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What Does Not Die











In Hampshire in an autumn wood the squirrel I found that came to say hello
In New Hampshire life’s voices went rippling human joys and sorrows and
In Union Square I saw the sun painting the green leaves with photon-paints
Allwhere life is a song written and sung in many a form in many a rainbow
A rainbow it is always allwhere marking the same shape of life-expressions

It is always in units of atoms
Units of photons and of cells
DNAs RNAs and neurons
Always the same rises ee falls
Always it is the song of cells

And the Empire State Building raised a spectacle in Manhattan skyline as
The traffic lit the air in all its expressions in the evening and in Scotland I
Saw heather and hyacinth in Swansea the light and its spread the same
Light the same song written and sung in many a form in many a rainbow
And it is the same that drives us to strive to stretch to reach to risk to rise

It is always magnetic
Always electric and
Chemical and active
Biochemical it is as
It shapes the cell-rise

I saw grace in human faces in Prague in Granada in Dhaka in Rome or in
London Manchester or York and found moss on city brick walls and saw
Butterflies on squeezed in greens of tiny spaces in town gardens and saw
Waters mining for life poetry in silence music in the ferns climbing onto
The trellis of light heard seagulls’ cries as human babies in all-everyday

In everyday momentary miracles
I saw life’s rainbow biochemistry
Unfolding noughts in paperboats
It is always the same song of love
That never dies and forever lives

:Munayem Mayenin: November 07: 2015

New Function of a Key Component in the Immune System Discovered













|| October 21: 2018: Lund University News || ά. The complement proteins, that circulate in our blood, are an important part of our immune system. They help identify bacteria, viruses and other harmful organisms, making it easier for our white blood cells to find and neutralise dangerous microbes. Researchers at Lund University in Sweden have now discovered a previously unknown function of the central complement protein, C3, which describes how C3 regulates autophagy. Autophagy is the basic mechanism, that controls cells’ ability to break down their own material, i.e, dispose of cellular waste and generate new energy by reusing their own components.

Disruption of the autophagy mechanism is thought to contribute to the development of several diseases. Therefore, this knowledge can play an important role in our understanding of the onset and treatment of Type Two Diabetes and other diseases. A few years ago, the research teams led by immunologist Ms Anna Blom and Diabetes Eesearcher Mr Erik Renström at Lund University showed that the complement system, which consists of some 40 proteins in the blood, is, also, present within our beta cells in the pancreas.

One protein, CD59, was shown to be essential for enabling beta cells to secrete insulin. Another protein, C3, was produced in large amounts in the beta cells but its exact role was unclear. In a new study, which has now been published in Cell Metabolism, the researchers discovered that the complement protein C3 can protect the beta cells from stress, e.g, long-term high blood sugar levels, when Diabetes is in progress.

When the researchers, using CRISPR:Cas9, removed the gene, that expresses the complement protein C3 from the beta cells, autophagy was disrupted and the cells died more easily from stress. They, also, found that C3 production in beta cells increases considerably in response to Diabetes and inflammation, probably, in an attempt to protect beta cells.

“C3 is a very old protein from an evolutionary perspective and we have now shown that it not only has a role in the relatively modern immune system in the blood but, also, within cells, where it is needed for one of the most fundamental cellular functions, autophagy. In all likelihood, this applies to many cell types and opens the way for new principles in the treatment of diseases, such as, Type Two Diabetes and certain neuro-degenerative diseases for which there is a need to protect cells from stress.” Says Ms Anna Blom.

The study was funded with support from the Knut and Alice Wallenberg Foundation, the Swedish Diabetes Foundation, the Greta and John Kock Foundation, the Royal Physiographic Society of Lund, the Lars Hierta Memorial Foundation, the Albert Påhlsson Foundation for Research and Charity, the Crafoord Foundation, the Tore Nilsson Foundation for Medical Research, the Swedish Heart-Lung Foundation and the Swedish Foundation for Strategic Research. 

The Paper: Complement component C3 is highly expressed in human pancreatic islets and prevents β-cell death via ATG16L1 interaction and autophagy regulation:::ω.

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Zoledronic Acid Improves Disease-Free Survival in Pre-Menopausal HR+ Early Breast Cancer


















|| October 21: 2018 || ά. Adjuvant treatment with the bone sparing drug Zoledronic Acid plus hormonal therapy with the aromatase inhibitor Letrozole, significantly, increases disease-free survival compared to Tamoxifen in pre-menopausal women with hormone receptor positive:HR+ early breast cancer, according to results reported at the European Society of Oncologists:ESMO Congress 2018 in Munich. It is the first study to assess this specific combination in pre-menopausal breast cancer and adds to previous observations with Zoledronic Acid and Anastrozole in pre-menopausal women receiving ovarian suppression.

