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Radicals, with their unpaired electrons, exhibit unique chemical and physical properties that have long intrigued chemists. Despite early skepticism about their stability, the discovery of persistent radicals has opened new possibilities for molecular interactions. This review examines the mechanisms and applications of radically driven self-assembly, focusing on key motifs such as naphthalene diimides, tetrathiafulvalenes, and viologens, which serve as models for radical assembly. The potential of radical interactions in the development of artificial molecular machines (AMMs) are also discussed. These AMMs, powered by radical-radical interactions, represent significant advancements in non-equilibrium chemistry, mimicking the functionalities of biological systems. From molecular switches to ratchets and pumps, the versatility and unique properties of radically powered AMMs are highlighted. Additionally, the applications of radical assembly in materials science are explored, particularly in creating smart materials with redox-responsive properties. The review concludes by comparing AMMs to biological molecular machines, offering insights into future directions. This overview underscores the impact of radical chemistry on molecular assembly and its promising applications in both synthetic and biological systems.

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INTRODUCTION: Eye drops are commonly used for delivering ophthalmic drugs despite many deficiencies including low bioavailability and poor compliance. Contact lenses can deliver drugs with high bioavailability but commercial contacts release drug rapidly, limiting benefits and necessitating modifications to improve the drug release characteristics. AREAS COVERED: This review covers the common approaches to prolong the release rates of drugs from contact lenses including molecular imprinting, incorporation of nano/microparticles, vitamin-E barriers, and layered/implant contact lenses. It also evaluates their suitability for commercialization and discusses challenges that need to be addressed before commercialization is possible. EXPERT OPINION: In spite of many benefits of contact lenses compared to eye drops, a drug-eluting contact lens has not emerged in the market due to many reasons including potential safety risks, patient and practitioner acceptance, and production and storage factors. Importantly, changes in the critical lens properties must also be considered such as ion and oxygen permeability, loss in modulus, optical and swelling properties, and protein adherence upon drug loading. Many technologies have addressed scientific and commercialization challenges and are currently being tested both in animal and clinical studies. It is likely that a drug-eluting contact lens will be commercialized in the future.

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The rapid emergence of novel psychoactive substances within the past decade has raised new concerns about the harms associated with unregulated drug use. Synthetic analogues-chemically related to established psychoactive substances like cannabis sativa and catha edulis-in particular have proliferated rapidly, allowing little opportunity for scientific research or the establishment of informal guidelines for safe use among consumers. To explore how synthetic substance use relates to other forms of use, this paper presents an analysis of polysubstance use among a sample of 676 people who use illicit substances in the United States. Participants were sampled from three greater metropolitan areas (Houston/Galveston, Texas; New York City; and New Orleans, Louisiana). Study researchers used cluster-type analyses to develop dendrogram visualizations of the interrelationships between substance types. Results suggest a considerable variation in substance and polysubstance use patterns across states in the U.S. Polysubstance use clustered around well-observed combinations like MDMA/cannabis and cocaine/heroin. Synthetic cannabinoids and cathinones showed no strong clustering with other substances. High rates of binge drinking among users of other substances further support the importance of interventions sensitive to the clinical challenges of polysubstance use.

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Ophthalmic delivery via iontophoresis is currently achieved by placing an electrode on the cornea with a counter electrode on the ear or forehead. Here we test the feasibility of placing both electrodes diametrically opposite on a contact lens to create field gradients to transport ionic drugs into the cornea. Commercial lenses loaded with nile blue and fluorescein as hydrophobic and hydrophilic drug analogs, respectively were placed on cadaver rabbit eyes. Electric field gradients were created by placing cathode and anode on the lens diametrically opposite to each other. The incorporation of an electric field (0.125 m-0.250 mA), showed an increased uptake of nile blue and the quantity was a function of the duration of the electric field and the amount of applied current. Similar increases in flux were observed for fluorescein. Confocal fluorescence imaging also shows increased penetration of the dyes in presence of the field. An equivalent circuit model suggests that the field gradients are much stronger in the direction perpendicular to the cornea, which results is minimal short circuiting of current through the tear film. The incorporation of an electric field into a lens could be a less invasive and more effective approach to achieve ophthalmic drug delivery via iontophoresis.

