Search

Abstract Introduction Bepirovirsen is a novel antisense oligonucleotide in development for chronic hepatitis B virus (HBV) infection therapy. Understanding the impact that clinical characteristics may have on bepirovirsen exposure is important for determining efficacious and well-tolerated dosing regimens. This analysis evaluated demographics and clinical characteristics associated with bepirovirsen exposure using a population pharmacokinetic (PK) analysis. Methods Population PK analyses were conducted using pooled data from three phase 1/2 clinical studies (NCT03020745/NCT02981602/NCT04449029) to construct a structural PK model for bepirovirsen that adequately described plasma concentration–time profiles and identify covariates that affect systemic exposure. The final population PK model was used to simulate bepirovirsen exposure measures to inform exposures at different dose levels and within different subpopulations. Results Bepirovirsen PK data were well-described by a linear, three-compartment model with first-order absorption and absorption delay. Chronic HBV infection status, body weight, and Asian versus non-Asian race were key covariates included in the final model. Visual inspection of correlation scatter plots confirmed general agreement between observed and predicted data from the studies. In simulations, bepirovirsen systemic exposure was dosed proportionally and predicted to be almost completely washed out by 12 weeks following the final 300-mg dose. Differences in body weight, Asian race, or disease status did not result in clinically relevant differences in exposure. Conclusions This analysis demonstrated that the linear three-compartmental model accurately described bepirovirsen PK data. The lack of clinically relevant differences seen in exposure indicate that dose adjustments are not recommended for bepirovirsen based on demographics or clinical characteristics.

Objective: Abdominal ultrasonography (AUS) assessment of the neonatal abdomen is emerging as a potential useful addition to traditional abdominal radiographs (AXR) to confirm the diagnosis of necrotizing enterocolitis (NEC). The goal of this study was to assess the abdominal sonographic findings of premature infants with NEC, in order to determine whether AUS is more effective than AXR in the diagnosis of NEC. Methods: This cross-sectional study was performed on consecutive neonates with clinical suspicion of NEC admitted in our hospital’s NICU (Ali-Asghar Children’s Hospital, Tehran, Iran). We prospectively evaluated the hospitalized subjects using AXR and AUS from May 2018 to May 2020. Results: A total of 53 neonates were included in the study. These patients were divided into two groups: suspected NEC patients (stage I) including 31 subjects and definite NEC patients (stage II and III) including 22 neonates. We found a substantial agreement between the two modalities regarding the detection of pneumoperitoneum and pneumatosis intestinalis (κ: 0·658 for both). The concordance concerning portal venous gas detection was considered slight (κ: 0·315). Thirty-eight patients did not show any signs of portal venous gas in either of AUS or AXR. On the contrary, four patients demonstrated evidences of portal venous gas in both AUS and AXR. AUS detected ten more portal venous gas than AXR. AXR found no cases with positive portal venous gas that were undetected by AUS. The most predictive indicator for surgical intervention in neonates was the presence of free echogenic ascites and loculated fluid. Conclusion: Our findings demonstrated that AUS is superior to AXR in demonstrating portal venous gas and pneumatosis intestinalis. Hence, it seems that AUS is a useful adjunct to AXR in the management of NEC.

Abstract The potential effects of Grand Ethiopian Renaissance Dam (GERD) failure on the downstream countries were numerically assessed. Flow discharge reaching Lake Nasser and the corresponding water levels were determined, and the inundated areas were defined as a result of GERD failure. High-resolution digital elevation model was developed with 2670-km length starting from GERD till Aswan High Dam. GERD’s reservoir, urban, and rural lands downstream of the GERD were presented using a numerical model. The modeled areas included parts of Ethiopia, Sudan, and Egypt, not to mention Toshka Spillway. The model areas were not divided into parts because of calculating the water levels at the existence of intermediate dams as model outputs. In case possible failure of GERD, Roseires and Sennar dams could collapse. Meanwhile, Merowe dam can sustain with the operation of its emergency spillway. Wave height reaches 100-m downstream of the GERD and 64-m and 31-m downstream of the Roseires and Merowe dams, respectively.

