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A hierarchical (triple scale) simulation methodology is presented for the prediction of the dynamical and rheological properties of high molecular-weight entangled polymer melts. The methodology consists of atomistic, moderately coarse-grained (mCG), and highly coarse-grained slip-spring (SLSP) simulations. At the mCG level, a few chemically bonded atoms are lumped into one coarse-grained bead. At this level, the chemical identity of the underlying atomistic system and the interchain topological constraints (entanglements) are preserved. The mCG interaction potentials are derived by matching local structural distributions of the mCG model to those of the atomistic model through iterative Boltzmann inversion. For matching mCG and atomistic dynamics, the mCG time is scaled by a time scaling factor, which compensates for the lower monomeric friction coefficient of the mCG model than that of the atomistic one. At the SLSP level, multiple Kuhn segments of a polymer chain are represented by one coarse-grained bead. The very soft nonbonded interactions between beads do not prevent chain crossing and, hence, can not capture entanglements. The topological constraints are represented by slip-springs, restricting the lateral motion of polymer chains. A compensating pair potential is used in the SLSP model to keep the static macromolecular properties unaltered upon the introduction of slip-springs. The static and kinetic parameters of the SLSP model are determined based on the lower-level simulation models. Particularly, matching the orientational autocorrelation of the end-to-end vector, we determine the number of slip-springs and calibrate the timescale of the SLSP model. As a test case, the hierarchical methodology is applied to cis-1,4-polybutadiene (cPB) at 413 K. Dynamical single-chain and linear viscoelastic properties of cPB melts are calculated for a broad range of molecular weights, ranging from unentangled to well-entangled chains. The calculations are compared, and found in good agreement, with experimental data from the literature.

Head lice infestation is a common and growing problem, primarily affecting school-aged children. There are growing numbers of treatment failures due to the emergence of treatment-resistant lice to the popular over-the-counter products that have been used for the past several decades. Resistance has also decreased the efficacy of lindane, a prescription pediculicide that has been commonly used for several generations. Malathion, recently reintroduced in the US as a prescription pediculicide, has been associated with some treatment resistance depending upon its formulation. Other insecticidal treatments, such as ivermectin, will have to be developed further, given the limited options presently available for the treatment of head lice. Given the number of anecdotal and market-driven reported studies on head lice, assessment of topical lice therapies requires standardised in vitro testing. Based on concerns about safety and decreasing efficacy due to resistance, a reassessment of the general topic of pediculicides for head lice is warranted.

To assess the chemical composition of cerumen by flash pyrolysis-gas chromatography/mass spectrometry.

Background: The incidence of head lice infestations in North America is escalating with an estimated 12 million cases of head lice per year despite the existence of insecticidal therapies.Objective: To evaluate certain characteristics of the human head louse, including their chitinous structure, nymphal developmental stages, legs with claw adaptations, antennae with sensory perceptions, and spiracles by which oxygen exchange occurs, for assessment of possible means to control the spread and growth of this insect.Methods: Scanning electron-microscopic examination of head lice was performed.Results: Newer treatments of head lice must acknowledge defense mechanisms that are based on anatomic structure and physiologic characteristics, details of louse transmission, and the insects' ability to ‘resurrect’ after sham death.Conclusions: An understanding of lice entomology is essential in the pursuit of novel means to control the lice epidemic.

Background: Benzoyl peroxide is the most widely used topical agent for acne since the 1960s. Concomitant treatment of benzoyl peroxide with oral, or topical antibiotics diminishes the multiplication of antibiotic-resistant strains of Propionibacteria acnes.Besides being antibacterial, the chemical also functions as a peeling agent, has comedolytic activity, reduces free fatty acid levels, and is touted to be sebosuppressive.Objective: The purpose was to determine the ability of topically applied benzoyl peroxide to suppress lipogenesis of the sebaceous glands.Methods: The data were obtained employing an animal model for human sebaceous glands, namely, the flank organs of female golden Syrian hamsters.Results: Our results reveal no inhibition of lipogenesis in sebaceous glands by topical application of benzoyl peroxide.Conclusion: Despite many functions beneficial in acne therapy, benzoyl peroxide does not possess sebosuppressive capabilities. With the advent of water-soluble organic peroxides revealing similar antimicrobial activity to benzoyl peroxide, all therapeutic parameters (save for sebosup-pression) will need to be assessed to weigh the benefits of these second-generation acne-fighting peroxides.

