Body

FINDINGS

In a UCLA-led phase I clinical trial, a new plant-based drug called APG-157 showed signs of helping patients fight oral and oropharyngeal cancers. These cancers are located in the head and the neck.

APG-157 is made up of multiple compounds produced by plants, including curcumin. UCLA Jonsson Comprehensive Cancer Center researchers found that treatment with this botanical drug resulted in high concentrations of curcumin and its byproducts circulating in the blood and absorbed by tumor tissues within three hours after being taken orally.

APG-157 reduced the concentration of cytokines -- proteins involved in inflammation -- in the saliva when administered to cancer patients. The therapy also reduced the relative abundance of Bacteroides species, a group of gram-negative bacteria. Gram negative refers to a group of dangerous bacteria that have an outer layer which hides them from the immune system. The relative abundance of gram-negative bacteria compared to the presence of other types of bacteria is correlated with oral cancer.

APG-157 also resulted in the expression of genes that are associated with attracting immune system T cells to the tumor area. This therapy could have a beneficial effect when used in combination with immunotherapy drugs that help immune system T cells recognize and kill tumors.

The treatment did not have any adverse effects on the study's participants.

BACKGROUND

Cancers of the head and neck account for 4% of all cancers. About 650,000 new cases are reported each year around the world. People with advanced head and neck cancers have a low survival rate and current treatment options such as surgery, radiation and chemotherapy can have adverse effects. Therefore, more effective and less toxic therapies are needed to help improve the quality of life and outcome for those with these cancers.

APG-157 is a botanical drug developed under the FDA's Botanical Drug Guidance, which includes requirements for production of plant-based therapies that are marketed as prescription medications. The drug is made up of botanical compounds including curcumin from the Curcuma longa plant, which is commonly referred to as turmeric and is a member of the ginger family.

Curcumin is one of the medicinally active or therapeutic molecules that has been tested as a possible treatment to help fight multiple cancers because it is an antioxidant that reduces swelling and inflammation. However, there is poor absorption into the bloodstream when curcumin is taken orally. In this study, UCLA researchers found that when APG-157 is taken through oral mucosal absorption, patients have high levels of curcumin circulating in their blood and absorbed by cancer tissues.

METHOD

UCLA researchers conducted the study of APG-157 comparing 12 people who had oral and oropharyngeal cancer with a control group of 13 people who did not have cancer. The reason both the people with cancer and without cancer were part of the study was to show that the drug was not toxic to either people with cancer or those without cancer.

The medication was given each hour for three hours and was delivered as a lozenge that slowly dissolved in the mouth. Blood and saliva samples were collected beforehand -- each of the three hours the medication was administered -- and 24 hours after the last dosage. The medication was given to 12 people (some who had cancer and some who did not) and a placebo was given to 13 people. Blood and electrocardiogram tests did not show increased toxicity in the people who took the active medication in comparison with the people who took the placebo, regardless of whether they had cancer or not.

For the cancer patients who took the medication, there was a decrease in Bacteroides and an increase in T cells in the tumor tissue as compared to cancer patients who took the placebo. Neither the subjects nor the investigators knew whether the drug or a placebo was given when reviewing the blood and saliva test results of the blinded study.

IMPACT

APG-157 is a botanical drug that has low toxicity. It works effectively to reduce inflammation that contributes to the growth of cancer cells. It also attracts T cells to the tumor micro-environment. When used in combination with immunotherapy drugs, APG-157 might have the ability to make the immune system more effective in attacking head and neck cancers. With potential to inhibit the growth of Bacteroides species, APG-157 could also improve cancer therapy through oral microbial changes.

An experimental fingerprint detection approach can identify traces of cocaine on human skin, even after someone has washed their hands - and the test is also smart enough to tell whether an individual has actually consumed the class A drug, or simply handled it.

In a paper published in Nature Publishing Group's Scientific Reports, a series of experiments by the University of Surrey detail how it is possible to carry out drug testing accurately and painlessly using a single fingerprint sample. For drug testing, it is necessary to be able to distinguish those who have handled cocaine from those who have ingested it because the legal ramifications are different (for example, consider drug driving) - the new research demonstrates that this is possible for the first time using high resolution mass spectrometry techniques.

A successful, commercially-available fingerprint drug screening system, using lateral flow assay technology and fluorescence-labelled antibodies to selectively detect specific drugs or their metabolites in eccrine sweat collected from fingerprints, is already available for point of care use from Intelligent Fingerprinting - who also offer a fingerprint-based laboratory confirmation service which uses Liquid Chromatography Mass Spectrometry techniques.

The team, from University of Surrey, Forensic Science Ireland, National Physical Laboratory and Intelligent Fingerprinting, took fingerprints from people seeking treatment at drug rehabilitation clinics who had testified to taking cocaine during the previous 24 hours. Fingerprints were collected from each patient, and the participants were then asked to wash their hands thoroughly with soap and water before giving another set of fingerprints. This same process was used to collect samples from a pool of drug non-users who had touched street cocaine.

