Stress cardiomyopathy as a cardiovascular manifestation of COVID-19.

Patients with coronavirus disease 2019 (COVID-19) may present with a broad spectrum of clinical manifestations, affecting several organ systems. Predominant cardiac manifestations include myocardial injury, heart failure, cardiogenic shock, and arrhythmias. Stress (takotsubo) cardiomyopathy, characterized by apical ballooning of the heart leading to acute left ventricular dysfunction, is rarely seen in patients with COVID-19. We present a case of COVID-19-associated stress cardiomyopathy in a female in her sixties.

Sugars and Sweet Taste: Addictive or Rewarding?

The notion of food "addiction" often focuses on the overconsumption of sweet tasting foods or so-called sugar "addiction". In the extreme, some have suggested that sugar and sweet tastes elicit neural and behavioral responses analogous to those observed with drugs of abuse. These concepts are complicated by the decades long uncertainty surrounding the validity and reproducibility of functional magnetic resonance imaging (fMRI) methodologies used to characterize neurobiological pathways related to sugar and sweet taste stimuli. There are also questions of whether sweet taste or post-ingestion metabolic consequences of sugar intake would lead to addiction or excessive caloric intake. Here, we present a focused narrative review of literature related to the reward value of sweet taste which suggests that reward value can be confounded with the construct of "addictive potential". Our review seeks to clarify some key distinctions between these constructs and questions the applicability of the addiction construct to human over-eating behaviors. To adequately frame this broad discussion requires the flexibility offered by the narrative review paradigm. We present selected literature on: techniques used to link sugar and sweet tastes to addiction neurobiology and behaviors; sugar and sweet taste "addiction"; the relationship of low calorie sweetener (LCS) intake to addictive behaviors and total calorie intake. Finally, we examined the reward value of sweet tastes and contrasted that with the literature describing addiction. The lack of reproducibility of fMRI data remains problematic for attributing a common neurobiological pathway activation of drugs and foods as conclusive evidence for sugar or sweet taste "addiction". Moreover, the complicated hedonics of sweet taste and reward value are suggested by validated population-level data which demonstrate that the consumption of sweet taste in the absence of calories does not increase total caloric intake. We believe the neurobiologies of reward value and addiction to be distinct and disagree with application of the addiction model to sweet food overconsumption. Most hypotheses of sugar "addiction" attribute the hedonics of sweet foods as the equivalent of "addiction". Further, when addictive behaviors and biology are critically examined in totality, they contrast dramatically from those associated with the desire for sweet taste. Finally, the evidence is strong that responses to the palatability of sweets rather than their metabolic consequences are the salient features for reward value. Thus, given the complexity of the controls of food intake in humans, we question the usefulness of the "addiction" model in dissecting the causes and effects of sweet food over-consumption.

Outbreak of Severe Vomiting in Dogs Associated with a Canine Enteric Coronavirus, United Kingdom.

The lack of population health surveillance for companion animal populations leaves them vulnerable to the effects of novel diseases without means of early detection. We present evidence on the effectiveness of a system that enabled early detection and rapid response a canine gastroenteritis outbreak in the United Kingdom. In January 2020, prolific vomiting among dogs was sporadically reported in the United Kingdom. Electronic health records from a nationwide sentinel network of veterinary practices confirmed a significant increase in dogs with signs of gastroenteric disease. Male dogs and dogs living with other vomiting dogs were more likely to be affected. Diet and vaccination status were not associated with the disease; however, a canine enteric coronavirus was significantly associated with illness. The system we describe potentially fills a gap in surveillance in neglected populations and could provide a blueprint for other countries.

A Progressive Nutrient Profiling System to Guide Improvements in Nutrient Density of Foods and Beverages.

Improving the nutrient density of processed foods is one way to bring the global food supply closer to the WHO Sustainable Development Goals. Nutrient profiling (NP) has emerged as the preferred method of monitoring the progress toward product innovation and reformulation. This paper presents PepsiCo Nutrition Criteria (PNC), a new internal NP model that was designed to guide and monitor improvements in nutrient density and overall nutritional quality of foods and beverages. The new PNC NP model assigns food products into four classes of increasing nutritional value, based on the content of nutrients to limit, along with nutrients and ingredients to encourage. The nutrient standards used for category assignment followed those developed by global dietary authorities. Standards are proposed for calories, sodium, added sugars, saturated, and industrially produced trans fats. Also included are minimum values for food groups to encourage, low-fat dairy, and for country-specific gap nutrients. Internal use of the NP model has spurred product changes that are consistent with WHO goals for industry transparency. An audited review of company products showed that 48% met added sugar, 65% met sodium, and 71% met saturated fat goals. By the end of 2020, in the top 26 regions in which products are sold, 48% of the total sales volume of global beverages had 100 kcal or less from added sugars per 355 ml serving representing 80% of beverage volume and over 90% of food volume sold globally. The PNC NP model is not consumer-facing but is specifically intended for internal use to motivate stepwise and incremental product innovation and reformulation. Transparent and published NP models further WHO goals of engaging industry stakeholders in the (re)formulation of processed foods and beverages consistent with public health goals.

