Month: July 2021

Categories : GeneticsTags :

Misattributed Paternity Decreasing – In Sweden, At Least

On By ModernMedia
Photo by Drew Hays on Unsplash

The frequency of misattributed paternity, where the assumed father is not the biological father, is low and decreasing in Sweden, according to an analysis of nearly 2 million family units with children born mainly between 1950 and 1990.

The rates of misattributed paternity are estimated to range from 0.8% to 30% across different countries and studies. Taking information from genetic and behavioural studies, the article characterised that individuals at higher risk being those who conceive younger, live in deprived circumstances, are in long term relationships (rather than marriages), or in certain cultural groups.

In the study published in the Journal of Internal Medicine, the overall rate of misattributed paternity was 1.7%, with rates closer to 1% in more recent decades.

The researchers used nationwide ABO blood group data and a nationwide register of familial relationships in Sweden. These data were analysed using both a frequentist Poisson model and the Bayesian Gibbs model. The study, which drew on 1.95 million mother-father-offspring family units estimated that the frequency of misattributed paternity was 1.7% in both models. Misattributed paternity was more common among parents with low educational levels, and has decreased over time to a current 1%.

The researchers noted that beyond its general scientific and societal relevance, the frequency of misattributed paternity has an effect on studies on hereditary conditions. Fortunately, the study’s findings indicate that misattributed paternity is unlikely to have large effects on such studies.
“Using simple but elegant methods, together with large-scale register data, we present population-based estimates of a peculiar question. These findings should once and for all put an end to the common misconception of overinflated occurrences of misattributed paternity in the general population,” said lead author Torsten Dahlén, of the Karolinska Institutet, in Sweden.

Source: EurekAlert!

Categories : Diseases, Syndromes and ConditionsTags :

Nerve Damage Observed as Liver Disease Progresses

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Photo by National Cancer Institute on Unsplash

Using an innovative 3D imaging technology, researchers at Karolinska Institutet have discovered that a part of the liver’s autonomic nervous system undergoes severe degeneration in non-alcoholic fatty liver disease.

The study showed that the degeneration of nerves is correlated with the severity of liver pathology. The findings are being published in the journal Science Advances.

With a global prevalence of about 25 percent, non-alcoholic fatty liver disease is the most common hepatic disorder. Approximately one third of all fatty liver cases progress to steatohepatitis, a severe disease seriously affecting the entire metabolism.

In the current paper, researchers explore the nervous system in fatty liver using volume immuno-imaging and light sheet microscopy ― a novel imaging technique, which together offers large-scale 3D visualisation with cellular resolution. According to the study, this technology can reveal even early, minor or hidden structural impairments of the liver.

“Now we know that nerves in the liver have multiple subtle regulatory roles” says Csaba Adori, researcher at the Department of Neuroscience, who led the study. “Their role, however, may be more essential during the fight-or-flight response or when subjected to metabolic challenges. Degeneration of liver sympathetic nerves and abnormal operation of the remaining nerve fibres in the fatty liver could compromise all these functions, which may contribute to further aggravation of the disease, as part of a vicious cycle.”

According to the study, changes in liver innervation are already underway in the early stages of fatty liver disease. As it progresses to more severe steatohepatitis, these impairments become a significant degradation of the nerves. The nerve pathology is also similar in mouse models of fatty liver and in human fatty liver samples. The team hopes this will open new avenues for  the treatment of steatohepatitis and portal hypertension, through targeting the liver sympathetic nervous system.

Source: Karolinska Institutet

Categories : COVIDTags :

Vitamin D Deficiency Shown to Increase COVID Severity and Mortality

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Photo by Julian Jagtenberg from Pexels

A new study conducted by the Azrieli Faculty of Medicine of Bar-Ilan University and its affiliate Galilee Medical Center (GMC) is one of the first to show that vitamin D deficiency before infection is associated with increased COVID severity and mortality. The study is available on the medRxiv preprint server, awaiting peer review.

Vitamin D has attracted attention in prevention of severe COVID as its levels are known to be related to risks of influenza and respiratory tract infections. It also has direct antiviral effects primarily against enveloped viruses, which include coronaviruses.

Previous studies that examined the link between vitamin D levels and SARS-CoV-2 infection had mixed results. Most measured vitamin D levels once patients were already sick, making interpretation of the results difficult. The new study assessed this correlation using low levels of vitamin D measured prior to infection and also focused on disease severity.

