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Genome-wide association studies (GWAS) and polygenic score (PGS) development are typically constrained by the data available in biobank repositories in which European cohorts are vastly overrepresented. Here, we increase the utility of non-European participant data within the UK Biobank (UKB) by characterizing the genetic affinities of UKB participants who self-identify as Bangladeshi, Indian, Pakistani, "White and Asian" (WA), and "Any Other Asian" (AOA), towards creating a more robust South Asian sample size for future genetic analyses. We assess the relationships between genetic structure and self-selected ethnic identities resulting in consistent patterns of clustering used to train a support vector machine (SVM). The SVM model was utilized to reassign n = 1,853 AOA and WA participants at the subcontinental level, and increase the sample size of the UKB South Asian group by 1,381 additional participants. We then leverage these samples to assess GWAS performance and PGS development. We further include environmental covariates in the height GWAS by implementing a rigorous covariate selection procedure, and compare the outputs of two GWAS models: GWAS null and GWAS env . We show that PGS performance derived from environmentally adjusted GWAS yields comparable prediction to PGS models developed with an order of magnitude larger training dataset ( R 2 =0.021 vs 0.026). Models with 7 - 8 environmental covariates double the variance explained by PGS alone. In summary, we demonstrate how GWAS performance can be improved by leveraging ambiguous ethnicity codes, ancestry matched imputation panels, and including environmental covariates.

Cellular senescence is characterized by a permanent growth arrest and is associated with tissue aging and cancer. Senescent cells secrete a number of different cytokines referred to as the senescence-associated secretory phenotype (SASP), which impacts the surrounding tissue and immune response. Here, we find that senescent cells exhibit higher rates of protein synthesis compared to proliferating cells and identify eIF5A as a crucial regulator of this process. Polyamine metabolism and hypusination of eIF5A play a pivotal role in sustaining elevated levels of protein synthesis in senescent cells. Mechanistically, we identify a p53-dependent program in senescent cells that maintains hypusination levels of eIF5A. Finally, we demonstrate that functional eIF5A is required for synthesizing mitochondrial ribosomal proteins and monitoring the immune clearance of premalignant senescent cells in vivo. Our findings establish an important role of protein synthesis during cellular senescence and suggest a link between eIF5A, polyamine metabolism, and senescence immune surveillance., (© 2024. The Author(s).)

Background: Facultative bacterial endosymbionts have the potential to influence the interactions between aphids, their natural enemies, and host plants. Among the facultative symbionts found in populations of the grain aphid Sitobion avenae in central Chile, the bacterium Regiella insecticola is the most prevalent. In this study, we aimed to investigate whether infected and cured aphid lineages exhibit differential responses to wheat cultivars containing varying levels of the benzoxazinoid DIMBOA (2,4-dihydroxy-7-methoxy-2H-1,4-benzoxazin-3(4H)-one), which is a xenobiotic compound produced by plants. Specifically, we examined the reproductive performance responses of the most frequently encountered genotypes of Sitobion avenae when reared on wheat seedlings expressing low, medium, and high concentrations of DIMBOA., Results: Our findings reveal that the intrinsic rate of population increase (r m ) in cured lineages of Sitobion avenae genotypes exhibits a biphasic pattern, characterized by the lowest r m and an extended time to first reproduction on wheat seedlings with medium levels of DIMBOA. In contrast, the aphid genotypes harbouring Regiella insecticola display idiosyncratic responses, with the two most prevalent genotypes demonstrating improved performance on seedlings featuring an intermediate content of DIMBOA compared to their cured counterparts., Conclusion: This study represents the first investigation into the mediating impact of facultative endosymbionts on aphid performance in plants exhibiting varying DIMBOA contents. These findings present exciting prospects for identifying novel targets for aphid control by manipulating the presence of aphid symbionts. © 2023 Society of Chemical Industry., (© 2023 Society of Chemical Industry.)

