Copper-Catalyzed Dearomative 1,2-Hydroamination.

Catalytic olefin hydroamination reactions are some of the most atom-economical transformations that bridge readily available starting materials-olefins and high-value-added amines. Despite significant advances in this field over the last two decades, the formal hydroamination of nonactivated aromatic compounds remains an unsolved challenge. Herein, we report the extension of olefin hydroamination to aromatic π-systems by using arenophile-mediated dearomatization and Cu-catalysis to perform 1,2-hydroamination on nonactivated arenes. This strategy was applied to a variety of substituted arenes and heteroarenes to provide general access to structurally complex amines. We conducted DFT calculations to inform mechanistic understanding and rationalize unexpected selectivity trends. Furthermore, we developed a practical, scalable desymmetrization to deliver enantioenriched dearomatized products and enable downstream synthetic applications. We ultimately used this dearomative strategy to efficiently synthesize a collection of densely functionalized small molecules.

Wilderness Medical Society Clinical Practice Guidelines for Medical Direction of Search and Rescue Teams.

The Wilderness Medical Society convened a panel to review available evidence supporting practices for medical direction of search and rescue teams. This panel included of members of the Wilderness Medical Society Search and Rescue Committee, the National Association of EMS Physicians Wilderness Committee, and leadership of the Mountain Rescue Association. Literature about definitions and terminology, epidemiology, currently accepted best practices, and regulatory and legal considerations was reviewed. The panel graded available evidence supporting practices according to the American College of Chest Physicians criteria and then made recommendations based on that evidence. Recommendations were based on the panel's collective clinical experience and judgment when published evidence was lacking.

Comparison of stochastic and deterministic models for gambiense sleeping sickness at different spatial scales: A health area analysis in the DRC.

The intensification of intervention activities against the fatal vector-borne disease gambiense human African trypanosomiasis (gHAT, sleeping sickness) in the last two decades has led to a large decline in the number of annually reported cases. However, while we move closer to achieving the ambitious target of elimination of transmission (EoT) to humans, pockets of infection remain, and it becomes increasingly important to quantitatively assess if different regions are on track for elimination, and where intervention efforts should be focused. We present a previously developed stochastic mathematical model for gHAT in the Democratic Republic of Congo (DRC) and show that this same formulation is able to capture the dynamics of gHAT observed at the health area level (approximately 10,000 people). This analysis was the first time any stochastic gHAT model has been fitted directly to case data and allows us to better quantify the uncertainty in our results. The analysis focuses on utilising a particle filter Markov chain Monte Carlo (MCMC) methodology to fit the model to the data from 16 health areas of Mosango health zone in Kwilu province as a case study. The spatial heterogeneity in cases is reflected in modelling results, where we predict that under the current intervention strategies, the health area of Kinzamba II, which has approximately one third of the health zone's cases, will have the latest expected year for EoT. We find that fitting the analogous deterministic version of the gHAT model using MCMC has substantially faster computation times than fitting the stochastic model using pMCMC, but produces virtually indistinguishable posterior parameterisation. This suggests that expanding health area fitting, to cover more of the DRC, should be done with deterministic fits for efficiency, but with stochastic projections used to capture both the parameter and stochastic variation in case reporting and elimination year estimations.

Accelerating Progress Towards the 2030 Neglected Tropical Diseases Targets: How Can Quantitative Modeling Support Programmatic Decisions?

Over the past decade, considerable progress has been made in the control, elimination, and eradication of neglected tropical diseases (NTDs). Despite these advances, most NTD programs have recently experienced important setbacks; for example, NTD interventions were some of the most frequently and severely impacted by service disruptions due to the coronavirus disease 2019 (COVID-19) pandemic. Mathematical modeling can help inform selection of interventions to meet the targets set out in the NTD road map 2021-2030, and such studies should prioritize questions that are relevant for decision-makers, especially those designing, implementing, and evaluating national and subnational programs. In September 2022, the World Health Organization hosted a stakeholder meeting to identify such priority modeling questions across a range of NTDs and to consider how modeling could inform local decision making. Here, we summarize the outputs of the meeting, highlight common themes in the questions being asked, and discuss how quantitative modeling can support programmatic decisions that may accelerate progress towards the 2030 targets.

Adaptive foraging behaviours in the Horn of Africa during Toba supereruption.