The researchers at Surrey used their world-leading experimental fingerprint drug testing approach (based on rapid, high resolution mass spectrometry) to cross-reference the information from the drug non-users who had touched cocaine with that of volunteers who testified ingesting it. They found that a molecule produced in the body when cocaine is ingested, benzoylecgonine, is essential in distinguishing those who have consumed the class A drug from those who have handled it. Benzoylecgonine was not present in samples from drug non-users, even after touching street cocaine and then washing their hands.

Dr Min Jang said: "A fingerprint is a great way to test for drugs as it is so quick and efficient to collect. Using our methodology, it is possible to analyse a fingerprint sample for drugs in less than 2 minutes".

Dr Catia Costa from the University of Surrey said: "We are excited about the possibilities for fingerprint drug testing. In addition to illicit drugs, we have found that we can detect pharmaceutical drugs in fingerprints and we are keen to see if we can use this to help patients to check that their medication is being delivered at the right dose."

Dr Melanie Bailey from the University of Surrey said: We think this research is really significant as our laboratory test using high resolution mass spectrometry can tell the difference between a person who has touched a drug and someone who has actually consumed it - just by taking their fingerprints.

Professor David Russell, Founder and Chief Scientific Officer at Intelligent Fingerprinting, said: "This University of Surrey laboratory study into cocaine testing using experimental high resolution mass spectrometry techniques validates the approach Intelligent Fingerprinting took when originally commercialising our portable fingerprint-based drug screening system for use at the point-of-care. Because our commercially-available test detects both cocaine traces and benzoylecgonine - the major metabolite of cocaine - our customers have been successfully using fingerprint-based drug tests since the Summer of 2017 to determine whether cocaine has actually been taken."

PLYMOUTH MEETING, PA [February 6, 2020] -- Survival outcomes for HPV-positive oropharyngeal squamous cell carcinoma of the head and neck (SCCHN) have made significant gains in recent years, but new research in the February 2020 issue of JNCCN--Journal of the National Comprehensive Cancer Network finds some groups are being left behind. Researchers from Massachusetts General Hospital--along with Yale University School of Medicine, UT Southwestern Medical Center, and UNC Chapel Hill School of Medicine--conducted the largest population-based analysis to date on the socioeconomic factors that affect outcomes in this cancer type, and found significant racial and socioeconomic disparities.

"When we examined outcomes by race and insurance status, adjusting for all clinical factors, those patients who were non-white or uninsured or poorly insured had much reduced cancer-specific survival compared to their white and well-insured peers," said Luke R. G. Pike, MD, DPhil, Department of Radiation Oncology, Massachusetts General Hospital. "It's unsettling that black and Hispanic men and women with HPV-positive oropharyngeal carcinoma--a disease we now recognize to be curable in many patients with even very advanced disease--appear to do disproportionately poorly as compared to their white peers. We also speculate that patients with insufficient insurance were unable to access high-quality radiotherapy, surgery, and chemotherapy, which is crucial to the successful treatment of locally advanced HPV-positive oropharyngeal cancer. We must strive to ensure that all men and women, no matter their insurance status or race, can get access to high-quality treatment for head and neck cancers."

The researchers used a custom SEER Database to identify 4,735 adult patients who were diagnosed with primary nonmetastatic SCCHN with a known HPV status in 2013 or 2014. The data showed that among those patients with HPV-positive oropharyngeal cancer, there was a 5.6% rate of cancer-specific death at 20 months for white individuals, compared to an 11.2% rate for non-whites. Separately, the rate of cancer-specific death for persons with health insurance was 6.2%, versus 14.8% for the uninsured. Those outcome disparities were not seen for non-oropharyngeal cancers, or prognostically less favorable HPV-negative SCCHN.

"The study by Pike, et al. highlights the socioeconomic differences between patients with HPV-positive and HPV-negative SCCHN and identifies striking racial disparities among individuals with HPV-positive oropharyngeal SCCHN, whereby non-white and uninsured patients with HPV-positive cancers had worse cancer-specific mortality," commented Francis Worden, MD, University of Michigan Rogel Cancer Center, and Member of the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) Panel for Head and Neck Cancers--who was not involved in this research. "While the exact reasons for these findings are speculative given the retrospective nature of this work, their data bring to light the importance for early diagnosis and treatment of all patients with HPV-positive oropharyngeal cancers and the importance of identifying and eliminating barriers to care. HPV-positive cancers are highly curable, but data does show that patients who present with higher stage disease (due primarily to delays in diagnosis and thus delays in treatment) have lower overall survival rates. Additionally, lower income, non-white populations may be less likely to obtain care at larger, more experienced cancer centers that treat higher volumes of head and neck cancers. Published data suggest that patient care at such centers of excellence leads to improved outcomes due to expertise in administering complex treatment plans and the high level of support that is provided during medical care."

A research group led by Professor NISHIMURA Noriyuki (Graduate School of Health Sciences, Kobe University) has developed a new method to monitor the residual disease after treatment in high-risk neuroblastoma patients. The method could be utilized to evaluate treatment response and facilitate early diagnosis of tumor relapse/regrowth.

This monitoring method was developed by a group consisting of Assistant Professor YAMAMOTO Nobuyuki and Project Assistant Professor UEMURA Suguru (both of the Graduate School of Medicine, Kobe University), and from Hyogo Prefectural Kobe Children's Hospital; Vice Director Dr. KOSAKA Yoshiyuki, Department Head Dr. HASEGAWA Daiichiro and chief physician Dr. ISHIDA Toshiaki. Research collaboration and support was also provided by SYSMEX.

