An overview of the current progress, challenges, and prospects of human biomonitoring and exposome studies.

Human Biomonitoring (HB), the process for determining whether and to what extent chemical substances penetrated our bodies, serves as a useful tool to quantify human exposure to pollutants. In cases of nutrition and physiologic status, HB plays a critical role in the identification of excess or deficiency of essential nutrients. In pollutant HB studies, levels of substances measured in body fluids (blood, urine, and breast milk) or tissues (hair, nails or teeth) aid in the identification of potential health risks or associated adverse effects. However, even as a widespread practice in several countries, most HB studies reflect exposure to a single compound or mixtures which are measured at a single time point in lifecycle. On the other hand, throughout an individual's lifespan, the contact with different physical, chemical, and social stressors occurs at varying intensities, differing times and durations. Further, the interaction between stressors and body receptors leads to dynamic responses of the entire biological system including proteome, metabolome, transcriptome, and adductome. Bearing this in mind, a relatively new vision in exposure science, defined as the exposome, is postulated to expand the traditional practice of measuring a single exposure to one or few chemicals at one-time point to an approach that addresses measures of exposure to multiple stressors throughout the lifespan. With the exposome concept, the science of exposure advances to an Environment-Wide Association Perspective, which might exhibit a stronger relationship with good health or disease conditions for an individual (phenotype). Thus, this critical review focused on the current progress of HB and exposome investigations, anticipating some challenges, strategies, and future needs to be taken into account for designing future surveys.

Simple Preparation of Thiol-Ene Particles in Glycerol and Surface Functionalization by Thiol-Ene Chemistry (TEC) and Surface Chain Transfer Free Radical Polymerization (SCT-FRP).

Thiol-ene (TE)-based polymer particles are traditionally prepared via emulsion polymerization in water (using surfactants, stabilizers, and cosolvents). Here, a green and simple alternative is presented with excellent control over particle size, while avoiding the addition of stabilizers. Glycerol is applied as a dispersing medium for the preparation of off-stoichiometric TE microparticles, where sizes in the range of 40-400 µm are obtained solely by changing the mixing speed of the emulsions prior to crosslinking. Control over surface chemistry is achieved by surface functionalization of excess thiol groups via photochemical thiol-ene chemistry resulting in a functional monolayer. In addition, surface chain transfer free radical polymerization is used for the first time to introduce a thicker polymer layer on the particle surface. The application potential of the system is demonstrated by using functional particles as adsorbent for metal ions and as a support for immobilized enzymes.

Optical waveguides for the evanescent wave-induced cleavage of photolabile linker compounds.

Functional surfaces and especially the control of surface properties depending on external parameters such as light illumination have gained increasing importance in the last few years. We present the characterization of polymers from the cycloolefin (co)polymer class (COC/COP) functionalized with an aminosilane as a basis for the further immobilization of compounds. In a first step, an assay using AlexaFluor®647 fluorescent dye was used to assess surface homogeneity and reproducibility. A coefficient of variation of less than 15% for dot-to-dot and less than 25% for chip-to-chip could be achieved. The same amino-functionalized surfaces were then used to immobilize a biotinylated photolabile linker compound, binding AlexaFluor®647-labeled streptavidin. The linker was photocleaved with high efficiency at λ = 365 nm and P = 0.15 mW/cm(2). Fluorescence measurements show that polymers of the COC/COP class can be used as versatile surfaces for the photoinduced release of compounds immobilized via photolabile linkers.

Development of a thiol-ene based screening platform for enzyme immobilization demonstrated using horseradish peroxidase.

Efficient immobilization of enzymes on support surfaces requires an exact match between the surface chemistry and the specific enzyme. A successful match would normally be identified through time consuming screening of conventional resins in multiple experiments testing individual immobilization strategies. In this study we present a versatile strategy that largely expands the number of possible surface functionalities for enzyme immobilization in a single, generic platform. The combination of many individual surface chemistries and thus immobilization methods in one modular system permits faster and more efficient screening, which we believe will result in a higher chance of discovery of optimal surface/enzyme interactions. The proposed system consists of a thiol-functional microplate prepared through fast photochemical curing of an off-stoichiometric thiol-ene (OSTE) mixture. Surface functionalization by thiol-ene chemistry (TEC) resulted in the formation of a functional monolayer in each well, whereas, polymer surface grafts were introduced through surface chain transfer free radical polymerization (SCT-FRP). Enzyme immobilization on the modified surfaces was evaluated by using a rhodamine labeled horseradish peroxidase (Rho-HRP) as a model enzyme, and the amount of immobilized enzyme was qualitatively assessed by fluorescence intensity (FI) measurements. Subsequently, Rho-HRP activity was measured directly on the surface. The broad range of utilized surface chemistries permits direct correlation of enzymatic activity to the surface functionality and improves the determination of promising enzyme-surface candidates. The results underline the high potential of this system as a screening platform for synergistic immobilization of enzymes onto thiol-ene polymer surfaces. © 2017 American Institute of Chemical Engineers Biotechnol. Prog., 33:1267-1277, 2017.

A Pilot Characterization of the Human Chronobiome.

