Colony Stimulating Factor-1 Receptor: An emerging target for neuroinflammation PET imaging and AD therapy.

Although neuroinflammation is a significant pathogenic feature of many neurologic disorders, its precise function in-vivo is still not completely known. PET imaging enables the longitudinal examination, quantification, and tracking of different neuroinflammation biomarkers in living subjects. Particularly, PET imaging of Microglia, specialised dynamic immune cells crucial for maintaining brain homeostasis in central nervous system (CNS), is crucial for staging the neuroinflammation. Colony Stimulating Factor- 1 Receptor (CSF-1R) PET imaging is a novel method for the quantification of neuroinflammation. CSF-1R is mainly expressed on microglia, and neurodegenerative disorders greatly up-regulate its expression. The present review primarily focuses on the development, pros and cons of all the CSF-1R PET tracers reported for neuroinflammation imaging. Apart from neuroinflammation imaging, CSF-1R inhibitors are also reported for the therapy of neurodegenerative diseases such as Alzheimer's disease (AD). AD is a prevalent, advancing, and fatal neurodegenerative condition that have the characteristic feature of persistent neuroinflammation and primarily affects the elderly. The aetiology of AD is profoundly influenced by amyloid-beta (Aß) plaques, intracellular neurofibrillary tangles, and microglial dysfunction. Increasing evidence suggests that CSF-1R inhibitors (CSF-1Ri) can be helpful in preclinical models of neurodegenerative diseases. This review article also summarises the most recent developments of CSF-1Ri-based therapy for AD.

ASTHMAXcel PRO patient satisfaction and usability field testing.

Background: ASTHMAXcel PRO, an enhanced version of the ASTHMAXcel mobile application, has been developed to deliver comprehensive, guideline-based asthma education while also facilitating the collection of patient-reported outcomes (PROs) and enhancing user experience.Objective: To perform field testing and conduct formative and summative evaluation of the ASTHMAXcel PRO application to assess its impact on patient satisfaction, usability, and usage.Methods: Twenty-eight adult patients completed a baseline visit during which ASTHMAXcel PRO was introduced, health literacy was assessed, and demographic data were collected. They were instructed to use the app for 4 weeks. The Questionnaire for User Interface Satisfaction (QUIS) and the Unified Theory of Acceptance and Use of Technology (UTAUT) questionnaire were administered at baseline and 4 weeks to assess user satisfaction and technology acceptance, respectively. Semi-structured interviews were conducted to gather feedback regarding the application from patients.Results: The baseline total scores were high for both UTAUT and QUIS (mean (SD): 64.2 (10.1), 6.8 (2.2) respectively) indicating that user satisfaction and acceptance began at high levels. UTAUT total score, as well as all domain scores, improved significantly from baseline to 4 weeks (p < 0.02). QUIS total score along with several domain scores (screen, system capabilities, usability) also increased from baseline to 4-weeks (p = 0.03, 0.01, 0.03, 0.01, respectively). These improvements remained significant when adjusting for age, gender, education, and health literacy. Patients reported that the application was helpful, informative, and easy to understand and use.Conclusion: The significant increases in satisfaction and technology adoption observed among ASTHMAXcel PRO users demonstrate that the application is viable and has the potential to improve upon usability challenges faced by existing mobile health applications.

Evaluation of advanced, pathophysiologic new targets for imaging of CNS.

The inadequate information about the in vivo pathological, physiological, and neurological impairments, as well as the absence of in vivo tools for assessing brain penetrance and the efficiency of newly designed drugs, has hampered the development of new techniques for the treatment for variety of new central nervous system (CNS) diseases. The searching sites such as Science Direct and PubMed were used to find out the numerous distinct tracers across 16 CNS targets including tau, synaptic vesicle glycoprotein, the adenosine 2A receptor, the phosphodiesterase enzyme PDE10A, and the purinoceptor, among others. Among the most encouraging are [18 F]FIMX for mGluR imaging, [11 C]Martinostat for Histone deacetylase, [18 F]MNI-444 for adenosine 2A imaging, [11 C]ER176 for translocator protein, and [18 F]MK-6240 for tau imaging. We also reviewed the findings for each tracer's features and potential for application in CNS pathophysiology and therapeutic evaluation investigations, including target specificity, binding efficacy, and pharmacokinetic factors. This review aims to present a current evaluation of modern positron emission tomography tracers for CNS targets, with a focus on recent advances for targets that have newly emerged for imaging in humans.

