Hydrogen peroxide (H2O2) is an endogenous reactive oxygen species that contributes to oxidative stress directly as a molecular oxidant and indirectly through free radical generation. Topically ...applied 1% to 45% H2O2 can be used for a range of clinical purposes, which will be reviewed here in addition to its safety. In concentrations from 1% to 6%, H2O2 has antimicrobial properties and can act as a debriding agent through its effervescence, making low-concentration H2O2 useful for wound care. H2O2 has also been shown to promote venous insufficiency ulcer healing, but studies in other wound types are needed. In 1% formulations, H2O2 is used outside the United States to treat acne and has shown efficacy similar to or greater than benzoyl peroxide, with reduced side effects. In a concentration of 40%, H2O2 is US Food and Drug Administration–approved to treat seborrheic keratoses and may cause fewer pigmentary changes than cryotherapy, although elimination often requires 2 to 4 treatments. However, H2O2 should be used with caution, as exposure can cause adverse effects through its oxidant capabilities. Low H2O2 concentrations cause only transient symptoms (blanching and blistering), but exposure to 9% to 45% H2O2 can cause more severe skin damage, including epidermal necrosis leading to erythema and bullae. Overall, H2O2 has numerous therapeutic uses, and novel indications, such as treating actinic keratoses and skin cancers, continue to be explored.
The goal was to determine the sensitivity and specificity of family history in identifying children with severe or genetic hyperlipidemias in a rural, predominantly white population.
A total of ...20,266 fifth-grade children in West Virginia, from the Coronary Artery Risk Detection in Appalachian Communities (CARDIAC) Project, who completed a family history and fasting lipid profile were used in analyses. The relationship between hyperlipidemia and family history was determined, and the use of family history to predict the need for pharmacologic treatment among children with dyslipidemia was evaluated.
A total of 71.4% of children met the National Cholesterol Education Program (NCEP) guidelines for cholesterol screening on the basis of positive family history. Of those, 1204 (8.3%) were considered to have dyslipidemia (low-density lipoprotein > or =130 mg/dL), and 1.2% of these children with dyslipidemia warranted possible pharmacologic treatment (low-density lipoprotein > or =160 mg/dL). Of the 28.6% who did not have a positive family history (did not meet NCEP guidelines), 548 (9.5%) had dyslipidemia, 1.7% of whom warranted pharmacologic treatment. Sensitivity and specificity data demonstrated that family history does not provide a strong indication as to whether pharmacologic treatment may be warranted.
Results indicate that the use of family history to determine the need for cholesterol screening in children would have (1) missed many with moderate dyslipidemia and (2) failed to detect a substantial number with likely genetic dyslipidemias that would require pharmacologic treatment. The use of universal cholesterol screening would identify all children with severe dyslipidemia, allowing for proper intervention and follow-up and leading to the prevention of future atherosclerotic disease.
AS1411 is a 26-mer G-rich DNA oligonucleotide that forms a variety of G-quadruplex structures. It was identified based on its cancer-selective antiproliferative activity and subsequently determined ...to be an aptamer to nucleolin, a multifunctional protein that preferentially binds quadruplex nucleic acids and which is present at high levels on the surface of cancer cells. AS1411 has exceptionally efficient cellular internalization compared to non-quadruplex DNA sequences.
Recent developments related to AS1411 will be examined, with a focus on its use for targeted delivery of therapeutic and imaging agents.
Numerous research groups have used AS1411 as a targeting agent to deliver nanoparticles, oligonucleotides, and small molecules into cancer cells. Studies in animal models have demonstrated that AS1411-linked materials can accumulate selectively in tumors following systemic administration. The mechanism underlying the cancer-targeting ability of AS1411 is not completely understood, but recent studies suggest a model that involves: (1) initial uptake by macropinocytosis, a form of endocytosis prevalent in cancer cells; (2) stimulation of macropinocytosis by a nucleolin-dependent mechanism resulting in further uptake; and (3) disruption of nucleolin-mediated trafficking and efflux leading to cargoes becoming trapped inside cancer cells.
Human trials have indicated that AS1411 is safe and can induce durable remissions in a few patients, but new strategies are needed to maximize its clinical impact. A better understanding of the mechanisms by which AS1411 targets and kills cancer cells may hasten the development of promising technologies using AS1411-linked nanoparticles or conjugates for cancer-targeted therapy and imaging. This article is part of a Special Issue entitled "G-quadruplex" Guest Editor: Dr. Concetta Giancola and Dr. Daniela Montesarchio.
