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Peptide Pain Drugs in Development Aimed at Alternative Targets

Neuron

(National Institute of General Medical Sciences, NIH)

15 August 2018. Pain drugs made from peptides, small protein-like compounds, and guided by antibodies are being developed as alternatives to prescription opioids to treat moderate to severe pain. Peptide Logic, a biotechnology company in San Diego, is receiving a 2-year $2.9 million Small Business Innovation Research award from National Institute on Drug Abuse, part of National Institutes of Health, to advance its lead pain therapy candidate to the the start of clinical trials.

Peptide Logic develops synthetic peptides, short chains of amino acids similar to proteins. The company’s peptides are designed to regulate G-protein-coupled receptors, a ubiquitous protein on cell surfaces and a target for up to half of today’s drugs. In this case, G-protein-coupled receptors act as gateways for kappa opioid receptors, or KORs, proteins found on the surface of nerve cells, which in their activated state can stop pain signals.

Today’s prescription opioid drugs target mu-opioid receptors to reduce the intensity of pain signals to the brain, particularly regions of the brain controlling emotion, which reduces effects of the pain stimulus. Abuse of prescription opioid drugs, as well as heroin and fentanyl sold on the street, has become a serious national public health emergency, with overdose deaths from these drugs in 2018 numbering more than 115 per day, according to National Institute on Drug Abuse. A report by the National Academies of Sciences, Engineering, and Medicine in July 2017 spells out the full scope of the crisis beyond overdose deaths, with some 2 million Americans age 12 and older addicted to prescription opioid drugs and another 600,000 addicted to heroin.

A key drawback of KORs, however, is that they too are found on brain cells. Peptide Logic’s solution takes an existing pain drug targeting KORs only in peripheral nerve cells, those outside of the brain and spinal cord, to relieve pain without affecting brain cells. This current drug, code-named CR845 by Cara Therapeutics, is being tested to treat several types of pain and severe itching. But it currently has a short active lifetime, according to Peptide Logic, requiring multiple intravenous doses a day. Peptide Logic proposes combining the KOR stimulators in CR845 with a Peptide Logic synthetic antibody acting as a persistent carrier to provide long-acting pain relief.

In an earlier preliminary study, Peptide Logic found a long-acting pain drug targeting KORs to be feasible. In the new project, the company plans to advance its technology to produce a treatment for moderate to severe pain that can be given once a week as an injection under the skin, instead of the multiple infusions needed today. Peptide Logic also expects to specify and validate a range of pain types the treatments can address, and test the treatment candidates in both female and male animals in preparation for an investigational new drug application to the Food and Drug Administration. That application is, in effect, a request to begin clinical trials.

The award for the project was made under NIH’s Small Business Innovation Research program that sets aside funding for small, early-stage businesses in the health care and life science fields. In the current (2018) fiscal year, NIH expects to channel more than $1 billion into its small business set-aside programs.

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Low-Dose Triple Pill Reduces Blood Pressure in More People

3 generic capsules

(The George Institute)

15 August 2018. A clinical trial shows a single medication with low doses of three common drugs reduces high blood pressure in more people with the condition than the normal care. Results of the trial, led by a team at the George Institute for Global Health in Newtown, Australia appear in yesterday’s issue of JAMA (paid subscription required), published by American Medical Association.

Investigators at the George Institute and colleagues in Sri Lanka led by medical researcher Ruth Webster are seeking easier ways for people with high blood pressure to control their condition. World Health Organization says high blood pressure is a global public health crisis, responsible for increases in heart disease, stroke and kidney failure and premature death and disability. WHO estimates 9.4 million people die each year from high blood pressure, and contribute to half (51%) of deaths due to stroke and nearly half (45%) of deaths from heart disease.

While the condition is treatable and manageable, treatment strategies for high blood pressure often impose burdens on patients. Webster explains in an institute statement that, “Patients are brought back at frequent intervals to see if they are meeting their targets with multiple visits required to tailor their treatments and dosage. This is not only time inefficient, it’s costly. We also know that many doctors and patients find it too complicated and often don’t stick to the process.”