Despite decades of research resulting in a comprehensive understanding of epicuticular wax metabolism, the function of these almost ubiquitous metabolites in plant-herbivore interactions remains unresolved. In this study, we examined the effects of CRISPR-induced knockout mutations in four Nicotiana glauca (tree tobacco) wax metabolism genes. These mutations cause a wide range of changes in epicuticular wax composition, leading to altered interactions with insects and snails. Three interaction classes were examined: chewing herbivory by seven caterpillars and one snail species, phloem feeding by Myzus persicae (green peach aphid) and oviposition by Bemisia tabaci (whitefly). Although total wax load and alkane abundance did not affect caterpillar growth, a correlation across species, showed that fatty alcohols, a minor component of N. glauca surface waxes, negatively affected the growth of both a generalist caterpillar (Spodoptera littoralis) and a tobacco-feeding specialist (Manduca sexta). This negative correlation was overshadowed by the stronger effect of anabasine, a nicotine isomer, and was apparent when fatty alcohols were added to an artificial lepidopteran diet. By contrast, snails fed more on waxy leaves. Aphid reproduction and feeding activity were unaffected by wax composition but were potentially affected by altered cutin composition. Wax crystal morphology could explain the preference of B. tabaci to lay eggs on waxy wild-type plants relative to both alkane and fatty alcohol-deficient mutants. Together, our results suggest that the varied responses among herbivore classes and species are likely to be a consequence of the co-evolution that shaped the specific effects of different surface wax components in plant-herbivore interactions., (© 2023 The Authors. Plant, Cell & Environment published by John Wiley & Sons Ltd.)

Cancer cell survival is highly dependent on its metabolic reprogramming, which supports not only cell growth but also confers to the tumor cells characteristics to initiate migration and colonization. Among the different mechanisms that are involved, translational control plays a significant role in oncogenesis; however, its impact on cancer progression still remains poorly understood. A study by Navickas and colleagues revealed that the RNA-binding protein heterogeneous nuclear ribonucleoprotein C (HNRNPC) functions as a translational regulator, and its downregulation in highly metastatic cells leads to the lengthening of 3' untranslated regions in HNRNPC-bound mRNAs, resulting in translational repression mediated by the AGO-miRNA RNA-induced silencing complex., (©2023 American Association for Cancer Research.)

Objectives: Collecting skeletal measurements from medical imaging databases remains a tedious task, limiting the research utility of biobank-level data. Here we present an automated phenotyping pipeline for obtaining skeletal measurements from DXA scans and compare its performance to manually collected measurements., Materials and Methods: A pipeline that extends the Advanced Normalization Tools (ANTs) framework was developed on 341 whole-body DXA scans of UK Biobank South Asian participants. A set of 10 measurements throughout the skeleton was automatically obtained via this process, and the performance of the method was tested on 20 additional DXA images by calculating percent error and concordance correlation coefficients (CCC) for manual and automated measurements. Stature was then regressed on the automated femoral and tibia lengths and compared to published stature regressions to further assess the reliability of the automated measurements., Results: Based on percent error and CCC, the performance of the automated measurements falls into three categories: poor (sacral and acetabular breadths), variable (trunk length, upper thoracic breadth, and innominate height), and high (maximum pelvic aperture breadth, bi-iliac breadth, femoral maximum length, and tibia length). Stature regression plots indicate that the automated measurements reflect realistic body proportions and appear consistent with published data reflecting these relationships in South Asian populations., Discussion: Based on the performance of this pipeline, a subset of measurements can be reliably extracted from DXA scans, greatly expanding the utility of biobank-level data for biological anthropologists and medical researchers., (© 2023 Wiley Periodicals LLC.)

