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The warm-up (WU) and re-warm-up (R-WU) regimes in many team-sports, especially football and competition, plays an essential role in improving physical function and increasing communication between brain networks. The present study aimed to evaluate the effects of the R-WU on brain networks and physical performance in young soccer players. After familiarizing the laboratory conditions, twelve young male soccer players (age 18.2 ± 0.5 years) performed only one WU protocol, which included 25 minutes and two parts of general and specialized warming up in one session. In addition to warming up in the next session, the participant performed an R-WU that included four sets of plyometric movements, five jumps from obstacles to a height of 40 cm, followed by crossing the agile ladder. Functional magnetic resonance imaging (fMRI), 20 m speed, and Illinois test were used to evaluate the function of brain networks and physical function. The subjects showed a significant increase in the performance of both speed and agility in the R-WU session compared to the warm-up session (P ≤ 0.01). Also, a positive relationship was observed between the performance of default, executive, and attention networks in the R-WU session compared to the WU session (P ≤ 0.01, P ≤ 0.03). The present study demonstrated that the R-WU program improved the relationship between brain networks and physical function in soccer players. [ABSTRACT FROM AUTHOR]

The software development life cycle relies heavily on the software release note, a crucial document. Various practitioners, including project managers and clients, benefit from release notes as they provide an overview of the latest software release. However, the manual generation of release notes is a time‐consuming and stressful task. Researchers have recently proposed automated techniques to generate release notes, saving developers' time and enhancing their understanding of software projects. Unfortunately, the adoption of these tools in practice remains limited. To address this gap, we have taken steps to understand the expectations and requirements of practitioners regarding release note generation techniques before implementing new automated approaches. Consequently, our approach involves two main stages: First, we conduct a comprehensive review of the relevant literature and analyze existing release notes from GitHub repositories to gain insights into the current practices. Second, we conduct an online survey study to gather input from practitioners and understand their expectations regarding release notes. We have reviewed 16 papers related to release notes and explored 3347 release notes from 21 GitHub repositories. Our analysis revealed key artifacts present in release note contents, including issues (29%), pull requests (32%), commits (19%), and common vulnerabilities and exposures (CVE) issues (6%). Additionally, we conducted a survey study involving 32 professionals to understand the essential information that should be included in release notes based on users' roles. For instance, project managers were more interested in learning about new features rather than less critical bug fixes. Furthermore, we identified gaps in existing systems and essential factors to consider when implementing release notes techniques in software engineering. The insights gained from our study can guide future research directions and assist practitioners in generating release notes with relevant content, thus improving the overall quality of documentation in software development. [ABSTRACT FROM AUTHOR]

Purpose: Dietary fats with an abundance of phytonutrients have garnered public attention beyond fatty acids per se. This study was set to investigate the impact of consuming diets with red palm olein (RPOO), extra virgin coconut oil (EVCO) and extra virgin olive oil (EVOO, as a control) on cardiometabolic risk biomarkers and lipid profile. Methods: We recruited a total of 156 individuals with central obesity, aged 25–45 years, with waist circumference ≥ 90 cm for men and ≥ 80 cm for women in a parallel single-blind 3-arm randomised controlled trial. The participants consumed isocaloric diets (~ 2400 kcal) enriched with respective test fats (RPOO, EVCO or EVOO) for a 12-week duration. Results: The mean of the primary outcome plasma high sensitivity C-reactive protein was statistically similar between the three diets after a 12-week intervention. EVOO resulted in significantly lower mean LDL cholesterol compared with RPOO and EVCO, despite similar effects on LDL and HDL cholesterol subfractions. The RPOO diet group showed elevated mean α and β -carotenes levels compared with EVCO and EVOO diet groups (P < 0.05), corresponding with the rich carotenoid content in RPOO. Conclusion: The three oils, each of which has unique phytonutrient and fatty acid compositions, manifested statistically similar cardiometabolic effects in individuals with central obesity at risk of developing cardiovascular diseases with distinct circulating antioxidant properties. Clinical trial registration: ClinicalTrials.gov (NCT05791370). [ABSTRACT FROM AUTHOR]

We investigated the pharmacokinetic pathway of berberine and its metabolites in vitro, in Caco-2 cells, and in human participants following the administration of dihydroberberine (DHB) and micellar berberine (LipoMicel®, LMB) formulations. A pilot trial involving nine healthy volunteers was conducted over a 24 h period; blood samples were collected and subjected to Ultra High-Performance Liquid Chromatography–High Resolution Mass Spectrometry (UHPLC-HRMS) analyses to quantify the concentrations of berberine and its metabolites. Pharmacokinetic correlations indicated that berberrubine and thalifendine follow distinct metabolic pathways. Additionally, jatrorrhizine sulfate appeared to undergo metabolism differently compared to the other sulfated metabolites. Moreover, berberrubine glucuronide likely has a unique metabolic pathway distinct from other glucuronides. The human trial revealed significantly higher blood concentrations of berberine metabolites in participants of the DHB treatment group compared to the LMB treatment group—except for berberrubine glucuronide, which was only detected in the LMB treatment group. Similarly, results from in vitro investigations showed significant differences in berberine metabolite profiles between DHB and LMB. Dihydroberberine, dihydroxy-berberrubine/thalifendine and jatrorrhizine sulfate were detected in LMB-treated cells, but not in DHB-treated cells; thalifendine and jatrorrhizine-glucuronide were detected in DHB-treated cells only. While DHB treatment provided higher blood concentrations of berberine and most berberine metabolites, both in vitro (Caco-2 cells) and in vivo human studies showed that treatment with LMB resulted in a higher proportion of unmetabolized berberine compared to DHB. These findings suggest potential clinical implications that merit further investigation in future large-scale trials. [ABSTRACT FROM AUTHOR]

Cardiomyopathies (CMP) represent a significant health problem as they have a poor long-term prognosis and often require transplantation. Heavy metals are known to have cardiotoxic effects and some of them, such as cadmium (Cd), are found to be elevated in the urine and blood of individuals with heart diseases; nevertheless, direct measurement of metals (e.g. zinc (Zn) which is necessary for normal heart function), in the myocardium of individuals with CMP has not been performed. Here, we aimed to analyze the levels of a group of metals in the myocardium of the left ventricle in individuals with CMP. At the Institute of Pathology, we collected 52 samples of left ventricle post-mortem, out of which 19 subjects had been diagnosed with CMP (mean age: 72 y ± 10), and 33 subjects had not suffered from any heart disease (mean age: 67 y ± 15). We found out that individuals with CMP had a significantly higher concentrations of lead, nickel, manganese and copper than non-CMP subjects (p = 0.002, p < 0.001, p = 0.011, and p = 0.002). Interestingly, zinc was significantly lower in CMP subjects than in n-CMP individuals (p = 0.017). Our results indicated the involvement of an increased lead, nickel, copper and manganese heart load in individuals with CMP coupled with lower concentrations of zinc. [ABSTRACT FROM AUTHOR]

We carried out a human volunteer study with 14 participants, eight of whom were asked to consume one cup of coffee at four different time points. Urine samples were collected at eight time points and analyzed by HPLC‐MS analysis. The LC‐MS data were subjected to unsupervised multivariate statistical analysis (principal component analysis) followed by supervised multivariate analysis (linear discriminant analysis). In an unbiased approach, in the absence of data preselection and filtering, the most important features explaining differences between coffee consumers and the control group observed showed variations in endogenous human hormonal steroid metabolites as well as xanthine derivatives. Only after a biased data treatment data revealed differences between the sample groups based on literature reported chlorogenic acid metabolites resulting directly from coffee intake. Such analysis could confirm the presence of 21 previously reported chlorogenic acid plasma metabolites as urinary metabolites. The application of tandem MS molecular networking revealed the presence of five bioavailable chlorogenic acid derivatives in urine previously not reported, including both quinic acid lactone and dimethoxy caffeoyl esters. Selected cinnamic acids were quantified in urine. [ABSTRACT FROM AUTHOR]

