Racial/ethnic disparities in exposure to e-cigarette advertising among U.S. youth.

OBJECTIVES: This study aims to assess exposure to e-cigarette advertising across multiple marketing channels among U.S. youth and to examine whether racial/ethnic disparities exist in exposure to e-cigarette advertisements. STUDY DESIGN: This is a cross-sectional study. METHODS: Cross-sectional data were drawn from a longitudinal survey of participants recruited from two nationally representative panels (NORC's AmeriSpeak® and GfK's KnowledgePanel). A total of 2043 youth aged 13-17 completed the initial 2018 survey, and 2013 youth completed the follow-up survey in 2019 (including a replenishment sample of 690 youth). Outcome variables were self-reported e-cigarette advertisement exposure in the past three months through various sources, such as television, point of sale, and online/social media. Generalized estimating equation models were used to estimate the adjusted odds ratios (AOR) of the association between racial/ethnic identity and e-cigarette advertisement exposure. RESULTS: The prevalence of reported exposure to e-cigarette advertisements through any channel was 79.8% (95% CI: 77.1-82.2) in 2018 and 74.9% (95% CI: 72.5-77.1) in 2019, respectively. Point of sale was the most common source of e-cigarette advertisement exposure in both years. Non-Hispanic Black and non-Hispanic Asian youth were more likely to report exposure to e-cigarette advertisements through television (AOR = 2.07, 95% CI: 1.44-2.99 and AOR = 2.11, 95% CI: 1.17-3.82, respectively) and online/social media (AOR = 1.61; 95% CI: 1.11-2.33 and AOR = 1.99, 95% CI: 1.10-3.59, respectively) channels compared with non-Hispanic White youth. CONCLUSIONS: A substantial proportion of U.S. youth reported exposure to e-cigarette advertising through a variety of marketing channels. Significant racial/ethnic disparities existed, with non-Hispanic Black and Asian youth reporting more marketing exposure than their non-Hispanic White counterparts.

Chondrocytic and pharmacokinetic properties of Phlpp inhibitors.

Objective: The pleckstrin homology domain leucine-rich repeat protein phosphatases (Phlpp1/2) were recently identified as potential therapeutic targets for cartilage regeneration in osteoarthritic joints. Phlpp inhibitors NSC 117079 and NSC 45586 increase chondrocyte proliferation and matrix production, but the pharmacodynamics and pharmacokinetics of these compounds are not known. Design: Chondrocytic effects of Phlpp inhibitors, NSC 117079 and NSC 45586, were measured by western blotting of Phlpp substrates, glycosaminoglycan (GAG) assays, and transcriptomic assays. Liquid chromatography/mass spectroscopy assays were established to measure NSC 117079 and NSC 45586 in vitro and in vivo. The effects of NSC 117079 and NSC 45586 on articular cartilage structure in vivo after intra-articular injection were determined by histology. Results: The Phlpp inhibitors NSC 117079 and NSC 45586 were highly stable in vitro and stimulated GAG, Sox9, proteoglycan 4 and collagen 2 production in maturing but not more differentiated chondrocytes in vitro. Both molecules reduced Phlpp1/2 levels and suppressed matrix degradation to functionally extend their inhibitory effect on these phosphatases. In vivo, NSC 117079 was eliminated from the bloodstream within 4 â€‹h after intravenous injection, while NSC 45586 was eliminated in 8 â€‹h and had a higher volume distribution. Both molecules increased articular cartilage area on lateral and medial tibial plateaus and femoral condyles by 15% in C57Bl/6 mice between four and five weeks of age. Conclusion: These data advance our understanding of how Phlpp inhibitors promote and preserve cartilage formation and provide a basis for understanding their safety and activity in vivo.

Interaction of 5-hydroxy-l-tryptophan and negative dietary cation-anion difference on calcium homeostasis in multiparous peripartum dairy cows.