Studies have shown reduced recurrence and breast cancer mortality with Zoledronic Acid plus hormonal therapy in HR+ breast cancer in post-menopausal women but the benefit in pre-menopausal women was previously less clear. Zoledronic Acid is a bisphosphonate, that reduces the rate of bone turnover; it is licensed to treat Osteopororosis and to reduce bone damage in advanced cancers involving bone and hypercalcaemia in cancer. Unlike Tamoxifen, which blocks Estradiol binding to the Estrogen receptor, Letrozole is an aromatase inhibitor, that, profoundly, suppresses Estradiol levels but has not, previously, been evaluated in pre-menopausal breast cancer.

The HOBOE-2 or Hormonal BOne Effects-2 phase 3 trial included 1,065 patients with Estrogen:Progesterone receptor positive early breast cancer, who had their last period within one year of randomisation. They were treated with the gonadotrophin-releasing hormone agonist Triptorelin, 3.75mg every four weeks, for five years up to the age of 55 to suppress ovarian function and nearly two-thirds, 63%, received chemotherapy before randomisation.

The patients were randomised to hormonal therapy with Tamoxifen, 20mg:day or Letrozole, 2.5mg:day or to combination therapy with Zoledronic Acid, 4mg IV every six months, plus Letrozole, 2.5mg:day, ZL, for a planned treatment duration of five years. The study was stopped early in May 2018 after a median follow-up of 65 months, when the Independent Monitoring Committee recommended sharing the data with the Early Breast Cancer Trialists’ Co-operative Group:EBCTCG2018 overview.

Results reported at ESMO 2018 showed there were 32 breast cancer recurrences or second breast or non-breast cancers or deaths in patients treated with ZL, giving a five-year disease-free survival:DFS probability of 0.93. There were 58 events in patients treated with Tamoxifen and 44 events in the Letrozole group, giving five-year DFS event rates of 0.85 and 0.93, respectively, p=0.008.

Disease-free survival was, significantly, improved in patients randomised to Zoledronic Acid plus Letrozole compared to those treated with Tamoxifen, with an absolute advantage of 08% in five-year DFS. The risk of breast cancer recurrence or non-cancer death was nearly halved in patients treated with ZL compared to those treated with T, hazard ratio:HR 0.52, 95% confidence interval 0.34-0.80, p=0.003.

The improvement in DFS with ZL compared to Tamoxifen was seen in all sub-groups of patients apart from the small sub-group of women with tumours overexpressing HER2, who showed greater benefit with Tamoxifen, interaction p=0.002.

There was no statistically significant difference in DFS comparing Letrozole with Tamoxifen, HR 0.72, 95% CI 0.48-1.07, p=0.06) or comparing ZL with Letrozole alone, HR 0.70, 95% CI 0.44-1.12, p=0.22.

As expected, side-effects were more frequent in patients treated with ZL, with 09% of patients experiencing grade 03-04 toxicity compared to 04% of those treated with T and 07% of those treated with L. Nearly one in five, 17%, patients treated with ZL stopped treatment before five years due to toxicity or refusal, compared to 07% of those on T and 07% of those on L. Among the most feared side-effects associated with the study drugs, there were four cases of jaw osteonecrosis in the ZL arm.

“HOBOE-2 strongly supports the hypothesis that combination treatment with an aromatase inhibitor and bisphosphonate plus Triptorelin, may, improve prognosis in pre-menopausal patients with HR-positive breast cancer.” said the Lead Author Professor Francesco Perrone, the Director of the Clinical Trials Unit at the Istituto Nazionale Tumori, Naples, Italy.

“We had previously shown that, in combination with Triptorelin, Letrozole suppresses Estradiol levels much more than Tamoxifen in pre-menopausal patients. And we know that suppressing Estradiol levels means cutting the fuel to endocrine-dependent breast cancer.

Our hypothesis is that the drug modifies the bone micro-environment, that is the niche, where breast cancer micro-metastases remain in a state of dormancy, potentially, for many years. Micro-environment modifications, may be, lethal for isolated cancer cells, reducing the risk of distant metastases over time. The two mechanisms are, partially, independent and, therefore, may, sum up to give an additive benefit.”

Reviewing the potential impact on clinical practice, Professor Perrone suggested, “If, the size of the benefit we saw is confirmed with longer follow-up, ZL treatment, might, turn out to be a highly cost-effective treatment for premenopausal HR+ breast cancer.” He noted that Zoledronic Acid and Letrozole are both very cheap drugs, so could be used widely.

Commenting on the study for ESMO, Professor Robert Coleman, Emeritus Professor of Medical Oncology, University of Sheffield, UK, said, “The findings add to existing information to support the use of more intensive treatment with an aromatase inhibitor and bisphosphonate in women at high risk for recurrence, either by virtue of node involvement or high-grade or large tumours. Both treatments add toxicity over and above Tamoxifen and so are best limited to women at intermediate to high risk where the risk-benefits are likely to be acceptable.”