Although modern humans left Africa multiple times over 100,000 years ago, those broadly ancestral to non-Africans dispersed less than 100,000 years ago1. Most models hold that these events occurred through green corridors created during humid periods because arid intervals constrained population movements2. Here we report an archaeological site-Shinfa-Metema 1, in the lowlands of northwest Ethiopia, with Youngest Toba Tuff cryptotephra dated to around 74,000 years ago-that provides early and rare evidence of intensive riverine-based foraging aided by the likely adoption of the bow and arrow. The diet included a wide range of terrestrial and aquatic animals. Stable oxygen isotopes from fossil mammal teeth and ostrich eggshell show that the site was occupied during a period of high seasonal aridity. The unusual abundance of fish suggests that capture occurred in the ever smaller and shallower waterholes of a seasonal river during a long dry season, revealing flexible adaptations to challenging climatic conditions during the Middle Stone Age. Adaptive foraging along dry-season waterholes would have transformed seasonal rivers into 'blue highway' corridors, potentially facilitating an out-of-Africa dispersal and suggesting that the event was not restricted to times of humid climates. The behavioural flexibility required to survive seasonally arid conditions in general, and the apparent short-term effects of the Toba supereruption in particular were probably key to the most recent dispersal and subsequent worldwide expansion of modern humans.

Arginine-Selective Bioconjugation Reagent for Effective 18F-labeling of Native Proteins.

Protein-based 18F-PET tracers offer new possibilities in early disease detection and personalized medicine. Their development relies heavily on the availability and effectiveness of 18F-prosthetic groups. We prepared and evaluated a novel arginine-selective prosthetic group, 4-[18F]fluorophenylglyoxal ([18F]FPG). [18F]FPG was radiosynthesized by a one-pot, two-step procedure with a non-decay-corrected (n.d.c.) isolated radiochemical yield (RCY) of 41 ± 8% (n = 10). [18F]FPG constitutes a generic tool for 18F-labeling of various proteins, including human serum albumin (HSA), ubiquitin, interleukin-2, and interleukin-4 in ∼30-60% n.d.c. isolated RCYs. [18F]FPG conjugation with arginine residues is highly selective, even in the presence of a large excess of lysine, cysteine, and histidine. [18F]FPG protein conjugates are able to preserve the binding affinity of the native proteins while also demonstrating excellent in vivo stability. The [18F]FPG-HSA conjugate has prolonged blood retention, which can be applied as a potential blood pool PET imaging agent. Thus, [18F]FPG is an arginine-selective bioconjugation reagent that can be effectively used for the development of 18F-labeled protein radiopharmaceuticals.

Wilderness Medical Society Clinical Practice Guidelines for the Treatment and Prevention of Drowning: 2024 Update.

The Wilderness Medical Society convened a panel to review available evidence supporting practices for acute management of drowning in out-of-hospital and emergency care settings. Literature about definitions and terminology, epidemiology, rescue, resuscitation, acute clinical management, disposition, and drowning prevention was reviewed. The panel graded available evidence supporting practices according to the American College of Chest Physicians criteria and then made recommendations based on that evidence. Recommendations were based on the panel's collective clinical experience and judgment when published evidence was lacking. This is the second update to the original practice guidelines published in 2016 and updated in 2019.

Identification of sleep and circadian alternative polyadenylation sites associated with APA-linked human brain disorders.

Sleep and circadian rhythm disruptions are comorbid features of many pathologies and can negatively influence numerous health conditions, including degenerative diseases, metabolic illnesses, cancer, and various neurological disorders. Genetic association studies linking sleep and circadian disturbances with disease susceptibility have mainly focused on changes in gene expression due to mutations, such as single-nucleotide polymorphisms. Thus, associations between sleep and/or circadian rhythm and alternative polyadenylation (APA), particularly in the context of other health challenges, are largely undescribed. APA is a process that generates various transcript isoforms from the same gene, resulting in effects on mRNA translation, stability, localization, and subsequent function. Here, we have identified unique APAs in rat brain that exhibit time-of-day-dependent oscillations in expression as well as APAs that are altered by sleep deprivation and the subsequent recovery period. Genes affected by APA usage include Mapt/Tau, Ntrk2, Homer1A, Sin3band Sorl. Sorl1 has two APAs which cycle with a 24 h period, one additional APA cycles with a 12 h period and one more that is reduced during recovery sleep. Finally, we compared sleep- or circadian-associated APAs with recently described APA-linked brain disorder susceptibility genes and found 46 genes in common.

