Discovery of Potent Glycosidases Enables Quantification of Smoke-Derived Phenolic Glycosides through Enzymatic Hydrolysis.

When grapes are exposed to wildfire smoke, certain smoke-related volatile phenols (VPs) can be absorbed into the fruit, where they can be then converted into volatile-phenol (VP) glycosides through glycosylation. These volatile-phenol glycosides can be particularly problematic from a winemaking standpoint as they can be hydrolyzed, releasing volatile phenols, which can contribute to smoke-related off-flavors. Current methods for quantitating these volatile-phenol glycosides present several challenges, including the requirement of expensive capital equipment, limited accuracy due to the molecular complexity of the glycosides, and the utilization of harsh reagents. To address these challenges, we proposed an enzymatic hydrolysis method enabled by a tailored enzyme cocktail of novel glycosidases discovered through genome mining, and the generated VPs from VP glycosides can be quantitated by gas chromatography-mass spectrometry (GC-MS). The enzyme cocktails displayed high activities and a broad substrate scope when using commercially available VP glycosides as the substrates for testing. When evaluated in an industrially relevant matrix of Cabernet Sauvignon wine and grapes, this enzymatic cocktail consistently achieved a comparable efficacy of acid hydrolysis. The proposed method offers a simple, safe, and affordable option for smoke taint analysis.

Computational Drug Design of Novel Agonists of the µ -Opioid Receptor to Inhibit Pain Signaling.

Opioids such as Morphine, Codeine, Hydrocodone, and Oxycodone target the µ-opioid receptor, a G-protein-coupled receptor (GPCR), blocking the transmission of nociceptive signals. In this study, four opioids were analyzed for ADMET properties and molecular interactions with a GPCR crystal structure (PDB ID: 8EF6). This aided in the computational design of two novel drug candidates with improved docking scores and ADMET properties when compared to Hydrocodone. Homology analysis indicated that a Mus musculus (house mouse) animal model could be used in the preclinical studies of these drug candidates in the development of safer and more effective opioid drugs for pain management with reduced side effects.

Sunburns and Sun Protection Behaviors among Male Hispanic Outdoor Day Laborers.

Individuals who work outside are at increased risk for skin cancer due to excessive exposure to ultraviolet (UV) radiation. Little is known about UV exposures and sun safety practices of outdoor day laborers, who are disproportionately Hispanic. This study identified the correlates of sunburn and sun protection behaviors in a sample of male, Hispanic day laborers (n = 175). More than half of the participants (54.9%) experienced one or more sunburns when working during the past summer, and 62.9% reported having one or more symptoms of heat illness. The frequency of engaging in sun protection behaviors was suboptimal, including sunglasses use (M = 2.68, SD = 1.71), staying in the shade (M = 2.30, SD = 0.94), wearing sunscreen (M = 2.10, SD = 1.39), and wearing a wide-brimmed hat (M = 1.75, SD = 1.32), based on a 5-point scale (1 = never; 5 = always). Lower education level, higher levels of skin sensitivity to the sun, any symptom of heat illness, fewer barriers to wearing a wide-brimmed hat, and not wearing a wide-brimmed hat were associated with a greater number of sunburns. Factors associated with each sun protection behavior varied. Implications and directions for future research are discussed.

Cost, reach, and representativeness of recruitment efforts for an online skin cancer risk reduction intervention trial for young adults.

Despite its increasing use, few studies have reported on demographic representativeness and costs of research recruitment via social media. It was hypothesized that cost, reach, enrollment, and demographic representativeness would differ by social media recruitment approach. Participants were 18-25 year-olds at moderate to high risk of skin cancer based on phenotypic and behavioral characteristics. Paid Instagram, Facebook, and Twitter ads, unpaid social media posts by study staff, and unpaid referrals were used to recruit participants. Demographic and other characteristics of the sample were compared with the 2015 National Health Interview Survey (NHIS) sample. Analyses demonstrated significant differences among recruitment approaches regarding cost efficiency, study participation, and representativeness. Costs were compared across 4,274 individuals who completed eligibility screeners over a 7-month period from: Instagram, 44.6% (of the sample) = 1,907, $9 (per individual screened); Facebook, 31.5% = 1,345, $8; Twitter, 1% = 42, $178; unpaid posts by study staff, 10.6% and referred, 6.5%, $1. The lowest rates of study enrollment among individuals screened was for Twitter. Most demographic and skin cancer risk factors of study participants differed from those of the 2015 NHIS sample and across social media recruitment approaches. Considering recruitment costs and number of participants enrolled, Facebook and Instagram appeared to be the most useful approaches for recruiting 18-25 year-olds. Findings suggest that project budget, target population and representativeness, and participation goals should inform selection and/or combination of existing and emerging online recruitment approaches.

