Shear shock wave injury in vivo: High frame-rate ultrasound observation and histological assessment.

Using high frame-rate ultrasound and ¡1µm sensitive motion tracking we previously showed that shear waves at the surface of ex vivo and in situ brains develop into shear shock waves deep inside the brain, with destructive local accelerations. However post-mortem tissue cannot develop injuries and has different viscoelastodynamic behavior from in vivo tissue. Here we present the ultrasonic measurement of the high-rate shear shock biomechanics in the in vivo porcine brain, and histological assessment of the resulting axonal pathology. A new biomechanical model of brain injury was developed consisting of a perforated mylar surface attached to the brain and vibrated using an electromechanical shaker. Using a custom sequence with 8 interleaved wide beam emissions, brain imaging and motion tracking were performed at 2900 images/s. Shear shock waves were observed for the first time in vivo wherein the shock acceleration was measured to be 2.6 times larger than the surface acceleration ( 95g vs. 36g). Histopathology showed axonal damage in the impacted side of the brain from the brain surface, accompanied by a local shock-front acceleration of >70g. This shows that axonal injury occurs deep in the brain even though the shear excitation was at the brain surface, and the acceleration measurements support the hypothesis that shear shock waves are responsible for deep traumatic brain injuries.

The Host-specific Microbiota is Required for Diet-Specific Metabolic Homeostasis.

In complex mammals, the importance and host-specificity of microbial communities have been demonstrated through their positive effects on host immune fitness or performance. However, whether host metabolic physiology homeostasis depends on a specific bacterial community exclusive to the host remains unclear. Here, we show that the coevolved host-specific microbiota is required to maintain diet-specific flexible and sufficient metabolic homeostasis through a high colonization rate, modulating gut metabolites, and related targets. Using germ-free (GF) mice, we tested whether the fitness benefiting the host metabolic phenotype of microbiota was host-specific. We demonstrated that GF mice associated with exogenous microbiota (human microbiota (HM)), which exhibited different and reduced gut microbial species diversity, significantly elevated metabolic rate, and exhibited metabolic insufficiency, all characteristics of GF mice. Strikingly, the absence of the host-specific microbiome attenuated high-fat diet-specific metabolism features. Different diets caused different metabolic changes in only host-specific microbiota-associated mice, not the host-microbiota mismatched mice. While RNA sequencing revealed subtle changes in the expression of genes in the liver, GF mice and HM mice showed considerably altered expression of genes associated with metabolic physiology compared to GF mice associated with host-specific microbiota. The effect of diet outweighed microbiota in the liver transcriptome. These changes occurred in the setting of decreased luminal short-chain fatty acids (SCFAs) and the secondary bile acid (BAs) pool and downstream gut signaling targets in HM and GF mice, which affects whole-body metabolism. These data indicate that a foreign microbial community provides little metabolic benefit to the host when compared to a host-specific microbiome, due to the colonization selection pressure and microbiota-derived metabolites dysfunction. Overall, microbiome fitness effects on the host metabolic phenotype were host-specific. Understanding the impact of the host-specificity of the microbiome on metabolic homeostasis may provide important insights for building a better probiotic. Highlights: Microbiome fitness effects on the host metabolic phenotype were host-specific in mammals.Human microbiota-associated mice exhibited lower host metabolic fitness or performance, and similar functional costs in GF mice.Different diets cause different metabolic changes only in host-specific microbiota-associated mice, not the host-microbiota mismatched mice.The defective gut microbiota in host-specific microbiota, microbial metabolites and related targets likely drive the metabolic homeostasis.

The Role of Toluidine Blue in Mohs Micrographic Surgery: A Systematic Review.

Toluidine blue (TB) is a metachromatic dye used as a stain in frozen sections in Mohs micrographic surgery (MMS). The current literature on the use of TB is sparse and generally qualitative in nature. The aim of this systematic review was to summarize and evaluate the existing literature analyzing TB use in MMS. The PubMed and Cochrane databases were searched for relevant studies published before December 1, 2019. Studies that analyzed the use of TB in frozen sections applicable to MMS were included. A total of 25 articles were reviewed, of which 12 fit the inclusion criteria. Our analysis showed that TB may play an important role in the successful diagnosis and treatment of particular cutaneous tumors.

Nodules on the Anterior Neck Following Poly-L-lactic Acid Injection.

Poly-L-lactic acid (PLLA) is a synthetic biologic polymer that is suspended in solution and can be injected for soft-tissue augmentation. The most common adverse events generally are transient in nature, such as swelling, tenderness, pain, bruising, and bleeding. Persistent adverse events of PLLA primarily are papule and nodule formation. Injecting PLLA into the anterior neck is an off-label procedure and may cause a higher incidence of nodule formation.

The Adjunct Use of Platelet-Rich Plasma in Split-Thickness Skin Grafts: A Systematic Review.

