Mild electrical stimulation with heat shock exerts protective effect against nephrotic syndrome – News-Medical.Net

Last Updated on November 30, 2020 by

A research team from Kumamoto University in Japan has found that the combination of weak pulsed electrical current and heat exerts anti-inflammatory and anti-fibrotic effects in the kidneys, as well as a protective effect against nephrotic syndrome (NS) by inhibiting apoptosis (cell death) of kidney cells. Clinical data have shown that this type of physical treatment is safe and effective for humans. The researchers believe that it can be applied clinically to simultaneously target multiple NS factors.

NS is a general term for renal disease that results in the leakage of large amounts of proteins from the blood into urine due to damage to the glomerulus, the part of the kidney that is responsible for urinary filtration, resulting in complications such as hypoalbuminemia and edema. Steroids are used as a first-line treatment and have shown some efficacy, but relapses frequently occur and some types of NS are steroid-resistant. These refractory NSs remain an issue due to their poor prognosis and treatment response. In addition, NS often requires long-term control which raises concerns about the emergence of side effects caused by long-term drug use. This is why the development of new, effective and safe therapies is desired.

Electricity, thermal and other physical stimuli have been used medically for a very long time and are empirically known to ameliorate some pathological conditions. Professor Hirofumi Kai and his team at Kumamoto University have been studying the usefulness of mild electrical stimulation (MES) optimized for biological activity in combination with heat shock (HS), which is intended to enhance the action of the current. So far, they have found that MES+HS effectively improves the pathology of various diseases, including type 2 diabetes (Morino, S. et al., PloS One, 2008) and psoriasis (Tsurekawa, Y. et al., Exp Derm, 2018).

For type 2 diabetes in particular, clinical studies conducted on human patients showed that the treatment could correct abnormal glucose metabolism without adverse effects (Kondo, T. et al., EbioMedicine, 2014). The researchers believed that MES+HS could be a safe, novel treatment for various diseases and thus began investigating the efficacy of MES+HS on NS.

After first inducing refractory NS in a mouse model by administering the drug adriamycin (ADR), they applied 10-minute-long MES+HS treatments twice a week for four weeks and monitored the pathological changes. Renal function analysis revealed that the amount of albumin leaking into the urine increased after the disease was induced (day 7 after ADR injection) and peaked on day 10. However, in the MES+HS treatment group, urinary albumin levels were 50% and 75% lower on day 7 and day 10 respectively compared to the untreated group.

MES+HS treatment also improved proteinuria scores. Furthermore, serum creatinine levels, which usually increase with NS pathogenesis, decreased by 36% and blood urea nitrogen levels decreased by 24% compared to the untreated group. These results indicate that MES+HS treatment ameliorated ADR-induced kidney dysfunction.

The researchers also analyzed renal histology. ADR injection resulted in sclerotic lesions in the glomeruli but in the MES+HS treatment group, ADR-induced sclerotic lesions were suppressed. Severe sclerotic lesions%mdash;where more than 75% of the glomerular area was sclerotic%mdash;were considerably reduced (59% decrease). An increased number of protein casts caused by ADR, which reflects NS tubular dysfunction, were also observed in the untreated group, but were reduced in the MES+HS group.

This suggests that MES+HS exerts a protective effect not only on the glomeruli but also on the tubules. Researchers then evaluated glomerular epithelial cells (podocytes) since they are the starting points for the primary refractory NS disease, focal segmental glomerulosclerosis. They found that podocyte loss observed in the disease was inhibited by MES+HS treatment, which suggests that, on top of its ability to suppress renal tissue damage caused by ADR, MES+HS may also regulate podocyte reduction through some unknown mechanism(s).

To explore these mechanisms, researchers examined the impact of MES+HS on cell death in renal tissue using TUNEL staining and found that MES+HS reduced the number of apoptotic cells caused by ADR. Consistent with these results, the increase in protein expression of activated Caspase 3, an executor of apoptosis, was also suppressed by MES+HS, indicating an anti-apoptotic effect.

They then focused on protein kinase B (Akt), a molecule that promotes cell survival. MES+HS was found to phosphorylate and activate Akt and deactivate its downstream apoptosis-promoting factor, BCL2-associated agonist of cell death (BAD). This was confirmed in an in vitro cell-based experimental system where treatment with a phosphorylation inhibitor of Akt (LY294002) abolished the anti-apoptotic effects of MES+HS, thus demonstrating its profound involvement in the Akt-BAD pathway.

Additionally, gene expression analysis of inflammation and fibrosis related to NS progression showed that MES+HS reduced the expression of inflammatory cytokines (e.g., Il1-β and Il6) and fibrotic factors (e.g., Tgf-β and Col1a1) suggesting that MES+HS can inhibit inflammation and fibrosis. The research shows that MES+HS, improves the renal pathology of ADR-induced NS by regulating the Akt-BAD pathway and exerting an anti-apoptotic effect while also inhibiting inflammation and fibrosis.

The physical stimulus from MES+HS has been shown by other clinical studies to be a potentially safe medical treatment for humans. Based on the results from this work, we expect that it can be used to target multiple factors related to NS simultaneously for clinical applications in the future.”