Background: To reduce the arbitrariness in the allocation of rare resources in intensive care units (ICU) in the context of the pandemic, tiebreakers were considered in some COVID-19 triage algorithms. They were also contemplated to facilitate the tragic decisions of healthcare workers when faced with two patients with similar prognosis and only one ICU bed available. Little is known about the public's perspective on tiebreakers., Objectives: To consolidate the available scientific literature on public consultations, particularly on tiebreakers and their underlying values. Also, to obtain an overview of the key arguments presented by the participating public and to identify potential gaps related to this topic., Methods: The steps described by Arksey and O'Malley was the preferred method to our approach. Seven electronic databases were searched from January 2020 to April 2022, using keywords for each database: PubMed, Medline, EMBASE, Web of Science, PsycINFO, EBM reviews, CINAHL complete. We also searched in Google and Google Scholar, and in the references of the articles found. Our analysis was mainly qualitative. A thematic analysis was performed to consider the public's perspectives on tiebreakers and their underlying values, according to these studies., Results: Of 477 publications found, 20 were selected. They carried out public consultations through various methods: surveys (80%), interviews (20%), deliberative processes (15%) and others (5%) in various countries: Australia, Brazil, Canada, China, France, Germany, India, Iran, Italy, Japan, Korea, Netherlands, Portugal, Spain, Switzerland, Thailand, United Kingdom, and United States. Five themes emerged from our analysis. The public favored the life cycle (50%) and absolute age (45%) as a tiebreaker. Other values considered important were reciprocity, solidarity, equality, instrumental value, patient merit, efficiency, and stewardship. Among the new findings were a preference for patient nationality and those affected by COVID-19., Conclusions: There is a preference for favoring younger patients over older patients when there is a tie between similar patients, with a slight tendency to favor intergenerational equity. Variability was found in the public's perspectives on tiebreakers and their values. This variability was related to socio-cultural and religious factors. More studies are needed to understand the public's perspective on tiebreakers., Supplementary Information: The online version contains supplementary material available at 10.1007/s44250-023-00027-9., Competing Interests: Competing interestsThe authors declare that they have no competing interests., (© Crown 2023.)

Background: Little is known about factors affecting implementation of patient safety programmes in low and middle-income countries. The goal of our study was to evaluate the implementation of a patient safety programme for paediatric care in Guatemala., Methods: We used a mixed methods design to examine the implementation of a patient safety programme across 11 paediatric units at the Roosevelt Hospital in Guatemala. The safety programme included: (1) tools to measure and foster safety culture, (2) education of patient safety, (3) local leadership engagement, (4) safety event reporting systems, and (5) quality improvement interventions. Key informant staff (n=82) participated in qualitative interviews and quantitative surveys to identify implementation challenges early during programme deployment from May to July 2018, with follow-up focus group discussions in two units 1 year later to identify opportunities for programme modification. Data were analysed using thematic analysis, and integrated using triangulation, complementarity and expansion to identify emerging themes using the Consolidated Framework for Implementation Research. Salience levels were reported according to coding frequency, with valence levels measured to characterise the degree to which each construct impacted implementation., Results: We found several facilitators to safety programme implementation, including high staff receptivity, orientation towards patient-centredness and a desire for protocols. Key barriers included competing clinical demands, lack of knowledge about patient safety, limited governance, human factors and poor organisational incentives. Modifications included use of tools for staff recognition, integration of education into error reporting mechanisms and designation of trained champions to lead unit-based safety interventions., Conclusion: Implementation of safety programmes in low-resource settings requires recognition of facilitators such as staff receptivity and patient-centredness as well as barriers such as lack of training in patient safety and poor organisational incentives. Embedding an implementation analysis during programme deployment allows for programme modification to enhance successful implementation., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Aphids (Hemiptera: Aphididae) are insects with one of the highest potentials for invasion. Several aphid species are present globally due to introduction events; they represent important pests of agroecosystems. The bird cherry-oat aphid Rhopalosiphum padi (Linnaeus) is a major pest of cereals and pasture grasses worldwide. Here, we report the genetic features of populations of R. padi that colonize different cereal crops in central Chile., Methods: Rhopalosiphum padi individuals were collected in central Chile and genotyped at six microsatellite loci. The most frequent multilocus genotype (MLG) was then studied further to assess its reproductive performance across cereal hosts under laboratory conditions., Results: Populations of R. padi in Chile are characterized by a low clonal diversity ( G / N = 62/377 = 0.16) and the overrepresentation of a few widely distributed MLGs. One of the MLGs constituted roughly half of the sample and was observed in all sampled populations at high frequencies. Furthermore, this putative aphid "superclone" exhibited variations in its reproductive performance on cereals most commonly cultivated in Chile. The sampled populations also exhibited weak signs of genetic differentiation among hosts and localities. Our findings suggest that (1) obligate parthenogenesis is the primary reproductive mode of R. padi in Chile in the sampled range and (2) its introduction involved the arrival of a few genotypes that multiplied asexually., Competing Interests: The authors declare that they have no competing interests.

