In Vitro and In Vivo Regulation of SRD5A mRNA Expression of Supercritical Carbon Dioxide Extract from Asparagus racemosus Willd. Root as Anti-Sebum and Pore-Minimizing Active Ingredients.

Oily skin from overactive sebaceous glands affects self-confidence and personality. There is report of an association between steroid 5-alpha reductase gene (SRD5A) expression and facial sebum production. There is no study of the effect of Asparagus racemosus Willd. root extract on the regulation of SRD5A mRNA expression and anti-sebum efficacy. This study extracted A. racemosus using the supercritical carbon dioxide fluid technique with ethanol and investigated its biological compounds and activities. The A. racemosus root extract had a high content of polyphenolic compounds, including quercetin, naringenin, and p-coumaric acid, and DPPH scavenging activity comparable to that of the standard L-ascorbic acid. A. racemosus root extract showed not only a significant reduction in SRD5A1 and SRD5A2 mRNA expression by about 45.45% and 90.86%, respectively, but also a reduction in the in vivo anti-sebum efficacy in male volunteers, with significantly superior percentage changes in facial sebum production and a reduction in the percentages of pore area after 15 and 30 days of treatment. It can be concluded that A. racemosus root extract with a high content of polyphenol compounds, great antioxidant effects, promising downregulation of SRD5A1 and SRD5A2, and predominant facial sebum reduction and pore-minimizing efficacy could be a candidate for an anti-sebum and pore-minimizing active ingredient to serve in functional cosmetic applications.

Superior even skin tone and anti-ageing benefit of a combination of 4-hexylresorcinol and niacinamide.

OBJECTIVES: To demonstrate the synergistic effect of 4-hexylresorcinol (4-HR) with niacinamide in boosting anti-melanogenic efficacy in vitro and establish the in vivo efficacy and safety of the combination in a human trial. METHODS: Primary human epidermal melanocytes and 3D pigmented skin equivalents were treated with 4-HR, niacinamide, and their combinations for their effect on pigmentation. This was followed by a randomized, double-blind, split-face clinical study in Chinese subjects, and effects on skin tone, hyperpigmentation, fine lines and wrinkles, hydration, and skin firmness were measured for a 12-week study period. RESULTS: In vitro tyrosinase enzyme activity studies showed that 4-HR is one of the most potent tyrosinase inhibitors. The combination of 4-HR and niacinamide showed a synergistic reduction in melanin production in cultured melanocytes and lightened the 3D skin equivalent model. In vitro as well as in the human trial, the combination of 4-HR and niacinamide showed significantly improved efficacy over niacinamide alone on hyperpigmentation spots as measured by L*, the visual appearance of fine lines and wrinkles in crow's feet and perioral area and skin firmness, with no product-related adverse events. CONCLUSIONS: A formulation containing a combination of 4-HR and niacinamide delivered superior skin tone and anti-ageing benefits significantly better than niacinamide alone with no adverse events. This study demonstrates that a product designed to affect multiple pathways of melanogenesis, inflammation, and ageing may provide an additional treatment option, beyond hydroquinone and retinoids, for hyperpigmentation and ageing.

OBJECTIFS: Démontrer l'effet synergique du 4-hexylrésorcinol (4-HR) associé au niacinamide pour stimuler in vitro l'efficacité antimélanogène, et établir l'efficacité et la sécurité d'emploi in vivo de cette association dans un essai chez l'homme. MÉTHODES: Des mélanocytes épidermiques humains primaires et des équivalents cutanés pigmentés en 3D ont été traités avec du 4-HR, du niacinamide et leurs combinaisons pour leur effet sur la pigmentation. Ceci a été suivi d'une étude clinique randomisée, en double aveugle en hémi-visage chez des sujets chinois, et les effets sur le teint, l'hyperpigmentation, les rides et ridules, l'hydratation et la fermeté de la peau ont été mesurés pendant une durée d'étude de 12 semaines. RÉSULTATS: Les études in vitro sur l'activité enzymatique de la tyrosinase ont montré que le 4-HR est l'un des inhibiteurs de la tyrosinase les plus puissants. L'association du 4-HR et du niacinamide a montré une réduction synergique de la production de mélanine dans les mélanocytes de culture et donné de la luminosité au modèle cutané 3D équivalent. Également in vitro avec l'étude chez l'homme, l'association du 4-HR et du niacinamide a fait ressortir une efficacité significativement plus élevée qu'avec le niacinamide seul sur les taches d'hyperpigmentation mesurées par L*, l'aspect visuel des rides et ridules des pattes d'oie et de la zone périorale, et la fermeté de la peau, sans événements indésirables liés au produit. CONCLUSIONS: Une formulation contenant une association de 4-HR et de niacinamide a permis d'obtenir un teint et un effet anti-âge nettement supérieurs à ceux du niacinamide seul, sans événements indésirables. Cette étude démontre qu'un produit conçu pour toucher plusieurs voies de mélanogenèse, d'inflammation et de vieillissement peut constituer une nouvelle option thérapeutique, au-delà de l'hydroquinone et des rétinoïdes, pour l'hyperpigmentation et le vieillissement.

