The Future of Precision Prevention for Advanced Melanoma

Precision prevention of advanced melanoma is fast becoming a realistic prospect, with personalized, holistic risk stratification allowing patients to be directed to an appropriate level of surveillance, ranging from skin self-examinations to regular total body photography with sequential digital dermoscopic imaging. This approach aims to address both underdiagnosis (a missed or delayed melanoma diagnosis) and overdiagnosis (the diagnosis and treatment of indolent lesions that would not have caused a problem). Holistic risk stratification considers several types of melanoma risk factors: clinical phenotype, comprehensive imaging-based phenotype, familial and polygenic risks. Artificial intelligence computer-aided diagnostics combines these risk factors to produce a personalized risk score, and can also assist in assessing the digital and molecular markers of individual lesions. However, to ensure uptake and efficient use of AI systems, researchers will need to carefully consider how best to incorporate privacy and standardization requirements, and above all address consumer trust concerns.

Leg and arm adiposity is inversely associated with diastolic hypertension in young and middle-aged United States adults

Background We sought to determine the association between appendicular adiposity and hypertension, with the purpose of better understanding the role of body fat distribution on blood pressure (BP). Methods We included 7411 adults aged 20 to 59 who were not taking antihypertensives and without cardiovascular disease from the 2011 to 2018 National Health and Nutrition Examination Surveys. Leg & arm adiposity, determined via dual-energy X-ray absorptiometry scans, was defined as percent of total body fat present in legs/arms (leg/total%, arm/total%). Measures were categorized into sex-specific tertiles. We estimated change in BP and odds ratios (ORs) of hypertension (BP ≥ 130/80) and hypertension subtypes using multivariable, survey design-adjusted linear & logistic regression, respectively. Results Of the participants, 49% were female, the average (standard deviation) age was 37.4 (0.3) years, and 24% had hypertension. Those in the highest tertile (T3) of leg/total% had 30% decreased adjusted ORs (aOR) of hypertension compared to the lowest tertile (T1; aOR, 0.70; 95% confidence interval [95% CI], 0.55–0.89). This association was not significant for arm/total% (0.89, 0.68–1.17). T3 of leg/total% was associated with 49% lower, 41% lower, and unchanged relative odds of isolated diastolic hypertension (IDH), systolic-diastolic hypertension (SDH), and isolated systolic hypertension (ISH) compared to T1 (IDH: 0.51, 0.37–0.70; SDH: 0.59, 0.43–0.80; ISH: 1.06, 0.70–1.59). For every 10% increase in leg/total%, diastolic BP decreased by an adjusted mean 3.5 mmHg (95% CI, − 4.8 to − 2.2) in males and 1.8 mmHg (95% CI, − 2.8 to − 0.8) in females (P < 0.001 for both). Conclusions A greater proportional distribution of fat around the legs is inversely, independently associated with hypertension, and more specifically, diastolic hypertension (IDH and SDH).

Lean body mass and total body weight versus body surface area as determinant of docetaxel pharmacokinetics and toxicity

Aim: In our study we examined whether anthropometric and body composition parameters, i.e. body surface area (BSA), lean body mass (LBM) and total body weight (TBW), are correlated with docetaxel clearance and exposure. In addition, LBM, TBW and a fixed dose were compared to BSA as dosing parameters for dose individualisation of docetaxel. Methods: Thirty-six patients affected by breast or castration-resistant prostate carcinoma receiving docetaxel chemotherapy entered the study. LBM was measured by a Dual Energy Xray Absorptiometry (DEXA) scanner before treatment. Blood samples were collected up to 180 minutes after dosing to analyse docetaxel concentrations and to determine individual pharmacokinetic (PK) parameters. Results: No significant correlations were found between the docetaxel pharmacokinetic parameters clearance and volume of distribution and the anthropometric and body composition variables BSA, LBM and TBW. AUC was significantly but poorly correlated with BSA (r=0.452 [p=0.016]) and with TBW (r=0.476 (p=0.011]). The Mean Absolute Percentage Error and Mean Error of simulated dosing based on LBM and fixed dosing ME were not significant different compared to BSA. For TBW, only the MAPE of dosing was significant higher compared to BSA (24.1 vs. 17.1, P=0.001). Conclusion: There is no correlations between docetaxel pharmacokinetics and the anthropometric and body composition variables BSA, LBM and TBW. Dose individualisation of docetaxel based on LBM or TBW or fixed dosing cannot be recommended over BSA based dosing.