Humanization of the mouse Tert gene reset telomeres to human length.

Telomeres undergo shortening with each cell division, serving as biomarkers of human aging, which is characterized by short telomeres and restricted telomerase expression in adult tissues. Contrarily, mice, featuring their longer telomeres and widespread telomerase activity, present limitations as models for understanding telomere-related human biology and diseases. To bridge this gap, we engineered a mouse strain with a humanized mTert gene, hmTert, wherein specific non-coding sequences were replaced with their human counterparts. The hmTert gene, encoding the wildtype mTert protein, was repressed in adult tissues beyond the gonads and thymus, closely resembling the regulatory pattern of the human TERT gene. Remarkably, the hmTert gene rescued telomere dysfunction in late generations of mTert-knockout mice. Through successive intercrosses of Terth/- mice, telomere length progressively declined, stabilizing below 10-kb. Terth/h mice achieved a human-like average telomere length of 10-12 kb, contrasting with the 50-kb length in wildtype C57BL/6J mice. Despite shortened telomeres, Terth/h mice maintained normal body weight and cell homeostasis in highly proliferative tissues. Notably, colonocyte proliferation decreased significantly in Terth/h mice during dextran sodium sulfate-induced ulcerative colitis-like pathology, suggesting limitations on cellular renewal due to short telomeres. Our findings underscore the genetic determination of telomere homeostasis in mice by the Tert gene. These mice, exhibiting humanized telomere homeostasis, serve as a valuable model for exploring fundamental questions related to human aging and cancer.

Self-concealment, secrecy, and guilt.

OBJECTIVE: Individuals with a tendency to conceal unflattering information about themselves are more likely to be preoccupied by their secrets and tend to report more negative affect. According to theory, this negative affect is due to self-concealers' conflicting motivation to be authentic in their relationship but fear the negative consequences should they reveal their secrets, which promotes ill-fated attempts to suppress. The purpose of the current study was to test a central component of this model. METHODS: Two studies of adults who were in a romantic relationship and keeping a secret from their partner (combined N = 635; 67.2% women; Mage  = 39.6, SD = 11.9) were surveyed on four biweekly occasions. Multilevel mediation analyses were conducted to test whether preoccupation and suppression mediated the link between self-concealing and negative affect and guilt. RESULTS: The data support the hypotheses. Self-concealers were more preoccupied with and prone to suppress their secret than those low on the trait, which, in turn, predicted greater negative affect and guilt. CONCLUSION: The findings suggest that self-concealers' insecurities and fear of the relational consequences of disclosure set the stage for the debilitating cycle of suppression and preoccupation that leaves them feeling anxious and guilty.

Spatio-temporal spread of Lassa virus and a new rodent host in the Mano River Union area, West Africa.

The spread of Lassa virus (LASV) in Guinea, Liberia and Sierra Leone, which together are named the Mano River Union (MRU) area, was examined phylogeographically. To provide a reliable evolutionary scenario, new rodent-derived, whole LASV sequences were included. These were generated by metatranscriptomic next-generation sequencing from rodents sampled between 2003 and 2020 in 21 localities of Guinea and Sierra Leone. An analysis was performed using BEAST to perform continuous phylogeographic inference and EvoLaps v36 to visualize spatio-temporal spread. LASV was identified as expected in its primary host reservoir, the Natal multimammate mouse (Mastomys natalensis), and also in two Guinean multimammate mice (Mastomys erythroleucus) in northern Sierra Leone and two rusty-bellied brush-furred mice (Lophuromys sikapusi) in southern Sierra Leone. This finding is consistent with the latter two species being secondary host reservoirs. The strains in these three species were very closely related in LASV lineage IV. Phylogenetic analysis indicated that the most recent common ancestor of lineage IV existed 316-374 years ago and revealed distinct, well-supported clades from Sierra Leone (Bo, Kabala and Kenema), Guinea (Faranah, Kissidougou-Guekedou and Macenta) and Liberia (Phebe-Ganta). The phylogeographic scenario suggests southern Guinea as the point of origin of LASV in the MRU area, with subsequent spread to towards Mali, Liberia and Sierra Leone at a mean speed of 1.6 to 1.1 km/year.