Professor Hirofumi Kai, research project leader

Source:

Journal reference:

Teramoto, K., et al. (2020) Mild electrical stimulation with heat shock attenuates renal pathology in adriamycin-induced nephrotic syndrome mouse model. Scientific Reports. doi.org/10.1038/s41598-020-75761-8.

Liver cirrhosis: Disease progression – EurekAlert

Last Updated on November 30, 2020 by

Patients with liver cirrhosis display a wide range of clinical symptoms. A prospective study conducted by MedUni Vienna has now shown that blood levels of biomarkers for systemic inflammation increase over the various stages of the disease and can predict the development of complications, even in previously asymptomatic patients.

Every year, liver cirrhosis is responsible for approximately 170,000 deaths in Europe and recent epidemiological data show Austria to be in second place in regard to prevalence of cirrhosis in Europe. Excessive alcohol consumption, poor dietary habits, and metabolic comorbidities are the most common causes of cirrhosis in the Western world.

Liver cirrhosis is characterized by chronic liver damage, which leads to fibrosis and loss of functioning liver tissue. These changes to the liver tissue result in increased resistance to the blood flow to the liver via the portal vein and cause so-called ‘portal hypertension’. In addition, experimental studies have shown that the intestinal barrier is weakened in cirrhosis, so that pathogenic germs and bacterial products can pass into the bloodstream and cause a chronic inflammatory response in the body, in other words ‘systemic inflammation’. All these factors drive the progression of the liver disease, which can manifest clinically as the transition from asymptomatic (compensated) to symptomatic (decompensated) cirrhosis. This goes hand-in-hand with an increased risk for death.

MedUni Vienna’s Hepatic Hemodynamic Laboratory as an international showcase model

In the recent MedUni Vienna study, portal vein pressure measurements were performed in nearly 170 patients, while simultaneously taking a blood sample to determine biomarkers for systemic inflammation. “Portal pressure measurement via hepatic vein catheterisation is currently the gold standard for assessing the severity of portal hypertension,” explains Thomas Reiberger, Head of the outpatient clinic for liver cirrhosis and the Vienna Hepatic Hemodynamic Laboratory at University Hospital Vienna. “At MedUni Vienna, we have established one of the largest hepatic hemodynamic laboratories in the world and are therefore able to offer this valuable prognostic test at our centre at the University Hospital Vienna, in order to optimise the treatment of our patients with cirrhosis.” The international standing of the Vienna Hepatic Hemodynamic Laboratory is also evidenced by regular shadowing placements, such as that of Dalila Costa from Portugal, who shares lead authorship of the study with Benedikt Simbrunner from the Division of Gastroenterology and Hepatology of MedUni Vienna and Vienna General Hospital.

Inflammation as a significant disease mechanism and prognostic factor

New findings produced by the study show that the severity of portal hypertension increases predominantly in patients with asymptomatic (compensated) cirrhosis, while biomarkers for systemic inflammation increase predominantly in more advanced (decompensated) stages of the disease. Interleukin-6, a biomarker for inflammation, can predict the risk of complications and mortality both in compensated and decompensated cirrhosis. “These data underline the significance of systemic inflammation for the course of cirrhosis. The mechanisms underlying the inflammatory signals and potential interactions of the gut and the liver need to be further elucidated in humans”, observes Simbrunner. The study has been published in the Journal of Hepatology (Impact factor 2019: 20,582), the number one journal in the field of gastroenterology and hepatology.

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Disclaimer: AAAS and EurekAlert! are not responsible for the accuracy of news releases posted to EurekAlert! by contributing institutions or for the use of any information through the EurekAlert system.

Conceptual understanding of CNS drugs with reference to medicinal chemistry – EurekAlert

Last Updated on November 30, 2020 by

The primary objective of this 4-volume book series is to educate PharmD students on the subject of medicinal chemistry. The book set Medicinal Chemistry for Pharmacy Students serves as a reference guide to pharmacists on aspects of chemical basis of drug action. The volumes are divided primarily based on the organ system and/or pharmacological basis of drug actions.

The first volume ‘The Fundamentals of Medicinal Chemistry and Drug Metabolism’ presents 8 chapters focusing on basic background information to build a firm knowledge base of medicinal chemistry by introducing important fundamental chemical concepts, clinically important biosynthetic pathways and drug metabolism. The other volumes comprising of 8 to 9 chapters each discuss in depth topics on pharmacological and chemical basis of drug action, ADMET outcomes, Drug-Interactions, and Adverse effects.

Volume 2 ‘Medicinal Chemistry of Drugs Affecting the Nervous System’ discusses the drugs affecting the nervous system in a clear and easily understandable manner for pharmacy and other health science students. The standout feature of this book is the layout of concepts in smaller volumes, pertinent to the areas of interest of the readers. It will also offer students the opportunity to educate themselves in a stepwise manner starting from a thorough discussion of fundamental concepts, and then progressing to advanced levels. Another practical aspect of the book is that all concepts in any of the three major sections are illustrated clearly with diagrams or figures with the keywords highlighted, bulleted or numbered. Wherever needed, special boxes and case studies are included. In addition, each chapter is reinforced with study guides and practice problems.

Each chapter includes a thorough discussion of key physicochemical parameters of therapeutic agents and how they affect the biochemical, pharmacological, pharmacokinetic processes and clinical uses of therapeutic agents.