Redesigned Hybrid Nylons with Optical Clarity and Chemical Recyclability.

Aliphatic polyamides, or nylons, are typically highly crystalline and thermally robust polymers used in high-performance applications. Nylon 6, a high-ceiling-temperature (HCT) polyamide from ε-caprolactam, lacks expedient chemical recyclability, while low-ceiling temperature (LCT) nylon 4 from pyrrolidone exhibits complete chemical recyclability, but it is thermally unstable and not melt-processable. Here, we introduce a hybrid nylon, nylon 4/6, based on a bicyclic lactam composed of both HCT ε-caprolactam and LCT pyrrolidone motifs in a hybridized offspring structure. Hybrid nylon 4/6 overcomes trade-offs in (de)polymerizability and performance properties of the parent nylons, exhibiting both excellent polymerization and facile depolymerization characteristics. This stereoregular polyamide forms nanocrystalline domains, allowing optical clarity and high thermal stability, however, without displaying a melting transition before decomposition. Of a series of statistical copolymers comprising nylon 4/6 and nylon 4, a 50/50 copolymer achieves the greatest synergy in both reactivity and polymer properties of each homopolymer, offering an amorphous nylon with favorable properties, including optical clarity, a high glass transition temperature, melt processability, and full chemical recyclability.

Unraveling the Influence of Thermal Drawing Parameters on the Microstructure and Thermo-Mechanical Properties of Multimaterial Fibers.

Multimaterial thermally drawn fibers are becoming important building blocks in several foreseen applications in surgical probes, protective gears, or medical textiles. Here, the influence of the thermal drawing parameters on the degree of polymer chain orientation, the related thermal shrinkage behavior, and the mechanical properties of the final fibers is investigated via thermo-mechanical testing and small- and wide-angle X-ray scattering (SAXS and WAXS) analyses. This study on polyetherimide fibers reveals that the drawing stress, which depends on the drawing speed and temperature, controls the thermal shrinkage behavior and mechanical properties. Furthermore, SAXS and WAXS analyses show that the degree of chain orientation increases with drawing stresses below 8 MPa and then saturates, which correlates with the amount of observed shrinkage. The use of this process-dependent polymer chain alignment to tune the mechanical and shrinkage properties of the fibers is highlighted and controlled bending multimaterial fibers made of two polymethyl methacrylates having different molecular weights are developed. Finally, a heat treatment procedure is proposed to relax the chain alignment and increase the dimensional stability of devices such as temperature sensors. This deeper understanding can serve as a guide for the processing of complex fibers requiring specific mechanical properties or enhanced thermal stability.

Benzoxazolone-arylpiperazinyl scaffold-based PET ligand for 5-HT7 : Synthesis and biological evaluation.