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PURPOSE: A drug loaded contact lens combined with electrodes positioned diametrically opposite and beyond the limbus can potentially deliver ionic drugs directly to the vitreous. METHODS: Commercial lenses are loaded with nile blue or fluorescein as the drug analogs and placed on cadaver rabbit eyes. Electrodes (19.6 mm2) are placed atop at opposite sides of the sclera to apply a constant current (0.125-0.250 mA) for 1-2 h. COMSOL simulations are conducted to determine the field distribution and the potential drop across various tissue layers and equivalent circuit model is developed to calculate the electrophoretic velocity and estimate the drug flux. RESULTS: The device delivered both hydrophobic and hydrophilic dyes to the tissue. The amount of fluorescein delivered to the vitreous directly correlated with the applied current and time duration. The electrophoretic mobility from the experimental data agreed with the model estimates. Confocal microscopy showed that nile blue penetrated through the conjunctiva-sclera barrier to reach the retina showing that the electric field can transport molecules through the ocular tissue and into the vitreous. The ex vivo model neglects transport into flowing capillaries in the choroid. However, the time scale for electrophoretic transport across the choroid was found to be 550-1300 fold shorter than that for uptake into the choroidal capillaries. CONCLUSION: Incorporation of an electric field with multiple electrodes on a single lens can effectively deliver ionic drugs to the posterior region at levels comparable to current methods with the benefits of being safer and less invasive.

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PURPOSE: Oxygen permeability or transmissibility is a crucial parameter for contact lenses to ensure that extended wear will not induce corneal hypoxia. This work tests a new method of using the oxidation of cysteamine, an oxygen-sensitive chemical, to quantify the oxygen transmissibility of current commercial contact lenses and contact lenses loaded with vitamin E. METHODS: 3D printing was used to modify eye drop bottles and quartz cuvettes to create systems that allowed insertion of a contact lens in between the cysteamine solution and air. Both systems were exposed to atmospheric conditions where the only path of entry for oxygen was through the contact lens. The entering oxygen reacted with cysteamine, and the rate of cysteamine oxidation was measured using UV-vis spectrophotometry. The rate was then stoichiometrically related to oxygen transmissibility. RESULTS: The eye drop method predicted transmissibility values within 9% of established, commercial values. The cuvette method predicted values within 10% of established values for silicone hydrogel lenses without any correction factor and within 11% for poly-hydroxyethyl-methacrylate lenses after correcting for oxygen entering the system. Incorporation of 20% (w/w) vitamin E into Acuvue® Oasys® lenses did not have a significant impact on the oxygen transmissibility. CONCLUSIONS: Both methods presented in this work can reliably measure oxygen transmissibility of contacts lenses or other materials. Further improvements in manufacturing could lead to improved accuracy and reliability, allowing wider use of this method for quantifying the oxygen transport in contact lenses.

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Cystinosis is a genetic disease that leads to the accumulation of intracellular cystine crystals in all organs including cornea due to the loss of cystine efflux transporters in the lysosome of the cells. While the mechanism for formation of intracellular cystine is well understood for most organs, it does not explain many observations for crystal accumulation in the cornea of cystinosis patients. First, the crystals in cornea are extracellular and needle-like with several hundred microns length which is in sharp contrast with the rectangular or hexagonal crystals found throughout other organs. Second, these crystals are arranged parallel to the stromal collagen, which is a unique to the cornea. Third, crystal growth in the cornea reaches a saturation point after where no further crystallization occurs. We propose a hypothesis supported by in vitro and ex vivo data to explain these observations. We hypothesize that the stroma crystals form extracellularly due to the ionic interactions between the cystine diffusing into the eye and collagen fibrils present in the stroma. We examine cystine crystal growth both with in vitro polymer solutions and ex vivo in rabbit cadaver eyes to show that negatively charged polymers lead to the formation of more cystine precipitation in aqueous solution and that needle-like cystine crystal formation can be observed only in presence of certain polyelectrolytes including collagen. This proposed mechanism explains many of the yet unanswered questions but it needs further support from in vivo studies. The improved understanding could lead to improved treatment of corneal cystinosis.

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Actomyosin stress fibers impinge on the nucleus and can exert compressive forces on it. These compressive forces have been proposed to elongate nuclei in fibroblasts, and lead to abnormally shaped nuclei in cancer cells. In these models, the elongated or flattened nuclear shape is proposed to store elastic energy. However, we found that deformed shapes of nuclei are unchanged even after removal of the cell with micro-dissection, both for smooth, elongated nuclei in fibroblasts and abnormally shaped nuclei in breast cancer cells. The lack of shape relaxation implies that the nuclear shape in spread cells does not store any elastic energy, and the cellular stresses that deform the nucleus are dissipative, not static. During cell spreading, the deviation of the nucleus from a convex shape increased in MDA-MB-231 cancer cells, but decreased in MCF-10A cells. Tracking changes of nuclear and cellular shape on micropatterned substrata revealed that fibroblast nuclei deform only during deformations in cell shape and only in the direction of nearby moving cell boundaries. We propose that motion of cell boundaries exert a stress on the nucleus, which allows the nucleus to mimic cell shape. The lack of elastic energy in the nuclear shape suggests that nuclear shape changes in cells occur at constant surface area and volume.

