Iberia Consensus on Strategies to Prevent and Manage Irritation by Topical Retinoids in Facial and Trunk Acne. / Consenso Iberia sobre estrategias de prevención y manejo de la irritación por retinoides tópicos en acné localizado en cara y tronco.

OBJECTIVE: To assess the level of agreement on various prevention and management strategies for irritation caused by topical retinoids in facial and trunk acne in an attempt to alleviate it and minimize treatment discontinuations as much as possible. METHOD: After reviewing the scientific medical literatura currently available, 4 different areas of uncertainty in the management of irritation caused by topical retinoids in acne were identified. A questionnaire with 34 recommendations was created and evaluated by a group of 133 dermatologists (Delphi methodology). RESULTS: In 82.3% of the recommendations (28 out of 34), some level of agreement was reached (≥85% agreement in 22 recommendations and≥70% agreement in 6). The results with the highest level of agreement focused on specific patient education strategies (explaining that irritation is an expected reaction at the beginning of treatment and tends to decrease over time), gradual and/or spaced application of topical retinoids (at night time to prevent and/or reduce skin irritation), and the importance of using adjuvant products, specific for acne-prone skin, hydration, photoprotection, and skin cleansing. These recommendations reflect a comprehensive approach to managing irritation associated with topical retinoids and promoting long-term adherence. CONCLUSIONS: Skin irritation caused by topical retinoids in facial and trunk acne is an expected, mild, and controllable reaction if proper prevention and management guidelines are followed, meaning that it should not be a reason for treatment discontinuation.

Endothelial ILK induces cardioprotection by preventing coronary microvascular dysfunction and endothelial-to-mesenchymal transition.

Endothelial dysfunction is an early event in coronary microvascular disease. Integrin-linked kinase (ILK) prevents endothelial nitric oxide synthase (eNOS) uncoupling and, thus, endothelial dysfunction. However, the specific role of endothelial ILK in cardiac function remains to be fully elucidated. We hypothesised that endothelial ILK plays a crucial role in maintaining coronary microvascular function and contractile performance in the heart. We generated an endothelial cell-specific ILK conditional knock-out mouse (ecILK cKO) and investigated cardiovascular function. Coronary endothelial ILK deletion significantly impaired cardiac function: ejection fraction, fractional shortening and cardiac output decreased, whilst left ventricle diastolic internal diameter decreased and E/A and E/E' ratios increased, indicating not only systolic but also diastolic dysfunction. The functional data correlated with extensive extracellular matrix remodelling and perivascular fibrosis, indicative of adverse cardiac remodelling. Mice with endothelial ILK deletion suffered early ischaemic-like events with ST elevation and transient increases in cardiac troponins, which correlated with fibrotic remodelling. In addition, ecILK cKO mice exhibited many features of coronary microvascular disease: reduced cardiac perfusion, impaired coronary flow reserve and arterial remodelling with patent epicardial coronary arteries. Moreover, endothelial ILK deletion induced a moderate increase in blood pressure, but the antihypertensive drug Losartan did not affect microvascular remodelling whilst only partially ameliorated fibrotic remodelling. The plasma miRNA profile reveals endothelial-to-mesenchymal transition (endMT) as an upregulated pathway in endothelial ILK conditional KO mice. Our results show that endothelial cells in the microvasculature in endothelial ILK conditional KO mice underwent endMT. Moreover, endothelial cells isolated from these mice and ILK-silenced human microvascular endothelial cells underwent endMT, indicating that decreased endothelial ILK contributes directly to this endothelial phenotype shift. Our results identify ILK as a crucial regulator of microvascular endothelial homeostasis. Endothelial ILK prevents microvascular dysfunction and cardiac remodelling, contributing to the maintenance of the endothelial cell phenotype.

A real life cohort of Mepolizumab treatment in severe eosinophilic asthma.