Mixed tree nuts (MTNs) are an excellent source of protein and healthy fat contributing to satiety. However, their relatively high caloric content might not be beneficial in a weight loss diet. The present study was designed to test whether including MTNs in a weight loss and maintenance program interferes with weight management compared to a refined carbohydrate pretzel snack (PS). We performed a randomized, controlled, two-arm study in 95 overweight individuals consuming 1.5 oz of MTNs or PS daily as part of a hypocaloric weight loss diet (-500 kcal) over 12 weeks followed by an isocaloric weight maintenance program for 12 weeks. Participants in both groups experienced significant weight loss (12 weeks: -1.6 and -1.9 and 24 weeks: -1.5 and -1.4 kg) compared to baseline in the MTN and PS groups, respectively. However, there was no difference in weight loss and other outcome parameters between the MTN and PS groups. The MTN group showed a significant increase in satiety at 24 weeks. Both groups had a decrease in diastolic blood pressure at 12 weeks. Participants in the MTN group showed significant decreases in heart rate at 4, 12, and 24 weeks. Plasma oleic acid was significantly increased at 12 and 24 weeks in the MTN group but only at 12 weeks in the PS group. Plasma MCP-1 was decreased significantly in the MTN group at 4 weeks. In summary, participants in both groups lost weight, but only the MTN intervention increased satiety at 24 weeks, enhanced retention, decreased heart rate, and increased serum oleic acid at 24 weeks.

We investigated the pharmacokinetic pathway of berberine and its metabolites in vitro, in Caco-2 cells, and in human participants following the administration of dihydroberberine (DHB) and micellar berberine (LipoMicel®, LMB) formulations. A pilot trial involving nine healthy volunteers was conducted over a 24 h period; blood samples were collected and subjected to Ultra High-Performance Liquid Chromatography–High Resolution Mass Spectrometry (UHPLC-HRMS) analyses to quantify the concentrations of berberine and its metabolites. Pharmacokinetic correlations indicated that berberrubine and thalifendine follow distinct metabolic pathways. Additionally, jatrorrhizine sulfate appeared to undergo metabolism differently compared to the other sulfated metabolites. Moreover, berberrubine glucuronide likely has a unique metabolic pathway distinct from other glucuronides. The human trial revealed significantly higher blood concentrations of berberine metabolites in participants of the DHB treatment group compared to the LMB treatment group—except for berberrubine glucuronide, which was only detected in the LMB treatment group. Similarly, results from in vitro investigations showed significant differences in berberine metabolite profiles between DHB and LMB. Dihydroberberine, dihydroxy-berberrubine/thalifendine and jatrorrhizine sulfate were detected in LMB-treated cells, but not in DHB-treated cells; thalifendine and jatrorrhizine-glucuronide were detected in DHB-treated cells only. While DHB treatment provided higher blood concentrations of berberine and most berberine metabolites, both in vitro (Caco-2 cells) and in vivo human studies showed that treatment with LMB resulted in a higher proportion of unmetabolized berberine compared to DHB. These findings suggest potential clinical implications that merit further investigation in future large-scale trials.

Lupinus angustifolius has a unique nutrient profile among legumes and may have beneficial health effects when included in the diet. The aim of this study was to investigate the biological properties of blue lupin (Lupinus angustifolius), its chemical components, and their relevance for monitoring biological and anthropometric health markers, including triglycerides (TGs), low-density lipoprotein cholesterol (LDL-C), BMI, weight, and glycemia, compared with control groups with other kinds of diets. PubMed, Web of Science, and Scopus databases, updated to December 2023, were searched. Out of the 194 studies identified, a total of 7 randomized controlled trials (RCTs) comprising 302 participants met the eligibility criteria. The results of our study indicated that the blue lupin diet has a direct relationship with parameters such as blood glucose, weight, and LDL-C but not with TGs or BMI. In conclusion, the research described in this review clearly indicates that L. angustifolius may play an important role in the dietary prevention of hyperlipidemia and hypertension. Therefore, it would be highly advisable to increase its consumption in diets. However, further studies, ideally in humans, are required to truly establish L. angustifolius's health-promoting properties. [ABSTRACT FROM AUTHOR]

Hearing aids help overcome the challenges associated with hearing loss, and thus greatly benefit and improve the lives of those living with hearing-impairment. Unfortunately, there is a lack of adoption of hearing aids among those that can benefit from hearing aids. Hearing researchers and audiologists are trying to address this problem through their research. However, the current proprietary hearing aid market makes it difficult for academic researchers to translate their findings into commercial use. In order to abridge this gap and accelerate research in hearing health care, we present the design and implementation of the Open Speech Platform (OSP), which consists of a co-design of open-source hardware and software. The hardware meets the industry standards and enables researchers to conduct experiments in the field. The software is designed with a systematic and modular approach to standardize algorithm implementation and simplify user interface development. We evaluate the performance of OSP regarding both its hardware and software, as well as demonstrate its usefulness via a self-fitting study involving human participants.

Nowadays, Artificial Intelligence systems have expanded their competence field from research to industry and daily life, so understanding how they make decisions is becoming fundamental to reducing the lack of trust between users and machines and increasing the transparency of the model. This paper aims to automate the generation of explanations for model-free Reinforcement Learning algorithms by answering "why" and "why not" questions. To this end, we use Bayesian Networks in combination with the NOTEARS algorithm for automatic structure learning. This approach complements an existing framework very well and demonstrates thus a step towards generating explanations with as little user input as possible. This approach is computationally evaluated in three benchmarks using different Reinforcement Learning methods to highlight that it is independent of the type of model used and the explanations are then rated through a human study. The results obtained are compared to other baseline explanation models to underline the satisfying performance of the framework presented in terms of increasing the understanding, transparency and trust in the action chosen by the agent. [ABSTRACT FROM AUTHOR]

Neurodegenerative diseases are caused by the gradual loss of neurons' function. These neurological illnesses remain incurable, and current medicines only alleviate the symptoms. Given the social and economic burden caused by the rising frequency of neurodegenerative diseases, there is an urgent need for the development of appropriate therapeutics. Natural compounds are gaining popularity as alternatives to synthetic drugs due to their neuroprotective properties and higher biocompatibility. While natural compounds' therapeutic effects for neurodegenerative disease treatment have been investigated in numerous in vitro and in vivo studies, only few have moved to clinical trials. This article provides the first systematic review of the clinical trials evaluating natural compounds' safety and efficacy for the treatment of the five most prevalent neurodegenerative disorders: Alzheimer's disease, Parkinson's disease, multiple sclerosis, amyotrophic lateral sclerosis, and Huntington's disease. [ABSTRACT FROM AUTHOR]