Volume 2 serves as a comprehensive resource of medicinal chemistry and drug action for pharmacy students as well as other health science students and educators.

The medicinal chemistry concepts of each drug class are illustrated by appropriate drug structures and relevant case studies. Drugs widely prescribed have been used as examples to reinforce the concepts.

The materials included in this book are suitable for college and university instructors in their classes and are being tested on continually by the series editors.

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Keywords:

medicinal chemistry, pharmacokinetic, biosynthetic pathways, drug metabolism, Drug-Interactions, Adverse effects, nervous system

For further details, please visit: http://bit.ly/3mnlWUC

Disclaimer: AAAS and EurekAlert! are not responsible for the accuracy of news releases posted to EurekAlert! by contributing institutions or for the use of any information through the EurekAlert system.

November Launch Pad: Bloating, hormones and Brotein, oh my – NutraIngredients-usa.com

Last Updated on November 30, 2020 by

Bloat Relief from Life Extension 

Life Extension has introduced a formula to combat occasional gas and bloating, just in time for the holidays. Bloat Relief combines artichoke and ginger extract with fennel seed oil and turmeric extract to promote gastrointestinal health and function as well as to relieve digestive discomfort.

Formulated with Prodigest, a patented blend of artichoke leaf and ginger root extract, Bloat Relief promotes healthy bile flow from the liver, which is another way to encourage food down the digestive tract. Meanwhile the ginger encourages gastric emptying.

Bloat Relief is available at Life Extension​ for $22. 

Femarelle Rejuvenate

Femarelle debuted Rejuvenate as a natural alternative to hormonal therapy. The formula aims to restore the body’s hormonal balance to promote feminine health for women who start to notice the primary signs that come with changes in their menstrual cycle.

With 56 capsules per pack and a twice-daily recommended dosage, Femarelle Rejuvenate aims to offer a natural solution to many of the primary symptoms of hormonal decline. 

Backed by multiple studies, the formula aims to improve skin, sleep, energy, mood and restore libido. 

Femarelle is available on Amazon ​for $31. 

Persona’s new lineup 

Based on consumer demand and feedback, Persona added several new formulations to its roster. These new additions complement 80 other offerings available through Persona’s personalized nutrition subscription service. Consumers can visit www.personanutrition.com to complete a free online nutritional assessment, which leads to their personalized vitamin recommendations.

Beauty Wake

This small translucent pink capsule consists of horsetail extract, magnesium and floating hyaluronic acid, along with other ingredients for energy support. Beauty Wake helps maintain health from the inside out.

Beauty Sleep

Sleep goes hand in hand with feeling beautiful, so Persona’s new Beauty Sleep supplement contains ingredients to help promote a more stress-free state. This formula contains collagen, horsetail extract, magnesium, floating hyaluronic acid and L-theanine, and is a complementary supplement to the Wake formula.

Immune Support

Persona’s new Immune Support supplement uses an ingredient blend of botanicals, including AP-Bio, astralagus, reishi and beta-glucans to help support the immune system. According to Persona, a randomized clinical trial found that supplementation with 200mg of AP-Bio andrographis botanicals for five days promoted immune function and supported respiratory comfort. 

Skin Probiotic

Probiotics are often associated with gut health, but can do so much more. Persona’s new Skin Probiotic features a unique mix of clinically studied probiotics and carotenoids like beta-carotene, lycopene and astaxanthin to support sun-exposed skin, promote hydrated skin and support a healthy scalp. 

Sleep Support 

To help aid in more restful and consistent sleep, Persona developed two updated melatonin products as part of its Sound Slumber Program. The supplements are sent in a rotating combination, keeping the body’s own ability to make melatonin in check. The “snow globe” capsules consist of clear liquid and suspended white melatonin beads to represent a drifting-off sensation.

Melatonin-3mg

The melatonin-3mg kick-starts the body and mind in the first 28-days promote a better sleep.

Melatonin-500mcg

The melatonin-500mcg formula provides a lower dosage of melatonin to help regulate the body’s internal clock and maintain consistent sleep.

Improved Multivitamin Formulas 

Foundation Multi

The new multivitamin, designed to reduce nutrient gaps, is packaged in a new purple veggie capsule that is easier to swallow. The purple veggie capsule is void of artificial colors or dyes and is sustainably sourced from purple carrots.

Bariatric Multi 

Developed from the American Society for Metabolic and Bariatric Surgery (ASMBS) guidelines, Persona’s newly formulated bariatric program features a multivitamin in a vegetarian softgel featuring nutrient levels these patients need as well as calcium citrate and iron formulated with vitamin C taken three times per day – all are packaged in individual tear-off pouches that can be easily taken on the go.

G-Force Advanced Dental Health Formula 

With ingredients like beetroot, zinc, jujube seed, berberine and turmeric, G-Force says their product produces whiter teeth, fresher breath and healthier gums within a few weeks by attacking bacteria and improving saliva with antioxidants and nutrients to ensure overall healing of dental problems. 

G-Force said their supplement starts works in three stages: 

The first stage is when the supplement creates an alkaline barrier that stops bacteria forming and breaks down the plaque.

