Category Archives: Gene Medicine

Dr David Glass - MBChB, FCOG (SA)

Today we celebrate our 100th blog on the subject of lifestyle medicine making wise choices in the area of diet, exercise, rest, sunlight, fresh air, water, relationships and spiritual connection. This is one area of medicine that seems to permeate all others. It is becoming increasingly important as diseases of poor lifestyle choices affect more and more people around the world resulting in rising incidences of heart disease, high blood pressure, diabetes, obesity, auto-immune diseases, cancer and dementia.

ALSO READ : Turning the Tide Lifestyle Medicine and Covid 19

Of course our minds are daily preoccupied with Covid-19, and so should they be. We are facing one of the most devastating challenges to health care and the economy the world has seen this century. Two weeks ago I presented a lifestyle approach to this pandemic, because we know that the virus is particularly aggressive in people who suffer chronic lifestyle diseases.

Today we will get back to our topic for this series breast cancer. Unfortunately Covid-19 doesnt make all the other diseases, to which we are so prone, go away. As mentioned before, this series is based on Dr Kristi Funks book Breasts: The owners manual. This week we will be looking at uncontrollable risk factors.

Next week we will briefly look at some of the interventions on offer in terms of treatment and screening to complete the series on breast cancer.

Stay safe, isolated as much as possible in your home. May you use this time for building family relationships and getting life priorities right. It is good to have some forced time for reflection when we are faced with the prospect of our own mortality or that of our friends and family.

Dave Glass

Dr David Glass MBChB, FCOG (SA)

Dr David Glass graduated from UCT in 1975. He spent the next 12 years working at a mission hospital in Lesotho, where much of his work involved health education and interventions to improve health, aside from the normal busy clinical work of an under-resourced mission hospital.

He returned to UCT in 1990 to specialise in obstetrics/gynaecology and then moved to the South Coast where he had the privilege of, amongst other things, ushering 7000 babies into the world. He no longer delivers babies but is still very clinically active in gynaecology.

An old passion, preventive health care, has now replaced the obstetrics side of his work. He is eager to share insights he has gathered over the years on how to prevent and reverse so many of the modern scourges of lifestyle obesity, diabetes, ischaemic heart disease, high blood pressure, arthritis, common cancers, etc.

He is a family man, with a supportive wife, and two grown children, and four beautiful grandchildren. His hobbies include walking, cycling, vegetable gardening, bird-watching, travelling and writing. He is active in community health outreach and deeply involved in church activities. He enjoys teaching and sharing information.

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Turning the Tide Lifestyle Medicine and Breast Cancer (Part 6) - South Coast Herald

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The coronavirus disease (Covid-19) first appeared in the Wuhan district of Hubei province of China in early December 2019. The first case was reported by China on January 7, 2020, and this aroused variable interest worldwide, with most countries initially ignoring the novel infection. Fortunately, Indian health authorities sensed the danger, largely because the country has always been alert to new infections. The scientific think-tank at the Indian council of Medical Research (ICMR) became active immediately and the first laboratory confirmed case was identified at ICMRs National Institute of Virology (NIV), Pune, sometime towards the end of January.

A look at the world Covid meter shows that there is striking variation in mortality rates across countries, ranging from 0.2% to 15% depending on age, the smoking habit and pre-existing co-morbidities. It may be too early to tell, but in general, countries in the Northern hemisphere have faced the maximum brunt, and those in the Southern hemisphere (and those located proximate to the Equator) have so far escaped high infection numbers.

Three factors seem to be playing a role in the observed lower numbers in India with almost zero occurrence of severe Covid-19 cases (until now). First, broad-based immunity in the population due to the extensive microbial load. The Indian population has been exposed to a vast variety of pathogens, including bacteria, parasites and viruses leading to the generation of broad specific memory T-cells in the system, ready to attack additional foreign invaders.

For example, the three main killers of Tuberculosis, HIV and Malaria have plagued India, Africa and several countries in the Southern hemisphere much more than the European and North American nations. In the context of CoV-2 coronavirus, the beneficial role of chloroquine and hydroxychloroquine has been much talked about and debated, while there has already been an extensive usage of this drug at the community level in India this too may ultimately prove beneficial.

Also read: In fight against coronavirus, India has age on its side. Numbers show

Second, epigenetic factors that include environment and food habits may also play a beneficial role for countries such as India; much literature is already available in Ayurveda and other Indian systems of medicine on the definitive beneficial effects of Indian spices in augmenting immunity.

Third, and most important, is the possible role of immune response genes in the Indian population. These genes are collectively referred to as comprising the human leucocyte antigen system or simply, the HLA genes. Their main biological function is to present invading foreign antigens to the immune systems, since T-cells, which act as the bodys soldiers come into play only when pathogens are presented to them in a more formal manner in association with HLA genes. In other words, the pathogen must first attach to compounds created by HLA genes before T-Cells attack it. If no such compounds are produced by the body, then the T-Cells are ineffective. As a consequence of the microbial load, the Indian population possesses a high genetic diversity of HLA, much more extensive than Caucasian populations. Indeed, studies by the author at the All India Institute of Medical Sciences, New Delhi, over several decades revealed the presence of several novel HLA genes and their alleles in the Indian population, most of which do not occur in other ethnic groups. Such genetic diversity of HLA could affect viral fitness.

The question then is:Why should genetic variation in HLA genes play a role in the Covid-19 progression? One hint comes from earlier studies in related viral diseases: Certain genetic variants of the HLA system provide protection against such viruses, while others increase genetic susceptibility to them. Another source of indirect evidence comes from recent clinical Covid-19 studies which showed that rapid T-cell response appears to be crucial for recovery from Covid-19, and reduced functional diversity of T cells in peripheral blood could predict progression of Covid-19.

The big question is:Does this give Indians a better chance at fighting the virus effectively? From the epidemiological data so far, it seems so (although much more extensive research is required). However, it is important for us to keep viral loads in check and below the threshold levels. In this context, the complete lockdown announced by the government is highly timely and most desirable. It is imperative that the virus replication cycle gets disrupted as early as possible before it gains numbers that may become difficult for us to counter.