Efforts are underway to improve the diagnosis and treatment for neurological disorders like depression, anxiety, epilepsy, and schizophrenia. The G-protein-coupled receptors (GPCRs) 5-HT7   receptor, the most recently identified member of 5-HT receptor family dysregulation has an association with various central nervous system (CNS) disorders and its ligands have an edge as potential therapeutics. Here, we report the synthesis, characterization, and biological evaluation of diversely substituted methoxy derivatives of 2-benzoxazolone arylpiperazine for targeting 5-HT7  receptors. Out of all derivatives, only C-2 substituted derivative, 3-(4-(4-(2-methoxyphenyl)piperazin-1-yl)butyl)benzoxazol-2(3H)-one/ABO demonstrate a high affinity for human 5-HT7 receptors. [11 C]ABO was obtained by O-methylation of desmethyl-precursor using [11 C]CH3 OTf in the presence of NaOH giving a high radiochemical yield of 25 ± 12% (decay-corrected, n = 7) with stability up to 1.5 h postradiolabeling. In vitro autoradiography displays binding of [11 C]ABO in accordance with 5-HT7 distribution with a decrease of approximately 80% and 40% activity in the hippocampus and cerebellum brain region when administered with 10 µM cold ligand. Prefatory positron emission tomography scan results in Sprague-Dawley (SD) rat brain revealed fast and high radioactivity build-up in 5-HT7 receptor-rich regions, namely, the hippocampus (2.75 ± 0.16 SUV) and the cerebral cortex (2.27 ± 0.02 SUV) establishing selective targeting of [11 C]ABO. In summary, these pieces of data designate [11 C]ABO as a promising 5-HT7  receptor ligand that can have possible roles in clinics after its further optimization on different animal models.

Tailoring Fibre Structure Enabled by X-ray Analytics for Targeted Biomedical Applications.

The rising interest in designing fibres via spinning techniques combining the properties of various polymeric materials into advanced functionalised materials is directed towards targeted biomedical applications such as drug delivery, wearable sensors or tissue engineering. Understanding how these functional polymers exhibit multiscale structures ranging from the molecular level to nano-, micro-and millimetre scale is a key prerequisite for their challenging applications that can be addressed by a non-destructive X-ray based analytical approach. X-ray multimodalities combining X-ray imaging, scattering and diffraction allow the study of morphology, molecular structure, and the analysis of nano-domain size and shape, crystallinity and preferential orientation in 3D arrangements. The incorporation of X-ray analytics in the design process of polymeric fibers via their nanostructure under non-ambient conditions (i.e. temperature, mechanical load, humidity…) allows for efficient optimization of the fabrication process as well as quality control along the product lifetime under operating environmental conditions. Here, we demonstrate the successful collaboration between the laboratory of Biomimetic Textiles and Membranes and the Center of X-ray Analytics at Empa for the design, characterisation and optimisation of advanced functionalised polymeric fibrous material systems.

Synthesis and biological evaluation of modified laminin peptide (N2S2-KDP) with enhanced affinity for neuronal growth and targeted molecular imaging (SPECT).

An analog of γ1 laminin (RDIAEIIKDI) decapeptide has been used to augment neuronal survival and regeneration after injuries, during aging and other CNS disorder. As a prime synthetic peptide, KDI, is responsible for the neurite outgrowth of human embryonic neurons. In this study, we have designed, modified a KDI derivative and synthesized by replacing isoleucine (I) with Pro (P) amino acid at C-terminal to enhance its potency towards neurite growth. -Cys-Gly-Cys (-CGC) N2S2 motif was also incorporated in the present design for peptide radiolabeling. The modified peptide showed a better binding with the desired 3T1M receptor for neurite growth. The peptide was synthesized using solid phase peptide synthesis and Fmoc-strategy with more than 80% yield. The receptor binding studies of 99mTc-N2S2-KDP in Neuro2A cell lines showed Kd value in 31 nM range and the complex showed appreciable brain uptake in mice. The results on human SH-SY5Y indicate that the unlabeled N2S2-KDP may perhaps be useful for neurite growth in neurodegenerative disorder.

Polarimetric imaging in backscattering for the structural characterization of strongly scattering birefringent fibrous media.

Interpreting the polarimetric data from fiber-like macromolecules constitutive of tissue can be difficult due to strong scattering. In this study, we probed the superficial layers of fibrous tissue models (membranes consisting of nanofibers) displaying varying degrees of alignment. To better understand the manifestation of membranes' degree of alignment in polarimetry, we analyzed the spatial variations of the backscattered light's Stokes vectors as a function of the orientation of the probing beam's linear polarization. The degree of linear polarization reflects the uniaxially birefringent behavior of the membranes. The rotational (a-)symmetry of the backscattered light's degree of linear polarization provides a measure of the membranes' degree of alignment.