In the second stage, it breaks down bacteria in the saliva, prevents blood from oozing out and fights against inflammation. Within a few weeks of consumption, G-Force pronises whiter teeth.

Third Stage: G-Force will tighten gums and improve saliva with antioxidants and nutrients to ensure overall healing of dental problems.  Improved saliva also helps to eliminate bad breath.

The supplement is only available at the G-Force website​ for $69 per bottle. 

Mike ‘The Situation’ Sorrentino launches BROTRITION 

The BROTRITION line offers a number of products, including protein, pre-workout, BCAAs and a fat burner. 

With his signature names, taglines and quotes of motivation on each bottle, ‘The Situation’ debuted a pure whey/pure whey isolate called BROtein that comes in three flavors: flavors of Vanilla, Chocolate and Funfettis. BROTRITION also created a pre-workout, BDS GRENADE, in flavors Fruit Punch, Blue Raspberry and Watermelon. 

And for good measure, SITUATION ABS are available as a fat burner to help speed up the metabolism and enhance the lipogenic fat burning effect.

BROTRITION is available at Brotrition.com​ for $29-$49 and in retail stores nationwide.

Trace Minerals Immune Support 

Trace Minerals announces the addition of six new products to its line of immune support products, including Apple Cider Vinegar Gummies, Immunity Gummies, Electrolyte Stamina Power Pak + Immunity, Elderberry Immunity Powder, Liquid Immunity+, and TMskincare Hand Sanitizer.

Apple Cider Vinegar Gummies​ helps support healthy bacteria for gut health, weight management, healthy blood sugar levels, immunity, and heart health. Each gummy provides 500 milligrams of unfiltered, organic ACV.

Immunity Gummies​ provide immune system-supporting nutrients to the diet to help keep the immune system strong and healthy, including 10 milligrams zinc, 250 milligrams vitamin C, 6 micrograms vitamin D, and 30 milligrams acerola cherry extract. 

Trace Minerals is also expanding its Electrolyte Stamina Power Pak line with the addition of a flavor that’s focused on immune support. Electrolyte Stamina Power Pak + Immunity​ is Trace’s classic Power Pak formula that contains essential immune supporting antioxidants, including 1,200 milligrams of vitamin C, manganese, and selenium, plus 200 milligrams of elderberry extract, 12 micrograms of vitamin D, and zinc that has been bumped up to 10 milligrams for even more immunity support. For those unfamiliar with Power Pak, it also features 15 additional B vitamins, minerals, and electrolytes for daily energy and hydration, plus a full spectrum ionic trace mineral complex for body mineral balance. 

Elderberry Immunity Powder​ is a natural Lemon Berry flavored drink mix that provides 200 milligrams of elderberry extract, 10 milligrams zinc, 1,000 milligrams vitamin C, and 100 milligrams of full spectrum, body mineral balancing ionic trace minerals for total defense immune support..

The final supplement focused on immune support is Liquid Immunity+​, a natural Mixed Berry flavored liquid that provides several immune supporting nutrients, including 200 milligrams elderberry, 15 milligrams zinc, 1,000 milligrams vitamin C, and 30 micrograms vitamin D for a multi-dimensional approach to support immune system function.

Available at Trace Minerals​, most products run under $30. 

Natrol Immunity

Natrol is also offering an immunity care package with zinc, vitamin D3, new Immune-Biotic powder packets, and melatonin.

Immune-Biotic​ is a quick-dissolve, no-water-needed powder that can be poured directly on the tongue to help support immune and digestive health.

Elderberry Gummies​ contains 90 mg of Vitamin C and 7.5 mg of zinc.

Easy-C Tablets​ are high potency vitamin C supplements that are easy on the stomach and available in 60 and 120 count packages.

Natrol Immune Boost​, which uses the clinically-tested superfood EpiCor (a fermented immune supporting yeast complex), in combination with high potency immune supporting supplements vitamin C, vitamin D3, selenium and zinc.

Vitamin D3​ is a no-water-needed fast dissolve, strawberry flavored tablet that helps support bones, teeth and immune health.

Most immune products are in the $10-$30 range and widely available online.

Natrol Relaxia

Natrol also wanted to help Americans calm down with Natrol Relaxia Ultimate Calm, a formula designed to manage daily stress. 

The proprietary blend contains calming herbs such as Ashwagandha, 5-HTP, L-Theanine and lemon balm. 

Available at Natrol ​for $26 and retailers like Target and Rite Aids for $17.

Pandemic to delay cancer advances by nearly 18 months, researchers fear – PharmiWeb.com

Last Updated on November 30, 2020 by

  •  Survey of more than 200 researchers details impact of pandemic at leading institute

 

  • Scientists estimate their own research has been put back by six months through loss of access to labs, facilities, trials and samples

 

  • Major advances in cancer research to be delayed by 17 months, through loss of national facilities and barriers to scientists working together

 

  • But science has now adapted to Covid-19 – and researchers believe donations and Government support could accelerate recovery

 

Cancer researchers fear advances for patients could be delayed by almost a year and a half because of the effects of the Covid-19 pandemic, a new survey reveals.

 

Scientists at The Institute of Cancer Research, London, told the survey that their own research advances would be pushed back by an average of six months by the initial lockdown, subsequent restrictions on laboratory capacity and the closure of national scientific facilities.