Staphylococcus aureus acts both as a colonizing commensal bacterium and invasive pathogen. Nasal colonization is associated with an increased risk of infection caused by the identical strain. In patients with atopic dermatitis (AD), the degree of S. aureus colonization is associated with the severity of the disease. Here, we comparatively analyzed the in vivo transcriptional profile of S. aureus colonizing the nose and non-diseased skin (non-lesional skin) as opposed to the diseased skin (lesional skin—defined here as infection) of 12 patients with AD. The transcriptional profile during the asymptomatic colonization of the nose closely resembled that of the lesional skin samples for many of the genes studied, with an elevated expression of the genes encoding adhesion-related proteins and proteases. In addition, the genes that modify and remodel the cell wall and encode proteins that facilitate immune evasion showed increased transcriptional activity. Notably, in a subgroup of patients, the global virulence regulator Agr (accessory gene regulator) and downstream target genes were inactive during nasal colonization but upregulated in the lesional and non-lesional skin samples. Taken together, our results demonstrate a colonization-like transcriptional profile on diseased skin and suggest a role for the peptide quorum sensing system Agr during the transition from asymptomatic nasal colonization to skin colonization/infection.

Abstract Non-melanoma skin cancer (NMSC) is the most common cancer in Caucasians worldwide. We investigated the pathophysiological role of MIF and its homolog D-DT in UVB- and chemically induced NMSC using Mif −/− , D-dt −/− and Mif −/− /D-dt −/− mice on a hairless SKH1 background. Knockout of both cytokines showed similar attenuating effects on inflammation after acute UVB irradiation and tumor formation during chronic UVB irradiation, without additive protective effects noted in double knockout mice, indicating that both cytokines activate a similar signaling threshold. In contrast, genetic deletion of Mif and D-dt had no major effects on chemically induced skin tumors. To get insight into the contributing mechanisms, we used an in vitro 3D skin model with incorporated macrophages. Application of recombinant MIF and D-DT led to an accumulation of macrophages within the epidermal part that could be reversed by selective inhibitors of MIF and D-DT pathways. In summary, our data indicate that MIF and D-DT contribute to the development and progression of UVB- but not chemically induced NMSC, a role at least partially accounted by effects of both cytokines on epidermal macrophage accumulation. These data highlight that MIF and D-DT are both potential therapeutic targets for the prevention of photocarcinogenesis but not chemical carcinogenesis.

Study region: Wadi Tayyibah is located in south Sinai, Egypt, in a region called Abou Zenima, and it is used to develop this study. Study focus: Flash floods tremendously impact many facets of human life due to their destructive consequences and the costs associated with mitigating efforts. This study aims to evaluate the harvesting of Runoff by delineating the watersheds using the Hydrologic Engineering Center-1 (HEC-1) model and ArcGIS software in trying to benefit from it in different ways. All morphometric parameters of the basin were considered, and the risk degree of the different sub-basins was determined. The suitable locations of dams were identified using a Geographical Information System (GIS) using the basin's morphometric characteristics. New hydrological insights for the region: The study proposed a total number of eight dams, including five dams that were recommended for sub-basin (1) and three dams in sub-basin (4), while sub-basins (2) and (3) are not suitable locations to build dams according to the contour map of Wadi Tayyibah. Results indicate that, based on the constructed flash flood hazard maps and the basin's detailed morphometric characteristics, the best locations of dams are Dam (3) in sub-basin (1) and Dam (7) in sub-basin (4), where the runoff volume reached 3.13 million cubic meters (Mm3) and 5.56 Mm3 for return period 100, respectively. This study is useful for decision-makers and designers for using morphometric parameters and flash flood hazard degree maps to select dam locations. Also, the cost-benefit analysis for using the morphometric parameters is required to be investigated.

