Character Sweet of Kurian Fudodo (栗庵風味堂) in Nagano, Japan

Hello Kitty Monaka

The sweet is designed to hang on the edge of cups. It has either chestnut or bean paste filling.

Black Cod with Miso

Ingredients

3 tablespoons mirin
3 tablespoons sake
1/2 cup white miso paste
1/3 cup sugar
6 (6 to 7 ounce) skinless black cod fillets (about 1-1/2 inches thick)
vegetable oil, for grilling
sauteed baby bok choy and pickled ginger, for serving

Method

  1. In a small saucepan, bring the mirin and sake to a boil. Whisk in the miso until dissolved. Add the sugar and cook over moderate heat, whisking, just until dissolved.
  2. Transfer the marinade to a large baking dish and let cool.
  3. Add the fish and turn to coat. Cover and refrigerate overnight.
  4. Preheat the oven to 400°F.
  5. Heat a grill pan and oil it. Scrape the marinade off the fish. Add the fish and cook over high heat until browned, about 2 minutes.
  6. Flip the fish onto a heavy rimmed baking sheet and roast for 10 minutes, until flaky. Transfer to plates and serve with pickled ginger and sauteed baby bok choy.

Makes 6 servings.

Source: Chef Nobu Matsuhisa

Thyroid Hormone Use May Raise Death Risk in Older Adults

Thyroid hormone replacement therapy in older adults is associated with a higher risk of death compared with no treatment, a large study finds. The study results were accepted for presentation at ENDO 2020, the Endocrine Society’s annual meeting, and publication in a special supplemental section of the Journal of the Endocrine Society.

When people have too little thyroid hormone, called hypothyroidism, they usually require lifelong treatment with levothyroxine to supplement the body’s thyroid hormone, thyroxine (T4). Some people have subclinical hypothyroidism, which occurs when the thyroid gland needs more stimulation to produce adequate thyroid hormone levels. These individuals will have modest elevations in thyroid-stimulating hormone (TSH), which stimulates thyroid hormone production.

Subclinical hypothyroidism is a mild or early form of thyroid disease, and these patients also routinely receive thyroid hormone replacement, said the study’s principal investigator, Jennifer Mammen, M.D., Ph.D., an assistant professor at Johns Hopkins University in Baltimore, Md. However, Mammen notes that this interpretation of high TSH with normal T4 levels may not be correct in all older adults.

“Many older adults have an elevation in TSH with normal thyroid levels. Our earlier research showed that this can reflect developing hypothyroidism in some, while in others, it is a form of adaptation to age-related changes in health instead of thyroid disease,” Mammen said. “As a result, some of these older people may be receiving inappropriate or excessive thyroid hormone therapy, treatment that may counteract important adaptations needed for healthy aging.”

The researchers studied the effects of levothyroxine therapy on survival in adults ages 65 and older. They used data from 1,054 participants of the Baltimore Longitudinal Study of Aging, a long-running observational study from the National Institute on Aging. All participants had at least one TSH and T4 measurement since 2003. Mammen’s research team looked at the risk of dying during one-year intervals from 2003 to 2018 and adjusted their statistical analyses for multiple demographic and health factors that may influence survival.

They found that among older adults, use of thyroid hormone increased risk of death 60% year over year (hazard ratio 1.6). They also limited the analysis to compare individuals with normal TSH levels, reflecting normal thyroid function, to those on thyroid hormone with normal TSH levels, who were therefore treated to target, and found those on treatment had almost double the risk of dying compared with untreated persons (hazard risk 1.9), Mammen reported.

Despite studies showing that hormone treatment of an isolated high TSH may not benefit older people, Mammen said, “we were surprised that we were able to demonstrate harm associated with thyroid hormone supplementation. Our work supports the growing calls to use age-specific TSH reference intervals to determine the threshold for thyroid hormone treatment.”

Mammen also recommended repeating testing after finding an isolated elevation of TSH in older adults, because levels can fluctuate. “We advocate being cautious and conservative when considering thyroid hormone treatment,” she said.

Source: Endocrine Society

Discovery of New Biomarker in Blood Could Lead to Early Test for Alzheimer’s Disease

Liezel Labios wrote . . . . . . . . .

Researchers at the University of California San Diego discovered that high blood levels of RNA produced by the PHGDH gene could serve as a biomarker for early detection of Alzheimer’s disease. The work could lead to the development of a blood test to identify individuals who will develop the disease years before they show symptoms.

The team published their findings in Current Biology.

The PHGDH gene produces RNA and proteins that are critical for brain development and function in infants, children and adolescents. As people get older, the gene typically ramps down its production of these RNAs and proteins. The new study, led by Sheng Zhong, a professor of bioengineering at the UC San Diego Jacobs School of Engineering in collaboration with Dr. Edward Koo, a professor of neuroscience at the UC San Diego School of Medicine, suggests that overproduction of a type of RNA, called extracellular RNA (exRNA), by the PHGDH gene in the elderly could provide an early warning sign of Alzheimer’s disease.

