clinically-important prostate cancers compared to using each test alone.

First author, Dr Alistair Grey (UCL Division of Surgery & Interventional Science), said:
“Our results provide an accurate test for prostate cancer in patients who were previously without one using a scan that’s cheap and easy to conduct.”

Also Read: Scientists attempt to alleviate nightmares by manipulating emotions in dreams

Nightmares, those horrific experiences that reappear in dreams, can become commonplace, visiting people numerous times each week for months on end.

Dreamers in treatment may be trained to practise happy versions of their most common nightmares. Still, in a study of such individuals published in the journal Current Biology, Swiss researchers go a step further. They observed that using a wireless headband to broadcast a sound connected with a happy daily experience during sleep may lessen the incidence of nightmares.

“There is a relationship between the types of emotions experienced in dreams and our emotional well-being,” says senior author Lampros Perogamvros, a psychiatrist at the Sleep Laboratory of the Geneva University Hospitals and the University of Geneva. “Based on this observation, we had the idea that we could help people by manipulating emotions in their dreams. In this study, we show that we can reduce the number of emotionally very strong and very negative dreams in patients suffering from nightmares.”

Epidemiological studies have found that up to 4 per cent of adults have chronic nightmares at any given time, a condition frequently associated with waking up during the night and poor sleep quality. Patients are frequently prescribed imagery rehearsal therapy, which requires them to rewrite the negative dream scenario and rehearse it during the day. While effective, some cases do not respond.

Perogamvros and his colleagues examined 36 patients who were all receiving imagery rehearsal therapy to see if sound exposure during sleep could improve success. The other half of the group was required to create an association between a positive version of their nightmare and a sound during an imagination exercise, which they needed to practice daily and to wear a headband that could send them the sound during REM sleep for two weeks. This is the stage of sleep where most nightmares occur.

“We were positively surprised by how well the participants respected and tolerated the study procedures, for example performing imagery rehearsal therapy every day and wearing the sleep headband during the night,” says Perogamvros.

“We observed a fast decrease in nightmares, together with dreams becoming emotionally more positive. For us, researchers and clinicians, these findings are very promising both for the study of emotional processing during sleep and for the development of new therapies.”

The number of nightmares per week decreased in both groups, but the half who received the combo therapy experienced fewer nightmares both throughout the intervention and three months later. They also experienced more delight in their dreams. The findings back up the hypothesis that such combination therapy should be studied on a bigger scale and with a diverse population to evaluate the degree and generalizability of its efficacy.

Also Read: Tuberculosis cases surged for the first time in many years: WHO

According to a recent analysis released by the US-based research group Health Effects Institute, practically the entire African continent suffers some of the world’s most severe health consequences due to air pollution, with numerous nations facing some of the world’s highest levels of air pollution (HEI).

The new report, The State of Air Quality and Health Impacts in Africa, provides a comprehensive analysis of major air pollution sources and related health impacts in Africa’s 1.2 billion-person population. The report, released just before the United Nations’ upcoming COP27 Climate Change Conference in Egypt, discovered that air pollution is the continent’s second leading cause of death.

Africa has five of the top ten most polluted countries in the world in terms of outdoor fine particulate matter (PM2.5). In studies of long-term air pollution exposure, outdoor PM2.5 is the most consistent predictor of deaths from cardiovascular, respiratory, and other diseases. In 2019, air pollution was responsible for an estimated 1.1 million deaths in Africa, with 63% of those deaths being linked to exposure to household air pollution (HAP).

Impacts of Air Pollution on Children

Access to clean energy is not provided equitably throughout Africa, resulting in greater illness loads in some places. Every day, an estimated 75% of the population in East, West, Central, and Southern Africa cooks using solid fuels such as coal, wood, and charcoal, exposing them to high concentrations of dangerous pollutants at home.

Newborns and children under the age of five are particularly sensitive in these locations to home air pollution induced by the use of solid fuels for cooking. In 2019, air pollution was responsible for 14% of all fatalities among African children under the age of five.

The effects on newborns and infants have long-term health consequences, including issues with lung development and increased susceptibility to communicable diseases such as lower respiratory infections in young children.

