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Background: The alveolar process is a tooth-dependent structure, and hence, removal of teeth results in the alteration of alveolar process. To alter bone remodeling after dental extraction, various techniques have been put forward for ridge preservation. Aim: The aim of this study is to evaluate and compare the changes of hard and soft tissues in postextraction socket after the application of bone graft material. Materials and Methods: Healthy patients of sample size of 40 were selected who underwent the extraction of anterior tooth irrespective of the arch, from premolar of one side to another, with the exception of incisors in mandible. Twenty patients were randomly selected as the control group and other 20 as the experimental group using an allograft bone material, i.e., beta-tricalcium phosphate to fill the socket. Cone-beam computed tomography (CBCT) was done as baseline preoperative and postoperative at 14 weeks after the extraction. CBCTs data help in recording linear and volumetric measurements which was performed by calibrated examiners to record all the measurements. After measurements, digital planning of dental implants was performed. Results: Forty participants were selected, in which 20 patients each were as the experimental and control groups. No significant difference was found at basal line at any of the cases. At follow-up of 14 weeks, statistical significance was seen in buccal and lingual plate height in the experimental group, and no significant difference was seen in the control group.(P = 0.023). Conclusions: This study clearly points out that an alveolar ridge preservation technique provides therapeutic benefit by limiting bone resorption in comparison to extraction alone.

We propose the design of a nonvolatile, low-loss optical phase shifter based on optical phase change material (O-PCM). The optical phase change material Ge2Sb2Se4Te1 (GSST), which exhibits low loss at telecommunication wavelength $1.55~\mu \text{m}$ as compared to other commonly used O-PCMs, is used in this work as the active material. Instead of direct interaction of the waveguide mode with the O-PCM, the design utilizes coupling between the primary SiN strip waveguide and a waveguide formed by O-PCM, in its amorphous state. The phase matching in the amorphous state inhibits the interaction of the waveguide mode with GSST in its highly lossy crystalline state resulting in low loss operation. Due to a high differential refractive index between the two states of GSST, the design requires a very small length of the phase shifter to accumulate the desired phase difference. The overall response of the Mach-Zehnder Interferometer (MZI) configuration using the designed phase shifter shows that the design can be used to obtain optical switching with a very small insertion loss and crosstalk over the entire C-band.

A compact seven-channel hybrid mode- and polarization-division multiplexer based on a silicon-on-insulator (SOI) waveguide platform is proposed for on-chip optical interconnects. Three independent signals are coupled into the T E 0 , T M 0 , and T E 1 mode of a three moded waveguide using a taper, a polarization beam splitter, and an asymmetric directional coupler in the first coupler section. In the adiabatically connected second and third sections, two collocated asymmetric directional couplers are used to couple two TE modes ( T E 2 , T E 3 ) and two TM modes ( T M 1 , T M 2 ) to reduce the footprint of the device. A coupling length of ∼ 44.29 µ m is achieved with low insertion loss < 0.09 d B and crosstalk better than − 30 d B at the designed wavelength of 1.55 µm.

Design of electro-optic ON-OFF switches based on well-known phase change material Ge2Sb2Te5(GST) is presented. The electro-optic switch is achieved by implementing by co-directional coupling between a 220 nm thick silicon nanowire and a silicon waveguide topped with ITO-GST-ITO layers at the 1.55μm wavelength. By introducing the electric field via the ITO electrodes, the GST layer can be changed between the amorphous and crystalline states. As the modal loss in the crystalline state is much higher than the amorphous state, through a rigorous modal analysis of the coupled silicon nanowire and GST waveguide by using the finite element method, the optimal ITO spacing is obtained at 75nm which is less sensitive to device parameter variations and thus offering better tolerances. The GST thickness is also optimized for the phase matching point at 25 nm in order to efficiently transfer power from silicon nanowire to GST waveguide to attain the OFF state. Once the device is phase matched in crystalline state, the power in the amorphous state will pass with very little interaction with the GST waveguide resulting in an ON state. The Eigenmode Expansion Method of Fimmprop is used as a junction analysis approach to calculate the optical power coupling efficiencies to the output silicon nanowire. The extinction ratio of the electro-optic switch and insertion loss in ON state at phase matching can be obtained as a function of the device length. A compact 1.75 μm long device shows a high extinction ratio of 22 dB with an insertion loss of only 0.56 dB.

