Archive for category: News

Spinal muscular atrophy (SMA) is a debilitating genetic disorder characterized by muscle weakness and degeneration that often leading to severe disability and shortened lifespan. A new therapy called apitegromab for patients revealed promising results in a recent phase 2 clinical trial published in the Neurology Journal.

Apitegromab is an investigational fully human monoclonal antibody that works by inhibiting myostatin that regulates skeletal muscle growth. Unlike the currently approved therapies for SMA that mainly focus on reversing degeneration, apitegromab targets the preservation of muscle mass to address the underlying impairment caused by neurodegeneration.

The phase 2 TOPAZ trial evaluated the safety and efficacy of apitegromab in individuals with later-onset type 2 and type 3 SMA. The study explored potential eligibility criteria and treatment regimens for future research that involved three cohorts of participants aged from 2 to 21 years. The trial was conducted across 16 sites in the United States and Europe that revealed promising results. 58 participants received apitegromab infusions every four weeks for 12 months. The primary efficacy measure using the Hammersmith Functional Motor Scale demonstrated improved motor function in participants across all cohorts.

The participants in cohort 3, who received apitegromab in combination with nusinersen showed the most significant improvement. At 12 months, the mean scores increased by 5.3 points for the 2-mg/kg arm and 7.1 points for the 20-mg/kg arm. Also, this therapy demonstrated a favorable safety profile with no deaths or serious adverse reactions reported.

These encouraging outcomes support the advancement of apitegromab into a randomized, placebo-controlled phase 3 trial for SMA patients. If successful, apitegromab could offer the much-needed treatment option that halts disease progression and further improves motor function by enhancing the quality of life for individuals living with SMA.

Source:

Crawford, T. O., Darras, B. T., Day, J. W., Dunaway Young, S., Duong, T., Nelson, L. L., Barrett, D., Song, G., Bilic, S., Cote, S., Sadanowicz, M., Iarrobino, R., Xu, T. J., O’Neil, J., Rossello, J., Place, A., Kertesz, N., Nomikos, G., & Chyung, Y. (2024). Safety and Efficacy of Apitegromab in Patients With Spinal Muscular Atrophy Types 2 and 3. In Neurology (Vol. 102, Issue 5). Ovid Technologies (Wolters Kluwer Health). https://doi.org/10.1212/wnl.0000000000209151

A recent study published in the Journal of Translational Medicine explored the intricate relationship between monocytic inflammation, C-reactive protein (CRP) and the onset of type 2 diabetes (T2D). The investigation looked into the association between systemic inflammation that assessed by joint cumulative high-sensitivity C-reactive protein (CumCRP), monocyte to high-density lipoprotein ratio (CumMHR)and the incidence of T2D within the general population.

Over 40,000 nondiabetic individuals participated in this prospective real-life cohort study, with biennial follow-ups that spanned from 2010/2011 to December 31, 2020. Through rigorous multivariable Cox regression analyses, the team evaluated adjusted hazard ratios (aHRs) of incident diabetes.

The findings revealed that over a median follow-up of nearly eight years, 4848 cases of T2D emerged. CumMHR and CumCRP was found to be significant predictors of T2D, both independently and in conjunction. The elevated CumMHR levels were found to increase the risk of developing diabetes across all CumCRP strata by indicating a relationship between these markers. The observation that individuals with concurrent elevations in CumMHR and CumCRP underwent the highest risk of T2D by emphasizing the importance of considering multiple markers in assessing diabetes risk was striking.

This study highlighted the influence of demographic and clinical factors such as age, sex, hypertension, dyslipidemia and prediabetes status on the observed risk. This precise understanding underlines the complexity of T2D development and the need for personalized risk assessment strategies. The addition of CumMHR and CumCRP to established risk factors significantly enhanced risk prediction and reclassification of diabetes by improvements in C-statistics and net reclassification improvement.

Reference:

Wu, D., Chen, G., Lan, Y., Chen, S., Ding, X., Wei, C., Balmer, L., Wang, W., Wu, S., & Xu, W. (2024). Measurement of cumulative high-sensitivity C-reactive protein and monocyte to high-density lipoprotein ratio in the risk prediction of type 2 diabetes: a prospective cohort study. In Journal of Translational Medicine (Vol. 22, Issue 1). Springer Science and Business Media LLC. https://doi.org/10.1186/s12967-024-04895-4

In a groundbreaking development for pediatric dentistry, researchers have explored an alternative to the long-established gold standard material, Mineral Trioxide Aggregate (MTA), for vital pulpotomy procedures in primary molars. The study concludes that TotalFill® BC RRM™ Fast Set Putty can be considered a viable alternative to MTA for primary molar pulpotomy.

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• Contrary to the longstanding belief in MTA as the gold standard, the study revealed that TotalFill® BC RRM™ Fast Set Putty can serve as a credible alternative in primary molar pulpotomy procedures.
• The research found no statistically significant difference in the success rates of pulpotomy procedures between MTA and BC RRM-F.
• Moreover, the choice of final restorative material proved to be a crucial factor.
• Survival analysis indicated that using glass ionomer (GI) instead of stainless-steel crowns (SSC) was associated with an increased risk of failure, emphasizing the significance of the overall treatment approach.

Also Read: Silver diamine fluoride additional tool for addressing dentine hypersensitivity and improving QoL of patients, states study

Further reading: One-year Radiographic and Clinical Performance of Bioactive Materials in Primary Molar Pulpotomy: A Randomized Controlled Trial. Doi: https://doi.org/10.1016/j.jdent.2024.104864

USA: A new study published in Microbiology Spectrum has shed light on the antimicrobial properties of tomato juice and peptides against typhoidal Salmonella. 