These results were first published in the Journal of Molecular Diagnostics on December 11, 2019.

Main Points

Disappearance/inactivation of residual disease after treatment (minimal residual disease: MRD) is essential for sustaining treatment effectiveness and ensuring the long-term survival of high-risk neuroblastoma patients. However, it has been difficult to monitor these changes in MRD using previous methods.

This research group developed a method for monitoring MRD by detecting the levels of 7 neuroblastoma-associated markers using droplet digital PCR (polymerase chain reaction) (*1).

This monitoring method enabled a precise monitoring of MRD and an early diagnosis of tumor relapse/regrowth in high-risk neuroblastoma patients.

This new method will enable the stratification of high-risk neuroblastoma patients and is expected to lead to the development of new treatment methods and improved patient prognoses.

Research Background

Neuroblastoma is a type of cancer that affects children. It is characterized by solid tumors that develop from immature nerve cells in the sympathetic nervous system, commonly in and around the adrenal glands. Over 50% of patients with high-risk neuroblastoma experience tumor relapse or regrowth and their long term survival rate is as low as 40%. Eliminating MRD is vital to sustain treatment effectiveness and improve patient prognosis, and various monitoring methods have been utilized.

Monitoring methods up until now have evaluated MRD using real-time PCR (qPCR) (*2). This monitoring has involved measuring the levels of various neuroblastoma-associated markers, high levels of which indicate the development of neuroblastoma cells across cancerous and non-cancerous stem cells.

The current study sought to more accurately evaluate these pathological changes. Out of the neuroblastoma-associated markers that are highly expressed in neuroblastoma cells, the research group selected seven markers that are particularly abundant in the cancer stem cells that cause tumor relapse/regrowth. To detect the levels of these seven markers, the research group used droplet digital PCR (ddPCR), which provides a more sensitive and reproducible way of measuring these markers in a sample than qPCR.

Research Methodology

This research team previously developed a qPCR-based system that was used to detect levels of eleven markers associated with the cancer stem cells that cause neuroblastoma reoccurrence. This method enabled them to monitor MRD in high-risk neuroblastoma patients. However, it was difficult to accurately track the changes taking place using qPCR. For the current study, the research group decided to use the more sensitive and reproducible ddPCR to evaluate MRD.

First of all, 208 bone marrow samples and 67 peripheral blood samples were taken from high- risk neuroblastoma patients, and 103 bone marrow samples and 107 peripheral blood samples were obtained from healthy individuals (control). Seven markers were selected from among the eleven markers that are highly expressed in the cancer stem cells that cause neuroblastoma regrowth/relapse. Using ddPCR, they calculated the levels of these seven markers in the bone marrow and peripheral blood samples.

The research group discovered that they could more accurately diagnose high-risk neuroblastoma patients when calculating the aggregated expression levels of all 7 markers using ddPCR, as opposed to looking at the expression level of each marker individually. The changes in the expression levels of these seven markers reflected the amount of tumors, the stage of illness (remission, stable, or progression) and the sample collection period (diagnosis, treatment, post-treatment, or relapse).

The expression levels of the 7 markers were calculated for 73 bone marrow samples obtained from post-treatment high-risk neuroblastoma patients. The expression levels of the markers in the bone marrow samples of the 17 patients who had suffered tumor relapse/regrowth was significantly higher compared to the levels in the 56 patients who hadn't. By comparing the two PCR methods using the same 73 samples, it was predicted that the expression levels of the seven markers calculated by ddPCR would be able to more accurately predict tumor relapse/regrowth than qPCR.

Based on these results, it is expected that the ddPCR monitoring method developed by this study will improve the monitoring of MRD in high-risk neuroblastoma patients, enabling the possibility of tumor relapse or regrowth to be more accurately predicted.

Further Developments

The results of this research suggest that it is possible to accurately monitor MRD in post-treatment high-risk neuroblastoma patients. Next, this methodology needs to be evaluated through prospective clinical studies on a larger number of patients across multiple hospitals. It is expected that this monitoring method can be used as a basis for predicting patients' prognoses and developing new treatments for high-risk neuroblastoma patients.

Glossary

*1. Droplet digital PCR (ddPCR)

PCR is a technique used to measure the amount of target DNA or RNA in a sample. In ddPCR, the sample is divided into a large number of individual drops prior to the PCR reaction. Compared to real-time PCR, ddPCR is: 1. More sensitive (it can be used to detect extremely low levels of the target), and 2. Reproducible (unlike qPCR it doesn't rely on a calibration curve). It is known as the third generation PCR technique.

*2. Real-time PCR (qPCR)

This PCR enables the detection of amplified DNA or RNA to be monitored and analyzed in real time. It is known as the second generation PCR technique.

*3. AUC (Area Under the Curve)

A ROC (Receiver Operating Characteristic) curve is used for accurate data evaluation and to compare new data. The AUC (Area Under the Curve) is the area underneath a ROC curve on a graph. The AUC has a value between 0 and 1; the closer the value is to 1, the higher the prognosis and diagnosis ability.