A plethora of head lice cases that require optimal therapeutic assessments are developing in elementary schools. Over-the-counter therapies continue to be the mainstream solution for most cases of pediculosis capitis, but the onset of resistant cases dictates a review of available treatment modalities. The increased efficacy of prescription drugs, namely topical 5% permethrin and oral ivermectin, underline the expanding role that physicians will serve in the eradication of head lice in our communities. (J Am Acad Dermatol 1998;38:979-82.)

With improved genetic testing and genomic sequencing, abnormalities are increasingly being identified in affected or germline tissues in DNA of patients with vascular tumors, vascular malformations, and lymphedema. Recognition of the genetics of vascular anomalies should help clinicians make more specific diagnoses, anticipate diagnosis-specific morbidities, provide better genetic counseling, and have a better understanding of the pathogenesis of these anomalies. Growing pharmacologic options, including therapies targeted to specific mutations, with obvious parallels to cancer treatment now allow the pediatric hematologist-oncologist to assume a more prominent role in clinical care and research for patients with these diagnoses. We summarize genes and genetic loci that have been associated with vascular anomalies and offer guidelines for patient evaluations.

IMPORTANCE Isotretinoin is the most effective treatment for acne. The ideal dosing regimen is unknown. OBJECTIVE To determine the rates of relapse of acne vulgaris and retrial of isotretinoin after high cumulative-dose treatment and the changes to the adverse effect profile. DESIGN, SETTING, AND PARTICIPANTS A prospective, observational, intervention study was conducted from August 1, 2008, to August 31, 2010, in a single academic tertiary care center with multiple providers. A total of 180 patients with acne resistant to other treatments were enrolled. Of these, 116 participated in the 12-month follow-up survey, for a response rate of 64.4%. EXPOSURE Patients received isotretinoin, with dosing based on the providers’ judgment. Patients were divided into 2 groups on the basis of cumulative dosing (<220 mg/kg and ≥220 mg/kg). MAIN OUTCOMES AND MEASURES Relapse (treatment with a prescription topical or oral acne medication after a course of isotretinoin) or retrial (retreatment with isotretinoin) at 12-month follow-up and adverse effects experienced during and after 12 months of treatment. RESULTS The mean age of the participants was 19.3 years, 51.9% were female, and 74.1% were white. At 12 months’ follow-up, 97.4% of the patients reported that their acne was improved. Overall, acne in 32.7% of patients in the study relapsed at 12 months, and 1.72% of the patients required a retrial. In the lower-dose treatment group (<220 mg/kg), the relapse rate was 47.4% (95% CI, 32.3%-63.0%) compared with 26.9% (95% CI, 18.3%-37.8%) in the high-dose group (P = .03). Almost 100% of the patients in both treatment groups developed cheilitis and xerosis during treatment. Retinoid dermatitis was significantly more common in the high-dose treatment group (53.8% vs 31.6%; P = .02). None of the other adverse effects was significantly different between the 2 groups. CONCLUSIONS AND RELEVANCE The dosing regimen used in the present study is considerably higher than that used in previous studies of isotretinoin. At 1 year after completion of isotretinoin treatment, we found that patients receiving 220 mg/kg or more had a significantly decreased risk of relapse. Rash was the only adverse effect that was significantly more common in the high-dose group during treatment. This study suggests that significantly higher doses of isotretinoin are effective for treating acne and decreasing relapse rates without increasing adverse effects.

Acne vulgaris is a common skin disorder that affects most individuals at some point in their lives. It may result in significant morbidity, including cutaneous scarring and psychological impairment. Current treatments include topical retinoids, benzoyl peroxide, topical and systemic antibiotics, and systemic isotretinoin. There are growing concerns of rising antibiotic resistance, significant side effects of isotretinoin therapy, and lack of safe and effective treatment for pregnant females. Recent advances in the pathogenesis of acne have led to a greater understanding of the underlying inflammatory mechanisms and the role the Propionibacterium acnesand biofilms. This has led to the development of new therapeutic targets. This article reviews emerging treatments of acne, including topical picolinic acid, topical antibiotic dapsone, systemic zinc salts, oral antibiotic lymecycline, new formulations of and synergistic combinations of benzoyl peroxide, photodynamic therapy with topical photosensitizers and potential acne vaccines.