Efficacy of Different Hair and Skin Decontamination Strategies with Identification of Associated Hazards to First Responders.

Background: Established procedures for mass casualty decontamination involve the deployment of equipment for showering with water (such as the ladder pipe system [LPS] and technical decontamination [TD]). This necessarily introduces a short, but critical delay. The incorporation of dry decontamination to the incident response process offers the potential to establish a more rapid and timely intervention. Objectives: To investigate the effectiveness of various dry (DD) and wet decontamination strategies for removing a chemical warfare simulant (methyl salicylate; MS) from the hair and skin of human volunteers. Methods: The simulant was applied to volunteers via whole body exposure to an aerosol. Three decontamination protocols (dry, LPS and technical decontamination) were applied, singly and in various combinations. The efficacy of the protocols was evaluated by fluorescent photography and analysis of residual MS from skin/hair swabs, decontamination materials and air samples. Results: Dry decontamination was effective, with the greatest reduction in skin and hair contamination arising from the "Triple Protocol" (DD+LPS+TD). Secondary hazards associated with contaminated individuals and equipment decreased as the number of decontamination procedures increased. In particular, dry decontamination reduced the potential contact and inhalation hazard arising from used washcloths, towels and vapor within the TD units. Discussion: The introduction of dry decontamination prior to wet forms of decontamination offers a simple strategy to initiate treatment at a much earlier opportunity, with a corresponding improvement in clinical outcomes and substantial reduction of secondary hazards associated with operational processes.

Toxicokinetics of a urinary metabolite of tebuconazole following controlled oral and dermal administration in human volunteers.

Tebuconazole (TEB) is a widely used triazole fungicide, but the toxicokinetics of its human metabolites are not fully described. For proper interpretation of biological monitoring data, knowledge on the metabolism and elimination of the compound is required. A human volunteer study was performed with the aim to describe the time courses of urinary excretion after controlled oral and dermal administration of TEB. Six healthy volunteers (three males and three females) received on separate occasions a single oral dose of 1.5 mg of TEB and a single dermal dose of 2.5 mg during 1 h. In addition to a pre-exposure urine sample, complete urine voids were collected over 48 h post-administration. The main metabolite hydroxy-tebuconazole (TEB-OH) was quantified in each urine sample. Peak excretion rates after oral and dermal administration were reached after 1.4 and 21 h, mean elimination half-lives were 7.8 and 16 h, and recoveries within 48 h were 38% and 1%, respectively. The time courses of excretion were compared to simulations with an established physiologically based toxicokinetic model for TEB that was extended with a parallel model for TEB-OH. Overall, TEB-OH was rapidly excreted into urine after oral exposure, and renal elimination was considerably slower after dermal exposure. Urinary time courses between individuals were similar. The model predictions were in good agreement with the observed time courses of excretion.

Chemical warfare agent simulants for human volunteer trials of emergency decontamination: A systematic review.