Initially identified as a factor involved in tyrosine kinase receptor signaling, Grb10-interacting GYF protein 2 (GIGYF2) has later been shown to interact with the 5' cap-binding protein 4EHP as part of a translation repression complex, and to mediate post-transcriptional repression of tethered reporter mRNAs. A current model proposes that GIGYF2 is indirectly recruited to mRNAs by specific RNA-binding proteins (RBPs) leading to translation repression through its association with 4EHP. Accordingly, we recently observed that GIGYF2 also interacts with the miRNA-induced silencing complex and probably modulates its translation repression activity. Here we have further investigated how GIGYF2 represses mRNA function. In a tethering reporter assay, we identify three independent domains of GIGYF2 with repressive activity. In this assay, GIGYF2-mediated repression is independent of 4EHP but largely dependent on the CCR4/NOT complex that GIGYF2 recruits through multiple interfaces. Importantly, we show that GIGYF2 is an RBP and identify for the first time endogenous mRNA targets that recapitulate 4EHP-independent repression. Altogether, we propose that GIGYF2 has two distinct mechanisms of repression: one depends on 4EHP binding and mainly affects translation; the other is 4EHP-independent and involves the CCR4/NOT complex and its deadenylation activity.

Programmes to modify the safety culture have led to lasting improvements in patient safety and quality of care in high-income settings around the world, although their use in low-income and middle-income countries (LMICs) has been limited. This analysis explores (1) how to measure the safety culture using a health culture survey in an LMIC and (2) how to use survey data to develop targeted safety initiatives using a paediatric nephrology unit in Guatemala as a field test case. We used the Safety, Communication, Operational Reliability, and Engagement survey to assess staff views towards 13 health climate and engagement domains. Domains with low scores included personal burnout, local leadership, teamwork and work-life balance. We held a series of debriefings to implement interventions targeted towards areas of need as defined by the survey. Programmes included the use of morning briefings, expansion of staff break resources and use of teamwork tools. Implementation challenges included the need for education of leadership, limited resources and hierarchical work relationships. This report can serve as an operational guide for providers in LMICs for use of a health culture survey to promote a strong safety culture and to guide their quality improvement and safety programmes., Competing Interests: Competing interests: None declared.

Understanding the function of the thousands of cellular proteins is a central question in molecular cell biology. As proteins are typically part of multiple dynamic and often overlapping macromolecular complexes exerting distinct functions, the identification of protein-protein interactions (PPI) and their assignment to specific complexes is a crucial but challenging task. We present a protein fragments complementation assay integrated with the proximity-dependent biotinylation technique BioID. Activated on the interaction of two proteins, split-BioID is a conditional proteomics approach that allows in a single and simple assay to both experimentally validate binary PPI and to unbiasedly identify additional interacting factors. Applying our method to the miRNA-mediated silencing pathway, we can probe the proteomes of two distinct functional complexes containing the Ago2 protein and uncover the protein GIGYF2 as a regulator of miRNA-mediated translation repression. Hence, we provide a novel tool to study dynamic spatiotemporally defined protein complexes in their native cellular environment.