Professor Coleman cautioned that the study was under-powered, with insufficient events for statistical confidence in the results. “This study is not definitive but adds to the information on these two treatment approaches and will contribute to the ongoing EBCTCG meta-analyses.” He considered that there were unlikely to be further trials with aromatase inhibitors and bisphosphonates as the focus is now on adding other targeted treatments.

About the European Society for Medical Oncology:ESMO: ESMO is the leading professional organisation for medical oncology. With 18,000 members representing oncology professionals from over 150 countries worldwide, ESMO is the society of reference for oncology education and information. ESMO is committed to offer the best care to people with cancer, through fostering integrated cancer care, supporting oncologists in their professional development, and advocating for sustainable cancer care worldwide:::ω.

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New Researchers Set to Pinpoint When Lung Health Declines in Younger Smokers




|| October 18: 2018 || ά. Researchers in Southampton and London have launched a national study, which aims to pinpoint, when lung health starts to decline in young adult smokers. Led by Professor Tom Wilkinson at the NIHR Southampton Biomedical Research Centre, it is hoped the project will help clinicians work towards a way of preventing Chronic Obstructive Pulmonary Disease:COPD. Funded by the British Lung Foundation, it will involve monitoring the lung function of smokers, aged between 30 and 45, over three years through check-up appointments every six months.

COPD is the name for a collection of lung diseases, including, Bronchitis and Emphysema and causes the airways in the lungs to become inflamed and narrowed, making it hard to breathe. It is the second most common lung disease in the UK after Asthma, affecting an estimated three million people, with two million of those undiagnosed and at risk of contracting a more severe form of the illness as they get older. The likelihood of developing COPD increases the more frequently and the longer an individual smokes. Although, there is currently no cure, treatment can help slow the progression of the condition and control symptoms.

“COPD develops slowly over a number of years but it is not currently known at what point the disease develops, as most people do not have any symptoms until significant lung damage has occurred.” said Professor Wilkinson, who is a Consultant in Respiratory Medicine at University Hospital Southampton NHS Foundation Trust.

“Regular lung function testing will allow us to pinpoint, when function begins to decline to help identify the onset of the disease. This study is about working towards helping us develop treatments, that, may be, available to prevent the disease as opposed to treating it after it is diagnosed, when much of the damage is done.”

Participants in the study, which is being run in collaboration with Imperial College Healthcare NHS Trust, will, also, offer advice and support on how to quit smoking. Ms Bethany Armstead, Respiratory Research Sister at the NIHR Southampton Biomedical Research Centre, said, “This study has the potential to be very important in advancing our knowledge about how smoking changes lung function pre-COPD, which, may, lead to improvements in recognising those at risk and the way treatments are managed.

It is, also, a great opportunity to utilise current public engagement with the Stoptober campaign and participants will, also, receive support to help them try to stop smoking, so, we are hopeful, we can obtain useful information while, also, helping people to quit along the way should they wish.”

If, you are interested in being involved, contact 023 8120 4479 or email COPDResearch at uhs.nhs.uk for more information.:::ω.

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New Research Identifies New Role of TIP60 Protein in Controlling Tumour





|| October 08: 2018: National University of Singapore News || ά. A new molecular pathway, that controls colorectal cancer development, has been identified by new research. Assistant Professor Sudhakar Jha, Principal Investigator at CSI Singapore and his colleagues found that TIP60 protein, a known cancer suppressor for breast and colorectal tumours, works with another protein, called, BRD4, to suppress the expression of a group of genes, called, endogenous retroviral elements:ERVs, which are, also, known as ‘jumping genes’ in tissues.

ERVs are capable of jumping across the genome during their replication. They can alter the sequences of other genes, that encode proteins and, even, result in mutations or changes in the genetic sequence. ERVs can, also, activate tissue inflammation, which supports tumour growth. TIP60 expression has been found to be greatly reduced in different tumour types, including, breast, colorectal and human papillomavirus-induced cervical cancer. “In our study, we found that in tissues with lower TIP60 protein presence, the jumping gene expression is uncontrolled and these tissues can develop an inflammatory response, which, in turn, can cause tumours to form.

This discovery of TIP60’s association with tissue inflammation is significant because it is known that in certain cancers, such as, liver and colorectal cancer, inflammation of tissues predisposes individuals to the development of early stage cancer. Thus, TIP60 protein can, potentially, be used to silence ERV expression and, essentially, stop tumour formation.” Mr Jha, who is, also, from the Department of Biochemistry under the NUS Yong Loo Lin School of Medicine.

When the researchers artificially introduced TIP60 in colorectal cancer cells, a slower growth of cells, that have higher TIP60 expression, was observed. This is consistent with its function as a tumour suppressor, that slows down or prevents the growth of tumour cells.