Incidents involving the release of chemical agents can pose significant risks to public health. In such an event, emergency decontamination of affected casualties may need to be undertaken to reduce injury and possible loss of life. To ensure these methods are effective, human volunteer trials (HVTs) of decontamination protocols, using simulant contaminants, have been conducted. Simulants must be used to mimic the physicochemical properties of more harmful chemicals, while remaining non-toxic at the dose applied. This review focuses on studies that employed chemical warfare agent simulants in decontamination contexts, to identify those simulants most suitable for use in HVTs of emergency decontamination. Twenty-two simulants were identified, of which 17 were determined unsuitable for use in HVTs. The remaining simulants (n = 5) were further scrutinized for potential suitability according to toxicity, physicochemical properties and similarities to their equivalent toxic counterparts. Three suitable simulants, for use in HVTs were identified; methyl salicylate (simulant for sulphur mustard), diethyl malonate (simulant for soman) and malathion (simulant for VX or toxic industrial chemicals). All have been safely used in previous HVTs, and have a range of physicochemical properties that would allow useful inference to more toxic chemicals when employed in future studies of emergency decontamination systems.

Models of wound healing: an emphasis on clinical studies.

BACKGROUND: The healing of wounds has always provided challenges for the medical community whether chronic or acute. Understanding the processes which enable wounds to heal is primarily carried out by the use of models, in vitro, animal and human. It is generally accepted that the use of human models offers the best opportunity to understand the factors that influence wound healing as well as to evaluate efficacy of treatments applied to wounds. OBJECTIVES: The objective of this article is to provide an overview of the different methodologies that are currently used to experimentally induce wounds of various depths in human volunteers and examines the information that may be gained from them. METHODS: There is a number of human volunteer healing models available varying in their invasiveness to reflect the different possible depth levels of wounds. RESULTS: Currently available wound healing models include sequential tape stripping, suction blister, abrasion, laser, dermatome, and biopsy techniques. The various techniques can be utilized to induce wounds of variable depth, from removing solely the stratum corneum barrier, the epidermis to even split-thickness or full thickness wounds. CONCLUSION: Depending on the study objective, a number of models exist to study wound healing in humans. These models provide efficient and reliable results to evaluate treatment modalities.

Evaluation of a new topical skin protectant (RD1433) for the prevention and treatment of incontinence-associated dermatitis.

Context Incontinence-associated dermatitis (IAD) is a type of moisture-associated dermatitis caused by repeated skin exposure to urine or stool. A product that could mitigate such symptoms would have a significant impact on cost of care and patients' quality of life. Objective This study compared the clinical efficacy of RD1433 and a comparator product (Vaseline®) in preventing and treating experimental IAD skin lesions. Materials and methods For the "prevention" part of the study, skin sites in eight human volunteers were treated daily for 5 d with either RD1433 or Vaseline® immediately prior to synthetic urine exposure. In the "treatment" part, exposure to synthetic urine was substituted for Vaseline® or RD1433 application on the first 2 d to promote the development of skin lesions prior to the application of the products from day three. Product efficacy was quantified by visual scoring and an array of biophysical instruments. Results Both RD1433 and Vaseline® significantly reduced lesion progression when applied as a prophylactic. When applied as a treatment (following establishment of skin lesions), RD1433 demonstrated a statistically significant improvement in several measures of skin function whereas there was no statistically significant improvement following treatment with Vaseline®. Conclusions The findings of this study suggest that RD1433 may be superior to Vaseline® in the prevention and treatment of experimental IAD lesions. Clearly, further work is required to establish the efficacy of RD1433 with patients in a clinical environment.

Sarcocystis heydorni, n. sp. (Apicomplexa: Sarcocystidae) with cattle (Bos taurus) and human (Homo sapiens) cycle.

