Body

Denver--February 10, 2020--In 2017, a group of lung cancer experts posed the question: "Can recent advances in tumor biology that have led to progress treating non-small cell lung cancer translate into improved outcomes for small cell lung cancer?"

According to the article "New Approaches to Small Cell Lung Cancer Therapy: From the Laboratory to the Clinic," published in the February issue of the Journal of Thoracic Oncology, the answer is "yes."

The article summarizes work presented at the Third Biennial IASLC Small Cell Lung Cancer Meeting and includes unpublished data from a variety of researchers in the field as presented at the 2019 IASLC SCLC Workshop.

Small cell lung cancer accounts for approximately 13% of all new lung cancer diagnoses. Patient outcomes have not yet been significantly impacted by the revolution in precision oncology, primarily due to a paucity of genetic alterations in actionable driver oncogenes.

The authors report that systemic therapies that include immunotherapy are beginning to show promise in the clinic. While these results are encouraging, many patients do not respond to or rapidly recur after current regimens, necessitating alternative or complementary therapeutic strategies.

In this review, the authors discuss ongoing investigations into the pathobiology of this recalcitrant cancer and the therapeutic vulnerabilities that are exposed by the disease state. Included within this discussion is a snapshot of the current biomarker and clinical trial landscapes for small cell lung cancer. The researchers identify key knowledge gaps that should be addressed in order to advance the field in pursuit of reduced small cell lung cancer mortality.

The authors point to the advantage of the recent addition of immune checkpoint blockade to first-line chemotherapy in extensive-stage SCLC. This has been the first significant improvement in several decades. However, the authors acknowledge that while the magnitude of the treatment effect was encouraging, it was modest at best. Beyond the addition of immunotherapy, the exploration of underlying disease mechanisms and the development of candidate predictive biomarkers remains in its infancy. There are discrete molecular subtypes of SCLC that can differ in their response to different therapies in preclinical models of the disease, providing a rich and untapped resource to mine for new therapeutic abilities.

"In light of the limited durability of benefit from current therapies, it is critical to continue to explore new biomarker-directed therapeutic strategies and treatment combinations both in the laboratory and the clinic," the report states. "Further exploration of the processes that drive different molecular subtypes of SCLC and the therapeutic liabilities induced by these states is warranted."

Berlin, Germany, 10 February 2020: Eternygen GmbH, a privately owned, Berlin-based metabolic diseases company, today announced that it is presenting a poster at the 3rd Global NASH Congress held in London, UK from February 10 - 11, 2020 (ElAgroudy et al.). The presentation provides data from a preclinical study which demonstrates that inhibiting the plasma-membrane tricarboxylate transporter INDY (I'm Not Dead Yet/NaCT), encoded by the longevity gene mIndy/SLC13A5, using a small molecule, is able to reverse nonalcoholic steatohepatitis (NASH) in a diet induced NASH mouse model.

INDY inhibition (INDYi) significantly reduced transaminase levels ALAT by 59% (146.2±29.2 U/L INDYi, 353.9±37.5 U/L vehicle, P

Prof. Dr. Andreas Birkenfeld, one of Eternygen's scientific founders and a recognized opinion leader in INDY research, said: "For the first time, these studies have validated the therapeutic potential of our target protein INDY in NASH. The data provide proof of concept that regulating intracellular metabolic processes through inhibition of INDY is a feasible approach to treat NASH. The current understanding of the pathophysiology fits nicely with this mode of action. Based on the new experiments and earlier data in INDY knockout mice, we see a unique profile with beneficial effects on early stage NASH, as well as on later stage inflammation and fibrosis as well as cardiovascular risk factors. These are encouraging results and provide new promise for patients and care givers."

In January 2020 Dr. Birkenfeld, Professor of Medicine, saw his research, "Solute Carrier Transporters as Potential Targets for the Treatment of Metabolic Disease" published in the peer-reviewed, Pharmacological Reviews from the American Society for Pharmacology and Experimental Therapeutics.

In October 2019, Prof. Birkenfeld was appointed Director of the Department of Diabetology, Endocrinology and Nephrology at the University Clinic, Tübingen. He is also now Director of the Helmholtz Center for Diabetes Research and Metabolic Diseases in Tübingen as well as a TransCampus Professor of Diabetes and Reader at King's College London.

Marco Janezic, CEO Eternygen GmbH, said: "These data confirm the unique pleiotropic mechanisms of INDY inhibition in addressing metabolic dysregulation as the root cause of NASH and subsequent complications (incl. inflammation and fibrosis) as well as validating its role in restoring liver function. We are now evaluating the next development steps necessary to bring this drug candidate into the clinic."

PHILADELPHIA - Among high-risk prostate cancer patients - those with high PSA and Gleason scores of 8 or more - many will develop a difficult-to-treat disease. Preliminary research suggests that two commonly prescribed medications, cholesterol-lowering statins and the diabetes therapy metformin may have anticancer effects. However, it is unclear which of these two medications - commonly prescribed together -- contributes the most and whether they can impact high-risk prostate cancer. New research shows that statins, alone or with metformin, increase survival in men with high-risk prostate cancer.