To this end, the images of crowds gathering in several places whether for panic buying or interstate movements are disturbing. They could jeopardise all efforts and mitigate whatever natural advantages we enjoy.

The State must act fast to enforce the lockdown, even forcibly if necessary. India may be the outlier in fighting the coronavirus infection and succeed in keeping the overall numbers lower than the rest of the world with minimal deaths.

Narinder Kumar Mehra is the ICMR National chair and former Dean of the All India Institute of Medical Sciences, New Delhi

The views expressed are personal

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Also read: Indias fight against Covid-19 needs wartime industrial production, not more red tape

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Indians seem to have genetic and regional advantages in fight against coronavirus - ThePrint

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As the COVID-19 pandemic spreads across the world, patients, technicians and scientists depend on state-of-the-art molecular-analysis instruments as they fight against SARS-CoV-2, the virus causing this disease. Optics and photonics technologies embedded in these instrumentssuch as high-quantum-efficiency multispectral cameras, visible-light laser diodes and LEDs, infrared bolometer arrays, narrowband optical filters and wideband multispectral optical spectrometersplay an essential part in the story.

Whether in the hospital or in the lab, optics technologies make possible rapid preliminary screening of potentially infected individuals, more accurate molecular diagnosis, reliable monitoring of disease progression and even, potentially, disinfection of contaminated surfaces. Our community developed these enabling technologies over the past several decades for applications ranging from telecommunications to machine and night vision. Now, theyre playing a life-saving role in the battle against SARS-CoV-2.

Early detection of infected patientsone of the primary challenges of the COVID-19 pandemicis complicated by the wide variability in the diseases symptoms. Monitoring for an increase in body temperature is the most commonly used preliminary screen. Under normal circumstances, direct body-cavity temperature measurements are the most accurate way to monitor a fever; however, given the pathogenicity of SARS-CoV-2, remote, non-contact options that employ infrared imaging cameras to simultaneously image and measure groups of individuals provide a significant safety advantage.

Many clinicians now rely on infrared-based thermometers for measuring forehead temperature. These imaging and spot-measurement thermometric devices provide medical personnel with a safer and useful non-contact patient screen. These thermometers are based on single detectors or arrays of MEMS-based microbolometers or semiconductor diode detectorsthermal sensors that are sensitive in the far-infrared spectral region (8 to 14 m) and detect changes in the blackbody radiation intensities in persons with above-normal body temperatures.

Cepheid doctors office RT-PCR instrument. [Image: Courtesy of Cepheid]

In TaqMan real-time polymerase chain reaction, a nucleic-acid probe molecule, tagged with a fluorescent molecule and an accompanying quencher, attaches to the stretch of DNA or RNA being copied. With each round of amplification, the fluorescent molecule is released into the buffer solution and separated from the quencher, allowing the amplification of the targeted genetic sequencesuch as one from SARS-CoV-2to be detected via fluorescence in real time. [Image: Wikimedia Commons]

If a patient presents with a fever or other symptoms typical of viral infection (sore throat, dry cough, muscle aches and fatigue), the next step is a molecular diagnostic test. This screen, based on a technique called real-time reverse transcription polymerase chain reaction (RT-PCR), uses sensitive spectroscopic methods to detect extremely small quantities of viral genetic material from a patients nasal or throat swab. And once again, optical technology is an essential component for disease detection.

The diagnostic procedure requires significant sample processing, beginning with a specimen collected from a patient. Real-time RT-PCR works by copying specific nucleic acid sequences within that sample, using probesnucleic-acid primersthat selectively bind very specifically to the RNA sequences present in the SARS-CoV-2 virus. The probes are tagged with molecules of fluorescent dye.

Enzymes are then used to copy the nucleic-acid sequences bound to the probes. The sample is thermally cycled roughly 40 times between37 C and 95 C. If the target nucleic-acid sequences are present, they are amplified twofold with each cycle.

It is optical technology that puts the real time in RT-PCR. As the amplification enzymes create the duplicate copies, the fluorescent molecules are released into the buffer solution. The overall fluorescence is measured in real time after each cycle, increasing as the number of amplicons increases for positive samples. By measuring the intensity buildup during the thermal cycling, the virus is detected and the amount of virus present (the viral load) can be estimated.

Real-time RT-PCR instruments employ narrowband visible laser diodes or LEDs as excitation sources and semiconductor diodes or photomultipliers with narrow band-pass optical filters for detection. These instruments are fully automated and can typically process 96 or 384 samples in parallel in less than an hour.

Real-time RT-PCR is one of the most sensitive and specific molecular-analysis techniques available today. This assay is crucial for tracking and controlling the spread of COVID-19. However, the overall sensitivity of the method may be limited by the efficiency of the sample collection and preparation process. The amount of virus present in the sampled tissue, which varies between individuals and as the disease progresses in each patient, may also be a limiting factor.

The false-negative rate of this approach is currently estimated at roughly 30%. Repeated testing can reduce this admittedly significant percentage, which is why many hospitals require two or three sequential negative real-time RT-PCR tests after a patient has recovered before that patient is classified as non-infectious.

In addition to molecular diagnostics, imaging of the lungs of COVID-19 patients has also proved very sensitive for detecting SARS-CoV-2 infection using high-resolution computed tomography (CT) scans. Clinicians look for signs of lung damage as evidenced by ground-glass patterns in the lung tissue or fluid accumulation as signatures of pneumonia. Clinics in China have reported that this approach can detect a significant number of infected individuals that have negative RT-PCR readingsonly, however, later in disease progression, once lung damage manifests.

If a patient is diagnosed with COVID-19, disease progression and respiratory function are determined using an oxygen-saturation meter, which measures the percentage of oxygenated hemoglobin in blood. As the disease progresses, breathing can become difficult, causing a reduction in oxygenated hemoglobinif levels dip below certain thresholds, then supplementary oxygen or a ventilator may be warranted.