Discovery of a natural cyan blue: A unique food-sourced anthocyanin could replace synthetic brilliant blue.

The color of food is critical to the food and beverage industries, as it influences many properties beyond eye-pleasing visuals including flavor, safety, and nutritional value. Blue is one of the rarest colors in nature's food palette-especially a cyan blue-giving scientists few sources for natural blue food colorants. Finding a natural cyan blue dye equivalent to FD&C Blue No. 1 remains an industry-wide challenge and the subject of several research programs worldwide. Computational simulations and large-array spectroscopic techniques were used to determine the 3D chemical structure, color expression, and stability of this previously uncharacterized cyan blue anthocyanin-based colorant. Synthetic biology and computational protein design tools were leveraged to develop an enzymatic transformation of red cabbage anthocyanins into the desired anthocyanin. More broadly, this research demonstrates the power of a multidisciplinary strategy to solve a long-standing challenge in the food industry.

Correction: Association Between State Indoor Tanning Legislation and Google Search Trends Data in the United States From 2006 to 2019: Time-Series Analysis.

[This corrects the article DOI: 10.2196/26707.].

Association Between State Indoor Tanning Legislation and Google Search Trends Data in the United States From 2006 to 2019: Time-Series Analysis.

BACKGROUND: Exposure to ultraviolet radiation from the sun or indoor tanning is the cause of most skin cancers. Although indoor tanning has decreased in recent years, it remains most common among adolescents and young adults, whose skin is particularly vulnerable to long-term damage. US states have adopted several types of legislation to attempt to minimize indoor tanning among minors: a ban on indoor tanning among all minors, a partial minor ban by age (eg, <14 years), or the requirement of parental consent or accompaniment for tanning. Currently, only 6 US states have no indoor tanning legislation for minors. OBJECTIVE: This study investigated whether internet searches (as an indicator of interest) related to indoor tanning varied across US states by the type of indoor tanning legislation, using data from Google Trends from 2006 to 2019. METHODS: We conducted a time-series analysis of Google Trends data on indoor tanning from 2006 to 2019 by US state. Time-series linear regression models were generated to assess the Google Trends data over time by the type of indoor tanning legislation. RESULTS: We found that indoor tanning search rates decreased significantly for all 50 states and the District of Columbia over time (P<.01). The searches peaked in 2012 when indoor tanning received marked attention (eg, indoor tanning was banned for all minors by the first state-California). The reduction in search rates was more marked for states with a complete ban among minors compared to those with less restrictive types of legislation. CONCLUSIONS: Our findings are consistent with those of other studies on the association between indoor tanning regulations and attitudinal and behavioral trends related to indoor tanning. The main limitation of the study is that raw search data were not available for more precise analysis. With changes in interest and norms, indoor tanning and skin cancer risk among young people may change. Future studies should continue to determine the impact of such public health policies in order to inform policy efforts and minimize risks to public health.

Prevalence and correlates of skin self-examination behaviors among melanoma survivors: a systematic review.