Hypocalcemia affects almost 50% of all dairy cows. Our laboratory has previously demonstrated that infusions of the serotonin precursor 5-hydroxy-l-tryptophan (5-HTP) increase circulating calcium concentrations in the Holstein transition cow. It is unknown whether feeding a negative dietary cation-anion difference (DCAD) diet alters the relationship between 5-HTP and hypocalcemia. The main objective of this study was to determine whether feeding a negative DCAD (-DCAD) diet before calving in conjunction with 5-HTP treatment could further diminish the magnitude of hypocalcemia at the time of calving. We used a randomized complete block design with a 2 × 2 factorial arrangement. Thirty-one multiparous Holstein cows were fed either a positive (+13 mEq/100 g) or negative (-13 mEq/100 g) DCAD diet 21 d before parturition and were intravenously infused daily with saline or 5-HTP (1 mg/kg) starting 7 d before the estimated date of parturition. Cows were blocked by parity and were randomly assigned to 1 of 4 treatment groups: positive DCAD plus saline, positive DCAD plus 5-HTP, negative DCAD plus saline, and negative DCAD plus 5-HTP, resulting in n = 8 per group. Total calcium (tCa), ionized calcium (iCa), and feed intake were recorded. The iCa was elevated prepartum in the -DCAD/5-HTP group compared with the other treatment groups as well as on d 0 and 1 postpartum. Although differences in tCa were not significant across the pre- or postpartum periods, tCa was numerically higher on d 0 and significantly higher on d 1 in -DCAD/5-HTP cows compared with all other groups. Prepartum the -DCAD/5-HTP treatment group ate less than the other treatment groups; however, postpartum dry matter intake differences were not significant. These findings demonstrate that feeding a -DCAD diet in conjunction with 5-HTP prepartum can increase postpartum circulating iCa concentrations and therefore diminish the magnitude of hypocalcemia at the time of parturition.

Temporarily decreasing progesterone after timed artificial insemination decreased expression of interferon-tau stimulated gene 15 (ISG15) in blood leukocytes, serum pregnancy-specific protein B concentrations, and embryo size in lactating Holstein cows.

Our objective was to evaluate the effects of temporarily decreasing progesterone (P4) after timed artificial insemination (TAI) on embryonic growth in dairy cows. Lactating Holstein cows (n = 80) were submitted to a Double-Ovsynch protocol for first TAI and were assigned randomly to receive 12.5 mg of PGF2α 5 d after the last GnRH treatment (LowP4) or remain untreated (control). Blood samples were collected thrice weekly from 5 to 29 d after TAI for all cows and from 32 to 67 d for pregnant cows, and were analyzed for P4 and pregnancy-specific protein B concentrations. Expression of interferon-tau stimulated gene 15 (ISG15) was assessed in blood leukocyte mRNA 18 and 20 d after TAI. Pregnancy diagnosis was performed weekly using ultrasound from 32 to 67 d after TAI, and embryonic crown-rump length was measured 32, 39, and 46 d after TAI. Data were analyzed by ANOVA and logistic regression using the MIXED and GLIMMIX procedures of SAS. The LowP4 cows had less P4 than control cows from 6 to 11 d after TAI; however, pregnancy outcomes 32 d after TAI and pregnancy loss from 32 to 67 d after TAI did not differ between treatments. Control cows diagnosed pregnant 32 d after TAI had greater expression of ISG15 20 d after TAI than LowP4 cows diagnosed pregnant 32 d after TAI, and pregnant control cows had greater pregnancy-specific protein B concentrations from 25 to 67 d after TAI than pregnant LowP4 cows. Embryo size did not differ between treatments 32 and 39 d after TAI, but control cows had larger embryos 46 d after TAI. In conclusion, temporarily decreasing P4 after TAI decreased embryonic growth during early pregnancy in lactating Holstein cows but did not affect pregnancies per artificial insemination or pregnancy loss.

Flavored e-cigarette use: Characterizing youth, young adult, and adult users.

The purpose of this study is to investigate how the use of flavored e-cigarettes varies between youth (12-17 years old), young adults (18-29 years old), and older adults (30 + years old). Cross-sectional surveys of school-going youth (n = 3907) and young adult college students (n = 5482) in Texas, and young adults and older adults (n = 6051) nationwide were administered in 2014-2015. Proportions and 95% confidence intervals were used to describe the percentage of e-cigarette use at initiation and in the past 30 days that was flavored, among current e-cigarette users. Chi-square tests were applied to examine differences by combustible tobacco product use and demographic factors. Most e-cigarette users said their first and "usual" e-cigarettes were flavored. At initiation, the majority of Texas school-going youth (98%), Texas young adult college students (95%), and young adults (71.2%) nationwide said their first e-cigarettes were flavored to taste like something other than tobacco, compared to 44.1% of older adults nationwide. Fruit and candy flavors predominated for all groups; and, for youth, flavors were an especially salient reason to use e-cigarettes. Among adults, the use of tobacco flavor at initiation was common among dual users (e-cigarettes + combustible tobacco), while other flavors were more common among former cigarette smokers (P = 0.03). Restricting the range of e-cigarette flavors (e.g., eliminating sweet flavors, like fruit and candy) may benefit youth and young adult prevention efforts. However, it is unclear what impact this change would have on adult smoking cessation.