Oxygen-saturation devices use LEDs emitting at two different wavelengths, typically around 665 nm and 894 nm. The oxygen-saturation percentage is measured from the ratio of the absorption at these two wavelengths. These battery-powered devices fit comfortably on a finger or toe, providing real-time measurement of oxygen-saturation levels.

96 sample well plate ELISA instrument. [Image: 2020 Berthold Technologies. Used under permission. http://www.berthold.com]

Schematic of ELISA, which measures the presence of specific antibodies in a COVID-19 patients sample. The technique relies on a colorimetric change in the sample generated by an enzyme attached to antibodies specific to SARS-CoV-2 virus. [Image: Cavitri/Wikimedia Commons, CC-BY 3.0]

Optical instruments are also used to test whether a person has been exposed to SARS-CoV-2 virus and has developed an immune response. These instrumentswhich can be automated to analyze hundreds to thousands of samples per dayuse a technique called an Enzyme-Linked Immunosorbent Assay (ELISA) to measure the presence of antibodies specific to the SARS-CoV-2 virus in a patients blood-serum sample.

In a typical assay, an antigen found on the virus surface is immobilized on the bottom of a sample well, which is optically transparent. Antibodies in the serum sample are attached to an enzyme (typically horseradish peroxidase) and allowed to incubate on the surface containing the immobilized antigen. Any antibodies specific for the SARS-CoV-2 antigen bind to the target and become immobilized on the surface of the optical window. The unbound, nonspecific antibodies are washed off.

A solution containing the enzymes substrate with a colorimetric indicator is then added to the sample well, and the enzyme linked to the antibody reacts with the substrate, producing a color change in the sample. The enzyme reacts with multiple substrate molecules, thereby amplifying the signal. SARS-CoV-2 antibodies in the blood serum can then be detected and quantified, via multispectral imaging of the sample substrates fluorescence or absorption indicator.

This approach is used to measure the extent of the virus spread within a community, even after the pandemic has passed; to measure the duration of an individuals immune response; and to investigate the efficacy of antiviral drug candidates and potential vaccines. Currently, medical workers who have recovered from COVID-19 and have a protective immune response to the virus are being identified using an ELISA. Once immunity is confirmed, these personnel safely resume working with infected patientsa common approach in pandemic medicine.

Optical devices also form the core technology for the most common high-throughput gene-sequencing instruments. These typically use high-quantum-efficiency, very-high-resolution multispectral cameras to map the sequences of hundreds of millions of target DNA molecules simultaneously and can sequence the complete genome of the SARS-CoV-2 virus in just a few hours. Virus genetic sequences can vary with location, since the SARS-CoV-2 virus occasionally mutates during its replication phase. Infections in separate geographic regions can be compared, and the origins of infections traced, by comparing the specific mutations in samples taken from patients in different locations.

High-throughput sequencing of the virus genome also can determine the proteins in the virus and identify suitable targets for synthetic vaccines that will safely stimulate immune response. This technology has greatly improved over the past 20 years, largely due to the human genome project, and will be an essential tool for developing effective vaccines and antiviral drugs to combat the COVID-19 pandemic.

Prototype of an LED sterilization system being tested by Bolb Inc. [Image: Bolb Inc.]

Beyond the molecular-biology lab, optics is emerging as a weapon on another vital front: the sterilization of surfaces. Most viruses and bacteria are very sensitive to ultraviolet light, particularly in the UV-C spectral region (200280 nm), which causes mutations in the RNA that is essential for viral replication. Recently, great progress has been made in the development of UV LEDs that emit in this region. LED arrays emitting hundreds of milliwatts have been developed with lifetimes of over 1000 hours and electrical efficiencies around 10%.

Arrays of these diodes can generate significant UV power levels to potentially decontaminate certain surfaces more efficiently than chemical reagents. Recent lab results indicate that exposure times of about 1 minute were sufficient to kill bacteria and viruses with a 1-W-average-power device located about 1 meter above a contaminated surface. Further testing on the efficacy of UV LEDs for decontaminating surfaces infected with SARS-CoV-2 virus is in progress.

As global health faces this novel and deadly threat, laboratories around the world are using technologies developed by the optics and photonics community to help stem the spread and save lives. In the near future, as social distancing begins to slow the spread of COVID-19 disease, medical focus will shift to the early detection and isolation of COVID-19 recurrence in hot spots, which will present new challenges for diagnostic and decontamination technologies. These challenges represent new opportunities for optics and photonics technologieswith their advantages of low cost, high speed, sensitivity and specificityto make major contributions to global health. OPN

Note: This article will also be published in the May 2020 issue of Optics & Photonics News.

2009 OSA President Thomas M. Baer (tmbaer@stanford.edu) is with Stanford University, USA. Christina E. Baer is with the University of Massachusetts Medical School, USA.

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Optics, Photonics and COVID-19 - Optics & Photonics News

A new international project aims to enroll 500 COVID-19 patients to search for genetic mutations that make some people more vulnerable to severe infection.

HHMI scientists are joining many of their colleagues worldwide in working to combat the new coronavirus.Theyre developing diagnostic testing, understanding the viruss basic biology, modeling the epidemiology, and developing potential therapies or vaccines. Over the next several weeks, we will be sharing stories of some of this work.

Hundreds of clinicians worldwide are banding together in an effort to study some types ofseverecases of the new coronavirus disease.

The project, led by Howard Hughes Medical Institute (HHMI) Investigator Jean-Laurent Casanova at The Rockefeller University, seeks to identify genetic errors that make some younger patients especially vulnerable to the virus that causes COVID-19, the infectious respiratory illness also known as coronavirus disease 2019.

Casanova aims to enroll 500 patients internationally who meet three broad criteria: theyre less than 50 years old, have been diagnosed with COVID-19 and admitted to an intensive care unit, and have no serious underlying illnesses, such as diabetes, heart disease, or lung disease.