Daily Eating Frequency in US Adults: Associations with Low-Calorie Sweeteners, Body Mass Index, and Nutrient Intake (NHANES 2007-2016).

Studies of relationships between eating frequency and/or timing and energy intake have not examined associations with low-calorie sweeteners (LCS). We assessed the frequency of eating behavior related to LCS consumption emphasizing timing, calorie intake, and body mass index (BMI) among United States (US) adults aged ≥19 years. Using the National Health and Nutrition Examination Survey (NHANES) 2007-2016, we defined eating episodes as food and/or beverage intake within 15 min of one another over the first 24-h dietary recall. We coded items ingested during episodes (n = 136,938) and assessed LCS presence using US Department of Agriculture (USDA) food files. Episode analysis found intakes of foods only (27.4%), beverages only (29.5%), and foods with beverages (43.0%). LCS items were consumed without concurrent calories from other sources in fewer than 2.7% of all episodes. Within participants having normal weight (29.4%), overweight (33.6%) and obese (37.1%) BMIs, LCS consumers (35.2% overall) evidenced: more episodes/day; and fewer: calories, carbohydrates, fats, and protein per episode. Per person, those consuming LCS had lower total calories and higher fiber intake per day. LCS consumption was associated with higher BMI. Number of eating episodes/day and longer hours when eating episodes occurred were also consistently associated with higher BMI. Consuming LCS did not modify these relationships. These results did not show that LCS consumption was associated with increased caloric intake from other dietary sources.

The Role of Gender, Academic Affiliation, and Subspecialty in Relation to Industry Payments to Orthopaedic Surgeons.

BACKGROUND: The Physician-Payments-Sunshine-Act (PPSA) was introduced in 2010 to provide transparency regarding physician-industry payments by making these payments publicly available. Given potential ethical implications, it is important to understand how these payments are being distributed, particularly as the women orthopaedic workforce increases. The purpose of this study was thus to determine the role of gender and academic affiliation in relation to industry payments within the orthopaedic subspecialties. METHODS: The PPSA website was used to abstract industry payments to Orthopaedic surgeons. The internet was then queried to identify each surgeon's professional listing and gender. Mann-Whitney U, Chi-square tests, and multivariable regression were used to explore the relationships. Significance was set at a value of P < 0.05. RESULTS: In total, 22,352 orthopaedic surgeons were included in the study. Payments were compared between 21,053 men and 1299 women, 2756 academic and 19,596 community surgeons, and across orthopaedic subspecialties. Women surgeons received smaller research and non-research payments than men (both, P < 0.001). There was a larger percentage of women in academics than men (15.9% vs 12.1%, P < 0.001). Subspecialties with a higher percentage of women (Foot & Ankle, Hand, and Pediatrics) were also the subspecialties with the lowest mean industry payments (all P < 0.001). Academic surgeons on average, received larger research and non-research industry payments, than community surgeons (both, P < 0.001). Multivariable linear regression demonstrated that male gender (P = 0.006, P = 0.029), adult reconstruction (both, P < 0.001) and spine (P = 0.008, P < 0.001) subspecialties, and academic rank (both, P < 0.001) were independent predictors of larger industry research and non-research payments. CONCLUSIONS: A large proportion of the US orthopaedic surgeon workforce received industry payments in 2014. Academic surgeons received larger payments than community surgeons. Despite having a larger percentage of surgeons in academia, women surgeons received lower payments than their male counterparts. Women also had a larger representation in the subspecialties with the lowest payments.

Preoperative liking and wanting for sweet beverages as predictors of body weight loss after Roux-en-Y gastric bypass and sleeve gastrectomy.