The researchers searched for vitamin D levels measured 14 to 730 days prior to positive PCR tests in the records of individuals admitted between April 2020 and February 2021 to GMC in Nahariya, Israel.

Of 1176 patients admitted, 253 had vitamin D levels recorded prior to COVID infection. Compared to mildly or moderately diseased patients, those with severe or critical COVID disease were more likely to have severe pre-infection vitamin D deficiency with levels less than 20 ng/mL.

“This study can highlight the risks of vitamin D deficiency in terms of COVID-19,” said Dr Amiel Dror, of GMC and the Azrieli Faculty of Medicine of Bar-Ilan University, who led the study. “Vitamin D is often associated with bone health. We’ve shown that it may also play an important role in other disease processes, such as infection.”

Prof Michael Edelstein, of the Azrieli Faculty of Medicine of Bar-Ilan University said, “It is still unclear why certain individuals suffer severe consequences of COVID-19 infection while others don’t. Our finding adds a new dimension to solving this lingering puzzle. In Israel, where vitamin D deficiency is common in certain population groups, this finding is particularly important.”

The authors said that the link between low pre-infection vitamin D levels and severe COVID does not necessarily imply that giving vitamin D to COVID patients will decrease the risk of severe disease. However, it does highlight the need to better manage vitamin D deficiency.

Source: Bar-Ilan University

Categories : Obstetrics & GynaecologyTags :

WHO-recommended Pregnancy Gap Too Long for Some Countries

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Researchers have found that a World Health Organization (WHO) recommendation to wait at least 24 months to conceive after a previous birth may be unnecessarily long for mothers in high-income countries.

Lead researcher Dr Gizachew Tessema from the Curtin School of Population Health said that since the WHO advice was based on limited evidence from resource-limited countries, it was necessary to check the recommendation in higher-income settings. The researchers’ findings were published in journal PLOS ONE.  

“We compared approximately 3 million births from 1.2 million women with at least three children and discovered the risk of adverse birth outcomes after an interpregnancy interval of less than six months was no greater than for those born after an 18-23 month interval,” Dr Tessema said.

“Given that the current recommendations on birth spacing is for a waiting time of at least 18 months to two years after livebirths, our findings are reassuring for families who conceive sooner than this.

“However, we found siblings born after a greater than 60-month interval had an increased risk of adverse birth outcomes.”

Dr Tessema said just as the current WHO recommendations are not age specific, the study’s results were not necessarily equally applicable to parents of all ages.

“Our next step with this research is to identify whether intervals between pregnancies affect the risk of adverse birth outcomes among women of different ages,” Dr Tessema said.

Dr Tessema is a perinatal and reproductive epidemiologist and conducted the study with senior author Professor Gavin Pereira, who are both from the Curtin School of Population Health and the new Curtin enAble Institute.

Source: Curtin University

Categories : COVIDTags :

Epsilon and Delta Variant Mutations Allow Immune Evasion

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Researchers found that the L452R mutation of the SARS-CoV-2 spike protein, common to two mutant strains, the Epsilon and Delta, can evade cellular immunity through the human leukocyte (HLA) A24 and can increase viral infectivity.

The study, by researchers at the Kumamoto University and Weizmann Institute of Science, was published in the journal Cell Host & Microbe. It showed emerging mutations L452R and Y453F in the SARS-CoV-2 spike receptor-binding motif evade (HLA) A24-restricted cellular immunity. The L452R mutation also enhances spike stability, viral fusogenicity, and viral infectivity. Hence, the findings suggest that HLA-restricted cellular immunity potentially affects the evolution of viral phenotypes.

Emerging variants of concern (VOC) may escape immune responses induced by vaccination or natural infection, threatening global vaccination efforts.

The first reported and well-studied mutant contains a D614G substitution in the spike (S) protein. The D614G mutation has recently been shown to enhance the binding affinity of SARS-CoV-2 to the ACE2 receptor. It is also more infectious and easily transmissible. However, there is no evidence suggesting that the D614G variant is tied to increased lethality.

At the end of 2020, the emergence of new variants was reported – the B.1.1.7 (Alpha), the B.1.351 (Beta), and the P.1 (Gamma) in the United Kingdom, South Africa, and Brazil, respectively. At the end of 2020, another lineage, the B.1.427 also called the CAL.20C, occurred in California, United States.

The Delta variant is becoming dominant globally, and has been linked to increased infectivity, transmissibility, severe illness, and even death.