Mice born blind have shown significant improvement in vision after undergoing a new gene therapy developed by a team of Japanese scientists.

The results were published on January 24th in Nature Communications.

This new method is an alternative strategy of gene supplementation, which involves supplementing the defective gene, such as the ones that can lead to inherited retinal degeneration, with a healthy one. The healthy gene is delivered via the adeno-associated virus (AAV). However, the virus can only hold only a small healthy gene, and the vast majority of patients with defects in a larger gene cannot be treated with this method.

"To overcome this problem, we developed a single AAV gene therapy platform that allows local replacement of a mutated sequence with its healthy counterpart that can treat almost any mutation," said Koji Nishiguchi, co-first author on the paper and associate professor in the Department of Advanced Ophthalmic Medicine at Tohoku University Graduate School of Medicine.

The single AAV gene therapy platform combines CRISPR-Cas9 technology with micro-homology-mediated end joining. These two thing act essentially as genetic scissors and genetic glue respectively. Researchers can target a specific defective gene, cut it out and glue in a healthy replacement.

In blind mice, this approach rescued approximately 10% of photoreceptors, resulting in improved light sensitivity and an increase in visual activity. The improvement in vision was about the same result gene supplementation can produce.

"By treating mice blinded by inherited retinal degeneration with the new treatment, we show that a robust visual restoration can be achieved at a level similar to that mediated by conventional gene supplementation, assuring its potential for clinical application," Nishiguchi said. "The platform paves the way for treating patients with mutations in larger genes, which comprise the vast majority of those with inherited retinal degeneration. Furthermore, a similar approach can be applied to treat almost any ocular and non-ocular inherited conditions."

Now, the researchers are applying the new genome editing platform to develop a therapy for human patients with retinitis pigmentosa, a group of rare conditions that can cause loss of peripheral vision and difficulty seeing at night. They will target common mutations among patients that remain untreatable by conventional gene therapy. Nishiguchi's team plans to have therapy in a clinical trial by as early as 2025.

Women with high blood pressure in their first pregnancy have a greater risk of heart attack or cardiovascular death, according to a Rutgers study.

The study is published in the Journal of Women's Health.

Approximately 2 to 8 percent of pregnant women worldwide are diagnosed with preeclampsia, a complication characterized by high blood pressure that usually begins after 20 weeks of pregnancy in women whose blood pressure had been normal. Doctors haven't identified a single cause, but it is thought to be related to insufficiently formed placental blood vessels. Preeclampsia is also the cause of 15 percent of premature births in the U.S.

The researchers analyzed cardiovascular disease in 6,360 women, age 18 to 54, who were pregnant for the first time and diagnosed with preeclampsia in New Jersey hospitals from 1999 to 2013 and compared them to pregnant women without preeclampsia. They found that those with the condition were four times more likely to suffer a heart attack or cardiovascular death and more than two times more likely to die from other causes during the 15-year study period.

"Women who were diagnosed with preeclampsia tended also to have a history of chronic high blood pressure, gestational diabetes and kidney disease and other medical conditions," said lead author Mary Downes Gastrich, an associate professor at Rutgers Robert Wood Johnson Medical School and a member of the Cardiovascular Institute of New Jersey.

Gastrich said the study suggests that all women be screened for preeclampsia throughout their pregnancy and that treatment be given to those with preeclampsia within five years after birth. "Medication such as low-dose aspirin also may be effective in bringing down blood pressure as early as the second trimester," she said.

Eric Prossnitz, PhD, and his team hope to help 93 million obese Americans fight their fat.

In a paper published in Science Translational Medicine, they reported that G-1, a cancer-fighting compound they discovered some years ago, reduces fat in obese mice. Although G-1 is currently in phase 1 clinical trials for cancer, Prossnitz and his team are planning preclinical studies to use G-1 to fight fat in obese people.

Obesity affects 40% of adults in the United States, resulting in health conditions that include heart disease, high blood pressure, type 2 diabetes and some cancers. According to the U.S. Centers for Disease Control and Prevention, obesity and its related conditions far outweigh other causes of death. Current drugs for obesity don't effectively reduce it or have undesirable side effects.

Prossnitz and his team have been studying GPER, the G protein-coupled estrogen receptor that G-1 activates, because GPER affects certain breast cancer cells. When breast cancer drugs like tamoxifen and fulvestrant block estrogen receptors in a cell's nucleus, they also activate GPER, which is found in cell membranes.

Prossnitz's previous studies showed that GPER may play a role in resistance to tamoxifen and similar drugs, and that led him to wonder how G-1 affects non-cancerous cells when estrogen is lacking.

Estrogen is considered a female hormone, although men produce it at low levels. Low estrogen in women is a hallmark of menopause, and postmenopausal women also have higher rates of heart disease, high blood pressure, obesity and diabetes. So to understand whether G-1 might affect metabolism in postmenopausal women, Prossnitz and his team studied mice with low estrogen levels.

In their studies, low-estrogen female mice gained weight rapidly, even on a normal diet, and quickly became obese and diabetic. When the researchers treated these obese female mice with G-1, the mice lost weight and their diabetes went away.