The monoecious anholocyclical aphid, Chaetosiphon fragaefolii (Cockerell) (Homoptera: Aphididae), was collected on a native strawberry, Fragaria chiloensis (L.) Duchesne (Rosales: Rosaceae) from different sites in Chile. The presence of this aphid was recorded during two consecutive years. F. chiloensis plants were collected from seven natural and cultivated growing areas in central and southern Chile. Aphids were genotyped by cross-species amplification of four microsatellite loci from other aphid species. In addition, the aphid borne virus Strawberry mild yellow edge virus was confirmed in F. chiloensis plants by double-antibody sandwich ELISA and RT-PCR. Genetic variability and structure of the aphid populations was assessed from the geo-referenced individuals through AMOVA and a Bayesian assignment test. The presence of C. fragaefolii, during the two-year study was detected in only four of the seven sites (Curepto, Contulmo, Chilián and Cucao). Genetic variation among these populations reached 19% of the total variance. When assigning the individuals to groups, these were separated in three genetic clusters geographically disjunct. Of the seven sampled sites, six were positive for the virus by RT-PCR, and five by double-antibody sandwich ELISA . The incidence of the virus ranged from 0-100%. Presence of the virus corresponded with the presence of the aphid in all but two sites (Chilian and Vilches). The greatest incidence of Strawberry mild yellow edge virus was related to the abundance of aphids. On the other hand, sequences of the coat protein gene of the different virus samples did not show correspondence with either the genetic groups of the aphids or the sampling sites. The genetic structure of aphids could suggest that dispersal is mainly through human activities, and the spread to natural areas has not yet occurred on a great scale.

Background: It is well known that there is a growing shortage of academic dermatologists in the U.S. The number of graduates of foreign dermatology residencies (GFDR) and graduates of military dermatology residencies (GMDR) who take full-time academic dermatology positions are currently unknown. It is likely that a higher proportion of GFDRs and GMDRs are more likely to enter academics and practice medical dermatology. The percentage of women in academic dermatology has not been reported since 1994., Objective: To determine the total number of GFDRs, GMDRs, and women who are full-time faculty members at U.S. dermatology residency programs., Methods: The educational background of all full-time faculty members of the 107 U.S. dermatology residency programs that were active as of December 2004 were determined through extensive Internet searches, telephone, and email correspondences with residency coordinators and faculty members. Pure PhDs, physicians who did not complete a dermatology residency program at an allopathic school, PharmDs, DDSs, and FNPs were excluded. The University of Puerto Rico was not considered a foreign residency program., Results: As of December 2004, there were 988 full-time dermatology faculty members in the US, 813 of which met our inclusion criteria. There were 30 GFDRs, accounting for 3.7 percent of full-time academic dermatologists. There were 29 GMDRs, accounting for 3.6 percent of all full-time academic dermatologists. Women accounted for 44.42 percent of academic dermatologists and 15.9 percent (14/107) of dermatology chairs/chiefs., Conclusion: GFDRs, GMDRs, and women comprise important proportions of full-time faculty members at U.S. dermatology residency programs.

Eight novel microsatellite primer pairs are presented for Eriosoma lanigerum, representing the first microsatellite markers available for this genus. Loci were characterized for 27 individuals from one single orchard in Central Chile. All loci were polymorphic within E. lanigerum (three to 11 alleles per locus; observed heterozygosity ranging from 0.41 to 0.93), and are therefore useful for population genetic studies within the species., (© 2008 The Authors. Journal compilation © 2008 Blackwell Publishing Ltd.)

Asexuality confers demographic advantages to invasive taxa, but generally limits adaptive potential for colonizing of new habitats. Therefore, pre-existing adaptations and habitat tolerance are essential in the success of asexual invaders. We investigated these key factors of invasiveness by assessing reproductive modes and host-plant adaptations in the pea aphid, Acyrthosiphon pisum, a pest recently introduced into Chile. The pea aphid encompasses lineages differing in their reproductive mode, ranging from obligatory cyclical parthenogenesis to fully asexual reproduction. This species also shows variation in host use, with distinct biotypes specialized on different species of legumes as well as more polyphagous populations. In central Chile, microsatellite genotyping of pea aphids sampled on five crops and wild legumes revealed three main clonal genotypes, which showed striking associations with particular host plants rather than sampling locations. Phenotypic analyses confirmed their strong host specialization and demonstrated parthenogenesis as their sole reproductive mode. The genetic relatedness of these clonal genotypes with corresponding host-specialized populations from the Old World indicated that each clone descended from a particular Eurasian biotype, which involved at least three successful introduction events followed by spread on different crops. This study illustrates that multiple introductions of highly specialized clones, rather than local evolution in resource use and/or selection of generalist genotypes, can explain the demographic success of a strictly asexual invader.