Summary: Background. Mepolizumab, a monoclonal antibody that interacts with IL-5, was the first anti-IL-5 approved for uncontrolled severe eosinophilic asthma. In several randomised, placebo-controlled trials, treatment with mepolizumab has shown a significant improvement in asthma symptoms and the need to use of oral corticosteroids (OCS). Several studies have correlated blood levels of eosinophil cationic protein (ECP) with the degree of eosinophilic inflammation, which could make it an indirect marker of eosinophilic activity. Methods. This was a single-centre retrospective study that included all patients diagnosed with severe eosinophilic asthma under treatment with mepolizumab. We recorded the number of exacerbations, daily prednisone intake, asthma control test scores and forced expiratory volume in the first second. Results. We followed 22 patients, 14 of whom were OCS-dependent with a mean daily dose of 15.85 ± 15.62 mg prednisone. After 12 months, only five continued taking OCS and the mean daily dose was reduced by up to 2.50 ± 3.84 mg (p less than 0.007). The exacerbation rate at baseline was 2.91 ± 2.27 and decreased to 0.82 ± 1.14 in the following year (p less than 0.001). ACT scores increased significantly from 16.00 ± 5.85 to 20.71 ± 4.45 after six months (p = 0.003). We also observed a decrease in ECP from 81.46 ± 43.99 µg/L to 19.12 ± 18.80 µg/L (p > 0.001). Conclusions. These real-life results are consistent with previous clinical trials demonstrating the efficacy and safety of mepolizumab in routine clinical practice for severe uncontrolled eosinophilic asthma. We observed a significant decrease in blood eosinophil counts and in ECP levels, suggesting a reduction in eosinophil activity following mepolizumab treatment.

Sustainable use of wastes as reactive material in permeable reactive barrier for remediation of acid mine drainage: Batch and continuous studies.

The aim of this work was to evaluate the feasibility of the use of different industrial and agricultural wastes as reactive materials in Permeable Reactive Barriers (PRB) for Acid Mine Drainage (AMD) remediation. Sugar foam (SF), paper mill sludge (PMS), drinking water sludge (DWS) and olive mill waste (OMW) were evaluated in terms of pH neutralization and metal removal from AMD. Laboratory batch tests and continuous pilot scale up-flow columns containing 82% of Volcanic Slag (VS), as porous fill material, and 18% w/w of one of the industrial and agricultural wastes previously indicated, were tested. From the batch tests it was observed that the reactive material presenting the best results were the SF and the PMS. The results obtained in all the PRB were accurately described by a pseudo-first order model, presenting coefficient of determination higher than 0.96 in all the cases. During the continuous operation of the PRB, the porosity and hydraulic retention time (HRT) of most of the up-flow columns strongly decreased due to chemical precipitation and biofilm growth. The SF presented a significant number of fine particles that were washed out by the liquid flow, generating an effluent with very high total suspended solid concentration. Despite SF was the material with the highest alkalinity potential, the reduction of the HRT limited its neutralization and metal removal capacity. PMS and DWS presented the best pollutant removal yields in the continuous operation of the PRB, ranging from 55 to 99% and 55-95% (except in the case of the Mn), respectively. These results allowed the metal removal from the AMD. Additionally, these wastes presented very good biological sulphate reduction. Based on these results, the use of PMS and DWS as reactive material in PRB would allow to simultaneously valorise the industrial waste, which is very interesting within the circular economy framework, and to remove metals from the AMD by means of a low-cost and environmentally sustainable procedure.

A critical review of textile industry wastewater: green technologies for the removal of indigo dyes.

The denim textile industry represents an important productive sector. It generates wastewater with low biodegradability due to the presence of persistent pollutants, which can produce toxic and carcinogenic compounds; therefore, wastewater treatment reduces risks to aquatic life and public health. This paper presents a review of 172 papers regarding textile industry wastewater treatment for the removal of contaminants, especially indigo dyes used in the denim industry, in the context of green technologies. The physicochemical characteristics of textile wastewater, its environmental and health impacts, and the permissible limit regulations in different countries were reviewed. Biological, physicochemical and advanced oxidation processes for the removal of indigo dyes were reviewed. The goal of this study was to analyze the characteristics of green technologies; however, the research does not clearly demonstrate an effect on energy consumption savings, carbon footprint decreases, and/or waste generation. Advanced oxidation processes showed the highest color removal efficiency (95 and 97% in synthetic or real wastewater, respectively). Photocatalysis and Fenton reactions were the most efficient processes. None of the revised works presented results regarding upscaling for industrial application, and the results should be discussed in terms of the guidelines and maximum permissible limits established by international legislation. New technologies need to be developed and evaluated in a sustainable context with real wastewater.