“We have, also, found that tumours, where we artificially deplete TIP60 protein are more sensitive to specific drugs, that are currently used against human immunodeficiency virus:HIV. This is of huge promise because these drugs have already been tested for their side effects in humans. We can look at cancer patient samples and see, if, they have low TIP60 levels by correlating with the expression of ERVs and inflammatory genes.

In this way, we can, potentially, identify the cohort of patients, that could benefit from this treatment.” said Dr Deepa Rajagopalan, a Research Fellow at CSI Singapore, who had carried out the research, when she was a doctoral student at the Department of Biochemistry at NUS Yong Loo Lin School of Medicine. She is, also, the First Author of the paper.

The research team is currently conducting studies to verify whether this mechanism of TIP60 silencing the jumping genes is true in other cancers, such as, liver and breast cancers. They are, also, in talks with other research groups at CSI Singapore on using an optimised platform to screen drug combinations that are highly efficient in killing cancer cells.

They hope to use a variety of different combinations of the anti-HIV drugs to treat colorectal cancer cells first and other tumours, such as, breast and liver, that, also, have low TIP60 levels. The researchers are looking to investigate the efficacy of drugs, that disable the function of BRD4, the protein, that works with TIP60 in tumour formation, in combination with anti-HIV drugs in tumour treatment. :::ω.

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New Structural Map of Bacterial Toxins Raises Hopes for New Anti-Infectives














|| September 27: 2018: Karolinska Institutet News || ά. The bacteria Pseudomonas Aeruginosa can cause serious and difficult to treat infections. The infection process involves the activation of toxic substances from the bacteria by a common protein in our cells. Researchers at Karolinska Institutet now show how this happens and how this activation can be stopped with drug-like molecules. The results are presented in Nature Communications.

Pseudomonas Aeruginosa infections are a common problem in hospitals. Antibiotic-resistant strains of the bacteria can cause life-threatening infections in patients with reduced immunity or large, open wounds. The bacteria, also, cause infection of the airways, which makes people with respiratory impairment, such as, cystic fibrosis, particularly vulnerable. To find new means of treating these infections, researchers at Karolinska Institutet, Umeå University and Yale University have mapped the three-dimensional structure of two toxic proteins, that the bacteria use to trigger the infection process.

The researchers have determined the structure of these toxins, called, ExoS and ExoT, along with a human protein, called, 14-3-3, which is known to be necessary for the toxins to become active. Previously, very little was known of the structure of one of the toxins, ExoS and how it binds to the human protein. But it was unclear how this contact could give rise to the bacterium’s toxic effects.

The research team has now found a large, hydrophobic contact interface between the human protein and the bacterial toxins and shown that, if, this surface is not protected by the human protein, the toxins form inactive clusters in the cell’s water-soluble environment. In other words, the protein makes the bacterial toxins active by acting as a protective ‘chaperone’.

This newly identified contact interface presents a possible target for drug molecules. The study identified two small organic molecules, that can prevent the infection between the bacterial toxins and the human protein. It, also, shows that the toxins lose their toxic activity, when these molecules are introduced. The effect is weak, but according to the researchers, the results show that the principle works.

The previously known contact between the bacterial toxins and the human protein takes place in an area, where many other proteins in the cell bind. Affecting this region with drug molecules would, probably, therefore, cause serious adverse effects. The newly discovered surface can prove a more specific target.

“Our study shows that it’s possible to block toxin activity with drug-like molecules via an interface, where no other proteins have yet been shown to interact.” says Principal Investigator Herwig Schüler, Associate Professor of Structure Biology at the Department of Biosciences and Nutrition, Karolinska Institutet.

The study was financed by the Swedish Research Council, the Swedish Foundation for Strategic Research, the Wenner-Gren Foundation and the IngaBritt and Arne Lundberg Research Foundation.

The Paper: 14-3-3 proteins activate Pseudomonas exotoxins-S and -T by chaperoning a hydrophobic surface: Tobias Karlberg, Peter Hornyak, Ana Filipa Pinto, Stefina Milanova, Mahsa Ebrahimi, Mikael Lindberg, Nikolai Püllen, Axel Nordström, Elinor Löverli, Rémi Caraballo, Emily V. Wong, Katja Näreoja, Ann-Gerd Thorsell, Mikael Elofsson, Enrique M. De La Cruz, Camilla Björkegren and Herwig Schüler: Nature Communications: Online: September 17: 2018:::ω.

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Do Not Mix and Match For They May Be Mixed But They Do Not Match: Mixing Energy Drinks With Alcohol Could Enhance the Negative Effects of Binge Drinking




|| August 14: 2018: University of Portsmouth News || ά. A key ingredient of energy drinks could be exacerbating some of the negative effects of binge drinking, according to a new study. Many people mix energy drinks with alcohol to counteract the sedative nature of alcohol, tricking users into feeling more awake and less drunk than they really are. However, when researchers from the University of Portsmouth and the Federal University of Santa Maria in Brazil tested the effects of taurine, a key ingredient of many energy drinks and alcohol on social and fear responses in Zebrafish, they found that taurine seemed to increase the fear-reducing properties of alcohol but, also, affected social communication.