The pathophysiology of different neurodegenerative illnesses is significantly influenced by the polarization regulation of microglia and macrophages. Traditional classifications of macrophage phenotypes include the pro-inflammatory M1 and the anti-inflammatory M2 phenotypes. Numerous studies demonstrated dynamic non-coding RNA modifications, which are catalyzed by microglia-induced neuroinflammation. Different nutraceuticals focus on the polarization of M1/M2 phenotypes of microglia and macrophages, offering a potent defense against neurodegeneration. Caeminaxin A, curcumin, aromatic-turmerone, myricetin, aurantiamide, 3,6′-disinapoylsucrose, and resveratrol reduced M1 microglial inflammatory markers while increased M2 indicators in Alzheimer’s disease. Amyloid beta-induced microglial M1 activation was suppressed by andrographolide, sulforaphane, triptolide, xanthoceraside, piperlongumine, and novel plant extracts which also prevented microglia-mediated necroptosis and apoptosis. Asarone, galangin, baicalein, and a-mangostin reduced oxidative stress and pro-inflammatory cytokines, such as interleukin (IL)-1, IL-6, and tumor necrosis factor-alpha in M1-activated microglia in Parkinson’s disease. Additionally, myrcene, icariin, and tenuigenin prevented the nod-like receptor family pyrin domain-containing 3 inflammasome and microglial neurotoxicity, while a-cyperone, citronellol, nobiletin, and taurine prevented NADPH oxidase 2 and nuclear factor kappa B activation. Furthermore, other nutraceuticals like plantamajoside, swertiamarin, urolithin A, kurarinone, Daphne genkwa flower, and Boswellia serrata extracts showed promising neuroprotection in treating Parkinson’s disease. In Huntington’s disease, elderberry, curcumin, iresine celosia, Schisandra chinensis, gintonin, and pomiferin showed promising results against microglial activation and improved patient symptoms. Meanwhile, linolenic acid, resveratrol, Huperzia serrata, icariin, and baicalein protected against activated macrophages and microglia in experimental autoimmune encephalomyelitis and multiple sclerosis. Additionally, emodin, esters of gallic and rosmarinic acids, Agathisflavone, and sinomenine offered promising multiple sclerosis treatments. This review highlights the therapeutic potential of using nutraceuticals to treat neurodegenerative diseases involving microglial-related pathways.

Pemphigus vulgaris is a life-threatening blistering skin disease caused by autoantibodies which destabilize cell adhesion of keratinocytes. The phosphodiesterase 4 inhibitor apremilast prevents skin blistering by stabilizing the keratin filament anchorage of desmosomes.

Abstract One of the critical challenges in multicarrier‐based systems is peak to average power ratio (PAPR). Recently, Filter Bank Multicarrier (FBMC) is proved to be a promising candidate that can replace the traditional orthogonal multiplexing division (OFDM) scheme due to its better spectral efficiency, reducing both inter‐channel interference (ICI) and PAPR. Due to their advantages in reducing the PAPR without impacting the BER, the Hadamard transform was used in the proposed FBMC based VLC system. Furthermore, here, the discreet cosine transform (DCT) precoding is also used to boost the potential for PAPR reduction and the BER efficiency. The negative signals are not clipped off as in traditional asymmetrically‐clipped optical OFDM (ACO‐OFDM) signals to reduce the impact of large‐amplitude signal reduction nor add dc biasing for cancelling negative signals as in traditional DC‐biased optical OFDM (DCO‐OFDM) signals. Furthermore, a Clipping ratio is introduced to allow a trade‐off between bit error rate (BER) and PAPR reduction, and the optimal PAPR reduction is investigated. The obtained results show that the proposed FBMC based VLC system with DCT and clipping technique can reduce the PAPR and achieve good BER efficiency compared to the OFDM based VLC system.