•AS1411 is a G-quadruplex DNA oligonucleotide that is also a nucleolin aptamer.•This review covers the structure, clinical status, uses, and mechanism of AS1411.•AS1411 is being widely used to deliver therapeutic and imaging agents to cancer cells.•Its cancer-targeting activity has been demonstrated in at least 30 animal studies.•Its targeting mechanism is not fully understood but may involve macropinocytosis.
The routinisation thesis expects technology to hollow out the middle of the employment structure, leading to a uniform pattern of polarisation across affluent countries. This article argues that ...occupational change is also shaped by labour supply – particularly education and immigration – and institutions. Polarisation therefore represents just one scenario of occupational change. Our study of Ireland and Switzerland examines long-term change in the employment structure (1970–2010), using census data and an encompassing definition of the labour force. Results show no simple trend of occupational upgrading morphing into polarisation. Occupational upgrading occurred in both countries, with the largest employment gains in high-paid occupations and the largest losses in low-paid ones. Patterns of occupational change largely aligned with the evolution of labour supply, upgrading in the 1990s and 2000s being driven in both countries by higher educated women. Immigration supplied labour for low-end and mid-level jobs in Ireland during the Celtic Tiger era, and for low-paid occupations in Switzerland during the 1980s.
Systemic delivery of conventional chemotherapies can cause negative systemic toxicity, including reduced immunity and damage to organs such as the heart and kidneys-limiting the maximum dose that can ...be administered. Targeted therapies appear to address this problem by having a specific target while mitigating off-target effects. Biocompatible perfluorocarbon-based nanodroplet emulsions encapsulated by a phospholipid shell are in development for delivery of molecular compounds and hold promise as vehicles for targeted delivery of chemotherapeutics to tumors. When ultrasound is applied, perfluorocarbon will undergo a phase change-ultimately inducing transient perforation of the cell membrane when in close proximity, which is more commonly known as "sonoporation." Sonoporation allows enhanced intracellular delivery of molecular compounds and will reseal to encapsulate the molecular compound intracellularly. In this study, we investigated delivery of thymoquinone (TQ), a natural hydrophobic phytochemical compound with bioactivity in cancer cells. In addition, we conjugated a G-quadruplex aptamer, 'AS1411', to TQ-loaded nanodroplets and explored their effects on multiple human cancer cell lines. AS1411 binds nucleolin, which is over-expressed on the surface of cancer cells, and in addition to its tumor-targeting properties AS1411 has also been shown to induce anti-cancer effects. Thymoquinone was loaded onto AS1411-conjugated nanodroplet emulsion to assess activity against cancer cells. Confocal microscopy indicated uptake of AS1411-conjugated nanodroplets by cancer cells. Furthermore, AS1411-conjugated nanoemulsions loaded with TQ significantly enhanced cytotoxicity in cancer cells compared to free compound. These results demonstrate that AS1411 can be conjugated onto nanodroplet emulsions for targeted delivery to human cancer cells. This novel formulation offers significant potential for targeted delivery of hydrophobic chemotherapeutics to tumors for cancer treatment.
The public has expressed growing concern for the well-being of fishes, including popular pet species such as the Siamese fighting fish (
). In captivity, male
behave aggressively, often causing ...injuries and death if housed together. As a result, they are typically isolated in small fishbowls, which has been widely criticised as cruel. To investigate the impact of keeping
in these conditions, we recorded the behaviour of individual males in containers of different sizes that were either bare or enriched with gravel, large rocks, and live plants. When male
were housed individually in small bowls (0.5 L) they spent less time swimming than they did when they were kept in larger aquaria (10, 38, and 208 L). Fish that were kept in enriched containers exhibited more instances of swimming. To determine if two male
housed together might coexist peacefully if given enough space and cover from plants and large rocks, we quantified the behaviour of pairs of male
in bare or enriched aquaria of different sizes (10, 38, 208, 378 L). Fish performed fewer approaches and aggressive displays, but not attacks, and more bouts of foraging, when in larger aquaria. This study shows that the small fishbowls typically used in pet stores suppress swimming behaviour in male
and at least a 10-L aquarium is required to ensure full expression of swimming behaviour. Furthermore, even the use of very large aquaria cannot guarantee peaceful cohabitation between two males.