Extrarenal Effects of Aldosterone on Potassium Homeostasis

The role of aldosterone in regulating K+ excretion in the distal nephron is well established in kidney physiology. In addition to effects on the kidney, aldosterone modulates K+ and Na+ transport in salivary fluid, sweat, airway epithelia, and colonic fluid. More controversial and less well defined is the role of aldosterone in determining the internal distribution of K+ across cell membranes in non-transporting epithelia. In vivo studies have been limited by the difficulty in accurately measuring overall K+ balance and factoring in both variability and secondary changes in acid-base balance, systemic hemodynamics, and other K+-regulatory factors such as hormones and adrenergic activity. Despite these limitations, the aggregate data support a contributory role of aldosterone along with insulin and catecholamines in the normal physiologic regulation of internal K+ distribution. The authors speculate differences in tissue sensitivity to aldosterone may also contribute to differential tissue response of cardiac and skeletal muscle to conditions of total body K+ depletion.

Children’s exposure to polycyclic aromatic hydrocarbon (PAHs): a review on urinary 1-hydroxypyrene and associated health effects

This article reviewed the published studies on the environmental exposure to polycyclic aromatic hydrocarbons (PAHs) among children and assessed the urinary 1-hydroxypyrene (1-OHP) level as a biomarker of exposure to PAHs. The current knowledge of the potential health effects of increased 1-OHP in children was reviewed. Additionally, the influence of genetic polymorphism on the urinary 1-OHP level was discussed in this review. The assembled data showed that children who are attending schools or living close to industrial and polluted urban areas might have greater exposure to higher concentrations of PAHs with a higher level of urinary 1-OHP when compared to those children living in rural areas. Urinary 1-OHP may be a reliable biomarker for determining the genotoxic effects, oxidative stress and inflammation caused by exposure to PAHs. Strong research evidence indicated that the total body burden of PAHs should be evaluated by biomonitoring of 1-OHP in line with other urinary PAHs metabolites (with 2–3 rings) to evaluate recent total exposure to PAHs. Overall, the study suggests implementing a mitigation plan to combat air pollution to provide a cleaner environment for children.

Relationships Between Serum Lipoprotein (a) And Sarcopenia In Elderly

Background: Examine the association of serum Lp(a) with sarcopenia in Chinese elderly.Methods: We conducted this study using 2015–2020 data from hospitalized Chinese people 60 years old and older. Total body fat percentage and appendicular skeletal muscle mass were assessed with a dual-energy X-ray absorptiometry scan. We classified the participants into four sarcopenia/obesity groups based on both total body fat percentage and appendicular skeletal muscle mass.Results: The analysis included data of 528 participants. the LP(a) level of sarcopenia was significantly higher than no sarcopenia, compared with obese or no obese groups. Furthermore, In the sarcopenic obesity group, the LP(a) level was highest. Correlation analysis showed that ASM/height2 was negatively correlated with LP(a). Logistic regression analysis showed that sarcopenia was positively associated with LP(a).Conclusions: Our study shows that sarcopenia appeared to be significantly associated with Lp(a) no matter the subjects had obesity or not.

Effect of dietary supplementation of lauric acid on growth performance, antioxidative capacity, intestinal development and gut microbiota on black sea bream (Acanthopagrus schlegelii)

A feeding trial of eight weeks was conducted to examine the influence of food supplementation with lauric acid (LA) on Acanthopagrus schlegelii (juvenile black sea bream). A 24 percent fish meal baseline diet was created, while the other two diets were generated with dietary supplementation of graded points of LA at 0.1 percent and 0.8 percent, respectively. Each diet was given a triplicate tank with 20 fish weighing 6.22 ± 0.19 g. In comparison with the control group, the weight gain rate, growth rate, as well as feed efficiency of fish fed of 0.1 percent diet of LA were considerably (P < 0.05) greater. The total body and dorsal muscle proximate compositions did not change significantly between groups (P > 0.05). Triglyceride (TG) content was considerably (P < 0.05) greater in the LA-supplemented meals eating group in comparison with the control group. In the group eating LA-supplemented meals, the height of villus and the number of goblet cells/villus were considerably (P < 0.05) larger. The microbial makeup of the gut was also studied. The differences in phyla, class, and family level were not statistically significant (P > 0.05). Firmicutes in the phylum, Betaproteobacteri, Gammaproteobacteria, and Clostridia in the class, and Clostridiaceae in the family were all substantially increased with higher levels of LA supplementation (P < 0.05). According to the findings of this study, an LA-supplemented diet improves fish development, antioxidative capability, gut microbiota and intestinal health.