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Amid scary headlines about disease, important progress against tuberculosis

As headlines focus on COVID-19 and, now, monkeypox, tuberculosis remains one of the great scourges of infectious disease around the world. Approximately 1.5…

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As headlines focus on COVID-19 and, now, monkeypox, tuberculosis remains one of the great scourges of infectious disease around the world. Approximately 1.5 million people died of tuberculosis in 2020, the World Health Organization reports. Alarmingly, that year marked the first increase in TB deaths in more than a decade. But doctors and scientists at the University of Virginia School of Medicine are making important progress in their longstanding efforts to better understand, prevent and treat tuberculosis, and they’ve received a $1.25 million boost for a partnership with colleagues in Tanzania to train the next generation of front-line soldiers in the war against the disease.

Credit: Courtesy Scott Heysell | UVA Health

As headlines focus on COVID-19 and, now, monkeypox, tuberculosis remains one of the great scourges of infectious disease around the world. Approximately 1.5 million people died of tuberculosis in 2020, the World Health Organization reports. Alarmingly, that year marked the first increase in TB deaths in more than a decade. But doctors and scientists at the University of Virginia School of Medicine are making important progress in their longstanding efforts to better understand, prevent and treat tuberculosis, and they’ve received a $1.25 million boost for a partnership with colleagues in Tanzania to train the next generation of front-line soldiers in the war against the disease.

Malnutrition’s Role in Tuberculosis

New discoveries from the researchers highlight the crucial role of malnutrition in global tuberculosis. In a new paper in the scientific journal The Lancet Microbe, the UVA researchers and their collaborators in Tanzania reveal how malnutrition and gut infections impair tuberculosis treatments for young children. The scientists found that children with these common gut infections have lower concentrations of the critical TB drugs in their bodies – and the more infections they have, the lower the concentration of the drugs. Based on these first-of-kind findings, the researchers say that doctors may be able to target the gut pathogens to improve tuberculosis treatment outcomes. 

“Blame for failure of tuberculosis treatment historically was placed on the patient and a lack of adherence to medicines,” said researcher Scott Heysell, MD, MPH, of UVA’s Division of Infectious Diseases and International Health. “Instead, the other germs in the gut of children from impoverished areas are leading to suboptimal levels of key medicines even if taken as directed. Some of the same pathogens in the gut that lead to malnutrition and predispose to malnutrition-related tuberculosis make tuberculosis even harder to treat.” 

Malnutrition is a vastly underappreciated contributor to tuberculosis, the researchers say. In a paper in the scientific journal The Lancet Infectious Diseases, the authors call malnutrition a “leading risk factor” for contracting the disease. There is an urgent need, they say, to better understand how nutritional deficiencies compromise the body’s immune system. This understanding would shed important light on how malnutrition and “undernutrition” affect the effectiveness of both tuberculosis vaccines and treatments.

In the paper, Heysell and his co-authors urge dramatic action against malnutrition and undernutrition: “It is time for governments, non-governmental organizations, philanthropic foundations and researchers to be invigorated by the challenge and not daunted by it. A rapid scale-up in funding and research is needed,” they write. “The payoff could be monumental. Investments in eradicating undernutrition will probably have long-reaching benefits, far beyond their impact on tuberculosis, and can be transformative, especially for low-income regions. We should consider a Haitian saying: ‘Giving people medicine for tuberculosis and not giving them food is like washing your hands and drying them in the dirt.’”

Training the Next Generation

Based, in part, on the new tuberculosis findings, the National Institutes of Health’s Fogarty International Center has awarded the UVA scientists a $1.25 million grant that will bolster a longstanding training partnership with their collaborators in Tanzania. The crucial funding will allow the partnership to train Tanzanian postdoctoral researchers to work specifically on the intersection malnutrition and tuberculosis.

Similar collaborative models through UVA’s Division of Infectious Diseases and Center for Global Health Equity have already trained 177 international students of varying academic stages over the last decade. Of those, almost 90% remain in research careers. “Prioritizing the education of international trainees in global health benefits us all,” Heysell said. “We can do more to follow the lead of young scientists in settings bearing disproportionate poverty.”