Correction: Genetic risk for schizophrenia and psychosis in Alzheimer disease.

A number of collaborators were not acknowledged for their contribution to this published article. The acknowledgements that were missing in this published article can now be found in the associated correction.

Morphologies of caustics and dislocation lines: some clues about their interrelation.

According to singular optics, the phase and intensity that characterize structured electromagnetic beams can be understood in terms of concepts that involve subspaces where they or their derivatives exhibit a particular behavior, such as giving rise to extreme values or not being well defined. Caustics are a paradigmatic example of the former, while helical dislocation lines exemplify the latter. In this work the interrelation of the morphology of caustics and the morphology of dislocation lines is theoretically studied. The analysis for highly structured beams requires an efficient methodology that allows the identification of optical vortices, their topological charge, and the helical dislocation lines they belong to. Such a methodology is introduced and applied to paraxial elliptic umbilic beams and nonparaxial Airy symmetric three-dimensional beams. Nonparaxial beams exhibit caustic surfaces that delimit regions with a finite volume and different intensity average. It is shown that in the high intensity region so defined, the dislocation lines play the role of an internal skeleton, i.e., an endoskeleton, of the beam. The exoskeleton created in the low intensity regions shows subtle and interesting features that complement those of the endoskeleton; the caustics that delimit low intensity regions have a strong influence on the morphology of the exoskeleton.

The morphometric acclimation to depth explains the long-term resilience of the seagrass Cymodocea nodosa in a shallow tidal lagoon.

Cadiz Bay is a shallow mesotidal lagoon with extensive populations of the seagrass Cymodocea nodosa at intertidal and shallow subtidal elevations. This work aims to understand the mechanisms behind the resilience of this species to gradual sea level rise by studying its acclimation capacity to depth along the shallow littoral, and therefore, to gradual variations in the light environment. To address this objective, these populations have been monitored seasonally over a 10 year period, representing the longest seasonal database available in the literature for this species. The monitoring included populations at 0.4, -0.08 and -0.5 m LAT. The results show that C. nodosa has a strong seasonality for demographic and shoot dynamic properties - with longer shoots and larger growth in summer (high temperature) than in winter (low temperature), but also some losses. Moreover, shoots have different leaf morphometry depending on depth, with small and dense shoots in the intertidal areas (0.4 m) and sparse large shoots in the subtidal ones (-0.08 and 0.5 m). These differences in morphometry and shoot dynamic properties, combined with the differences in shoot density, explain the lack of differences in meadow production balance (i.e. meadow growth - meadow losses) between the intertidal (0.4 m) and the deepest population (-0.5 m), supporting the long term resilience of Cymodocea nodosa in Cadiz Bay. This study contributes to the understanding of the mechanisms behind seagrass stability and resilience, which is particularly important towards predicting the effects of climate change on these key coastal ecosystems, and also highlights the value of continuous long-term monitoring efforts to evaluate seagrass trajectories.

Toward more sustainable photovoltaic solar electrochemical oxidation treatments: Influence of hydraulic and electrical distribution.