Responsive Nanofibers with Embedded Hierarchical Lipid Self-Assemblies.

We introduce the design and study of a hybrid electrospun membrane with a dedicated nanoscale structural hierarchy for controlled functions in the biomedical domain. The hybrid system comprises submicrometer-sized internally self-assembled lipid nanoparticles (ISAsomes or mesosomes) embedded into the electrospun membrane with a nanofibrous polymer network. The internal structure of ISAsomes, studied by small-angle X-ray scattering (SAXS) and electron microscopy, demonstrated a spontaneous response to variations in the environmental conditions as they undergo a bicontinuous inverse cubic phase (cubosomes) in solution to a crystalline lamellar phase in the polymer membrane; nevertheless, this phase reorganization is reversible. As revealed by in situ SAXS measurements, if the membrane was put in contact with aqueous media, the cubic phase reappeared and submicrometer-sized cubosomes were released upon dissolution of the nanofibers. Furthermore, the hybrid membranes exhibited a specific anisotropic feature and morphological response under an external strain. While nanofibers were aligned under external strain in the microscale, the semicrystalline domains from the polymer phase were positioned perpendicular to the lamellae of the lipid phase in the nanoscale. The fabricated membranes and their spontaneous responses offer new strategies for the development of structure-controlled functions in electrospun nanofibers for biomedical applications, such as drug delivery or controlled interactions with biointerfaces.

Developing and evaluating ASTHMAXcel adventures: A novel gamified mobile application for pediatric patients with asthma.

BACKGROUND: The ASTHMAXcel mobile application has been linked to favorable outcomes among adult patients with asthma. OBJECTIVE: To assess the impact of ASTHMAXcel Adventures, a gamified, guideline-based, pediatric version on asthma control, knowledge, health care utilization, and patient satisfaction. METHODS: Pediatric patients with asthma received the ASTHMAXcel Adventures mobile intervention on-site only at baseline (visit 1), 4 months (visit 2), and 6 months (visit 3). The asthma control test, asthma illness representation scale-self-administered, pediatric asthma impact survey, and Client Satisfaction Questionnaire-8 were used to assess asthma control, knowledge, and patient satisfaction. Patients reported the number of asthma-related emergency department (ED) visits, hospitalizations, and oral prednisone use. RESULTS: A total of 39 patients completed the study. The proportion of controlled asthma increased from visit 1 to visits 2 and 3 (30.8% vs 53.9%, P = .04; 30.8% vs 59.0%, P = .02), and largely seen in boys. The mean asthma illness representation scale-self-administered scores increased from baseline pre- to postintervention, with sustained improvements at visits 2 and 3 (3.55 vs 3.76, P < .001; 3.55 vs 3.80, P = .001; 3.55 vs 3.99, P < .001). The pediatric asthma impact survey scores improved from baseline to visits 2 and 3 (43.33 vs 34.08, P < .001; 43.33 vs 31.74, P < .001). ED visits and prednisone use significantly decreased from baseline to visits 2 and 3 (ED: 0.46 vs 0.13, P = .03; 0.46 vs 0.02, P = .02; prednisone use, 0.49 vs 0.13, P = .02; 0.49 vs 0.03, P = .003. Satisfaction was high with mean client satisfaction questionnaire score of approximately 30 (out of 32) at all visits. CONCLUSION: ASTHMAXcel Adventures improved asthma control, knowledge, and quality of life, and reduced ED visits and prednisone use with high satisfaction scores.

Chalcone Based Homodimeric PET Agent, 11C-(Chal)2DEA-Me, for Beta Amyloid Imaging: Synthesis and Bioevaluation.