In the study, published in the Journal of Psychiatric Research, the researchers tested how taurine and alcohol, at volumes reflecting levels, that would induce moderate human intoxication, affected the behaviour of 192 Zebrafish. The fish were divided into shoals, with four fish per shoal and were exposed to just water or taurine and alcohol separately or taurine and alcohol for one hour. Their shoaling behaviours were then analysed at different time intervals; at 0-5 minutes, 30-35 minutes and 55-60 minutes. The fish were, also, tested for their fear-like responses to a predator by dividing the tank into four areas, with the furthest area used to mimic a predator fish.

Co-author of the study Dr Matt Parker, Senior Lecturer in Behavioural Pharmacology and Molecular Neuroscience at the University of Portsmouth, said, “The effects of mixing alcohol and energy drinks is yet to be established. This study is the first to show that the two together, may be, exacerbating some of the negative effects of binge drinking, that is reduction of fear and problems in social communication while intoxicated, which collectively increase the risk of fighting, violence and participation in risky behaviours.”

The fish, that were exposed to both alcohol and taurine had fewer interactions with other fish in the shoal compared to those exposed to water alone or just alcohol. These fish, also, showed more ‘risky’ behaviour, spending more time in the predator zone than other groups.

Dr Parker said, “Binge drinking and general alcohol misuse is a key problem in the UK and across the world, with the numbers of hospital admissions resulting from illness or injury following intoxication costing the NHS millions per year. Alcohol reduces our inhibitions and in low doses can cause relaxation and euphoria.

However, in higher doses this low inhibition can cause problems with fighting or risky behaviour. Zebrafish have similar biological and behavioural responses to alcohol and are a highly social species, making them ideal for studying the effects of alcohol on behaviour. 

Here, we found that the addition of taurine, an ingredient in many ‘energy’ drinks, appears to exacerbate risky choices in Zebrafish, as well as, reducing their social cohesion. Taken together, these data appear to suggest that mixing alcohol and taurine, might be, a factor in increasing some of the negative effects of alcohol. People should be aware that drinking energy drinks in combination with alcohol, may, impair their judgement and should do so with caution.” :::ω.

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Nano-Tech Diagnostic Can Indicate Cancer Or Thrombotic Risk in One Drop of Blood




|| July 22: 2018: Trinity College Dublin News || ά. A team of international researchers led by Professor Martin Hegner, Investigator in CRANN and Trinity’s School of Physics, have developed an automated diagnostic platform, that can quantify bleeding and thrombotic risks in a single drop of blood, within seconds. The researchers exploited micro-resonators for real-time measurements of the evolving strength of the blood plasma clot.

Along with the clinically measured clotting time, other insightful parameters, from specific factor deficiency to global coagulation parameters, used to assess fibrinolysis, can, also, be extracted. These technical developments introduce a miniaturised global haemostasis assay with the capability of fine-tuning factor replacement or anti-coagulation therapies. In collaboration with the multi-national, Hoffman-la-Roche, the researchers report a new strategy for quick, reliable and quantitative diagnostics of expression patterns of non-coding short RNA in blood plasma or cell cultures.

They directly detect label-free specific miRNA biomarkers relevant to cancer and adverse drug effects in blood-based samples. Professor Hegner’s work focuses on the development of innovative nano-technological automated diagnostic platforms, that underpin next-generation medical devices.

The collaboration with the multinational Hoffman-la-Roche, a world leader in in-vitro diagnostics, enabled this scientific study and provides the possibility to further miniaturise this device for portable point of care testing for the market and society.

Professor Hegner said, “This has significant implications for a non-invasive, rapid and personalised diagnosis using nanomechanical sensors. We believe that the comprehensive direct diagnostic approach to analyse blood haemostasis and the abundance of specific miRNA in cells and serum has a significant impact on various areas, including but not limited to cancer diagnostics or drug-adverse effects where such markers are excreted into the blood stream.”

The research has been published in Nanoscale journal of the Royal Society of Chemistry.

Professor Hegner was awarded a Science Foundation Ireland Principal Investigator award in 2016, valued at €01.3m, which will enable him to continue his work in this field. :::ω.

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New Research Discovers Potential New Drug for Two Life-Threatening Diseases: Schistosomiasis and Fascioliasis




|| July 15: 2018: Cardiff University News || ά. Derived from nature, a potential new drug to treat two life-threatening tropical diseases has been discovered as a result of collaboration between two Welsh universities. The team of researchers, led by Professor Andrew Westwell from Cardiff University, has successfully created a drug compound, from the Goji Berry plant, that is active against the parasites, that cause Schistosomiasis and Fascioliasis.