OBJECTIVE: To summarize the available literature on platelet-rich plasma (PRP) as an adjunct to split-thickness skin graft (STSG) in an organized and easy-to-read format. These data may encourage surgeons to integrate PRP into their skin graft protocol. DATA SOURCES: The authors conducted a systematic search using the PubMed, Cochrane, and ClinicalTrials.gov databases for articles published from their respective inceptions to October 1, 2019, to identify relevant studies. STUDY SELECTION: A total of 629 articles were reviewed, and 5 were identified for inclusion in this study. The population of all studies was patients receiving an STSG to close a skin defect. DATA EXTRACTION: Articles were screened for the following outcome measures: graft take rates, edema or hematoma formation, instant adhesion of graft, healing time, length of hospital stay, scar hypertrophy, and frequency of dressing changes. DATA SYNTHESIS: The data were organized into two tables describing the studies and the selected outcome measures. CONCLUSIONS: The data suggest that PRP in STSG reduces healing time, length of hospital stay, and scarring and that it eliminates the need for sutures/staples. Further, these benefits may correlate with a decrease in overall expenditure. This systematic review suggests that further research on PRP and skin grafts is warranted.

Platelet-rich plasma in noninvasive procedures for atrophic acne scars: A systematic review and meta-analysis.

BACKGROUND: The use of platelet-rich plasma (PRP) combined with noninvasive, nonenergy procedures for atrophic acne scars has shown promise. To date, there has not been a systematic review or meta-analysis of the effectiveness of this therapy. AIMS: To use meta-analysis to compare Goodman and Baron qualitative scores, patient satisfaction outcomes, and adverse effects in patients undergoing combination procedures with PRP, combination procedures without PRP, and noninvasive monotherapy without PRP in the treatment of patients with atrophic acne scars. PATIENTS/METHODS: The Pubmed and Cochrane library databases were searched for relevant studies published before May 1, 2019. PRISMA guidelines were utilized. Studies that compared the use of PRP in combination with a noninvasive procedure and therapies without PRP for the treatment of atrophic acne scars were included. Cochrane's handbook was utilized to assess the individual biases of the included studies. Publication bias was assessed. RESULTS: A total of 311 participants (153 whole-face participants and 158 split-face participants) were reviewed across eight included studies. Quantitative analysis of 241 participants across six included studies showed a statistically significant reduction in scar severity scores in favor of microneedling or subcision with PRP (P < .001). Combination therapy with intradermal or topical PRP was significantly more effective than monotherapy alone and combination therapy with an adjunct other than PRP (P < .001 and .001, respectively). CONCLUSION: This systematic review and meta-analysis demonstrated that microneedling or subcision with PRP produced statistically significant improvement in validated outcomes over microneedling or subcision alone.

Is Syringocystadenoma Papilliferum Incidental in This Verrucous Carcinoma?

This case report presents a case in which a collision tumor consisting of three separate pathological entities-a verrucous carcinoma (VC), syringocystadenoma papilliferum (SCAP), and a basal cell carcinoma (BCC). The presentation of this collision tumor is unexpected. It presented as an exophytic mass on the scalp. While collisions of SCAP and VC are present in the literature, this case included an additional pathologic entity. The association of these entities and the unreported location of the lesion may provide some further insight as to the etiology of VC.

Mechanics and nanovoid nucleation dynamics: effects of polar functionality in glassy polymer networks.

We use molecular simulations and experiments to rationalize the properties of a class of networks based on dicyclopentadiene (DCPD), a polymer with excellent fracture toughness and a high glass transition temperature (Tg), copolymerized with 5-norbornene-2-methanol (NBOH). DCPD is a highly non-polar hydrocarbon, while NBOH contains a hydroxy group, introducing polar functionality and hydrogen bonds (H-bonds). NBOH thus represents a possible route to improve the chemical compatibility of DCPD-based networks with less-hydrophobic materials. We systematically vary the NBOH content (polar chemistry) in DCPD networks, while keeping other network parameters nearly constant, including the molecular weight between cross-links, chain rigidity, and Tg. Using molecular dynamics (MD) simulations, we quantify the thermovolumetric and mechanical properties, including Tg, cohesive energy density, stiffness, and yield strength. We compare these results with experiments on networks of similar composition, finding good agreement. The relation between these properties and polar chemistry are studied by examining a secondary network of physical cross-links, formed by hydrogen bonds between NBOH units. Further, we examine nanovoid formation, an energy dissipation mechanism hypothesized to contribute to the toughness of pDCPD. Using metadynamics to accelerate sampling, we quantify the nanovoid nucleation rate under hydrostatic tension, similar to the stress state in the plastic zone preceding a crack tip. Small additions of NBOH have minimal effect, but the rate drops steeply with larger amounts. Several properties are mapped at nanometer scales, including stiffness and mobility, and associated with void nucleation. Estimates of the length- and time-scale of the plastic zone near a crack tip are used in discussing nanovoid formation as a plausible toughening mechanism in these materials. Overall, the results suggest that pDCPD tolerates the addition of some polar chemistry without degrading its excellent mechanical properties.