By studying these patients' DNA, scientists may pinpoint genetic mutations that make some people more susceptible to infection. Such information could one day help doctors identify people who are most at risk of developing severe coronavirus disease, says Casanova, a pediatrician at Rockefeller. It could also offer clues for scientists searching for new therapeutics. For example, if patients cells arent making enough of a particular molecule, doctors may be able to offer a supplement as treatment.

Were going to try to find the genetic basis of severe coronavirus infection in young people.

Jean-Laurent Casanova, HHMI Investigator at The Rockefeller University

That day may still be years away. This is not a short-term effort, Casanova says. Some scientists have hypothesized that COVID-19 might be a seasonal illness, with infections ebbing in the spring and summer, and then returning in the fall. But Casanovas team is optimistic. They have already begun enrolling patients and have started sequencing their exomes spelling out all of the DNA letters in every gene in a persons genome. Were going to try to find the genetic basis of severe coronavirus infection in young people.

Late last year, when the first coronavirus infections began cropping up in China, Casanova started reaching out to his colleagues there. Though the most severe cases seemed to concentrate among older adults and those with other conditions, Casanova was interested in the outliers kids and young adults hit hard by the illness who didnt have any of the usual risk factors, such as age or underlying illness.

His team kicked off a new project to study these mysterious cases, and in January just weeks after the Wuhan outbreak began enrolling patients. Clinicians mailed patient blood and DNA to his lab, and researchers there and elsewhere began processing samples the first steps needed for scientists to peer into patients genomes. Now, the project is global, and Casanova is collaborating with scientists and healthcare workers from Europe to Africa, Asia, and Oceania.

We will recruit children and adults <50 yo without risk factor admitted to ICU for idiopathic #COVID19. We will test the hypothesis that they carry inborn errors of immunity to this virus. Please refer patients to @casanova_lab and please RT. pic.twitter.com/DXPoFKieEy

Hunting for the genetic underpinnings of severe infectious diseases is nothing new for Casanovas team. What were doing with coronavirus is what my lab has been doing for 25 years with other infections, he says.

They look for weak spots in peoples immune systems small genetic changes that make people more vulnerable to disease. His group has previously searched the genomes of patients infected with viruses, bacteria, fungi, and even parasites. The infection closest to COVID-19 his team has studied is severe influenza pneumonitis, for which theyve discovered three genetic links. Theyve also identified specific genetic errors that can predispose patients with herpes to viral encephalitis. And theyve found that children with mutations in an immunity gene called IFN-gamma are vulnerable to the bacteria that cause tuberculosis. These children make low levels of the IFN-gamma protein, which is critical for fighting off bacterial infections.

Casanovas team has put these findings to use clinically. For example, the researchers have shown that tuberculosis patients with these genetic errors can benefit from treatment with IFN-gamma. Hes hoping to identify problematic genes in patients with severe coronavirus infection that can bring similar clinical gains. These genes could tell scientists which cellular defenses are crucial for warding off COVID-19 and pave the way for understanding whether such defenses are derailed in older adults or patients with an underlying medical condition.

In the US and around the world, severe coronavirus disease seems to hit older patients hardest, though scientists have reported some country-to-country variation. As of March 24, more than 44,000 confirmed and presumptive positive cases have been reported in the US. Fatality has been highest in people over 85 years old, according to a recent report from the Centers for Disease Control and Prevention (CDC). Though young people may be more susceptible than scientists once suspected,the older you are, the higher the likelihood you have a severe form of the disease, Casanova says.

Last week, Rockefeller closed all labs except those working on the coronavirus, and Casanova whittled his team to a skeleton crew of about eight people down from 35 who rotate so there is only one person per room at a time. He and his lab members are following CDC recommendations, and taking protective measures to keep themselves and others safe, including social distancing, washing hands, and disinfecting surfaces. Theyve also taken to Twitter to get the word out about their work. A tweet posted from Casanovas lab last week about recruiting new patients to their study has since been retweeted more than 400 times.

Soon, theyll be testing their genetic theory on a pandemic thats occurring in real time. Im grateful weve been able to start this new project so quickly, he says. God willing, it will be of clinical usein two or three years.

Follow the Casanova lab on Twitter (@casanova_lab) to learn the latest about their work. Doctors interested in enrolling patients in the study can contact Jean-Laurent Casanova at jean-laurent.casanova@rockefeller.edu.

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Patients with Severe Forms of Coronavirus Disease Could Offer Clues to Treatment - Howard Hughes Medical Institute

The coronavirus pandemic has led to a spike in sales of products, includinghand sanitizer, toilet paper and pasta.

More than likely, however, there is no need to buy too much of anything, Dr. Amy Edwards, a pediatric infectious disease specialist at University Hospitals who works with the UH Roe Green Center for Travel Medicine & Global Health,tells Grow. "My advice would be to be vigilant, but calm, and not to panic."

To protect yourself from coronavirus, health professionals say the most important thing to do is wash your hands regularly. Don't forget to clean your phone regularly, too. "I clean my phone at least once a day," says Edwards. She advises others to do the same and many medical experts agree.

"It's often said that your phone is like a third hand because you're constantly touching it," says cleaning influencer Melissa Maker.

People take their phones out to eat, on the train, and to the bathroom. As a result, cellphones carry more than 17,000 bacterial gene copies each, according to a 2017 study. The report concluded that this "may play a role in the spread of infectious agents."

More from Grow:What to buy when your grocery store is out of pasta, beans, juiceHow a hairdresser plans to stretch her $4,000 savings while out of work3 smart ways to improve your finances while you're at home

Cleaning phones daily, at least, is smart, says Edwards."Certainly, if you are letting a lot of people use your phone, you would want to clean it to help prevent spread."

It's often said that your phone is like a third hand because you're constantly touching it.

Melissa Maker

Cleaning Influencer

If you want to clean your phone effectively, Maker says not to use a Lysolwipe or disinfectant wipe, as it may strip the coating of your phone over time. "The chemicals that are used in those disinfectant wipes are not meant to be used on electronics," she says.