Serotonin and calcium homeostasis during the transition period.

The transition from pregnancy to lactation puts significant, sudden demands on maternal energy and calcium reserves. Although most mammals are able to effectively manage these metabolic adaptations, the lactating dairy cow is acutely susceptible to transition-related disorders because of the high amounts of milk being produced. Hypocalcemia is a common metabolic disorder that occurs at the onset of lactation. Hypocalcemia is also known to result in poor animal welfare conditions. In addition, cows that develop hypocalcemia are more susceptible to a host of other negative health outcomes. Different feeding tactics, including manipulating the dietary cation-anion difference and administering low-calcium diets, are commonly used preventative strategies. Despite these interventions, the incidence of hypocalcemia in the subclinical form is still as high as 25% to 30% in the United States dairy cow population, with a 5% to 10% incidence of clinical hypocalcemia. In addition, although there are various effective treatments in place, they are administered only after the cow has become noticeably ill, at which point there is already significant metabolic damage. This emphasizes the need for developing alternative prevention strategies, with the monoamine serotonin implicated as a potential therapeutic target. Our research in rodents has shown that serotonin is critical for the induction of mammary parathyroid hormone-related protein, which is necessary for the mobilization of bone tissue and subsequent restoration of maternal calcium stores during lactation. We have shown that circulating serotonin concentrations are positively correlated with serum total calcium on the first day of lactation in dairy cattle. Administration of serotonin's immediate precursor through feeding, injection, or infusion to various mammalian species has been shown to increase circulating serotonin concentrations, with positive effects on other components of maternal metabolism. Most recently, preliminary data suggest that manipulation of the serotonergic axis precalving may positively affect postcalving calcium dynamics. Combined, our research suggests a potential mechanism by which serotonin acts on the mammary gland to maintain circulating maternal calcium concentrations. Further research into serotonin's potential as a therapeutic target could contribute significantly as a preventive strategy against hypocalcemia in early lactation dairy cows.

Use of the RatLoft decreases pup mortality in lactating mice.

Lactating mice in laboratory conditions are thought to be under considerable stress. Dams may manifest this stress through a decrease in milk yield and/or increase in infanticide. The purpose of this study was to examine the effect of access to an environmental enrichment device called the RatLoft on milk yield, circulating serotonin, and pup mortality using both wild-type mice and mice genetically deficient in tryptophan hydroxylase 1 (TPH1(-/-); the rate-limiting enzyme in the non-neuronal serotonin synthesis pathway). Presence or absence of the RatLoft did not affect milk yield or circulating serotonin concentrations overall, but serotonin concentrations decreased throughout the 21-day lactation period. Serotonin concentrations were increased in TPH1-deficient mice with access to the RatLoft compared with those without the RatLoft on day 21. Pup mortality tended to decrease for dams with access to the RatLoft as compared to no RatLoft. Within the TPH1(-/-) groups, dams with access to the RatLoft tended to kill less pups per dam than dams without the RatLoft. These results demonstrate that access to the RatLoft during lactation decreases pup infanticide by dams. This environmental enrichment may be particularly beneficial to TPH1(-/-) dams that, in addition to decreased infanticide, had increased serotonin concentrations, possibly indicating enhanced well-being. Use of the RatLoft could prove beneficial to researchers working with lactating mouse models to increase the number of pups weaned and positively impact the welfare of the dam.

Autocrine-paracrine regulation of the mammary gland.