Background/Aims: Hyaluronan (HA) oligosaccharides are involved in several biological processes, primarily collagen remodeling and wound healing. Collagen remodeling is retarded in aging skin and causes wrinkles. The aim of this study was to evaluate the effect of 2‐kDa HA oligosaccharides (HA2k) on wrinkles by permeation through the stratum corneum and promotion of collagen remodeling. Methods: A 3D skin model and excised human skin were used to evaluate the permeation of fluorescein‐labeled HA2k. The effect of HA2k on collagen metabolism was evaluated by measuring the protein level of type 1 pro‐collagen (COL1A1) and matrix metalloproteinase‐1 (MMP‐1) in the 3D skin model. 0.1% HA2k solution and vehicle control was applied to the human forearm for 8 weeks to evaluate dermal collagen density. To evaluate the effect of HA2k on depth of facial wrinkles, a randomized controlled trial was conducted with 0.1% HA2k lotion and vehicle lotion for 8 weeks. Results: HA2k was confirmed to permeate through the stratum corneum by fluorescent microscopy. Both COL1A1 and MMP‐1 were upregulated by HA2k application in a 3D skin model culture. The collagen density was higher for the HA2k‐treated forearm than for the vehicle control‐treated forearm after 4 weeks. The maximum wrinkle depths in the nasolabial fold and crow's feet area were significantly shallower in the HA2k lotion group than in the control group. Conclusion: HA2k permeated the stratum corneum, activated collagen synthesis and degradation simultaneously, and ameliorated wrinkles. [ABSTRACT FROM AUTHOR]

Context: Clarification of the association among phenotypes, genetic, and environmental factors with clinical laboratory traits can reveal the cause of diseases and assist in developing methods for the prediction and prevention of diseases. It is difficult to investigate the environmental effect on phenotypes using individual samples because their genetic and environmental factors differ, but we can easily investigate the influence of environmental factors using monozygotic (MZ) twins because they have the same genetic factors. Objective: We aimed to examine the methylation level of CpG sites as an environmental factor affecting adiponectin levels on the basis of the same genetic background using MZ twins and to identify the epigenetic factors related to adiponectin levels and the genetic factors associated with sensitivity to acquired changes in adiponectin. Methods: Using 2 groups built from each twin of 232 MZ twin pairs, we performed a replicated epigenome-wide association study to clarify the epigenetic factors affecting adiponectin levels adjusted by genetic risk score. Moreover, we divided twin pairs into concordant and discordant for adiponectin levels. We conducted a genome-wide association study to identify a genetic background specific for discordance. Results: Methylation levels at 38 CpG sites were reproducibly associated with adjusted adiponectin levels, and some of these CpG sites were in genes related to adiponectin, including CDH13. Some genes related to adiponectin or insulin resistance were found to be genetic factors specific for discordance. Conclusion: We clarified specific epigenetic factors affecting adiponectin levels and genetic factors associated with sensitivity to acquired changes in adiponectin. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate histologically and histomorphometrically the effect of a delayed load on healing at implants with a moderately rough surface. Materials and Methods: Two solid titanium screw-shaped devices, 5 mm long and 3.5 mm in diameter, were inserted in the distal segments of the alveolar ridge of 16 volunteer patients in a nonsubmerged fashion. After 2 months, one implant was loaded, while the other was left unloaded. After 2 months, the two implants were collected from 10 patients using a sonic instrument, and ground sections were prepared from the biopsy specimens. Histomorphometric analyses were performed. Results: After 4 months of healing, biopsy specimens from 10 patients were available for analyses (n = 10). The total bone-to-implant contact percentage was 86.8% ± 6.5% and 84.6% ± 3.7% for loaded and unloaded implants, respectively. New bone was represented by 85.5% ± 6.7% and 83.4% ± 3.9% at the loaded and unloaded sites, respectively. A very small amount of old parent bone was found. The density of the mineralized bone was 76.8% ± 8.3% for the loaded sites and 74.1% ± 10.5% for the unloaded sites. The percentages of new and old bone densities were 69.0% ± 8.3% and 7.8% ± 3.9% at the loaded sites, and 65.9% ± 10.3% and 8.2% ± 4.5% at the unloaded sites, respectively. No statistically significant differences were disclosed. Conclusion: Applying a delayed load to implants supporting single crowns did not yield statistically significant differences, and only a tendency of higher osseointegration and bone density was observed at loaded sites compared with the unloaded sites. [ABSTRACT FROM AUTHOR]

Zinc, an indispensable micronutrient for human health, might play an important role in the development of atherosclerosis. Zinc could be involved in the atherogenic process through interaction with atherogenic cells, such as endothelial cells (ECs), vascular smooth muscle cells (VSMCs), and immune cells. In addition, zinc also exerts important positive or negative functions in various atherosclerosis-related risk factors, including lipid metabolism, glucose metabolism, and blood pressure. Currently, evidence focusing on the relationship between zinc status and atherogenic risk factors has been well established, while the direct interaction between zinc and atherosclerosis has not been fully understood. In this review, we aimed to summarize the association between zinc and atherosclerosis and explore current findings on how zinc and zinc homeostasis-associated proteins act in the atherogenic processes. [ABSTRACT FROM AUTHOR]

Depressive disorders (DDs) are an increasingly common health problem that affects all age groups. DDs pathogenesis is multifactorial. However, it was proven that stress is one of the most important environmental factors contributing to the development of these conditions. In recent years, there has been growing interest in the role of the glutamatergic system in the context of pharmacotherapy of DDs. Thus, it has become increasingly important to explore the functioning of excitatory synapses in pathogenesis and pharmacological treatment of psychiatric disorders (including DDs). This knowledge may lead to the description of new mechanisms of depression and indicate new potential targets for the pharmacotherapy of illness. An excitatory synapse is a highly complex and very dynamic structure, containing a vast number of proteins. This review aimed to discuss in detail the role of the key postsynaptic proteins (e.g., NMDAR, AMPAR, mGluR5, PSD-95, Homer, NOS etc.) in the excitatory synapse and to systematize the knowledge about changes that occur in the clinical course of depression and after antidepressant treatment. In addition, a discussion on the potential use of ligands and/or modulators of postsynaptic proteins at the excitatory synapse has been presented. [ABSTRACT FROM AUTHOR]

Petals of edible flowers (EF) are rich in biologically active compounds with many proven benefits for human health. However, studies on the effects of EF in humans after consumption are lacking. This pilot explorative study evaluated the changes in urinary phenolic excretion in healthy volunteers to whom different doses of phenolics from edible roses (Gourmet Roses™) have been added to a meal. Rose petals were picked fresh once a week for three weeks, showing significantly increasing values of total phenolic content, total anthocyanin content, and antioxidant activity (measured as ferric reducing antioxidant power (FRAP) and as DPPH • and ABTS •+ scavenging activities) from the first to the third week. After the meal, direct associations between urinary phenolics and both the EF phenolic content and the antioxidant activity were found in a multiple regression model. These new insights on EF consumption, to be confirmed by larger trials, suggest that the urinary phenolic excretion of healthy volunteers increases with increasing rose phenolic content.

Lupinus angustifolius has a unique nutrient profile among legumes and may have beneficial health effects when included in the diet. The aim of this study was to investigate the biological properties of blue lupin (Lupinus angustifolius), its chemical components, and their relevance for monitoring biological and anthropometric health markers, including triglycerides (TGs), low-density lipoprotein cholesterol (LDL-C), BMI, weight, and glycemia, compared with control groups with other kinds of diets. PubMed, Web of Science, and Scopus databases, updated to December 2023, were searched. Out of the 194 studies identified, a total of 7 randomized controlled trials (RCTs) comprising 302 participants met the eligibility criteria. The results of our study indicated that the blue lupin diet has a direct relationship with parameters such as blood glucose, weight, and LDL-C but not with TGs or BMI. In conclusion, the research described in this review clearly indicates that L. angustifolius may play an important role in the dietary prevention of hyperlipidemia and hypertension. Therefore, it would be highly advisable to increase its consumption in diets. However, further studies, ideally in humans, are required to truly establish L. angustifolius’s health-promoting properties.