Cattle (Bos taurus) are intermediate hosts for four species of Sarcocystis, namely Sarcocystis cruzi, Sarcocystis hirsuta, Sarcocystis hominis, and Sarcocystis rommeli. Of these four species, mature sarcocysts of S. cruzi are thin-walled (<1 µm), whereas S. hirsuta, S. hominis, and S. rommeli have thick walls (4 µm or more). Here, we describe a new species of Sarcocystis with thin-walled sarcocysts in cattle. Two newborn calves were fed with sporocysts from the feces of a human volunteer who had ingested raw beef. The calves were killed 111 and 222 days later. In addition to thick-walled sarcocysts of S. hominis, both calves were coinfected with a Sarcocystis species that had a thin-walled sarcocysts, distinct from S. cruzi. The sarcocysts were mature, microscopic, up to 80 µm wide, and up to 1060 µm long. By light microscopy, the sarcocyst wall was thin (<1 µm thick) and had minute protrusions. By transmission electron microscopy, the sarcocyst wall had short, conical villar protrusions (vp) that were up to 0.5 µm long and up to 0.5 µm wide, similar to type 29. The vp on the sarcocyst wall lacked microtubules but had six or more disc-shaped plaques. The ground substance layer was smooth, approximately 0.5 µm thick, and without microtubules. The bradyzoites were 8-11 µm long. The structure of the sarcocyst wall was distinct from any species of Sarcocystis reported from livestock. This unique species is named in honor of Dr. Alfred Otto Heydorn who provided the sporocysts.

Optimisation of a dosing regime for a topical skin protectant (barrier cream).

CONTEXT: Topical skin protectants (barrier creams) have the potential to reduce or enhance the severity of dermal lesions following exposure to allergens or irritants. Therefore, it is essential that such products are subject to appropriate clinical evaluation prior to marketing. Consequently, it is important to accurately define a dosing regime in order to assess test products under appropriate conditions. OBJECTIVE: In this study, we extended the use of a standard rubefacient (methyl nicotinate; MN) assay to establish the optimum thickness and duration of action of a novel barrier cream (RD1433). White petroleum jelly (Vaseline(®)) was used as a comparator product. METHODS: The dermal response to MN was measured on the volar forearm skin of volunteers (n = 12; average age 47.5 years) using an array of biophysical instruments and visual scoring. When applied at a nominal thickness of 0.1 mm, RD1433 retained effectiveness against MN for up to six hours. In contrast, Vaseline(®) was relatively ineffective. Moreover, RD1433 provoked no measurable signs of irritation and so can be considered acceptable for further clinical evaluation. CONCLUSION: Future clinical studies using RD1433 should be based on topical application of a 0.1 mm thickness layer every six hours.

The effect of reclined seatback angles on the motion of booster-seated children during lateral-oblique low-acceleration impacts.

Belt-positioning boosters (BPB) may prevent submarining in novel seating configurations such as seats with reclined seatbacks. However, several knowledge gaps in the motion of reclined child occupants remain as previous reclined child studies only examined responses of a child anthropomorphic test device (ATD) and the PIPER finite element (FE) model in frontal impacts. The aim of this study is to investigate the effect of reclined seatback angles and two types of BPBs on the motion of child volunteer occupants in low-acceleration far-side lateral-oblique impacts. Six healthy children (3 males, 3 females, 6-8 years, seated height: 66±3.2 cm, weight: 25.2±3.2 kg) were seated on two types of low-back BPB (standard and lightweight) on a vehicle seat and restrained by a 3-point simulated-integrated seatbelt on a low-acceleration sled. The sled exposed the participants to a low-speed lateral-oblique (80° from frontal) pulse (2 g). Three seatback recline angles (25°, 45°, 60° from vertical) with two BPB (standard and lightweight) were tested. A 10-camera 3D-motion-capture system (Natural Point Inc.) was used to capture peak lateral head and trunk displacements and forward knee-head distance. Three seat-belt load cells (Denton ATD Inc) captured peak seatbelt loads. Electromyography (EMG, Delsys Inc) recorded muscle activation. Repeated Measure 2-way ANOVAs were performed to evaluate the effect of seatback recline angle and BPB on kinematics. Tukey's post-hoc test for pairwise comparisons was used. P-level was set to 0.05. Peak lateral head and trunk displacement decreased with the increasing seatback recline angle (p < 0.005, p < 0.001, respectively). Lateral peak head displacement was greater in the 25° compared to the 60° condition (p < 0.002) and in the 45° condition compared to the 60° condition (p < 0.04). Lateral peak trunk displacement was greater in the 25° condition than the 45° condition (p < 0.009) and the 60° condition (p < 0.001), and in the 45° condition than the 60° condition (p < 0.03). Overall peak lateral head and trunk displacements and knee-head forward distance were slightly greater in the standard than the lightweight BPB (p < 0.04), however these differences between BPBs were small (∼10 mm). Shoulder belt peak load decreased as the reclined seatback angle increased (p < 0.03): the shoulder belt peak load was statistically greater in the 25° condition than the 60° condition (p < 0.02). Muscle activation from the neck, upper trunk, and lower legs showed great activation. Neck muscles activation increased with the increase in seatback recline angle. Thighs, upper arms, and abdominal muscles showed small activation and no effect of conditions. Child volunteers showed decreased displacement suggesting that reclined seatbacks placed the booster-seated children in a more favorable position within the shoulder belt in a low-acceleration lateral-oblique impact, compared to nominal seatback angles. BPB type seemed to minimally influence the children's motion: the small differences found may have been due to the slight difference in heights between the two BPBs. Future research with more severe pulses is needed to better understand reclined children's motion in far-side lateral-oblique impacts.