Until recently, Apple advised against the use oftraditional cleaning products or compressed air.But earlier this month, Apple updated its instructions to say you can clean your phone with disinfectant wipes, as long as you wipe gently and avoid getting any liquid in charging ports.

GuidelinesforAndroidhandsets still advise steering clear of disinfectant wipes.

One alternative: Cleaning wipes that are specifically made for electronic devices. A 210-pack of individually wrapped lens- and screen-cleaning wipes is $16.99 on Amazon right now.

Maker suggests using a microfiber cloth. "Microfiber has the ability to pick up bacteria," Makers says. "Then you can launder the microfiber cloth."A six-pack of microfiber cleaning clothes is $9.99 on Amazon right now.

A damp microfiber cloth can remove microorganisms including viruses and bacteria and is more effective than a cotton rag, microbiologist Kristen Gibson told the The Wall Street Journal. It won't damage your phone the way a Lysol wipe might, either.

You can also pair onewith a homemade cleaner that is equal parts water and rubbing alcohol. Dip the cloth in the mixture, make sure it's not excessively wet, and then wipe down all parts ofyour phone. This will serve as an effective disinfectant.

And, of course, make sure you frequently wash your hands.

The article Clean Your Phone At Least Once a Day, Says Infectious Disease Specialist originally appeared on Grow by Acorns + CNBC.

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Clean your phone 'at least once a day,' medical experts say. Here's howwithout damaging the screen - CNBC

- Leveraging proprietary technology and manufacturing platform to develop transformativegene therapies for multiple rare diseases with high unmet needs -

- Pipeline led by Phase 3 gene therapy candidate for treatment of recessive dystrophic epidermolysis bullosa (RDEB), with a BLA filing targeted for 2021 -

- Backed by world-class group of biotech operators and investors -

EXTON, Pa., March 25, 2020 (GLOBE NEWSWIRE) -- Castle Creek Biosciences, Inc., a privately held, late-stage gene therapy company, announced that it has received a new investment of $75 million to support the advancement of its clinical development pipeline. Castle Creek Biosciences is a portfolio company of Paragon Biosciences, which led the $55 million equity investment from Fidelity Management & Research Company and Valor Equity Partners, along with a $20 million venture loan from Horizon Technology Finance Corporation (HRZN).

Castle Creek Biosciences is leveraging its proprietary technology platform and commercial-scale manufacturing infrastructure to develop personalized gene therapies for rare diseases with high unmet needs. The company plans to use the funding to advance and expand its gene therapy pipeline, led by the Phase 3 clinical development of FCX-007 (NCT04213261), its gene therapy candidate for the treatment of RDEB. It will also use the funding to expand its current good manufacturing practices (cGMP) infrastructure located in the greater Philadelphia region.

Clinical results from the ongoing Phase 1/2 clinical trial for FCX-007 continue to show positive trends in safety and wound healing in RDEB patients. Current data from this clinical trial were presented at the inaugural World Congress on Epidermolysis Bullosa held in London during January of 2020. FCX-007 was administered to 10 non-healing chronic wounds of which eight achieved complete wound closure 12 weeks post-administration (80%) vs. no wound closure in intra-patient, matched non-treated wounds (0%). FCX-007 continues to be well tolerated up to 52 weeks post administration.

We are proud to have the strategic support of world-class investors whose impact enables our efforts to transform the lives of patients and the future of medicine, said John Maslowski, Chief Executive Officer of Castle Creek Biosciences. We are steadfast in our commitment to the epidermolysis bullosa community and will continue to keep patients, caregivers and clinicians informed on the progress of our current programs, including FCX-007 and diacerein topical ointment, while we expand the scope of our gene therapy platform.

Castle Creek Biosciences is led by a strong executive leadership team with a proven record of developing innovative and potentially life-changing treatments for conditions with the greatest medical need, said Jeffery Aronin, Chairman and Chief Executive Officer of Paragon Biosciences. As investors, we are excited by the progress that the team has made and are committed to growing the Castle Creek Biosciences platform to address multiple rare genetic diseases.

About Castle Creek Biosciences, Inc. Castle Creek Biosciences is a privately held company that develops and commercializes gene therapies for patients with rare and serious genetic diseases. The companys lead gene therapy candidate, FCX-007, is being evaluated for the treatment of recessive dystrophic epidermolysis bullosa (RDEB), the most severe and debilitating form of epidermolysis bullosa (EB). The company is also advancing clinical research evaluating a diacerein topical ointment, CCP-020, for the treatment of epidermolysis bullosa simplex (EBS) and other forms of EB. In addition, Castle Creek Biosciences is developing FCX-013, a gene therapy for the treatment of moderate to severe localized scleroderma. Castle Creek Biosciences is a portfolio company of Paragon Biosciences. For more information, visit castlecreekbio.com or follow Castle Creek on Twitter @CastleCreekBio.

About Paragon BiosciencesParagon is a life science innovator that invests in, builds, and advises bioscience companies. Our mission is to serve patients living with severe medical conditions which do not yet have adequate treatments. Paragons portfolio of independently-run bioscience companies focus on biopharmaceuticals, AI-enabled life science products, and advanced treatments such as cell and gene therapies. We help people live longer, healthier lives. For more information, please visit: ParagonBioSci.com.

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Castle Creek Biosciences Announces $75 Million Investment to Advance Development of Multiple Gene Therapy Candidates for Rare Diseases - Yahoo Finance

Though the number of human genomes sequenced continues to rise rapidly since the completion of the Human Genome Project a scientific endeavor spanning multiple decades and countries aimed at detailing human DNA in 2003, less than 10 percent of those genomes to date correspond to individuals of Asian descent. The GenomeAsia 100K Project, a non-profit consortium, seeks to change this lack of knowledge surrounding a major portion of the worlds ethnicities. The conglomeration of researchers and private sector executives from around the world from Seoul, South Korea to the University plans to add 100,000 novel genomes from individuals of Asian ethnicity to new open-access databases.