Drug‐resistant epilepsy (DRE) is characterized by recurrent seizures despite appropriate treatment with antiseizure medication (ASM). Due to their regenerative and immunomodulatory potential, therapies with biologics such as mesenchymal stem cells (MSCs) offer a potential therapeutic benefit for structural causes of epilepsy, such as hippocampal sclerosis. In this article, we report a systematic review of the literature evaluating the preclinical and clinical studies of MSCs for DRE. Medline, Ovid EMBASE, Scopus, and the Cochrane Databases were searched electronically from their dates of inception to November 2021 using the following keywords: (("mesenchymal") AND ("stem cell")) AND (("epilepsy") OR ("convulsion") OR ("seizures")). This review followed Preferred Reporting Items for Systemic Reviews and Meta‐Analyses (PRISMA) guidelines. The initial query identified 488 studies representing 323 unique manuscripts. After application of selection criteria, 15 studies were included in this systematic review; 11 were preclinical studies and 4 were clinical studies. All preclinical studies were performed in rodents and all clinical studies were phase 1 trials. Thus far, therapy with MSCs appears to be safe for use in humans, as no severe adverse events related directly to the therapy were reported. Furthermore, MSC therapy appears to provide a statistically significant clinical benefit by reducing the seizure burden of patients, reducing the electrophysiological biomarkers of epilepsy, and improving their comorbidities, such as depression and anxiety. In addition, animal studies reveal that the therapy exerts its effect by reducing aberrant mossy fiber sprouting (reduce excitatory pathways) and increasing γ‐aminobutyric acid (GABA)ergic interneurons (increase inhibitory pathways). Both preclinical and clinical studies have shown MSC therapy to be safe and preliminary effective, thus warranting further studies to investigate its therapeutic potential. [ABSTRACT FROM AUTHOR]

MucoRice-CTB is a promising cold-chain-free oral cholera vaccine candidate. Here, we report a double-blind, randomized, placebo-controlled, phase I study conducted in the USA in which vaccination with the 6-g dose of MucoRice-CTB induced cross-reactive antigen-specific antibodies against the B subunit of cholera toxin (CTB) and enterotoxigenic Escherichia coli heat-labile enterotoxin without inducing serious adverse events. This dosage was acceptably safe and tolerable in healthy men and women. In addition, it induced a CTB-specific IgA response in the saliva of two of the nine treated subjects; in one subject, the immunological kinetics of the salivary IgA were similar to those of the serum CTB-specific IgA. Antibodies from three of the five responders to the vaccine prevented CTB from binding its GM1 ganglioside receptor. These results are consistent with those of the phase I study in Japan, suggesting that oral MucoRice-CTB induces neutralizing antibodies against diarrheal toxins regardless of ethnicity. [ABSTRACT FROM AUTHOR]

• An association between pitch and cortical bone thickness was identified. • Pitch had a high negative correlation with the primary stability of a mini-implant. • Cortical bone thickness had a positive correlation with the primary stability. • The primary stability tests demonstrated a pitch-dependent decrease. The purpose of this study was to mathematically evaluate the influence of variations in thread pitch and cortical bone thickness on the maximum insertion torque (MIT) and implant stability (IS) of miniscrew implants (MIs). Sixty custom made MIs with a 0.4-, 0.6-, 0.8-, 1.0-, or 1.2-mm thread pitch,12 for each pitch, were randomly placed into the palates of 10 embalmed human maxillae. The MIT was measured with a hand-operated digital torque reader screwdriver with a holding guide, and the IS test was performed using Anycheck. Conebeam computerized tomography was used to measure the cortical bone thickness(CBT) at each MI site. One-way ANOVA, Tukey post hoc test, Pearson's correlation,and multiple linear regression models were performed using the SPSS program. The MIT and IS tests demonstrated a pitch-dependent decrease. The pitch had a strong negative correlation with MIT and IS, while the CBT had a strong positive correlation with those outcomes. The association between pitch and CBT significantly influenced MI primary stability. Moreover, a strong correlation was found between MIT and IS. The MI primary stability, MIT, and IS are strongly influenced by theassociation between MI thread pitch and CBT. [ABSTRACT FROM AUTHOR]

Arterial spin labeling (ASL) imaging is a powerful magnetic resonance imaging technique that allows to quantitatively measure blood perfusion non‐invasively, which has great potential for assessing tissue viability in various clinical settings. However, the clinical applications of ASL are currently limited by its low signal‐to‐noise ratio (SNR), limited spatial resolution, and long imaging time. In this work, we propose an unsupervised deep learning‐based image denoising and reconstruction framework to improve the SNR and accelerate the imaging speed of high resolution ASL imaging. The unique feature of the proposed framework is that it does not require any prior training pairs but only the subject's own anatomical prior, such as T1‐weighted images, as network input. The neural network was trained from scratch in the denoising or reconstruction process, with noisy images or sparely sampled k‐space data as training labels. Performance of the proposed method was evaluated using in vivo experiment data obtained from 3 healthy subjects on a 3T MR scanner, using ASL images acquired with 44‐min acquisition time as the ground truth. Both qualitative and quantitative analyses demonstrate the superior performance of the proposed txtc framework over the reference methods. In summary, our proposed unsupervised deep learning‐based denoising and reconstruction framework can improve the image quality and accelerate the imaging speed of ASL imaging. [ABSTRACT FROM AUTHOR]

Carotenoids have been the object of numerous observational, pre-clinical and interventional studies focused on elucidating their potential impacts on human health. However, the large heterogeneity among the trials, in terms of study duration and characteristics of participants, makes any conclusion difficult to draw. The present study aimed to explore the current carotenoid research trends by analyzing the characteristics of the registered clinical trials. A total of 193 registered trials on ClinicalTrials.gov and ISRCTN were included in the revision. Eighty-three studies were performed with foods, one-hundred-five with food supplements, and five with both. Among the foods tested, tomatoes and tomato-based foods, and eggs were the most studied. Lutein, lycopene, and astaxanthin were the most carotenoids investigated. Regarding the goals, 52 trials were focused on studying carotenoids' bioavailability, and 140 studies investigated the effects of carotenoids on human health. The main topics included eye and cardiovascular health. Recently, the research has focused also on two new topics: cognitive function and carotenoid–gut microbiota interactions. However, the current research on carotenoids is still mostly focused on the bioavailability and metabolism of carotenoids from foods and food supplements. Within this context, the impacts/contributions of food technologies and the development of new carotenoid formulations are discussed. In addition, the research is still corroborating the previous findings on vision and cardiovascular health. Much attention has also been devoted to new research areas, such as the carotenoid–microbiota interactions, which could contribute to explaining the metabolism and the health effects of carotenoids; and the relation between carotenoids and cognitive function. However, for these topics the research is still only beginning, and further studies are need. [ABSTRACT FROM AUTHOR]

Recently, there is a growing concern about the use of curcumin supplements owing to a few reported hepatotoxicity related adverse events among some of the long-term consumers. Even though no clear evidence was elucidated for the suspected toxicity, the addition of adjuvants that inhibits body’s essential detoxification pathways, adulteration with synthetic curcumin, and presence of contaminants including heavy metals, chromate, illegal dyes, non-steroidal anti-inflammatory agents, and pyrrole alkaloids were suggested as plausible reasons. Considering these incidences and speculations, there is a need to critically evaluate the safety of curcumin supplements for prolonged intake. The present study is an evaluation of the safety of curcumin-galactomannoside complex (CGM), a highly bioavailable curcumin formulation with demonstrated high free curcuminoids delivery. Twenty healthy human volunteers were evaluated for toxic manifestations of CGM when supplemented with 1000 mg per day (∼380 mg curcuminoids) for 90-days. CGM supplementation did not cause any adverse effects or clinically significant variations in the vital signs, hematological parameters, lipid profile and renal function markers of the volunteers, indicating its safety. Liver function enzymes aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), gamma-glutamyl transferase (GGT) and bilirubin were in the normal range after 90-day supplementation of CGM. In summary, no adverse effects were observed under the conditions of the study. CGM can be considered as a safe curcumin supplement for regular consumption and is devoid of any adulterants or contaminants.