Caradee Wright, the Chief Specialist Scientist with the South African Medical Research Council, said, “This report gives evidence of the substantial threat air pollution poses to the health, and even life, of babies and children under the age of 5 years. This vulnerable group needs special attention to mitigate their exposures, for example, through policy and intensive awareness campaigns with practical solutions for mothers and caregivers.”

Air Pollution Sources Across the Continent

Many of the same sources of PM2.5 found elsewhere in the world are present in Africa, including the use of solid fuels for cooking, the use of fossil fuels (coal, oil, and gas) for energy production, vehicles, industrial and semi-industrial activities such as artisanal mining, agriculture, forest fires, and open waste fire pits. Windblown dust, a natural source of air pollution, is also a major contributor to PM2.5 levels in some parts of Africa.

Air pollution sources and health consequences can vary greatly across the continent. Western Africa has the highest average concentration of PM2.5 pollution at 64.1 g/m3, while Southern Africa has the lowest at 26.5 g/m3. The use of fossil fuels contributes up to 41 per cent of total outdoor PM2.5 levels in Southern Africa, but only 11 per cent in Eastern Africa.

Targeted Actions are Beginning: More Needed

While air pollution levels are high, African countries are implementing a variety of programs to mitigate the effects of air pollution. So far, 17 African countries have implemented national air quality policies, with many including action on air pollution sources, particularly household air pollution, as part of their country’s Nationally Determined Contributions (NDCs). In 2019, Africa had one of the world’s lowest rates of energy access, with fewer than one in every 20 people in the Democratic Republic of the Congo, Ethiopia, Madagascar, Mozambique, Niger, Uganda, and Tanzania having access to clean cooking fuels.

At the same time, a scarcity of ground-level air quality monitoring stations means countries are not able to accurately track their progress towards meeting air quality objectives and standards.

Dr Patrick de Marie Katoto of the Catholic University of Bukavu, Democratic Republic of the Congo, said, “Air pollution greatly contributes to the rising frequency of chronic noncommunicable diseases in Africa, putting further strain on a health system already stretched by chronic infectious diseases and, more recently, COVID-19. These findings call for the African Union and member states to promote, plan, and fund air quality interventions to prevent unnecessary disabilities and deaths throughout the continent.”

Key Connections Between Air Pollution and Climate

When the world’s nations convene in Egypt next month for the COP27 climate negotiations, Africa will discuss how energy transitions might be planned to be efficient, economically practical, sustainable, and ecologically friendly. This complicated problem demands a sophisticated discussion of energy, climate, air quality, and health. African Union nations have also ratified “Agenda 2063,” a continent-wide programme that establishes a strategic framework for achieving the African Union’s aim of inclusive and sustainable development for all people by 2063. In the face of these issues, Africa will benefit from improved public health as well as fewer greenhouse gas emissions.

Also Read: Tuberculosis cases surged for the first time in many years: WHO

Children aged 8 and younger, according to The Pediatric Infectious Illness Journal, the official publication of The European Society for Paediatric Infectious Diseases, should be considered a group at high risk for more serious monkeypox disease. The journal is published by Wolters Kluwer under the Lippincott banner.

According to the review by Petra Zimmermann, MD, Ph.D., of the University of Fribourg, Switzerland, and Nigel Curtis, Ph.D., of The University of Melbourne and Murdoch Children’s Research Institute, Australia, young children would be a key target group for smallpox vaccination and other urgent measures if the outbreak widens. They offer a professional viewpoint on “What doctors need to know” about childhood monkeypox.

Past outbreaks raise concerns about monkeypox risks in young children

Nearly 47,000 monkeypox cases with laboratory confirmation had been reported globally as of August 2022. Only 211 of these were in children and adolescents under the age of 18. The monkeypox virus appears to have been transmitted most widely in the present outbreak through sexual or another close contact. It is still unknown how other transmission pathways, such as droplets and contaminated surfaces and objects, play a part.