Interestingly, mutated viruses are mainly due to error-prone viral replication, and the spread of new variants is linked to their escape from immune responses. SARS-CoV-2 mutants may resist neutralising mediated antibodies from COVID patients and vaccinated individuals.

Further, the new emerging variants may escape the cellular immunity conferred by cytotoxic T lymphocytes (CTLs), which recognise non-self epitopes present on virus-infected cells through the HLA class I molecules. This is called CTL-mediated antiviral immunity.

Human CTLs were recently shown to be able to recognise HLA-restricted SARS-CoV-2-derived epitopes. Also, the functionality of virus-specific cellular immunity correlates inversely with COVID-19 severity. Thus, CTLs play pivotal roles in controlling SARS-CoV-2 infection.

The team explored the potential emergence of SARS-CoV-2 mutants that can evade HLA-restricted cellular immunity in the current study.

The team used immunological experiments to show that an antigen to the SARS-CoV-2 spike protein is strongly recognised by the HLA-A24-restricted cellular immunity, which is often seen in Japanese people.

The team also conducted a large-scale sequence analysis of SARS-CoV-2 strains and demonstrated that HLA-A24 could recognize mutations in the spike protein region.

The team found that at least two naturally occurring substitutions in the receptor-binding motif of the SARS-CoV-2 spike protein, the L452R and Y453F identified in the B.1.427 and B1.1.298, can be resistant to the HLA-A24 cellular immunity.

The mutants also increase ACE2 binding affinity. Pseudovirus experiments show that L452R also enhances viral infectivity. The L452R mutation does so by stabilising the S protein, enhancing viral replication.

“These data suggest that HLA-restricted cellular immunity potentially affects the evolution of viral phenotypes and that a further threat of the SARS-CoV-2 pandemic is its ability to escape cellular immunity,” the team concluded in the study.

Investigating the L452R mutation further should be a priority since it is borne by the highly infectious Delta variant. 

Source: News-Medical.Net

Categories : Injury & TraumaTags :

New Wound Healing Scoring System Proposed

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Photo by Tara Winstead from Pexels

Researchers have proposed a new scoring system for wound healing in mice based on parameters in each phase of healing.

The researchers described the system in an article in the peer-reviewed journal Stem Cells and Development.

Wound healing processes consist of a sequence of molecular and cellular events which occur after the onset of a tissue lesion in order to restore the damaged tissue. In order to evaluate the efficacy of new treatments, there is a need to monitor wound progression accurately and reproducibly over time. 

The parameters include re-epithelisation, epithelial thickness index, keratinisation, granulation tissue thickness, remodeling, and the scar elevation index. These parameters can be assessed using either Hematoxylin & Eosin or Masson’s Trichrome staining. Mari van de Vyver, from Stellenbosch University, and colleagues developed this histology scoring system for cutaneous wounds in mice. They then validated the system in four different types of murine skin wound models.

“This histological scoring system defines and describes the minimum recommended criteria for assessing wound healing dynamics,” state the authors. “The experience and ability of investigators to accurately identify structures in histology slides at different stages of healing is crucial for consistency and repeatability of measures to deliver meaningful results.”

“The development and validation of this scoring system in a randomized blinded investigation by researchers from Stellenbosch University (South Africa), Polish Academy of Sciences in Olsztyn (Poland), University of Texas Southwestern Medical Center (Texas, USA) and Obatala Sciences Inc. (New Orleans, USA) represents a truly international effort to advance the robust and accurate assessment of wound healing,” stated Graham C Parker, PhD, Editor-in-Chief of Stem Cells and Development and The Carman and Ann Adams Department of Pediatrics, Wayne State University School of Medicine, Detroit, MI.

Source: Mary Ann Liebert, Inc.

Journal information: van de Vyver, M., et al. (2021) Histology Scoring System for Murine Cutaneous Wounds. Stem Cells and Development.doi.org/10.1089/scd.2021.0124.

Categories : Neurodegenerative DiseasesTags :

Sustained Antipsychotic Benefits of Pimavanesirn Shown in Study

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Evidence of the sustained benefits of an investigational antipsychotic treatment for people with dementia-related psychosis has been published.

Up to half of the 45 million people worldwide who are living with Alzheimer’s disease will experience psychotic episodes, a figure that is even higher in some other forms of dementia. Psychosis is linked to a faster deterioration in dementia, and currently there is no safe and effective treatment for it. Widely-used antipsychotics have significant drawbacks in people with dementia, leading to sedation, falls and increased risk of deaths.