Influence of molecular weight between crosslinks on the mechanical properties of polymers formed via ring-opening metathesis.

The apparent molecular weight between crosslinks (Mc,a) in a polymer network plays a fundamental role in the network mechanical response. We systematically varied Mc,a independent of strong noncovalent bonding by using ring-opening metathesis polymerization (ROMP) to co-polymerize dicyclopentadiene (DCPD) with a chain extender that increases Mc,a or a di-functional crosslinker that decreases Mc,a. We compared the ROMP series quasi-static modulus (E), tensile yield stress (σy), and fracture toughness (KIC and GIC) in the glassy regime with literature data for more polar thermosets. ROMP resins showed high KIC (>1.5 MPa m0.5), high GIC (>1000 J m-2), and 4-5 times higher high rate impact resistance than typical polar thermosets with similar Tg values (100 °C to 178 °C). The overall E values were lower for ROMP systems. The σy dependence on Mc,a and T-Tg for ROMP resins was qualitatively similar to more polar thermosets, but the overall σy values were lower. In contrast to more polar thermosets, the KIC and GIC values of the ROMP resins showed strong Mc,a and T-Tg dependence. High rate impact (∼104-105 s-1) trends were similar to the KIC and GIC behavior, but were also correlated to σy. Overall, a ductile failure mode was observed for quasi-static and high rate results for a linear ROMP polymer (Mc,a = 1506 g mol-1 due to chain entanglement), and this gradually transitioned to a fully brittle failure mode for highly crosslinked ROMP polymers (Mc,a ≤ 270 g mol-1). Molecular dynamics (MD) simulations showed that low Mc,a ROMP resins were more likely to form molecular scale nanovoids. The higher chain stiffness in low Mc,a ROMP resins inhibited stress relaxation in the vicinity of these nanovoids, which correlated with brittle mechanical responses. Overall, these differences in mechanical properties were attributed to the weak non-covalent interactions in ROMP resins.

Long-term release of a thiobenzamide from a backbone functionalized poly(lactic acid).

Hydrogen sulfide is emerging as a critically important molecule in medicine, yet there are few methods for the long-term delivery of molecules that degrade to release H2S. In this paper the first long-term release of a thiobenzamide that degrades to release H2S is described. A series of polymers were synthesized by the copolymerization of L-lactide and a lactide functionalized with 4-hydroxythiobenzamide. A new method to attach functional groups to a derivative of L-lactide is described based on the addition of a thiol to an α,ß-unsaturated lactide using catalytic I2. This reaction proceeded under mild conditions and did not ring-open the lactone. The copolymers had molecular weights from 8 to 88 kg mol-1 with PDIs below 1.50. Two sets of microparticles were fabricated from a copolymer; the average diameters of the microparticles were 0.53 and 12 µm. The degradation of the smaller microparticles was investigated in buffered water to demonstrate the slow release of thiobenzamide over 4 weeks. Based on the ability to synthesize polymers with different loadings of thiobenzamide and that thiobenzamide is a known precursor to H2S, these particles provide a polymer-based method to deliver H2S over days to weeks.

Tissue distribution of enrofloxacin in African clawed frogs (Xenopus laevis) after intramuscular and subcutaneous administration.

As part of an enrofloxacin pharmacokinetic study, concentrations of enrofloxacin and ciprofloxacin (metabolite) were measured in various tissues (brain, heart, kidney, liver, lung, and spleen) collected from treated (subcutaneous delivery, n = 3; intramuscular delivery, n = 3; untreated controls, n = 2) adult female Xenopus laevis by using HPLC. Enrofloxacin was rapidly absorbed after administration by either route and readily diffused into all sampled tissues. Enrofloxacin and ciprofloxacin were present in the tissue samples collected at 8 h. The highest average tissue concentrations for enrofloxacin were found in kidney, with the lowest concentrations in liver. Ciprofloxacin tissue concentrations paralleled but were always lower than those of enrofloxacin for all time points and tissues except brain and kidney. These results, together with previously published pharmacokinetic data and known minimal inhibitory concentrations of common pathogenic bacteria, provide a strong evidence-based rationale for choosing enrofloxacin to treat infectious diseases in X. laevis.

Retention of palladium and phosphine ligands using nanoporous polydicyclopentadiene thimbles.

Thimbles composed of polydicyclopentadiene retained Pd and phosphines used in Buchwald-Hartwig and Sonogashira coupling reactions but allowed the products to permeate. The products were isolated in high yields on the exteriors of the thimbles with no detectable contamination from phosphine and with Pd loadings as low as < 5.5 ppm.