Although, not widely known, Schistosomiasis is the most devastating human parasitic disease after Malaria, with approximately 600 million people currently affected and causing approximately 300,000 deaths per year. Likewise, 17 million people are currently infected with Fascioliasis, with figures set to increase. Schistosomiasis is caused by a waterborne parasite, while Fascioliasis is caused by a foodborne parasite. 

Both of these neglected diseases are treated with a single drug, which is widely administered to the population where these diseases are most prevalent.  However, this type of single treatment, often, leads to drug resistance, which is now the case for many people at risk of contracting these diseases.

As a result, a team of researchers at Cardiff University joined forces with Aberystwyth University’s Institute of Biological, Environmental and Rural Sciences, led by Professor Karl Hoffmann, in a collaboration to find a new drug treatment.

Speaking of the research, Professor Westwell from Cardiff University’s School of Pharmacy and Pharmaceutical Sciences, said, “Discovering a potential new treatment for two such prevalent diseases is an exciting find and we hope that this research will lead to major health benefits for some of the world’s poorest people, who are at risk of contracting Schistosomiasis and Fascioliasis.”

Funded by the Welsh Government’s Life Science Research Network of Wales, the drug design was carried out at Cardiff University’s School of Pharmacy and Pharmaceutical Sciences and the testing of its effectiveness has taken place at Aberystwyth University.

The Paper: Design, synthesis and anthelmintic activity of 7-keto-sempervirol analogues: Published in the European Journal of Medical Chemistry.::ω.

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Higher Inflammation in Older Age is Linked to Lower Bone Density


|| June 24: 2018: University of Southampton News || ά. Although, inflammation can arise from infection or injury, chronic inflammation can occur in older age due to ageing processes in the immune system. Higher levels of inflammation in older age has been linked to lower bone density, according to a new study carried out at the University of Southampton. Scientists from the University’s Medical Research Council Lifecourse Epidemiology Unit examined the relationship between levels of inflammation in early old age and bone density at the spine and the hip.

The relationship between levels of inflammation and change in bone density over a period of five years was, also, explored. The study, published in Osteoporosis International, showed that higher levels of adiponectin was related to lower bone density at the spine and hip and lower levels of interleukin-10:IL-10 was associated with faster decline in bone density at the spine. Adiponectin and IL-10 each modify the pro- and anti-inflammatory balance.

Lead Author, Mr Nicholas Fuggle, Researcher at the University of Southampton, said, “Low bone density increases the risk of osteoporosis, which affects so many older people and is extremely debilitating. This study highlights the importance of inflammatory markers in the development of osteoporosis. We hope that this study will help us develop potential ways of combatting the condition, which will lead to improvements in quality of life.”

Professor Cyrus Cooper, Director of the MRCLEU, said, “Poor bone health in older age is a leading cause of disability worldwide and has huge economic costs for society. These results will inform the development of lifecourse intervention strategies to promote better musculoskeletal health in later life.”

The study involved 365 men and women, aged 59-71 years when inflammation was assessed from the Hertfordshire Cohort Study and was funded by the Medical Research Council.

The work was funded and supported by the Medical Research Council of the UK, NIHR Biomedical Research Centres Southampton, Birmingham and Oxford, Arthritis Research UK, British Heart Foundation; and International Osteoporosis Foundation.

The Paper: Relationships between markers of inflammation and bone density: findings from the Hertfordshire Cohort Study: Published in Osteoporosis International:::ω.

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Lipid Molecules Can Be Used for Cancer Growth



|| June 10: 2018: Karolinska Institutet News: || ά. Cancer cells can, when the blood supply is low, use lipid molecules as fuel instead of blood glucose. This has been shown in animal tumour models by researchers at Karolinska Institutet in Sweden in a study, published in Cell Metabolism. The mechanism, may, help explain why tumours, often, develop resistance to cancer drugs, that inhibit the formation of blood vessels.

Tumour growth and spread rely on angiogenesis, a process of growing new blood vessels, that supply the cancer cells with nutrients and hormones, including, glucose. Treatment with anti-angiogenic drugs reduces the number of blood vessels in the tumour, as well as, the blood glucose supply. Many such drugs have been developed and are now used in human patients for treating various cancer types.

However, the clinical benefits of anti-angiogenic drugs in cancer patients are generally low and the cancers treated, often, develop a resistance to drugs, especially, cancer types, that grow close to fat tissues, such as, breast cancer, pancreatic cancer, liver cancer and prostate cancers.
In collaboration with Japanese and Chinese scientists, a research group at Karolinska Institutet in Sweden has discovered a new mechanism by which cancers can evade anti-angiogenic treatment and become resistant.

The reduction of tumour blood vessels results in low oxygenation in tumour tissues, a process, called, hypoxia. In the current study, the researchers show that hypoxia acts as a trigger to tell fat cells surrounding or within tumour tissues to break down the stored excessive lipid energy molecules. These lipid energy molecules can, when the blood supply is low, be used for cancer tissue expansion.