Physiological function, disease expression and drug effects vary by time-of-day. Clock disruption in mice results in cardio-metabolic, immunological and neurological dysfunction; circadian misalignment using forced desynchrony increases cardiovascular risk factors in humans. Here we integrated data from remote sensors, physiological and multi-omics analyses to assess the feasibility of detecting time dependent signals - the chronobiome - despite the "noise" attributable to the behavioral differences of free-living human volunteers. The majority (62%) of sensor readouts showed time-specific variability including the expected variation in blood pressure, heart rate, and cortisol. While variance in the multi-omics is dominated by inter-individual differences, temporal patterns are evident in the metabolome (5.4% in plasma, 5.6% in saliva) and in several genera of the oral microbiome. This demonstrates, despite a small sample size and limited sampling, the feasibility of characterizing at scale the human chronobiome "in the wild". Such reference data at scale are a prerequisite to detect and mechanistically interpret discordant data derived from patients with temporal patterns of disease expression, to develop time-specific therapeutic strategies and to refine existing treatments.

Mixed self-assembled monolayers (SAMs) consisting of methoxy-tri(ethylene glycol)-terminated and alkyl-terminated dimethylchlorosilanes control the non-specific adsorption of proteins at oxidic surfaces.

Monolayers from the newly synthesized compound methoxy-tri(ethylene glycol)-undecenyldimethylchlorosilane (CH3O(CH2CH2O)3(CH2)11Si(CH3)2Cl, MeO(EG)3C11DMS) and dodecyldimethylchlorosilane (DDMS), both pure and mixed, were prepared by self-assembly from organic solution in the presence of an organic base. The films obtained were characterized by advancing and receding contact angle measurements and ellipsometry to confirm the formation of self-assembled monolayers (SAMs). The resulting data on the covalently attached dimethylsilanes were compared to known oligo(ethylene glycol) (OEG)-terminated SAM systems based on terminal alkenes, thiolates or trihydrolyzable silanes. The composition of the mixed SAMs was found to depend directly and linearly on the composition of the silanization solution. Enhanced protein repellent properties were found for the SAMs using a variety of proteins, including the Ras Binding Domain (RBD), a protein with high relevance for cancer diagnostics. Roughly a RBD protein monolayer amount was adsorbed to silicon oxide surfaces silanized with DDMS or non-silanized silicon wafers, and in contrast, no RBD was adsorbed to surfaces silanized with MeO(EG)3C11DMS or to mixed monolayers consisting of DDMS and MeO(EG)3C11DMS if the content of OEG-silane overcame a critical content of X(EG) approximately 0.9.

The growth of Staphylococcus aureus and Escherichia coli in low-direct current electric fields.

Electrical potentials up to 800 mV can be observed between different metallic dental restorations. These potentials produce fields in the mouth that may interfere with microbial communities. The present study focuses on the impact of different electric field strengths (EFS) on the growth of Staphylococcus aureus (ATCC 25923) and Escherichia coli (ATCC 25922) in vitro. Cultures of S. aureus and E. coli in fluid and gel medium were exposed to different EFS. Effects were determined by calculation of viable counts and measurement of inhibition zones. In gel medium, anodic inhibition zones for S. aureus were larger than those for E. coli at all field strength levels. In fluid medium, the maximum decrease in the viable count of S. aureus cells was at 10 V⋅m(-1). Field-treated S. aureus cells presented ruptured cell walls and disintegrated cytoplasm. Conclusively, S. aureus is more sensitive to increasing electric field strength than E. coli.

Influence of osteotomy procedure and surgical experience on early complications after orthognathic surgery in the mandible.

INTRODUCTION: This study evaluated the influence of osteotomy procedure and surgical experience on early complication rates following orthognathic surgery in the mandible. MATERIALS AND METHODS: In a retrospective study, patients who underwent a mandibular osteotomy (Obwegeser-Dal Pont (ODP) and Hunsuk-Epker (HE)) were included. Incidence of "bad splits", "bleeding episodes", "delayed wound healing", "failed osteosynthesis" and "nerve lesions" at 2 months post-operatively were recorded. Surgical experience was classified as: beginner (<10), intermediate (10-40) and expert (>40). Complications were correlated to the surgical approach and the experience level of the surgeon. RESULTS: 400 patients were included. 200 underwent a bimaxillary approach. 186 patients were operated using the ODP technique, 214 according to HE. Multivariate analysis confirmed significantly more unwanted fractures and bleeding events for ODP when compared to HE (p = 0.28, p = 0.003). Experienced surgeons had more osteosynthesis failures (0.047) and significantly more nerve lesions than the other groups (p = 0.01). DISCUSSION: The HE osteotomy showed a more reliable fracture mechanism with less relevant bleeding episodes. Differences between the surgeons of varying training status were marginal with exception of a higher rate of osteosynthesis failure and temporary hypoesthesia in the experienced group.

Biomimetic assembly of polyelectrolyte multilayers containing phosvitin monitored with reflectometric interference spectroscopy.

Coatings of biomaterials or implants that facilitate biomineralization possess a great potential for applications focused to the replacement, augmentation, and regeneration of bone tissue. Biomimetic approaches utilize biomolecules for either templating or supporting the crystallization process. One of these promising biomolecules is phosvitin (PV), an egg yolk protein known to transport and store inorganic phosphates and calcium ions. The incorporation of PV into polyelectrolyte multilayers is favorable due to PVs high degree of phosphorylation and thus a high acidity. Utilizing the reflectometric interference spectroscopy, the adsorption kinetics of this novel polyelectrolyte system composed of poly-L-lysine and the heavily phosphorylated phosvitin were monitored. The results demonstrate an unexpected nonregular growth regime called overshoot. Effective measures of shifting this irregular polyelectrolyte adsorption process back to a regular multilayer growth regime are reported in this paper.