Head contacts in second-row pediatric occupants when the front-seat is reclined during automated emergency braking.

Seating configurations for autonomous driving will include reclined front seated occupants, which may expose child occupants seated directly behind to head impacts even in pre-crash scenarios. This study used mathematical modelling to investigate head contact for second-row child occupants seated behind a reclined front-seat during an automatic emergency braking (AEB) scenario. Although characterized by low speed (<1 m/s), head contacts were observed for a seatbelt-restrained 10-year-old and a 6-year-old in a low-back booster when the front-seat was reclined and in an aftward track position. Future seating configurations should consider the potential for head contact by second-row child occupants during crash-avoidance scenarios.

Novel bioactive formulation derived from the conditioned medium of mesenchymal stromal cells reduces under-eye dark circles in human volunteers.

BACKGROUND: Under-eye dark circles are a common condition observed in dermatology practice. Mesenchymal stromal cell-derived conditioned medium (MSC-CM) contains an array of growth factors and cytokines reported to promote periorbital rejuvenation and may be useful in removing the dark circle around the eyes. AIMS: The aim of the present study was to evaluate the safety and efficacy of developed bioactive formulation containing mesenchymal stromal cell-derived conditioned medium in reducing the under-eye dark circles. PATIENTS/METHODS: We tested the safety profile of MSC-CM along with antioxidants, in vitro using human melanocytes cultures. The bioactive formulation containing MSC-CM was developed and tested for physicochemical parameters. The dermatological safety was evaluated by primary irritant patch-test under complete occlusion on healthy human subjects. To elucidate its safety and efficacy, monocentric, open-label, single-arm study was carried out in 20 Indian female subjects for the duration of 12 weeks. Parameters such as eye puffiness, radiance, skin smoothness, even skin tone, periorbital fine lines and wrinkles, crow's feet, whitening, pigmentation, skin tightening, and refreshing/soothing effect were used to investigate the rejuvenating property of the bioactive formulation. RESULTS: Mesenchymal stromal cell-derived conditioned medium along with antioxidants decreased the melanin content compared to the CM alone in the melanocyte cultures. Besides, the bioactive formulation was safe and emerged as a non-irritant product. Improvement in the majority of the clinical parameters assessed through efficacy study was observed within 4 weeks of topical application of the formulation twice daily, and showed continued improvement for 12 weeks as evaluated by the dermatologists as well as self-assessment by the subjects. CONCLUSION: The bioactive formulation containing MSC-CM was safe and effective in reducing the under-eye dark circles and was beneficial in improving the overall appearance of the eye area.

Identification of Novel Simulants for Toxic Industrial Chemicals and Chemical Warfare Agents for Human Decontamination Studies: A Systematic Review and Categorisation of Physicochemical Characteristics.

Chemical simulants have long been used in human trials of mass decontamination to determine the efficacy of decontamination interventions against more toxic agents. Until now, reliance has mostly been on individual chemicals as surrogates to specific agents (e.g., methyl salicylate for sulphur mustard). A literature review was conducted to identify chemicals that had been previously tested on human volunteers and that represent diverse physicochemical characteristics in order to create a repository for chemical simulants. Of the 171 unique chemicals identified, 78 were discounted for the risk they could pose to human volunteers, 39 were deemed suitable for use, and a further 54 were considered to be possible simulants but would require further research. Suitable simulants included both solid and liquid chemicals spanning a wide range of physicochemical properties including molecular weight, octanol/water partition coefficient, vapour pressure, and solubility. This review identifies an array of potential simulants suitable for use in human volunteer decontamination studies and is of relevance to future studies on systemic absorption and surface decontamination.