Melanoma is the most common cause of skin cancer deaths, and individuals who have had melanoma have an increased risk of developing new melanomas. Doing regular self-examinations of skin enables one to detect thinner melanomas earlier when the disease is more treatable. The aim of this systematic review is to characterize and evaluate the existing literature on the prevalence and correlates of skin self-examination (SSE) behaviors among adult melanoma survivors in the USA and Canada. A computerized literature search was performed using PubMed, Google Scholar, and ScienceDirect. The inclusion criteria for the studies were: (a) reported results for adult melanoma survivors in the USA or Canada, (b) papers described empirical research, (c) assessed SSE and related behaviors, and (d) papers were published in a peer-reviewed journal in the past 20 years. Key phrases such as "skin self-examination/SSE in melanoma survivors in the United States" and "correlates of skin self-examination/SSE" were used. Based on the inclusion criteria, 30 studies were included in the systematic review. SSE prevalence varied depending on how SSE was defined. Demographics and factors (gender, education level, patient characteristics, partner assistance, and physician support) associated with SSE were identified. Findings of this review show evidence for the need to have a consistent way to assess SSE and suggest different types of correlates on which to focus in order to promote SSE and reduce the risk of melanoma recurrence in survivors. This systematic review and its protocol have been registered in the international database of prospectively registered systematic reviews in health and social care (PROSPERO; ID: 148878).

Development and Initial Psychometric Properties of Two Itch-Related Measures: Scratch Intensity and Impact, Sleep-Related Itch and Scratch.

Self-report measures are needed to better understand the relationships among sleep, itching, scratching, and chronic itch conditions and their associations with disease severity, QOL, health, and functioning. Two scales related to sleep and/or scratch were recently developed and assessed in 137 patients with chronic itch and atopic dermatitis or psoriasis. The Scratch Intensity and Impact Scale consisted of two factors (scratching intensity and impact of scratching on QOL) that accounted for 64.59% of the variance with a total of 13 items, overall Cronbach's α of 0.93, and test-retest reliability of 0.66. The Sleep-Related Itch and Scratch Scale consisted of one factor that accounted for 63.01% of the variance with a total of 16 items, overall Cronbach's α of 0.98, and test-retest reliability of 0.66. Both measures demonstrated significant correlations with each other as well as other itch-related measures and nonsignificant correlations with scales hypothesized to be unrelated. The final measures demonstrated adequate preliminary psychometric characteristics. It is hoped that these scales will be used for future research and clinical purposes to help fill recognized gaps in understanding about sleep, itch, scratching, atopic dermatitis, and psoriasis.

Development and psychometrics of the English version of the Itch Cognitions Questionnaire.

BACKGROUND: The aim of this study was to validate the English version of the Itch Cognition Questionnaire in a sample of patients with chronic itch due to psoriasis or atopic dermatitis. An English-language version of an instrument assessing itch-related cognitions is needed since cognitions can contribute to a worsening of itch, and chronic itch is prevalent in English-speaking counties and internationally. METHODS: The German Itch Cognitions Questionnaire was translated into English, and cognitive interviewing was conducted to finalize item wording. Internal and test-retest reliability, item discrimination, responsiveness to change, and construct, convergent, and discriminant validity were assessed in a national sample of 137 individuals with chronic itch due to atopic dermatitis or psoriasis recruited online. RESULTS: Internal reliability was high with Cronbach's alphas of 0.93 for the Catastrophizing subscale and 0.88-0.90 for Coping. The Pearson's correlation assessing 1-month test-retest reliability for the Catastrophizing subscale was r = 0.62 and for the Coping subscale was r = 0.61. The corrected item-total correlation revealed that items were relatively consistent with the scores for the subscales (with correlations ranging from 0.58 to 0.79), indicating very good item discrimination. Results of factor analysis, convergent and discriminant, and responsiveness to change analyses provided evidence for validity. CONCLUSIONS: This study showed good psychometric characteristics of the English version of the Itch Cognitions Questionnaire. We suggest that future studies investigate the use of the measure in clinical practice to assist with treatment planning and outcome assessment related to itch as well as address study limitations such as sampling and replication.

Awareness, understanding, use, and impact of the UV index: A systematic review of over two decades of international research.