"Both metformin and statins have been associated with longer life in prostate cancer patients, yet because they are commonly prescribed together, no study we know of has looked at these two medications separately," says senior author Grace Lu-Yao, PhD, associate director of Population Science at the Sidney Kimmel Cancer Center--Jefferson Health, one of only eight NCI-designated cancer centers nationwide with a prostate cancer program of excellence.

The study, published in Cancer Medicine on Feb 8th, looked at a number of statin therapies, and metformin, an anti-diabetic medication, in high-risk prostate cancer populations.

Using data from the Surveillance, Epidemiology and End Results (SEER-18) database linked with Medicare files, Dr. Lu-Yao and colleagues looked at patients diagnosed with cancer from 2007 through to 2011. Based on 12,700 patients, the researchers observed that statins alone or in combination with metformin was significantly associated with reduced mortality from all causes.

Dr. Lu-Yao and colleagues saw the highest median survival of 3.9 months in men who took both metformin and statins, 3.6 with statins alone and 3.1 years with metformin alone. The median survival for those who did not use either drug was also 3.1 years.

"With respect to prostate mortality, metformin plus statin was associated with a 36% reduction in risk of death followed by statins alone," says Dr. Lu-Yao. "Those taking metformin alone were relatively rare, and there was no significant association with all-cause mortality."

Interestingly, the study revealed that men who took atorvastatin, pravastatin, or rosuvastatin - but not lovastatin - demonstrated a reduction in mortality compared with non-users, which is consistent with the findings from a recent population-based cohort study using Taiwan National Health Insurance Research Data. The Taiwanese research showed that these three statins are more effective at lowering triglycerides and low-density lipoprotein cholesterol and raising high-density lipoprotein cholesterol than other statins in patients with hypercholesterolemia.

Of the three statins studied, men on atorvastatin did have a longer median time to progression on androgen deprivation therapy compared to those who weren't treated with statins. "Although the exact mechanisms remain unknown, it is worth noting that atorvastatin exhibits a potent lipid-lowering effect per dose of any statin, and has the greatest bioavailability and one of the longest half-lives," says to Dr. Lu-Yao.

The data presented in the current study provide crucial insight for the design of future randomized clinical trials of statin for high-risk patients with prostate cancer. Based on the existing evidence, a well-designed clinical trial is warranted to investigate the roles of statins and combination statins/metformin to reduce the mortality cancer of the prostate.

"Our study showed that the effects were more pronounced in patients taking statins after the diagnosis of prostate cancer, 54% reduction in PCA mortality among patients with high-risk prostate cancer," says Lu-Yao. "This magnitude of reduction is comparable to the results of men treated with androgen signaling inhibitors." Statins are relatively inexpensive with good safety records. Further studies to understand the mechanisms of the observed association and its potential clinical utility are warranted.

LOS ANGELES (Feb. 9, 2020) -- Patients with thyroid eye disease who used the minimally invasive insulin-like growth factor I blocking antibody, teprotumumab, experienced improvement in their symptoms, appearance and quality of life, according to a study recently published in the New England Journal of Medicine.

The randomized, double-blind, placebo-controlled trial was conducted by the department of surgery at Cedars-Sinai and at other medical centers nationwide.

Thyroid eye disease is a rare and vision-threatening autoimmune condition that causes the muscles and fatty tissues behind the eye to become inflamed and enlarged, leading to bulging of the eyes. In addition to the bulging appearance, patients can experience double vision and light sensitivity. The disease can lead to blindness.

"The study demonstrates that medical treatment with teprotumumab is effective at reversing the manifestations of disease, providing new hope for patients," said the study's principal investigator Raymond Douglas, MD, PhD, director of the Orbital and Thyroid Eye Disease Program at Cedars-Sinai.

Patients received the drug intravenously once every week for three weeks over a 21-week period. Results showed:

Patients who were administered teprotumumab experienced effective response in two doses or six weeks of administration.

After 24 weeks, the study showed 83% of people on the drug had measurable reduction in eye bulge versus 10% of those on a placebo.

The overall response rate was 78% among those taking the drug compared to 7% of people taking a placebo.

The new discovery contributed to the fast track drug approval by the U.S. Food and Drug Administration, marketed under the brand name Tepezza, making it the first drug approved for the condition.

"Other than highly invasive surgical procedures, patients with thyroid eye disease had no real treatment alternatives," Douglas said. "This is a medical breakthrough for a very large percentage of the patient population to receive an alternative medical infusion treatment with great results, quickly."

Teprotumumab is a fully human monoclonal antibody which blocks the inflammatory autoimmune pathophysiology that underlies thyroid eye disease.