“Several known changes associated with Alzheimer’s disease usually show up around the time of clinical diagnosis, which is a little too late. We had a hunch that there is a molecular predictor that would show up years before, and that’s what motivated this study,” Zhong said.

The discovery was made possible thanks to a technique developed by Zhong and colleagues that is sensitive enough to sequence tens of thousands of exRNAs in less than one drop of blood. The method, dubbed SILVER-SEQ, was used to analyze the exRNA profiles in blood samples of 35 elderly individuals 70 years and older who were monitored up to 15 years prior to death. The subjects consisted of 15 patients with Alzheimer’s disease; 11 “converters,” which are subjects who were initially healthy then later developed Alzheimer’s; and 9 healthy controls. Clinical diagnoses were confirmed by analysis of post-mortem brain tissue.

The results showed a steep increase in PHGDH exRNA production in all converters approximately two years before they were clinically diagnosed with Alzheimer’s. PHGDH exRNA levels were on average higher in Alzheimer’s patients. They did not exhibit an increasing trend in the controls, except for in one control that became classified as a converter.

The researchers note some uncertainty regarding the anomalous converter. Since the subject died sometime during the 15-year monitoring, it is unclear whether that individual would have indeed developed Alzheimer’s if he or she lived longer, Zhong said.

The team acknowledges additional limitations of the study.

“This is a retrospective study based on clinical follow-ups from the past, not a randomized clinical trial on a larger sample size. So we are not yet calling this a verified blood test for Alzheimer’s disease,” said co-first author Zixu Zhou, a bioengineering alumnus from Zhong’s lab who is now at Genemo Inc., a startup founded by Zhong. “Nevertheless, our data, which were from clinically collected samples, strongly support the discovery of a biomarker for predicting the development of Alzheimer’s disease.”

In addition to randomized trials, future studies will include testing if the PHGDH biomarker can be used to identify patients who will respond to drugs for Alzheimer’s disease.

The team is also open to collaborating with Alzheimer’s research groups that might be interested in testing and validating this biomarker.

“If our results can be replicated by other centers and expanded to more cases, then it suggests that there are biomarkers outside of the brain that are altered before clinical disease onset and that these changes also predict the possible onset or development of Alzheimer’s disease,” Koo said. “If this PDGDH signal is shown to be accurate, it can be quite informative for diagnosis and even treatment response for Alzheimer’s research.”

Source: UC San Diego

FDA Pulls Heartburn Drug Zantac From Market

All versions of the heartburn drug Zantac (ranitidine) have been pulled from the U.S. market due to possible contamination with a probable cancer-causing chemical, the U.S. Food and Drug Administration said Wednesday.

This is the latest step in an ongoing investigation of N-Nitrosodimethylamine (NDMA) in ranitidine medications, the agency noted.

In some ranitidine products, NDMA increases over time and when the drugs are stored at higher temperatures, which may result in people being exposed to unacceptable levels of the chemical, according to the FDA.

The agency’s order for immediate withdrawal of all ranitidine products means they won’t be available either by prescription or over-the-counter (OTC) in the United States.

“Today’s action requesting companies to withdraw all remaining ranitidine products the U.S. market is being taken out of an abundance of caution,” Dr. Janet Woodcock, director of the FDA’s Center for Drug Evaluation and Research, said in an agency news briefing on Wednesday.

“Even though these products when they come off the factory line don’t contain unacceptable levels of (NDMA), we don’t know if they’re stored under various conditions what will end up at the end of the day,” she explained.

According to Woodcock, storage temperature appears to be key to the accumulation of NDMA in ranitidine.

“With ranitidine, the NDMA does not appear to be formed during manufacturing, but instead appears over time in storage, especially when stored at higher than room temperature,” she said. Packaging or specific formulations of the drug might play a role, too.

All of that means that the buildup of NDMA in stored Zantac “may be a fixable problem,” she told reporters. “We’re open to companies demonstrating that they’ve reformulated their product in a way that is stable.”

But for now, consumers taking OTC ranitidine should stop taking any tablets or liquid they have, dispose of them properly and not buy more. Those who want to continue treating their condition should consider using other approved OTC products, the FDA recommended.

Patients taking prescription ranitidine should talk with their health care provider about other treatment options before they stop taking the medicine, the FDA said. There are multiple drugs approved for the same or similar uses as ranitidine that don’t have risks from NDMA.

FDA tests have not found NDMA in famotidine (Pepcid), cimetidine (Tagamet), esomeprazole (Nexium), lansoprazole (Prevacid) or omeprazole (Prilosec).

Due to the current coronavirus pandemic, people shouldn’t take their ranitidine medications to a drug take-back location, the FDA noted. Follow the disposal instructions in the medication guide or package insert, or follow the FDA’s recommendations on how to safely dispose of the medications at home, the agency said.

NDMA is an environmental contaminant that can be found in water and foods and has been classified as a “probable human carcinogen” by the World Health Organization.

The presence of NDMA in minute quantities has already led to the recall of many types of blood pressure medications, such as valsartan and losartan.

NDMA’s potential presence in Zantac and generic versions of ranitidine was first reported in September 2019.

Source: HealthDay


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