Feasibility study of a safe sled environment for reclined frontal deceleration tests with human volunteers.

Objective: The goal of the study was to assess the feasibility of a safe crash environment for volunteer tests in reclined seating positions. An iterative multimodal approach was chosen, consisting of full-body human body model (HBM) simulations, anthropomorphic test device (ATD) physical testing, and volunteer testing.Methods: To estimate a noninjurious deceleration pulse, the iterative inclination of the seat was supported through HBM simulations and physical ATD testing. One male volunteer was exposed to 5 low-speed frontal sled impacts with stepwise reclined seat angles. The volunteer was restrained with a non-pretensioned 3-point seat belt. All procedures were approved by the relevant ethics boards.Results: Volunteer sled tests in 3 different seat configurations were performed with one volunteer at noninjurious deceleration levels. Inclination of the seat and the absence of a footrest resulted in elevated axial seat reaction forces and almost pure translational motion of the human body.Conclusions: A maximum speed of 7.1 km/h and peak deceleration of 3.0 g was found to be a safe pulse for volunteer testing in frontal impacts with a rigid reclined seat. Larger soft tissue deformations were observed when reclined, possibly associated with higher shear loads within the soft tissue. Preliminary results highlight trade-offs between the degree of seat angulation, friction force, and restraint capability of a 3-point seat belt, thus causing forward translation and/or axial spinal compression of the occupant that may need to be addressed in the future.

Modeling Human Volunteers in Multidirectional, Uni-axial Sled Tests Using a Finite Element Human Body Model.

A goal of the Human Research Program at National Aeronautics and Space Administration (NASA) is to analyze and mitigate the risk of occupant injury due to dynamic loads. Experimental tests of human subjects and biofidelic anthropomorphic test devices provide valuable kinematic and kinetic data related to injury risk exposure. However, these experiments are expensive and time consuming compared to computational simulations of similar impact events. This study aimed to simulate human volunteer biodynamic response to unidirectional accelerative loading. Data from seven experimental studies involving 212 volunteer tests performed at the Air Force Research Laboratory were used to reconstruct 13 unique loading conditions across four different loading directions using finite element human body model (HBM) simulations. Acceleration pulses and boundary conditions from the experimental tests were applied to the Global Human Body Models Consortium (GHBMC) simplified 50th percentile male occupant (M50-OS) using the LS-Dyna finite element solver. Head acceleration, chest acceleration, and seat belt force traces were compared between the experimental and matched simulation signals using correlation and analysis (CORA) software and averaged into a comprehensive response score ranging from 0 to 1 with 1 representing a perfect match. The mean comprehensive response scores were 0.689 ± 0.018 (mean ± 1 standard deviation) in two frontal simulations, 0.683 ± 0.060 in four rear simulations, 0.676 ± 0.043 in five lateral simulations, and 0.774 ± 0.013 in two vertical simulations. The CORA scores for head and chest accelerations in these simulations exceeded mean scores reported in the original development and validation of the GHBMC M50-OS model. Collectively, the CORA scores indicated that the HBM in these boundary conditions closely replicated the kinematics of the human volunteers across all loading directions.

Targeting Alzheimer's Disease at the Right Time and the Right Place: Validation of a Personalized Approach to Diagnosis and Treatment.

Cautious optimism is appropriate for a near future (five years) time frame for a number of drugs acting on the different pathophysiological components of Alzheimer's disease (amyloid deposition, tau hyperphosphorylation, neuroinflammation, vascular changes, to name the most important known so far). Since the relative weight of these components will be different between individuals and will even change over time for each individual, a 'one drug fit for all' approach is no longer defensible. Precision medicine using biomarkers in the diagnosis and treatment of Alzheimer's disease is the new strategy.

Wearable Water Content Sensor Based on Ultrasound and Magnetic Sensing.