Addressing the Main Barrier to Sarcopenia Identification: Utility of Practical Office-Based Bioimpedance Tools Vs. Dual Energy X-ray Absorptiometry (DXA) Body Composition for Identification of Low Muscle Mass in Older Adults.

Background: Sarcopenia is associated with increased morbidity and mortality. Clinically, sarcopenia can be overlooked, especially in obesity. Sarcopenia diagnostic criteria include muscle mass (MM) and function assessments. Muscle function can be readily assessed in a clinic setting (grip strength, chair stand test). However, MM requires dual-energy X-ray absorptiometry (DXA) Body Composition (BC) or other costly tools, not readily available. Methods: Observational cohort pilot study of independently mobile, community dwelling older adults, comparing MM using two office-based, direct-to-consumer bioimpedance (BIA) scales (Ozeri® [manufactured in China] and OMRON® [OMRON HBF-510® Full Body Sensor, Shiokoji Horikawa, Kyoto, Japan] to DXA. The OMRON differs from the Ozeri scale because the OMRON also includes hand sensors. The European Working Group on Sarcopenia in Older People (EWGSOP) DXA or BIA low MM diagnostic cut-offs were used to classify participants as having low or normal MM. Results: Fifty participants: 11 men, 39 women. Forty-two completed DXA. Age 75.8 yrs [67-90]. 81% obese based on body fat cut-offs. With DXA [ASM/height2], 15 had low MM. Using BIA [mmass/height2], 7 with Ozeri, and 27 with OMRON, had low MM. Positive predictive value for low MM versus DXA (as the gold standard) for Ozeri was 73.3% and OMRON was 92.8%. Good correlation between BIA scales and DXA for body fat estimates. Conclusions: OMRON captured all low MM participants identified by DXA plus all on DXA diagnostic borderline. Prevalence of obesity was high. Clinically, sarcopenic obese is the most difficult phenotype, as obesity masks low muscle mass. Low cost, readily available, direct-to-consumer BIA BC scales, especially with hand sensors, provide immediate, reliable information on muscle and fat mass. This can prompt appropriate investigation and/or intervention for sarcopenia or sarcopenic obesity.

Delayed mucosal anti-viral responses despite robust peripheral inflammation in fatal COVID-19.

BACKGROUND: While inflammatory and immune responses to SARS-CoV-2 infection in peripheral blood are extensively described, responses at the upper respiratory mucosal site of initial infection are relatively poorly defined. We sought to identify mucosal cytokine/chemokine signatures that distinguished COVID-19 severity categories, and relate these to disease progression and peripheral inflammation. METHODS: We measured 35 cytokines and chemokines in nasal samples from 274 patients hospitalised with COVID-19. Analysis considered the timing of sampling during disease, as either the early (0-5 days post-symptom onset) or late (6-20 days post-symptom onset). RESULTS: Patients that survived severe COVID-19 showed IFN-dominated mucosal immune responses (IFN-γ, CXCL10 and CXCL13) early in infection. These early mucosal responses were absent in patients that would progress to fatal disease despite equivalent SARS-CoV-2 viral load. Mucosal inflammation in later disease was dominated by IL-2, IL-10, IFN-γ, and IL-12p70, which scaled with severity but did not differentiate patients who would survive or succumb to disease. Cytokines and chemokines in the mucosa showed distinctions from responses evident in the peripheral blood, particularly during fatal disease. CONCLUSIONS: Defective early mucosal anti-viral responses anticipate fatal COVID-19 but are not associated with viral load. Early mucosal immune responses may define the trajectory of severe COVID-19.

Low-Cost Fishhook Removal Simulation.