The George Institute proposed a simpler treatment they call the Triple Pill. This pill, taken once a day, contains half-doses of three leading blood pressure medications: telmisartan, amlodipine, and chlorthalidone. Telmisartan works by blocking certain proteins that tighten blood vessels allowing for easier blood flow. Amlodipine, known as a calcium channel blocker, relaxes blood vessels reducing strain on the heart. Chlorthalidone helps the kidneys reduce excess water and salt in the blood that contribute to high blood pressure.

The clinical trial tested the Triple Pill among 700 individuals in Sri Lanka with high blood pressure, defined as systolic/diastolic readings of 140/90 or higher. Participants averaged 56 years in age, 58 percent were women, and 29 percent also had diabetes. At the start of the study, the blood pressure of participants was 154/90. Individuals in the study were randomly assigned to receive the Triple Pill or follow their usual treatments for 6 months. Nearly all (96%) of participants completed the study.

The study looked primarily at changes in systolic/diastolic blood pressure readings, particularly the number of participants able to lower their scores below the target of 140/90, or 130/80 if the individual also had diabetes or chronic kidney disease. The results show 7 in 10 (70%) of Triple Pill recipients achieved this goal, compared to just over half (55%) of those receiving the usual care, a large enough difference to be statistically reliable.

About equal percentages of Triple Pill recipients (38%) experienced adverse effects such as muscle pain, dizziness, and fainting, as those receiving the usual care (35%). And about 7 percent of each group had to leave the study because of adverse events.

The George Institute plans to amplify the trial’s results among medical and public health communities, particularly governments and insurance companies, to promote the Triple Pill as a low-cost and effective alternative for controlling high blood pressure.

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Maintaining a Productive Workforce

– Contributed content –

Group handshake

(Pexels.com)

15 August 2018. Your employees keep your business up and running. So, it’s important that you ensure that they are as productive as possible at all times. This is easier said than done. But there are a few different ways that you can boost their output. Here are a few to consider.

Measuring productivity

If you want your employees to work consistently and to a high standard, you should actively observe them. Various studies have shown that people are more likely to do what they’re meant to be doing if they are aware that an authority figure is monitoring them. Now, this doesn’t mean that you should quite literally be watching over your employees’ shoulders at any given moment. This is actually more likely to interrupt their workflow and throw them off track, as they’ll be focussing more attention on you watching them than they will be putting into their work. But what it does mean is that you should consider tracking and charting each individual’s progress in their role?

You can do this quantitatively by working out the number of leads that they have generated, sales they have made, or contracts that they have secured. This will give both you and your employee a good overview of how their work is progressing and whether they are keeping up with the average that is expected of them. Remember to try to only use the results that you find in a positive manner. Bear in mind that there could be various professional or personal factors beyond their control that affect their progress. For example, they may be suffering from illness or other personal problems, or there might be a delay in raw materials being delivered, or the internet and phone lines may have gone down.

Rewarding achievements

If you find that a particular employee has gone above and beyond what is generally expected in their role, you should reward them. Not only will this ensure that their hard work is recognised (making them feel appreciated and valued), but it will give your other employees a push to do the same. This will result in higher levels of productivity all-round, as your whole workforce will strive to match outstanding member of staff’s achievements. There are all sorts of rewards that you can offer, but make sure that they are consistent. One member of staff shouldn’t receive more than another being rewarded. Consider options like crystal vases, certificates, or plaques.

Ensure everyone has sufficient breaks

Many employers want to get the most for their money and are thus reducing the amount or length of breaks that their employees take throughout the working day. But this isn’t necessarily the best move. Workers need a rest to be boost their energy levels. If someone is working non-stop all day, their productivity will slowly drop as time goes on. So, ensure everyone has a sufficiently long lunch break and a couple of coffee breaks throughout their shift.

These are just a few different ways to maintain a productive workforce. Incorporate the above steps into your business regimen. You really will profit from them.