Smallpox and monkeypox viruses are both orthopoxviruses, and the epidemic is a reflection of inadequate population immunity as a result of low rates of smallpox immunization. The majority of monkeypox cases are “self-limiting,” with the rash developing and going away in 2 to 4 weeks. However, the absence or mildness of the symptoms might lead to missed diagnoses and the possibility of future spread.

Despite the low reported rates in children so far, there are special concerns about complications and other serious outcomes of monkeypox in children. “Children are reported to have an increased hospitalization rate and increased mortality, even in high-income countries,” Drs. Zimmermann and Curtis write. Based mainly on data from low-income countries, children under 8 are particularly at higher risk of complications, including potentially serious bacterial infections. Young children may also be at increased risk of complications related to scratching and spreading the infection to other parts of the body, including the eyes.

With supportive care, the majority of monkeypox patients will recover. For severe cases and high-risk groups, such as children under 8 years old and people with underlying skin disorders, more specialized care is required. Pregnant individuals, immunocompromised patients, those with eczema, and those who have monkeypox rash around the mouth, eyes, or genitalia are additional risk populations.

Antiviral drugs such as tecovirimat, which is effective against orthopoxviruses, and vaccinia immune globulin (VIG), which is used to treat side effects of smallpox vaccination, are therapy choices in these high-risk situations.

However, “None of these treatments have been proven to be effective against monkeypox virus in humans in clinical trials, and they are currently only recommended after consultation with national health authorities,” the reviewers write.

Although the length of protection is unknown, the smallpox vaccine is effective in preventing monkeypox. Many people have never received a smallpox vaccination because the practice was abandoned when the disease was declared eliminated, which occurred in the United States in 1972.

The FDA has approved a new vaccine (MVA-BN) for the protection of monkeypox, although children have not been “licensed or carefully studied” with it.

Again, there is “very limited data” to support the use of drugs or vaccines to prevent monkeypox in children who have been exposed to the virus. The reviewers also go through certain unique issues for expectant mothers, nursing mothers, and babies born to infected mothers.

Monkeypox can be asymptomatic, thus the outbreak could get out of hand and affect vulnerable populations like young children. The smallpox vaccine would be essential, and “extra urgent steps” would be required in that situation. Drs. Zimmermann and Curtis conclude that smallpox vaccination provides protection against monkeypox. Authorities should be ready to rapidly adopt immunisation of this age group if the present outbreak expand to youngsters.

Also Read: COVID-19 pandemic was, more likely than not, the result of a research-related incident: US Senate report

According to the World Health Organization’s 2022 Global TB report, an estimated 10.6 million individuals were ill with tuberculosis (TB) in 2021, a 4.5% rise from 2020, and 1.6 million died from the disease. The burden of drug-resistant tuberculosis (DR-TB) grew by 3% between 2020 and 2021, with 450 000 additional cases of rifampicin-resistant tuberculosis (RR-TB) in 2021.

This is the first time in many years an increase has been reported in the number of people falling ill with TB and drug resistant TB, according to the WHO report. TB services are among many others disrupted by the COVID-19 pandemic in 2021, but its impact on the TB response has been particularly severe. Ongoing conflicts across Eastern Europe, Africa and the Middle East have further exacerbated the situation for vulnerable populations.

“If the pandemic has taught us anything, it’s that with solidarity, determination, innovation and the equitable use of tools, we can overcome severe health threats. Let’s apply those lessons to tuberculosis. It is time to put a stop to this long-time killer. Working together, we can end TB,” said Tedros Adhanom Ghebreyesus, WHO Director-General.

Due to ongoing difficulty in delivering and obtaining basic TB services, many persons with TB were undiagnosed and untreated. According to the data, the number of persons newly diagnosed with tuberculosis declined from 7.1 million in 2019 to 5.8 million in 2020. Although there was a modest rebound to 6.4 million in 2021, this was still far lower than pre-pandemic levels.

According to WHO, reductions in the reported number of people diagnosed with TB suggest that the number of people with undiagnosed and untreated TB has grown, resulting first in an increased number of TB deaths and more community transmission of infection and then, with some lag-time, increased numbers of people developing TB.