Background: Atopic dermatitis (AD) is classified as extrinsic and intrinsic, representing approximately 80% and 20% of patients with the disease, respectively. Although sharing a similar clinical phenotype, only extrinsic AD is characterized by high serum IgE levels. Because most patients with AD exhibit high IgE levels, an ‘‘allergic’’/IgE-mediated disease pathogenesis was hypothesized. However, current models associate AD with T-cell activation, particularly TH2/TH22 polarization, and epidermal barrier defects. Objective: We sought to define whether both variants share a common pathogenesis. Methods: We stratified 51 patients with severe AD into extrinsic AD (n 5 42) and intrinsic AD (n 5 9) groups (with similar mean disease activity/SCORAD scores) and analyzed the molecular and cellular skin pathology of lesional and nonlesional intrinsic AD and extrinsic AD by using gene expression (real-time PCR) and immunohistochemistry. Results: A significant correlation between IgE levels and SCORAD scores (r 5 0.76, P

Current atopic dermatitis (AD) models link epidermal abnormalities in lesional skin to cytokine activation. However, there is evolving evidence of systemic immune activation and detectable abnormalities in nonlesional skin. Because some of the best single correlations with severity (Scoring of AD, or SCORAD) are detected not only in lesional but also nonlesional skin and blood, more complex biomarker models of AD are needed. We thus performed extensive biomarker measures in these compartments using univariate and multivariate approaches to correlate disease biomarkers with SCORAD and with a combined hyperplasia score [thickness and keratin 16 (K16) mRNA] at baseline and after cyclosporine A treatment in 25 moderate to severe AD patients. Increases in serum cytokines and chemokines (IL-13, IL-22, CCL17) were found in AD versus healthy individuals and were reduced with treatment. SCORAD correlated with immune (IL-13, IL-22) and epidermal (thickness, K16) measures in lesional and, even more strongly, in nonlesional AD. Serum cytokines also had higher correlations with nonlesional markers at baseline and with treatment. Multivariate U statistics improved baseline and treatment-response SCORAD correlations. Nonlesional models showed the strongest correlations, with further improvement upon integration of serum markers. Even better correlations were obtained between biomarkers and the hyperplasia score. Larger cohorts are needed to confirm these preliminary data.

This paper reports on the design optimization of compact optical ON-OFF switches based on a GST-clad silicon rib waveguide and compares it to a GST-clad silicon nanowire at the telecommunication wavelength 1.55 µm. Effective index and modal loss of the quasi-TE modes are calculated by a full-vectorial H-field finite element method. It shows that the electro-refraction effect-based switch may not be viable because of the higher modal loss in the GST crystalline state. On the other hand, the larger modal loss difference between GST amorphous and crystalline states would be more suitable for an electro-absorption type switch design. The effect of silicon slab thickness, silicon core width, and GST layer thickness for both the waveguides are presented. As the presence of the GST layer modifies the mode field profiles, so the incurring coupling loss at the butt-coupled junctions between the input/output silicon waveguide and Si-GST waveguide are also calculated by using the least squares boundary residual method. These results show that the GST-clad silicon rib waveguide with a 500-nm-wide silicon core, 60-90 nm thick silicon slab, and 15-25 nm thick GST layer is the optimal self-sustained switch design. In this case, a very compact, 2-5 µm long device is expected to show an extinction ratio of more than 20 dB with the total insertion loss of only 0.36 dB.