“Based on this mechanism, we propose that a combination therapy consisting of anti-angiogenic drugs and drugs blocking lipid energy pathways, would be more effective for treating cancers.

In animal tumour models, we have validated this very important concept, showing that combination therapy is superior to monotherapy.” says Professor Yihai Cao, at the Department of Microbiology, Tumour and Cell Biology at Karolinska Institutet, who led the study.
Professor Cao’s group now plans to work with drug companies and clinical oncologists to explore whether such a new combination therapy would improve the quality of life and lifespan in human cancer patients.

The study was financed by the Swedish Research Council, the Swedish Cancer Foundation, Karolinska Institutet, the Torsten Söderberg Foundation, the Tore Nilson Foundation, the Ruth and Richard Julin Foundation, the Ögonfonden Foundation, the Wera Ekström Foundation, the Lars Hierta Memorial Foundation, National Natural Science Foundation of China, the International Research Fund for Subsidy of Kyushu University School of Medicine Alumni, the Martin Rind Foundation, the Maud and Birger Foundation, the Alex and Eva Wallström Foundation, the Robert Lundberg Memorial Foundation, the Swedish Diabetes Foundation, the Swedish Childhood Cancer Fund, the European Research Council, the Knut and Alice Wallenberg Foundation, and the Novo Nordisk Foundation.

The Paper: Cancer lipid metabolism confers antiangiogenic drug resistance: Hideki Iwamoto, Mitsuhiko Abe, Yunlong Yang, Dongmei Cui, Takahiro Seki, Masaki Nakamura, Kayoko Hosaka, Sharon Lim, Jieyu Wu, Xingkang He, Xiaoting Sun, Yongtian Lu, Qingjun Zhou, Weiyun Shi, Takuji Torimura, Guohui Nie, Qi Li, and Yihai Cao: Cell Metabolism: Online: 31 May 31: 2018

Caption: Professor Yihai Cao: Karolinska Instituted: Image: Ulf Sirborn::: ω.

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The International Society of Pharmaceutical Engineers and the Parenteral Drug Association Sign Memorandum of Understanding to Work Closely to Advance Quality Metrics and Culture


|| May 07: 2018 || ά. The International Society of Pharmaceutical Engineers:ISPE and the Parenteral Drug Association:PDA have signed a Memorandum of Understanding to exchange information regarding their respective efforts on Quality Metrics and Quality Culture. ISPE published their Culture Excellence Report in May of 2017, that shared the vision of quality culture improvements across six dimensions and has, also, collected, analyse, and published industry survey data, that correlates pharmaceutical manufacturing metrics to quality outcomes.

PDA pursued a Quality Culture Assessment to define quality culture attributes and has collected, analysed and published data and worked to establish a correlation to operational excellence. Under the MOU, the two organisations agree to share relevant documents developed by their respective quality metrics and culture teams. The MOU leaves open the possibility that ISPE and PDA could directly collaborate on these topics in the future.

About ISPE: The International Society for Pharmaceutical Engineering:ISPE is the world’s largest not for profit association serving its members through leading scientific, technical and regulatory advancement across the entire pharmaceutical life cycle. The more than 18,500 members of ISPE are building solutions in the development and manufacture of safe, effective pharmaceutical and biologic medicines and medical delivery devices in more than 90 countries around the world. Founded in 1980, ISPE has its worldwide headquarters in Bethesda, Maryland USA and an operations and training centre in Tampa, Florida USA. ::: ω.

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Doctors are Using A Protein in Blood to Help Liver Patients Fight Infection

|| April 14: 2018 || ά. Researchers in Southampton are using a protein found in the blood to help improve the effectiveness of antibiotics in patients with liver disease. Patients with end-stage liver disease, known as, decompensated cirrhosis, can not produce albumin, which binds calcium, hormones, vitamins and drugs through the bloodstream. Levels of the hormone prostaglandin E2 are high in this group of patients, leaving their immune systems compromised and prone to, potentially, life-threatening infections.

By administering the protein, which is given via injection, doctors at Southampton General Hospital and 26 other centres across the UK hope to bring patients’ albumin levels close to those of a healthy person, which will inactivate the hormone and boost their immune systems. More than 600,000 people in England and Wales have some form of liver disease and 60,000 of those have cirrhosis, scarring caused by long-term damage. It is the fifth largest cause of death in the UK and the third most common cause of death among people between the ages of 35 and 65 years.

Liver disease occurs, most commonly, as a result of alcohol misuse, hepatitis B and C infection and non-alcoholic fatty liver disease:NAFLD, caused by obesity. As the condition can go undetected until the liver is severely damaged, more than three-quarters of patients arrive at emergency departments having never seen a liver specialist and one in four admitted with liver failure will not survive to one year following an admission to hospital.

“It is vital patients with cirrhosis are assessed for infections and treated with antibiotics to prevent potentially serious complications.” says Dr Janisha Patel, a Consultant Hepatologist at University Hospital Southampton NHS Foundation Trust.