Homodimeric chalcone based 11C-PET radiotracer, 11C-(Chal)2DEA-Me, was synthesized, and binding affinity toward beta amyloid (Aß) was evaluated. The computational studies revealed multiple binding of the tracer at the recognition sites of Aß fibrils. The bivalent ligand 11C-(Chal)2DEA-Me displayed higher binding affinity compared to the corresponding monomer, 11C-Chal-Me, and classical Aß agents. The radiolabeling yield with carbon-11 was 40-55% (decay corrected) with specific activity of 65-90 GBq/µmol. A significant ( p < 0.0001) improvement in the binding affinity of 11C-(Chal)2DEA-Me with synthetic Aß42 aggregates over the monomer, 11C-Chal-Me, demonstrates the utility of the bivalent approach. The PET imaging and biodistribution data displayed suitable brain pharmacokinetics of both ligands with higher brain uptake in the case of the bivalent ligand. Metabolite analysis of healthy ddY mouse brain homogenates exhibited high stability of the radiotracers in the brain with >93% intact tracer at 30 min post injection. Both chalcone derivatives were fluorescent in nature and demonstrated significant changes in the emission properties after binding with Aß42. The preliminary analysis indicates high potential of 11C-(Chal)2DEA-Me as in vivo Aß42 imaging tracer and highlights the significance of the bivalent approach to achieve a higher biological response for detection of early stages of amyloidosis.

A 90-year-old man with factious disorder: Separating fact from fiction.

Objective Factitious disorders are known to exist in the medical community but are not commonly diagnosed in clinical practice. The majority of the literature on factitious disorder comes from case reports or case series. This particular case is unusual because it describes a patient who initially presented with purely physical complaints, but over time, the symptoms transitioned into predominantly psychiatric concerns. This case describes the patient's unique presentation and is followed by a discussion of the management of factitious disorder. Methods The patient was seen during the course of an inpatient psychiatric hospitalization. Electronic chart review was conducted, and information from each prior hospitalization was gathered between the dates of first initial documented presentation available in the electronic record in 1995 to most recent hospitalization in 2017. Results The patient still continues to present to the emergency department. Upon each presentation, staff work to objectively assess his complaints to be sure that there is no true underlying medical emergency. There is also a focus on providing non-judgmental, supportive, and compassionate care. Conclusion This case highlights the importance of corroborating objective findings with the patient's subjective reports gathered during a history and physical, and to recognize that patients with this disorder can present to any specialty. Thus, the collaboration between specialties is critical in the care of these patients to minimize unnecessary, costly, and sometimes dangerous interventions.

Zinc complex of tryptophan appended 1,4,7,10-tetraazacyclododecane as potential anticancer agent: Synthesis and evaluation.

With the rising incidences of cancer cases, the quest for new metal based anticancer drugs has led to extensive research in cancer biology. Zinc complexes of amino acid residue side chains are well recognized for hydrolysis of phosphodiester bond in DNA at faster rate. In the presented work, a Zn(II) complex of cyclen substituted with two l-tryptophan units, Zn(II)-Cyclen-(Trp)2 has been synthesized and evaluated for antiproliferative activity. Zn(II)-Cyclen-(Trp)2 was synthesized in ∼70% yield and its DNA binding potential was evaluated through QM/MM study which suggested good binding (G=-9.426) with B-DNA. The decrease in intensity of the positive and negative bands of CT-DNA at 278nm and 240nm, respectively demonstrated an effective unwinding of the DNA helix with loss of helicity. The complex was identified as an antiproliferative agent against U-87MG cells with 5 fold increase in apoptosis with respect to control (2h post incubation, IC50 25µM). Electrophoresis and comet assay studies exhibited an increase in DNA breakage after treatment with complex while caspase-3/ß-actin cleavage established a caspase-3 dependent apoptosis pathway in U-87 MG cells after triggering DNA damage. In vivo tumor specificity of the developed ligand was validated after radiocomplexation with 99mTc (>98% radiochemical yield and specific activity of 2.56GBq/µmol). Avid tumor/muscle ratio of >6 was depicted in biodistribution and SPECT imaging studies in U-87 MG xenograft model nude mice.

In vitro evaluation of excess copper affecting seedlings and their biochemical characteristics in Carthamus tinctorius L. (variety PBNS-12).