Purpose. The purpose of the study is to show the connection of romanticism with the anthropological doctrine that goes back to Hegelianism and Kantianism, and at the same time – with the concepts of the future, structuralism and postmodernism. Theoretical basis. The man is a central figure of the Romantic literary, therefore it makes sense to single out romantic human anthropological doctrine and the image of man associated with a specific historical and cultural era called the "epoch of romanticism"; to show that many romantic philosophical positions remained relevant to the basic foundations of contemporary anthropological research and coincide with it in analytical and critical thinking about a man, a person, his historical and evolutionary fate. Originality. The romantic worldview determined the specifics of anthropological discourse, both logical and illogical, remaining symbols and attaching, as for example, a real historical anecdote, a popular history, a philosophical thought, a myth, a famous literary episode and the arts multiplied by creative inspiration and imagination. This tendency determined the fragmentation of thinking and the scientific image of man as a dual being, nevertheless, presented and described in all the variety of relations with the world and with himself, that allows us to call this area of thought "the romantic human science". Conclusions. Structural analysis of numerous romantic texts allows us to draw the following conclusion: with mythopoetic imagery and anthropological thought about a man, romantic writers introduced the reader to any wisdom, to philosophical understanding of their human essence, to past and modern teachings, in a way processed antique, medieval and enlightening views, in which an important place was given to reflections on the place of man in nature, society, and history. Correlating the well-known statements about a person as a descendant of the "old Adam", "person", "personality", "soul", with the modern idea of historical and social development, about the evolution of the consciousness of a person who revealed himself as an individual in modern times, with scientific and aesthetic views, the writers of the first half of the XIX century gave romantic thought anthropological meaning and, in fact, laid the foundations of historical, social, psychological, cultural and psychoanalytic anthropology.

The identification and validation of biomarkers of food intake (BFIs) is a promising approach to develop more objective and complementary tools to the traditional dietary assessment methods. Concerning dairy, their evaluation in terms of intake is not simple, given the variety of existing foods, making it difficult to establish the association between specific dairy products consumption and the effects on human health, which is also dependent on the study population. Here, we aimed at identifying BFI of both milk (M) and yogurt (Y) in 14 healthy young (20–35 years) and 14 older (65–80 years). After a 3-week run-in period of dairy exclusion from the diet, the subjects acutely consumed 600 ml of M or Y. Metabolomics analyses were conducted on serum samples during the following 6 h (LC-MS and GC-MS). Several metabolites showing increased iAUC after milk or yogurt intake were considered as potential BFI, including lactose (M > Y, 2-fold), galactitol (M > Y, 1.5-fold), galactonate (M > Y, 1.2-fold), sphingosine-1-phosphate (M > Y from 2.1-fold), as well as an annotated disaccharide (Y > M, 3.6-fold). Delayed serum kinetics were also observed after Y compared to M intake lysine (+22 min), phenylalanine (+45 min), tyrosine (+30min), threonine (+38 min) 3-phenyllactic acid (+30 min), lactose (+30 min), galactitol (+45min) and galactonate (+30 min). The statistical significance of certain discriminant metabolites, such as sphingosine-1-phosphate and several free fatty acids, was not maintained in the older group. This could be related to the physiological modifications induced by aging, like dysregulated lipid metabolism, including delayed appearance of dodecanoic acid (+60 min) or altered postprandial appearance of myristic acid (+70% Cmax), 3-dehydroxycarnitine (−26% Cmin), decanoylcarnitine (−51% Cmin) and dodecanoylcarnitine (−40% Cmin). In conclusion, candidate BFI of milk or yogurt could be identified based on the modified postprandial response resulting from the fermentation of milk to yogurt. Moreover, population specificities (e.g., aging) should also be considered in future studies to obtain more accurate and specific BFI.

The effects of Sparassis crispa (Hanabiratake Mushroom: HM) on the anti-cancer action, anti-diabetic action, and anti-immune deficiency have been published and these effects are due to the p-1,3-glucans. However, the recent in vitro studies suggest that HM activates the estrogen related signal transduction without any stimulation of estrogen-induced cancer cell. In this clinical study, we focused on lessen of physical and psychological discomforts seen in the women menopausal symptoms using HM. This randomized double-blind placebo-controlled trials advertised 122 healthy Japanese women and enrolled 50 subjects experiencing discomfort in the women menopausal symptoms (WMS). This study conducted from 11/11/19 to 2/22/2〇. Subjects were randomly allocated into either the test diet group (IT-HM) or the placebo group using a computerized random number generator. Subjects consumed three tablets per day of test diet (IT-HM: 200mg) or placebo diet for a period of 12 weeks. The primary outcome was composite the Simplified Menopausal Index (SMI) and the secondly outcome was Likert scale. In each group, 25 subjects were analyzed as a per-protocol dataset. In the test diet group but not the placebo group, the significant differences between before and 12 weeks of SMI score were detected. Particularly, were significantly reduced compared to placebo group of SMI (N 51)in the IT-HM group were remarkably improved. Furthermore, no adverse events were observed. Hence, this study suggests that the consequent intake of HM improve the psychological and physical discomforts in WMS due to the activation of estrogen related serotonergic neuron in the brain. [ABSTRACT FROM AUTHOR]

Context: Hyperphosphatemia and high levels of fibroblast growth factor 23 (FGF23) are risk factors for cardiovascular events in patients with chronic kidney diseases. However, the impact of an inorganic phosphorus additive in healthy people is largely unknown. Objective: We aimed to investigate the acute effect of excessive dietary phosphorus administered as sodium dihydrogen phosphate on the postprandial levels of Pi and FGF23 and the response to food. Methods: This study was a double-blind placebo-controlled crossover study with 29 healthy male and female participants from the general community who were administered a single dose of either 700 mg phosphorus (NaH2PO4) or a sodium-adjusted placebo in combination with a test meal. Postprandial plasma levels of Pi and FGF23 were measured. Results: Compared with placebo, oral phosphorus increased the plasma Pi level, which remained elevated during the ensuing 8 hours (at 480 minutes: 1.31 vs 1.16 mmol/l; P < 0.001), increased urinary Pi (iAUC0-480 789 vs 95 mmol/mmol; P < 0.001), reduced tubular Pi reabsorption (iAUC0-480 −31.5 vs −6.2; P < 0.001), decreased urinary calcium (iAUC0-240 30.6 vs 53.0 mmol/mmol; P = 0.009), and stimulated the release of parathyroid hormone (iAUC0-480 2212 vs 768 ng/l; P < 0.001). However, the FGF23 levels did not change. Postprandial levels of glucose, insulin, and lipids were not substantially affected by phosphorus vs placebo. Conclusion: An oral phosphorus load can induce elevated postprandial levels of circulating Pi for hours in healthy subjects, despite rapid homeostatic counterreactions. FGF23 levels and the postprandial response to food were not affected. [ABSTRACT FROM AUTHOR]

