In spite of established indications for early operative repair of orbital floor fractures 7-10% of patients treated nonoperatively develop enophthalmos. Clearly further indications for repair are required to prevent these post-injury complications. Rounding of the inferior rectus muscle on coronal computerized tomography (CT) scan results from a loss of soft tissue and bony support and may therefore be predictive of late enophthalmos.A four-year institutional review was conducted to identify patients with orbital floor fractures that had been treated nonoperatively. Patients were recruited for late clinical follow-up (mean 30 months) where clinically significant enophthalmos and diplopia were measured. Clinical results were correlated with measurements of the height-to-width ratio of the inferior rectus muscle on CT scans by a blinded examiner. Eighteen of 78 patients were available for late follow-up. Sixteen patients had no enophthalmos whereas 2 patients had enophthalmos. The inferior rectus height-to-width ratios measured in the unaffected orbits were statistically similar between the two groups. There was a significantly increased height-to-width ratio exceeding 1.00 in the affected orbit when the enophthalmos group was compared to the no enophthalmos group.A height-to-width ratio of the inferior rectus muscle on coronal CT scan of greater than or equal to 1.00 is predictive of late enophthalmos.
Wounds are structural and functional disruptions of the skin that occur because of an accident. Chronic wounds are caused by a breakdown in the finely coordinated cascade of events that occurs during wound healing. Wound healing is a long process that split into at least three continuous and overlapping processes: an inflammatory response, a proliferative phase that leads to tissue repair, and third one is tissue remodeling. Therefore, wound healing studies are extensively studied to develop techniques that can achieve maximum recovery with minimum scar. Several growth hormones and cytokines secreted at the wound site tightly regulate wound healing processes. The traditional approach for wound management has been represented by topical treatments. Metal nanoparticles (e.g., silver, gold, zinc) are increasingly being employed in dermatology due to their favorable effects on wound healing, as well as in treating and preventing bacterial infections. The development of wound dressings materials has now been used to overcome the issues of external environments. The impregnated nanomaterials have provided moist environment that removes the exudates and avoid maceration. This review highlights the mechanism and focus on the current advancement of various nanoparticles impregnation material for wound healing process that can protect wound from infection and maintain the optimum exchange of gases.
Abstract Ras proteins promote cell proliferation and survival, controlling signal transduction that involves two major pathways, such as Raf/MEK/ERK and PI3K/Akt. K-Ras4B is the most abundant oncogenic isoform. In calcium- and calmodulin (CaM)-rich environments, such as ductal tissues, it plays a critical role in adenocarcinomas promoting PI3K/Akt signaling, particularly in pancreatic, lung, and colorectal cancers. It was suggested that in adenocarcinomas with elevated calcium levels, Ca2+/CaM recruits PI3Kα through interaction with its n/cSH2 domains and sequesters K-Ras4B from the membrane, organizing a CaM/K-Ras4B/PI3Kα ternary complex. Ca2+/CaM can replace the missing receptor tyrosine kinase (RTK) signal, acting to fully activate PI3Kα. Structural data suggests that CaM uniquely binds GTP-bound K-Ras4B but not N-Ras or H-Ras isoforms. Experimental evidence points to the farnesylated hypervariable region (HVR) of K-Ras4B as a major binding domain for CaM. Here, using molecular dynamics (MD) simulations we modeled K-Ras4B HVR interaction with Ca2+/CaM. Initial contacts of K-Ras4B HVR with CaM were determined by the nuclear magnetic resonance (NMR) chemical shift perturbation(CSP) data, which guided major interacting residue pairs between the HVR and CaM. In the simulations, two different topologies of Ca2+/CaM were modeled: CaM with stretched and flexible linkers. CaM has N- and C-lobes connected by a linker, and each lobe has its own hydrophobic pocket. Thus, the hydrophobic farnesyl tail of the HVR can dock into either lobe of CaM. We observed that the HVR strongly interacts with the linker of CaM. The K-Ras4B HVR is highly polybasic with lysine-rich, while the linker region of CaM is negatively charged. The docking of the farnesyl group into the hydrophobic pocket additionally helps to stabilize the HVR/CaM interaction. This added stabilization by the farnesyl