The present study was focused to recognize the changes in the Safflower (Carthamus tinctorius L. variety PBNS-12), when exposed to different concentration of copper (25, 50 and 100 µM) along with control (0.5 µM) for 10 and 20 days. This experiment used Hoagland's nutrient solution to meet the external nutrient conditions, which includes micro and macronutrients equivalent to soil solution with copper sulphate (CuSO4. 5H2O) as a metal stress. The plant samples were harvested after 10 and 20 days. The effect of increased concentrations of copper was indicated by the reduction in overall growth with reduced fresh and dry weight. Copper stress caused significant increase in the non- enzymatic antioxidants (polyphenols and flavonoids) in leaves of treated safflower seedlings as compared to the control. Also, enhanced accumulation of proline was observed in the safflower leaves. In response to excess copper concentration, the level of MDA content was found to be increased. The results showed that the copper has time and dose-dependent effects on safflower seedlings.

Characterization of a novel acetamidobenzoxazolone-based PET ligand for translocator protein (18 kDa) imaging of neuroinflammation in the brain.

We developed the novel positron emission tomography (PET) ligand 2-[5-(4-[(11)C]methoxyphenyl)-2-oxo-1,3-benzoxazol-3(2H)-yl]-N-methyl-N-phenylacetamide ([(11)C]MBMP) for translocator protein (18 kDa, TSPO) imaging and evaluated its efficacy in ischemic rat brains. [(11)C]MBMP was synthesized by reacting desmethyl precursor (1) with [(11)C]CH3 I in radiochemical purity of ≥ 98% and specific activity of 85 ± 30 GBq/µmol (n = 18) at the end of synthesis. Biodistribution study on mice showed high accumulation of radioactivity in the TSPO-rich organs, e.g., the lungs, heart, kidneys, and adrenal glands. The metabolite analysis in mice brain homogenate showed 80.1 ± 2.7% intact [(11)C]MBMP at 60 min after injection. To determine the specific binding of [(11)C]MBMP with TSPO in the brain, in vitro autoradiography and PET studies were performed in an ischemic rat model. In vitro autoradiography indicated significantly increased binding on the ipsilateral side compared with that on the contralateral side of ischemic rat brains. This result was supported firmly by the contrast of radioactivity between the ipsilateral and contralateral sides in PET images. Displacement experiments with unlabelled MBMP or PK11195 minimized the difference in uptake between the two sides. In summary, [(11)C]MBMP is a potential PET imaging agent for TSPO and, consequently, for the up-regulation of microglia during neuroinflammation.

Synthesis and evaluation of new (18)F-labelled acetamidobenzoxazolone-based radioligands for imaging of the translocator protein (18 kDa, TSPO) in the brain.

The visualization of the activated microglia/TSPO is one of the main aspects of neuroimaging. Here we describe two new (18)F-labelled molecules, 2-[5-(4-[(18)F]fluoroethoxyphenyl)- ([(18)F]2) and 2-[5-(4-[(18)F]fluoropropyloxyphenyl)- ([(18)F]3) -2-oxo-1,3-benzoxazol-3(2H)-yl]-N-methyl-N-phenylacetamide as novel PET ligands for imaging the translocator protein (18 kDa, TSPO) in the brain. The three-D pharmacophore evaluation and docking studies suggested their high affinity for the TSPO and in vitro binding assays of the TSPO showed binding affinities 6.6 ± 0.7 nM and 16.7 ± 2.5 nM for 2 and 3, respectively. The radiochemical yields for [(18)F]2 and [(18)F]3 were found to be 22 ± 4% (n = 8) and 5 ± 2% (n = 5), respectively at EOB. The radiochemical purity for both was found ≥98% and the specific activity was in the range of 98-364 GBq µmol(-1) at EOS. In vitro autoradiography with an ischemic rat brain showed significantly increased binding on the ipsilateral side compared to the contralateral side. The specificity of [(18)F]2 and [(18)F]3 for binding TSPO was confirmed using the TSPO ligands PK11195 and MBMP. The biodistribution patterns of both PET ligands were evaluated in normal mice by 1 h dynamic PET imaging. In the brain, regional radioactivity reached the maximum very rapidly within 0-4 min for both ligands, similar to (R)[(11)C]PK11195. The metabolite study of [(18)F]2 also favoured a more favourable profile for quantification in comparison to (R)[(11)C]PK11195. In summary, these data indicated that [(18)F]2 and [(18)F]3 have good potential to work as PET ligands, therefore there are merits to use these radioligands for the in vivo evaluation in animal models to see their efficacy in the living brain.