 

With broader effects on charity funding, disruption of collaboration and personal interaction between scientists, and diversion of research efforts to Covid-19, the respondents estimated that major advances in cancer research would be delayed by an average of 17 months.

 

But the researchers said science had now adapted in many ways to the pandemic and that long-lasting damage to cancer research could be mitigated through extra funding from charitable donations or Government support – calling for investment in staffing, new technology such as robotics and computing power.

 

The Institute of Cancer Research (ICR), which has discovered more cancer drugs than any other academic centre in the world, has like many research organisations been hit by cuts to its own fundraising income and to grants from other charities. The ICR had to pause much of its work during the initial lockdown, and is now running a major fundraising appeal to help kick-start its research and make up for lost time.

 

The ICR surveyed 239 of its researchers in order to detail the impact the pandemic has had on its research and to point towards ways of moving research forward again as quickly as possible.

 

Respondents said they had lost an average of 10 weeks of research time to the first lockdown itself, and that their own scientific advances would be pushed back by an average of six months. Almost all said Covid-19 had had an impact on their work – with 36 per cent saying it had had a ‘moderate’ impact, another 36 per cent a ‘substantial’ impact and 5 per cent an ‘extreme’ impact.

 

Some 91 per cent said the biggest problem had been the closure of labs during lockdown and subsequent restrictions in access to facilities and equipment – citing, for example, closure of major, national research facilities. The average ICR researcher spent 53 per cent of their working time in a lab before lockdown, plummeting to 5 per cent during lockdown and since recovering to 34 per cent.

 

The next most cited impacts were inability to enrol patients on clinical trials (60 per cent), to access clinical samples (46 per cent) or to interact in person with colleagues (41 per cent) – with video conferencing seen as a poor substitute for meeting in person at conferences and other events.

 

Many researchers were, however, able to use the time productively – for example through doing training (48 per cent), or carrying out desk-based (62 per cent) or computational (33 per cent) research. Some carried out research into Covid-19 (5 per cent), including studies that have given us greater insight into the effects of Covid-19 on cancer treatment pathways.

 

But the survey nevertheless laid bare the emotional impact of the pandemic on researchers. Some 69 per cent of researchers said the impact of the pandemic on their work had left them ‘frustrated’, 39 per cent had been ‘saddened’ and 25 per cent ‘depressed’.

 

The respondents were strongly supportive of efforts to keep labs open to prevent any further disruption to research advances for cancer patients. The ICR’s labs have managed to stay open during the second lockdown period while taking significant measures to help prevent risk of spread.

 

The ICR’s researchers did feel that science had adapted to Covid-19 and that there were various ways to make up for lost time – over 60 per cent felt funding for extra staff time would help; almost 40 per cent wanted upgrades in technology, for example for robotics, and 29 per cent increased computing power.

 

Professor Paul Workman, Chief Executive of The Institute of Cancer Research, London, said:

 

“Our researchers are passionate about making advances to benefit patients, so it has been hugely frustrating that their work has been so disrupted, although also inspiring to see how well they have adapted to the restrictions the pandemic has imposed on our lives.

 

“It is sobering to see that our researchers are estimating that their own research advances will be delayed by six months – and that the wider impact, because of the interconnectedness of science, is likely to push back major advances for patients by nearly a year and a half.

 

“Our survey though does provide solutions to mitigate the impact – in the form of investment in staffing, new technologies and computing power. For that, we need more of the generous donations we have been receiving to our emergency appeal, along with a commitment from the Government to help fill the funding gap for the life sciences left by the pandemic.”

 

Dr Sebastian Guettler, Deputy Head of Structural Biology at The Institute of Cancer Research, London, said:

 

“Our work is reliant on access to shared infrastucture in London and nationally, and during the first lockdown this became impossible. These facilities have now introduced or widened remote access – we can control experiments hundreds of miles away from our own homes, with good broadband internet speeds. But we continue to be limited when it comes to preparing samples in the lab, which are then shipped to these facilities for experiments. It’s been an intensely frustrating time, and some teams are much more affected than others – depending on which facilities they need.

 

“The coronavirus has also reduced or stopped the spontaneous interactions with colleagues that science is so dependent on for generating new ideas. Video conferencing has helped us stay connected as a lab and a community, but it’s not a true replacement for those light bulb moments you might get from chatting with someone at a conference or over coffee in the canteen.

 

“There are some positives from this period. Being able to access shared facilities remotely will be helpful in the future, and we know we can make up for some of the lost time if we have more funding for people and equipment to catch up on the lost laboratory work.”

 

Professor Emma Hall, Deputy Director of the Clinical Trials and Statistics Unit at The Institute of Cancer Research, London, said:

 

“Our work relies on new clinical trials starting up and existing ones continuing to happen – and Covid-19 has made that incredibly challenging. The pandemic has meant that it will take longer to answer the questions asked in our trials, and that will delay new treatments getting to patients.

 

“During the initial lockdown, non-Covid clinical research pretty much shut down within the NHS. A lot of our trials were effectively paused because the hospitals that host them had to redeploy resources to Covid-19 research or treatment.