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Multi-Function Stretchable Sensor Platform Developed

Stretchable 3-D electronic sensor bandage

Stretchable 3-D electronic sensor bandage and U.S. dollar coin (Zhenlong Huang, University of California in San Diego)

14 August 2018. An engineering team created a system that combines multiple electronic sensors into a single 3-D stretchable device that can be worn on various body locations to monitor different functions. Researchers at University of California in San Diego describe their technology in yesterday’s issue of the journal Nature Electronics (paid subscription required).

The team from UC-San Diego’s research group led by electrical and computer engineering professor Sheng Xu is seeking ways to add more functions to stretchable and wearable electronics for monitoring a person’s health, while keeping down the amount of real estate these devices occupy. The lab’s approach is to go three-dimensional, stacking layers of electronic sensors on stretchable surfaces. While that concept may be easy to understand and feasible for rigid materials, making the idea work with fabrics and stretchable polymers was anything but simple.

“The problem isn’t stacking the layers,” says Xu in a university statement. “It’s creating electrical connections between them so they can communicate with each other,” Xu and colleagues address that issue by connecting the layers of circuits with lasers. In rigid materials, holes can be drilled allowing for conductive materials to link various layers, but that approach won’t work with stretchable materials or fabrics. The team instead uses black organic dyes that absorb and conduct energy from laser beams, thus allowing for electronic connections between layers of materials that bend and stretch. As long as the conductive regions of each layer overlap while stretched, electronic signals can be sent and received between layers.

For a proof-of-concept, the researchers created a system with 4 layers of circuits configured into a rubber-like stretchable polymer plastic. The individual circuits perform designated electronic functions, such as sensor, accelerometer, amplifier, and Bluetooth transmission. While each circuit is printed on rigid materials, they’re small enough to allow for the plastic layers encasing the chips to bend. And the individual layers are physically connected with tiny copper springs that enable the entire device to stretch and bend. The area of the device itself is about the same as a U.S. dollar coin that has a diameter of 26.5 millimeters, slightly more than 1 inch, and about the same 2 millimeter thickness.

The San Diego team demonstrated their system as a device with multiple functions. Worn on the chest, the system can measure heart rate like an electrocardiogram, while on the forehead it can detect brain signals like an electroencephalogram or EEG, and on the forearm, the device measures muscle activity. In addition, the prototype device can also measure respiration, skin temperature, and body motion. The system’s Bluetooth communications allow for transmitting signals up to 10 meters away. As the video below demonstrates, the communications and body motion functions make it possible for the device to control a remote robotic arm.

The device uses about 35.6 milliwatts of power, but Xu’s group is also working on stretchable lithium-ion batteries. The university says the lab is collaborating with industry partners to advance the technology to the point of clinical tests.

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Profitability In Business Is About Planning And Organization

– Contributed content –

Meeting at window

(Christina Morillo, Pexels.com)

14 August 2018. While the title of this article might seem rather obvious and evident to any entrepreneur, it’s surprising to see so many businesses fail because they lack a proper plan or structure. It’s not enough to have a great idea or even a great workforce. If you want your company to be profitable then you need a structured overview of its many different aspects. You need to plan and organize every little detail. There are so many opportunities to slash costs and increase profits that many companies don’t utilize. In this post, we’re going to talk about some improvements you could make to your company’s business model.

Create an efficient workplace.

Efficiency in the workplace is vital to profitability. Take a look at your workforce. Are they as productive as they could be? If you can give your workers a reason to put in additional effort then you’ll be improving customer service and increasing work output without having to hire any new members of staff. Rewarding an “Employee Of The Week” with a bonus or other perks is a great way to encourage people to work harder.

Of course, you need to focus on warehouse efficiency as well as office efficiency. There’s a lot you could do to improve operations there. You might even want to check out a company such as Tonbridge Fuels for red diesel to fuel your machinery and heavy equipment. It’s cheaper than white diesel because there’s no tax. Increasing profitability in business is about taking a good look at your operations and finding ways to do the same thing more efficiently (both in terms of time and money).