One of the strengths of the program is its diversity. Eleven of the faculty members are from UVA, and seven are Tanzanian. Eight are women. That allows the program to connect the postdocs with Tanzanian mentors and with secondary mentors from UVA, providing the trainees access to a broad breadth of experience and expertise. The program will be led by Heysell and Stellah Mpagama, MD, PhD, director of research and innovation at Tanzania’s Kibong’oto Infectious Diseases Hospital, adjunct faculty at UVA, and the recipient of the Dr. Maria Kamm Best Female Scientist in Tanzania for 2022.

“This program will enable Tanzanians to develop research leaders that will take forward the agenda of ‘End TB’ in the country,” Mpagama said. “In the past decade, the collaborative research we conducted enlightened us a lot on the various challenges that impede TB control. The next steps are to develop solutions simultaneously with development of research leaders to ensure continuity of the scientific efforts to curb this long-standing epidemic.”

The researchers are excited about the potential of the training partnership to not only help prevent and treat tuberculosis in Tanzania but to generate new discoveries that will help battle diseases of poverty around the world.

“As ancient human conditions, malnutrition and tuberculosis do not often grab headlines,” Heysell said. “Yet our collective progress in improving these conditions is a bellwether in how well we are doing to reduce other socioeconomic inequities.”

About the Tanzania Tuberculosis Effort

UVA faculty and staff participating in the training partnership include Rebecca Dillingham, Tania Thomas, Eric Houpt, James Platts-Mills, Marcel Durieux, Amber Steen, Mark DeBoer, Richard Guerrant, Rebecca Scharf, Margaret Kosek, Christopher Moore and Megan Null Toerien. The effort is supported by UVA’s Office of the Provost and the School of Medicine. 

The Lancet Microbe paper was authored by Daniel Van Aartsen, Museveni Justine, Estomih Mduma, Stellah G. Mpagama, Mohammad H. Alshaer, Charles A. Peloquin, Buliga Mujaga, Athanasia Maro, Jean Gratz, Margaret Kosek, Jie Liu, Elizabeth T. Rogawski McQuade, Eric R. Houpt, Tania A. Thomas and Scott K. Heysell. The work was funded by the National Institutes of Health’s National Institute of Allergy and Infectious Diseases, grants U01AI115594 and T32AI007046.

The Lancet Infectious Diseases paper was authored by Pranay Sinha, Knut Lönnroth, Anurag Bhargava, Scott K. Heysell, Sonali Sarkar, Padmini Salgame, William Rudgard, Delia Boccia, Daniel Van Aartsen and Natasha S Hochberg. 

The NIH Fogarty grant is project No. 1D43TW012247-01. 

To keep up with the latest medical research news from UVA, subscribe to the Making of Medicine blog at http://makingofmedicine.virginia.edu.


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New Hampshire Governor Vetoes Ivermectin Bill

New Hampshire Governor Vetoes Ivermectin Bill

Authored by Alice Giordano via The Epoch Times (emphasis ours),

New Hampshire’s Republican…

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New Hampshire Governor Vetoes Ivermectin Bill

Authored by Alice Giordano via The Epoch Times (emphasis ours),

New Hampshire’s Republican Gov. Chris Sununu vetoed a bill that would have made Ivermectin available without a prescription.

Ivermectin tablets packaged for human use. (Natasha Holt/The Epoch Times)

The Republican governor vetoed the bill on June 24, the same day that the U.S. Supreme Court overturned Roe v. Wade. Some fellow Republicans questioned the timing.

It certainly seemed like a convenient way to bury a veto of a bill that won support from the vast majority of Republicans in New Hampshire,” JR Hoell, co-founder of the conservative watchdog group RebuildNH, told The Epoch Times.

Hoell is a former four-term House Republican planning to seek re-election after a four-year hiatus from the the New Hampshire legislature.

