Day: January 30, 2023

Categories : PaediatricsTags : Leave a comment

Outdoor Play can Mitigate the Worst Effects of Kids’ Screen Time

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Photo by Emily Wade on Unsplash

Children around the world are spending more and more time with screens, which is a great concern for parents and physicians alike. New research from Japan indicates that more screen time at age 2 is associated with poorer communication and daily living skills at age 4 – but playing outdoor seems to reduce some of the negative effects.

For their study, published in JAMA Pediatrics, the researchers followed 885 children from 18 months to 4 years of age. They looked at the relationship between three key features: average amount of screen time per day at age 2, amount of outdoor play at age 2 years 8 months, and neurodevelopmental outcomes at age 4: communication, daily living skills, and socialization scores according to a standardised assessment tool called Vineland Adaptive Behavior Scale-II.

“Although both communication and daily living skills were worse in 4-year-old children who had had more screen time at aged 2, outdoor play time had very different effects on these two neurodevelopmental outcomes,” explains Kenji J. Tsuchiya, Professor at Osaka University and lead author of the study. “We were surprised to find that outdoor play didn’t really alter the negative effects of screen time on communication – but it did have an effect on daily living skills.”

Specifically, almost one-fifth of the effects of screen time on daily living skills were mediated by outdoor play, meaning that increasing outdoor play time could reduce the negative effects of screen time on daily living skills by almost 20%. The researchers also found that, although it was not linked to screen time, socialisation was better in 4-year-olds who had spent more time playing outside at 2 years 8 months of age.

“Taken together, our findings indicate that optimizing screen time in young children is really important for appropriate neurodevelopment,” says Tomoko Nishimura, senior author of the study. “We also found that screen time is not related to social outcomes, and that even if screen time is relatively high, encouraging more outdoor play time might help to keep kids healthy and developing appropriately.”

These results are particularly important given the recent COVID-related lockdowns around the world, which have generally led to more screen time and less outdoor time for children. Because the use of digital devices is difficult to avoid even in very young children, further research looking at how to balance the risks and benefits of screen time in young children is eagerly awaited.

Source: Osaka University

Categories : Diet and Nutrition NeurologyTags : Leave a comment

High-fat Diets Overload the Ability to Moderate Calorie Intake

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Regularly eating a high fat/calorie diet could reduce the brain’s ability to regulate calorie intake, according to a study published in The Journal of Physiology. Rat studies revealed a signalling pathway which causes a quick response to high fat/high calorie intake, reducing food and calorie intake. But continuously eating a high fat/calorie diet seems to disrupt this signalling pathway, sabotaging this short-term protection.

Senior author Dr Kirsteen Browning said, “Calorie intake seems to be regulated in the short-term by astrocytes. We found that a brief exposure (three to five days) of high fat/calorie diet has the greatest effect on astrocytes, triggering the normal signalling pathway to control the stomach. Over time, astrocytes seem to desensitise to the high fat food. Around 10–14 days of eating high fat/calorie diet, astrocytes seem to fail to react and the brain’s ability to regulate calorie intake seems to be lost. This disrupts the signalling to the stomach and delays how it empties.”

Astrocytes initially react when high fat/calorie food is ingested, triggering the release of gliotransmitters, chemicals (including glutamate and ATP) that excite nerve cells and enable normal signalling pathways to stimulate neurons that control stomach function. This ensures the stomach contracts correctly to fill and empty in response to food passing through the digestive system. When astrocytes are inhibited, the cascade is disrupted. The decrease in signalling chemicals leads to a delay in digestion because the stomach doesn’t fill and empty appropriately.

The vigorous investigation used behavioural observation to monitor food intake in rats which were fed a control or high fat/calorie diet for one, three, five or 14 days. This was combined with pharmacological and specialist genetic approaches (both in vivo and in vitro) to target distinct neural circuits, which enabled the researchers to specifically inhibit astrocytes in a particular region of the brainstem. In this way, they assessed the response of individual neurons.

Human studies will need to be carried out to confirm if the same mechanism occurs in humans. If this is the case, further testing will be required to assess if the mechanism could be safely targeted without disrupting other neural pathways.

The researchers have plans to further explore the mechanism. Dr Browning said, “We have yet to find out whether the loss of astrocyte activity and the signalling mechanism is the cause of overeating or that it occurs in response to the overeating. We are eager to find out whether it is possible to reactivate the brain’s apparent lost ability to regulate calorie intake. If this is the case, it could lead to interventions to help restore calorie regulation in humans.”

Source: The Physiological Society

Categories : CancerTags : Leave a comment

Actin Filaments Act as Pipelines for Metastatic Factors

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Lung cancer cells in the process of metastasising. Source: National Cancer Institute on Unsplash

When cancer cells metastasise, they have to break connections with neighbouring cells and migrate to other tissues. Both processes are promoted by signalling molecules released by the cancer cells, which thereby increase the malignancy of tumours. Researchers found that the release of these ‘prometastatic’ factors is influenced by the cellular skeleton – specifically, actin filaments. The study was published in Advanced Science.