Reduce unnecessary overhead costs.

The word “unnecessary” is important here. So many businesses try to slash costs and boost profit margins by getting rid of essential things (e.g. members of staff or certain products), but there are plenty of unnecessary costs that they miss. For starters, you might want to take an environmental approach to running your business. You could insulate your office to reduce your energy bills, for example. You could even encourage employees to work from home to reduce the need for traveling to the office; you’ll be saving the planet and reducing the need to cover the expenses that come with having so many people in the office. By reducing unnecessary overhead costs, you’ll have bigger profit margins. It’s as simple as that.

Do you have a plan of action when it comes to your existing client base? If not then it’s time to get yourself organized. Your existing customers hold the potential to increase your business’ profits. Word-of-mouth marketing is the best press a business can get. People are much more likely to trust the word of their friends or family than a company that’s clearly trying to promote itself. If you can get customers to refer others to your business then you’ll gain a steadily growing client base. Maybe you could encourage clients to tell their friends about you by starting a referral scheme. You could give them a discount or a voucher if they get their friend to buy your products or services.

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FDA Clears Fertility Awareness App for Birth Control

Natural Cycles app and device

Natural Cycles app and temperature device (Natural Cycles AB)

13 August 2018. A mobile app for determining a woman’s fertility state on any given day was cleared for marketing in the U.S. as a birth control method. The Natural Cycles app, made by NaturalCycles AB in Stockholm, Sweden, received marketing authorization from the Food and Drug Administration on Friday, which the agency says is the first mobile app it permits to prevent pregnancies.

Natural Cycles calculates a woman’s daily fertility with an algorithm based on her body temperature and menstrual cycles. The app asks the woman to measure her basal body temperature — a more sensitive temperature measurement than regular thermometers — upon waking in the morning, where a rise in temperature of about 0.5 degrees F indicates ovulation occurred and the hormone progesterone is released. After taking these measurements for a few menstrual cycles, the app’s algorithm becomes familiar enough with the woman’s cycles to calculate days when fertility is at its peak.

These most fertile days are called “red days,” referring to the color of message on the app, when protection against pregnancy, such as condoms, are recommended. Infertile days are known as “green days,” when protection may not be required. Natural Cycles recommends a separate luteinizing hormone test for ovulation that measures the woman’s urine for this hormone that increases 1 to 1.5 days before ovulation. The company says adding a luteinizing hormone test increases the number of green days by 5 percent and helps the algorithm better predict red days for planning a pregnancy.

FDA based its authorization of Natural Cycles in part on a clinical trial of 15,570 women who tested the app for an average of 8 months over a 2-year period, out of nearly 23,000 enrolled. The app’s effectiveness for predicting fertile and infertile days was based on the Pearl Index, a standard method of measuring contraception techniques that calculates device or method failures per 100 woman using the technique for 1 year. When the app is used and pregnancies occur for any reason, including errors by the app or the users — such as having unprotected sex on a red or fertile day — the app’s failure rate is 6.5 percent. When participants use the app as directed and pregnancies occur due to an error in the app to predict an infertile day, or contraception failed on a correctly-indicated fertile day by the app, the failure rate is 1.8 percent.

FDA cleared natural Cycles for pre-menopausal women age 18 and older. The app is not recommended for women who are currently using birth control or hormonal treatments that limit ovulation, or who have a condition where pregnancy would risk her health that of the fetus. The company notes that the app does not protect against sexually transmitted diseases.

The Natural Cycles company was founded by two physicists, Elina Berglund and Raoul Scherwitzl, while working at CERN in Switzerland, but then relocated to Stockholm. FDA authorized Natural Cycles under its de novo premarket review pathway for new types of low- to moderate-risk medical devices. In addition to FDA clearance, the app previously received a CE mark which permits marketing in Europe.

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Start-Up to Tackle Neurodegenerative Diseases, Raises $31 Million

Magnolia Neurosciences

(Magnolia Neurosciences Corp.)