"This treatment has the potential to alter the course of the disease, potentially sparing patients from needing multiple invasive surgeries by providing an alternative, nonsurgical treatment option," said Wiley Chambers, M.D., deputy director of the Division of Transplant and Ophthalmology Products in the FDA's Center for Drug Evaluation and Research.

While sitting in the dentist's office, Hollings Cancer Center researcher Matthew Carpenter, Ph.D., of the Medical University of South Carolina, had a bright idea.

As he received his goody bag with dental hygiene products, he wondered why not conduct a study and have primary care providers do the same thing for their patients who use tobacco. The bags would contain educational material, free lozenges and tobacco cessation medications to encourage people to stop smoking.

Results from the study, recently published online in Addiction, weren't surprising to Carpenter. He and colleagues found providing smokers with a free, two?week starter kit of nicotine replacement therapy (NRT) increased quit attempts, use of stop smoking medications, and smoking abstinence as compared with standard care in a primary care setting.

"Not a day went by in this study when I was not excited by it because I knew that we were having an impact on real patients in the real world with their doctors," Carpenter said. "This gets the patients to know that their doctor cares, and they have something they can use right now."

Carpenter believes a smoker's annual visit to the doctor creates the perfect window of opportunity for a physician to provide a quick intervention, while providing tools to help smokers begin the process of quitting. Along with advice on why and how a patient should stop smoking, a person should be able to walk away with a product they can use immediately to try and stop their dependence on nicotine.

"About 70 percent of smokers will see their primary care providers on a yearly basis," Carpenter said. "It's a clinical encounter to do something, but I think we can offer them tools other than words."

In the U.S., 34 million adults currently smoke cigarettes and nearly 70 percent of U.S. adults who smoke say they want to quit, according to the 2020 Surgeon General's Report.

The $2 million study, Tobacco Intervention in Primary Care: Treatment Opportunities for Providers, also known as Tip Top, included 22 clinics throughout South Carolina and was conducted in collaboration with the National Institute of Drug Abuse (NIDA). A total of 1,245 patients participated in the study.

The study included 652 patients from 12 of the clinics who only received advice on the importance of quitting smoking. The remaining 593 patients at 10 clinics were provided with samples of medication to use including nicotine patches and lozenges. During the study, all smokers were advised to quit through a regular conversation with their physician.

They also received information and resources to help them quit smoking and information about Quitline, a tobacco cessation service available through a toll-free telephone number.

Carpenter said that the study was well-received by primary care providers, who welcomed the goody bag as a conversation starter. "The doctors are giving something that is concrete and immediately actionable," Carpenter said. "The patient can go home and use the products that day."

During this study, 26 percent of patients who received the NRT samples achieved at least one week without smoking. "If you can achieve seven days in a row of not smoking, I'm going to call that success," Carpenter said.

The study also found that 12 percent of patients were quit at final follow-up (six months). While this may seem a modest amount, it's more than 150 patients who potentially will save thousands in medical costs if they are able to quit smoking, all for just the cost of a $70 intervention. "That has to be cost-effective no matter you slice it," says Carpenter.

On average, it takes a patient seven to 10 attempts of trying to quit smoking before becoming successful, so interventions such as this can be helpful in the process. Even for the smokers who didn't use the products, it planted a seed, he said.

An interesting finding during this study showed that the smoking cessation bags with information and medication were more beneficial to patients who had a lower income, lower education or if they were in the more rural areas of the state. The finding on income, education, and rurality is an area Carpenter would like to study more in the future.

"It's about access," Carpenter said. "We're helping people who are struggling out there to find and succeed in treatment."

Given the toll of smoking-related health conditions, Carpenter said he hopes insurance companies will see the value and provide funding in the future so that primary care physicians could offer this to their patients. The concept also could be used for smokers who are leaving the hospital, or even those who have been incarcerated.

"These samples can be given out almost universally - even to smokers who may not want to quit and who may not yet be ready to try medications," Carpenter said. "It's a pragmatic and brief intervention that takes minutes to deliver and is scalable as an intervention to be used a variety of settings."

Smoking cessation reduces the risk of twelve cancers, including cancers of the lung; larynx; oral cavity and pharynx; esophagus; pancreas; bladder; stomach; colon and rectum; liver; cervix; kidney; and acute myeloid leukemia.

Carpenter said the intervention provides patients a starting point to their journey of becoming smoke-free and it's simple to use for primary care providers, who don't feel pressured to have a long lecture. They can just offer their patients support.

"This is about cancer prevention. Smoking cessation is cancer prevention," Carpenter said.

In 20 - 40% of patients with cancer, metastasis (the development of secondary tumors) in the central nervous system (CNS) occurs. CNS metastatis impacts negatively on a patient's quality of life, and is associated with a poor health prognosis. In a form of cancer known as ALK-rearranged non-small-cell lung cancer (NSCLC), CNS metastatis is known to persist when drugs targeting primary tumors are used. Now, Seiji Yano from Kanazawa University and colleagues have investigated the origins for the resistence to such drugs, and tested a new therapeutic strategy on a mouse model.