Audience: The target audiences for this hands-on innovation are health care providers including medical students and emergency medicine residents. This simulation is also appropriate for small group sessions teaching the layperson. Background: While generally not life-threating fishhook injuries are commonplace. They can end a day of recreation or an outdoor trip and possibly result in a visit to an emergency department or urgent care. Hands-on education on fishhook removal techniques that minimize tissue damage is rarely provided in wilderness first aid or traditional medical education. To the best of our knowledge, to date there are only two studies on fishhook removal simulations in medical and wilderness first aid education.1,2 The previously described simulation models are limited by accessibility of materials, realism, and cost. Educational Objectives: The goal of this small group session is to fill the gap in training on fishhook injuries. At the end of the session participants should be able to describe the parts of a fishhook, as well as demonstrate and have increased confidence in performing multiple fishhook removal techniques. Educational Methods: Social learning theory is the conceptual framework for this small group session.3,4 This reflects the idea that students learn not only through repetition with trial and error, but through social interactions, observing and modeling successes of others. As a result, while this simulation requires a facilitator ensure the required items are available it does not necessitate a facilitator be present over the entire duration. Participants perform common fishhook removal techniques with hands-on skill development using commercially available silicone sponge injection pad trainers. Research Methods: Evaluating this small group session at a wilderness medicine training attended by medical and physician assistant students and their guests, self-reported confidence in fishhook removal before and after the simulation was assessed with a paired t-test. Survey results of perceived effectiveness and value of the simulation were also evaluated. Results: The average confidence increased 58% after the simulation (p<0.005). The mean level of effectiveness was 87% and the participant perceived monetary value of the simulation materials was greater than actual cost. Discussion: This innovation is a cost-friendly way to provide education and practice on fishhook removal. It requires minimal set up time and pre-learning can be easily modified to the expected knowledge and experience of participants. Understanding the fishhook removal techniques and increased levels of confidence has the potential to make participants more efficient when caring for patients. It may result in greater likelihood of success in removing fishhooks with minimal tissue damage. Topics: Fishhook injuries, medical simulation, emergency medical education, wilderness first aid, wound management, injection pad trainers.

Dietary intake of preformed vitamin A and provitamin A carotenoids are not associated with serum retinol and carotenoid concentrations among children 36-59 months of age in rural Burkina Faso: a cross-sectional study.

PURPOSE: This study aimed to assess the association between dietary intake of preformed vitamin A (VA) and pro-VA carotenoids and serum retinol and carotenoid concentrations among 36-59-month-old children in a rural area in Burkina Faso. METHODS: Two community-based cross-sectional studies were conducted in a rural area of Burkina Faso and included 115 children aged 36-59 months. Dietary intake of preformed VA and pro-VA was assessed directly by 24-h dietary recall. Serum retinol and carotenoid (α- and ß-carotene, and ß-cryptoxanthin) concentrations were measured. The associations between serum retinol and carotenoid concentrations and their respective dietary intake were assessed by multiple linear regression. RESULTS: Geometric mean [95% CI] adjusted serum retinol concentration in children was 0.86 [0.81; 0.92] µmol/L. The prevalence of low adjusted serum retinol concentration (< 0.7 µmol/L) was 26.8%. Geometric mean [95% CI] serum carotenoid concentrations were: α-carotene (0.03 [0.02; 0.03] µmol/L), ß-carotene (0.14 [0.12; 0.16] µmol/L), and ß-cryptoxanthin (0.17 [0.15; 0.21] µmol/L). Dietary intakes of α- and ß-carotene and adjusted serum retinol and α-carotene concentrations were significantly higher during the rainy season. In multiple linear regressions, no associations were found between dietary intakes of preformed VA and pro-VA carotenoids and serum retinol and carotenoid concentrations in children aged 36-59 months in Burkina Faso. There was no effect of season on the associations between preformed VA and pro-VA carotenoids intake and serum retinol and carotenoid concentrations. CONCLUSIONS: This study shows that dietary intakes of preformed VA and pro-VA carotenoids based on 24-h dietary recall method cannot be used as proxy of serum retinol and carotenoid concentrations in this population. TRIAL REGISTRATION: The study was registered retrospectively (22 March 2018) as a clinical trial with the Pan African Clinical Trials Registry (Cochrane South Africa; PACTR201803002999356).

NOP16 is a histone mimetic that regulates Histone H3K27 methylation and gene repression.

Post-translational modifications of histone tails alter chromatin accessibility to regulate gene expression. Some viruses exploit the importance of histone modifications by expressing histone mimetic proteins that contain histone-like sequences to sequester complexes that recognize modified histones. Here we identify an evolutionarily conserved and ubiquitously expressed, endogenous mammalian protein Nucleolar protein 16 (NOP16) that functions as a H3K27 mimic. NOP16 binds to EED in the H3K27 trimethylation PRC2 complex and to the H3K27 demethylase JMJD3. NOP16 knockout selectively globally increases H3K27me3, a heterochromatin mark, without altering methylation of H3K4, H3K9, or H3K36 or acetylation of H3K27. NOP16 is overexpressed and linked to poor prognosis in breast cancer. Depletion of NOP16 in breast cancer cell lines causes cell cycle arrest, decreases cell proliferation and selectively decreases expression of E2F target genes and of genes involved in cell cycle, growth and apoptosis. Conversely, ectopic NOP16 expression in triple negative breast cancer cell lines increases cell proliferation, cell migration and invasivity in vitro and tumor growth in vivo , while NOP16 knockout or knockdown has the opposite effect. Thus, NOP16 is a histone mimic that competes with Histone H3 for H3K27 methylation and demethylation. When it is overexpressed in cancer, it derepresses genes that promote cell cycle progression to augment breast cancer growth.