The ultraviolet radiation index (UVI) was adopted internationally to raise awareness about and encourage the public to protect their skin from skin cancer. The current paper is a systematic review of over 20 years of research investigating awareness, comprehension, use, and impact of the UVI. Thirty-one studies were included from the USA, Canada, Europe, Australia, New Zealand, and elsewhere. Awareness of the UVI varies by country, with samples from some countries demonstrating high awareness. However, comprehension and use of the UVI to inform sun safety behaviors are typically much lower. In fact, greater UVI awareness has sometimes been associated with riskier UV-related behaviors such as intentional tanning. Fewer studies have evaluated interventions, and their results have been mixed. In summary, more research is needed to determine how to help the public understand and use the UVI for effective skin protection. This review offers suggestions for future use of and research with the UVI.

Using community-based participatory research to develop healthy retail strategies in Native American-owned convenience stores: The THRIVE study.

In rural Native American communities, access to healthy foods is limited and diet-related disparities are significant. Tribally owned and operated convenience stores, small food stores that sell ready-to-eat foods and snacks primarily high in fat and sugar, serve as the primary and, in some areas, the only food stores. The Tribal Health and Resilience in Vulnerable Environments or "THRIVE" study, implemented between 2013 and 2018, is the first healthy retail intervention study implemented in tribally owned and operated convenience stores. THRIVE aims to increase vegetable and fruit intake among Native Americans living within the Chickasaw and Choctaw Nation of Oklahoma. The study comprises three phases: 1) formative research assessing tribal community food environments and associated health outcomes; 2) intervention development to assess convenience stores and tailor healthy retail product, pricing, promotion, and placement strategies; and 3) intervention implementation and evaluation. In this paper we share the participatory research process employed by our tribal-university partnership to develop this healthy retail intervention within the unique contexts of tribal convenience stores. We summarize our methods to engage tribal leaders across diverse health, government, and commerce sectors and adapt and localize intervention strategies that test the ability of tribal nations to increase fruit and vegetable purchasing and consumption among tribal members. Study processes will assist in developing a literature base for policy and environmental strategies that intervene broadly to improve Native community food environments and eliminate diet-related disparities among Native Americans.

Effects of a Course of Right Unilateral Ultrabrief Pulse Electroconvulsive Therapy Combined With Venlafaxine on Insomnia Symptoms in Elderly Depressed Patients.

OBJECTIVE: Antidepressant medications have a variety of effects on sleep, apart from their antidepressant effects. It is unknown whether electroconvulsive therapy (ECT) has effects on perceived sleep in depressed patients. This secondary analysis examines the effects of ECT on perceived sleep, separate from its antidepressant effects. METHODS: Elderly patients with major depressive disorder, as defined by DSM-IV, received open-label high-dose, right unilateral ultrabrief pulse ECT, combined with venlafaxine, as part of participating in phase 1 of the National Institute of Mental Health-supported study Prolonging Remission in Depressed Elderly (PRIDE). Phase 1 of PRIDE participant enrollment period extended from February 2009 to August 2014. Depression severity was measured with the Hamilton Depression Rating Scale-24 item (HDRS24), and measures of insomnia severity were extracted from the HDRS24. Participants were characterized at baseline as either "high-insomnia" or "low-insomnia" subtypes, based upon the sum of the 3 HDRS24 sleep items as either 4-6 or 0-3, respectively. Insomnia scores were followed during ECT and were adjusted for the sum of all the HDRS24 non-sleep items. Generalized linear models were used for longitudinal analysis of insomnia scores. RESULTS: Two hundred forty patients participated, with 48.3% in the high-insomnia and 51.7% in the low-insomnia group. Although there was a reduction in the insomnia scores in the high-insomnia group, only 12.4% of them experienced remission of insomnia after a course of ECT, despite an increase in utilization of sleep aids across the course of ECT, from 8.6% to 23.2%. The degree of improvement in insomnia symptoms paralleled the degree of improvement in non-insomnia symptoms. A "low" amount of improvement on the sum of the HDRS non-insomnia items (HDRS-sleep) was accompanied by a "low" amount of improvement in insomnia scores (change of -1.6 ± 1.2, P < .0001), while a "high" amount of improvement on the sum of the HDRS non-insomnia items was accompanied by a "higher" amount of improvement in insomnia scores (change of -3.1 ± 1.6, P < .0001). After adjustment for non-insomnia symptoms, there was no change in insomnia in the low-insomnia group. CONCLUSIONS: We found that ECT, combined with venlafaxine, has a modest anti-insomnia effect that is linked to its antidepressant effect. Most patients will have some degree of residual insomnia after ECT, and will require some consideration of whether additional, targeted assessment and treatment of insomnia is warranted. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01028508.