Powering electrochemical technologies with renewable energies is a promising way to get more sustainable environmental remediation techniques. However, the operational conditions of those processes must be optimized to undergo fast and efficient treatments. In this work, the influence of electrical and hydraulic connections in the performance of a set of two electrolyzers directly powered by photovoltaic panels was evaluated. Despite both electrolyzers were assembled using the same electrode material, they showed different performances. Results indicate that the electrolyzer with higher ohmic resistance and higher overpotential attained a greater production of oxidant species, being produced under the most efficient strategy around 4.8 and 15.1 mmol of oxidants per Ah by electrolyzer 1 and 2, respectively. Nevertheless, an excess of oxidant production because of an inefficient energy management, led to low removal efficiencies as a consequence of a waste of energy into undesirable reactions. Regarding the hydraulic distribution of wastewater between the cells, it was found to influence on the total remediation attained, being the serial connection 2.5 and 1.8 more efficient than a parallel wastewater distribution under series and parallel electrical strategies, respectively. Regarding electrical strategies, parallel connections maximize the use of power produced by the photovoltaic panels. Furthermore, this allows the system to work under lower current densities, reducing the mass transfer limitations. Considering both advantages, a hydraulic connection of the cells in series and an electrical connection in parallel was found to reach the highest specific removal of pollutant, 2.52 mg clopyralid (Wh)-1. Conversely, the opposite strategy (parallel hydraulic connection-series electrical connection) showed the lowest remediation ratio, 0.48 mg clopyralid (Wh)-1. These results are important to be considered in the design of electrolytic treatments of waste directly powered by photovoltaic panels, because they show the way to optimize the cells stack layout in full-scale applications, exhibiting significant impact on the sustainability of the electrochemical application.

Platelet-Derived Growth Factor C in Alcoholics.

AIMS: Platelet-derived growth factor (PDGF) promotes liver collagen deposition, acting on hepatic stellate cells. Despite this, low serum PDGF levels were reported in chronic hepatitis C or B infection, although some studies yield the opposite result. Since PDGF may be related not only to fibrosis but also with vascular, neuronal or muscle disease, it is important to analyze its behavior in alcoholics. METHODS: In total, 17 controls and 62 alcoholic patients consecutively admitted to the hospitalization unit of the Internal Medicine Service were included. We determined serum levels of PDGF C, routine laboratory evaluation, tumor necrosis factor-α, interleukin (IL)-6 and IL-8 and malondialdehyde (MDA) levels. We analyzed the relationships between PDGF and liver function, ethanol intake and inflammatory reaction by both univariate and multivariate analysis to discern which variables PDGF levels depend on. RESULTS: Serum PDGF levels were significantly lower among patients (675 ± 466 pg/ml) than among controls (1074 ± 337 pg/ml; Z = 3.70; P < 0.001), and even lower among cirrhotics (549 ± 412 among cirrhotics vs 778 ± 487 among non-cirrhotics; Z = 2.33; P = 0.02). PDGF levels showed a direct correlation with prothrombin activity (ρ = 0.50; P < 0.001), platelet count (ρ = 0.44; P < 0.001) and inverse ones with bilirubin (ρ = -0.39; P = 0.002), IL-6 (ρ = -0.33; P = 0.016), IL-8 (ρ = -0.47; P < 0.001), and MDA levels (ρ = -0.44; P < 0.001). By multivariate analysis, only prothrombin activity and platelet count were independently related to PDGF. CONCLUSION: PDGF-C levels are decreased in alcoholics, especially among cirrhotics. Multivariate analysis discloses that only prothrombin activity and platelet count are independently related to PDGF-C levels.

3D Strain in 2D Materials: To What Extent is Monolayer Graphene Graphite?

This work addresses a fundamental question: To what extent is graphene graphite? In particular does 2D graphene have many of the same 3D mechanical properties as graphite, such as the bulk modulus and elastic constant c_{33}? We have obtained, for the first time, unambiguous Raman spectra from unsupported monolayer graphene under pressure. We have used these data to quantify the out-of-plane stiffness of monolayer graphene, which is hard to define due to its 2D nature. Our data indicate a first physically meaningful out-of-plane stiffness of monolayer graphene, and find it to be consistent with that of graphite. We also report a shift rate of the in-plane phonon frequency of unsupported monolayer graphene to be 5.4 cm^{-1} GPa^{-1}, very close to that of graphite (4.7 cm^{-1} GPa^{-1}), contrary to the previous value for supported graphene. Our results imply that monolayer graphene has similar in-plane and out-of-plane stiffnesses, and anharmonicities to graphite.

Genetic risk for schizophrenia and psychosis in Alzheimer disease.