The number of people provided with treatment for RR-TB and multidrug-resistant TB (MDR-TB) has also declined between 2019 and 2020. The reported number of people started on treatment for RR-TB in 2021 was 161 746, only about one in three of those in need.

“The report notes a decline in global spending on essential TB services from USUSD6 billion in 2019 to USUSD5.4 billion in 2021, which is less than half of the global target of USUSD13 billion annually by 2022. As in the previous 10 years, most of the funding used in 2021 (79per cent) was from domestic sources. In other low- and middle-income countries, international donor funding remains crucial,” the WHO said.

The main source is the Global Fund to Fight AIDS, Tuberculosis and Malaria (the Global Fund). The United States Government is the largest contributor of funding to the Global Fund and is also the largest bilateral donor; overall, it contributes close to 50 per cent of international donor funding for TB.

“The report provides important new evidence and makes a strong case on the need to join forces and urgently redouble efforts to get the TB response back-on-track to reach TB targets and save lives,” said Dr Tereza Kasaeva, Director of WHO’s Global TB Programme. “This will be an essential tool for countries, partners and civil society as they review progress and prepare for the 2nd UN High Level Meeting on TB mandated for 2023.”

Also Read: COVID-19 pandemic was, more likely than not, the result of a research-related incident: US Senate report

The US Senate released an initial report on the origins of Covid-19 on Thursday. The panel’s leading member, Richard Burr, expressed optimism that the study will serve as a reference for the World Health Organization (WHO) and other international institutions and scholars.

“With COVID-19 still in our midst, it is critical that we continue international efforts to uncover additional information regarding the origins of this deadly virus. I hope this report will guide the World Health Organization and other international institutions and researchers as they proceed with planned work to continue investigating the origins of this virus. Uncovering the answers to this critical question is imperative to our national and international ability to ensure that a pandemic of this size and scope does not happen again,” Richard said.

“This is an interim report produced by HELP Committee Minority oversight staff. The objective was to review publicly available, open-source information to examine the two prevailing theories of the origin of the Covid-19 virus: a natural zoonotic outbreak or a research-related incident. This Senate Health, Education, Labor, and Pensions (HELP) Committee Minority oversight staff report is the product of that review,” Richard further said

“This is an interim report produced by HELP Committee Minority oversight staff. The objective was to review publicly available, open-source information to examine the two prevailing theories of the origin of the Covid-19 virus: a natural zoonotic outbreak or a research-related incident. This Senate Health, Education, Labor, and Pensions (HELP) Committee Minority oversight staff report is the product of that review,” Richard further said

“Based on the analysis of the publicly available information, it appears reasonable to conclude that the COVID-19 pandemic was, more likely than not, the result of a research-related incident. New information, made publicly available and independently verifiable, could change this assessment,” reads the report.

In the report it has been mentioned that the Wuhan Institute of Virology hasn’t maintained biosafety, “Patents by WIV researchers published in 2018, 2019, and 2020, and procurements made by the WIV in 2019, indicate that the WIV struggled to maintain key biosafety capabilities at its high-containment BSL3 and BSL4 laboratories.”

The report has also given examples to explain bio-safety measures that WIV should have followed.

In conclusion, the report has mentioned that more precise information is required to arrive at the final conclusion, “As noted by the WHO Scientific Advisory Group for the Origins of Novel Pathogens, the COVID-19 Lancet Commission, and the U.S. Office of the Director of National Intelligence 90-Day Assessment on the COVID-19 Origins, more information is needed to arrive at a more precise, if not a definitive, understanding of the origins of SARS-CoV-2 and how the COVID-19 pandemic began. 225 Governments, leaders, public health officials, and scientists involved in addressing the COVID-19 pandemic and working to prevent future pandemics, must commit to greater transparency, engagement, and responsibility in their efforts”

Further, this report has also raised a few questions on the origin of SARS-CoV-2, “However, the hypothesis of a natural zoonotic origin no longer deserves the benefit of the doubt or the presumption of accuracy.