Abstract Background Despite large outbreaks in humans seeming improbable for a number of zoonotic pathogens, several pose a concern due to their epidemiological characteristics and evolutionary potential. To enable effective responses to these pathogens in the event that they undergo future emergence, the Coalition for Epidemic Preparedness Innovations is advancing the development of vaccines for several pathogens prioritized by the World Health Organization. A major challenge in this pursuit is anticipating demand for a vaccine stockpile to support outbreak response. Methods We developed a modeling framework for outbreak response for emerging zoonoses under three reactive vaccination strategies to assess sustainable vaccine manufacturing needs, vaccine stockpile requirements, and the potential impact of the outbreak response. This framework incorporates geographically variable zoonotic spillover rates, human-to-human transmission, and the implementation of reactive vaccination campaigns in response to disease outbreaks. As proof of concept, we applied the framework to four priority pathogens: Lassa virus, Nipah virus, MERS coronavirus, and Rift Valley virus. Results Annual vaccine regimen requirements for a population-wide strategy ranged from > 670,000 (95% prediction interval 0–3,630,000) regimens for Lassa virus to 1,190,000 (95% PrI 0–8,480,000) regimens for Rift Valley fever virus, while the regimens required for ring vaccination or targeting healthcare workers (HCWs) were several orders of magnitude lower (between 1/25 and 1/700) than those required by a population-wide strategy. For each pathogen and vaccination strategy, reactive vaccination typically prevented fewer than 10% of cases, because of their presently low R 0 values. Targeting HCWs had a higher per-regimen impact than population-wide vaccination. Conclusions Our framework provides a flexible methodology for estimating vaccine stockpile needs and the geographic distribution of demand under a range of outbreak response scenarios. Uncertainties in our model estimates highlight several knowledge gaps that need to be addressed to target vulnerable populations more accurately. These include surveillance gaps that mask the true geographic distribution of each pathogen, details of key routes of spillover from animal reservoirs to humans, and the role of human-to-human transmission outside of healthcare settings. In addition, our estimates are based on the current epidemiology of each pathogen, but pathogen evolution could alter vaccine stockpile requirements.

IntroductionOutcomes of catheter ablation for non-paroxysmal atrial fibrillation (AF) remain suboptimal. Non-invasive stratification of patients based on the presence of atrial cardiomyopathy (ACM) could allow to identify the best responders to pulmonary vein isolation (PVI).MethodsObservational multicentre retrospective study in patients undergoing cryoballoon-PVI for non-paroxysmal AF. The duration of amplified P-wave (APW) was measured from a digitally recorded 12-lead electrocardiogram during the procedure. If patients were in AF, direct-current cardioversion was performed to allow APW measurement in sinus rhythm. An APW cut-off of 150 ms was used to identify patients with significant ACM. We assessed freedom from arrhythmia recurrence at long-term follow-up in patients with APW ≥ 150 ms vs. APW

Abstract The development of a new dynamic lattice element method (dynamicLEM) as well as its application in the simulation of the propagation of body waves in discontinuous and heterogeneous media is the focus of this research paper. The conventional static lattice models are efficient numerical methods to simulate crack initiation and propagation in cemented geomaterials. The advantages of the LEM and the developed dynamic solution, such as simulation of arbitrary crack initiation and propagation, illustration and simulation of existing inherent material heterogeneity as well as stress redistribution upon crack opening, opens a new engineering field and tool for material analysis. To realize the time dependency of the dynamic LEM, the equation of motion of forced vibration is solved while using the Newmark- $$\beta$$ β method and implementing the non-linear Newton–Raphson Jacobian method. The method validation is done according to the results of a boundary element method (BEM) in the plane P-SV-wave propagation within a plane strain domain. Further tests comparing the generated wave types, simulation and study of crack discontinuities as well as inherent heterogeneities in the geomaterials are conducted to illustrate the accurate applicability of the new dynamic lattice method. The results indicate that with increasing heterogeneity within the material, the wave field becomes significantly scattered and further analysis of wave fields according to the wavelength/heterogeneity ratio become indispensable. Therefore, in a heterogeneous medium, the application of continuum methods in relation to structural health monitoring should be precisely investigated and improved. The developed dynamic lattice element method is an ideal simulation tool to consider particle scale irregularities, crack distributions and inherent material heterogeneities and can be easily implemented in various engineering applications.