Psychotic symptoms, defined as the occurrence of delusions or hallucinations, are frequent in Alzheimer disease (AD), affecting ~40 to 60% of individuals with AD (AD with psychosis (AD+P)). In comparison with AD subjects without psychosis, AD+P subjects have more rapid cognitive decline and poor outcomes. Prior studies have estimated the heritability of psychosis in AD at 61%, but the underlying genetic sources of this risk are not known. We evaluated a Discovery Cohort of 2876 AD subjects with (N=1761) or without psychosis (N=1115). All subjects were genotyped using a custom genotyping array designed to evaluate single-nucleotide polymorphisms (SNPs) with evidence of genetic association with AD+P and include SNPs affecting or putatively affecting risk for schizophrenia and AD. Results were replicated in an independent cohort of 2194 AD subjects with (N=734) or without psychosis (N=1460). We found that AD+P is associated with polygenic risk for a set of novel loci and inversely associated with polygenic risk for schizophrenia. Among the biologic pathways identified by the associations of schizophrenia SNPs with AD+P are endosomal trafficking, autophagy and calcium channel signaling. To the best of our knowledge, these findings provide the first clear demonstration that AD+P is associated with common genetic variation. In addition, they provide an unbiased link between polygenic risk for schizophrenia and a lower risk of psychosis in AD. This provides an opportunity to leverage progress made in identifying the biologic effects of schizophrenia alleles to identify novel mechanisms protecting against more rapid cognitive decline and psychosis risk in AD.

Asthma Exacerbations in the Pediatric Emergency Department at a Tertiary Hospital: Association With Environmental Factors.

INTRODUCTION: Children with asthma experience recurrent respiratory symptoms and exacerbations due to multiple environmental factors. The aim of this study was to describe the prevalence and triggers of asthma exacerbations and their management in a cohort of pediatric patients attended in an emergency department (ED). METHODS: We performed an observational, retrospective, single-center study in the pediatric ED of Hospital Universitario La Paz, Madrid, Spain in 2015. Children with asthma exacerbations attending the ED were included after a thorough search using our institutional computer database. Pollen and atmospheric mold spore counts and pollution data were collected for that period from official websites. Multiple logistic regression was used to assess the association between daily pollution (NO2, PM10, ozone, pollen, and molds) and admissions to the ED because of asthma. RESULTS: During 2015, a total of 50 619 patients were attended in the ED of our hospital. Of these, 2609 (5%) were diagnosed with asthma exacerbation/bronchospasm. The patient had to be admitted to hospital in 21.7% of cases. The main triggers of asthma exacerbations were respiratory infection in 1841 cases (70.6%). A significant correlation was found between grass pollen counts and ED admissions (P<.0001). A positive correlation was also found between ED admissions and NO2 0.58 (95%CI, 0.02-0.87) and PM10 0.75 (95%CI, 0.31-0.93) (P<.05). CONCLUSION: Environmental factors such as grass pollen counts and pollution (NO2 and PM10) are associated with a higher frequency of admission to the ED.

'Desculturización,' urbanization, and nutrition transition among urban Kichwas Indigenous communities residing in the Andes highlands of Ecuador.

BACKGROUND: The nutrition transition continues to affect populations throughout the world. The added impact of market integration and urbanization exacerbates the impact of the nutrition transition upon Indigenous populations worldwide. OBJECTIVES: This study aims to explore the nutritional concerns of the urban Kichwas community residing in the Andes highlands of Ecuador. STUDY DESIGN: This is a qualitative study. METHODS: Eight focus groups were conducted with Kichwas men and women in November 2015 in the Imbabura province of the Andes in Ecuador. DATA ANALYSIS: Applied thematic analysis was used to analyze findings regarding nutrition. RESULTS: The participants shared concerns regarding increased intake of fast food, poor meal timing, and a shift in the child's food preferences that rejects traditional foods. They attributed these concerns to urbanization resulting from an increase in dual-income households and a loss of cultural identity. CONCLUSIONS: Synergistic cultural factors are related to nutritional concerns voiced by the urban Kichwas community. PUBLIC HEALTH IMPLICATIONS: Syndemic theory is a useful interpretive lens regarding nutritional trends within the Kichwas communities as they relate to the increased risk of chronic disease.

Risk and resiliency: the syndemic nature of HIV/AIDS in the indigenous highland communities of Ecuador.