 

“Covid-19 has forced some changes in how we work that are for the better though. We can capture and manage data remotely rather than relying on paper. The Covid-19 trials have also shown how research can benefit from easier access to routine medical data – hopefully this will be translated to other clinical research and mean more streamlined, simpler to run trials.

 

“I hope we can use this experience to benefit cancer patients in the long term, but that will only be possible with more support or future advances will be delayed.”

 

Mother of two Sally Steadman-South, from Sheffield, is living with stage 4 melanoma. She was first diagnosed in 2014 at the age 35, after having a mole removed on her chest. Despite trying numerous treatments including surgery, radiotherapy and immunotherapy, the cancer continued to spread.

 

For the last two years she has been on the targeted drugs, dabrafenib – a treatment underpinned by the ICR’s science – and trametinib, and currently has no evidence of disease.

 

This year Sally celebrated her 40th birthday with her family – a milestone she never thought she would reach.

 

Sally shared her concerns about the impact of Covid-19 on cancer patients:

 

“The coronavirus has been especially devastating for many cancer patients – I have been lucky my treatment has been unaffected but we know many have not and their care has been affected.  It’s also clear that future research advances have also been delayed. 

 

“I feel lucky that my treatment has worked well so far but I know that the cancer could become resistant to the drugs at any time. When you get a diagnosis like mine it changes what time means to you – maybe this pandemic has made many more people value and appreciate quality time with family and loved ones. I want to be around for school plays and sports days, see my daughter go to secondary school and see my son enjoy his time there too and start planning his own future.

 

“We recently went to pick our Christmas tree and they are planting fields of new trees which will be ready in 2028.  We agreed that this would be our new goal.  I would be there to see this new field of Christmas trees and we would go as a family to pick one.  We need to make up for the time lost to this virus so people like me can live longer and make important memories like these.”

Support the ICR’s kick-start appeal and help their researchers make up for lost time by donating at ICR.ac.uk/KickstartICR

Infant Brain Circuitry Shaped by Language Exposure – SciTechDaily

Last Updated on November 30, 2020 by

Infant Wears LENA Audio Recording Device

An infant wears the LENA audio recording device in a pocket on the front of a special vest. Credit: Dr. Kathryn L. Humphreys

Taking turns in “conversation” with caregivers relates to synchronized activation in language areas.

The type and quantity of an infant’s language exposure relates to their brain function, according to new research published in JNeurosci.

Babies learn their native language by interacting with their caregivers. Rather than simply overhearing adult words, taking turns in a “conversation” predicts an infant’s future language abilities. But it is unclear how language exposure shapes brain circuitry. The brain’s language networks may develop in two stages: a bottom-up auditory-processing network begins developing in gestation, and a top-down network for processing more complex syntax and semantics develops in early childhood.

King et al. documented the at-home language exposure of 5 to 8-month-old infants and used fMRI to measure their resting language network activity while they slept in the scanner. Regions in each of the two language subnetworks activated together, indicating coordinated activity. Participating in a greater number of conversational turns at home was associated with weaker connectivity in the bottom-up subnetwork.

Brain connections can both weaken and strengthen as they are refined throughout development; future research may reveal how weaker connectivity related to more conversations influences infant language development.

Regardless, the results highlight the importance of early life environments in shaping infant brain function and development, and the need to support caregivers in providing enriching environments.

Reference: “Naturalistic Language Input is Associated with Resting-State Functional Connectivity in Infancy” 30 November 2020, Journal of Neuroscience.
DOI: 10.1523/JNEUROSCI.0779-20.2020

Older adults with dementia exhibit financial symptoms up to six years before diagnosis – EurekAlert

Last Updated on November 30, 2020 by

A new study led by researchers at the Johns Hopkins Bloomberg School of Public Health and the Federal Reserve Board of Governors found that Medicare beneficiaries who go on to be diagnosed with dementia are more likely to miss payments on bills as early as six years before a clinical diagnosis.

The study also found that beneficiaries diagnosed with dementia who had a lower educational status missed payments on bills beginning as early as seven years before a clinical diagnosis as compared to 2.5 years prior to a diagnosis for beneficiaries with higher educational status.

The study, which included researchers from the University of Michigan Medical School, also found that these missed payments and other adverse financial outcomes lead to increased risk of developing subprime credit scores starting 2.5 years before a dementia diagnosis. Subprime credit scores fall in the fair and lower range.

The findings, published online November 30 in JAMA Internal Medicine, suggest that financial symptoms such as missing payments on routine bills could be used as early predictors of dementia and highlight the benefits of earlier detection.

“Currently there are no effective treatments to delay or reverse symptoms of dementia,” says lead author Lauren Hersch Nicholas, PhD, associate professor in the Department of Health Policy and Management at the Bloomberg School. “However, earlier screening and detection, combined with information about the risk of irreversible financial events, like foreclosure and repossession, are important to protect the financial well-being of the patient and their families.”

The analysis found that the elevated risk of payment delinquency with dementia accounted for 5.2 percent of delinquencies among those six years prior to diagnosis, reaching a maximum of 17.9 percent nine months after diagnosis. Rates of elevated payment delinquency and subprime credit risk persisted for up to 3.5 years after beneficiaries received dementia diagnoses, suggesting an ongoing need for assistance managing money.