FABP7: a glial integrator of sleep, circadian rhythms, plasticity, and metabolic function.

Sleep and circadian rhythms are observed broadly throughout animal phyla and influence neural plasticity and cognitive function. However, the few phylogenetically conserved cellular and molecular pathways that are implicated in these processes are largely focused on neuronal cells. Research on these topics has traditionally segregated sleep homeostatic behavior from circadian rest-activity rhythms. Here we posit an alternative perspective, whereby mechanisms underlying the integration of sleep and circadian rhythms that affect behavioral state, plasticity, and cognition reside within glial cells. The brain-type fatty acid binding protein, FABP7, is part of a larger family of lipid chaperone proteins that regulate the subcellular trafficking of fatty acids for a wide range of cellular functions, including gene expression, growth, survival, inflammation, and metabolism. FABP7 is enriched in glial cells of the central nervous system and has been shown to be a clock-controlled gene implicated in sleep/wake regulation and cognitive processing. FABP7 is known to affect gene transcription, cellular outgrowth, and its subcellular localization in the fine perisynaptic astrocytic processes (PAPs) varies based on time-of-day. Future studies determining the effects of FABP7 on behavioral state- and circadian-dependent plasticity and cognitive processes, in addition to functional consequences on cellular and molecular mechanisms related to neural-glial interactions, lipid storage, and blood brain barrier integrity will be important for our knowledge of basic sleep function. Given the comorbidity of sleep disturbance with neurological disorders, these studies will also be important for our understanding of the etiology and pathophysiology of how these diseases affect or are affected by sleep.

The Fontan Udenafil Exercise Longitudinal Trial: Subgroup Analysis.

The Pediatric Heart Network's Fontan Udenafil Exercise Longitudinal (FUEL) Trial (Mezzion Pharma Co. Ltd., NCT02741115) demonstrated improvements in some measures of exercise capacity and in the myocardial performance index following 6 months of treatment with udenafil (87.5 mg twice daily). In this post hoc analysis, we evaluate whether subgroups within the population experienced a differential effect on exercise performance in response to treatment. The effect of udenafil on exercise was evaluated within subgroups defined by baseline characteristics, including peak oxygen consumption (VO2), serum brain-type natriuretic peptide level, weight, race, gender, and ventricular morphology. Differences among subgroups were evaluated using ANCOVA modeling with fixed factors for treatment arm and subgroup and the interaction between treatment arm and subgroup. Within-subgroup analyses demonstrated trends toward quantitative improvements in peak VO2, work rate at the ventilatory anaerobic threshold (VAT), VO2 at VAT, and ventilatory efficiency (VE/VCO2) for those randomized to udenafil compared to placebo in nearly all subgroups. There was no identified differential response to udenafil based on baseline peak VO2, baseline BNP level, weight, race and ethnicity, gender, or ventricular morphology, although participants in the lowest tertile of baseline peak VO2 trended toward larger improvements. The absence of a differential response across subgroups in response to treatment with udenafil suggests that the treatment benefit may not be restricted to specific sub-populations. Further work is warranted to confirm the potential benefit of udenafil and to evaluate the long-term tolerability and safety of treatment and to determine the impact of udenafil on the development of other morbidities related to the Fontan circulation.Trial Registration NCT0274115.

Atopic Dermatitis.

Atopic dermatitis (AD) is a common, chronic relapsing, and remitting inflammatory skin disease that is characterized by erythematous, scaly, and pruritic lesions often located over the flexural surfaces. Treatment goals of AD include the reduction of itching and burning, as well as the reduction of skin changes. Treatment of AD includes emollients and skin care, topical therapies including topical corticosteroids and steroid-sparing therapies, systemic therapies, and phototherapy.