The mammary gland has a remarkable capacity for regulation at a local level, particularly with respect to its main function: milk secretion. Regulation of milk synthesis has significant effects on animal and human health, at the level of both the mother and the neonate. Control by the mammary gland of its essential function, milk synthesis, is an evolutionary necessity and is therefore tightly regulated at a local level. For at least the last 60 yr, researchers have been interested in elucidating the mechanisms underpinning the mammary gland's ability to self-regulate, largely without the influence from systemic hormones or signals. By the 1960s, scientists realized the importance of milk removal in the capacity of the gland to produce milk and that the dynamics of this removal, including emptying of the alveolar spaces and frequency of milking, were controlled locally as opposed to traditional systemic hormonal regulation. Using both in vitro systems and various mammalian species, including goats, marsupials, humans, and dairy cows, it has been demonstrated that the mammary gland is largely self-regulating in its capacity to support the young, which is the evolutionary basis for milk production. Local control occurs at the level of the mammary epithelial cell through pressure and stretching negative-feedback mechanisms, and also in an autocrine fashion through bioactive factors within the milk which act as inhibitors, regulating milk secretion within the alveoli themselves. It is only within the last 20 to 30 yr that potential candidates for these bioactive factors have been examined at a molecular level. Several, including parathyroid hormone-related protein, growth factors (transforming growth factor, insulin-like growth factor, epidermal growth factor), and serotonin, are synthesized within and act upon the gland and possess dynamic receptor activity resulting in diverse effects on growth, calcium homeostasis, and milk composition. This review will focus on the autocrine-paracrine regulation of the mammary gland, with an examination of both foundational work and the progress made within the last 10 to 20 yr of research.

Evaluation of eluents for the recovery of an enveloped virus from hands by whole-hand sampling.

AIMS: The objective of this research is to evaluate eluents for recovery of an enveloped bacteriophage, Φ6, using whole-hand sampling. METHODS AND RESULTS: Virus was applied to the hands of volunteers and sampled by the glove juice method with 1.5% beef extract (BE), phosphate buffered saline (PBS), 0.01 and 0.1% Tween 80, tryptic soy broth (TSB) and 9% NaCl. Each volunteer underwent multiple rounds application and hand sampling. Mean log10 virus loss across trials was 2.6 for BE, 2.8 for PBS, 2.4 for TSB, 3.8 for NaCl, 3.0 for 0.1% Tween 80, and 2.9 for 0.01% Tween 80. Within each volunteer, there was a decline in viral loss from the first to last trial. CONCLUSIONS: These eluents can recover Φ6 from hands with approx. 2-3 log10 loss, comparable to recoveries previously reported for influenza. Protein and detergent-based eluents may have similar recoveries, but recovery may still vary across repeated sampling. SIGNIFICANCE AND IMPACT OF THE STUDY: Based on current work, protein-based eluents such as beef extract can maximize recovery of enveloped viruses during hand sampling, providing methods for evaluating survival and transmission of enveloped viruses on hands. Further exploration is needed of the effect of repeated sampling on recovery from whole-hand sampling.

Feeding 5-hydroxy-l-tryptophan during the transition from pregnancy to lactation increases calcium mobilization from bone in rats.

An increasing demand for calcium during pregnancy and lactation can result in both clinical and subclinical hypocalcemia during the early lactation period in several mammalian species, in particular the dairy cow. Serotonin (5-HT) was recently identified as a regulator of lactation and bone turnover. The purpose of this study was to determine whether supplementation of the maternal diet with a 5-HT precursor would increase maternal bone turnover and calcium mobilization to maintain appropriate circulating maternal concentrations of ionized calcium during lactation. Female Sprague-Dawley rats (n = 30) were fed either a control diet (n = 15) or a diet supplemented with the 5-HT precursor 5-hydroxytryptophan (5-HTP, 0.2%; n = 15) from day 13 of pregnancy through day 9 of lactation. Maternal serum and plasma (day 1 and day 9 of lactation), milk and pup weight (daily), mammary gland and bone tissue (day 9 of lactation) were collected for analysis. The 5-HTP diet elevated circulating maternal concentrations of 5-HT on day 1 and day 9 of lactation and parathyroid hormone related-protein (PTHrP) on day 9 of lactation (P < 0.033). In addition, 5-HTP supplementation increased total serum calcium concentrations on day 1 of lactation and total milk calcium concentration on day 9 of lactation (P < 0.032). Supplemental 5-HTP did not alter milk yield, maternal body weight, mammary gland structure, or pup litter weights (P > 0.05). Supplemental 5-HTP also resulted in increased concentrations of mammary 5-HT and PTHrP, as well as increased mRNA expression of rate-limiting enzyme in 5-HT synthesis, tryptophan hydroxylase 1, and Pthrp mRNA on day 9 of lactation (P < 0.028). In addition, supplementation of 5-HTP resulted in increased mRNA expression of maternal mammary calcium transporters and resorption of bone in the femur, indicated by increase osteoclast number and diameter as well as mRNA expression of classical markers of bone resorption on day 9 of lactation (P < 0.048). These results show that increasing 5-HT biosynthesis during the transition from pregnancy to lactation could be a potential therapeutic target to explore for prevention of subclinical and clinical hypocalcemia.