Background: Over-the-counter insecticidal solutions continue to be the mainstream treatment for most cases of head lice. Recorded insecticidal activity 15 years ago was at 100%, with ovicidal kill at 80%. Recently scattered accounts of possible resistance have surfaced.Objective: This article is to document the general consensus that head lice are becoming resistant to standard over-the-counter therapies.Methods: Direct testing of lethality of adult lice with permethrin and pyrethroid was assessed.Results: Present over-the-counter products proved to be successful in only 9of 32 head lice tested (28% insecticidal activity).Conclusions: Our series of cases further documents that over-the-counter head lice preparations no longer achieve high levels of insecticidal activity, suggesting increased resistance to these insecticides.

AbstractBackground:Benzoyl peroxide (BP) is the most widely used topical agent for acne since its introduction in the 1960s. Concomitant topical treatment of BP and erythromycin is stated to be superior to BP alone. However, no synergistic activity has been found with this combination. Instead, such combination therapies are hypothesized to gain their efficacy by the coupled action of two effective treatments. The antibiotic kills all susceptible bacteria and the BP eliminates the resistant strains. Objective:The purpose was to compare radical production by BP alone and with various antibiotics to determine whether certain antibiotics increase radical formation by BP, as the antibacterial activity of BP may correlate with the amount of radicals it forms. Methods:Polymerization of tetraethylene glycol dimethacrylate was used as a test of BP radical activity. Results:The results suggest that radical activity increases upon addition of certain antibiotics, such as erythromycin, to a solution of BP. Conclusion:Radical activity of BP in tetraethylene glycol dimethacrylate is increased when tested in consort with several antibiotics, such as the macrolides. We propose that the tertiary amines contained on certain antibiotics are responsible for catalysis of BP radical formation. If increased radical formation correlates with enhanced biological effect, then these data reveal the possibility of a biological synergism in mixtures of BP and antibiotics. An understanding of the mechanism of catalysis of BP radical formation by antibiotics may lead to the discovery of improved treatments for acne.Copyright © 2000 S. Karger AG, Basel

The systematic coarse graining of polymeric systems is a usual route in order to extend the range of spatiotemporal scales and systems accessible to molecular simulations. Here, we present a bottom-up methodology in order to obtain coarse-grained (CG) models for copolymers, derived from more than one species of monomers via detailed atomistic simulations. In the proposed scheme, each monomer type is represented as a different CG particle. The effective CG interactions are obtained via a dual-stage multi-component iterative Boltzmann inversion optimization scheme, in which the single-component terms of the CG model are obtained from homopolymer simulations, whereas the interactions between different CG-type particles (mixed terms of the CG model) are obtained from the simulation of a symmetric composition copolymer. As an example, the proposed optimization scheme is applied on polybutadiene (PB) copolymers consisting of cis-1,4, trans-1,4, and vinyl-1,2 isomers. The derived CG PB copolymer model is examined with respect to its transferability across molecular weight and copolymer composition. In addition, using the newly derived CG model, various PB copolymers across a broad range of cis-1,4, trans-1,4, and vinyl-1,2 compositions are examined. Structural and dynamical properties of PB copolymers are presented. The vinyl component is found to have a large impact on the conformational properties of PB copolymer melts because of the different packing imposed by side groups. Standard composition mixing rules are used to predict the time mapping factors for the calculation of both segmental and center-of-mass dynamics of the PB copolymer, coming from the CG model.

A recently proposed hierarchical triple-scale simulation methodology (Behbahani et al., Macromolecules, 2021,54,2740–2762) is applied to cis-1,4 polyisoprene melts of a broad range of molecular weights, from oligomers to commercial-grade entangled materials. Dynamics are systematically probed over 12 orders of magnitude in time using a combination of atomistic and bottom-up parameterized coarse-grained and slip-spring simulations. Following calibration of the slip-spring simulations using the end-to-end autocorrelation function, generated data are contrasted to dielectric relaxation spectroscopy experiments and rheological measurements in the literature. A good agreement is found, particularly for highly entangled polymer melts, supporting the ability of the scheme to provide bottom-up parameter-free predictions on the dynamics of polymeric materials. Finally, we systematically examine the application of theoretical models to our strictly monodisperse cis-1,4 polyisoprene melts and provide estimates of the phenomenological parameters employed.