Thermal stability and kinetic constants for 129 variants of a family 1 glycoside hydrolase reveal that enzyme activity and stability can be separately designed.

Accurate modeling of enzyme activity and stability is an important goal of the protein engineering community. However, studies seeking to evaluate current progress are limited by small data sets of quantitative kinetic constants and thermal stability measurements. Here, we report quantitative measurements of soluble protein expression in E. coli, thermal stability, and Michaelis-Menten constants (kcat, KM, and kcat/KM) for 129 designed mutants of a glycoside hydrolase. Statistical analyses reveal that functional Tm is independent of kcat, KM, and kcat/KM in this system, illustrating that an individual mutation can modulate these functional parameters independently. In addition, this data set is used to evaluate computational predictions of protein stability using the established Rosetta and FoldX algorithms. Predictions for both are found to correlate only weakly with experimental measurements, suggesting improvements are needed in the underlying algorithms.

Hypnotic Medications and Suicide: Risk, Mechanisms, Mitigation, and the FDA.

OBJECTIVE: Insomnia is associated with increased risk for suicide. The Food and Drug Administration (FDA) has mandated that warnings regarding suicide be included in the prescribing information for hypnotic medications. The authors conducted a review of the evidence for and against the claim that hypnotics increase the risk of suicide. METHOD: This review focused on modern, FDA-approved hypnotics, beginning with the introduction of benzodiazepines, limiting its findings to adults. PubMed and Web of Science were searched, crossing the terms "suicide" and "suicidal" with each of the modern FDA-approved hypnotics. The FDA web site was searched for postmarketing safety reviews, and the FDA was contacted with requests to provide detailed case reports for hypnotic-related suicide deaths reported through its Adverse Event Reporting System. RESULTS: Epidemiological studies show that hypnotics are associated with an increased risk for suicide. However, none of these studies adequately controlled for depression or other psychiatric disorders that may be linked with insomnia. Suicide deaths have been reported from single-agent hypnotic overdoses. A separate concern is that benzodiazepine receptor agonist hypnotics can cause parasomnias, which in rare cases may lead to suicidal ideation or suicidal behavior in persons who were not known to be suicidal. On the other hand, ongoing research is testing whether treatment of insomnia may reduce suicidality in adults with depression. CONCLUSIONS: The review findings indicate that hypnotic medications are associated with suicidal ideation. Future studies should be designed to assess whether increases in suicidality result from CNS impairments from a given hypnotic medication or whether such medication decreases suicidality because of improvements in insomnia.

Effects of a right unilateral ultrabrief pulse electroconvulsive therapy course on health related quality of life in elderly depressed patients.

INTRODUCTION: Patients with Major Depressive Disorder (MDD) referred for electroconvulsive therapy (ECT) have poorer Health Related Quality of Life (HRQOL), compared with other patients with MDD, but ECT is associated with significant and durable improvement in HRQOL. However, no prior research has focused exclusively on elderly patients with MDD receiving ECT. METHODS: HRQOL data from 240 depressed patients over the age of 60 was measured with the Medical Outcomes Study Short Form 36 (SF-36). The SF-36 was measured before and after a course of acute ECT. Predictors of change in HRQOL scores were identified by generalized linear modeling. RESULTS: At baseline, participants showed very poor HRQOL. After treatment with ECT, the full sample showed marked and significant improvement across all SF-36 measures, with the largest gains seen in dimensions of mental health. Across all participants, the Physical Component Summary (PCS) score improved by 2.1 standardized points (95% CI, 0.61,3.56), while the Mental Component Summary (MCS) score improved by 12.5 points (95% CI, 7.2,10.8) Compared with non-remitters, remitters showed a trend toward greater improvement in the PCS summary score of 2.7 points (95%CI, -0.45, 5.9), while the improvement in the MCS summary score was significantly greater (8.5 points, 95% CI, 4.6,12.3) in the remitters than non-remitters. Post-ECT SF-36 measurements were consistently and positively related to baseline scores and remitter/non-remitter status or change in depression severity from baseline. Objective measures of cognitive function had no significant relationships to changes in SF-36 scores. LIMITATIONS: This study's limitations include that it was an open label study with no comparison group, and generalizability is limited to elderly patients. DISCUSSION: ECT providers and elderly patients with MDD treated with ECT can be confident that ECT will result in improved HRQOL in the short-term. Attaining remission is a key factor in the improvement of HRQOL. Acute changes in select cognitive functions were outweighed by improvement in depressive symptoms in determining the short term HRQOL of the participants treated with ECT.