The following are critical outstanding questions that would need to be addressed to be able to more definitively conclude the origins of SARS-CoV-2: What is the intermediate host species for SARS-CoV-2? Where did it first infect humans? Where is SARS-CoV-2’s viral reservoir? How did Covid-19 acquire its unique genetic features, such as its furin cleavage site?
Advocates of a zoonotic origin theory must provide clear and convincing evidence that a natural zoonotic spill-over is the source of the pandemic, as was demonstrated for the 2002-2004 SARS outbreak.”

“In other words, there needs to be verifiable evidence that a natural zoonotic spill-over actually occurred, not simply that such a spill-over could have occurred,” it said.

Also Read: Scientists find new treatment methods for the new Lassa virus fever

The Medical Counseling Committee issued an official notification on Wednesday declaring that the NEET PG round 1 counselling 2022, which was announced yesterday, is being revoked.

“All candidates participating in NEET PG counselling 2022 are hereby informed that the provisional result for Round-1 of PG counselling which was uploaded yesterday (27-9-2022) is being withdrawn since some PG DNB institutes did not complete their address profile on the portal due to which the seats were not visible when ‘State Filter’ was applied by the candidates during choice filling, even though their seats were included in the seat matrix of round-1 and were available for choice filling.” stated notice issued by MCC.

“Keeping in view the larger public interest, the competent authority has decided to open the choice filling again and issue a fresh result for Round – 1 as per the following schedule. Kindly note that candidates who are satisfied with their choices exercised earlier need not make any changes and the software will pick earlier locked choices of candidates for seat processing. However, those who want to make changes in their choices can unfreeze their choices after giving ‘Consent’ on the MCC portal.” it said further.

Dr Rohan Krishnan, National President, Federation of All India Medical Association demanded for transparency in the system.

“We don’t know who should be held responsible for such delays. We don’t know who is responsible for PG counselling, or who is responsible for UG counselling. We don’t even know how the members are being selected. The elected members of the council, the National Medical Commission are also getting elected without any transparency. There is no proper documentation,” he said.

However, the Federation Of Resident Doctors Association (FORDA) tweeted that Union Health Ministry should make strict rules and regulations.

“Every step has its own disappointments, why there can’t be strict rules and regulations?? Why can’t the adherence to rules be checked upon?? Sadism has become a character; Most unfortunate is: ‘Health Ministry remains silent spectator,” it tweeted.

Also Read: Scientists find new treatment methods for the new Lassa virus fever

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A recent study from the La Jolla Institute for Immunology (LJI) offers researchers advice on neutralising the Lassa virus using a trio of unique antibodies acquired from Lassa virus survivors.

Lassa virus is a fatal virus native to West Africa that is mostly spread by rodents. The virus causes Lassa fever, a condition that affects up to 300,000 people each year and often begins with flu-like symptoms but can escalate to severe illness, death, and long-term issues such as hearing. The Lassa virus is highly dangerous for pregnant women, with over 90% of infections resulting in death.

LJI researchers can now demonstrate how a mixture of three human antibodies can prevent viral infection. These antibodies may be useful in planned clinical trials for Lassa therapies, and the LJI team intends to use their newly discovered map of the Lassa virus surface glycoprotein to develop a much-needed vaccine.

“We now know where these three therapeutic antibodies act and how exactly they act,” says Kathryn Hastie, Ph.D., an LJI Instructor and the Director of the Antibody Discovery Center at LJI.

The findings were published in Science Translational Medicine as a cover story on October 26, 2022. The research was led by the Saphire Lab at LJI, including Instructor Haoyang Li, Ph.D., Hastie, and Professor Erica Ollmann Saphire, Ph.D., in collaboration with Luis Branco, Ph.D., of Zalgen Labs LLC.

The power of neutralizing antibodies

In 2017, Hastie and her colleagues at Scripps Research’s Saphire Lab published the first structural photos of the Lassa virus glycoprotein. Lassa enters host cells via glycoproteins and initiates infection. The structure of Hastie’s glycoprotein gave researchers a sense of what they were up against.

Hastie’s discovery emerged while researchers searched for the rare human antibodies that could overcome Lassa’s defenses. Researchers hoped to use these neutralizing antibodies to produce Lassa fever treatments or vaccinations.