The researchers looked at the drug alectinib. Although used in standard treatments for advanced ALK-rearranged NSCLC, approximately 20 - 30% of patients treated with alectinib develop CNS metastatis, which is attributed to acquired resistance to the drug.

By treating mice first injected with tumor cells with alectinib daily for 16 weeks, the scientists obtained a mouse model displaying alectinib resistance. By biochemical analyses of the mouse brains, Yano and colleagues were able to link the resistance to the activation of a protein known as epidermal growth factor receptor (EGFR). This activation is, in turn, a result of an increase in production of amphiregulin (AREG), a protein that binds to EGFR and in doing so 'activates' it.

Based on this insight, the researchers tested the effect of administering drugs used for inhibiting the action of EGFR in combination with alectinib treatment. The experiments showed that a combination treatment of alctinib with either erlotinib or osimertinib -- two existing EGFR-inibiting drugs -- prevented the progression of CNS metastasis, controlling the condition for over 30 days.

The scientists conclude that the combined use of alectinib and EGFR-inhibitors could overcome alectinib resistance in the mouse model of leptomeningeal carcinomatosis (LMC), a particular type of CNS metastasis. Quoting Yano and colleagues: "Our findings may provide rationale for clinical trials to investigate the effects of novel therapies dual-targeting ALK and EGFR in ALK-rearranged NSCLC with alectinib-resistant LMC."

[Background]

Non-small-cell lung cancer

Non-small-cell lung carcinoma (NSCLC) and small-cell lung carcinoma (SCLC) are the two types of lung cancer. 85% of all lung cancers are of the NSCLC type. NSCLCs are less sensitive to chemotherapy than SCLCs, making drug treatment of the highest importance.
Alectinib is a drug used for treating NSCLC, with good efficiency. However, 20-30% of patients taking the drug develop secondary cancer in the central nervous system (CNS), which is associated with an acquired resistance to alectinib. Seiji Yano from Kanazawa University and colleagues have now made progress towards a novel therapy against this resistance: a combination of alectinib with other drugs.

Epidermal growth factor receptor inhibitors

The drugs that Yano and colleagues tested in combination with alectinib on a mouse model were of a type known as epidermal growth factor receptor (EGFR) inhibitors, including osimertinib and erlotinib. Both are being used as medication for treating NSCLC. The former was approved in 2017 as cancer treatment by the U.S. Food and Drug Administration and the European Commission. Yano and colleagues obtained results showing that EGFR inhibitors counteract resistance to alectinib and have therefore potential in novel therapies for NSCLC and secondary cancers in the CNS.

Topologically stabilized spin structures at the nanoscale magnets, including domain walls, vortices and skyrmions, have recently received much attention. Among the nanoscale non-linear spin textures, vortex is a typical and well-known magnetic domain in dimensionally confined systems with a symmetry determined by its polarity and chirality. Because of its stability at the nanoscale and its robust control on nanosecond timescales, the magnetic vortex can be a promising candidate for next-generation magnetic data-storage devices [1].

Recently, emergent phenomena were discovered in manganites with strong electron correlation, such as the nonvolatile tunable magnetoresistance [2], ultralow-current-induced domain-wall motion [3], anisotropic resistance switching [4], topological Hall effect [5] and the high-frequency spin-wave propagation [6] etc., which are strongly affected by their mesoscopic domains. Magnetic domains in manganites are sensitive to various external stimuli such as strain, size, electric/magnetic fields etc., making them a model system to manipulate their spin textures (e.g. vortex, chiral domain walls). However, magnetic vortices were usually observed in spatially confined nanostructures such as the square-shaped, triangle-shaped, and disc-shaped nano-islands, and the shape-induced magnetic anisotropy is assumed to be the major mechanism for the formation of the magnetic vortex.

Using variable-temperature magnetic force microscopy (VT-MFM) and in-situ magnetoresistance measurements, Chinese researchers in collaboration with German scientists discover that magnetic vortex clusters in epitaxial LSMO structure can be stabilized by artificially engineering its strain state. Phase-field modeling further supports that the vortex state in this one-dimensional manganite originate from the inhomogeneous strain. Enhancement of the uniaxial strain relaxation-induced magnetic anisotropy in wires and its competition with the shape-induced anisotropies plays an important role in stabilizing the flux closure spin structure. This work offers a new strategy to build up emergent spin textures in strongly correlated magnets and may trigger new designs for magnetoelectronic devices.

Fast, reliable and automatic assessment of the severity of myoclonic jerks from video footage is now possible, thanks to an algorithm using deep convolutional neural network architecture and pretrained models that identify and track keypoints in the human body. Published in Seizure, the study is a joint effort by the Epilepsy Centre at Kuopio University Hospital, the University of Eastern Finland and Neuro Event Labs.