Earlier this year, the New Hampshire Department of Children Youth and Family (DCYF) tried to take custody of Hoell’s 13-year old son after a nurse reported him for giving human-grade ivermectin to the teen months earlier.

Several states have introduced bills to make human-grade ivermectin available without a prescription at a brick and mortar store. Currently, it can be ordered online from another country. In April, Tennessee became the the first state to sign such a measure into law. New Hampshire lawmakers were first to introduce the idea.

Both chambers of the state’s Republican controlled legislature approved the bill.

In his statement explaining the veto, Sununu noted that there are only four other controlled medications available without a prescription in New Hampshire and that each were only made available after “rigorous reviews and vetting to ensure” before being dispensed.

“Patients should always consult their doctor before taking medications so that they are fully aware of treatment options and potential unintended consequences of taking a medication that may limit other treatment options in the future,” Sununu said in his statement.

Sununu’s statement is very similar to testimony given by Paula Minnehan, senior vice president of state government regulations for the New Hampshire Hospital Association, at hearings on the bill.

Minnehan too placed emphasis on the review that went into the four prescription medications the state made available under a standing order. They include naloxone, the generic name for Narcan, which is used to counter opioid overdoses, hormone replacement therapy drugs, and a prescription-version of the morning after pill.

It also includes a collection of smoking cessation therapy drugs like Chantix, which has been linked to suicide, depression, and other neuropsychiatric conditions. Last year, Pfizer, the leading maker of the FDA-approved drug, conducted a voluntarily recall of Chantix. Narcan has also been linked to deaths caused by severe withdrawals that have led to acute respiratory distress.

Rep. Melissa Blasek, a Republican co-sponsor of the New Hampshire ivermectin bill, told The Epoch Times, that one could veto any drug-related bill under the pretense of overdose concerns.

The reality is you can overdose on Tylenol,” she said. “Ivermectin has one of the safest track records of any drug.”

The use of human-grade ivermectin became controversial when some doctors began promoting it for the treatment and prevention of COVID-19. Government agencies including the FDA and CDC issued warnings against its use while groups like Front Line COVID-19 Critical Care Alliance (FLCCC) heavily promoted it.

Some doctors were  disciplined for prescribing human-grade ivermectin for COVID-19 including a Maine doctor whose medical license was suspended by the state.

Read more here...

Tyler Durden Thu, 06/30/2022 - 20:30

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Aging-US | Time makes histone H3 modifications drift in mouse liver

BUFFALO, NY- June 30, 2022 – A new research paper was published in Aging (Aging-US) on the cover of Volume 14, Issue 12, entitled, “Time makes histone…

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BUFFALO, NY- June 30, 2022 – A new research paper was published in Aging (Aging-US) on the cover of Volume 14, Issue 12, entitled, “Time makes histone H3 modifications drift in mouse liver.”

Credit: Hillje et al.

BUFFALO, NY- June 30, 2022 – A new research paper was published in Aging (Aging-US) on the cover of Volume 14, Issue 12, entitled, “Time makes histone H3 modifications drift in mouse liver.”

Aging is known to involve epigenetic histone modifications, which are associated with transcriptional changes, occurring throughout the entire lifespan of an individual.

“So far, no study discloses any drift of histone marks in mammals which is time-dependent or influenced by pro-longevity caloric restriction treatment.”

To detect the epigenetic drift of time passing, researchers—from Istituto di Ricovero e Cura a Carattere Scientifico, University of Urbino ‘Carlo Bo’, University of Milan, and University of Padua—determined the genome-wide distributions of mono- and tri-methylated lysine 4 and acetylated and tri-methylated lysine 27 of histone H3 in the livers of healthy 3, 6 and 12 months old C57BL/6 mice. 

“In this study, we used chromatin immunoprecipitation sequencing technology to acquire 108 high-resolution profiles of H3K4me3, H3K4me1, H3K27me3 and H3K27ac from the livers of mice aged between 3 months and 12 months and fed 30% caloric restriction diet (CR) or standard diet (SD).”