Dementia, identified as diagnostic codes for Alzheimer’s Disease and related dementias in the study, is a progressive brain disorder that slowly diminishes memory and cognitive skills and limits the ability to carry out basic daily activities, including managing personal finances. About 14.7 percent of American adults over the age of 70 are diagnosed with the disease. The onset of dementia can lead to costly financial errors, irregular bill payments, and increased susceptibility to financial fraud.

For their study, the researchers linked de-identified Medicare claims and credit report data. They analyzed information on 81,364 Medicare beneficiaries living in single-person households, with 54,062 never receiving a dementia diagnosis between 1999 and 2014 and 27,302 with a dementia diagnosis during the same period. The researchers compared financial outcomes spanning 1999 to 2018 of those with and without a clinical diagnosis of dementia for up to seven years prior to a diagnosis and four years following a diagnosis. The researchers focused on missing payments for one or more credit accounts that were at least 30 days past due, and subprime credit scores, indicative of an individual’s risk of defaulting on loans based on credit history.

To determine whether the financial symptoms observed were unique to dementia, the researchers also compared financial outcomes of missed payments and subprime credit scores to other health outcomes including arthritis, glaucoma, heart attacks, and hip fractures. They found no association of increased missed payments or subprime credit scores prior to a diagnosis for arthritis, glaucoma, or a hip fracture. No long-term associations were found with heart attacks.

“We don’t see the same pattern with other health conditions,” says Nicholas. “Dementia was the only medical condition where we saw consistent financial symptoms, especially the long period of deteriorating outcomes before clinical recognition. Our study is the first to provide large-scale quantitative evidence of the medical adage that the first place to look for dementia is in the checkbook.”

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“The Financial Presentation of Alzheimer’s Disease and Related Dementias” was written by Lauren Hersch Nicholas, Kenneth M. Langa, Julie P. W. Bynum, and Joanne W. Hsu.

The study was funded by the National Institute on Aging (R21AG 053698) and the Social Security Administration (RRC08098401-10).

Disclaimer: AAAS and EurekAlert! are not responsible for the accuracy of news releases posted to EurekAlert! by contributing institutions or for the use of any information through the EurekAlert system.

WHO urges against large end year festivities as COVID-19 war rages on – cgtn.com

Last Updated on November 30, 2020 by

WHO Director-General Tedros Adhanom Ghebreyesus /Photo by James Chau

The World Health Organization has urged the world to scale down festive celebrations to avoid fanning the spread of COVID-19.

Speaking at a media briefing on Monday, WHO Director General Tedros Adhanom urged those planning to hold celebrations not to organize or attend large parties, as that would put them at risk of contracting the virus.

“Being with family and friends is not worth putting them or yourself at risk,” said Tedros. “We all need to consider whose life we might be gambling with in the decisions we make.”

The call comes as the Christmas and other end year festivities are fast approaching.

As of Monday, the number of confirmed COVID-19 infections globally surpassed the 62.95 million mark, with a death toll exceeding 1.46 million.

Often, millions of people around the world travel far distances in December to join their families and friends in planned festivities.

“The first question to ask yourself is, do you need to travel? Do you really need to travel?” said Tedros.

“For many people, this is a season for staying home and staying safe.”

He urged those who will travel, join or host celebrations to do so I adherence to the various COVID-19 protocols in order to avoid spreading the virus.

Gene therapy gives man with sickle cell disease the chance for a better future – EurekAlert

Last Updated on November 30, 2020 by

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IMAGE: Evie Junior
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Credit: UCLA Broad Stem Cell Research Center

For Evie Junior, living with sickle cell disease has been like running a marathon.

“But it’s a marathon where as you keep going, the trail gets rockier and then you lose your shoes,” the 27-year-old said. “It gets harder as you get older. Things start to fail and all you can think about is how much worse it’s going to get down the road.”

In sickle cell disease, a genetic mutation causes the blood-forming stem cells — which give rise to all blood and immune cells — to produce hard, sickle-shaped red blood cells. These misshapen cells die early, leaving an insufficient number of red blood cells to carry oxygen throughout the body. Because of their sickle shape, these cells also get stuck in blood vessels, blocking blood flow and resulting in excruciating bouts of pain that come on with no warning and can leave patients hospitalized for days.

The disease affects 100,000 people in the United States and millions around the world, the majority of whom are of African or Hispanic descent. It can ultimately lead to strokes, organ damage and early death.

As a child growing up in the Bronx, New York, Junior had to have his gall bladder and spleen removed due to complications from the disease, but he refused to let his condition limit him. He played football, basketball and baseball during the day, even though on some nights he experienced pain crises so severe he couldn’t walk.

“It was just really routine if I had a sickle cell crisis,” he said. “Going to the emergency room, staying in the hospital, coming out in a few days and then getting back to normal life.”

‘I want to create a better future’

When he was 24 and living in Portland, Oregon, Junior began working as an emergency medical technician. He adopted the same mentality — trying to treat his pain episodes the best he could, and hoping they would resolve overnight so he could get back to work. Around that time, though, the crises became harder to manage. He developed pericarditis, an inflammation in the layers of tissue around his heart, and needed six weeks to recover.