Actin’s multiple role functions in cancer propagation

Actin filaments are part of the cell skeleton and essential for stability and motility. They form a network that dynamically builds up and gets broken down by the addition or detachment of building blocks at the filaments’ ends. These processes are precisely regulated by other molecules, such as formins. The dynamics of the actin network enable the movement of cells, for example during development or wound closure, but also that of spreading cancer cells. Actin also plays a role in the transport of substances within the cell. However, this is less well understood than that of other intracellular transport mechanisms.

The research team led by Prof Dr Robert Grosse and Dr Carsten Schwan from the University of Freiburg, now found that the actin network also enables the release of prometastatic factors, such as ANGPTL4 which is an important prometastatic factor that promotes the formation of metastases in various types of cancer. For their study, they used high-resolution microscopy to track the movement of individual transport vesicles within living cancer cells.

“We observed that ANGPTL4-loaded vesicles are conveyed to the periphery of the cell by means of dynamic and localised polymerisation of actin filaments,” says Grosse, who is a member of the Cluster of Excellence CIBSS – Centre for Integrative Biological Signalling Studies at the University of Freiburg.

Transportation along actin filaments

Based on microscopic observations and genetic analyses, the scientists conclude that the vesicles’ movement is controlled by the formin-like molecule FMNL2 by initiating polymerisation (ie elongation) of actin filaments directly at the vesicle. “We already knew that increased FMNL2 activity has prometastatic effects in many types of tumours,” says Grosse. “In our current work we could now demonstrate an important underlying process and a connection to the TGFbeta signalling pathway.” According to the scientist, this knowledge could be used for tumour diagnostics or therapy. for example, by developing an antibody that indicates the presence of active FMNL2 or pharmacologically targets active, phosphorylated FMNL2.

Source: University of Freiburg

Categories : Cancer New Compounds and TreatmentsTags : Leave a comment

Momelotinib Trumps Standard Care in Treating Myelofibrosis

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Photo by Louise Reed on Unsplash

A Phase III trial testing the targeted therapy momelotinib showed that patients with myelofibrosis had clinically significant improvement in disease-related symptoms, including anaemia and spleen enlargement.

The findings, published in The Lancet, support the use of momelotinib over the standard therapy (danazol) in treating myelofibrosis patients that were resistant, refractory or intolerant to firstline therapy, especially symptomatic patients and those with anemia.

“Current options for managing anaemia in our myelofibrosis patients provide only modest and temporary benefits, so we are excited about these findings,” said study lead Srdan Verstovsek, MD, PhD, professor of Leukemia at University of Texas. “The trial results suggest that momelotinib is safe, well-tolerated and can improve one of the most common and debilitating clinical problems for this patient population.”

Myelofibrosis is an uncommon bone marrow cancer that is part of a group of diseases known as myeloproliferative neoplasms. A hallmark of the disease is dysregulated JAK signalling, which disrupts blood cell production and leads to symptoms including an enlarged spleen and anaemia. Chronic anaemia in these patients is associated with poor prognoses.

Currently approved JAK inhibitors can improve spleen responses and other disease-related symptoms, but they also can worsen anaemia. In this trial, momelotinib improved anaemia and reduced transfusion dependency in myelofibrosis patients previously treated with a JAK inhibitor. Momelotinib, a potent ACVR1/ALK2 and JAK1/2 inhibitor, can be administered and maintained at full dose because it does not suppress bone marrow activity like other JAK inhibitors.  

The randomised Phase III MOMENTUM trial was designed to compare the clinical benefits of momelotinib to danazol, a synthetic androgen currently used to treat anaemia in symptomatic myelofibrosis patients.

The trial enrolled 195 adult patients (63% male, 37% female) from 107 research sites across 21 countries. Trial participants were randomised (2:1) to receive momelotinib plus placebo or danazol plus placebo. A significantly greater proportion of patients who received momelotinib saw benefits in their disease symptoms (25%) compared to those receiving danazol (9%).

Patients treated with momelotinib also experienced a significant reduction in their spleen size, with 25% responding after 24 weeks of therapy. Additionally, these patients required fewer blood transfusions compared to those receiving danazol.

The safety profile of momelotinib was comparable to previous clinical trials. The most common non-haematological side effects experienced by trial participants in the momelotinib group included diarrhoea, nausea, weakness and itching or irritated skin.

“If approved, momelotinib could offer an effective option for patients with myelofibrosis to improve anemia, splenomegaly and other disease-related symptoms over other approved medications so far,” Verstovsek said. “Momelotinib may also be an ideal partner for combinations with other investigational agents in development to further control myelofibrosis symptoms.”

Patient follow-up is ongoing and long-term survival continues to be monitored.

Source: University of Texas MD Anderson Cancer Center