The researchers determined that the weight loss wasn't due to the mice eating less or moving around more; it resulted from what their bodies did with the calories they ate. Instead of storing calories as fat, the mice used them as fuel.

"Their metabolism changed," Prossnitz says. "The mice showed an increased energy expenditure."

Prossnitz's team also studied male mice, which have naturally low levels of estrogen. The male mice were fed a high-fat diet, which made them obese and diabetic, and then some were treated with G-1. Although the treated mice did not lose weight, they did not gain additional weight either, like the untreated mice. More importantly, their diabetes improved.

"This result suggests that G-1 has separate effects on obesity and diabetes," Prossnitz says. "The G-1-treated male mice were metabolically healthier, even though they were still obese."

Finally, the team also fed a high-fat diet to low-estrogen female mice. These mice became obese very quickly, but just like their sisters on a normal mouse diet, they lost weight and their diabetes improved when they were treated with G-1. These results, says Prossnitz, could point to a sex difference in the effects of the drug or in the way GPER signals in the cells of males and females.

To learn about how G-1 increases energy expenditure, the team studied brown fat cells, which generate heat instead of storing excess calories as fat. What they found surprised them: when treated with G-1, the cells expended more energy.

"This fits nicely with what we saw in mice," Prossnitz says, "and suggests that G-1 may reduce obesity by targeting brown fat cells that burn extra calories."

In a future series of experiments, Prossnitz plans to study how signals from GPER induce the cellular changes that cause more energy to be used. He hopes that one day soon G-1 could revolutionize the treatment of metabolic disorders.

In the meantime, he and his team are starting the long path toward clinical trials that will test the ability G-1 to fight obesity and diabetes in people.

ANN ARBOR, Mich. - A new study finds that one side effect of lupus could also make patients with the autoimmune condition more vulnerable to a skin infection, or spreading the infection to others.

In the paper, published in the Journal of Investigative Dermatology, researchers found that 50% of skin rashes in patients with lupus contained an abnormally high presence of a common bacteria responsible for skin infections: staphylococcus aureus, or more commonly known as staph.

"Fifty percent of the patients we investigated were colonized by staph, which means the person with the rash is a carrier for the bacteria and can spread it to others," says J. Michelle Kahlenberg, M.D., Ph.D., associate professor of rheumatology at Michigan Medicine and senior author of the paper.

"In addition, we identified that a protein in the skin of patients with lupus, called interferon, increases the stickiness of staph aureus to their skin."

Kahlenberg had already done previous studies into interferons of the skin of patients with lupus.

"Because our previous work has shown the importance of interferons for sensitivity to sunlight and inflammation in lupus, we then wanted to study whether the interferons and staph were linked," she says.

Kahlenberg notes that while skin rashes are a common side effect of lupus, she and her team were surprised by the abnormally high presence of staph colonization on the rashes.

"Using a University of Michigan lupus cohort, we found that patients with lupus had staph colonization on their skin at a rate higher than that reported in healthy adults - 40% compared to 30%," Kahlenberg says. "And when the patients with lupus had active skin rashes or lesions, that rate increased to 50%."

Kahlenberg says the focus on staph bacteria began because it's a leading cause of infection in patients with lupus.

"Others have shown it may be associated with disease flares and development of lupus nephritis, or inflammation of the kidney in patients with lupus," Kahlenberg says.

She is currently enrolling patients in a clinical trial that is testing whether topical antibiotics can decrease inflammation and rashes in the skin of patients with lupus.

"This is important because if true, the addition of topical antibiotics may be a simple way to improve treatment response in lupus skin and reduce the ability for those rashes to be colonized by staph," Kahlenberg says.

A new study led by Texas A&M AgriLife Research scientists shows how a natural compound found in many well-known and widely consumed vegetables can also be used to fight fatty liver disease.

The study demonstrates how non-alcoholic fatty liver disease, or NAFLD, can be controlled by indole, a natural compound found in gut bacteria - and in cruciferous vegetables such as cabbage, kale, cauliflower and Brussels sprouts. It also addresses how this natural compound may lead to new treatments or preventive measures for NAFLD.

The study was recently published in Hepatology and can be found on PubMed.gov.

"Based on this research, we believe healthy foods with high capacity for indole production are essential for preventing NAFLD and are beneficial for improving the health of those with it," said Chaodong Wu, M.D., Ph.D., a Texas A&M AgriLife Research Faculty Fellow and principal investigator for the study. "This is another example where altering the diet can help prevent or treat disease and improve the well-being of the individual."

About NAFLD and indole

NAFLD occurs when the liver becomes "marbled" with fat, sometimes due to unhealthy nutrition, such as excessive intake of saturated fats. If not properly addressed, this condition can lead to life-threatening liver disease, including cirrhosis or liver cancer.

Many diverse factors contribute to NAFLD. Fatty liver is seven to 10 times more common in people with obesity than in the general population. In addition, obesity causes inflammation in the body. Driving this inflammation are macrophages, types of white blood cells that normally battle infection. This inflammation exacerbates liver damage in those with liver disease.

Gut bacteria can also have an effect - either positive or negative -- on the progression of fatty liver disease. These bacteria produce many different compounds, one of which is indole. This product of the amino acid tryptophan has been identified by clinical nutritionists and nutrition scientists as likely having preventive and therapeutic benefits to people with NAFLD.