Academic institutions and private sector companies came together in 2016 to launch the GenomeAsia 100K Project. While the research organization MedGenome and Nanyang Technological University in Singapore originally founded the non-profit consortium, representatives from other businesses and schools including Genentech, Macrogen and the University of California, San Francisco have joined the association.

Since genome sequencing can reveal the unique characteristics of each persons genetic material, it can help determine a persons ancestry and the propensity for certain medical conditions. According to GenomeAsia 100K, Asians constitute nearly half of the worlds population, and the distinct ethnicities and communities offer a relatively untapped repository of genetic diversity. The project hopes to provide new insights into inherited diseases as well as those caused by a combination of genetic and environmental factors.

Aakrosh Ratan, assistant professor of public health sciences and researcher for GenomeAsia 100K, explained that in particular, the information the initiative collects may help develop medical treatments based on peoples specific genetic makeup, instead of relying on traditional general treatments that may not target the unique root cause of each patients form of a disease.

The goal of precision medicine is to tailor treatment towards a persons genetic background, and that dream cannot be realized until you have the proper reference databases, Ratan said.

Mutations in humans DNA sequences lead to different copies of the same gene within a person and amongst ethnicities. These different versions of a gene can act as markers of diseases that are inherited or influenced by genetic makeup. For example, the disorder sickle cell anemia is caused by the change of a single point in the DNA sequence. When someone is born with copies of this particular gene from both parents contain the mutation, he or she will suffer from often debilitating pain resulting from red blood cells that cannot effectively transport oxygen.

Ratan explained that genome sequencing can highlight mutations in a persons DNA that may cause illnesses such as sickle cell anemia.

One of the ways we identify the mutations that drive a rare disease is by identifying the mutations and then prioritizing those mutations based on their prevalence in healthy populations, Ratan said. With the medical datasets we have compiled, we can actually improve such analyses for patients of Asian descent.

As of December 2019, the GenomeAsia 100K Project has completed the analysis of 1,739 genomes from 219 populations and 64 countries worldwide. Preliminary findings appeared that same month in the scientific journal Nature. The paper concluded that the sample provided a reasonable framework for sequencing practices and studying the history and health of Asian populations. Ratan and his lab at the University supervised the identification and contributed to the analysis of these genetic variants.

Once the 100,000 genomes have been collected and sequenced, the data will be publicly available as a controlled dataset. As a result, experts investigating topics from heart disease to human evolution can easily access the genome sequences.

One of the real gaps in human genetics studies of disease has been the underrepresentation of non-Europeans, Charles Farber, associate professor of public health sciences, said in an email to The Cavalier Daily. The work of the GenomeAsia 100K Consortium provided critical insight into the extent and nature of genome variation in individuals of Asian ancestry and will be critical in making disease genetic studies more inclusive of all global populations.

Ani Manichaikul, assistant professor of public health sciences in the Center for Public Health Genomics, expressed enthusiasm for the GenomeAsia 100K Project. She claimed that the additional genetic information could augment her research as part of the Multi-Ethnic Study of Atherosclerosis, a cardiovascular disease where fatty deposits accumulate and potentially block arteries. The study currently focuses on Caucasian, African American, Hispanic and Chinese American individuals.

The GenomeAsia project is very useful because there are some instances where particular genetic variants are only observed in particular genetic groups, Manichaikul said. Those markers can be unique to those sequenced through the project, which means we would not have necessarily have observed those particular variants otherwise.

Manichaikul also suggested that expanding existing repositories of hereditary statistics would improve methods of assigning people risk scores for diseases based on their DNA. The National Human Genome Research Institute describes polygenic risk score, which indicates a persons likelihood of certain diseases based on the presence of mutations known to be associated with a given disorder. Companies such as 23andMe have started to provide consumers with this metric, but without a comprehensive database of genomes from different populations, score reliability can decrease.

Since indicators of genetically-linked conditions often appear in certain alleles, or different versions of a gene, knowing whether one has a disease marker can help patients take preventative measures if need be. However, in the absence of comprehensive information on the range of disease markers that appear in different ethnicities, whole populations may lack the potential benefits of this burgeoning healthcare statistic.

The only way we can create risk prediction models that are accurate across populations is if we also have corresponding databases available with individuals that represent that diversity, Manichaikul said.

Following the findings in the preliminary study, GenomeAsia 100K Project collaborators will continue to sequence more genomes of Asian individuals. The hope is that, once researchers have access to the data, insights from 100,000 genomes will drive the development of new therapeutic strategies that will benefit people around the world.

I would like more researchers to have access to this data, Ratan said. This is a resource. Were working to establish these reference datasets, and we would definitely like them to be used.

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Bridging the gap study sequences Asian genomes to diversify genetic databases - University of Virginia The Cavalier Daily

Working at a breakneck pace, a team of hundreds of scientists has identified 50 drugs that may be effective treatments for people infected with the coronavirus.

Many scientists are seeking drugs that attack the virus itself. But the Quantitative Biosciences Institute Coronavirus Research Group, based at the University of California, San Francisco, is testing an unusual new approach.

The researchers are looking for drugs that shield proteins in our own cells that the coronavirus depends on to thrive and reproduce.

Many of the candidate drugs are already approved to treat diseases, such as cancer, that would seem to have nothing to do with Covid-19, the illness caused by the coronavirus.

Scientists at Mount Sinai Hospital in New York and at the Pasteur Institute in Paris have already begun to test the drugs against the coronavirus growing in their labs. The far-flung research group is preparing to release its findings at the end of the week.

There is no antiviral drug proven to be effective against the virus. When people get infected, the best that doctors can offer is supportive care the patient is getting enough oxygen, managing fever and using a ventilator to push air into the lungs, if needed to give the immune system time to fight the infection.

If the research effort succeeds, it will be a significant scientific achievement: an antiviral identified in just months to treat a virus that no one knew existed until January.

Im really impressed at the speed and the scale at which theyre moving, said John Young, the global head of infectious diseases at Roche Pharma Research and Early Development, which is collaborating on some of the work.

We think this approach has real potential, he said.