A multi-site randomized clinical trial to reduce suicidal ideation in suicidal adult outpatients with Major Depressive Disorder: Development of a methodology to enhance safety.

BACKGROUND/AIMS: Suicide is a major public health concern, yet there are very few randomized clinical trials that have been conducted to reduce suicidal ideation in patients at risk of suicide. We describe the rationale and refinements of such a trial that is designed to assess the effect of a hypnotic medication on suicidal ideation in adult outpatients currently experiencing suicidal ideation. METHODS: "Reducing Suicidal Ideation Through Insomnia Treatment" is a multi-site randomized clinical trial that includes three recruiting sites and one data management site. This 4-year study is in its second year of recruitment. The purpose of the study is to compare hypnotic medication versus placebo as an add-on treatment to a selective serotonin reuptake inhibitor as a means of reducing suicidal ideation in depressed adult outpatients with insomnia and suicidal ideation. The safety features of the study follow the 2001 National Institutes of Health guidelines for studies that include patients at risk of suicide. RESULTS: In total, 584 potential participants have undergone telephone screening; 67% of these failed the phone screen, most often due to an absence of expressed suicidal ideation (26% of the telephone screen fails). A total of 115 people appeared for a face-to-face baseline assessment, and 40 of these had completed a taper off of their ineffective psychotropic medications before the baseline assessments. In all, 64% of those who completed baseline assessments failed to proceed to randomization, most commonly because of no clinically significant suicidal ideation (51% of those excluded at baseline). One participant was offered and accepted voluntary psychiatric hospitalization in lieu of study participation. Thus far, 40 participants have been randomized into the study and 88.7% of scheduled visits have been attended, with 93.8% adherence to the selective serotonin reuptake inhibitor and 91.6% adherence to the randomized hypnotic versus placebo. None of the randomized participants have required hospitalization or had a suicide attempt. CONCLUSION: By carefully considering the inclusion and exclusion criteria and other safety features, the safe conduct of randomized clinical trials in suicidal adult patients is possible, including the inclusion of participants who have undergone a prescribed tapering off of psychotropic medications prior to baseline assessment.

Thrombotic thrombocytopenic purpura (TTP) following coronary artery bypass: case series and review of the literature.

We reviewed 10 cases of thrombotic thrombocytopenic purpura (TTP) following cardiac surgery since November 1998. The object of the study was to define the natural history of post-CABG-TTP and to assess response to therapy. All patients underwent CABG; four also underwent aortic valve replacement and six mitral valve replacement. Eight patients had mental status changes and/or unexplained fever. All patients received plasmapheresis ranging from 5 to 24 days and nine required hemodialysis or continuous renal replacement therapy. All had significant improvement in their platelet count, LDH, renal function, and mental status changes at discharge. None of the five surviving patients has relapsed at follow-up ranging from 8 months to 6 years. Early recognition of this syndrome and early institution of plasmapheresis are important for a favorable outcome.

Can α-lipoic acid mitigate progression of aging-related decline caused by oxidative stress?

Aging is progressively deteriorating physiological function that leads to increasing risks of illness and death. Increases in life expectancy and the aging of a large segment of the population have made age-related disability and morbidity increasingly important issues. Supplements such as α-lipoic acid may have antiaging effects by positively affecting oxidative stress, cognitive function, and cardiovascular function.