Nikhil Dhingra, BSa,b,c, Mayte Suarez-Farinas, PhDa,c, Judilyn Fuentes-Duculan, MDa, Julia K. Gittler, BAa,d, Avner Shemer, MDe, Assaf Raz, PhDf, Vincent A. Fischetti, PhDf, James G. Krueger, MD, PhDa, and Emma Guttman-Yassky, MD, PhDa,g Emma Guttman-Yassky: eguttman@rockefeller.edu aThe Laboratory for Investigative Dermatology, The Rockefeller University, New York, NY bColumbia University College of Physicians & Surgeons, New York, NY cThe Center for Clinical and Translational Science, The Rockefeller University, New York, NY dAlbert Einstein College of Medicine, Bronx, NY eThe Department of Dermatology, Tel-Hashomer, Tel Aviv, Israel fThe Laboratory of Bacterial Pathogenesis and Immunology, The Rockefeller University, New York, NY gThe Department of Dermatology, Icahn School of Medicine at Mount Sinai, New York, NY

Atopic dermatitis (AD) is a common inflammatory skin disease regulated by genetic and environmental factors. Both skin barrier defects and aberrant immune responses are believed to drive cutaneous inflammation in AD. Existing therapies rely largely on allergen avoidance, emollients and topical and systemic immune-suppressants, some with significant toxicity and transient efficacy; no specific targeted therapies are in clinical use today. As our specific understanding of the immune and molecular pathways that cause different subsets of AD increases, a variety of experimental agents, particularly biologic agents that target pathogenic molecules bring the promise of safe and effective therapeutics for long-term use.This paper discusses the molecular pathways characterizing AD, the contributions of barrier and immune abnormalities to its pathogenesis, and development of new treatments that target key molecules in these pathways. In this review, we will discuss a variety of biologic therapies that are in development or in clinical trials for AD, perhaps revolutionizing treatment of this disease.Biologic agents in moderate to severe AD offer promise for controlling a disease that currently lacks good and safe therapeutics posing a large unmet need. Unfortunately, existing treatments for AD aim to decrease cutaneous inflammation, but are not specific for the pathways driving this disease. An increasing understanding of the immune mechanisms underlying AD brings the promise of narrow targeted therapies as has occurred for psoriasis, another inflammatory skin disease, for which specific biologic agents have been demonstrated to both control the disease and prevent occurrence of new skin lesions. Although no biologic is yet approved for AD, these are exciting times for active therapeutic development in AD that might lead to revolutionary therapeutics for this disease.

Petrolatum is a common moisturizer often used in the prevention of skin infections after ambulatory surgeries and as a maintenance therapy of atopic dermatitis (AD). However, the molecular responses induced by petrolatum in the skin have never been assessed.We sought to define the cutaneous molecular and structural effects induced by petrolatum.Thirty-six healthy subjects and 13 patients with moderate AD (mean SCORAD score, 39) were studied by using RT-PCR, gene arrays, immunohistochemistry, and immunofluorescence performed on control skin, petrolatum-occluded skin, and skin occluded with a Finn chamber only.Significant upregulations of antimicrobial peptides (S100A8/fold change [FCH], 13.04; S100A9/FCH, 11.28; CCL20/FCH, 8.36; PI3 [elafin]/FCH, 15.40; lipocalin 2/FCH, 6.94, human β-defensin 2 [DEFB4A]/FCH, 4.96; P.001 for all) and innate immune genes (IL6, IL8, and IL1B; P.01) were observed in petrolatum-occluded skin compared with expression in both control and occluded-only skin. Application of petrolatum also induced expression of key barrier differentiation markers (filaggrin and loricrin), increased stratum corneum thickness, and significantly reduced T-cell infiltrates in the setting of "normal-appearing" or nonlesional AD skin, which is known to harbor barrier and immune defects.Petrolatum robustly modulates antimicrobials and epidermal differentiation barrier measures. These data shed light on the beneficial molecular responses of petrolatum in barrier-defective states, such as AD and postoperative wound care.