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OBJECTIVE: Both media reports and preliminary research suggest that problem drinking is a concern in the U.S. fire service. However, no national epidemiological research has been conducted. This study presents the first national data on alcohol consumption patterns among firefighters. METHOD: Data are from 954 male firefighters at 20 career fire departments. The departments covered 14 U.S. states, commonwealths, and/or territories and each of the four major U.S. Census Bureau Regions. Alcohol use was assessed through both surveys and, in a subsample, 24-hour dietary recall interviews from an off-duty day. RESULTS: More than 85% of participants consumed alcohol, nearly half reported excessive drinking, and approximately one third reported episodic heavy use when off duty. Firefighters (in comparison with officers or chiefs) and those with fewer years of service had particularly high levels of alcohol intake. Among firefighters who drank, the energy derived from alcohol averaged 539 kcals, or nearly 18% of total energy. Twenty five percent of firefighters consumed more than 770 kcals from alcohol in a single day. CONCLUSIONS: Given the high prevalence of excessive and episodic heavy drinking and the impact of alcohol on energy intake in this population, national surveillance programs and targeted prevention interventions for problem drinking in the U.S. fire service are critically needed.

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INTRODUCTION: National guidelines state that health care professionals (HCPs) should advise patients on the importance of maintaining a healthy weight. Firefighters have high rates of obesity, and cardiovascular events are the leading cause of line-of-duty deaths in firefighters. This study assessed the association of age and body mass index (BMI) with HCP weight recommendations among male firefighters. METHODS: We used data on self-reported HCP weight recommendations and measured BMI from a 2011-2012 national sample of male firefighters (N = 1,002). HCP recommendations were recorded as no advice, maintain, gain, or lose weight, and BMI was categorized as normal (<25.0 kg/m(2)), overweight (25.0-29.9 kg/m(2)), class I obese (30.0-34.9 kg/m(2)), and class II or III obese (≥35.0 kg/m(2)). We used multinomial logistic regression to estimate the odds of receiving weight advice by age and BMI categories. RESULTS: Most firefighters (96%) reported visiting an HCP in the past year. Most (69%) firefighters and 48% of class I to III obese firefighters reported receiving no weight advice. Higher BMI predicted HCP advice to lose weight (odds ratio class I obese vs normal weight: 12.98; 95% confidence interval: 5.38-31.34). Younger firefighters were less likely to receive weight loss advice than older firefighters, except among those who were class II or III obese. CONCLUSIONS: HCPs are important sources of health information for firefighters. Overweight and obese firefighters, particularly those who are younger, do not consistently receive HCP advice to lose weight. This marks a missed opportunity to prevent further weight gain and reduce obesity-related health outcomes.

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OBJECTIVE: Quantify the association between adiposity and frequency of self-reported poor health days among male firefighters. METHODS: Measures were taken for body mass index, waist circumference, and percentage of body fat. Firefighters self-reported the outcome of the number of poor health days in the past 30 days. Zero-inflated negative binomial models and fractional polynomial plots were used to determine the impact of adiposity on the frequency of self-reported poor health days. RESULTS: Body mass index (rate ratio [RR]: 1.037; 95% confidence interval [CI]: 1.003 to 1.073), waist circumference (RR: 1.012; 95% CI: 0.999 to 1.030), and percentage of body fat (RR: 1.021; 95% CI: 0.999 to 1.041) were associated with self-reported poor health days. CONCLUSIONS: Adiposity is positively associated with frequency of self-reported poor health days among male firefighters. Future efforts to improve health among firefighters should emphasize reductions in adiposity.