Introduction: Fixed functional appliances are devices which are fixed and effective 24 hours a day with minimal patient compliance which is a major advantage of fixed functional appliance. PowerScope is the latest innovation in Class II Correction which is a direct derivative of the Herbst Type II appliance. Material and Methods: 10 Patients with Class II Malocclusion Who Required Orthodontic Treatment were selected from the department of orthodontics and dentofacial orthopaedics, Al-Ameen Dental College and Hospital, Vijaypura for the study. Lateral cephalograms prior to the commencement of the treatment were recorded of 10 patients. Further, lateral cephelograms were taken prior to placement and after removal of PowerScope. The cephalograms were compared on Set of 33 cephalometric parameter divided into sagittal, vertical and angular measurements followed by statistical analysis with matched paired T test to determine the significance Result: In this study, mean and standard deviation of all the cephalometric values for before placing the powerscope and after removal of powerscope were compared out of all the 33 set of cephalometric Values, sagittal parameter Olp- Pg was statistically highly significant with p=

Healthy human skin is constantly exposed to sterile and microbial agents. The skin immune system plays an important role in immune surveillance between tolerance and immune activation. This is mainly mediated by neutrophils, macrophages and most importantly lymphocytes. Keratinocytes, which form the outer skin barrier (epidermis) are also critical for cutaneous homeostasis. Being a non-professional immune cell, recognition of danger signals in keratinocytes is mediated by innate immune receptors (pattern recognition receptors, PRR). While Toll-like receptors are located on the cell membrane or the endosomes, nucleotide-binding domain and leucine-rich repeat containing gene family receptors (NLR) are intracellular PRRs. Some of these, once activated, trigger the formation of inflammasomes. Inflammasomes are multiprotein complexes and serve as platforms that mediate the release of innate cytokines after successful recognition, thereby attracting immune cells. Moreover, they mediate the pro-inflammatory cell death pyroptosis. Best characterized is the NLRP3 inflammasome. The function of inflammasomes differs significantly between different cell types (keratinocytes versus immune cells) and between different species (human versus mouse). In recent years, great progress has been made in deciphering the activation mechanisms. Dysregulation of inflammasomes can lead to diseases with varying degrees of severity. Here we focus on the structure, function, and associated pathologies of the NLRP1 inflammasome, which is the most relevant inflammasome in keratinocytes.

Aims and Objectives: There is a profuse tendency for researches to focus on accelerating methods for tooth movement due to the huge demand from adults for a shorter orthodontic treatment time. Photobiomodulation is an emerging area of science that has clinical applications in number of human biological processes. Low-Intensity laser therapy (LILT) has been discussed in many fields of dentistry and hence this study was undertaken to evaluate the efficacy of Low Intensity Diode Laser to accelerate orthodontic tooth movement and correlating the IL6 and TNF α - levels in gingival crevicular fluid. Materials and Methods: Twenty patients aged from 15 to 22 years were randomly selected and among these patients, ten patients were allotted for experimental and ten patients served as controlled groups by flip coin method. Treatment was initiated by bonding fixed appliances in both the arches. The experimental group was treated with LILT using Diode Laser. GCF was collected by intrasulcular technique at different period of intervals and subjected to laboratory assessment. Results: There was statistical significance in the rate of tooth movement in the experimental group (LILT). Increased levels of TNF-α and IL-6 were also observed in GCF samples of experimental group as compared with the control group. Conclusion: Application of low-level laser therapy in adjunctive to orthodontic forces accelerated orthodontic tooth movement along with increased the levels of TNF-α and IL-6 in gingival crevicular fluid.