Some researchers at the Q.B.I. began studying the coronavirus in January. But last month, the threat became more imminent: A woman in California was found to be infected although she had not recently traveled outside the country.

That finding suggested that the virus was already circulating in the community.

I got to the lab and said weve got to drop everything else, recalled Nevan Krogan, director of the Quantitative Biosciences Institute. Everybody has got to work around the clock on this.

Dr. Krogan and his colleagues set about finding proteins in our cells that the coronavirus uses to grow. Normally, such a project might take two years. But the working group, which includes 22 laboratories, completed it in a few weeks.

You have 30 scientists on a Zoom call its the most exhausting, amazing thing, Dr. Krogan said, referring to a teleconferencing service.

Viruses reproduce by injecting their genes inside a human cell. The cells own gene-reading machinery then manufactures viral proteins, which latch onto cellular proteins to create new viruses. They eventually escape the cell and infect others.

In 2011, Dr. Krogan and his colleagues developed a way to find all the human proteins that viruses use to manipulate our cells a map, as Dr. Krogan calls it. They created their first map for H.I.V.

That virus has 18 genes, each of which encodes a protein. The scientists eventually found that H.I.V. interacts, in one way or another, with 435 proteins in a human cell.

Dr. Krogan and his colleagues went on to make similar maps for viruses such as Ebola and dengue. Each pathogen hijacks its host cell by manipulating a different combination of proteins. Once scientists have a map, they can use it to search for new treatments.

In February, the research group synthesized genes from the coronavirus and injected them into cells. They uncovered over 400 human proteins that the virus seems to rely on.

The flulike symptoms observed in infected people are the result of the coronavirus attacking cells in the respiratory tract. The new map shows that the viruss proteins travel throughout the human cell, engaging even with proteins that do not seem to have anything to do with making new viruses.

One of the viral proteins, for example, latches onto BRD2, a human protein that tends to our DNA, switching genes on and off. Experts on proteins are now using the map to figure out why the coronavirus needs these molecules.

Kevan Shokat, a chemist at U.C.S.F., is poring through 20,000 drugs approved by the Food and Drug Administration for signs that they may interact with the proteins on the map created by Dr. Krogans lab.

Dr. Shokat and his colleagues have found 50 promising candidates. The protein BRD2, for example, can be targeted by a drug called JQ1. Researchers originally discovered JQ1 as a potential treatment for several types of cancer.

On Thursday, Dr. Shokat and his colleagues filled a box with the first 10 drugs on the list and shipped them overnight to New York to be tested against the living coronavirus.

The drugs arrived at the lab of Adolfo Garcia-Sastre, director of the Global Health and Emerging Pathogens Institute at the Icahn School of Medicine at Mount Sinai Hospital. Dr. Garcia-Sastre recently began growing the coronavirus in monkey cells.

Over the weekend, the team at the institute began treating infected cells with the drugs to see if any stop the viruses. We have started experiments, but it will take us a week to get the first data here, Dr. Garcia-Sastre said on Tuesday.

The researchers in San Francisco also sent the batch of drugs to the Pasteur Institute in Paris, where investigators also have begun testing them against coronaviruses.

If promising drugs are found, investigators plan to try them in an animal infected with the coronavirus perhaps ferrets, because theyre known to get SARS, an illness closely related to Covid-19.

Even if some of these drugs are effective treatments, scientists will still need to make sure they are safe for treating Covid-19. It may turn out, for example, that the dose needed to clear the virus from the body might also lead to dangerous side effects.

This collaboration is far from the only effort to find an antiviral drug effective against the coronavirus. One of the most closely watched efforts involves an antiviral called remdesivir.

In past studies on animals, remdesivir blocked a number of viruses. The drug works by preventing viruses from building new genes.

In February, a team of researchers found that remdesivir could eliminate the coronavirus from infected cells. Since then, five clinical trials have begun to see if the drug will be safe and effective against Covid-19 in people.

Other researchers have taken startling new approaches. On Saturday, Stanford University researchers reported using the gene-editing technology Crispr to destroy coronavirus genes in infected cells.

As the Bay Area went into lockdown on Monday, Dr. Krogan and his colleagues were finishing their map. They are now preparing a report to post online by the end of the week, while also submitting it to a journal for publication.

Their paper will include a list of drugs that the researchers consider prime candidates to treat people ill with the coronavirus.

Whoever is capable of trying them, please try them, Dr. Krogan said.

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Coronavirus Treatment: Hundreds of Scientists Scramble to Find One - The New York Times

AstraZeneca has announced a collaboration with UK biotech Silence Therapeutics to develop gene silencing drugs for cardiovascular, renal, metabolic and respiratory diseases.

The deal could see AZ adding small interfering RNA (siRNA) technology to its pipeline in one of its main areas of research.

Silence Therapeutics says its technology can selectively inhibit any gene in the genome, specifically silencing the production of disease-causing proteins.

The UK biotech says it has achieved an additional level of accuracy by delivering its therapeutic RNA molecules exclusively to target cells.

siRNA is a technology that showed much promise after biologists Andrew Fire and Craig Mello received the Nobel Prize in Physiology or Medicine for discovering the technology in 2006.

But in 2010 it became apparent that it was harder to convert into a working therapy because of the challenge of delivering therapeutic RNA molecules to target tissues and big pharma quickly lost interest.

But companies like Silence have managed to overcome this hurdle and its rival Alnylam made history in 2018 when its siRNA drug Onpattro was approved by the FDA to treat hereditary transthyretin (hATTR) amyloidosis, which causes the build-up of amyloid protein in nerves and organs.

AZ will pay $60 million up front and invest $20 million in Silence, and will pay up to $400 million in milestone payments plus tiered royalties.

The companies expect to work on five targets within the first three years of the collaboration, and AstraZeneca has the option to extend it to a further five targets.

Silence has technology that can inhibit liver-expressed gene targets and the companies will collaborate to find siRNA molecules to other tissues including the heart, kidney and lung.