There are fewer dermatologists entering and being retained in academics. We investigated the hypothesis that MD/PhDs are more likely than MDs to enter a career in academic dermatology. This retrospective study of university dermatology departments and divisions studied MDs, DOs, and MD/PhDs who completed a dermatology program in the U.S. and were serving as full-time dermatology faculty members at a US dermatology program as of December 2004. The main outcome measures were percentage of MD/PhDs who chose a career in academics compared to the percentage of MDs who chose a career in academics; MDs, DOs, MD/PhDs and serving as full-time faculty members and the number serving as chair or chief of dermatology. The total number of MD/PhDs and percentage of MD/PhDs as full-time faculty in 107 U.S. dermatology programs were determined. As of December 2004, there were 782 full-time faculty MDs who completed a residency in the US, with 72 (9.2%) MD/PhDs who completed a US dermatology residency program. MD/PhDs were 1.63 times (p < or =0.001) more likely to go into academics compared to MDs. The programs with the highest number of MD/PhDs as full-time faculty and the programs with the highest percentage of MD/PhDs as full-time faculty were tabulated. Seven out of an eligible 101 dermatology chiefs/chairs were MD/PhDs. The assumption that 5.8 percent of dermatology residents who were MD/PhD during 2004-2007 could be extrapolated to the 35 year period of 1970-2004. MD/PhDs are an important source of physician-scientists in academic dermatology and were 1.63 times more likely compared to MDs to choose a career in academics and remain in academics.

Background: The only dermatology rankings in the past were based on National Institutes of Health (NIH) funding and journal citations., Objective: To determine the highest ranking academic dermatology programs based on 5 outcome measures and on an overall ranking scale. To the best of our knowledge, this is the first report to rank the dermatology programs on 4 of the following outcome measures of academic achievement and with an overall ranking., Methods: We collected extensive 2001 to 2004 data ranging from total publications to grant funding on 107 U.S. dermatology programs and their full-time faculty. Data from part-time and volunteer faculty were not used., Main Outcome Measures: Publications in 2001 to 2004; NIH funding in 2004; Dermatology Foundation grants in 2001 to 2004; faculty lectures in 2004 delivered at national conferences; number of full-time faculty members who were on the editorial boards of the top 3 U.S. dermatology journals and the top 4 subspecialty journals, Results: We used the 5 outcome measures to tabulate the highest ranking programs in each category. Using a weighted ranking system, we also tabulated the overall top 30 dermatology programs based on these 5 outcome measures., Limitations: We were not able to determine the total amount of NIH funding in dollars of the dermatology divisions. The impact factors of the journal in which these publications appeared was not factored into our calculations. Since faculty members may collaborate on the same publication, some publications may have been double-counted., Conclusion: In descending order, the 5 highest ranked academic programs are the University of Pennsylvania; University of California, San Francisco; Yale-New Haven Medical Center; New York University; and University of Michigan. This ranking system may allow residents and faculty to improve the academic achievements at their respective programs.

Anopheline species of the subgenus Kerteszia, including Anopheles (Kerteszia) cruzii Dyar & Knab (Diptera: Culicidae), are bromeliad-malaria vectors in the Atlantic rain forest of Brazil. Morphological, genetic, and molecular polymorphisms among different populations of An. cruzii have been reported, and it has been suggested that this taxon includes a complex of cryptic species. Specimens of An. cruzii were collected in the states of SHo Paulo and Santa Catarina, from locations where autochthonous malaria cases have been reported during the last decade. The second internal transcribed spacers (ITS2) of nuclear ribosomal DNA of the captured specimens were sequenced and compared with each other. Intraspecific ITS2 sequence polymorphisms were identified, and nucleotide divergence among specimens varied from 0.3 to 0.9%. The number of nucleotides in the ITS2 sequences of these mosquitoes varied from 327 to 334, and the CG contents varied from 61.7 to 62%. The data provide further indication of An. cruzii being a complex of cryptic species.