This hope was realized when Tulane University and Zalgen Labs LLC researchers discovered a promising group of Lassa-fighting antibodies from the blood of Lassa disease survivors. The University of Texas Medical Branch then tested a combination of three neutralizing antibodies in nonhuman primates. This antibody therapy, known as Arevirumab-3, was completely efficient in curing Lassa fever in animals with advanced disease.

“This was a groundbreaking finding,” says Saphire. “The dogma had been that antibodies would not be protective against Lassa virus.”

When it came time to put the combination through human clinical trials, the researchers ran into a snag. The US Food and Drug Administration refused to allow clinical trials to begin unless researchers identified the mechanism that made the therapy so effective. How did these neutralizing antibodies specifically target the Lassa virus glycoprotein and prevent infection?

Researchers needed a more detailed map of Lassa glycoprotein to address the question. Hastie’s original glycoprotein structure required complex molecular engineering to offer enough stability for imaging. Her structure provided scientists with a key peek of the Lassa glycoprotein, but not the complete picture. Furthermore, certain prospective therapeutic antibodies were unable to identify this or any other type of modified Lassa glycoprotein. For additional research, the researchers were required to extract a natural glycoprotein target.

Fortunately, the Saphire Lab had the tools and expertise to reveal these molecular details. Li led the effort to produce a “native” Lassa glycoprotein. Thanks to advances in protein production and three years of perseverance, Li’s version of the glycoprotein was a copy of the real thing and could be recognized by all three antibodies used in Arevirumab-3. Li then used a technique called cryo-electron microscopy single-particle analysis to image the native glycoprotein together with the three antibodies.

“Haoyang’s ingenuity and hard work enabled us to see the structures we couldn’t see before,” says Hastie.

A new map of the Lassa virus targets

The scientists discovered how the three antibodies utilized in Arevirumab-3 neutralize the Lassa virus using high-resolution structures and various functional experiments.

Hastie was taken aback when he saw how antibody 8.9F binds to the very top of the glycoprotein molecule. This region of the glycoprotein is where three molecules (called protomers) combine to form a “trimer,” which Hastie characterizes as a “twisted trefoil.” Lassa would typically use this section of the glycoprotein to attach to host cell receptors, but Li’s structure shows how a single 8.9F leaps in and binds to all three protomers at the same time to prevent infection.

“The structure is really a beautiful illumination of how this antibody essentially mimics the host receptor to block the glycoprotein receptor from binding,” says Hastie. “It’s an absolutely gorgeous structure to see.”

Meanwhile, the neutralizing antibody 12.1F attaches to only one of the three-sided trimer’s protomers. Fortunately, any treatment would have a large number of copies of 12.1F. Each 12.1F antibody can bind to a protomer to aid in virus neutralization when moving as a team of three.

Simultaneously, copies of antibody 37.2D target the Lassa virus by binding in a way that binds adjacent protomers together. This antibody activity is a major issue for Lassa, as the virus has to open up its trimer (where the protomers come together) in order to infect host cells. With 37.2D on the scene, its entry mechanism is rendered inoperable.

“Lassa has another trick. It shields itself using a thick coat of human carbohydrate molecules — like a wolf in sheep’s clothing,” says Saphire, “Haoyang’s structures clearly show how these potent, protective antibodies breach or even utilize the carbohydrates to target and neutralize the virus.”

“The findings fill a critical gap in Lassa virus research and may pave the way for Arevirumab-3 to move into clinical trials,” says Branco, who will lead the Zalgen team to perform future clinical trials.

Also Read: Study finds cutting on carbs may lower risk of diabetes

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According to new research published today in the peer-reviewed journal Arte by the American Heart Association, the cardiovascular effects of cigarettes and e-cigarettes are strikingly similar, and these harmful effects on blood vessel function are likely caused by airway irritation caused by inhalation of a foreign substance, rather than a specific component of cigarette smoke or e-cigarette vapour (aerosol) (ATVB).

Cigarette smoking and e-cigarette vaping are both known to increase endothelial dysfunction, which is the inability of large blood vessels to open adequately to provide adequate blood flow to the heart and other tissues.