Sudden bilateral reversible vision loss: a rare presentation of acute intermittent porphyria.

Acute intermittent porphyria is a rare disorder, characterised clinically by variable patterns of neurological and metabolic disturbances. We report a rare presentation with sudden onset painless bilateral reversible vision loss of cerebral origin along with a brief review of the underlying pathophysiology.

Comparison of bone loss around submerged and non-submerged implants during osseointegration phase.

Background: In Modern dentistry, the implant is the most popular and desirable management of tooth loss. Traditionally two stage (submerged) or one-stage (non-submerged) system has been added by many investigators. In the present study we evaluated the crestal bone loss during osseointegration phase among the three groups (i.e. submerged implants, non-submerged implants with anatomical healing abutment and non- submerged implants with esthetic healing abutment). Material and Methods: 10 subjects with 30 implants, were enrolled in the study. Subjects were randomized in three groups i.e., group 1 submerged (n=10), group 2 non-submerged with anatomical healing abutment (n=10), group 3 non submerged with esthetic healing abutments (n=10). Intraoral periapical radiograph (IOPA), IMAGE J software and CBCT were used to evaluate the crestal bone loss around each implant at baseline, 1 and 3 months after implant placement. Results: Crestal bone loss at the end of the 3months (osseointegration phase) was lowest in the submerged group (0.18+-0.06mm) followed by non-submerged esthetic group (0.21+-0.03mm) but it was statistically insignificant. Maximum amount of bone loss was observed in non-submerged anatomical abutment group (0.34+-0.03mm) which was highly significant. Conclusion: It can be concluded that submerged implants technique is a better option in comparison to non-submerged implant technique in terms of radiographical performance during initial phases of osseointegration.

Laminin mimetic angiogenic and collagen peptide hydrogel for enhance dermal wound healing.

Laminins are essential in basement membrane architecture and critical in re-epithelialization and angiogenesis. These processes and collagen deposition are vital in skin wound healing. The role of angiogenic peptides in accelerating the wound-healing process has been known. The bioactive peptides could be a potential approach due to their similar effects as growth factors and inherent biocompatible and biodegradable nature with lower cost. They can also recognize ligand-receptor interaction and mimic the extracellular matrix. Here, we report novel angiogenic DYVRLAI, CDYVRLAI, angiogenic-collagen PGPIKVAV, and Ac-PGPIKVAV peptides conjugated sodium carboxymethyl cellulose hydrogel, which was designed from laminin. The designed peptide exhibits a better binding with the α3ß1, αvß3, and α5ß1 integrins and CXCR2 receptor, indicating their angiogenic and collagen binding efficiency. The peptides were evaluated to stimulate wound healing in full-thickness excision wounds in normal and diabetic mice (type II). They demonstrated their efficacy in terms of angiogenesis (CD31), re-epithelialization through regeneration of the epidermis (H&E), and collagen deposition (MT). The synthesized peptide hydrogel (DYVRLAI and CDYVRLAI) showed enhanced wound contraction up to 10.1 % and 12.3 % on day 7th compared to standard becaplermin gel (49 %) in a normal wound model. The encouraging results were also observed with the diabetic model, where these peptides showed a significant decrease of 5.20 and 5.17 % in wound size on day 10th compared to the commercial gel (9.27 %). These outcomes signify that the modified angiogenic peptide is a cost effective, novel peptide motif to promote dermal wound healing in both models.