The study was done by a team of researchers at the The Hebrew University-Hadassah Medical School, led by Bracha Ochana and Daniel Nudelman, under the supervision of
Prof. Tommy Kaplan, Prof. Yuval Dor and Prof. Ruth Shemer.
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Prof. Tommy Kaplan[/caption]
MedicalResearch.com: What is the background for this study?
Response: DNA methylation is a key epigenetic modification that annotates the human genome. It is established during development and cellular differentiation, and is associated with maintenance of cell type identity and control of gene expression. Nonetheless, few regions in the human genome change with age and serves as a powerful biomarker for estimating chronological and biological age. However, most current epigenetic clocks rely on average methylation at individual CpG sites using array-based data, which overlook complex regional patterns across neighboring methylation sites. This study aimed to understand how time and age are encoded at the molecular and cellular level, and to develop a highly accurate age predictor, based on regional methylation dynamics.
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Prof. Ruth Shemer[/caption]
MedicalResearch.com: What types of cells were used in the study, ie keratinocytes, muscle cells etc?
Response: The primary tissue used in this study was peripheral blood from over 300 healthy human donors (18-78 years old). To further understand how the methylation changes are associated with changes in blood cell composition, we also sorted immune cell types including neutrophils, monocytes, B cells, and T cells. For forensics applications, we also tested the clock on urine and saliva samples.
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Prof. Yuval Dor[/caption]
MedicalResearch.com: Does this study relate at all to telomere length?Response:
Response: No, this study does not investigate or reference telomere length. It focuses entirely on DNA methylation changes at few genomics regions, each covering multiple clustered DNA methylation sites, where methylation changes are indicative of chronological age, independently of telomere biology.
MedicalResearch.com: What are the main findings?
Response: - A single-molecule analysis using DNA sequencing, revealed that
age-related methylation changes often occur regionally across multiple neighboring methylation sites, either in a stochastic or in a block-like manner.
- A deep neural network model, called MAgeNet, was trained on methylation patterns from two specific genomic loci (ELOVL2 and C1orf132) and was able to predict chronological age (of held-out test-set donors) at a median accuracy of 1.36 years (for individuals under 50).
- These predictions are robust to sex, smoking, BMI, and biological age markers, and accurate even from as few as 50 cells or at low-depth sequencing.
- Longitudinal sampling of healthy donors at the age of 32 and 42, shows that early deviations from predicted age persist over time, suggesting that as we age, methylation changes faithfully encode the passage of time.
Dr. Campanella[/caption]
Gabriele Campanella, PhD
Assistant Professor
Windreich Department of Artificial Intelligence and Human Health
Icahn School of Medicine at Mount Sinai
MedicalResearch.com: What is the background for this study?
Response: Lung cancer is the most lethal cancer in the US. Lung adenocarcinoma (LUAD) is the most common form of lung cancer with an incidence of over 100k per year in the US. EGFR mutations are common driver mutations in LUAD, and importantly, these mutations can be targeted by TKI therapy, which has high response rates. Because of this, EGFR testing via NGS (Next Generation Sequencing) is considered mandatory by guidelines for any LUAD diagnosis.
In high-resource settings, rapid EGFR testing is done while waiting for confirmation via NGS. This is because NGS takes about 2 weeks on average, while the rapid testing has a median TAT of 2 days. Early treatment decisions could be made based on the rapid test results. Rapid tests have some important drawbacks, most notably, it exhausts tissue. In lung cancer, tissue is scarce in the first place, and up to 25% of cases, after rapid testing there is not enough tissue for NGS. In those circumstances, patients have to be biopsied again, which adds unnecessary risk for the patient. Even worse, in some cases, the NGS is never done. A non-tissue-exhaustive computational biomarker could be used instead of the tissue-based rapid test.
However, did you know that your diet also has a connection with your sexual life? Without the right diet men can be predisposed to sexual problems. In this article, we are going to explore the relationship between diet and one such sexual health issue that occurs in men known as impotence ED. Consider ED or erectile dysfunction as a form of sexual health issue that does not allow you to get a hard erection. Men may treat this problem with the help of medications such as 
Dr. Lopes[/caption]
Gilberto Lopes, M.D.
Professor, Chief, Division of Medical Oncology
Associate Director for the Cancer Center and
Medical Director for International Affairs
Sylvester Comprehensive Cancer Center
MedicalResearch.com: What is the background for this study?
Response: There is growing evidence linking alcohol consumption to increased cancer risk and mortality. This association was recently emphasized by the former U.S. Surgeon General, prompting renewed public health interest. In response to these concerns, under the mentorship of Dr. Lopes, we evaluated national trends in alcohol-associated cancer mortality using data from the Global Burden of Disease database.
Dr. Piper[/caption]
Brian J. Piper, PhD
Department of Medical Education
Center for Pharmacy Innovation & Outcomes
Geisinger College of Health Sciences
Scranton, PA 18509
MedicalResearch.com: What is the background for this study?
Dr. Piper: Tapentadol has an unusual mechanism of action. This opioid is similar to morphine in that it activates mu, the main opiate receptor which is important for pain. This drug also acts similar to an antidepressant like duloxetine (Cymbalta) with equal ability to block both the norepinephrine and the serotonin transporters (Figure 1). The combination of opioid and monoaminergic activity may influence both therapeutic and side effect profiles.
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Figure 1. Biological mechanism of action of the atypical opioid tapentadol involves binding to the mu opiate receptor, blocking the norepinephrine transporter (NET), and blocking the serotonin transporter (SERT) [1].[/caption]Tapentadol is approved in the US for moderate to severe acute pain, moderate to severe chronic pain, and neuropathic pain associated with diabetic peripheral neuropathy. However, tapentadol is not generally considered first-line for any of these indications. Although this agent has a high potential for abuse and is classified as a Schedule II substance, a manufacturer of extended release tapentadol (Grunenthal) has conducted a misinformation campaign claiming tapentadol has a “minimum potential of abuse”, does not cause respiratory depression (a well-known opioid effect), does not cause any euphoric feelings, has no street value, and is not an opioid [2]. Prior pharmacoepidemiological studies have examined the use patterns of other prescription opioids that can be misused like oxycodone [3], fentanyl [4], meperidine [5] and methadone [6] but there is limited national information about the use of tapentadol.