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OBJECTIVES: We conducted a longitudinal assessment of tobacco pricing in military retail outlets, including trends within each service branch. METHODS: We determined the price of a single pack of Marlboro Red cigarettes at military retail stores located in the continental United States, Alaska, and Hawaii and at their nearest Walmarts in spring 2011 and 2013 (n = 128 for pairs available at both assessments). RESULTS: The average difference between cigarettes sold in military retail outlets and Walmarts decreased from 24.5% in 2011 to 12.5% in 2013. The decrease was partially attributable to significant price decreases at Walmarts. The largest increases in cigarette prices occurred on naval installations. Potential savings at stores on several installations remained substantial in 2013; the largest approached $6 per pack. Stores on 17 military installations decreased cigarette prices during the study period. CONCLUSIONS: Tobacco can be purchased in military retail stores at substantial savings over civilian stores. If tobacco pricing is to cease to be an incentive for use among personnel, a revised military tobacco pricing policy is needed.

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Toll-like receptor 4 (TLR4) is a key factor in the innate immune recognition of lipopolysaccharide (LPS) from Gram-negative bacteria. Previous studies from our group identified differences in the expression profile of TLR4 and genes affected by the TLR4 signaling pathway among pigs that shed varying levels of Salmonella, a Gram-negative bacterium. Therefore, genetic variation in this gene may be involved with the host's immune response to bacterial infections. The current study screened for single nucleotide polymorphisms (SNPs) in the TLR4 gene and tested their association with Salmonella fecal shedding. Pigs (n = 117) were intranasally challenged at 7 weeks of age with 1 × 10(9) CFU of S. Typhimurium χ4232 and were classified as low or persistent Salmonella shedders based on the levels of Salmonella being excreted in fecal material. Salmonella fecal shedding was determined by quantitative bacteriology on days 2, 7, 14, and 20/21 post exposure, and the cumulative levels of Salmonella were calculated to identify the low (n = 20) and persistent (n = 20) Salmonella shedder pigs. From those 40 animals, the TLR4 region was sequenced, and 18 single nucleotide polymorphisms (SNPs) in TLR4 were identified. Twelve SNPs have been previously described and six are novel SNPs of which five are in the 5' untranslated region and one is in intron 2. Single marker association test identified 13 SNPs associated with the qualitative trait of Salmonella fecal shedding, and seven of those SNPs were also associated with a quantitative measurement of fecal shedding (P < 0.05). Using a stepwise regression process, a haplotype composed of SNPs rs80787918 and rs80907449 (P ≤ 4.0 × 10(-3)) spanning a region of 4.9 Kb was identified, thereby providing additional information of the influence of those SNPs on Salmonella fecal shedding in pigs.

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BACKGROUND: Rates of occupational injuries among firefighters are high because of the physically demanding and variable tasks required by their job. While descriptive data about injuries exist, few studies have explored individual risk factors and their relationship to occupational injury. METHODS: The current study presents data from a population-based sample of 462 career firefighters from 11 randomly-selected fire departments in the Missouri Valley region of the USA (Kansas, Missouri, Iowa, North Dakota, South Dakota, Colorado, Wyoming, Nebraska) who participated in a study evaluating risks for negative cardiovascular outcomes and injury. Relationships were examined between injury and demographic characteristics, body composition, fitness, and health behaviours. RESULTS: Participants were most likely to be injured during physical exercise and those who reported regular on-duty exercise had a fourfold increase in risk for exercise-related injury compared with those who did not exercise on duty (OR=4.06, 95% CI 1.73 to 12.24). However, those who exercised were half as likely to sustain non-exercise injuries (OR=0.53, 95% CI 0.32 to 0.85). CONCLUSIONS: Findings highlight the benefit of physical training for firefighters despite the risk of injury during exercise.

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Primary mucinous carcinoma of the skin is a rare malignant neoplasm, often with periocular involvement, believed to originate from eccrine sweat glands. It is slow growing and locally destructive, at times forming tumour satellites. We present a case with six local recurrences treated with surgical resections over a period of 30 years. We have not been able to find longer follow-up in the literature, and believe this case may offer insight into the management of these uniquely indolent malignancies.