Objective: To examine the characteristics of 107 dermatology residency programs to determine which factors are correlated with producing academic dermatologists to help reverse the trend of a growing shortage of academic dermatologists., Design: We collected data ranging from total publications to grant funding. Extensive Internet searches were completed to obtain most of the data. Individual programs were contacted as needed to obtain any missing data that were not found on the program's Web site., Setting: Dermatology residency programs (departments and divisions) in the United States., Main Outcome Measures: Factors that correlated with producing full-time academic dermatologists., Results: We tabulated and analyzed characteristics of 107 dermatology residency programs. Total full-time faculty members in 2004, total publications in 2004, and total publications from January 1, 2001, to December 31, 2004, were the 3 factors most strongly correlated with producing full-time faculty. National Institutes of Health and Dermatology Foundation grants and American Skin Association grant recipients were the 3 characteristics most strongly inversely correlated with producing full-time faculty. Those who entered academic dermatology tended to stay at the same program where they completed a dermatology residency, especially if this program was considered a "smaller" program., Conclusions: The programs' characteristics of total publications in 2004 and from 2001 to 2004 were 2 of the 3 factors most strongly positively correlated with dermatology residents entering academic dermatology. Encouraging residents to publish may be a window to motivate them toward a career in academic dermatology.

Actinic keratosis (AK) constitutes the initial lesion in a disease continuum that can progress to invasive squamous cell carcinoma (SCC). In this article, we describe the mechanisms of action, tolerability, and efficacy of the most frequently used chemopreventative, chemotherapeutic, destructive, and novel immunologic methods for the control and treatment of actinic keratoses.

Background: It has been reported that topical application of imiquimod 5% cream induces interferon-alpha, an antifibrotic cytokine., Objective: To determine the tolerability and effectiveness on the cosmetic outcome of the application of imiquimod to postsurgical excision sites., Materials and Methods: A prospective, double-blinded, randomized, vehicle-controlled trial was conducted among 20 patients with two skin lesions clinically diagnosed as melanocytic nevi. Imiquimod 5% cream was applied to one of the sutured surgical wounds starting the night of the excision nightly for a period of 4 weeks. The second sutured excision site was treated with vehicle cream. Scar cosmesis, erythema, pigmentary alterations, induration, tenderness, and pain were assessed using a visual analogue scale 2, 4, and 8 weeks after surgery., Results: Eighteen subjects completed the study, with a total of 36 excision sites; no wound site dehisced, and no signs of infection were noted. Surgical wounds treated with imiquimod had more erythema, pigmentary alterations, and lower cosmesis rated by the investigator compared with wounds treated with placebo, both becoming nonsignificant in further evaluations. For pigmentary alterations, induration, and cosmesis rated by the patients, no statistically significant difference between treatment groups was observed at week 8., Conclusion: Treatment of surgical excision-site wounds with imiquimod was well tolerated and without serious adverse events. Evaluations for cosmesis of placebo-treated surgical sites were better than imiquimod-treated sites at week 8, becoming nonsignificant later.

Background: Results from in vitro and animal studies suggest that cyclooxygenase (COX) inhibitors may reduce the risk of melanoma, but among humans, the evidence remains limited., Objective: In a pilot retrospective cohort, to determine the relationship between the use of COX inhibitors and the incidence, recurrence, and metastases of melanoma in high-risk patients., Methods: Reviewing computerized records at the Miami Veterans Affairs Medical Center, we retrospectively examined the association between COX inhibitor use and melanoma incidence, recurrence, and metastases in high-risk subjects: white subjects previously diagnosed with melanoma (1996-2003). We evaluated three potential outcomes: new melanoma diagnosis, recurrence of a previous melanoma, and melanoma metastasis., Results: Eighty-three subjects with melanoma were included. There was one metastasis among 28 subjects prescribed COX inhibitors, whereas four new melanomas (7.3%), two melanoma recurrences, and six metastases (10.9%) occurred among 55 patients not prescribed COX inhibitors. Although no individual outcomes measures reached statistical significance, combining the three measures, these were significantly lower in users of COX inhibitors compared with nonusers (1 vs 12; p = .05). After adjustment for age and tumor depth of invasion, COX inhibitor users had significantly lower rates of melanoma outcome measures (odds ratio 0.08; 95% confidence interval 0.01-0.77; p = .03)., Conclusion: Potential exists for chemoprevention of melanoma among high-risk patients.