The National Cancer Institute also notes the benefits of indole-3-carbinol found in cruciferous vegetables, including their anti-inflammatory and cancer-fighting properties.

A comprehensive and multi-level study on fatty liver disease

The present study examined the effect of indole concentrations on people, animal models and individual cells to help determine indole's effect on liver inflammation and its potential benefits to people with NAFLD. It investigated the extent to which indole alleviates non-alcoholic fatty liver disease, incorporating previous findings on gut bacteria, intestinal inflammation and liver inflammation. It also incorporated investigation into how indole improves fatty liver in animal models.

For the study, researchers investigated the effects of indole on individuals with fatty livers. As research collaborator Qifu Li, M.D., was also a physician at Chongqing Medical University in China, the team decided he should lead the clinical research using Chinese participants.

In 137 subjects, the research team discovered people with a higher body mass index tended to have lower levels of indole in their blood. Additionally, the indole levels in those who were clinically obese were significantly lower than those who were considered lean. And in those with lower indole levels, there was also a higher amount of fat deposition in the liver.

This result will likely extend to other ethnicities, Li noted, though ethnic background may have some influence on gut bacteria populations and the exact levels of metabolites.

To further determine the impact of indole, the research team used animal models fed a low-fat diet as a control and high-fat diet to simulate the effects of NAFLD.

"The comparisons of animal models fed a low-fat diet and high-fat diet gave us a better understanding of how indole is relevant to NAFLD," said Gianfranco Alpini, M.D., a study collaborator and former distinguished professor of Texas A&M Health Science Center, now the director of the Indiana Center for Liver Research.

Alpini said treatment of NAFLD-mimicking animal models with indole significantly decreased fat accumulation and inflammation in the liver.

The research team also studied how indole affected individual cells.

Shannon Glaser, M.D., a professor of Texas A&M Health Science Center, said that in addition to reducing the amount of fat in liver cells, indole also acts on cells in the intestine, which send out molecular signals that dampen inflammation.

"The link between the gut and the liver adds another layer of complexity to studies on non-alcoholic fatty liver disease, and future studies are very much needed to fully understand the role of indole," Glaser said.

Additional nutrition research needed

"Foods with a high capacity of indole production or medicines that mimic its effects may be new therapies for treatment of NAFLD," Wu said, adding prevention is another important aspect to consider.

"Preventing NAFLD's development and progression may depend on nutritional approaches to ensure that gut microbes allow indole and other metabolites to function effectively," he said. "Future research is needed to investigate how certain diets may be able to achieve this."

Wu said in future research he hopes to collaborate with food scientists and clinical nutritionists to examine what healthy foods can alter gut microbiota and increase indole production.

What The Study Did: Whether there are differences in treatment of acne by race/ethnicity, sex and type of insurance was the focus of this observational study that analyzed treatment and prescribing patterns for acne for nearly 30,000 patients.

To access the embargoed study: Visit our For The Media website at this link https://media.jamanetwork.com/

Authors: Junko Takeshita, M.D., Ph.D., M.S.C.E., of the Perelman School of Medicine at the University of Pennsylvania in Philadelphia, is the corresponding author.

(doi:10.1001/jamadermatol.2019.4818)

Editor's Note: The article includes conflict of interest and funding/support disclosures. Please see the article for additional information, including other authors, author contributions and affiliations, financial disclosures, funding and support, etc.

CHICAGO --- Paternal involvement can have positive health impacts for a mother and her baby, according to a new study by Northwestern Medicine and the Centers for Disease Control and Prevention (CDC).

The study found unmarried mothers - with or without an acknowledgement of paternity (AOP) - a document signed by unmarried parents to establish the child's legal father - are more likely to engage in health-risk behaviors and less likely to engage in protective health behaviors around the time of pregnancy compared to married mothers. The study used information from birth certificates to measure marital status and AOPs for unmarried mothers.

Unmarried women are less likely to have prenatal care during the first trimester of pregnancy, to ever breastfeed, to breastfeed at least eight weeks and are more likely to drink alcohol and smoke during and after pregnancy. The frequency for any of these outcomes was even greater when the mother was both unmarried and an acknowledgement of paternity was not completed.

The paper was published Feb. 5 in the journal Public Health Reports.

"The period of time when a woman is pregnant and eventually delivers her baby (the perinatal period) is a significant period of time because the health behaviors she adopts can impact her health and that of the baby," said co-author Dr. Craig Garfield, professor of pediatrics and medical social sciences at Northwestern University Feinberg School of medicine and a physician at Ann & Robert H. Lurie Children's Hospital of Chicago.

Not much is known about how the presence of a father affects families and children, especially for unmarried couples having kids, which represents about 40% of U.S. births today. This study aimed to gain more insight in this area.

The study analyzed data from 32 Pregnancy Risk Assessment Monitoring System (PRAMS) sites from 2012 to 2015 and a total of 113,020 participants. PRAMS is an ongoing state-based surveillance system of maternal behaviors, attitudes and experiences before, during and shortly after pregnancy.