Pimavanserin works by blocking serotonin 5HT2A receptors, with no interaction with dopamine receptors. In the US, it is licensed to treat hallucinations and delusions in people with Parkinson’s disease psychosis.

To test this drug, a clinical trial was conducted in 392 people with psychosis associated with Alzheimer’s disease, Parkinson’s disease, Lewy body, frontotemporal, or vascular dementia. All participants were given pimavanserin for 12 weeks, with those reaching a certain level of symptom improvement were then assigned to pimavanserin or placebo for up to 26 weeks. Due to positive efficacy results however, the trial was concluded early. 

Of the 351 participants, 217 (61.8%) had a sustained initial treatment benefit, of whom 112 were assigned to placebo and 105 to pimavanserin. Relapse occurred in 28/99 (28.3%) of the placebo group, compared to 12/95 (12.6%) of the pimvanserin group, with pimvanserin more than halving the relapse rate and significantly improving the sustained benefit.

Professor Clive Ballard, Executive Dean of the University of Exeter Medical School, said: “Psychosis affects up to half of all people with dementia, and it’s a particularly distressing symptom – yet there’s currently no safe and effective treatment. Currently used antipsychotics are known to cause harms, and best practice guidelines recommend prescribing for no longer than 12 weeks for people with dementia as a result. We urgently need alternatives. It’s exciting that the relapse rate in the pimavanserin group was lower than the placebo group, indicating that the treatment benefits may be sustained over time. We now need longer and larger scale trials to explore this further.”

The trial found headache, urinary tract infection and constipation occurred more frequently in the pimavanserin group, but there was no increase in mortality or the other serious events, such as stroke, which are seen in other antipsychotics.

The full paper is published in the New England Journal of Medicine.

Source: EurekAlert!

Categories : Skeletal SystemTags :

Plant-derived Substance Shows Osteoprotective Properties

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Researchers have found that a substance derived from Saussurea controversa, a member of the thistle family, may have significant potential in recovering lost bone mass.

Metabolic bone diseases such as osteoporosis are called the silent epidemic of the 21st century. A person may only become aware of their condition by sustaining a hip or spine fracture.

According to statistics, every third woman and every fifth man after 50 have osteoporosis. Thus, it is promising to search for and obtain substances and materials for implants that have osteoinductive properties and are capable of initiating the processes of transformation of stem cells into bone.

Certain trace elements, such as calcium and magnesium, influence the processes of bone regeneration and the maintenance of their normal structure. Organic molecules that can bind to them provide an improvement in the selectivity of their therapeutic action – the resulting complexes play a significant role in bone formation and development. From this point of view, salts of chelidonic acid have great potential, for example, from the Saussurea controversa known since ancient times for its healing properties.

Researchers from the Immanuel Kant Baltic Federal University, Siberian State Medical University, and Tomsk Polytechnic University had previously discovered that calcium chelidonate is a promising drug for bone volume restoration. 

In their latest work, they obtained this substance in a semisynthetic way: extracts from Saussurea controversa were the source of the chelidonic acid, to which an alkali solution and calcium chloride were added.

“The content of this substance differs in the samples of raw material and, most likely, its biosynthesis depends on the amount of calcium in the soil. For pharmaceutical purposes, it is advisable to use calcium chelidonate obtained by a semisynthetic method,” explained Elena Avdeeva, candidate of pharmaceutical sciences, researcher, Siberian State Medical University

An X-ray analysis confirmed that the substance has a structure identical to a natural compound. Researchers tested the effect of the substance in vitro and in vivo: it promoted the conversion of human stem cells derived from adipose tissue (hAMMSC) and mouse mesenchymal stromal cells into osteoblasts respectively. 

Calcium chelidonate is non-toxic and promotes bone regeneration: in vitro studies have shown that a dose of only 10mg/L increases the number of viable stem cells. Titanium implants coated with calcium phosphate and bearing autologous bone marrow were introduced into mice. The researchers found that calcium chelidonate stimulated the growth of new bone on the surface of the implant with daily administration of the drug for 35 days.

“The use of substances with osteoprotective properties, in particular, calcium chelidonate, is promising for the treatment of several diseases associated with bone defects or bone metabolism disorders. We are considering the development of a pharmaceutical form of the substance and its introduction into practical medicine,” concluded Larisa Litvinova, Doctor of Medicine, professor, head of the laboratory of immunology and cellular biotechnology at the IKBFU.