13 August 2018. A new company is forming to develop treatments that protect against destruction of brain cells in Alzheimer’s disease and comparable nerve damage from chemotherapy. Magnolia Neurosciences Corp. in New York, a spin-off enterprise from the Neurodegeneration Consortium and M.D. Anderson Cancer Center, is raising $31 million in its first venture funding round, backed by several venture investment and pharmaceutical companies.

Magnolia Neurosciences is taking on the combination of neurodegenerative diseases, such as Alzheimer’s, and peripheral nerve damage, which the company says affects some 20 million people in the U.S. The company is commercializing research by the Neurodegeneration Consortium, based in Houston, on programmed cell death, a natural and controlled process to eliminate excess nerve cells, or neurons, during embryonic development that becomes reactivated in the brain during Alzheimer’s disease. The group studies aspects of programmed cell death promoting degeneration of neurons in the brain, and discovered drug candidates that in tests with animals show promise in protecting against this damage.

“There is a critical need to develop medicines that slow or stop neuronal loss in these patients, and a growing body of data suggests that inhibition of these specific pathways has the potential to preserve neuron viability across a variety of disease states and pathological conditions,” says Jim Ray, director of the Neurodegeneration Consortium in a Magnolia statement. Neurodegeneration Consortium is a joint undertaking of researchers from M.D. Anderson Cancer Center, Baylor College of Medicine, Mount Sinai medical school in New York, and MIT.

Another target of Magnolia Neurosciences is peripheral nerve damage from chemotherapy, which according to M.D. Anderson affects as many as two-thirds of the 700,000 people in the U.S. receiving chemotherapy. Symptoms include pain, burning, loss of sensation, and balance problems. But more than 200,000 people also encounter general cognitive and memory problems, called “chemobrain,” that can last for years.

Magnolia Neurosciences is expected to develop discoveries from M.D. Anderson’s Institute for Applied Cancer Science addressing chemotherapy-induced peripheral nerve damage. In addition to preventing these adverse effects, new treatments for this condition would help cancer patients adhere to their chemotherapy, avoid dose reductions, and improve their chances for survival. M.D. Anderson, part of the University of Texas System, is also based in Houston.

Magnolia Neurosciences is being formed by venture investor Accelerator Life Science Partners in New York, that also led the company’s first venture financing round, raising $31 million. Other venture investors taking part include Alexandria Venture Investments, ARCH Venture Partners, Innovate NY Fund, Partnership Fund for New York City, Watson Fund, L.P., and 180 Degree Capital Corp. Several corporate venture funds are backing Magnolia, mainly from pharmaceutical companies: AbbVie Ventures, Eli Lilly and Company, Johnson & Johnson Innovation, Pfizer Ventures, and WuXi AppTec’s Corporate Venture Fund. Thong Q. Le, CEO of Accelerated Life Science Partners, is also the interim CEO of Magnolia.

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Disclosure: The author owns shares in Johnson & Johnson and Pfizer.

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Why Your Business Needs a Good Database

– Contributed content –

Glasses, computer screens

(Kevin Ku, Pexels.com)

13 August 2018. If you operate a business then you will know more than anyone how important it is for you to have a good IT system. If you don’t have a quality IT system however then you could be missing out, and here’s why:

Centralized system

If you have a business that is constantly growing and you have a team of staff who are going to help you to run it then it’s so important that you are able to keep track of the amount of data that you have. If you have a good database system however then this can help you to manage all of your business needs and even any central data you have as well. This will help your business to stay way more secure and it will also greatly increase your chances of success for the future.

Human resources

When you are able to use a HR database, you can then manage your growing staff records. This can save you a ton of time and money and it will also help you to streamline any HR tasks that you have. When you are able to do this, you can then automate any routine jobs and you can also speed up the processing data as well. This includes your benefits, your payroll, your staff hours and more. This will really help you to make sure that you are doing the best you can with the resources you have, and it will also mean that your business runs at a much higher level of efficiency as a result. If you work in the governmental sector, you may also want to look into federal IT services.