BACKGROUND/OBJECTIVES: Patients who receive Roux-en-Y gastric bypass (RYGB) lose more weight than those who receive vertical sleeve gastrectomy (VSG). RYGB and VSG alter hedonic responses to sweet flavor, but whether baseline differences in hedonic responses modulate weight loss after RYGB or VSG remains untested. PARTICIPANTS/METHODS: Male and female candidates (n = 66) for RYGB or VSG were recruited and tested for their subjective liking and wanting ratings of sucrose solutions and flavored beverages sweetened with aspartame. Participants were classified by unsupervised hierarchical clustering for their liking and wanting ratings of sucrose and aspartame. Participant liking ratings were also used in a supervised classification using pre-established categories of liking ratings (liker, disliker, and inverted u-shape). Effects of categories obtained from unsupervised or supervised classification on body weight loss and their interaction with surgery type were analyzed separately at 3 and 12 months after surgery using linear models corrected for sex and age. RESULTS: RYGB participants lost more body weight compared with VSG participants at 3 and 12 months after surgery (P < 0.001 for both time points). Unsupervised clustering analysis identified clusters corresponding to high and low wanting or liking ratings for sucrose or aspartame. RYGB participants in high-wanting clusters based on sucrose, but not aspartame, lost more weight than VSG at both 3 (P = 0.01) and 12 months (P = 0.03), yielding a significant cluster by surgery interaction. Categories based on supervised classification using liking ratings for sucrose or aspartame showed no significant effects on body weight loss between RYGB and VSG participants. CONCLUSIONS: Classification of patients into high/low-wanting ratings for sucrose before surgery can predict differential body weight loss after RYGB or VSG in adults and could be used to advise on surgery type.

Low-Calorie Sweeteners in Foods, Beverages, and Food and Beverage Additions: NHANES 2007-2012.

BACKGROUND: Most publications about low-calorie sweeteners (LCSs) focus on person-level intake prevalence. OBJECTIVE: We assessed LCS distribution in foods, beverages, and food and beverage additions (FBAs), e.g., mayonnaise, in the US adult diet as reported in the NHANES (2007-2012). METHODS: Dietary items reported in the first 24-h recall were coded for LCS and/or nutritive sweeteners (NSs) with the use of USDA What We Eat in America food files. We calculated the number of times items were reported and LCS/NS content. RESULTS: Of reported items, 56.1% were foods, 29.1% were beverages, and 14.8% were FBAs. LCS was contained in 0.7% of foods, 8.1% of beverages, and 10.4% of FBAs. This food-level analysis identified FBAs as a significant source of LCSs in the US diet. CONCLUSION: Identifying the diversity of LCS and NS sources will enhance exposure classification for examining diet and health relations, including body weight management.

Low-Calorie Sweeteners: Exploring Underutilized Database Resources to Understand Dietary Patterns and Obesity.

The use and impact of low-calorie sweeteners (LCS) in relation to the national challenges of overweight and obesity are complex and controversial. Most research on LCS have focused on the prevalence of consumption of LCS in beverages. The 2015 Dietary Guidelines Advisory Committee emphasized dietary patterns and health rather than a focus on specific nutrients or foods. The committee took this approach to shift the national emphasis onto the context of total rather than individual nutrient consumption. A broader research paradigm is needed to elucidate the actual exposure to LCS and how they are consumed within dietary patterns in the US population. National-level databases exist that can be used to broaden scientific understanding of the effects of LCS and health outcomes. These databases are underutilized, and they provide potential tools for grasping a fuller picture of LCS in the US diet.

Reported Consumption of Low-Calorie Sweetener in Foods, Beverages, and Food and Beverage Additions by US Adults: NHANES 2007-2012.

BACKGROUND: Low-calorie sweeteners (LCSs), artificial sweeteners, or high-intensity sweeteners are incorporated into foods, beverages, and food and beverage additions (FBAs). Many prior studies have focused on LCS beverage consumption, but not included LCS consumption from foods or FBAs. OBJECTIVES: We aimed to describe the prevalence of LCS consumption by US adults, and to examine the relation between intake of products containing LCSs and macronutrients. METHODS: Two nonconsecutive 24-h dietary recalls from NHANES 2007-2012 and the National Cancer Institute usual intake method were used to estimate prevalence of LCS intake from foods, beverages, and FBAs, and macronutrients among US adults aged ≥19 y (n = 14,098, weighted n = 218,391,752) in a cross-sectional study. The prevalence of LCS consumption from reported foods, beverages, and FBAs among US adults was examined by sociodemographic characteristics and body mass index (BMI). Logistic regression estimated ORs and 95% CIs for associations between sociodemographic characteristics and LCS use (overall and in foods, beverages, and FBAs). RESULTS: Among adults, 47.8% reported intake of ≥1 food, beverage, or FBA containing LCSs over 2 d. Intake was higher among: women non-Hispanic whites, college graduates or higher, and those with higher income and obese BMIs (P < 0.001). Intake of beverages containing LCSs was higher for ages 51-70 y than 19-30 y and those with overweight and obese BMIs (P < 0.001) than for normal-weight individuals. Calories, carbohydrate, and sugar intake were lower and fiber was higher in LCS-consumers than in nonconsumers. Specifically, calories from beverages were lower in those who reported LCS intake. CONCLUSIONS: Individuals reporting LCS consumption demonstrated lower total energy intake than did individuals without LCS intake. Although the main source of LCSs in the US adult diet was beverages (31.9%), we found that FBAs also present a significant contribution (25.2%), surpassing food (9.3%). This enables targeted understanding of national consumption of these products as well as dietary education and intervention opportunities.