Myoclonus refers to brief, involuntary twitching of muscles and it is the most disabling and progressive drug-resistant symptom in patients with progressive myoclonus epilepsy type 1 (EPM1). It is stimulus sensitive and its severity fluctuates during the day. In addition, stress, sleep deprivation and anxiety can cause significant aggravation of myoclonic symptoms. Clinical objective follow-up of myoclonus is challenging and requires extensive expertise from the treating physician. Therefore, physicians and the medical industry have been seeking automatic tools to improve the consistency and reliability of serial myoclonus evaluations in order to reliably estimate treatment effect and disease progression.

Unified myoclonus rating scale (UMRS), a clinical videorecorded test panel, is the gold standard currently used to evaluate myoclonus. The researchers analysed 10 videorecorded UMRS test panels using automatic pose estimation and keypoint detection methods. The automatic methods were successful in detecting and tracking predefined keypoints in the human body during movement. The researchers also analysed speed changes and the smoothness of movement to detect and quantify myoclonic jerks during an active seizure. The scores obtained using automatic myoclonus detection correlated well with the clinical UMRS myoclonus with action and functional tests scores evaluated by an experienced clinical researcher.

The study showed that the automatic method involving keypoint detection and pose estimation from video footage reliably quantified myoclonic jerks in EPM1 patients. The automatic quantification of myoclonus correlated well with the clinical evaluation. It also effectively quantified the smoothness of movement, and was sensitive enough to detect small-amplitude and high-frequency myoclonic jerks.

Is it possible to investigate menopausal age, or not? In more than one in three women aged 50, the body provides no clear answer about the menopause, a University of Gothenburg study shows. Increased use of hormonal intrauterine devices and contraceptive pills are the cause.

The springboard for the study was previous research, published in the scientific journal Menopause, showing that women's menopausal age had risen over time. The question addressed this time was whether this trend has persisted.

This trend of rising menopausal age emerged very clearly from a study published by researchers at Sahlgrenska Academy, University of Gothenburg, in 2003. This study was based on the Prospective Population Study of Women in Gothenburg, a major project commenced in 1968.

The data concerned women born between 1908 and 1930, and those born towards the end of this period proved to be older at the onset of menopause. On average, for every ten years later a woman was born, her menopause came when she was one year older.

The causes were assumed to be the same as those of women's menarche (onset of menstruation) occurring at an ever younger age: better diet and health, along with improved maternity care. The statistical significance of the rise in menopausal age was high, and could not be explained by the women's hormone use, smoking, socioeconomic group, BMI, number of children, or age at menarche.

The Prospective Population Study of Women in Gothenburg has continued to survey women aged 38 and 50, most recently in 2016 and 2017. However, in the present, follow-up study, the researchers encountered a problem: for many of the 50-year-old women it was not possible to establish their exact menopausal age.

"We investigated the numbers of 50-year-olds who were still menstruating and those who had stopped menstruating, and found that after 1992 the part still menstruating was somewhat smaller than 1992. However, there's great uncertainty, since many of the women were taking hormones," says Kerstin Rodstrom, general practitioner, researcher at the University of Gothenburg, and the first author of the study.

Just over 37 percent of the women used hormonal intrauterine devices (IUDs), contraceptive pills, or other forms of birth control involving hormones that affect the volume of menstrual flow, menopausal ailments, or both. This group also included women who were no longer menstruating because they had undergone uterine surgery.

Cecilia Bjorkelund, a general practitioner and professor of general practice at the University of Gothenburg, is the senior author of the article.

"Nowadays, the period around the age of menopause is a very active part of women's lives, and the study shows that women today assume great responsibility for, and are in control of, their own fertility and well-being during an important life phase: the middle age," Bjorkelund says.

February 7, 2020 - Pneumococcal conjugate vaccines (PCVs) have been highly effective in reducing pneumonia and other invasive infections caused by Streptococcus pneumoniae bacteria. But rates of meningitis have shown little change, as pneumococcal strains not targeted by PCVs emerge as more important causes of meningitis, reports a paper in The Pediatric Infectious Disease Journal, the official journal of The European Society for Paediatric Infectious Diseases. The journal is published in the Lippincott portfolio by Wolters Kluwer.

Reshmi Mukerji, MPH, and David E. Briles, PhD, of University of Alabama at Birmingham analyze evidence on how pneumococcal meningitis has changed since the introduction of PCVs. To make progress in reducing rates of meningitis worldwide, the researchers believe that new vaccines targeting all pneumococcal strains colonizing the nose and throat, irrespective of capsular type, will be needed.

PCV Vaccines Linked to Emergence of New Strains Causing Meningitis

The PCV7 and PCV13 vaccines - targeting seven and thirteen strains of pneumococcal bacteria, respectively - have been highly effective in reducing rates of invasive pneumococcal disease, including pneumonia and bloodstream infection or sepsis. But despite the use of PCVs, pneumococcal bacteria remain the leading cause of meningitis in children. Worldwide, meningitis rates of up to 13 cases per 100,000 children have been reported.