OBJECTIVES: This community-based study explores the syndemic nature of HIV/AIDS risk and resilience among Indigenous Kichwa communities in the province of Imbabura, Ecuador. This study elucidates individual and community-level factors that serve to exacerbate HIV/AIDS risk, as they relate to underlying macrolevel, structural forces. Critically, this study also elicited opportunities for community-based opportunities for resiliency from HIV/AIDS. STUDY DESIGN: Exploratory qualitative study. METHODS: Guided by syndemic theory, a qualitative study was conducted to explore HIV risk and resilience among Indigenous Kichwa communities in the Northern Andean highlands of Ecuador. Eight focus groups (n = 59) with men and women from two communities were conducted. The data were analyzed using applied thematic analysis techniques. RESULTS: Identified risk factors for HIV/AIDS centered around the following themes: (1) parents leaving the community for work, (2) alcohol and drug consumption, (3) unprotected sex, and (4) barriers to health care. Identified HIV/AIDS resiliency factors included the preservation of Indigenous culture and family-focused interventions. CONCLUSIONS: The identified risk factors for HIV/AIDS are interrelated within a complex syndemic relationship. The mutually reinforcing individual-level risk factors of substance abuse and risky sexual behavior coalesce with violence to exacerbate the risk for HIV/AIDS acquisition among Ecuadorian Highland Indigenous communities. Moreover, HIV/AIDS risk prevails in the macrolevel context of disproportionate unemployment among Indigenous peoples and a systematically fragmented healthcare system. It is critical that public health professionals work to revolutionize the systematic discrimination that underpins indigenous health disparities at-large.

The anti-CD6 antibody itolizumab provides clinical benefit without lymphopenia in rheumatoid arthritis patients: results from a 6-month, open-label Phase I clinical trial.

Itolizumab is a humanized anti-CD6 monoclonal antibody (mAb) that has previously shown encouraging results, in terms of safety and positive clinical effects, in a 6-week monotherapy clinical trial conducted in rheumatoid arthritis (RA) patients. The current Phase I study evaluated the safety and clinical response for a longer treatment of 12 itolizumab intravenous doses in subjects with active RA despite previous disease-modifying anti-rheumatic drug (DMARD) therapy. Twenty-one subjects were enrolled into four dosage groups (0·1, 0·2, 0·4 and 0·8 mg/kg). Efficacy end-points including American College of Rheumatology (ACR)20, ACR50 and ACR70 response rates and disease activity score in 28 joints (DAS28) were monitored at baseline and at specific time-points during a 10-week follow-up period. Itolizumab was well tolerated up to the highest tested dose. No related serious adverse events were reported and most adverse events were mild. Remarkably, itolizumab treatment did not produce lymphopenia and, therefore, was not associated with infections. All patients achieved a clinical response (ACR20) at least once during the study. Eleven subjects (55%) achieved at least a 20% improvement in ACR just 1 week after the first itolizumab administration. The clinical response was observed from the beginning of the treatment and was sustained during 24 weeks. The efficacy profile of this 12-week treatment was similar to that of the previous study (6-week treatment). These results reinforce the safety profile of itolizumab and provide further evidence on the clinical benefit from the use of this anti-CD6 mAb in RA patients.

Genome-wide significant risk factors for Alzheimer's disease: role in progression to dementia due to Alzheimer's disease among subjects with mild cognitive impairment.

Few data are available concerning the role of risk markers for Alzheimer's disease (AD) in progression to AD dementia among subjects with mild cognitive impairment (MCI). We therefore investigated the role of well-known AD-associated single-nucleotide polymorphism (SNP) in the progression from MCI to AD dementia. Four independent MCI data sets were included in the analysis: (a) the German study on Aging, Cognition and Dementia in primary care patients (n=853); (b) the German Dementia Competence Network (n=812); (c) the Fundació ACE from Barcelona, Spain (n=1245); and (d) the MCI data set of the Amsterdam Dementia Cohort (n=306). The effects of single markers and combined polygenic scores were measured using Cox proportional hazards models and meta-analyses. The clusterin (CLU) locus was an independent genetic risk factor for MCI to AD progression (CLU rs9331888: hazard ratio (HR)=1.187 (1.054-1.32); P=0.0035). A polygenic score (PGS1) comprising nine established genome-wide AD risk loci predicted a small effect on the risk of MCI to AD progression in APOE-ɛ4 (apolipoprotein E-ɛ4) carriers (HR=1.746 (1.029-2.965); P=0.038). The novel AD loci reported by the International Genomics of Alzheimer's Project were not implicated in MCI to AD dementia progression. SNP-based polygenic risk scores comprising currently available AD genetic markers did not predict MCI to AD progression. We conclude that SNPs in CLU are potential markers for MCI to AD progression.