Hamamelis virginiana L. a rich source of both condensed and hydrolyzable tannins, utilized to treat dermatological disorders. Since no experimental and clinical data is available for its use as oral formulation in skin related disorders, the purpose of this study was to investigate the effects of Hamaforton™ (Hamamelis virginiana extract) metabolites on gene dysregulation induced by ultraviolet A radiation in cultured human dermal fibroblasts. A combination of in vivo and ex vivo experimental designs has been exploited in order to take into account the polyphenol metabolic transformation that occurs in humans. 12 healthy volunteers received either a capsule of Hamaforton™ or a placebo in a randomized, blinded crossover trial. After Hamaforton™ ingestion, the kinetic of appearance of galloyl derivatives was measured in plasma. Then, in the ex vivo experiment, the serum isolated after supplementation was used as a source of Hamaforton™ metabolites to enrich the culture medium of dermal fibroblasts exposed to ultraviolet A radiation. Three different gallic acid metabolites (4-O-methyl gallic acid, 4-O-methyl gallic acid sulphate and trimethyl gallic acid glucuronide) were identified in volunteer plasma. While, ultraviolet A irradiation of dermal fibroblasts affected the expression of extracellular matrix genes, the presence of Hamaforton™ metabolites in the culture media did not affect the expression of most of those genes. However, the activation of the expression of 10 different genes involved in repair processes for the maintenance of skin integrity, suggest that the metabolites can play a role in damage recovery. To our knowledge, this is the first study that demonstrates the bioavailability of Hamaforton™ phenolic compounds, and the effects of its metabolites on cultured dermal fibroblast response to ultraviolet A irradiation. [ABSTRACT FROM AUTHOR]

Nowadays, Artificial Intelligence systems have expanded their competence field from research to industry and daily life, so understanding how they make decisions is becoming fundamental to reducing the lack of trust between users and machines and increasing the transparency of the model. This paper aims to automate the generation of explanations for model-free Reinforcement Learning algorithms by answering “why” and “why not” questions. To this end, we use Bayesian Networks in combination with the NOTEARS algorithm for automatic structure learning. This approach complements an existing framework very well and demonstrates thus a step towards generating explanations with as little user input as possible. This approach is computationally evaluated in three benchmarks using different Reinforcement Learning methods to highlight that it is independent of the type of model used and the explanations are then rated through a human study. The results obtained are compared to other baseline explanation models to underline the satisfying performance of the framework presented in terms of increasing the understanding, transparency and trust in the action chosen by the agent.

Neurodegenerative diseases are caused by the gradual loss of neurons’ function. These neurological illnesses remain incurable, and current medicines only alleviate the symptoms. Given the social and economic burden caused by the rising frequency of neurodegenerative diseases, there is an urgent need for the development of appropriate therapeutics. Natural compounds are gaining popularity as alternatives to synthetic drugs due to their neuroprotective properties and higher biocompatibility. While natural compounds’ therapeutic effects for neurodegenerative disease treatment have been investigated in numerous in vitro and in vivo studies, only few have moved to clinical trials. This article provides the first systematic review of the clinical trials evaluating natural compounds’ safety and efficacy for the treatment of the five most prevalent neurodegenerative disorders: Alzheimer’s disease, Parkinson’s disease, multiple sclerosis, amyotrophic lateral sclerosis, and Huntington’s disease.

Hamamelis virginiana L. a rich source of both condensed and hydrolyzable tannins, utilized to treat dermatological disorders. Since no experimental and clinical data is available for its use as oral formulation in skin related disorders, the purpose of this study was to investigate the effects of Hamaforton™ (Hamamelis virginiana extract) metabolites on gene dysregulation induced by ultraviolet A radiation in cultured human dermal fibroblasts. A combination of in vivo and ex vivo experimental designs has been exploited in order to take into account the polyphenol metabolic transformation that occurs in humans. 12 healthy volunteers received either a capsule of Hamaforton™ or a placebo in a randomized, blinded crossover trial. After Hamaforton™ ingestion, the kinetic of appearance of galloyl derivatives was measured in plasma. Then, in the ex vivo experiment, the serum isolated after supplementation was used as a source of Hamaforton™ metabolites to enrich the culture medium of dermal fibroblasts exposed to ultraviolet A radiation. Three different gallic acid metabolites (4-O-methyl gallic acid, 4-O-methyl gallic acid sulphate and trimethyl gallic acid glucuronide) were identified in volunteer plasma. While, ultraviolet A irradiation of dermal fibroblasts affected the expression of extracellular matrix genes, the presence of Hamaforton™ metabolites in the culture media did not affect the expression of most of those genes. However, the activation of the expression of 10 different genes involved in repair processes for the maintenance of skin integrity, suggest that the metabolites can play a role in damage recovery. To our knowledge, this is the first study that demonstrates the bioavailability of Hamaforton™ phenolic compounds, and the effects of its metabolites on cultured dermal fibroblast response to ultraviolet A irradiation.

Folate, a vital water-soluble vitamin (B 9 ), requires specific attention as its recommended daily intake frequently is not reached in countries without mandatory fortification. In this regard, biofortification with microorganisms like Bifidobacterium and Streptococcus offers a compelling approach for enhancing food with natural folates. A randomized, nonblinded, and monocentric human pilot study is conducted to assess the bioavailability of a folate-biofortified fermented whey beverage, comprising 3 intervention days and a controlled replenishment phase before and during the assay. Folate plasma concentration (5-CH 3 -H 4 folate) is determined using a stable isotope dilution assay and LC-MS/MS detection. Biokinetic parameters (c max and t max ) are determined, and areas under the curve (AUC) normalized to the basal folate plasma concentration are calculated. An average bioavailability of 17.1% in relation to the 5-CH 3 -H 4 folate supplement, ranging from 0% to 39.8%, is obtained. These results reiterate the significance of additional research into folate bioavailability in general and dairy products. Further investigations are warranted into folate-binding proteins (FBP) and other potential limiting factors within the food and individual factors. In summary, biofortification via fermentation emerges as a promising avenue for enhancing the natural folate content in dairy and other food products., (© 2024 The Author(s). Molecular Nutrition & Food Research published by Wiley‐VCH GmbH.)

Microneedle (MN) patches are being developed for many different kinds of drugs, but are often limited to delivering sub-milligram doses. This is because larger patches can be more difficult to apply to the skin, and acceptability of larger MN patches by human subjects has received limited study. Here, we fabricated 18 different large MN patch designs by laser microfabrication with different MN length (800–1500 μm), number of MNs (225 to 900 MNs per patch), space between MNs (600–1100 μm), and MN base diameter (200–250 μm). After manual application of these patches to human participants, we assessed dose delivery efficiency, total dose delivered, dose delivered per MN, depth of MN penetration and whole-MN delivery efficiency. We found that all of these parameters generally increased with decreased MN length, increased number of MNs (among those ≤1000 μm in length) and increased MN-MN spacing. All MN patch designs caused less pain than a pin prick sensation and were generally considered acceptable by the study participants. The MN patches induced mild, or sometimes moderate, transient erythema on skin. Study participants showed higher preference for MN patches for long-acting contraception compared with conventional options, indicating strong interest and acceptability of MN patches in this study. [Display omitted] • Fabrication of 18 large MN patch designs with different geometrical parameters. • Patches with 800 μm long MNs have higher delivery efficiency than longer MNs. • Wide space between MNs can reduce "bed-of-nails" effect and enable insertion. • All MN patches were well tolerated and caused less pain than hypodermic needle. • High acceptability of MNs for long-acting contraception by study subjects [ABSTRACT FROM AUTHOR]