Life after lower extremity amputation in diabetics.

UNLABELLED: Lower limb amputees typically have reduced mobility which affects their ability to perform daily tasks and to successfully reintegrate into community life. A major goal of rehabilitation for amputees is to improve quality of life (QOL). This study therefore focussed on QOL and functional independence for persons with lower limb amputations secondary to diabetes. OBJECTIVE: To determine the QOL and functional independence of lower limb diabetic amputees one to three years post amputation, using variables such as age, gender and amputation level. METHOD: A total of 87 participants were selected from the 2006-2009 physiotherapy records at the St Ann's Bay Hospital. These participants completed the World Health Organization Quality of Life Scale (WHO QOL-BREF) and the Functional Independence Measure (FIM). Data were analysed using SPSS (version 12) and the mean values for QOL and functional independence were calculated. Relationships between the variables: age, gender and level of amputation with QOL and functional independence were analysed using descriptive and inferential statistical techniques. RESULTS: Among the 35 males and 52 females participating in the study, below knee amputees recorded higher scores for QOL (p < 0.05) and functional independence (p < 0.0001) compared to the above knee amputees. The result also showed that females had a significantly higher average score than males among the four domains for QOL. Similar results were obtained from the FIM where women again had significantly higher scores than males (p < 0.0001). The majority of females across the age groups reported average to high QOL (p < 0.0001) compared to the males. A positive correlation (r = 0.5999, p < 0.0001) was found between functional independence and quality of life of all participants. CONCLUSION: The results showed that below knee amputees functioned better than those with above knee amputations and that females were more likely to cope and function with the disability than males.

Comparison of special interest computed tomography, endosonography and histopathological stage of oesophageal cancer.

AIMS: To assess the strength of agreement between the perceived pre-operative stage of oesophageal tumours as determined by spiral computed tomography (CT) and endoscopic ultrasound (EUS), both alone and in combination, with the histopathological stage. METHODS: Sixty patients with oesophageal cancer underwent both pre-operative CT and EUS performed by two consultant radiologists with a special interest in upper gastrointestinal radiology. The strength of the agreement between the radiological stage and the histopathological stage was determined by means of the weighted Kappa statistic (Kw). RESULTS: Sensitivity for T and N stages was 58% and 79% for CT, and 72% and 91% for EUS. Specificity for T and N stages was 80% and 84% for CT, and 85% and 68% for EUS. Kw for T and N stages was 0.455 (p=0.0001) and 0.603 (p=0.0001) for CT compared with 0.604 (p=0.0001) and 0.610 (p=0.0001) for EUS. In patients when CT and EUS agreed regarding the T and N stages, the strength of agreement between the radiological and the histopathological stage was greater (Kw T 0.613 (p=0.0001), Kw N 0.781 (p=0.0001)). CONCLUSION: CT and EUS are complimentary techniques for the staging of oesophageal tumours, and these results reinforce the importance of specialist radiology in stage directed management.

Magnetic resonance imaging in the preoperative assessment of clinical stage I endometrial carcinoma.

Magnetic resonance (MR) imaging may aid in preoperative treatment planning of endometrial carcinoma by accurately estimating tumor volume, depth of myometrial invasion, and extrauterine extension. Preoperative MR scans were obtained on 24 women with clinical stage I endometrial cancer. MR scans were evaluated for uterine size, as an indirect measure of tumor volume, and depth of myometrial invasion. MR detected deep invasion (greater than or equal to 50% of myometrial thickness) with a sensitivity of 71% and specificity of 83% (accuracy 79%) when compared with the pathologic findings. MR staging may assist in deciding which patients should have lymph node dissection at surgery and may aid in decisions regarding adjunctive radiation therapy.