When D. H. Lawrence wrote his classic study of American
literature, he claimed that youth was the "true myth" of America.
Beginning from this assertion, Emily A. Murphy traces the ways that
youth ...began to embody national hopes and fears at a time when the
United States was transitioning to a new position of world power.
In the aftermath of World War II, persistent calls for the nation
to "grow up" and move beyond innocence became common, and the child
that had long served as a symbol of the nation was suddenly
discarded in favor of a rebellious adolescent. This era marked the
beginning of a crisis of identity, where literary critics and
writers both sought to redefine U.S. national identity in light of
the nation's new global position. The figure of the adolescent is
central to an understanding of U.S. national identity, both past
and present, and of the cultural forms (e.g., literature) that
participate in the ongoing process of representing the diverse
experiences of Americans. In tracing the evolution of this youthful
figure, Murphy revisits classics of American literature, including
J. D. Salinger's The Catcher in the Rye and Vladimir
Nabokov's Lolita , alongside contemporary bestsellers. The
influence of the adolescent on some of America's greatest writers
demonstrates the endurance of the myth that Lawrence first
identified in 1923 and signals a powerful link between youth and
one of the most persistent questions for the nation: What does it
mean to be an American?
Many dermatologists consider social media to be a useful tool for building their practices and personal brands. However, limited data exists on patients' perceptions of the value of social media in ...dermatology.
To examine how social media influences patients when choosing a dermatologist and which aspects of dermatologists' sites offer the most benefit to patients.
A cross-sectional study was completed by sampling a diverse online population using a 10-question survey.
The survey was sent to 1,481 individuals; of the 57.5% who qualified, 98.5% completed the survey (N=715). Of the qualified respondents, 58% were female and 42% were male. Twenty five percent were 18-29 years, 24% were 30-44 years, 33% were 45-60 years, and 19% were over 60 years. Fifty-seven percent reported that social media is only slightly important or not at all important when selecting a dermatologist. According to respondents, patient reviews (68%), years of experience (61%), and medical information written by the dermatologist (59%) were the most important aspects of dermatologists' social media sites. Cosmetic patients (P<0.0001), younger patients (P<0.0001), and participants with fewer years of education (P=0.0006) valued social media significantly more when selecting a dermatologist compared to their counterpart populations.
Selection bias is possible given the survey was distributed only to SurveyMonkey® users.
Given the majority of patients reported that social media is not important or only slightly important, dermatologists should consider means other than social media to attract new patients to their practices. For dermatologists who use social media, they should highlight patient reviews, experience level, and original medical content. J Drugs Dermatol. 2020;19(5): doi:10.36849/JDD.2020.4849.
Tuberous sclerosis is a developmental genetic disorder caused by mutations in TSC1, which results in epilepsy, autism, and intellectual disability. The cause of these neurological deficits remains ...unresolved. Imaging studies suggest that the thalamus may be affected in tuberous sclerosis patients, but this has not been experimentally interrogated. We hypothesized that thalamic deletion of Tsc1 at distinct stages of mouse brain development would produce differential phenotypes. We show that mosaic Tsc1 deletion within thalamic precursors at embryonic day (E) 12.5 disrupts thalamic circuitry and alters neuronal physiology. Tsc1 deletion at this early stage is unique in causing both seizures and compulsive grooming in adult mice. In contrast, only a subset of these phenotypes occurs when thalamic Tsc1 is deleted at a later embryonic stage. Our findings demonstrate that abnormalities in a discrete population of neurons can cause global brain dysfunction and that phenotype severity depends on developmental timing and degree of genetic mosaicism.
•Spatially and temporally controlled Tsc1 deletion mimics genetic mosaicism•Early Tsc1 deletion causes abnormal thalamic neuron physiology•Tsc1 mutant thalamic circuits alter somatosensory cortex patterning and function•Tsc1 deletion within developing thalamus causes abnormal grooming and seizures
Tuberous sclerosis is a genetic disorder involving autism, epilepsy, and intellectual disability. Using genetic mouse models, Normand et al. show how developmental timing of gene deletion, number of mutant neurons, and the brain regions affected contribute to these complex disease phenotypes.
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