Bacterial meningitis is infection of the brain and spinal cord membranes: it is difficult to treat, often fatal, and causes lasting complications in survivors. Recent studies have shown that child and adult pneumococcal meningitis rates have been stable or increased, largely due to bacterial strains not targeted by PCVs.

"Widespread use of vaccines resulted in the emergence of a broad diversity of replacement non-PCV type strains," Ms. Mukerji and Dr. Briles write. Although this serotype replacement has occurred worldwide, evidence suggests that rates are highest in Europe and North America. These non-vaccine-type strains cause meningitis at least as severe as the types targeted by PCV7 and PCV13.

Many pneumococci covered by PCV 13 form capsules that shield them from the body's immune system in the lung and blood. However, the replacement strains seldom cause sepsis - suggesting that their non-PCV capsules don't allow them to survive well in the bloodstream. The pneumococci with non-PCV type capsules may be traveling to the brain directly from the nose, throat and ear, through the olfactory and auditory nerves, rather than through the bloodstream.

This could occur when the nose and throat are colonized by pneumococci of non-PCV capsular types, which have largely replaced the bacteria targeted by current PCVs. To prevent such cases of meningitis, new vaccines will need to be developed to prevent or greatly reduce colonization with these capsular, non-vaccine-type bacteria.

The problem is that there are more than 98 different capsular types - it would be difficult or impossible to target them all in a single vaccine. The most promising alternative might be vaccines directed at specific proteins involved in pneumococcal capsule formation and colonization. The authors outline an approach where this strategy could first be tested in small-scale studies, before larger studies to confirm its effectiveness in preventing meningitis.

"Because virtually all cases of pneumococcal meningitis lead to either permanent neurologic sequelae [complications] or death, it would be well worth the effort to develop a new vaccine capable of preventing pneumococcal meningitis regardless of capsular type," Ms. Mukerji and Dr. Briles conclude. "Such a vaccine would need to protect against colonization with most, if not all, pneumococci."

Up to now, cancer is still one of the major diseases that threaten the survival of mankind, and it is difficult to cure clinically. In addition to single or combined surgery, chemotherapy and radiotherapy, which are commonly used clinically, a number of promising therapeutic strategies have been recently put forward including immunotherapy and gene therapy, photothermal therapy (PTT), photodynamic therapy, and so on. However, these techniques usually rely on chemical and genetic drugs or exotic nanomaterials to actualize treatments, making them quite difficult or debatable for practical clinical applications in near future due to the uncertainties of potential biotoxicity and biohazards, and related genetic and ethical issues; and immunotherapy and gene therapy are complex and expensive. Therefore, the popularization of these techniques in clinical practice is restricted. Consequently, developing simple, green, efficient and cheap treatment method is an urgent need to combat cancer.

Hydrogen, owing to its small molecular size and physiological inertness, resistance to oxidation, and good gas diffusivity in-vivo, is considered as a kind of green and endogenous gas. It performs the eminent physiological/pathological regulation functions, which is widely used for the treatment many diseases, such as, Alzheimer's disease, arthritis, diabetes and especially cancer. As early as 1975, researchers have applied the antioxidation of H2 to treat skin squamous cell carcinoma, but it requires using diving medical equipment to provide high pressure H2 which is restricted for clinic tumor therapy applications, how to produce H2 non-invasively and sufficiently without using nanomaterials and how to realize H2 releasing on demand in vivo are two huge challenges facing for the H2 therapy of cancers.

Acupuncture is a traditional and unique minimally-invasive method to treat diseases in China. It is quite effective to treat systemic diseases, especially for arthritis, cervical spondylopathy, psoatic strain and so on. But applying it to the treatment of major diseases, such as cancers is still a great challenge.

In a new research article published in the Beijing-based National Science Review, scientists at the State Key Laboratory of Electroanalytical Chemistry, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, China, and at School of Public Health, Jilin University, Changchun, China present the latest advances a green, efficient and precise hydrogen therapy of cancer based on in-vivo electrochemistry. Co-authors Guo-Hua Qi, Bo Wang, Xiangfu Song, Haijuan Li and Yong-dong Jin report the hydrogen cancer therapy in vivo with electrochemical. They have summarized the development of hydrogen in the treatment of cancer and the key problems limiting its development of clinical application.

These scientists have developed a simple and precise cancer therapy approach based on selective electrochemical generation of H2 in tumor region, termed in-vivo H2 generation electrochemotherapy (H2-ECT) by innovative combined use of traditional Chinese acupuncture Fe needle (electrode) and in-vivo electrochemistry. The H2-ECT method enables large-scale tumor therapy by applying gas diffusion effect, avoiding the shortcoming of limited effective area for classic electrochemical reactions. Moreover, due to the puncture positioning and acidic tumor microenvironment (compared to normal tissue), the method provides ideal selectivity and targeting to precisely kill tumors with minimal damage to normal tissue, which is very promising for potential clinic applications. The effectiveness of the method has been demonstrated by successful and fast treatment of glioma and breast cancers in mice in this study. The cost of cancer therapy is very low and less than 1 $ for each treatment.