The El Nino Southern Oscillation (ENSO) influences the weather around the world and, therefore, has strong impacts on society. Here, the authors show that ENSO is associated with child nutrition in many countries, with warmer El Niño conditions leading to more child undernutrition in large parts of the developing world.

Abstract The identification of structural damages takes a more and more important role within the modern economy, where often the monitoring of an infrastructure is the last approach to keep it under public use. Conventional monitoring methods require specialized engineers and are mainly time-consuming. This research paper considers the ability of neural networks to recognize the initial or alteration of structural properties based on the training processes. The presented model, a spatially asymmetric encoder–decoder network, is based on 1D-Convolutional Neural Networks (CNN) for wave field pattern recognition, or more specifically the wave field change recognition. The proposed model is used to identify the change within propagating wave fields after a crack initiation within the structure. The paper describes the implemented method and the required training procedure to get a successful crack detection accuracy, where the training data are based on the dynamic lattice model. Although the training of the model is still time-consuming, the proposed new method has an enormous potential to become a new crack detection or structural health monitoring approach within the conventional monitoring methods.

Newly emerged pathogens are inherently difficult to forecast, due to many unknowns about their biology early in an epidemic. Here, the authors assess forecasts of a suite of models during the Zika epidemic in Colombia, finding that the models that performed best changed over the course of the epidemic.

Staphylococci are commensals of human skin and mucous membranes, but some species can also cause serious infections. Host niches during both colonization and infection differ greatly and are characterized by specific environmental conditions (pH, temperature, oxygen, nutrient availability, and microbiota) that can affect gene expression and virulence of microbes. To successfully occupy extremely different habitats at different anatomical sites, Staphylococci are equipped with a variety of regulatory elements that allow specific adaptation to the changing environments. Not surprisingly, gene expression in vivo can be significantly different from the expression pattern observed in vitro. Niche specific stimuli that influence the bacterial ability to either cause infection or maintain colonization are only partially understood. Here, we describe habitat specific conditions and discuss the available literature analyzing staphylococcal gene expression, focusing on Staphylococcus aureus and S. epidermidis during colonization of the nose and skin.

Molecular mechanisms underlying auto-antibody-induced acantholysis in pemphigus vulgaris are subject of current research to date. To decipher the discrepancy between ubiquitous antibody binding to the epidermal desmosomes, but discontinuous disease manifestation, we were able to identify Ultraviolet A (UVA) as a cofactor for acantholysis. UVA induces interleukin (IL)-1 secretion in keratinocytes, mirroring innate immune system activation. In an in vitro keratinocyte dissociation assay increased fragmentation was observed when UVA was added to anti-Desmoglein 3 Immunoglobulins (anti-Dsg3 IgG). These results were confirmed in skin explants where UVA enhanced anti-Dsg3-mediated loss of epidermal adhesion. The UVA-mediated effect was blocked in vitro by the pan-caspase-inhibitor zVAD-fmk. Thus, we introduce UVA as a caspase-dependent exogenous cofactor for acantholysis which suggests that local innate immune responses largely contribute to overt clinical blister formation upon autoantibody binding to epidermal cells in pemphigus vulgaris.