Cutaneous changes may indicate the presence of or herald the incipient development of internal malignancies. The authors review 24 cutaneous signs, symptoms, diseases, and syndromes associated with internal malignancies. Early recognition of these cutaneous changes may allow for vigilance for, and prompt detection and management of, the underlying neoplasm.

Background: Dermatologic procedures often cause some degree of pain. A self-warming patch containing lidocaine and tetracaine (L/T) was developed to provide topical local anesthesia prior to painful procedures., Objectives: To evaluate the safety and efficacy of a self-warming L/T patch to provide anesthesia in adult patients undergoing minor dermatologic procedures., Methods: An active or placebo study drug was placed on adults 30 minutes prior to minor dermatologic surgical procedures in a prospectively randomized, double-blinded manner. Subcutaneous lidocaine injection was available during the procedure as a rescue medication if requested by the subject. Immediately following the procedure, the subjects, the investigator, and an independent observer rated pain intensity and adverse events were recorded., Results: Patient-reported pain intensity was significantly lower in the L/T patch group (p<.001). Investigators and an independent observer rated the pain in the L/T patch group to be less than in the placebo patch group (p = .004 and p<.001, respectively). Forty-nine percent of patients in the placebo group required rescue subcutaneous lidocaine compared with 22% in the L/T patch study group (p = .008). One patient in the L/T patch group reported a transient moderate burning sensation., Conclusion: The self-warming L/T patch was effective in providing clinically useful local anesthesia for minor dermatologic procedures in adult patients.

Erythromelalgia is a rare syndrome that is characterized by episodic attacks of burning pain, erythema, and increased temperature usually affecting the extremities, which is aggravated by warmth or exercise. We describe a patient with a 3-year history of refractory burning pain and red ears. A review of clinical features, disease classification, associated diseases, and treatment of this disease is presented.

Numerous treatments have been described for the treatment and prevention of scars, but the optimal management strategy is yet to be defined. In this article we present and evaluate new opportunities for the treatment and prevention of hypertrophic scars, keloids, and atrophic scars. Clinical, animal, and in vitro studies reporting novel techniques for the treatment and prevention of scarring were identified primarily from the MEDLINE/PubMed database. We found that a variety of new treatments exist with potential effectiveness for the treatment of hypertrophic scars and keloids, including interferon, imiquimod 5% cream, tacrolimus, botulinum toxin, 5-fluorouracil, bleomycin, and verapamil. For atrophic scars, different types of lasers represent modern treatment modalities with satisfactory results. Several agents have been reported to be effective in reducing scarring in vitro and in animal studies, representing potential opportunities for scarring management. We conclude that several novel modalities may be potential therapies for scarring.

Anopheles cruzii is the most common species of mosquito in Southeast Brazil and a vector of human and monkey malaria. The banding pattern of the ovarian polytene chromosomes and the frequencies of paracentric inversions of individuals from two populations were studied. A new sequence of bands on the sex chromosome, defined as form C, was disclosed. In both populations where forms A (considered as standard) and C are sympatric no heterozygotes were detected. A sequence of events that could account for the observed changes in the banding sequences of the X chromosome forms was proposed. The frequencies of 22 paracentric inversions were used to assess panmixia and the results indicated the presence of two distinct genetic pools in each population. We consider these results as evidence of another sibling species in the taxon cruzii, characterized by a distinctive form of the X chromosome and provisionally designated Anopheles cruzii species C.