Scientifically, a green and conceptually new in-vivo H2 generation electrochemotherapy (H2-ECT) of tumor has been developed. Prof. Yongdong Jin said that in a broader perspective, the H2-ECT provides a reliable method for the treatment of cancer and solves the heavy economic burden of cancer therapy bring to the family by high cost, so that it is easily popularized in poor country.

Few cannabis consumers understand what the THC numbers on packages of cannabis edibles really mean, according to a new University of Waterloo study.

The study, which surveyed nearly 1,000 Canadians aged 16 to 30, found that most consumers could not identify whether a cannabis edible contained 'low' or 'high' levels of THC based on the label.

The researchers also found that descriptive information, such as symbols and words, are more effective in helping consumers understand THC potency and approximate serving sizes for cannabis products.

"Using THC numbers to express potency of cannabis products has little or no meaning to most young Canadians," said David Hammond of Waterloo's School of Public Health and Health Systems. "We've known for many years that people struggle to understand the numbers on the back of food packages and cigarette packages. Consumers seem to have equal or even more difficulty with THC numbers, which are used to indicate the potency of cannabis products."

He added, "Effective THC labelling and packaging could help reduce to accidental over-consumption of cannabis edibles and adverse events, which have increased in jurisdictions that have legalized recreational cannabis."

Health Canada currently requires cannabis packages to list the ingredients, product type, potency and other essential information, including weight in grams, and percentage of THC (or CBD, depending on the product), but not symbols or intuitive labeling on THC levels.

The researchers conducted two experiments with 870 Canadians aged 16-30 in 2017: The first investigated whether consumers could understand how many servings there were in a package, and the second examined if consumers could identify how potent the product was.

The study found approximately 6 per cent of consumers could correctly identify serving size on products that had no label, or only listed the weight. Seventy-seven per cent could identify the serving when the dosage was listed.

The study also found that a 'traffic light' system, which uses traffic light colours to indicate potency, allowed two-thirds of respondents to identify products with high levels of THC, compared to 33 per cent of respondents who only used numerical THC information.

In 2018, Statistics Canada found that 32 per cent of cannabis users consumed edibles.

"New regulations that limit cannabis edibles to a maximum of 10 mg per package are particularly important given that most consumers do not understand THC numbers," Hammond said. "However, the findings suggest that consumers will need easier-to-understand THC information for other products, including oils, concentrates and dried flower."

The study, "Cannabis labelling and consumer understanding of THC levels and serving sizes," was published in the Journal of Drug and Alcohol Dependence, and co-authored by Cesar Leos-Toro, Geoffrey Fong, Samantha Meyer and David Hammond, all at the University of Waterloo.

Pathogens don't pay attention to international borders, with transmission and endemic areas often stretching between countries. In the new work, Moses Katabarwa of the Carter Center, USA, and colleagues report in PLOS Neglected Tropical Diseases the first known and successful coordinated cross-border mass drug administration (MDA) effort with ivermectin to stop onchocerciasis.

Onchocerciasis is a tropical disease caused by the parasitic worm Onchocerca volvulus, spread through Simulium flies that breed in fast flowing rivers and streams in Africa. The disease, also called "river blindness," can cause skin and eye symptoms. An onchocerciasis transmission zone known as Galabat-Metema is shared between Sudan and Ethiopia respectively, both countries having established a nationwide policy for elimination of the disease. Baseline disease mapping of 0-18% among 14 villages in Galabat, Sudan and 14-44% in 17 villages in the Metema district of Ethiopia.

Mass drug administration was provided once and subsequently twice per year in the area, with two doses per eligible person-per-year beginning in 2016 in Ethiopia and 2008 in Sudan. To determine if transmission had been interrupted on both side of the border, blood tests for onchocerciasis antibody were carried out in children and vector Simullium black flies were tested in 'pools' of 100 flies/pool for O. volvulus DNA in both countries.

Blood tests on 10,003 children were all negative and only one vector positive pool among 36,731 flies was positive. The WHO criteria for stopping MDA were met, and MDA was halted at the end of 2017 in a coordinated binational manner through a process of close collaboration and communication between the governments of Sudan and Ethiopia. This is the first repot of such a cross border stop MDA decision.

"Onchocerciasis transmission zones may cross international borders and so present a unique challenge of coordination between the different national program activities on each side of the border," the researchers say. "Several lessons were learned from this experience."

Missing a single ophthalmology appointment over a two-year period was associated with decreased visual acuity for patients with macular degeneration -- a leading cause of permanent vision loss in the elderly -- according to a new Penn Medicine study. The findings, published today in JAMA Ophthalmology, suggest that more attention should be paid to ensuring visit adherence for this patient population. The authors say the results of the study also have financial implications for clinicians, due to impending changes in Medicare reimbursement. These changes will reportedly shift financial risks to the physician, while also accounting for patient outcomes.