is significant in the K-Ras4B/CaM interaction even though the interaction with the Ras catalytic domain is involved. K-Ras4B has only farnesyl modification, while other isoforms bear farnesyl and palmitoyl groups. The additional lipid modification in the HVR would obstruct CaM binding, suggesting CaM's K-Ras4B-specific action. Our structural model of K-Ras4B/CaM association provides plausible clues to the PI3Kα activation involving the ternary complex. The abundant Ca2+/CaM can bind to the p85 domain of PI3Kα while binding to the K-Ras4B farnesylated HVR, releasing catalytic kinase domain autoinhibition and allosterically leading to full PI3Kα activation. Funded by Frederick National Laboratory for Cancer Research, National Institutes of Health, under contract HHSN261200800001E. Citation Format: Hyunbum Jang, Avik Banerjee, Vadim Gaponenko, Ruth Nussinov. High affinity interaction of K-Ras4B HVR with calmodulin [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 5229. doi:10.1158/1538-7445.AM2017-5229
Oncogenic mutant K-Ras promotes cancer cell proliferation, migration, invasion, and survival by assembling signaling complexes. To date, the functional and structural roles of K-Ras mutations within these complexes are incompletely understood despite their mechanistic and therapeutic significance. Here, we review recent advances in understanding specific binding between K-Ras and the calcium sensor calmodulin. This interaction positively and negatively regulates diverse functions of K-Ras in cancer, suggesting flexibility in K-Ras/calmodulin complex formation. Also, structural data suggest that oncogenic K-Ras likely samples several conformational states, influencing its distinct assemblies with calmodulin and with other proteins. Understanding how K-Ras interacts with calmodulin and with other partners is essential to discovering novel inhibitors of K-Ras in cancer.
End-binding proteins (EBs) associate with the growing microtubule plus ends to regulate microtubule dynamics as well as the interaction with intracellular structures. EB3 contributes to pathological vascular leakage through interacting with the inositol 1,4,5-trisphosphate receptor 3 (IP3R3), a calcium channel located at the endoplasmic reticulum membrane. The C-terminal domain of EB3 (residues 200–281) is functionally important for this interaction because it contains the effector binding sites, a prerequisite for EB3 activity and specificity. Structural data for this domain is limited. Here, we report the backbone chemical shift assignments for the human EB3 C-terminal domain and computationally explore its EB3 conformations. Backbone assignments, along with computational models, will allow future investigation of EB3 structural dynamics, interactions with effectors, and will facilitate the development of novel EB3 inhibitors.
Infections of the central nervous system (CNS) are common and routinely encountered. Our aim was to evaluate the neuroimaging features of the various infections of the CNS so as to differentiate them from tumoral, vascular, and other entities that warrant a different line of therapy.Our aim was to analyze the biochemical and magnetic resonance imaging (MRI) features in CNS infections.This was a longitudinal, prospective study over a period of 1½ years.We studied cerebrospinal fluid (CSF) findings and MRI patterns in 27 patients of 0-20 years age group with clinical features of CNS infections. MRI was performed on MAGNETOM Avanto 18 Channel 1.5 Tesla MR machine by Siemens India Ltd. The MRI protocol consisted of diffusion-weighted and apparent diffusion coefficient imaging, turbo spin echo T2-weighted, spin echo T1-weighted, fluid-attenuated inversion recovery (FLAIR), and gradient-echo in axial, FLAIR in coronal, and T2-weighted in sagittal plane. Contrast-enhanced T1-weighted sequence and MR spectroscopy were done whenever indicated.We found that most of the children belong to 1-10 years age group. Fungal infections were uncommon, mean CSF adenosine deaminase values specific for tuberculosis and mean CSF glucose-lowered in pyogenic. Hemorrhagic involvement of thalamus with/without basal ganglia and brainstem involvement may indicate Japanese encephalitis or dengue encephalitis. Diffusion restriction or hemorrhage in not expected in the brainstem afflicted lesions of rabies. Congenital cytomegalovirus can cause cortical malformations. T1 hyperintensities with diffusion restriction may represent viral encephalitis. Lesions of acute disseminated encephalomyelitis (ADEM) may mimic viral encephalitis. Leptomeningeal enhancement is predominant in pyogenic meningitis. Basilar meningitis in the presence of tuberculomas is highly sensitive and specific for tuberculosis.