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OBJECTIVE: To evaluate the efficacy of a special program for training pediatric residents to address tobacco. METHODS: In a study conducted at the New Jersey Medical School, sixteen pediatric residency training programs in the New York/New Jersey metropolitan area were assigned randomly to either special or standard training conditions. All of the residents were invited to take part in the training. Only second- and third-year residents participated in data collection activities (baseline and follow-up tobacco surveys and objective structured clinical examinations [OSCEs]). Baseline data were collected in the spring of 2001, and follow-up data were collected annually through the spring of 2005. Special training consisted of a hybrid website/CD-ROM training program on tobacco, a seminar series, companion intervention material, and clinic mobilization. Standard training residents participated in the seminar series and utilized standard educational and self-help material. RESULTS: The percent of residents in special training, but not of those in standard training, who provided assistance for modifying environmental tobacco smoke, preventing use, and helping patients and parents stop smoking increased significantly from baseline to year 4 of training, as did the percent who felt prepared to address tobacco. Performance on the OSCEs was consistent with survey outcomes as special training residents revealed mastery of key interviewing and intervention skills. CONCLUSION: The special training program, with Solutions for Smoking as its centerpiece, was found to be effective for training pediatric residents to address tobacco, and it may serve as a model for pediatric residency training programs. Ways of improving the program are discussed.

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This study provides a comparison of cigarette smoking among two cohorts of U.S. Air Force recruits. The first cohort, Air Force 1, entered the military between August 1995 and August 1996. The second cohort, Air Force 2, entered between October 1999 and September 2000. Cigarette use significantly increased among both men (7.0-percentage point increase) and women (7.3-percentage point increase) between the two cohorts. This difference remained statistically significant in models adjusted for demographic differences between the two groups of recruits. Direct standardization methods were then used to compare rates in both Air Force surveys with rates of current smoking reported for a national sample from the Behavioral Risk Factor Surveillance System surveys from the same years. Although the average number of cigarettes smoked and years of smoking decreased between the two cohorts, troops from Air Force 2 reported being less motivated to quit. This study suggests that efforts to reduce smoking among junior enlisted troops in the Air Force should be bolstered.

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OBJECTIVES: The Pediatric Residency Training on Tobacco Project is a four-year randomized prospective study of the efficacy of training pediatric residents to intervene on tobacco. At the start of the study (baseline), the pediatric residents uniformly agreed that environmental tobacco smoke (ETS) and tobacco use pose serious threats to the health of young people, and pediatricians should play a leadership role in the antismoking arena. However, very few went beyond advising patients and parents to modify their behavior by providing actual assistance, and many of them lacked necessary tobacco intervention skills and knowledge. We hypothesized that both standard training and special training programs would yield positive changes in intervention skills and activities, although the changes would be greater in residents exposed to the special training condition. In the present report, we present two-year outcome data from the resident tobacco surveys and objective structured clinical examinations (OSCEs) administered to independent waves of third-year residents in each experimental condition at baseline and year 2. METHODS: Fifteen pediatric residency training programs in the New York/New Jersey metropolitan area were assigned randomly to special and standard training conditions (eight to special and seven to standard training). Resident tobacco surveys and OSCEs were administered to third-year residents at the start of the training programs (baseline) and at years 1 and 2 of the study. Comparisons between sequential waves of third-year residents with no (baseline) or two-year exposure to the training programs permitted assessment of changes in resident beliefs, intervention activities and intervention skills within each experimental condition. RESULTS: By year 2, the residents associated with each training condition benefited from the training program, but the annual surveys and OSCEs revealed more significant positive changes for waves of residents in the special training condition. Most important, third-year residents exposed to the special training condition for two years were more likely than comparable residents in the standard training condition to reveal significant increases in the degree to which they provided active assistance for modifying smoking and ETS. CONCLUSIONS: The two-year findings from the pediatric tobacco project are encouraging and suggest that the special training program is efficacious, although aspects of the program in need of improvement were identified.

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OBJECTIVES: The purpose of this study was to evaluate the antimicrobial effect of toluidine blue O (TBO), in combination with either a helium/neon (HeNe) laser or a light-emitting diode (LED), on the viability and architecture of Streptococcus mutans biofilms. METHODS: Biofilms were grown on hydroxyapatite discs in a constant depth film fermentor fed with artificial saliva that was supplemented with 2% sucrose four times a day, thus producing a typical 'Stephan pH curve'. Photodynamic therapy was subsequently carried out on biofilms of various ages with light from either the HeNe laser or LED using energy densities of between 49 and 294 J/cm(2). RESULTS: Significant decreases in the viability of S. mutans biofilms were only observed when biofilms were exposed to both TBO and light, when reductions in viability of up to 99.99% were observed with both light sources. Overall, the results showed that the bactericidal effect was light dose-dependent and that older biofilms were less susceptible to photodynamic therapy. Confocal laser scanning microscopy images suggested that lethal photosensitization occurred predominantly in the outermost layers of the biofilms. CONCLUSIONS: Photodynamic therapy may be a useful approach in the treatment of dental plaque-related diseases.

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