Elevated serum uric acid (SUA)—hyperuricemia—is caused by overproduction of urate or by its decreased renal and/or intestinal excretion. This disease, which is increasing in prevalence worldwide, is associated with both gout and metabolic diseases. Several studies have reported relationships between apolipoprotein E (APOE) haplotypes and SUA levels in humans; however, their results remain inconsistent. This prompted us to investigate the relationship between APOE polymorphisms and SUA levels. Our subjects were 5,272 Japanese men, premenopausal women, and postmenopausal women. Multiple linear regression analyses revealed the ε2 haplotype of APOE to be independently associated with higher SUA in men (N = 1,726) and postmenopausal women (N = 1,753), but not in premenopausal women (N = 1,793). In contrast, the ε4 haplotype was little related to SUA levels in each group. Moreover, to examine the effect of Apoe deficiency on SUA levels, we conducted animal experiments using Apoe knockout mice, which mimics ε2/ε2 carriers. We found that SUA levels in Apoe knockout mice were significantly higher than those in wild-type mice, which is consistent with the SUA-raising effect of the ε2 haplotype observed in our clinico-genetic analyses. Further analyses suggested that renal rather than intestinal underexcretion of urate could be involved in Apoe deficiency-related SUA increase. In conclusion, we successfully demonstrated that the ε2 haplotype, but not the ε4 haplotype, increases SUA levels. These findings will improve our understanding of genetic factors affecting SUA levels. [ABSTRACT FROM AUTHOR]

Petals of edible flowers (EF) are rich in biologically active compounds with many proven benefits for human health. However, studies on the effects of EF in humans after consumption are lacking. This pilot explorative study evaluated the changes in urinary phenolic excretion in healthy volunteers to whom different doses of phenolics from edible roses (Gourmet Roses™) have been added to a meal. Rose petals were picked fresh once a week for three weeks, showing significantly increasing values of total phenolic content, total anthocyanin content, and antioxidant activity (measured as ferric reducing antioxidant power (FRAP) and as DPPH• and ABTS•+ scavenging activities) from the first to the third week. After the meal, direct associations between urinary phenolics and both the EF phenolic content and the antioxidant activity were found in a multiple regression model. These new insights on EF consumption, to be confirmed by larger trials, suggest that the urinary phenolic excretion of healthy volunteers increases with increasing rose phenolic content. [ABSTRACT FROM AUTHOR]

Purpose: We present a unique opportunity to compare standard neck injury criteria (used by the automotive industry to predict injury) with real-life injuries. The injuries sustained during, and the overall kinematics of, a television demonstration of whiplash mechanics were used to inform and validate a vertebral level model of neck mechanics to examine the relevance of current injury criteria used by the automotive industry. Methods: Frontal and rear impact pulses, obtained from videos of sled motion, were used to drive a MADYMO human model to generate detailed segmental level biomechanics. The maximum amplitude of the frontal and rear crash pulses was 166 ms−2 and 196 ms−2, respectively, both with a duration of 0.137 s. The MADYMO model was used to predict standard automotive neck injury criteria as well as detailed mechanics of each cervical segment. Results: Whilst the subject suffered significant upper neck injuries, these were not predicted by conventional upper neck injury criteria (Nij and Nkm). However, the model did predict anterior accelerations of C1 and C2 of 40 g, which is 5 times higher than the threshold of the acceleration for alar ligament injury. Similarly, excessive anterior shear displacement (15 mm) of the skull relative to C2 was predicted. Predictions of NIC, an injury criterion relevant to the lower neck, as well as maximum flexion angles for the lower cervical segments (C3–T1) exceeded injury thresholds. Conclusion: The criteria used by the automotive industry as standard surrogates for upper neck injury (Nij and Nkm) did not predict the significant cranio-cervical junction injury observed clinically. [ABSTRACT FROM AUTHOR]

Isoquercitrin has been drawing increasing commercial concern since it has better bioavailability than quercetin and displays a wide range of in-vivo and in-vitro pharmacological effects. The main objective of the present study was to evaluate the pharmacokinetics of the IQC-γCD inclusion complex in Sprague-Dawley (SD) rats and in a controlled non-randomized, double-blind, and crossover study among the healthy volunteers. For instance, in SD rats administrated with IQC-γCD formulation by oral gavage feeding (0.05 mM/Kg body weight) showed significantly higher bioavailability (P

Background: The ketogenic diet (KD), a high-fat low-carbohydrate diet, has gained in popularity in recent years, which is reflected by an increasing number of scientific articles, books, websites, and other publications related to low carbohydrate (LC) diets and KDs. Numerous preclinical studies in different animal models of cancer have examined the effect of KDs on cancer growth, but no large randomized controlled studies or prospective cohort studies are available for human cancer patients. Evidence supporting the use of KDs as an adjunct to traditional cancer therapy has come predominantly from anecdotes and case reports. The first KD clinical trials in patients with glioblastoma revealed good acceptance and a possible anti-tumor effect. Metabolic therapy options such as the KD are not yet part of the standard of care in cancer patients. However, many cancer patients have begun implementing a KD or LC diet on their own. The aim of the present study was to gather information, via an online questionnaire, about how cancer patients go about implementing a KD or LC diet, what resources they rely on, whether they perceive benefits from the diet on quality of life (QoL), and what factors influence feasibility and adherence to the diet.Method: Recruitment of participants was carried out via social media platforms, forums and cooperating physicians (April 2018 through November 2018). To be eligible for the study, participants had to be diagnosed with cancer and on a KD or LC diet at the time of participating in the study or been on a KD or LC diet during cancer treatment. Study participants were asked to fill out an online questionnaire. The questionnaire was divided into four parts and contained a total of 64 questions. The questions were focused on the current health status of the participant, type of cancer, time since diagnosis, and treatment regimen. In addition, questions addressed social support, extent of professional counseling, food preferences and QoL.Results: A total of 96 participants (77 F, 17 M) submitted the questionnaire, of which 94 were included in the final data analysis. Ages ranged between 24 and 79 years (mean 50.1 ± 12.1 years). In 73.4% of the participants, the tumor had not formed metastases at the time of initial diagnosis. Twenty-four (26%) participants had a PET-positive tumor, 8 (9%) a PET-negative tumor, and the remainder (66.0%) did not report a PET scan. Eighty seven percent had undergone surgery in the course of their cancer treatment. The most frequent tumor type was breast cancer, followed by cervical cancer, prostate cancer, colorectal cancer and melanoma. Fifty nine percent of the study participants stated that they followed a KD during cancer therapy, 21% followed a low carbohydrate/high fat (LCHF) diet and 12% followed a low glycemic index (LOGI) diet. Sixty nine percent reported an improvement of QoL because of the diet. Almost half of the study participants sourced their initial information on KDs and LC diets from the internet. We found a significant correlation between weight loss upon implementation of a KD and the extent of overweight (p < 0.001). Weight loss in already lean participants was not reported. Overall, 67% of the participants found long-term adherence to the diet to be “easy” and 10.6% described it as being “very easy.” Participants who like fatty foods tended to perceive the diet as being easier to follow (p = 0.063).Conclusion: The KD or LC diet improved self-reported QoL in more than two-thirds of study participants. The KD had a normalizing effect on body weight. The majority of the participants rated the diet as easy or very easy to follow long term. There was an obvious gap between patients' desire for professional dietary counseling and what is currently offered by health care providers. In the future, efforts should be made to invest in nutrition experts who are trained in the KD to support cancer patients with implementation of a KD.