Atopic dermatitis (AD) is generally regarded as a type 2 helper T (Th2)-mediated inflammatory skin disease. Although the number of IL-17A-producing cells is increased in the peripheral blood and in acute skin lesion of AD patients, the role of IL-17A in the pathogenesis of AD remains unclear. To clarify this issue, we used murine AD models in an IL-17A-deficient condition. In a repeated hapten application-induced AD model, skin inflammation, IL-4 production in the draining lymph nodes (LNs), and hapten-specific IgG1 and IgE induction were suppressed in IL-17A-deficient mice. Vγ4(+) γδ T cells in the skin-draining LNs and Vγ5(-) dermal γδ T cells in the skin were the major sources of IL-17A. Consistently, in flaky-tail (Flg(ft/ft) ma/ma) mice, spontaneous development of AD-like dermatitis and IgE induction were attenuated by IL-17A deficiency. Moreover, Th2 differentiation from naive T cells was promoted in vitro by the addition of IL-17A. Taken together, our results suggest that IL-17A mediates Th2-type immune responses and that IL-17A signal may be a therapeutic target of AD.

Atopic dermatitis (AD) is a common inflammatory skin disease characterized by wet, oozing, erythematous, pruritic lesions in the acute stage and xerotic, lichenified plaques in the chronic stage. It frequently coexists with asthma and allergic rhinitis, sharing some mechanistic features with these diseases as part of the "atopic march." Controversy exists as to whether immune abnormalities, epidermal barrier defects, or both are the primary factors responsible for disease pathogenesis. In AD patients, there is often a coexisting irritant contact dermatitis (ICD) or allergic contact dermatitis (ACD) that is sometimes clinically difficult to distinguish from AD. ACD shares molecular mechanisms with AD, including increased cellular infiltrates and cytokine activation (Gittler et al., 2013). In this issue, Newell et al. (2013) used an experimental contact sensitization model with dinitrochlorobenzene (DNCB) to gain insight into the unique immune phenotype of AD patients.

BackgroundSevere atopic dermatitis (AD) has a high unmet need for effective and safe therapeutics. In early-phase trials, dupilumab, a fully human mAb targeting IL-4 receptor α, markedly improved disease activity, but the effect of IL-4/IL-13 blockade on AD at the molecular level has not been characterized.ObjectivesWe sought to evaluate dupilumab modulation of the AD molecular signature.MethodsWe performed transcriptomic analyses of pretreatment and posttreatment skin biopsy specimens from patients with moderate-to-severe AD treated weekly with 150 or 300 mg of dupilumab or placebo.ResultsExacerbation of the AD transcriptome was observed in placebo-treated patients. Dupilumab improved the AD signature in a dose-dependent manner. Expression of genes upregulated in AD lesions decreased in patients treated with dupilumab by 26% (95% CI, 21% to 32%) and 65% (95% CI, 60% to 71%) for treatment with 150 and 300 mg, respectively. Genes downregulated in AD lesions increased by 21% (95% CI, 16% to 27%) and 32% (95% CI, 26% to 37%) with dupilumab (150 and 300 mg, respectively). The molecular changes paralleled improvements in clinical scores. A dupilumab treatment signature of 821 probes (>2-fold change, P < .05) significantly modulated in the 300-mg dupilumab group at week 4 compared with baseline was identified in this sample set. Significant (P < .05) decreases in mRNA expression of genes related to hyperplasia (K16 and MKI67), T cells, and dendritic cells (CD1b and CD1c) and potent inhibition of TH2-associated chemokines (CCL17, CCL18, CCL22, and CCL26) were noted without significant modulation of TH1-associated genes (IFNG).ConclusionsThis is the first report showing rapid improvement of the AD molecular signature with targeted anti–IL-4 receptor α therapy. These data suggest that IL-4 and IL-13 drive a complex, TH2-centered inflammatory axis in patients with AD.