The severe autoimmune blistering disease Pemphigus vulgaris (PV) is mainly caused by autoantibodies (IgG) against desmoglein (Dsg) 3 and Dsg1. The mechanisms leading to the development of blisters are not fully understood, but intracellular signaling seems to play an important role. Sheddases ADAM10 and ADAM17 are involved in the turnover of the desmosomal cadherin Dsg2 and ADAM10 has been shown to contribute to acantholysis in a murine pemphigus model. In the present study, we further examined the role of ADAM10 and ADAM17 both in keratinocyte adhesion and in the pathogenesis of PV. First, we found that inhibition of ADAM10 enhanced adhesion of primary human keratinocytes but not of immortalized keratinocytes. In dissociation assays, inhibition of ADAM10 shifted keratinocyte adhesion towards a hyperadhesive state. However, ADAM inhibition did neither modulate protein levels of Dsg1 and Dsg3 nor activation of EGFR at Y1068 and Y845. In primary human keratinocytes, inhibition of ADAM10, but not ADAM17, reduced loss of cell adhesion and fragmentation of Dsg1 and Dsg3 immunostaining in response to a PV1-IgG from a mucocutaneous PV patient. Similarly, inhibition of ADAM10 in dissociation assay decreased fragmentation of primary keratinocytes induced by a monoclonal antibody against Dsg3 and by PV-IgG from two other patients both suffering from mucosal PV. However, such protective effect was not observed in both cultured cells and ex vivo disease models, when another mucocutaneous PV4-IgG containing more Dsg1 autoantibodies was used. Taken together, ADAM10 modulates both hyperadhesion and PV-IgG-induced loss of cell adhesion dependent on the autoantibody profile.

In this paper, a new non-redundant three-layer peak-to-average power ratio (PAPR) reduction technique is proposed for filter bank multicarrier communication based visible light communication (FBMC based VLC) systems. In the proposed technique, the FBMC based VLC data signal is overlapped with two new non-redundant signals. The initial-layer signals are the FBMC modulated signals. For PAPR reduction, the second-layer signals are constructed to decrease initial-layer large-amplitude signals, while the last-layer signals are used to improve the initial-layer small-amplitude signals. The two non-redundant signals do not overlap with the data signals in the frequency domain, because data signals are distributed on odd subcarriers, while even subcarriers are occupied by the constructed signals. To mitigate the effect of large-amplitude signal reduction in the proposed technique, the negative signals are converted into positive, rather than being clipped off as in conventional FBMC based VLC systems. In order to realize a trade-off between PAPR reduction and bit error rate (BER), we introduce a scaling factor in the converted signals. The performance of the proposed technique is calculated in terms of complementary cumulative distribution function (CCDF) and BER. The obtained results indicate that FBMC based VLC systems with the proposed technique can achieve a good trade-off between PAPR reduction and BER and outperforms the corresponding orthogonal frequency division multiplexing (OFDM) based VLC systems.

The virulence factors of the opportunistic human pathogen Staphylococcus epidermidis have been a main subject of research. In contrast, limited information is available on the mechanisms that allow the bacterium to accommodate to the conditions during carriage, a prerequisite for pathogenicity. Here, we tested the hypothesis that the adaptation of S. epidermidis at different anatomical sites is reflected by differential gene regulation. We used qPCR to profile S. epidermidis gene expression in vivo in nose and skin swabs of 11 healthy individuals. Despite some heterogeneity between individuals, significant site-specific differences were detected. For example, expression of the S. epidermidis regulator sarA was found similarly in the nose and on the skin of all individuals. Also, genes encoding colonization and immune evasion factors (sdrG, capC, and dltA), as well as the sphingomyelinase encoding gene sph, were expressed at both anatomical sites. In contrast, expression of the global regulator agr was almost inactive in the nose but readily present on the skin. A similar site-specific expression profile was also identified for the putative chitinase-encoding SE0760. In contrast, expression of the autolysine-encoding gene sceD and the wall teichoic acid (WTA) biosynthesis gene tagB were more pronounced in the nose as compared to the skin. In summary, our analysis identifies site-specific gene expression patterns of S. epidermidis during colonization. In addition, the observed expression signature was significantly different from growth in vitro. Interestingly, the strong transcription of sphingomyelinase together with the low expression of genes encoding the tricarboxylic acid cycle (TCA) suggests very good nutrient supply in both anatomical niches, even on the skin where one might have suspected a rather lower nutrient supply compared to the nose.