Fluid accumulation in the lower extremities is an early indicator of disease deterioration in cardiac failure, chronic venous insufficiency and lymphedema. At-home wearable monitoring and early detection of fluid accumulation can potentially lead to prompt medical intervention and avoidance of hospitalization. Current methods of fluid accumulation monitoring either suffer from lack of specificity and sensitivity or are invasive and cost-prohibitive to use on a daily basis. Ultrasound velocity in animal and human tissue has been found to change with water content. However, previous prototype fluid monitoring sensors based on ultrasound are cumbersome and not wearable. Hence, in this research a compact water content sensor based on a wearable instrumented elastic band is proposed. A novel integration of magnetic sensing and ultrasonic sensing is utilized, where the magnetic sensor provides distance measurement and the ultrasonic sensor produces time-of-flight measurement. Magnetic field modeling with a Kalman filter and least squares linear fitting algorithms are employed to ensure robust sensor performance on a wearable device. The combination of the two measurements yields ultrasound velocity measurement in tissue. The water content sensor prototype was tested on a tissue phantom, on animal tissue and on a human leg. The error in velocity measurement is shown to be small enough for early detection of tissue edema.

Impact of the biological definition of Alzheimer's disease using amyloid, tau and neurodegeneration (ATN): what about the role of vascular changes, inflammation, Lewy body pathology?

BACKGROUND: The NIA-AA research framework proposes a biological definition of Alzheimer's disease, where asymptomatic persons with amyloid deposition would be considered as having this disease prior to symptoms. DISCUSSION: Notwithstanding the fact that amyloid deposition in isolation is not associated with dementia, even the combined association of amyloid and tau pathology does not inevitably need to dementia over age 65. Other pathological factors may play a leading or an accelerating role in age-associated cognitive decline, including vascular small vessel disease, neuroinflammation and Lewy Body pathology. CONCLUSION: Research should aim at understanding the interaction between all these factors, rather than focusing on them individually. Hopefully this will lead to a personalized approach to the prevention of brain aging, based on individual biological, genetic and cognitive profiles.

Human in vivo and in vitro studies on gastrointestinal absorption of titanium dioxide nanoparticles.

The study was designed to conduct human in vivo and in vitro studies on the gastrointestinal absorption of nanoparticles, using titanium dioxide as a model compound, and to compare nanoparticle behaviour with that of larger particles. A supplier's characterisation data may not fully describe a particle formulation. Most particles tested agreed with their supplied characterisation when assessed by particle number but significant proportions of 'nanoparticle formulations' were particles >100nm when assessed by particle weight. Oral doses are measured by weight and it is therefore important that the weight characterisation is taken into consideration. The human volunteer studies demonstrated that very little titanium dioxide is absorbed gastrointestinally after an oral challenge. There was no demonstrable difference in absorption for any of the three particle sizes tested. All tested formulations were shown to agglomerate in simulated gastric fluid, particularly in the smaller particle formulations. Further agglomeration was observed when dispersing formulations in polymeric or elemental foods. Virtually no translocation of titanium dioxide particles across the cell layer was demonstrated. This study found no evidence that nanoparticulate titanium dioxide is more likely to be absorbed in the gut than micron-sized particles.

The application of global sensitivity analysis in the development of a physiologically based pharmacokinetic model for m-xylene and ethanol co-exposure in humans.

Global sensitivity analysis (SA) was used during the development phase of a binary chemical physiologically based pharmacokinetic (PBPK) model used for the analysis of m-xylene and ethanol co-exposure in humans. SA was used to identify those parameters which had the most significant impact on variability of venous blood and exhaled m-xylene and urinary excretion of the major metabolite of m-xylene metabolism, 3-methyl hippuric acid. This analysis informed the selection of parameters for estimation/calibration by fitting to measured biological monitoring (BM) data in a Bayesian framework using Markov chain Monte Carlo (MCMC) simulation. Data generated in controlled human studies were shown to be useful for investigating the structure and quantitative outputs of PBPK models as well as the biological plausibility and variability of parameters for which measured values were not available. This approach ensured that a priori knowledge in the form of prior distributions was ascribed only to those parameters that were identified as having the greatest impact on variability. This is an efficient approach which helps reduce computational cost.