It did not analyze parental involvement in same-sex couples because the data used in the study was from statewide databases that acknowledge paternity - not parenting - roles. Garfield said more research is needed on how the support of any partner - man or woman - impacts the health of the mother and baby.

The study's findings could help motivate doctors who care for children and families to explore the status and quality of the parents' relationship, Garfield said.

"Let's say a mom attends health care visits alone. Simply asking about the home situation and level of paternal involvement may provide insight into the need for assistance or support," Garfield said. "In contrast, if both parents attend the visit together, this visit may serve as an opportunity to engage fathers on the importance of their role in their child's well-being, and to educate and support them in their transition to parenthood."

By identifying paternal presence during this period, physicians could develop and tailor appropriate interventions and practices based on parental relationship dynamics to improve the health of the baby, Garfield said.

"We know that health-risk maternal behaviors during pregnancy and after delivery can increase the risk of adverse infant health outcomes," said lead author Katherine Kortsmit in the Division of Reproductive Health at the CDC. "While we weren't able to directly assess paternal involvement with the data available, this study suggests that engaging fathers and paternal figures may help improve maternal health behaviors around the time of pregnancy."

UNIVERSITY PARK, Pa. -- Applying for a job? Don't come across as self-absorbed on your Facebook page. Don't express your strong views on potentially controversial topics either. According to researchers at Penn State, job recruiters are less likely to select candidates who appear to be too self-involved or opinionated in their social media posts. The team also found that recruiters are less likely to hire employees who post content suggestive of drug or alcohol use.

"In 2018, 70% of employers reported looking at social media sites to help them evaluate potential employees, and almost that many -- 60% -- eliminated candidates on the basis of negative content," said Michael Tews, associate professor of hospitality management, citing a recent report by CareerBuilder. "It's important for job candidates to be aware of how they portray themselves in social media."

Tews noted that little is known about how much weight hiring managers give to potentially negative social media content. Therefore, he and his colleagues investigated the effects of three potentially negative topics--self-absorption, opinionatedness and alcohol and drug use--on hiring managers' decision making.

The team recruited 436 hiring managers from a variety of organizations, 61% of whom were employed in the hospitality industry and the remainder in industries ranging from information technology to healthcare. The researchers gave participants a scenario to read depicting a hypothetical job candidate who answered interview questions well and exhibited enthusiasm, but also appeared to be prone to job hopping. Next, they asked the participants to review components of the candidates Facebook profiles and to rate their employment suitability.

Each of the participants was randomly assigned to view one of 16 different Facebook profiles showing either a male or female exhibiting self-absorption or not, opinionatedness or not and alcohol and drug use or not. After reading these profiles, the hiring managers evaluated the candidates' employment suitability by providing an assessment of person-organization fit and an overall candidate evaluation. The team's results appeared on Dec. 10 in the International Journal of Selection and Assessment.

The researchers found that self-absorption negatively impacted recruiters' perceptions of candidates' employment suitability and that self-absorption was more important than opinionatedness or drug and alcohol use in driving these negative perceptions.

"Social networking sites are often lamented as incubators of self-absorption, motivating people to tell others about their every deed and thought," said Tews. "It could be that hiring managers view individuals who are more self-absorbed and focused on their own interests to be less likely to sacrifice for the benefit of other employees and the organization."

The team also found that opinionatedness negatively affected perceptions of employment suitability.

"Social networking sites have given rise to unprecedented numbers of individuals expressing extreme and controversial ideas in a public forum," said Tews. "People who post divisive subject matter may be viewed as more argumentative and less cooperative. Additionally, their views could run counter to those of hiring managers, which may influence managers' beliefs in candidates' qualifications for jobs."

Finally, the team found that content suggesting alcohol and drug use negatively affected hiring managers' perceptions of employment suitability, although the effect was much smaller than for self-absorption and opinionatedness.

"The social media content we showed hiring managers was fairly benign; there was no reference to binge drinking or actual drug use," said Tews. "One possible reason for the relatively small effect alcohol and drug use content is that hiring managers may perceive the content as relatively normal. It is also possible that people have become accustomed to references to marijuana in the United States as more states have legalized its consumption for both medicinal and recreational use."

The researchers conclude that individuals should refrain from posting content on social networking sites that suggest self-absorption, opinionatedness and alcohol and drug use during the job search process.

"From the employer perspective, hiring managers should be trained on how best to use social networking content in making selection decisions," said Tews. "To maximize the benefit of using social networking content for selection purposes, organizations should set guidelines for what content is relevant and should be examined, specify what content is irrelevant and potentially discriminatory and develop standardized rating systems to make the evaluation process more objective."

INDIANAPOLIS - Universal early screening for autism is recommended for all children but is not routinely performed. A new study from Regenstrief Institute and Indiana University School of Medicine researchers, published in JAMA Network Open, reports that the system they designed and developed called CHICA (short for Child Health Improvement through Computer Automation), increased the autism screening rate at 24 months of age from zero to 100 percent.

CHICA is a computerized decision support tool that can interface with any electronic health record (EHR) system. Responses to questions entered on a tablet computer by parents in the waiting room alert CHICA to produce personalized, evidence-based recommendations allowing the pediatrician to focus on what the specific patient really needs. CHICA may highlight the need for screening for autism, depression, diabetes, tuberculosis, or anemia, counseling for the parents on smoking or on proper child car seat installation.