Eccrine sweat glands associate with the human hair follicle within a defined compartment of dermal white adipose tissue.

BACKGROUND: Eccrine sweat glands (ESGs) are critical for thermoregulation and are involved in wound healing. ESGs have traditionally been considered as separate skin appendages without connection to the pilosebaceous unit (PSU). However, recent preliminary evidence has encouraged the hypothesis that the PSU and ESG are more interconnected than previously thought. OBJECTIVES: To re-evaluate the morphology of human skin adnexa with an integrated three-dimensional (3D) perspective in order to explore the possible interconnections that the PSU and the ESG may form. METHODS: A systematic 3D reconstruction method of skin sections, direct visualization of human scalp follicular unit transplant grafts and a scalp strip ex vivo were used to validate and further explore the hypothesis. RESULTS: We demonstrate that the coiled portion of most ESGs is morphologically integrated into the PSU of human scalp skin and forms a structural unit that is embedded into a specific, hair follicle-associated region of dermal white adipose tissue (dWAT). This newly recognized unit is easily accessible and experimentally tractable by organ culture of follicular units and can be visualized intravitally. CONCLUSIONS: We propose a model of functional human skin anatomy in which ESGs are closely associated with the PSU and the dWAT to form a common homeostatic tissue environment, which may best be encapsulated in the term 'adnexal skin unit'. The challenge now is to dissect how each component of this superstructure of human skin functionally cooperates with and influences the other under physiological conditions, during regeneration and repair and in selected skin diseases.

Socioeconomic and demographic predictors of resident knowledge, attitude, and practice regarding arthropod-borne viruses in Panama.

BACKGROUND: We sought to identify if socioeconomic and demographic factors play a role in resident knowledge, attitude, and practice regarding Dengue, Chikungunya, and Zika in order to inform effective management procedures for disease prevention in Panama, a middle-income tropical country in Central America. All three are arthropod-borne viruses transmitted by Aedes mosquito vectors present in the focal region of Panama City, the largest city in Central America and an urban region of extreme socioeconomic polarization. METHODS: Between November 2017 and February 2018, we administered standardized, anonymous knowledge, attitude, and practice surveys to 263 residents split between two neighborhoods of high socioeconomic status (SES) and two neighborhoods of low SES. We then summed the knowledge, attitude, and practice scores respectively, and used linear and logistic regressions to quantify relationships with socioeconomic and demographic factors. RESULTS: Low-SES neighborhoods with high proportions of low income residents, residents over 70 years old had lower mean knowledge scores compared to other groups. Furthermore, residents in neighborhoods of low SES reported more mosquito biting relative to residents in neighborhoods of high SES, yet comparably lower level of concerns for disease transmission. Additionally, knowledge was lower for the more novel emergent threats of Chikungunya and Zika, compared to the endemic Dengue. CONCLUSION: Findings suggest that low-SES neighborhoods with high proportions of low income, low education, and elderly residents should be targeted for outreach programs designed to prevent DENV, CHIKV, or ZIKV in Panama City. These outcomes support our initial hypotheses as lower relative knowledge and fewer practices related to the prevention of Dengue, Chikungunya, and Zika were found in low-SES neighborhoods. There is also a widespread lack of adequate knowledge regarding these diseases as well as low levels of concern in areas of highly reported mosquito biting. We provide suggestions for taking neighborhood socioeconomic status and specific aspects resident health literacy and attitude into account for creating more effective outreach campaigns as both endemic and novel arthropod-borne disease rates continue to increase throughout Latin America.