Managing customer data

If you know that your customers are the lifeblood of your business then it’s so important that you have a good relationship with them. For this reason, you do need to make sure that you have some kind of CRM plan. When you have a CRM database you can then power everything and you can also process the data that you have. This includes their interaction history, the purchases that they have made in the past and even their accounts. You can also invest in new lucrative business opportunities by using this data and this will really help you out in the future.

Inventory tracking

If you do not manage your inventory very well then you may feel as though the whole thing is like a balancing act. You may never know what is on your shelves and you may also miscount on a regular basis. You may even find that you have trouble with your spreadsheets as well. This is the last thing that you need but a good database can really help you to avoid all of this with ease. You can minimize any sales that could be potentially lost while also unlocking the true potential of your business.

So as you can see, there are so many reasons why you should have a good business database because if you don’t then this could cause you real issues in the future.

Editor’s note: The opinions in this post are the contributor’s and not those of Science & Enterprise.

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In Case You Missed It …

(tigerlily713, Pixabay)

12 August 2018. Many of today’s cancer drugs are given with intravenous infusions to bypass digestive acids and enzymes that degrade and interfere with the active ingredients. We reported last week on a team at University of Colorado’s medical campus in Denver proposing a way to formulate cancer therapies as oral drugs. Their technique — use the components in milk that enable mothers to pass antibodies to their babies, shielded from the digestive system. NIH is funding the research with a 4-year award.

For this task, the researchers plan to harness exosomes, a topic we’ve written on a few times recently. Exosomes are tiny — 40 to 150 nanometer — lipid-membrane containers in cells that gather up and secrete cytoplasm, the gel-like material outside the cell nucleus. While originally believed to carry out waste removal and other maintenance tasks, exosomes are shown in recent years to perform useful delivery functions carrying proteins and genetic material to other cells, and drawing increased attention from a range of biological disciplines.

Here are other stories we covered last week:

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Five Ways To Host Better Conferences

– Contributed content –

Conference audience

(ArtMuseumTeaching.com)

12 August 2018. Nobody wants to attend a dull or disorganized conference. The best conferences have an element of intrigue and fun – they make people eager to attend and they create a lasting impression afterwards. Here are just five tricks for hosting the ultimate conference.

Make it feel exclusive

While some conferences can be open to the public, more often than they’re targeted at specific people. In order to encourage these people to attend, it can be worth emphasizing the fact that it’s an exclusive opportunity. If it’s a sales conference, you could even offer exclusive deals to those that attend. You can even invite a special guest along such as a local mayor or an expert in a certain field to encourage people to come along for the exclusive opportunity to meet this person. Also consider mailing each of your guests a VIP pass – having a private ticket will help to add to the sense of exclusivity.

Choose a memorable location

Choosing a unique location will make your conference more memorable – especially for those that visit conferences all the time. Look into unique venues that you can rent out such as conference rooms in museums, historical buildings or local entertainment venues. If people are traveling from far and wide, you could even host the conference in a hotel so that they can book accommodation there as well. You could even hire a marquee and host a conference outdoors.

Make it interactive

Listening to someone talk at you for hours on end can be very dull – spice your conference up by making it more interactive. If you’re hosting a product demo, give people the chance to get hands on with your product and test it out for themselves. Allow people to ask questions and offer the chance for one on one conversations at the end. You could also use the opportunity for market research by getting people to take part in polls. Make your conference feel like less of a talk and more like an experience.

Cater to your guests’ individual needs

Certain guests may have individual needs – you may need consider disabled access whilst foreign-speaking guests may require interpreter services. You may even have VIPs coming who you can book private transport for. By thinking about the personal needs of each guest, you’ll endear yourself on a more individual level.

Give your guests a physical reminder to take away

Physical reminders – no matter how small and trivial – will help to leave a lasting impression. You could give everyone a branded pen or you could give everyone an information booklet to take home with them. You could even consider offering a voucher that gives each of your guests a discount. Make sure you have enough of these items to give away – you don’t want to be left in an awkward situation where someone feels left out.

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