This has the potential to be an early indicator of cardiovascular disease. Endothelial cells line the inside of all blood vessels and control blood vessel opening, material exchange between the bloodstream and surrounding tissues, and immunological and inflammatory responses.

“The goal of this project was to determine why a growing number of inhaled tobacco products, including combustible cigarettes, heated tobacco products, and e-cigarettes, all impair endothelial function despite fundamental differences in these products,” said the lead researcher of both studies Matthew L. Springer, Ph.D., a professor of medicine in the division of cardiology at the University of California, San Francisco.

“Thousands of chemicals have been identified in tobacco smoke, some of which are also present in e-cigarette aerosols, either as an original ingredient or as a chemical reaction product of the heating process. We sought to find which specific component of smoke or e-cigarette vapor may be responsible for interfering with blood vessels’ ability to function efficiently.”

Springer and colleagues conducted two experiments in rats and humans to investigate the effects of smoking and vaping on cardiovascular function.

Rather than a particular smoke ingredient, cigarette smoke inhibits endothelial function owing to vagal input from the airway.

In the rat study, the ability of blood vessels to expand was studied before and after exposure to smoke from four types of traditional combustible cigarettes: conventional nicotine, reduced nicotine, conventional nicotine with added menthol, and reduced nicotine with additional menthol.

Menthol is contained in many tobacco products, and it may minimise the irritation caused by smoking, especially in new smokers, as well as play a crucial role in promoting nicotine addiction.

The study’s findings revealed that blood vessel dilatation was reduced after smoking all four types of cigarettes, with the magnitude of the reduction varying from 20-46% depending on the cigarette type. Although nicotine was not necessary for vascular function impairment, higher nicotine levels were linked with a greater decrease in FMD than lower nicotine levels, and menthol products were related to a lesser decrease in FMD than non-menthol products.

Springer stressed that the discovery that menthol reduced the severity of flow-mediated dilation impairment should not be taken as menthol is a useful component in smoking and vaping products because the impairment was still significant and menthol has additional adverse consequences.

The rats were also given two of the primary gases found in both smoke and e-cigarette aerosol, as well as clean carbon nanoparticles, to see how they affected blood vessel dilatation. Despite being fundamentally different chemical and physical components of smoke, the gases and carbon particles displayed identical impairment effects to whole tobacco smoke.

“Because flow-mediated dilation was impaired by whole smoke, gas phase components of smoke, and plain carbon particles, with no single constituent uniquely responsible, we then explored whether the mechanism involved a common irritation response from the airway involving the vagus nerve,” Springer said.

The vagus nerve is an important part of the parasympathetic nervous system, which regulates involuntary organ activities. It regulates digestion, heart rate, respiratory rate, vascular dilation, inflammatory reactions, and pulmonary functions like cough reflex and mucus formation.

Researchers tested this idea by exposing anesthetized rats to smoke after cutting the vagus nerves. They discovered that stopping nerve signals from reaching the rest of the body from the rats’ lungs fully avoided any vascular functional impairment caused by smoke.

Endothelial dysfunction may be triggered by a vagus nerve-dependent process caused by respiratory irritation and pulmonary sensory nerves, according to these studies.

“We were surprised to discover that it’s not a specific foreign material being inhaled that causes harmful cardiovascular effects – it’s the fact that some kind of irritant is being inhaled in the first place, regardless of what it was,” Springer said. “All inhaled products are likely to have similar harmful effects on vascular function.”

Springer stated that because there is no single toxin that accounts for vascular damage, regulatory bodies cannot rely on forbidding specific chemicals to minimize the negative consequences of inhaled products.

The National Heart, Lung, and Blood Institute, a division of the National Institutes of Health (NIH), and the U.S. Food and Drug Administration Center for Tobacco Products funded this research, as did the National Cancer Institute at the NIH and the Elfenworks Foundation (in memory of Deb O’Keefe) and the Roy E Thomas Medical Foundation.