“The big worry with sickle cell disease is that you’re going to die young from some type of complications or damage to your organs,” he said. “In the last couple of years, I’ve been seeing that slowly happen to me and I can only suspect that it’s going to keep getting worse. I want to create a better future for myself.”

In July 2019, in pursuit of that future, Junior enrolled in a clinical trial for an experimental stem cell gene therapy for sickle cell disease. The study is led by UCLA Broad Stem Cell Research Center physician-scientists Dr. Donald Kohn and Dr. Gary Schiller and funded by the California Institute for Regenerative Medicine.

The therapy, developed by Kohn over the past 10 years, is intended to correct the mutation in patients’ blood-forming stem cells to allow them to produce healthy red blood cells. Kohn has already applied the same concept to successfully treat several immune system deficiencies, including a cure for a form of severe combined immune deficiency, also known as bubble baby disease.

But sickle cell disease has proven more difficult to treat with gene therapy than those other conditions. Junior volunteered for the trial knowing there was a chance the therapy wouldn’t cure him.

“Even if it doesn’t work for me, I’m hoping that it can be a cure later down the road for millions of people,” he said.

In July 2020, Junior received an infusion of his own blood-forming stem cells that had been genetically modified to overcome the mutation that causes his disease.

“The goal of this treatment is to give him a future, let him plan for college, family or whatever he wants without worrying about getting hospitalized because of another pain crisis,” said Kohn, a distinguished professor of microbiology, immunology and molecular genetics, pediatrics, and molecular and medical pharmacology at the David Geffen School of Medicine at UCLA.

Reason for optimism

Three months after his treatment, blood tests indicated that 70% of Junior’s blood stem cells had the new corrected gene. Kohn and Schiller estimate that even a 20% correction would be enough to prevent future sickle cell complications. Junior said he hasn’t had a pain crisis since undergoing the treatment and he has more energy and feels out of breath less often.

“I noticed a big difference in my cardiovascular endurance in general — even going for a light jog with my dogs, I could feel it,” he said.

Junior and his doctors are cautiously optimistic about the results.

“It’s too early to declare victory, but it’s looking quite promising at this point,” Kohn said. “Once we’re at six months to a year, if it looks like it does now, I’ll feel very comfortable that he’s likely to have a permanent benefit.”

After a lifetime of dealing with the unwelcome surprises of the disease, Junior is even more cautious than his doctors. But as the weeks pass, he’s slowly allowing a glimmer of hope that he could soon be someone who used to have sickle cell disease. For him, that hope feels like “a burst of happiness” that’s followed by thoughts of all the things he could do with a healthy future: pursue his dream of becoming a firefighter, get married and start a family.

“I want to be present in my kids’ lives, so I’ve always said I’m not going to have kids unless I can get this cured,” he said. “But if this works, it means I could start a family one day.”

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(Note to reporters: Watch a video about Evie’s treatment with an experimental gene therapy for sickle cell disease here: https://www.youtube.com/watch?v=XmQJpuLx07Y)

Disclaimer: AAAS and EurekAlert! are not responsible for the accuracy of news releases posted to EurekAlert! by contributing institutions or for the use of any information through the EurekAlert system.

Man United star among those roped in to help promote the UK’s first Covid vaccine – We All Follow United

Last Updated on November 30, 2020 by

Marcus Rashford believed to be among those aiding push for UK’s first Covid vaccine

According to the Daily Mail, Manchester United star Marcus Rashford is believed to be among those lined up to help push UK’s first Covid vaccine.

The treatment could be rolled out in days. A variety of celebrities including the United ace are believed to be lending their support to it.

While the number of famous names is yet to be confirmed, the ace striker is believed to be in the mix.

Manchester United star Marcus Rashford is  believed to be among those lined up to help push UK's first Covid vaccine.
Manchester Untied star Marcus Rashford believed to be among those aiding UKs first Covid vaccine push

The government is making use of celebrities and social media influencers in promoting the vaccine and curb conspiracy theorists online.

There are fears that the anti-vax content on social media sites could lead to a low take-up of the vaccine, affecting the chances of achieving herd immunity.

The worry is not without reason as a recent survey in the US and UK found that public willingness to take a Covid vaccine fell by 6.4% after reading anti-vax posts.

Health bosses and ministers are in talks with ‘responsible’ high-profile stars to post positive messages about the vaccine. According to the report, Rashford and the Royal Family are considered to be the ideal candidates.

Marcus Rashford England
Rashford’s actions have seen him find support even amongst rival fans

Rashford has emerged in recent months as the face of social welfare thanks to his philanthropic activities.

His fight against child hunger has seen him pick up numerous accolades and also earn him popular status even amongst fans of rival clubs.

The young star belied his age to bring about positive change in society. He forced the Government into a second U-turn in November. It saw Prime Minister Boris Johnson agree to fund an extra £400million of free school meals.

Marcus Rashford is United's top scorer this season
Marcus Rashford has also started a book club

More Manchester United News

The young striker also recently started a book club. The initiative has been made to promote reading and literacy among children from all socio-economic backgrounds

His efforts to bring about a positive change in society makes him a figure that can be relied upon. It would appear that efforts are now being made to make use of that trustworthy image to help push the vaccine.