“However, their immune systems are compromised, which enhances the aggressiveness of infections. So, by boosting the albumin to bring it close to the same levels as a healthy person, we can help restore their immune systems and boost the power of antibiotics they are given.”

Dr Patel says that the approach can not only improve patients’ recovery in hospital but, may, improve their survival after discharge. “Through this trial we aim to give patients albumin to study their recovery from the time they are admitted to hospital and up to six months after, which will allow us to understand the longer-term benefit to them.” she says.

“Patients, who go on to make positive changes to their lifestyle, such as, giving up alcohol and better controlling their diabetes, have an 80% chance of survival over two years, so this intervention has the potential to make a significant impact during their acute illness.” ::: ω.

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For Stories Published in Biochemistry in Year Gamma Arkive


|| April 06: 2018 || ά. The Humanion was first published on September 24, 2015 and has been run, since that day, on a complete voluntary basis without any 'formal' or 'constituted' manner or form and, it was run on as a Human Enterprise, which is an idea of Humanics, in which, ownership is replaced by belongingship and, thus, in a Humanical Society, no one owns anything but everyone belongs to the whole as the whole belongs to everyone lawfully and equally and, it neither believes in nor makes money but human utilities, needs, aspirations, creativity, imagination and dreams are served without money, where everyone works and creates for all others as all others create and work for all others, thus, bringing in meaning and purpose to life along with it come natural justice, equality and liberty, that establish a true civilisation within the Rule of Law. And in one word, this system of human affairs management is called, Humanics and a society that runs itself in humanics is called a humanical society. Today, we have begun the process of 'constituting' this Human Enterprise, which does not exist in the current system, but the next closest thing to it, that exists in the UK Law is Social Enterprise. Therefore, today, Friday, April 06, 2018, we are beginning Regine Humanics Foundation, that is the 'Agency', that will lead, run, manage and develop everything, that The Humanion has been trying to do.

Regine Humanics Foundation is established by the Thinker, Author, Poet, Novelist, Playwright, Editor of The Humanion, Festival Director of London Poetry Festival and a Humanicsxian: hu: maa: neek: tian: One, that believes in, lives and exists by Humanics, Mr Munayem Mayenin, of London, England, United Kingdom. Mr Mayenin says, ''Humanics is a vision; people, may, call it, utopia, we, call it our Humanicsovicsopia; Humanics. Humanics is our philosophy, our faith, our conviction, our resolution, our way of existing, thinking, being and doing: to seek and try to do so in the determination that all we must do and be is to exist to advance the human condition. People, readers and agencies and organisations, from all across England, Scotland, Northern Ireland, Wales and the whole of the United Kingdom and Australasia, Africa, Asia, Europe, North and South America, from all walks and strata of life, have supported our endeavours, supported The Humanion and The Humanion Team, who volunteered their time to run things, since the beginning of The Humanion and long before that, when other things, that are now part of The Foundation, were developing. Nothing has changed in terms of the nature and value of what we have been seeking to do.''

''But the founding of The Foundation brings it all in a solid foundation so that we can keep on building this 'vision' so that it keeps on going regardless of who come to take the vision-mission of The Foundation forward. The Foundation runs along with time and along with the flowing humanity. This is the dream, this is the vision, this the hope in founding this Foundation. And, in this, we hope and invite all our readers, supporters, well wishers and all agencies and organisations to support our endeavours to build something, a Human Enterprise, which we are in the process of registering as a Social Enterprise, as a Community Interest Company, working for the common good of the one and common humanity. No one makes or takes profit out of The Foundation, which now runs The Humanion and everything else, that is part of it. The Foundation, once registered, will have an Asset Lock, which means that in any event, should The Foundation dissolve itself, all its existing assets shall go to a similar Social Enterprise. Therefore, we invite everyone to support The Foundation, support The Humanion in whatever way they can. And, there are endless number of ways people and organisations can support The Foundation and The Humanion.'' ::: ω.

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Charing Cross Hospital: Please, Note, The CCH Clock Does Work Perfectly


















University College Hospital London















Eastman Dental Hospital















Life's Laurel Is You In One-Line-Poetry A Heaven-Bound Propagated Ray Of Light Off The Eye Of The Book Of Life: Love For You Are Only Once



Life: You Are The Law The Flow The Glow: In Joys In Hurts You Are The Vine-Songs On The Light-Trellis


























|| All copyrights @ The Humanion: London: England: United Kingdom || Contact: The Humanion: editor at thehumanion.com || Regine Humanics Foundation Ltd: reginehumanics at reginehumanicsfoundation.com || Editor: Munayem Mayenin || First Published: September 24: 2015 ||
|| Regine Humanics Foundation Ltd: A Human Enterprise: Registered as a Not For Profit Social Enterprise in England and Wales: Company No: 11346648 ||