The comparison of different age profiles of histone H3 marks revealed global redistribution of histone H3 modifications with time, in particular in intergenic regions and near transcription start sites, as well as altered correlation between the profiles of different histone modifications. Moreover, feeding mice with caloric restriction diet, a treatment known to retard aging, reduced the extent of changes occurring during the first year of life in these genomic regions.

“In conclusion, while our data do not establish that the observed changes in H3 modification are causally involved in aging, they indicate age, buffered by caloric restriction, releases the histone H3 marking process of transcriptional suppression in gene desert regions of mouse liver genome most of which remain to be functionally understood.”

DOI: https://doi.org/10.18632/aging.204107 

Corresponding Author: Marco Giorgio – marco.giorgio@unipd.it 

Keywords: epigenetics, aging, histones, ChIP-seq, diet

Sign up for free Altmetric alerts about this article:  https://aging.altmetric.com/details/email_updates?id=10.18632%2Faging.204107

About Aging-US:

Launched in 2009, Aging (Aging-US) publishes papers of general interest and biological significance in all fields of aging research and age-related diseases, including cancer—and now, with a special focus on COVID-19 vulnerability as an age-dependent syndrome. Topics in Aging go beyond traditional gerontology, including, but not limited to, cellular and molecular biology, human age-related diseases, pathology in model organisms, signal transduction pathways (e.g., p53, sirtuins, and PI-3K/AKT/mTOR, among others), and approaches to modulating these signaling pathways.

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For media inquiries, please contact media@impactjournals.com.

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FDA asks for COVID boosters to fight Omicron’s BA.4, BA.5 subvariants

The U.S. Food and Drug Administration on Thursday recommended booster doses of COVID-19 vaccines be modified beginning this fall to include components…

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FDA asks for COVID boosters to fight Omicron’s BA.4, BA.5 subvariants

By Michael Erman

June 30 (Reuters) – The U.S. Food and Drug Administration on Thursday recommended booster doses of COVID-19 vaccines be modified beginning this fall to include components tailored to combat the currently dominant Omicron BA.4 and BA.5 subvariants of the coronavirus.

The FDA said manufacturers would not need to change the vaccine for the primary vaccination series, saying the coming year will be “a transitional period when this modified booster vaccine may be introduced.”

FILE PHOTO: Signage is seen outside of the Food and Drug Administration (FDA) headquarters in White Oak, Maryland, U.S., August 29, 2020. REUTERS/Andrew Kelly/File Photo

The new booster shots would be bivalent vaccines, meaning doses would target both the original virus as well as the Omicron subvariants.

The decision follows a recommendation by the agency’s outside advisers to change the design of the shots this fall in order to combat more prevalent versions of the coronavirus. read more

BA.4 and BA.5 are now estimated to account for more than 50% of U.S. infections, according the U.S. Centers for Disease Control and Prevention, and have also become dominant elsewhere.

The FDA said in a statement on Thursday that it hoped the modified vaccines could be used in early to mid-fall.

Pfizer Inc (PFE.N) with partner BioNTech SE (22UAy.DE) and Moderna Inc (MRNA.O) have been testing versions of their vaccines modified to combat the BA.1 Omicron variant that caused the massive surge in cases last winter.

Although they have said those vaccines worked against BA.1 and the more recently circulating variants, they did see a lower immune response against BA.4 and BA.5.

The companies had already been manufacturing their BA.1 vaccines, and said on Tuesday that swapping to a BA.4/BA.5 version could slow the rollout.

Pfizer/BioNTech, which on Wednesday announced a $3.2 billion contract to supply more COVID vaccine doses to the United States, said they would have a substantial amount of BA.4/BA.5 vaccine ready for distribution by the first week of October. read more

Moderna said it would be late October or early November before it would have the newly modified vaccine ready.

Reporting by Michael Erman in New Jersey and Leroy Leo in Bengaluru; Editing by Jonathan Oatis and Bill Berkrot

Our Standards: The Thomson Reuters Trust Principles.

Source: Reuters

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