The research revealed that tomato juice demonstrates significant antimicrobial properties against Salmonella Typhi, a deadly human-specific pathogen that specifically affects humans and is responsible for causing typhoid fever. 

“Tomato juice can kill Salmonella Typhi and other bacteria that can harm people’s digestive and urinary tract health,” the researchers reported. 

“Our main goal in this study was to find out if tomato and tomato juice can kill enteric pathogens, including Salmonella Typhi, and if so, what qualities they have that make them work,” said principal study investigator Jeongmin Song, Ph.D., Associate Professor, Department of Microbiology & Immunology, Cornell University.

First, the researchers, in laboratory experiments, checked to see if tomato juice really does kill Salmonella Typhi. Once they ascertained it did, the team looked at the tomato’s genome to find the antimicrobial peptides that were involved. Antimicrobial peptides are very small proteins that impair the bacterial membrane that keep them as intact organisms. The researchers chose 4 possible antimicrobial peptides and tested how well they worked against Salmonella Typhi. This helped them find 2 antimicrobial peptides effective against Salmonella Typhi.

The research team conducted more tests on Salmonella Typhi variants that appear in places where the disease is common. They also did a computer study to learn more about how the antibacterial peptides kill Salmonella Typhi and other enteric pathogens. Lastly, they looked at how well tomato juice worked against other enteric pathogens that can hurt people’s digestive and urinary tract health.

The most significant discovery is that tomato juice is effective in eliminating Salmonella Typhi, its hypervirulent variants, and other bacteria that can harm people’s digestive and urinary tract health. In particular, 2 antimicrobial peptides can eliminate these pathogens by impairing the bacterial membrane, a protective layer that surrounds the pathogen.

“Our research shows that tomato and tomato juice can get rid of enteric bacteria like Salmonella,” Song said. The researchers said they hope that when the general public, particularly children and teenagers, learns about the study outcome, they will want to eat and drink more tomatoes as well as other fruits and vegetables because they provide natural antibacterial benefits to consumers.

Reference:

Ryan S. Kwon, Gi Young Lee, Sohyoung Lee, Jeongmin Song. Antimicrobial properties of tomato juice and peptides against typhoidal Salmonella. Microbiology Spectrum, 2024; DOI: 10.1128/spectrum.03102-23.

In a bid to enhance public health in
the 21st century, the spotlight is now on preventing heart failure (HF), and a
groundbreaking study sheds light on a potentially transformative approach. The
Objective Physical Activity and Cardiovascular Health (OPACH) in Older Women
study, conducted from March 2012 to April 2014, reveals a compelling link
between accelerometer-measured physical activity (PA), sedentary time, and
incident HF in older women, offering insights into HF subtypes—preserved
ejection fraction (HFpEF) and reduced ejection fraction (HFrEF).

The study results were published in
the journal JAMA Cardiology.

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Heart failure (HF) poses a significant
challenge for the aging US population, especially impacting women, older
adults, and diverse groups. The lack of clear therapies for preserved EF
(HFpEF) underscores the importance of HF prevention. The Objective Physical
Activity and Cardiovascular Health (OPACH) study aims to address these gaps,
utilizing accelerometer-measured physical activity to explore associations with
incident overall HF, HFpEF, and HFrEF in older women. The study’s hypothesis
suggests that higher physical activity levels are associated with reduced HF
risk, while increased sedentary time correlates with higher HF risk.

The cohort, consisting of 5951 women
aged 63 to 99 years without known HF, embarked on a seven-day journey with
hip-worn triaxial accelerometry. Follow-up for incident HF extended through
February 2022, unraveling a wealth of data and associations.

The study, analyzing various facets of
daily PA such as total, light, and moderate to vigorous PA (MVPA), along with
steps taken, and sedentary behavior including total sedentary time and mean
bout duration, delivers nuanced insights into HF prevention.

Findings:

• 
  Among the racially and ethnically
  diverse cohort—comprising non-Hispanic Black, Hispanic, and non-Hispanic White
  women—407 HF cases surfaced during an average follow-up of 7.5 years, with 257
  classified as HFpEF and 110 as HFrEF.

• The study’s fully adjusted hazard
  ratios (HRs) underscore the impact of physical activity on HF prevention.

• A 1-standard deviation increment in
  minutes per day of total PA yielded striking HRs of 0.85 (95% CI, 0.75-0.95)
  for overall HF, 0.78 (95% CI, 0.67-0.91) for HFpEF, and 1.02 (95% CI,
  0.81-1.28) for HFrEF.

• Steps per day and total sedentary time
  also exhibited significant associations with HF subtypes.
  

• 
  The study’s cubic spline curves paint
  a vivid picture, emphasizing the significance of total PA and steps per day.

• An inverse relationship is evident,
  indicating that increased physical activity correlates with a decreased risk of
  overall HF and HFpEF.

• Conversely, total sedentary time
  showed a positive association, underlining the potential risks of prolonged
  inactivity.
  

• 
  Light PA and MVPA emerged as champions
  in the fight against HF, showcasing inverse associations with overall HF and
  HFpEF.

Also Read: Study suggests excess vitamin B3 could increase heart disease risk

This underscores the role of various intensities of physical activity in
preventing heart failure among older women.

These findings carry profound
implications, suggesting that a strategic focus on increasing physical activity
and reducing sedentary time could serve as a formidable strategy for primary
HFpEF prevention. As discussions surrounding heart failure prevention gain
momentum in public health, this study provides actionable insights that could
significantly impact cardiovascular resilience and foster healthy aging among
older women.

Further reading: LaMonte MJ, LaCroix AZ, Nguyen S, et al. Accelerometer-Measured Physical Activity, Sedentary Time, and Heart Failure Risk in Women Aged 63 to 99 Years. JAMA Cardiol. Published online February 21, 2024. doi:10.1001/jamacardio.2023.5692