"The dramatic increase in autism screening by physicians during our trial was achieved because, with CHICA, we have completely automated the screening process, potentially making a difference for so many children and their families," said Regenstrief Research Scientist Stephen Downs, M.D., Jean and Jerry Bepko Professor of Pediatrics at IU School of Medicine, who led the study and is the founder of CHICA. "We know that children on the autism spectrum can be identified as young as 18 months; with CHICA we can get them evaluated and enrolled in early intervention programs which could improve their lives and save society millions, perhaps billions, of dollars."

The likelihood of benefit for a child who is referred for applied behavioral analysis (ABA) after an autism diagnosis decreases with age. Currently, the mean age of autism diagnosis for all children in the United States is four and a half years, more than two and a half years later than optimal, according to Dr. Downs.

"Autism rates do not vary by race or ethnicity, but autism is underdiagnosed or diagnosed later in life in underrepresented racial and ethnic minorities in the U.S," he said. "Automating the screening process as we did with CHICA avoids these kinds of biases and decreases health inequities." A majority of the children in the study were African American or Hispanic.

CHICA provides an action trigger, communicating with the child's EHR, analyzing the child's demographics, diagnoses and medications and then selecting the 20 highest-priority yes or no questions covering a wide range of primary care issues to ask the family in English or Spanish.

CHICA analyzes the responses to these questions, conducts a tailored health risk assessment and determines the six most important prompts for the physician. These are assembled into a patient's current visit agenda for the doctor and stored for future decision support.

CHICA also includes a library of handouts (autism, lead exposure, adolescent depression screening and infant car seat installation are among the topics covered) that can be printed as needed for dissemination to parents, based on the individualized issues of particular concern identified by CHICA.

There is still much more work to be done. The new study also found that while CHICA increased screening to 100 percent, the continuation of the process, requiring a human (the physician) to follow through with a post-screening referral for diagnostic evaluation, turned out to be the weak link. In the study only slightly more than half (57 percent) of those children who screened positive for autism were referred for further evaluation.

Dr. Downs believes that automating the referral process through CHICA provides a solution to the low number of physician referrals for appropriate further evaluation. "We built CHICA to optimize care. We call it an 'everything system' because it has a universe of guidelines and is able to sort out which ones are of most value to the specific patient and prioritize these items," he said. "But CHICA could also automate the referral process for diagnostic evaluation so more young children with autism are identified and can get early ABA therapy that can result in significant increases in IQ, even into the normal range with improved likelihood of mainstreaming in school."

The Centers for Disease Control and Prevention (CDC) estimates prevalence of autism spectrum disorders in 2014 to be one in 59 eight-year-olds in the U.S. The American Academy of Pediatrics recommends that toddlers be routinely screened for autism during their 18- and 24-month doctor visits.

"Effect of a Computer-Based Decision Support Intervention on Autism Spectrum Disorder Screening in Pediatric Primary Care Clinics" is published in JAMA Network Open. The cluster randomized clinical trial was conducted in urban pediatric clinics to determine whether computer-automated screening and clinical decision support built into an existing EHR system improves autism screening rates.

Authors of the study, in addition to Dr. Downs, are Nerissa S. Bauer, M.D., MPH, formerly of IU School of Medicine and now with Axon Health Associates; Chandan Saha, Ph.D. and Susan Ofner, M.S., of IU School of Medicine and Aaron E. Carroll, M.D., M.S. of Regenstrief Institute and IU School of Medicine. They note in the paper that, "Too often, there are insufficient resources available to make proper diagnoses of ASD and even fewer resources available to treat children with a diagnosis of ASD. Improving those factors will be necessary to improve the outlook of the many children in the United States who have ASD."

An International Journal of Cancer study that examined lung cancer rates in young adults in 40 countries across five continents uncovered a trend of higher lung cancer rates in women compared with men in recent years.

The emerging trend was widespread, affecting countries across varied geographic locations and income levels. The changes appeared to be driven by a rising rate of adenocarcinoma lung cancer among women.

Historically, lung cancer rates have been higher among men than women because men started smoking in large numbers earlier and smoked at higher rates; however, recent studies have reported converging lung cancer incidence rates between sexes.

Additional research is needed to identify the reasons for the elevated incidence of lung cancer among young women observed in this study.

As the population ages, the number of cancer patients with dementia has increased. A recent study published in Geriatrics & Gerontology International found that cancer patients with dementia were less likely to achieve a "good death" than those without.

In the study, quality of death was measured from nurses' reports and factored in life completion, place of death, and symptom management.

Of the 508 patients with cancer in the study, 156 (30.7%) had dementia. Dementia was associated with a reduced quality of death among patients.

The study's authors note that it may be difficult to confirm patients' end-of-life preferences because of cognitive decline. Their findings point to the importance of enhancing end-of-life care discussions with patients and their families.

"In order to provide high quality of end-of-life care, we should facilitate end-of-life care discussions and improve symptom management especially for cancer patients with dementia," said lead author Kayo Hirooka, RN, PhD, of Keio University, in Japan.