Age-related macular degeneration (AMD) happens when debris builds up in the central portion of the retina, called the macula, causing it to lose function, which leads to gradual wavy or blurred eyesight. There are two types: dry, which is more common and less serious, and wet, which is less common but much more severe. AMD is the leading cause of permanent vision loss in people over age 50, with an estimated 1.8 million Americans suffering and another 7.3 million at risk of developing the disease, according to the Centers for Disease Control and Prevention.

While there is no cure for wet AMD, vision can be maintained and often improved with anti-VEGF (intravitreal anti-vascular endothelial growth factor) drugs, which must be injected into the eye by an ophthalmologist. However, this treatment comes with a significant burden to the patient -- mandating frequent, sometimes monthly, trips to the eye doctor.

"Research of other diseases has shown the importance of appointment adherence. In patients with HIV, for example, studies have found that showing up to appointments has been linked to lower mortality rates and reduced viral loads. But unlike HIV patients, who can have prescriptions filled over the phone by any physician, anti-VEGF therapy can only be administered by an ophthalmologist, making visit adherence even more critical for those with macular degeneration," said Brian VanderBeek, MD, a professor of Ophthalmology at the University of Pennsylvania's Perelman School of Medicine. "I wanted to quantify the link between regular visits to the eye doctor and visual outcomes for these patients."

VanderBeek and a research team analyzed data from the Comparison of Age-related Macular Degeneration Treatment Trail (CATT) randomized clinical trial. The dataset included 1,178 patients recruited from 44 clinical centers in the United States. During the two-year clinical trial, patients were required to visit, but not necessarily be treated with injections, by an ophthalmologist once every four weeks, totaling 26 visits. The research team devised four different metrics to assess how well or poorly patients adhered to their visits, including: total number of missed visits, average number of days between visits, longest duration between visits, and visit constancy (the total of 3-month periods with at least one visit attended). Those metrics were then compared to the patients' outcomes on their final vision tests.

For all four metrics, patients who best adhered to their scheduled visits had better visual outcomes. In fact, each missed visit was associated with an average visual acuity letter score decline of 0.7. Compared to those who attended all of their visits, those who averaged between 36 to 60 days between visits lost 6.1 letters, and those who went more than 60 days between visits lost 12.5 letters.

Since anti-VEGF treatment for AMD began in 2006, there has been much discussion in the medical community about the number of anti-VEGF injections that are appropriate to give a patient. However, when the Penn Medicine researchers controlled for number of injections, they found that visit adherence was still associated with visual outcomes, independent of how many treatments someone received.

"It's important to reframe how we think about this. Let's worry less about predicting a specific number of injections a patient needs and more about getting them into the doctor's office," VanderBeek said.

The study authors note that the findings are important, not only for improving patient outcomes, but also due to impending changes in insurance reimbursement. It has been reported that Medicare's future goal will be to shift financial risks to the physician, while also accounting for patient outcomes.

"Nowhere in ophthalmology will this conflict arise more than in the treatment of patients with AMD," they write.

A combination of social, financial, and educational barriers can prevent patients from attending scheduled doctor appointments. VanderBeek said that future studies should investigate how physicians, individual practices, and health systems can create policies and practices to overcome these obstacles and improve health outcomes.

Steroids should be avoided in the treatment of the current novel coronavirus, experts have advised.

A commentary article published in The Lancet concludes that, based on evidence from previous outbreaks of similar types of infection such as SARS, steroids provide little benefit to patients and could do more harm than good.

They say that clinicians should still administer the treatment for conditions such as asthma and other inflammatory diseases.

Steroids are often used by doctors to reduce inflammation, which is present in the lungs of patients with novel coronavirus. Lung inflammation was observed during the SARS and MERS outbreaks, which were caused by coronaviruses.

However, steroids also impair the immune system's ability to fight viruses and other infections that often develop in patients with life-threatening illness. Experts say that, on balance, using the drugs could cause significant harm.

One retrospective study of critically-ill patients with MERS found that almost half of the people that received steroids needed additional treatments such as assistance in breathing, drugs to increase blood pressure, and a form of dialysis. Those given steroids were found to take longer to clear the virus from their bodies.

Other studies found that steroids caused harm in the SARS outbreak, with the virus still present in those who took the drugs up to three weeks after infection.

Dr J. Kenneth Baillie, lead author of the commentary article and Academic Consultant in Critical Care Medicine at University of Edinburgh, said: "During this current coronavirus outbreak clinicians are faced with some tough decisions on how to treat people who have been infected. After looking carefully at what evidence is available, we would advise that steroids should not be used for treatment of lung injury caused by this new virus. If steroids are used, it should be as part of a clinical trial so that we can find out if they are helping or harming patients."