BACKGROUND: Propolis is a natural product collected by worker bees from a variety of plant species. As a type of propolis, Brazilian green propolis contains a large amount of artepillin C. Artepillin C is a cinnamic acid derivative and has been shown to have a wide variety of biological functions, including anti-inflammatory, antiviral and antitumor activities, in both cell culture and animal models. However, how propolis is digested and absorbed remains to be elucidated. Moreover, blood artepillin C levels after propolis intake have not been shown in human studies. RESULTS: A randomized, single-blind placebo-controlled study on the effect of Brazilian green propolis on serum artepillin C levels was conducted with healthy volunteers. The participants (n = 133) were randomly allocated in an approximately 2:1 ratio to two groups: propolis (n = 91) and placebo (n = 42). The participants took daily propolis or placebo, and blood tests were performed on day 0 (before propolis intake) and days 1, 3 and 7. Artepillin C was detected in serum in almost all individuals in the propolis groups. No serum artepillin C was detected in the placebo group. Serum artepillin C levels in the female group tended to be higher than those in the male group. In the female group, menstrual status was unrelated to serum artepillin C levels. CONCLUSION: These results suggested that propolis intake might be more effective for females than for males. [ABSTRACT FROM AUTHOR]

Objective: This cross-sectional study determined whether acute sensory irritative or (sub)chronic inflammatory effects of the eyes, nose or respiratory tract are observed in employees who are exposed to naphthalene at the workplace. Methods: Thirtynine healthy and non-smoking male employees with either moderate (n = 22) or high (n = 17) exposure to naphthalene were compared to 22 male employees from the same plants with no or only rare exposure to naphthalene. (Sub)clinical endpoint measures included nasal endoscopy, smell sensitivity, self-reported work-related complaints and the intensity of naphthalene odor and irritation. In addition, cellular and soluble mediators in blood, nasal lavage fluid (NALF) and induced sputum (IS) were analysed. All measurements were carried out pre-shift on Monday and post-shift on Thursday. Personal air monitoring revealed naphthalene shift concentrations up to 11.6 mg/m3 with short-term peak concentrations up to 145.8 mg/m3 and 1- and 2-naphthol levels (sum) in post-shift urine up to 10.1 mg/L. Results: Acute sensory irritating effects at the eyes and upper airways were reported to occur when directly handling naphthalene (e.g., sieving pure naphthalene). Generally, naphthalene odor was described as intense and unpleasant. Habituation effects or olfactory fatigue were not observed. Endoscopic examination revealed mild inflammatory effects at the nasal mucosa of exposed employees in terms of reddening and swelling and abnormal mucus production. No consistent pattern of cellular and soluble mediators in blood, NALF or IS was observed which would indicate a chronic or acute inflammatory effect of naphthalene in exposed workers. Conclusions: The results suggest that exposure to naphthalene induces acute sensory irritative effects in exposed workers. No (sub)chronic inflammatory effects on the nasal epithelium or the respiratory tract could be observed under the study conditions described here. [ABSTRACT FROM AUTHOR]

Abstract Neuropathological follow-up of patients with Alzheimer’s disease (AD) who participated in the first clinical trial of Amyloid-β 42 (Aβ42) immunization (AN1792, Elan Pharmaceuticals) has shown that immunization can induce removal of Aβ42 and Aβ40 from plaques, whereas analysis of the cerebral vessels has shown increased levels of these Aβ peptides in cerebral amyloid angiopathy (CAA). Aβ43 has been less frequently studied in AD, but its aggregation propensity and neurotoxic properties suggest it may have an important pathogenic role. In the current study we show by using immunohistochemistry that in unimmunized AD patients Aβ43 is a frequent constituent of plaques (6.0% immunostained area), similar to Aβ42 (3.9% immunostained area). Aβ43 immunostained area was significantly higher than that of Aβ40 (2.3%, p = 0.006). In addition, we show that Aβ43 is only a minor component of CAA in both parenchymal vessels (1.5 Aβ43-positive vessels per cm2 cortex vs. 5.3 Aβ42-positive vessels, p = 0.03, and 6.2 Aβ40-positive vessels, p = 0.045) and leptomeningeal vessels (5.6% Aβ43-positive vessels vs. 17.3% Aβ42-positive vessels, p = 0.007, and 27.4% Aβ40-positive vessels, p = 0.003). Furthermore, we have shown that Aβ43 is cleared from plaques after Aβ immunotherapy, similar to Aβ42 and Aβ40. Cerebrovascular Aβ43 levels did not change after immunotherapy.

OBJECTIVES: The widespread application of nano-enabled products and the increasing likelihood for workplace exposures make understanding engineered nanomaterial (ENM) effects in exposed workers a public and occupational health priority. The aim of this study was to report on the current state of knowledge on possible adverse effects induced by ENM in humans to determine the toxicological profile of each type of ENM and potential biomarkers for early detection of such effects in workers. METHODS: A systematic review of human studies and epidemiological investigations of exposed workers relative to the possible adverse effects for the most widely used ENM was performed through searches of major scientific databases including Web of Science, Scopus, and PubMed. RESULTS: Twenty-seven studies were identified. Most of the epidemiological investigations were cross-sectional. The review found limited evidence of adverse effects in workers exposed to the most commonly used ENM. However, some biological alterations are suggestive for possible adverse impacts. The primary targets of some ENM exposures were the respiratory and cardiovascular systems. Changes in biomarker levels compared with controls were also observed; however, limited exposure data and the relatively short period since the first exposure may have influenced the incidence of adverse effects found in epidemiological studies. CONCLUSIONS: There is a need for longitudinal epidemiologic investigations with clear exposure characterizations for various ENM to discover potential adverse health effects and identify possible indicators of early biological alterations. In this state of uncertainty, precautionary controls for each ENM are warranted while further study of potential health effects continues.

With the progress of Artificial Intelligence, intelligent agents are increasingly being deployed in tasks for which ethical guidelines and moral values apply. As artificial agents do not have a legal position, humans should be held accountable if actions do not comply, implying humans need to exercise control. This is often labeled as Meaningful Human Control (MHC). In this paper, achieving MHC is addressed as a design problem, defining the collaboration between humans and agents. We propose three possible team designs (Team Design Patterns), varying in the level of autonomy on the agent’s part. The team designs include explanations given by the agent to clarify its reasoning and decision-making. The designs were implemented in a simulation of a medical triage task, to be executed by a domain expert and an artificial agent. The triage task simulates making decisions under time pressure, with too few resources available to comply with all medical guidelines all the time, hence involving moral choices. Domain experts (i.e., health care professionals) participated in the present study. One goal was to assess the ecological relevance of the simulation. Secondly, to explore the control that the human has over the agent to warrant moral compliant behavior in each proposed team design. Thirdly, to evaluate the role of agent explanations on the human’s understanding in the agent’s reasoning. Results showed that the experts overall found the task a believable simulation of what might occur in reality. Domain experts experienced control over the team’s moral compliance when consequences were quickly noticeable. When instead the consequences emerged much later, the experts experienced less control and felt less responsible. Possibly due to the experienced time pressure implemented in the task or over trust in the agent, the experts did not use explanations much during the task; when asked afterwards they however considered these to be useful. It is concluded that a team design should emphasize and support the human to develop a sense of responsibility for the agent’s behavior and for the team’s decisions. The design should include explanations that fit with the assigned team roles as well as the human cognitive state.