The UK biotech will design SiRNA molecules against gene targets selected by AZ, and will manufacture material to support toxicology and phase 1 clinical studies.

AZ and Silence will collaborate during the discovery phase, while AZ will lead clinical trials and marketing.

Silence will have the option to negotiate for co-development of two drugs of their choice starting from phase 2.

AZ will pay an option fee of $10 million for each selected target when a drug candidate is nominated, and Silence could receive up to $140 million in development milestones, and up to $250 million in market milestones.

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AZ adds gene silencing tech to pipeline with Silence Therapeutics deal - - pharmaphorum

TAMPA, Fla. & DUBLIN--(BUSINESS WIRE)-- Vycellix, Inc., an immuno-discovery cell & gene therapy company, and Avectas Limited, a cell engineering technology business, today jointly announced that the companies have entered into a collaboration agreement to develop proprietary approaches for cell-based immunotherapeutic products.

The companies will collaborate on the delivery of Vycellix's novel RNA immunomodulator VY-M using Avectas' cell engineering platform, Solupore. The collaboration will address current limitations for cell-based therapies, in particular with respect to the need to accelerate the manufacturing process, reduce the cost of manufacture, and ultimately improve patient outcomes.

"We are delighted to partner with Vycellix and join forces in the development of novel cell-based products," stated Michael Maguire, Ph.D., CEO of Avectas. "We believe Solupore will play a critical role in the manufacture of cell-based therapies and will support a path towards effective patient outcomes."

According to Vycellixs President, Douglas Calder, Solupore represents a new paradigm for delivery of transgenes, and our initial studies will evaluate Solupore to deliver our product candidate, VY-M, to T cells and natural killer (NK) cells. We expect to accelerate the expansion-time of T cells and NK cells by decreasing the non-dividing lag time, resulting in much shorter vein-to-vein delivery-time to patients. The studies will be conducted at Avectas Dublin-based facility and at Karolinska Institutet, Stockholm, Sweden.

Both Vycellix and Avectas are collaborative partners within NextGenNK, a newly established competence center for development of next-generation NK cell-based cancer immunotherapies based at Karolinska Institutet, Stockholm, Sweden. It is envisioned that Vycellix and Avectas will further expand their collaboration within the NextGenNK constellation.

We are excited to see the NextGenNK Competence Center catalyzing interactions among its industrial partners to advance NK cell-based immunotherapies, said Hans-Gustaf Ljunggren, M.D., Ph.D., Director of the NextGenNK Competence Center. The present collaboration may pave the way for similar collaborations among NextGenNK partners.

About Vycellix, Inc.: Vycellix is a private, immuno-discovery, life science company at the forefront of innovation in the development of cell & gene-based therapies targeting indications in, but not limited to, hematology/oncology, autoimmunity/chronic inflammatory diseases, and organ/tissue transplantation.

The Companys portfolio of transformational platform technologies encompass novel tools urgently sought after to enable broad global adoption of advanced therapies including: 1) the ability to generate Universal Cells (VY-UC), without the need to alter expression of any of the cellular components that control self-recognition (HLA Class I or II), obviating the need for immune-suppressive drugs and redefining the path towards off-the-shelf therapies; 2) the ability to amplify cell-potency through the upregulation of internal cytotoxic mechanisms (VY-X); 3) the ability to accelerate the expansion of cells for immunotherapy by near-elimination of non-dividing lag time to leap forward to shorter vein-to-vein time with expanded cells (VY-M); and, 4) the ability to markedly enhance gene transduction levels using viral vectors with implications for autologous and allogeneic CAR-T and CAR-NK cell development (VY-OZ).

The Companys platforms were all discovered by scientists at the world-renowned Karolinska Institutet (KI) in Stockholm, Sweden. KI is globally recognized for its Nobel Assembly, which awards the Nobel Prize in Physiology or Medicine. For more information, please visit the Companys website at: http://www.Vycellix.com and follow its Twitter feed at: @Vycellix.

About Avectas Limited: Avectas is a cell engineering technology business developing a unique delivery platform to enable the ex-vivo manufacture of our partners' gene-modified cell therapy products, which will retain high in-vivo functionality. Our vision is to be a leading non-viral cell engineering technology provider, integrated into manufacturing processes for multiple autologous and allogeneic therapies, commercialized through development and license agreements. For more information, please visit the Company's website at http://www.avectas.com.

Forward Looking Statements: This press release contains forward-looking statements. All statements other than statements of historical facts are forward-looking statements, including those relating to future events. In some cases, forward-looking statements can be identified by terminology such as plan, expect, anticipate, may, might, will, should, project, believe, estimate, predict, potential, intend, or continue and other words or terms of similar meaning. These statements include, without limitation, statements related to the pre-clinical, regulatory, clinical and/or commercial development and all anticipated uses of VY-OZ, VY-X, VY-M and VY-UC, and the Companys plans for seeking out-licensing opportunities for these assets. These forward-looking statements are based on current plans, objectives, estimates, expectations and intentions, and inherently involve significant risks and uncertainties. Actual results and the timing of events could differ materially from those anticipated in such forward-looking statements as a result of these risks and uncertainties, which include, without limitation, risks and uncertainties associated with immuno-discovery product development, including risks associated with advancing products to human clinical trials and/or ultimately regulatory and commercial success which is subject to the uncertainty of regulatory approval, market adoption and other risks and uncertainties affecting Vycellix and its development programs. Other risks and uncertainties of which Vycellix is not currently aware may also affect Vycellixs forward-looking statements and may cause actual results and the timing of events to differ materially from those anticipated. The forward-looking statements herein are made only as of the date hereof. Vycellix undertakes no obligation to update or supplement any forward-looking statements to reflect actual results, new information, future events, changes in its expectations or other circumstances that exist after the date as of which the forward-looking statements were made.

View source version on businesswire.com: https://www.businesswire.com/news/home/20200325005026/en/

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Vycellix and Avectas Announce Collaboration to Advance Next-Generation Solutions for the Optimized Manufacture of Cell & Gene Therapies - BioSpace