Copper Chelation Inhibits BRAFV600E-Driven Melanomagenesis and Counters Resistance to BRAFV600E and MEK1/2 Inhibitors.

MEK1/2 and BRAFV600E inhibitors are used to treat BRAFV600E-positive melanoma, with other cancers under evaluation. Genetic perturbation of copper import or pharmacologic reduction of copper with the clinical copper chelator TTM inhibits MEK1/2 kinase activity and reduces BRAFV600E-driven tumorigenesis. In this study, we report that TTM inhibited transformed growth of melanoma cell lines resistant to BRAF or MEK1/2 inhibitors and enhanced the antineoplastic activity of these inhibitors. TTM also provided a survival advantage in a genetically engineered mouse model of melanoma, and when accounting for putative overdosing, trended toward an increase in the survival benefit afforded by BRAF inhibition. This effect was phenocopied by genetically inhibiting copper import in tumors, which was linked to a reduction in MAPK signaling. Thus, TTM reduces copper levels and MAPK signaling, thereby inhibiting BRAFV600E-driven melanoma tumor growth. These observations inform and support clinical evaluation of TTM in melanoma. Cancer Res; 77(22); 6240-52. ©2017 AACR.

Cyclin E1 and RTK/RAS signaling drive CDK inhibitor resistance via activation of E2F and ETS.

High-grade serous ovarian cancers (HGSOC) are genomically complex, heterogeneous cancers with a high mortality rate, due to acquired chemoresistance and lack of targeted therapy options. Cyclin-dependent kinase inhibitors (CDKi) target the retinoblastoma (RB) signaling network, and have been successfully incorporated into treatment regimens for breast and other cancers. Here, we have compared mechanisms of response and resistance to three CDKi that target either CDK4/6 or CDK2 and abrogate E2F target gene expression. We identify CCNE1 gain and RB1 loss as mechanisms of resistance to CDK4/6 inhibition, whereas receptor tyrosine kinase (RTK) and RAS signaling is associated with CDK2 inhibitor resistance. Mechanistically, we show that ETS factors are mediators of RTK/RAS signaling that cooperate with E2F in cell cycle progression. Consequently, CDK2 inhibition sensitizes cyclin E1-driven but not RAS-driven ovarian cancer cells to platinum-based chemotherapy. In summary, this study outlines a rational approach for incorporating CDKi into treatment regimens for HGSOC.

Chromium picolinate does not produce chromosome damage.

Chromium picolinate (CrPic) is used as a dietary supplement and has beneficial effects in reducing diabetes risk factors. The present study evaluated the cytogenetic effects of CrPic in bone marrow cells of Sprague-Dawley rats (5 animals/sex/group). Test animals were dosed orally with 33, 250 or 2000 mg/kg of CrPic, which corresponded to doses of 4.1, 30.8 and 246 mg/kg of chromium. The lowest dose of CrPic, 33 mg/kg is estimated to be the human equivalent for a 50 kg person (200 mcg Cr). The animals were dosed once, and sacrificed either 18 or 42 hours (h) later. The mitotic index was determined for each rat. Metaphase cells (50 or 100/rats) were examined for interstitial deletions, chromatid and chromosome gap, breaks or other anomalies. The average percentage of damaged cells at 18 h in vehicle treated males and females were 1.2% and 0.6%, respectively. The mean values at 18 h for doses of 33, 250 and 2000 mg/kg, were 0.4%, 0.8%, 0.4% for males and 0.6%, 0.2% and 0.6% for females, respectively. At 42 h, the mean values for vehicle treated males and females were 0.4% and 0.2%, respectively. For doses of 33, 250 and 2000 mg/kg at 42 h the average percent damage was 14%, 0.8% and 0.4% for males and 0.2%, 0.2% and 0.0% for females, respectively. None of these values were statistically increased compared to the vehicle controls. The positive control Cyclophosphamide (CPM) induced a significant increase in chromosomal damage at 18 h averaging 30% in males and 37% in females, respectively (p<0.001). In the current study CrPic did not induce chromosomal damage in bone marrow cells at single doses of 33, 250 and 2000 mg/kg of body weight and thus there was no indication of any toxicity of CrPic.