Source: News-Medical.Net

Journal information: Avdeeva, E., et al. (2021) Calcium Chelidonate: Semi-Synthesis, Crystallography, and Osteoinductive Activity In Vitro and In Vivo. Pharmaceuticals. doi.org/10.3390/ph14060579.

Categories : CancerTags :

MRI Clear Cell Likelihood Score Matches Renal Carcinoma Growth

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According to a new study, the MRI-derived standardised non-invasive clear cell likelihood score (ccLS) is correlated with the growth rate of small renal masses (cT1a, <4 cm) and could help guide personalised management.

The study was published in the American Roentgen Ray Society’s American Journal of Roentgenology. Extracted from clinical reports, “the ccLS scores the likelihood that the small renal mass represents clear cell renal cell carcinoma, from 1 (very unlikely) to 5 (very likely),” explained corresponding author Ivan Pedrosa from the University of Texas Southwestern Medical Center at Dallas. “Small renal masses with lower ccLS may be considered for active surveillance, whereas small renal masses with higher ccLS may warrant earlier intervention.”

The team’s retrospective study included consecutive small renal masses assigned a ccLS on clinical MRI exams performed from June 2016 to November 2019. Tumour size measurements were obtained from available prior and follow-up cross-sectional imaging examinations, up to June 2020.

Among 389 small renal masses in 339 patients (198 men, 141 women; median age, 65 years) on active surveillance that were assigned a ccLS on clinical MRI examinations, those with ccLS4-5 grew significantly faster (9% diameter, 29% volume yearly) than those with ccLS1-2 (5% diameter, p<.001; 16% volume, p<.001) or ccLS3 (4% diameter, p<.001; 15% volume, p<.001).

With a lack of validated imaging markers to characterise biologic aggressiveness of small renal masses hindering medical decision making, “growth is associated with ccLS in small renal masses,” the authors reiterated, “with higher ccLS correlating with faster growth.”

Source: EurekAlert!

Categories : Antibiotics CancerTags :

Old Antibiotics as New Weapons against Melanoma

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Researchers may have hit upon a new weapon in the fight against melanoma: antibiotics that target a vulnerability in the ‘power plants’ of cancer cells when they try to survive cancer therapy.

“As the cancer evolves, some melanoma cells may escape the treatment and stop proliferating to ‘hide’ from the immune system. These are the cells that have the potential to form a new tumor mass at a later stage,” explains cancer researcher and RNA biologist Eleonora Leucci at KU Leuven, Belgium. “In order to survive the cancer treatment however, those inactive cells need to keep their ‘power plants’—the mitochondria—switched on at all times.” As mitochondria derive from bacteria that, over time, started living inside cells, they are very vulnerable to a specific class of antibiotics. This is what gave us the idea to use these antibiotics as anti-melanoma agents.”

The researchers implanted patient-derived tumors into mice, which were then treated with antibiotics, either as alone or in combined with existing anti-melanoma therapies. Leucci observed: “The antibiotics quickly killed many cancer cells and could thus be used to buy the precious time needed for immunotherapy to kick in. In tumors that were no longer responding to targeted therapies, the antibiotics extended the lifespan of—and in some cases even cured—the mice.”

The researchers made use of nearly antibiotics rendered nearly obsolete because of antibiotic resistance. However, this does not affect the efficacy of the treatment in this study, Leucci explained. “The cancer cells show high sensitivity to these antibiotics, so we can now look to repurpose them to treat cancer instead of bacterial infections.”

However, patients with melanoma should not try to experiment, warned Leucci. “Our findings are based on research in mice, so we don’t know how effective this treatment is in human beings. Our study mentions only one human case where a melanoma patient received antibiotics to treat a bacterial infection, and this re-sensitized a resistant melanoma lesion to standard therapy. This result is cause for optimism, but we need more research and clinical studies to examine the use of antibiotics to treat cancer patients. Together with oncologist Oliver Bechter (KU Leuven/UZ Leuven), who is a co-author of this study, we are currently exploring our options.”

Source: KU Leuven

Journal information: Roberto Vendramin et al, Activation of the integrated stress response confers vulnerability to mitoribosome-targeting antibiotics in melanoma, Journal of Experimental Medicine (2021). DOI: 10.1084/jem.20210571