Chronic e-cigarette/vaping use impairs endothelial function on the physiological and cellular levels

The second study was conducted at different locations and included people who said they smoked combustible cigarettes on a regular basis, people who said they used e-cigarette products on a regular basis, and people who said they didn’t use any nicotine products at all. Researchers measured endothelial function and performed cell culture studies to investigate the association of chronic e-cigarette use on levels of vascular impairment in all subjects at a specific point in time.

Nitric oxide production, a vital component for correctly functioning blood arteries, and endothelial cell permeability, which shows how easily chemicals can leak out of blood vessels, were among the measures taken.

Increased vessel permeability leads to the leakage of larger molecules and may contribute to edema, or swelling caused by excess fluid in tissues, inflammation, heart disease, and other diseases such as cancer.

“Because the combustible cigarette smoke and e-cigarette aerosol that people inhale doesn’t have direct contact with the blood vessels, and the blood does, we took blood serum (the clear liquid in the blood that remains after it clots) from every participant and put it in contact with endothelial cells in a culture dish to evaluate how the different serum samples affected the functional behavior of those cells,” Springer said.

“This enabled us to investigate the effects on endothelial cells of substances in smoke/aerosol that are absorbed through the lungs and enter the bloodstream, and also any other circulating molecules that the body might produce in response to inhaling the smoke and/or aerosol, including proteins involved in the inflammatory response.”

The study recruited 120 adults between the ages of 21 and 50 who were free of cardiovascular disease. People who smoked more than 5 combustible cigarettes per day for a year or longer; people who used electronic cigarette devices 5 or more times per week for 3 months or longer; and people who did not now smoke or vape were eligible to participate.

The study discovered that both long-term vaping and cigarette smoking generate blood alterations that impact endothelial function, albeit in different ways.

* Endothelial cells submerged in blood serum from people who smoked regularly and those who vaped regularly generated less nitric oxide, indicating that the endothelial cells were functionally compromised.

* Condensed e-cigarette aerosol did not directly inhibit nitric oxide synthesis, indicating that the chemicals in the blood that affected nitric oxide generation did not come directly from the aerosol and were instead created by the body in reaction to inhalation.

* Blood serum from participants who regularly vaped, but not those who regularly smoked, increased endothelial cell permeability, allowing more substances to pass through the cells and causing them to behave more like those in leaky blood vessels, which can cause tissue edoema.

* Blood serum from participants who regularly vaped also caused endothelial cells to produce molecules that cause oxidative stress, which is the imbalance of free radicals and antioxidants.

* When compared to persons who did not routinely smoke or vape, people who used e-cigarettes or smoked combustible cigarettes had changes in circulating indicators of inflammation, blood clotting factors, and cell adhesion.

* Certain inflammatory indicators were enhanced in the blood serum of those who smoked combustible cigarettes on a regular basis, but not in those who used e-cigarettes. Other inflammatory indicators were raised in the blood serum of those who vaped regularly but not in those who smoked combustible cigarettes.

“The distinct patterns of these heart disease risk biomarkers in blood serum of frequent users of combustible cigarettes and e-cigarette products indicate that, despite the similar physiological effects, e-cigarette use and smoking trigger fundamentally different molecular responses.

Our findings suggest that vaping, although not smoking combustible cigarettes, causes changes in the blood that increase the potential for leakage in the blood vessels and that both smoking and vaping cause changes in the blood that lead to endothelial dysfunction and an increased risk of future cardiovascular events in otherwise healthy people,” Springer said.

The study also discovered that flow-mediated dilatation was significantly smaller (by more than 5%) among those who used e-cigarettes on a regular basis and those who smoked combustible cigarettes on a regular basis compared to people who neither smoked nor vaped. Previous research has linked a 2% decrease in artery dilation to a 15% increase in heart disease risk, indicating that smoking and vaping have a clinically significant influence.

“It’s important for regulators, clinicians, and the public to realize that vaping is not harmless,” Springer said.

“Smoking and vaping can have similar harmful cardiovascular effects but each condition causes some potentially harmful effects that the other does not. These differences indicate that dual product use, meaning smoking combustible cigarettes and also using e-cigarette products, may actually be worse for vascular health than either smoking or vaping alone.”

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